Ahmadi, S, Ebrahimi Warkiani, M, Rabiee, M, Iravani, S & Rabiee, N 2023, 'Carbon-based nanomaterials against SARS-CoV-2: Therapeutic and diagnostic applications', OpenNano, vol. 10, pp. 100121-100121.
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Alqudah, A, AbuDalo, R, Qnais, E, Wedyan, M, Oqal, M & McClements, L 2023, 'The emerging importance of immunophilins in fibrosis development', Molecular and Cellular Biochemistry, vol. 478, no. 6, pp. 1281-1291.
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AbstractImmunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins’ pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis.
Chhor, M, Law, W, Pavlovic, M, Aksentijevic, D, McGrath, K & McClements, L 2023, 'Diagnostic and prognostic biomarkers reflective of cardiac remodelling in diabetes mellitus: A scoping review', Diabetic Medicine, vol. 40, no. 5.
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AbstractAimsThe aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease. We aim to discuss the biomarkers' pathophysiological roles as a reflection of the cardiac remodelling mechanisms in the presence of DM.MethodsWe performed the literature search to include studies from 2003 to 2021 using the following databases: MEDLINE, Scopus, Web of Science, PubMed, and Cochrane library. Articles that met our inclusion criteria were screened and appraised before being included in this review. The PRISMA guidelines for Scoping Reviews were followed.ResultsOur literature search identified a total of 43 eligible articles, which were included in this scoping review. We identified 15 different biomarkers, each described by at least two studies, that were used to determine signs of cardiac remodelling in cardiovascular disease (CVD) and people with DM. NT‐proBNP was identified as the most frequently employed biomarker in this context; however, we also identified emerging biomarkers including hs‐CRP, hs‐cTnT, and Galectin‐3.ConclusionThere is a complex relationship between DM and cardiovascular health, where more research is needed. Current biomarkers reflective of adverse cardiac remodelling in DM are often used to diagnose other CVDs, such as NT‐proBNP for heart failure. Hence there is a need for identification of specific biomarkers that can detect early signs of cardiac remodelling in the presence of DM. Further research into these biomarkers and mechanisms can deepen our understanding of their role in DM‐associated CVD and lead to better preve...
Clarke, RJ, Lev, B, Chennath, M, Allen, TW, Cranfield, CG, Blayney, E-L & Cornelius, F 2023, 'Involvement of alpha-subunit N-termini in the mechanism and regulation of the Na+,K+- and H+,K+-ATPases', Biophysical Journal, vol. 122, no. 3, pp. 529a-529a.
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Cui, Y, Miao, MZ, Wang, M, Su, QP, Qiu, K, Arbeeva, L, Chubinskaya, S, Diekman, BO & Loeser, RF 2023, 'Yes-associated protein nuclear translocation promotes anabolic activity in human articular chondrocytes', Osteoarthritis and Cartilage, vol. 31, no. 8, pp. 1078-1090.
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OBJECTIVE: Yes-associated protein (YAP) has been widely studied as a mechanotransducer in many cell types, but its function in cartilage is controversial. The aim of this study was to identify the effect of YAP phosphorylation and nuclear translocation on the chondrocyte response to stimuli relevant to osteoarthritis (OA). DESIGN: Cultured normal human articular chondrocytes from 81 donors were treated with increased osmolarity media as an in vitro model of mechanical stimulation, fibronectin fragments (FN-f) or IL-1β as catabolic stimuli, and IGF-1 as an anabolic stimulus. YAP function was assessed with gene knockdown and inhibition by verteporfin. Nuclear translocation of YAP and its transcriptional co-activator TAZ and site-specific YAP phosphorylation were determined by immunoblotting. Immunohistochemistry and immunofluorescence to detect YAP were performed on normal and OA human cartilage with different degrees of damage. RESULTS: Chondrocyte YAP/TAZ nuclear translocation increased under physiological osmolarity (400 mOsm) and IGF-1 stimulation, which was associated with YAP phosphorylation at Ser128. In contrast, catabolic stimulation decreased the levels of nuclear YAP/TAZ through YAP phosphorylation at Ser127. Following YAP inhibition, anabolic gene expression and transcriptional activity decreased. Additionally, YAP knockdown reduced proteoglycan staining and levels of type II collagen. Total YAP immunostaining was greater in OA cartilage, but YAP was sequestered in the cytosol in cartilage areas with more severe damage. CONCLUSIONS: YAP chondrocyte nuclear translocation is regulated by differential phosphorylation in response to anabolic and catabolic stimuli. Decreased nuclear YAP in OA chondrocytes may contribute to reduced anabolic activity and promotion of further cartilage loss.
Ding, L, Oh, S, Shrestha, J, Lam, A, Wang, Y, Radfar, P & Warkiani, ME 2023, 'Scaling up stem cell production: harnessing the potential of microfluidic devices', Biotechnology Advances, vol. 69, pp. 108271-108271.
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Fang, G, Chen, Y, Lu, H & Jin, D 2023, 'Advances in Spheroids and Organoids on a Chip', Advanced Functional Materials, vol. 33, no. 19, pp. 2215043-2215043.
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AbstractMulticellular spheroids and organoids are promising in vitro 3D models in personalized medicine and drug screening. They replicate the structural and functional characteristics of human organs in vivo. Microfluidic technology and micro‐nano fabrication can fulfill the high requirement of the engineering approach in the growing research interest in spheroids and organoids. In this review, spheroids and organoids are comparatively introduced. Then it is illustrated how spheroids‐ and organoids‐on‐a‐chip technology facilitates their establishment, expansion, and application through spatial‐temporal control, mechanical cues modeling, high‐throughput analysis, co‐culture, multi‐tissue interactions, biosensing, and bioimaging integration. The potential opportunities and challenges in developing spheroids‐ and organoids‐on‐a‐chip technology are finally outlooked.
Fu, S, Shi, W, Luo, T, He, Y, Zhou, L, Yang, J, Yang, Z, Liu, J, Liu, X, Guo, Z, Yang, C, Liu, C, Huang, Z-L, Ries, J, Zhang, M, Xi, P, Jin, D & Li, Y 2023, 'Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging', Nature Methods, vol. 20, no. 3, pp. 459-468.
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Ghorbanpour, S, Kaitu'u-Lino, TJ, Hannan, NJ, Tong, S & McClements, L 2023, 'PO6_24. Validation of FKBPL and CD44 as emerging biomarkers for early-onset preeclampsia diagnosis', Pregnancy Hypertension, vol. 33, pp. e40-e40.
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Ghorbanpour, SM, Richards, C, Pienaar, D, Sesperez, K, Aboulkheyr Es., H, Nikolic, VN, Karadzov Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Alqudah, A, Cole, L, Gorrie, C, McGrath, K, Kavurma, MM, Ebrahimi Warkiani, M & McClements, L 2023, 'A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia', Cellular and Molecular Life Sciences, vol. 80, no. 2.
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AbstractPreeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.
Goss, DM, Vasilescu, SA, Sacks, G, Gardner, DK & Warkiani, ME 2023, 'Microfluidics facilitating the use of small extracellular vesicles in innovative approaches to male infertility', Nature Reviews Urology, vol. 20, no. 2, pp. 66-95.
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Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.
Haghighitalab, A, Dominici, M, Matin, MM, Shekari, F, Ebrahimi Warkiani, M, Lim, R, Ahmadiankia, N, Mirahmadi, M, Bahrami, AR & Bidkhori, HR 2023, 'Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases', Frontiers in Immunology, vol. 14, p. 1090416.
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The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases’ vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status; MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs’ unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.
Hazeri, AH, Abouei Mehrizi, A, Mohseni, SS, Ebrahimi Warkiani, M & Razavi Bazaz, S 2023, 'A Novel Strategy for Square-Wave Micromixers: A Survey of RBC Lysis for Further Biological Analysis', Industrial & Engineering Chemistry Research, vol. 62, no. 40, pp. 16215-16224.
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Hossain, KR, Turkewitz, DR, Holt, SA, Le Brun, AP & Valenzuela, SM 2023, 'Sterol Structural Features’ Impact on the Spontaneous Membrane Insertion of CLIC1 into Artificial Lipid Membranes', Langmuir, vol. 39, no. 9, pp. 3286-3300.
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Huang, Y, Du, Z, Bao, G, Fang, G, Cappadona, M, McClements, L, Tuch, BE, Lu, H & Xu, X 2023, 'Smart Drug-Delivery System of Upconversion Nanoparticles Coated with Mesoporous Silica for Controlled Release', Pharmaceutics, vol. 15, no. 1, pp. 89-89.
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Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)—mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers.
Jiang, T, Li, X, Li, T, Lin, G, Liu, H, Jin, D & Jiang, L 2023, 'Ultra‐Fast Wetting of the Fresh Popcorn', Advanced Functional Materials, vol. 33, no. 14, pp. 2213036-2213036.
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AbstractWithout chewing, the fresh popcorn dissolves immediately upon being put in the mouth. Such good taste decay dramatically with increasing the exposure time in air, especially in humid air. However, the involving mechanism of the saliva wetting the popcorn remains unclear. Here, it is revealed that the ultra‐fast wetting property of the fresh popcorn is the key for its good taste. For the fresh popcorn, the unique 3D throughout micro‐porous structure facilitates capillary flows both in‐plane and off‐plane at micro‐/nano‐ scale, and the water‐soluble crystalized starch further prompts the water spreading, which cooperatively leads to an immediate structural collapse. The unique ultra‐fast wetting of the fresh popcorn is therefore featured as the wetting with dissolving. After cooling down, the crystalized starch changes gradually into an insoluble amorphous state by absorbing water molecule, as is confirmed by the in situ XRD and infrared spectroscopy. As a result, the ultra‐fast wetting decays drastically with prolonging the in‐air exposure time, as well as the taste, which makes immediate cooking vital for the good taste. It is demonstrated that heating can partially restore the ultra‐fast wetting. It is envisioned that the result will inspire the innovative micro‐fabrication of various starch food by engineering the starch crystalline structure.
Kang, Y, Xu, J, Meng, L, Su, Y, Fang, H, Liu, J, Cheng, YY, Jiang, D, Nie, Y & Song, K 2023, '3D bioprinting of dECM/Gel/QCS/nHAp hybrid scaffolds laden with mesenchymal stem cell-derived exosomes to improve angiogenesis and osteogenesis', Biofabrication, vol. 15, no. 2, pp. 024103-024103.
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Abstract Craniofacial bone regeneration is a coupled process of angiogenesis and osteogenesis, which, associated with infection, still remains a challenge in bone defects after trauma or tumor resection. 3D tissue engineering scaffolds with multifunctional-therapeutic properties can offer many advantages for the angiogenesis and osteogenesis of infected bone defects. Hence, in the present study, a microchannel networks-enriched 3D hybrid scaffold composed of decellularized extracellular matrix (dECM), gelatin (Gel), quaterinized chitosan (QCS) and nano-hydroxyapatite (nHAp) (dGQH) was fabricated by an extrusion 3D bioprinting technology. And enlightened by the characteristics of natural bone microstructure and the demands of vascularized bone regeneration, the exosomes (Exos) isolated from human adipose derived stem cells as angiogenic and osteogenic factors were then co-loaded into the desired dGQH20 hybrid scaffold based on an electrostatic interaction. The results of the hybrid scaffolds performance characterization showed that these hybrid scaffolds exhibited an interconnected pore structure and appropriate degradability (>61% after 8 weeks of treatment), and the dGQH20 hybrid scaffold displayed the highest porosity (83.93 ± 7.38%) and mechanical properties (tensile modulus: 62.68 ± 10.29 MPa, compressive modulus: 16.22 ± 3.61 MPa) among the dGQH hybrid scaffolds. Moreover, the dGQH20 hybrid scaffold presented good antibacterial activities (against 94.90 ± 2.44% of Escherichia coli and 95.41 ± 2.65% of Staphylococcus aureus, respectively) as well as excellent hemocompatibility and biocompatibility. Furthermore, the results of applying the Exos to the dGQH20 hybrid scaffold showed that the Exo promoted the cell attachment and proliferation on the scaffold, and also...
Lankage, UM, Holt, SA, Bridge, S, Cornell, B & Cranfield, CG 2023, 'Triglyceride-Tethered Membrane Lipase Sensor', ACS Applied Materials & Interfaces.
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Sensors that can quickly measure the lipase activity from biological samples are useful in enzyme production and medical diagnostics. However, current lipase sensors have limitations such as requiring fluorescent labels, pH control of buffer vehicles, or lengthy assay preparation. We introduce a sparsely tethered triglyceride substrate anchored off of a gold electrode for the impedance sensing of real-time lipase activity. The tethered substrate is self-assembled using a rapid solvent exchange technique and can form an anchored bilayer 1 nm off the gold electrode. This allows for an aqueous reservoir region, providing access to ions transported through membrane defects caused by triglyceride enzymatic hydrolysis. Electrical impedance spectroscopy techniques can readily detect the decrease in resistance caused by enzymatically induced defects. This rapid and reliable lipase detection method can have potential applications in disease studies, monitoring of lipase production, and as point-of-care diagnostic devices.
Lev, B, Chennath, M, Cranfield, CG, Cornelius, F, Allen, TW & Clarke, RJ 2023, 'Involvement of the alpha-subunit N-terminus in the mechanism of the Na+,K+-ATPase', Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1870, no. 7, pp. 119539-119539.
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Lin, G, Khan, JU, Zhand, S, Liu, Y & Jin, D 2023, 'Modular DNAzymes-Hydrogel Membrane Carriers for Highly Sensitive Isothermal Cross-Cascade Detection of Pathogenic Bacteria Nucleic Acids', Analytical Chemistry, vol. 95, no. 35, pp. 13353-13360.
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The increasing prevalence of antimicrobial resistance has called for improved diagnostic testing of pathogenic bacteria. However, the development of rapid, cost-effective, and easy-to-use tests for bacterial infections remains a constant challenge. Here, we report a class of modular hydrogel membrane carriers incorporated with composite DNAzymes, which enable rapid and highly sensitive detection of pathogenic bacteria gene target analytes. We apply free radical polymerization to incorporate composite DNAzymes, consisting of an RNA substrate component and a DNAzyme component (e.g., 10-23 or 8-17 DNAzymes), into polyethylene glycol diacrylate polymer networks. Initiated by a nucleic acid target acting as an assembly facilitator, multicomponent DNAzymes are combined to cleave the RNA substrate component in the hydrogel carriers, which releases the DNAzyme component to cleave RNA reporter probes to generate fluorescence. We modulate the morphology, composition, and microporous structures of the DNAzyme carriers to achieve quantitative assay performance. We demonstrate a rapid and high-sensitivity detection of C. trachomatis gene target analytes as low as 50 fM in a short assay time of 25 min. The work represents a crucial step forward in the development of a generic, isothermal, and protein enzyme-free pathogenic bacteria testing platform technology.
Lin, J, Xing, B & Jin, D 2023, 'Optical Bioimaging and Therapy', Advanced Optical Materials, vol. 11, no. 11.
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Liu, Y, Lin, G, Medina-Sánchez, M, Guix, M, Makarov, D & Jin, D 2023, 'Responsive Magnetic Nanocomposites for Intelligent Shape-Morphing Microrobots', ACS Nano, vol. 17, no. 10, pp. 8899-8917.
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Liu, Y, Wen, S, Wang, F, Zuo, C, Chen, C, Zhou, J & Jin, D 2023, 'Population Control of Upconversion Energy Transfer for Stimulation Emission Depletion Nanoscopy', Advanced Science, vol. 10, no. 20.
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AbstractUpconverting stimulated emission depletion microscopy (U‐STED) is emerging as an effective approach for super‐resolution imaging due to its significantly low depletion power and its ability to surpass the limitations of the square‐root law and achieve higher resolution. Though the compelling performance, a trade‐off between the spatial resolution and imaging quality in U‐STED has been recognized in restricting the usability due to the low excitation power drove high depletion efficiency. Moreover, it is a burden to search for the right power relying on trial and error as the underpinning mechanism is unknown. Here, a method is proposed that can easily predict the ideal excitation power for high depletion efficiency with the assistance of the non‐saturate excitation based on the dynamic cross‐relaxation (CR) energy transfer of upconversion nanoparticles. This allows the authors to employ the rate equation model to simulate the populations of each relevant energy state of lanthanides and predict the ideal excitation power for high depletion efficiency. The authors demonstrate that the resolution of STED with the assistance of nonsaturated confocal super‐resolution results can easily achieve the highest resolution of sub‐40 nm, 1/24th of the excitation wavelengths. The finding on the CR effect provides opportunities for population control in realizing low‐power high‐resolution nanoscopy.
Liu, Y, Zhou, J, Wen, S, Wang, F, Wu, H, Chen, Q, Zuo, C & Jin, D 2023, 'On-Chip Mirror Enhanced Multiphoton Upconversion Super-Resolution Microscopy', Nano Letters, vol. 23, no. 12, pp. 5514-5519.
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Lotfi, M, Morshedi Rad, D, Mashhadi, SS, Ashouri, A, Mojarrad, M, Mozaffari-Jovin, S, Farrokhi, S, Hashemi, M, Lotfi, M, Ebrahimi Warkiani, M & Abbaszadegan, MR 2023, 'Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells', Stem Cell Reviews and Reports, vol. 19, no. 8, pp. 2576-2596.
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Abstract Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells. Graphical Abstract
Luo, X, Zhang, C, Yu, Z, Wen, S & Xian, Y 2023, 'Recent advances in responsive lanthanide-doped luminescence nanoprobes in the near-infrared-II window', TrAC Trends in Analytical Chemistry, vol. 169, pp. 117368-117368.
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Ma, H, Yu, K, Wang, H, Liu, J, Cheng, YY, Kang, Y, Wang, H, Zhang, J & Song, K 2023, 'Fabrication and detection of a novel hybrid conductive scaffold based on alginate/gelatin/carboxylated carbon nanotubes (Alg/Gel/mMWCNTs) for neural tissue engineering', Tissue and Cell, vol. 80, pp. 101995-101995.
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Ma, H, Zheng, L, Yang, S, Cheng, YY, Liu, T, Wu, S, Wang, H, Zhang, J & Song, K 2023, 'Construction and properties detection of 3D micro-structure scaffolds base on decellularized sheep kidney before and after crosslinking', Journal of Biomaterials Applications, vol. 37, no. 9, pp. 1593-1604.
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Decellularized extracellular matrix is one form of natural material in tissue engineering. The process of dECM retains the tissue microstructure, provides good cell adhesion sites, maintains most of biological signals that promotes the survival and differentiation ability of cells. In this study, sheep kidney was decellularized followed by histochemical staining, elemental analysis and scanning electron microscopy characterizations. The dECM scaffold was prepared with different sequences of freeze drying technology, crosslinking and the water absorption, porosity, mechanical strength with subsequent thermogravimetric analysis, Infrared spectroscopy and biocompatibility tests. Our results indicated that these decellularized treatments of sheep kidney can effectively remove DNA and retain uniform pore size distribution. After crosslinking the scaffold’s water absorption decreased from 987.56 ± 40.21% to 934.39 ± 39.61%, the porosity decreased from 89.64 ± 3.2% to 85.09 ± 17.63%, and the compression modulus increased from 304.32 ± 25.43 kPa to 459.53 ± 38.92 kPa, with thermal process the percentage of weight loss decreased from 66.57% to 44.731%, in addition, the composition didn’t change significantly, crosslinking could also promote the stability. In terms of biocompatibility, the number of viable cells increased significantly with the days. In conclusion, the crosslinked decellularized sheep kidney extracellular matrix scaffold reduced water absorption and porosity slightly, but has a significant increase in mechanical properties, and presented excellent biocompatibility which are beneficial to cell adhesion, growth and differentiation.
MacDermott-Opeskin, H, Clarke, C, Wu, X, Roseblade, A, York, E, Pacchini, E, Roy, R, Cranfield, C, Gale, PA, O'Mara, ML, Murray, M & Rawling, T 2023, 'Protonophoric and mitochondrial uncoupling activity of aryl-carbamate substituted fatty acids', Organic & Biomolecular Chemistry, vol. 21, no. 1, pp. 132-139.
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Aryl-carbamate substituted fatty acids are protonophores that uncouple mitochondrial oxidative phosphorylation. The proton transport cycle requires self-assembly into membrane permeable dimers. The findings demonstrate the anion transport capability of the carbamate group.
Masoumeh Ghorbanpour, S, Wen, S, Kaitu'u‐Lino, TJ, Hannan, NJ, Jin, D & McClements, L 2023, 'Quantitative Point of Care Tests for Timely Diagnosis of Early‐Onset Preeclampsia with High Sensitivity and Specificity', Angewandte Chemie International Edition, vol. 62, no. 26.
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AbstractPreeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early‐onset preeclampsia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml−1 for FKBPL and 15 pg ml−1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical samples, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preeclampsia.
Masoumeh Ghorbanpour, S, Wen, S, Kaitu'u‐Lino, TJ, Hannan, NJ, Jin, D & McClements, L 2023, 'Quantitative Point of Care Tests for Timely Diagnosis of Early‐Onset Preeclampsia with High Sensitivity and Specificity', Angewandte Chemie, vol. 135, no. 26.
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AbstractPreeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early‐onset preeclampsia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml−1 for FKBPL and 15 pg ml−1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical samples, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preeclampsia.
Mi, C, Zhang, X, Yang, C, Wu, J, Chen, X, Ma, C, Wu, S, Yang, Z, Qiao, P, Liu, Y, Wu, W, Guo, Z, Liao, J, Zhou, J, Guan, M, Liang, C, Liu, C & Jin, D 2023, 'Bone disease imaging through the near-infrared-II window', Nature Communications, vol. 14, no. 1, p. 6287.
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AbstractSkeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.
Mirakhorli, F, Razavi Bazaz, S, Warkiani, ME & Ralph, PJ 2023, 'Ultra-high throughput microfluidic concentrator for harvesting of Tetraselmis sp. (Chlorodendrophyceae, Chlorophyta)', Algal Research, vol. 72, pp. 103145-103145.
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Mohkam, M, Sadraeian, M, Lauto, A, Gholami, A, Nabavizadeh, SH, Esmaeilzadeh, H & Alyasin, S 2023, 'Exploring the potential and safety of quantum dots in allergy diagnostics', Microsystems & Nanoengineering, vol. 9, no. 1, p. 145.
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AbstractBiomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy. Quantum dots (QDs) are promising nanomaterials that possess a wide array of advantageous properties, including electronic properties, optical properties, and engineered biocompatibility under physiological conditions. Due to these characteristics, QDs are mainly used for biomedical labeling and theranostic (therapeutic-diagnostic) agents. QDs can be functionalized with ligands to facilitate their interaction with the immune system, specific IgE, and effector cell receptors. However, undesirable side effects such as hypersensitivity and toxicity may occur, requiring further assessment. This review systematically summarizes the potential uses of QDs in the allergy field. An overview of the definition and development of QDs is provided, along with the applications of QDs in allergy studies, including the detection of allergen-specific IgE (sIgE), food allergens, and sIgE in cellular tests. The potential treatment of allergies with QDs is also described, highlighting the toxicity and biocompatibility of these nanodevices. Finally, we discuss the current findings on the immunotoxicity of QDs. Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.
Morshedi Rad, D, Hansen, WP, Zhand, S, Cranfield, C & Ebrahimi Warkiani, M 2023, 'A hybridized mechano-electroporation technique for efficient immune cell engineering', Journal of Advanced Research.
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Nazari, H, Shrestha, J, Naei, VY, Bazaz, SR, Sabbagh, M, Thiery, JP & Warkiani, ME 2023, 'Advances in TEER measurements of biological barriers in microphysiological systems', Biosensors and Bioelectronics, vol. 234, pp. 115355-115355.
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Owen, B, Kechagidis, K, Bazaz, SR, Enjalbert, R, Essmann, E, Mallorie, C, Mirghaderi, F, Schaaf, C, Thota, K, Vernekar, R, Zhou, Q, Warkiani, ME, Stark, H & Krüger, T 2023, 'Lattice-Boltzmann modelling for inertial particle microfluidics applications - a tutorial review', Advances in Physics: X, vol. 8, no. 1.
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Phan, TH, Shi, H, Denes, CE, Cole, AJ, Wang, Y, Cheng, YY, Hesselson, D, Roelofs, SH, Neely, GG, Jang, J-H & Chrzanowski, W 2023, 'Advanced pathophysiology mimicking lung models for accelerated drug discovery', Biomaterials Research, vol. 27, no. 1.
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Abstract Background Respiratory diseases are the 2 nd leading cause of death globally. The current treatments for chronic lung diseases are only supportive. Very few new classes of therapeutics have been introduced for lung diseases in the last 40 years, due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing. To accelerate the development of new therapeutics for lung diseases, we established two classes of lung-mimicking models: (i) healthy, and (ii) diseased lungs – COPD. Methods To establish models that mimic the lung complexity to different extents, we used five design components: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. To determine whether the lung models are reproducible and reliable, we developed a quality control (QC) strategy, which integrated the real-time and end-point quantitative and qualitative measurements of cellular barrier function, permeability, tight junctions, tissue structure, tissue composition, and cytokine secretion. Results The healthy model is characterised by (i) continuous tight junctions, (ii) physiological cellular barrier function, (iii) a full thickness epithelium composed of multiple cell layers, and (iv) the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease: (i) dysfunctional cellular barrier function, (ii) depletion of ciliated cells, and (ii) overproduction of goblet cells. The models developed here have...
Rabiee, N, Dokmeci, MR, Zarrabi, A, Makvandi, P, Saeb, MR, Karimi-Maleh, H, Jafarzadeh, S, Karaman, C, Yamauchi, Y, Warkiani, ME, Bencherif, SA, Mehta, G, Eguchi, M, Kaushik, A, Shahbazi, M-A, Paiva-Santos, AC, Ryl, J, Lima, EC, Hamblin, MR, Varma, RS, Huh, Y, Vilian, ATE, Gupta, PK, Lakhera, SK, Kesari, KK, Liu, Y-T, Tahriri, M, Rama Raju, GS, Adeli, M, Mohammadi, A, Wang, J, Ansari, MZ, Aminabhavi, T, Savoji, H, Sethi, G, Bączek, T, Kot-Wasik, A, Penoff, ME, Nafchi, AM, Kucinska-Lipka, J, Zargar, M, Asadnia, M, Aref, AR, Safarkhani, M, Ashrafizadeh, M, Umapathi, R, Ghasemi, A & Radisic, M 2023, 'Green Biomaterials : fundamental principles', Green Biomaterials, vol. 1, no. 1, pp. 1-4.
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Radfar, P, Ding, L, de la Fuente, LR, Aboulkheyr, H, Gallego-Ortega, D & Warkiani, ME 2023, 'Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics', Biosensors and Bioelectronics, vol. 223, pp. 114966-114966.
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Effective isolation and in-depth analysis of Circulating Tumour Cells (CTCs) are greatly needed in diagnosis, prognosis and monitoring of the therapeutic response of cancer patients but have not been completely fulfilled by conventional approaches. The rarity of CTCs and the lack of reliable biomarkers to distinguish them from peripheral blood cells have remained outstanding challenges for their clinical implementation. Herein, we developed a high throughput Static Droplet Microfluidic (SDM) device with 38,400 chambers, capable of isolating and classifying the number of metabolically active CTCs in peripheral blood at single-cell resolution. Owing to the miniaturisation and compartmentalisation capability of our device, we first demonstrated the ability to precisely measure the lactate production of different types of cancer cells inside 125 pL droplets at single-cell resolution. Furthermore, we compared the metabolomic activity of leukocytes from healthy donors to cancer cells and showed the ability to differentiate them. To further prove the clinical relevance, we spiked cancer cell lines in human healthy blood and showed the possibility to detect the cancer cells from leukocytes. Lastly, we tested the workflow on 8 preclinical mammary mouse models including syngeneic 67NR (non-metastatic) and 4T1.2 (metastatic) models with Triple-Negative Breast Cancer (TNBC) as well as transgenic mouses (12-week-old MMTV-PyMT). The results have shown the ability to precisely distinguish metabolically active CTCs from the blood using the proposed SDM device. The workflow is simple and robust which can eliminate the need for specialised equipment and expertise required for single-cell analysis of CTCs and facilitate on-site metabolic screening of cancer cells.
Radfar, P, Ding, L, Es, HA & Warkiani, ME 2023, 'A Microfluidic Approach for Enrichment and Single-Cell Characterization of Circulating Tumor Cells from Peripheral Blood', pp. 141-150.
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Razavi Bazaz, S, Zhand, S, Salomon, R, Beheshti, EH, Jin, D & Warkiani, ME 2023, 'ImmunoInertial microfluidics: A novel strategy for isolation of small EV subpopulations', Applied Materials Today, vol. 30, pp. 101730-101730.
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Cancer-specific small extracellular vesicles (sEVs), known as exosomes, have shown a great promise to serve as novel biomarkers for cancer diagnosis and prognosis in liquid biopsies. However, the high heterogeneity of sEVs posed great technical challenges to acquiring their molecular information. A simple and reproducible method for isolating subpopulations of sEVs can significantly enhance the detection and stratification of these circulating biomarkers and their function. This study used the synergic effects of the immunoaffinity-based approach and inertial microfluidics (ImmunoInertial microfluidics) to isolate specific subpopulations of sEVs. At first, the cancer cell-derived sEVs were captured on microbeads of varying sizes which were functionalized with specific capture antibodies such as epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and the programmed death-ligand 1 (PD-L1), facilitating the selective capture of sEVs. The sEVs-bearing microbeads were subsequently introduced to a series of inertial microfluidic channels, called iZExoSub (inertial zigzag microfluidics for exosome subpopulation separation), for size-based bead separation. Results revealed more than 90% efficiency in sEVs subpopulation separation, further proved via flow cytometry analysis data. Our approach is capable of selective isolation and quantitative detection of important biomarkers from sEVs subpopulations with high sensitivity and low cost and has the capacity to process samples of varying volumes, ranging from µL up to mL continuously. This system can outperform FACS machines in terms of sample throughput by orders of magnitudes. In addition, this study emphasized the necessity of using a consistent sEV marker (as capture and detector) across different samples for accurate assessment of subpopulations.
Rennie, C, Huang, Y, Siwakoti, P, Du, Z, Padula, M, Bao, G, Tuch, BE, Xu, X & McClements, L 2023, 'In vitroevaluation of a hybrid drug-delivery nanosystem for fibrosis prevention in cell therapy for Type 1 diabetes', Nanomedicine, vol. 18, no. 1, pp. 53-66.
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Background: Implantation of insulin-secreting cells has been trialed as a treatment for Type 1 diabetes mellitus; however, the host immunogenic response limits their effectiveness. Methodology: The authors developed a core-shell nanostructure of upconversion nanoparticle-mesoporous silica for controlled local delivery of an immunomodulatory agent, MCC950, using near-infrared light and validated it in in vitro models of fibrosis. Results: The individual components of the nanosystem did not affect the proliferation of insulin-secreting cells, unlike fibroblast proliferation (p < 0.01). The nanosystem is effective at releasing MCC950 and preventing fibroblast differentiation (p < 0.01), inflammation (IL-6 expression; p < 0.05) and monocyte adhesion (p < 0.01). Conclusion: This MCC950-loaded nanomedicine system could be used in the future together with insulin-secreting cell implants to increase their longevity as a curative treatment for Type 1 diabetes mellitus.
Sadeghirad, H, Bahrami, T, Layeghi, SM, Yousefi, H, Rezaei, M, Hosseini‐Fard, SR, Radfar, P, Warkiani, ME, O'Byrne, K & Kulasinghe, A 2023, 'Immunotherapeutic targets in non‐small cell lung cancer', Immunology, vol. 168, no. 2, pp. 256-272.
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AbstractNon‐small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5‐year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in‐depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.
Shao, D, Su, F, Zou, X, Lu, J, Wu, S, Tian, R, Ran, D, Guo, Z & Jin, D 2023, 'Pixel-Level Classification of Five Histologic Patterns of Lung Adenocarcinoma', Analytical Chemistry, vol. 95, no. 5, pp. 2664-2670.
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Shrestha, J, Paudel, KR, Nazari, H, Dharwal, V, Bazaz, SR, Johansen, MD, Dua, K, Hansbro, PM & Warkiani, ME 2023, 'Advanced models for respiratory disease and drug studies', Medicinal Research Reviews, vol. 43, no. 5, pp. 1470-1503.
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AbstractThe global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID‐19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung‐on‐a‐chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.
Siwakoti, P, Rennie, C, Huang, Y, Li, JJ, Tuch, BE, McClements, L & Xu, X 2023, 'Challenges with Cell-based Therapies for Type 1 Diabetes Mellitus', Stem Cell Reviews and Reports, vol. 19, no. 3, pp. 601-624.
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Type 1 diabetes (T1D) is a chronic, lifelong metabolic disease. It is characterised by the autoimmune-mediated loss of insulin-producing pancreatic β cells in the islets of Langerhans (β-islets), resulting in disrupted glucose homeostasis. Administration of exogenous insulin is the most common management method for T1D, but this requires lifelong reliance on insulin injections and invasive blood glucose monitoring. Replacement therapies with beta cells are being developed as an advanced curative treatment for T1D. Unfortunately, this approach is limited by the lack of donated pancreatic tissue, the difficulties in beta cell isolation and viability maintenance, the longevity of the transplanted cells in vivo, and consequently high costs. Emerging approaches to address these limitations are under intensive investigations, including the production of insulin-producing beta cells from various stem cells, and the development of bioengineered devices including nanotechnologies for improving islet transplantation efficacy without the need for recipients taking toxic anti-rejection drugs. These emerging approaches present promising prospects, while the challenges with the new techniques need to be tackled for ultimately clinical treatment of T1D. This review discussed the benefits and limitations of the cell-based therapies for beta cell replacement as potential curative treatment for T1D, and the applications of bioengineered devices including nanotechnology to overcome the challenges associated with beta cell transplantation.
Song, Y, Zhao, H, Zi, Y, Qiu, J, Song, Z, Bai, X, Liao, J & Yang, Z 2023, 'X-ray-Irradiation-Induced Discoloration and Persistent Radioluminescence for Reversible Dual-Mode Imaging and Detection Applications', ACS Energy Letters, vol. 8, no. 5, pp. 2232-2240.
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Su, Y, Hu, X, Kang, Y, Zhang, C, Cheng, YY, Jiao, Z, Nie, Y & Song, K 2023, 'Curcumin nanoparticles combined with 3D printed bionic tumor models for breast cancer treatment', Biofabrication, vol. 15, no. 1, pp. 014105-014105.
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Abstract Compared with conventional therapeutic approaches, nanomedicines are attracting a growing interest due to their better targeting ability, higher delivery efficiency, and good water solubility. However, conventional drug efficacy assessment methods are based on a two-dimensional (2D) culture approach of single cells to obtain in vitro therapeutic effects, which may not be representative of actual tumors. Based on the above considerations, the three-dimensional (3D) cell culture models became a better choice since they can increase the complexity of in vitro systems and provide a biomimetic microenvironment that is closer to the in vivo native than 2D cultures. In our study, curcumin nanoparticle (CurNPs) with good water solubility and good tumor therapeutic effects were prepared by combining polymeric non-ionic surfactant (Pluronic F127) with curcumin. The hybrid scaffolds based on nano-clay, sodium alginate, and gelatin were also prepared, which showed good printability and excellent biocompatibility. We then studied the therapeutic effects of CurNPs on metastatic breast cancer using a 3D tumor model fabricated with scaffold-bound metastatic breast cancer (MDA-MB-231) cells. It was showed that the 3D cell model presented better cell proliferation effect while compared with 2D version. Additionally, there was good enhanced permeability and retention effect when CurNPs entered with better accumulate in 3D cell ‘tumor’ sites which represented more realistic response of a more real tumor treatment effect for breast cancer cells. Our study indicated that the combinational of nanomaterials with 3D cell ‘tumor’ models provided an alternative and better platform for drug screening and has great potential be used as safe and effective treatment screening for breast cancer.
Tang, Q, Xue, N, Ding, X, Tsai, KH-Y, Hew, JJ, Jiang, R, Huang, R, Cheng, X, Ding, X, Yee Cheng, Y, Chen, J & Wang, Y 2023, 'Role of wound microbiome, strategies of microbiota delivery system and clinical management', Advanced Drug Delivery Reviews, vol. 192, pp. 114671-114671.
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Tang, S-J, Zhang, M, Sun, J, Meng, J-W, Xiong, X, Gong, Q, Jin, D, Yang, Q-F & Xiao, Y-F 2023, 'Single-particle photoacoustic vibrational spectroscopy using optical microresonators', Nature Photonics, vol. 17, no. 11, pp. 951-956.
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Tripathi, A, Zalogina, A, Liao, J, Wurdack, M, Estrecho, E, Zhou, J, Jin, D, Kruk, SS & Kivshar, Y 2023, 'Metasurface-Controlled Photonic Rashba Effect for Upconversion Photoluminescence', Nano Letters, vol. 23, no. 6, pp. 2228-2232.
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Tu, L, Wu, K, Luo, Y, Wang, E, Yuan, J, Zuo, J, Zhou, D, Li, B, Zhou, J, Jin, D & Zhang, H 2023, 'Significant Enhancement of the Upconversion Emission in Highly Er3+‐Doped Nanoparticles at Cryogenic Temperatures', Angewandte Chemie International Edition, vol. 62, no. 7.
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AbstractRelatively low efficiency is the bottleneck for the application of lanthanide‐doped upconversion nanoparticles (UCNPs). The high‐level doping strategy realized in recent years has not improved the efficiency as much as expected. It is argued that cross relaxation (CR) is not detrimental to upconversion. Here we combine theoretical simulation and spectroscopy to elucidate the role of CR in upconversion process of Er3+ highly doped (HD) UCNPs. It is found that if CR is purposively suppressed, upconversion efficiency can be significantly improved. Specifically, we demonstrate experimentally that inhibition of CR by introducing cryogenic environment (40 K) enhances upconversion emission by more than two orders of magnitude. This work not only elucidates the nature of CR and its non‐negligible adverse effects, but also provides a new perspective for improving upconversion efficiency. The result can be directly applied to cryogenic imaging and wide range temperature sensing.
Tu, L, Wu, K, Luo, Y, Wang, E, Yuan, J, Zuo, J, Zhou, D, Li, B, Zhou, J, Jin, D & Zhang, H 2023, 'Significant Enhancement of the Upconversion Emission in Highly Er3+‐Doped Nanoparticles at Cryogenic Temperatures', Angewandte Chemie, vol. 135, no. 7.
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AbstractRelatively low efficiency is the bottleneck for the application of lanthanide‐doped upconversion nanoparticles (UCNPs). The high‐level doping strategy realized in recent years has not improved the efficiency as much as expected. It is argued that cross relaxation (CR) is not detrimental to upconversion. Here we combine theoretical simulation and spectroscopy to elucidate the role of CR in upconversion process of Er3+ highly doped (HD) UCNPs. It is found that if CR is purposively suppressed, upconversion efficiency can be significantly improved. Specifically, we demonstrate experimentally that inhibition of CR by introducing cryogenic environment (40 K) enhances upconversion emission by more than two orders of magnitude. This work not only elucidates the nature of CR and its non‐negligible adverse effects, but also provides a new perspective for improving upconversion efficiency. The result can be directly applied to cryogenic imaging and wide range temperature sensing.
Vasilescu, SA, Ding, L, Parast, FY, Nosrati, R & Warkiani, ME 2023, 'Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods', Microsystems & Nanoengineering, vol. 9, no. 1, p. 37.
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AbstractSperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.
Wang, D, Wang, Y, Di, X, Wang, F, Wanninayaka, A, Carnell, M, Hardeman, EC, Jin, D & Gunning, PW 2023, 'Cortical tension drug screen links mitotic spindle integrity to Rho pathway', Current Biology, vol. 33, no. 20, pp. 4458-4469.e4.
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Wu, S, Yang, Z, Ma, C, Zhang, X, Mi, C, Zhou, J, Guo, Z & Jin, D 2023, 'Deep learning enhanced NIR-II volumetric imaging of whole mice vasculature', Opto-Electronic Advances, vol. 6, no. 4, pp. 220105-220105.
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Yaghoubi Naei, V, Bordhan, P, Mirakhorli, F, Khorrami, M, Shrestha, J, Nazari, H, Kulasinghe, A & Ebrahimi Warkiani, M 2023, 'Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA', Therapeutic Advances in Medical Oncology, vol. 15.
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Over the past decade, the detection and analysis of liquid biopsy biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have advanced significantly. They have received recognition for their clinical usefulness in detecting cancer at an early stage, monitoring disease, and evaluating treatment response. The emergence of liquid biopsy has been a helpful development, as it offers a minimally invasive, rapid, real-time monitoring, and possible alternative to traditional tissue biopsies. In resource-limited settings, the ideal platform for liquid biopsy should not only extract more CTCs or ctDNA from a minimal sample volume but also accurately represent the molecular heterogeneity of the patient’s disease. This review covers novel strategies and advancements in CTC and ctDNA-based liquid biopsy platforms, including microfluidic applications and comprehensive analysis of molecular complexity. We discuss these systems’ operational principles and performance efficiencies, as well as future opportunities and challenges for their implementation in clinical settings. In addition, we emphasize the importance of integrated platforms that incorporate machine learning and artificial intelligence in accurate liquid biopsy detection systems, which can greatly improve cancer management and enable precision diagnostics.
Zhand, S, Zhu, Y, Nazari, H, Sadraeian, M, Warkiani, ME & Jin, D 2023, 'Correction to “Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA”', Analytical Chemistry, vol. 95, no. 32, pp. 12193-12193.
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Zhand, S, Zhu, Y, Nazari, H, Sadraeian, M, Warkiani, ME & Jin, D 2023, 'Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA', Analytical Chemistry, vol. 95, no. 6, pp. 3228-3237.
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Catalytic DNAzymes have been used for isothermal amplification and rapid detection of nucleic acids, holding the potential for point-of-care testing applications. However, when Subzymes (universal substrate and DNAzyme) are tethered to the polystyrene magnetic microparticles via biotin-streptavidin bonds, the residual free Subzymes are often detached from the microparticle surface, which causes a significant degree of false positives. Here, we attached dithiol-modified Subzyme to gold nanoparticle and improved the limit of detection (LoD) by 200 times compared to that using magnetic microparticles. As a proof of concept, we applied our new method for the detection of exosomal programed cell-death ligand 1 (PD-L1) RNA. As the classical immune checkpoint, molecule PD-L1, found in small extracellular vesicles (sEVs, traditionally called exosomes), can reflect the antitumor immune response for predicting immunotherapy response. We achieved the LoD as low as 50 fM in detecting both the RNA homologous to the PD-L1 gene and exosomal PD-L1 RNAs extracted from epithelioid and nonepithelioid subtypes of mesothelioma cell lines, which only takes 8 min of reaction time. As the first application of isothermal DNAzymes for detecting exosomal PD-L1 RNA, this work suggests new point-of-care testing potentials toward clinical translations.
Zhang, H, Chen, Y, Hua, W, Gu, W, Zhuang, H, Li, H, Jiang, X, Mao, Y, Liu, Y, Jin, D & Bu, W 2023, 'Heterostructures with Built‐in Electric Fields for Long‐lasting Chemodynamic Therapy', Angewandte Chemie International Edition, vol. 62, no. 15.
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AbstractSustained signal activation by hydroxyl radicals (⋅OH) has great significance, especially for tumor treatment, but remains challenging. Here, a built‐in electric field (BIEF)‐driven strategy was proposed for sustainable generation of ⋅OH, thereby achieving long‐lasting chemodynamic therapy (LCDT). As a proof of concept, a novel Janus‐like Fe@Fe3O4−Cu2O heterogeneous catalyst was designed and synthesized, in which the BIEF induced the transfer of electrons in the Fe core to the surface, reducing ≡Cu2+ to ≡Cu+, thus achieving continuous Fenton‐like reactions and ⋅OH release for over 18 h, which is approximately 12 times longer than that of Fe3O4−Cu2O and 72 times longer than that of Cu2O nanoparticles. In vitro and in vivo antitumor results indicated that sustained ⋅OH levels led to persistent extracellular regulated protein kinases (ERK) signal activation and irreparable oxidative damage to tumor cells, which promoted irreversible tumor apoptosis. Importantly, this strategy provides ideas for developing long‐acting nanoplatforms for various applications.
Zhang, H, Chen, Y, Hua, W, Gu, W, Zhuang, H, Li, H, Jiang, X, Mao, Y, Liu, Y, Jin, D & Bu, W 2023, 'Heterostructures with Built‐in Electric Fields for Long‐lasting Chemodynamic Therapy', Angewandte Chemie, vol. 135, no. 15.
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AbstractSustained signal activation by hydroxyl radicals (⋅OH) has great significance, especially for tumor treatment, but remains challenging. Here, a built‐in electric field (BIEF)‐driven strategy was proposed for sustainable generation of ⋅OH, thereby achieving long‐lasting chemodynamic therapy (LCDT). As a proof of concept, a novel Janus‐like Fe@Fe3O4−Cu2O heterogeneous catalyst was designed and synthesized, in which the BIEF induced the transfer of electrons in the Fe core to the surface, reducing ≡Cu2+ to ≡Cu+, thus achieving continuous Fenton‐like reactions and ⋅OH release for over 18 h, which is approximately 12 times longer than that of Fe3O4−Cu2O and 72 times longer than that of Cu2O nanoparticles. In vitro and in vivo antitumor results indicated that sustained ⋅OH levels led to persistent extracellular regulated protein kinases (ERK) signal activation and irreparable oxidative damage to tumor cells, which promoted irreversible tumor apoptosis. Importantly, this strategy provides ideas for developing long‐acting nanoplatforms for various applications.
Zhang, L & Jin, D 2023, 'Cytometry and analytical methods in COVID‐19 diagnostics and potential treatment: A special issue on Cytometry Part A', Cytometry Part A, vol. 103, no. 2, pp. 105-106.
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Zhang, L, Cao, C, Tay, SS, Chen, C, Macmillan, A, Wen, S, Jin, D, McCarroll, J & Stenzel, MH 2023, 'Exploring the Effect of Drug Loading on the Biological Fate of Polymer-Coated Solid Nanoparticles', Chemistry of Materials, vol. 35, no. 11, pp. 4471-4488.
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Zhao, YC, Zhang, Y, Wang, Z, Jiang, F, Kyanian, K, Aye, S, Hong, T, Vatankhah, P, Nasser, A, Sun, A, Moldovan, L, Su, QP, Cho, A, Wang, Y, Passam, F, Ang, T & Ju, LA 2023, 'Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis', Advanced Functional Materials, vol. 33, no. 23.
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AbstractThe Vein‐Chip recapitulates CVST Virchow's triad and enables systematic characterization of venous thrombogenesis with respect to fibrin formation and platelet aggregation. Distinct from the arterial setting, platelets universally adhere across the entire CVS Vein‐Chip independent of stenotic geometry and flow disturbance. Intriguingly, fibrin propagates along with the flow direction, but exclusively deposits to the inner vessel wall. Upon inflammatory endothelial injury, fibrin deposition mirrors to the outer vessel wall, but still not in the lumen. Together, the Vein‐Chip promises future applications for personalized thrombotic assessment and monitoring.
Zhao, YC, Zhang, Y, Wang, Z, Jiang, F, Kyanian, K, Aye, S, Hong, T, Vatankhah, P, Nasser, A, Sun, A, Moldovan, L, Su, QP, Cho, A, Wang, Y, Passam, F, Ang, T & Ju, LA 2023, 'Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis (Adv. Funct. Mater. 23/2023)', Advanced Functional Materials, vol. 33, no. 23.
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Zhu, Y, Luo, X, Yu, Z, Wen, S, Bao, G, Zhang, L, Zhang, C & Xian, Y 2023, 'Dye-sensitized rare-earth-doped nanoprobe for simultaneously enhanced NIR-II imaging and precise treatment of bacterial infection', Acta Biomaterialia, vol. 170, pp. 532-542.
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Zou, F, Liu, Y, Chen, Z, Zhanghao, K & Jin, D 2023, 'Fourier Channel Attention Powered Lightweight Network for Image Segmentation', IEEE Journal of Translational Engineering in Health and Medicine, vol. 11, pp. 252-260.
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Afrose, D, Nikolic, V, Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Hansbro, P, Su, P & McClements, L 2023, 'Uric acid is a promising biomarker and target of preeclampsia', Elsevier BV, pp. e50-e50.
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Cai, Y, Shang, Y, Qin, X, Jin, D & zhou, J 2023, 'Anisotropic surface quenching of upconversion nanoparticles', Research Square Platform LLC.
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Cartland, SP, Patil, M, Boccanfuso, L, Kelland, E, Patrick, R, Manuneedhi Cholan, P, Su, P, Alwis, I, Ganss, R, Harvey, RP, Griffith, TS, Powell, J, Patel, S & Kavurma, MM 2023, 'Abstract 597: TRAIL-TRAIL-R Ligation Regulates EC-pericyte Crosstalk To Generate Stable Microvessel Networks In Ischemia', Ovid Technologies (Wolters Kluwer Health).
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Endothelial cell (EC)-pericyte crosstalk is essential for generating stable capillary networks. Capillary function and development is disrupted in CVD, and processes mediating this are poorly understood. TNF-related apoptosis-inducing ligand (TRAIL) stimulates blood vessel development in pre-clinical models, while circulating levels are suppressed in CVD patients. The contribution of EC-specific TRAIL to angiogenesis in ischemia is unknown. To address this, an EC-specific TRAIL knockout ( Trail EC-/- ) was generated. Compared to Trail EC+/+ , Trail EC-/- mice had ~60% reduction in plasma TRAIL, revealing the endothelium as a significant source of TRAIL in the healthy circulation. Angiogenesis was quantified in the Matrigel plug, aortic sprouting and hindlimb ischemia (HLI) models. EC/pericyte content in plugs were ~50-60% less in Trail EC-/- than Trail EC+/+ mice, with a ~50% reduction in mRNA expression of angiogenesis/pericyte markers. Trail EC-/- aortic segments had reduced microvascular sprouts in hypoxia, and ECs lacking TRAIL had an impaired ability to form tubules and recruit pericytes. CD31 + SMA + microvessel numbers (measure of EC-pericyte interaction) were signif...
Ghorbanpour, S, Richards, C, Cole, L, McGrath, K, Warkiani, ME & McClements, L 2023, 'New 3D multicellular models of placental tissue for studying important mechanisms of preeclampsia', Elsevier BV, pp. e6-e6.
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Ghorbanpour, S, Richards, C, Pienaar, D, Sesperez, K, Aboulkheyr Es, H, Nikolic, V, Karadzov-Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Alqudah, A, Cole, L, Gorrie, C, Mcgrath, K, Kavurma, MM, Warkiani, ME & McClements, L 2023, 'SC3_3. FKBPL signalling in placental development and preeclampsia', Elsevier BV, pp. e77-e78.
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Goss, DM, Vasilescu, SA, Vasilescu, PA, Cooke, S, Kim, SHK, Sacks, GP, Gardner, DK & Warkiani, ME 2023, 'AI facilitated sperm detection in azoospermic samples for use in ICSI', Cold Spring Harbor Laboratory.
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Jin, D, Mi, C, Zhang, X, Yang, C, Wu, J, Chen, X, Ma, C, Wu, S, Yang, Z, Qiao, P, Liu, Y, Wu, W, Guo, Z, Liao, J, zhou, J, Guan, M, Liang, C & Liu, C 2023, 'Bone Disease Imaging through the Near-Infrared-II Window', Research Square Platform LLC.
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Ju, L, Wang, H, Vatankhah, P, Wang, Y, Russel, B, Su, Q, Zhou, Z, Cox, C & Jin, J 2023, 'Microscale geometrical modulation of PIEZO1 mediated cell mechanosensing via cytoskeletal redistribution buckle', Research Square Platform LLC.
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McClements, L, Ghorbanpour, S, Cartland, S, Seth, S, Ecker, R, Richards, C, McGrath, K, Cole, L, Warkiani, M & Kavurma, M 2023, 'FK506-Binding Protein Like (FKBPL) Regulates Hypoxia-induced Factor-α and Restores Endothelial Function and Vascular Integrity in Ischaemia-induced Angiogenesis', Elsevier BV, pp. S412-S412.
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Mi, C, Zhang, X, Yang, C, Wu, J, Chen, X, Ma, C, Wu, S, Yang, Z, Qiao, P, Liu, Y, Wu, W, Guo, Z, Liao, J, Zhou, J, Guan, M, Liang, C, Liu, C & Jin, D 2023, 'Nanoparticles Passive Targeting Allows Optical Imaging of Bone Diseases'.
Owen, B, Kechagidis, K, Bazaz, SR, Enjalbert, R, Essmann, E, Mallorie, C, Mirghaderi, F, Schaaf, C, Thota, K, Vernekar, R, Zhou, Q, Warkiani, ME, Stark, H & Krüger, T 2023, 'Lattice-Boltzmann Modelling for Inertial Particle Microfluidics Applications — A Tutorial Review', Cold Spring Harbor Laboratory.
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Phan, TH, Shi, H, Denes, CE, Cole, AJ, Wang, Y, Cheng, YY, Hesselson, D, Neely, GG, Jang, J-H & Chrzanowski, W 2023, 'Advanced pathophysiology mimicking lung models for accelerated drug discovery', Research Square Platform LLC.
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Ren, B, He, H, Cao, M, Gao, Y, Zheng, P, Yan, S, Zhong, J-H, Wang, L & Jin, D 2023, 'Noise Learning of Instruments for High-contrast, High-resolution and Fast Hyperspectral Microscopy and Nanoscopy', Research Square Platform LLC.
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Richards, C, Rad, DM, Zhand, S, Warkiani, M & McClements, L 2023, 'Evaluating gene delivery technologies to investigate the role of FKBPL in trophoblast function and the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles', Elsevier BV, pp. e48-e49.
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Shrestha, J, Paudel, KR, Nazari, H, Dharwal, V, Bazaz, SR, Johansen, MD, Dua, K, Hansbro, PM & Warkiani, ME 2023, 'Front Cover Image, Volume 43, Issue 5', Wiley, pp. i-i.
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Stylianou, N, Sebina, I, Matigian, N, Monkman, J, Doehler, H, Röhl, J, Allenby, M, Nam, A, Pan, L, Rockstroh, A, Sadeghirad, H, Chung, K, Sobanski, T, O’Byrne, K, Ana Clara Simoes, FA, Rebutini, PZ, Machado-Souza, C, Stonoga, ETS, Warkiani, ME, Salomon, C, Short, K, McClements, L, de Noronha, L, Huang, R, Belz, GT, Souza-Fonseca-Guimaraes, F, Clifton, V & Kulasinghe, A 2023, 'Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures', Cold Spring Harbor Laboratory.
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Tang, S-J, Zhang, M, Sun, J, Meng, J-W, Xiong, X, Gong, Q, Jin, D, Yang, Q-F & Xiao, Y-F 2023, 'Single-particle vibrational spectroscopy using optical microresonators'.
Xi, P, Xu, X, Wang, W, Qiao, L, Fu, Y, Ge, X, Zhao, K, Zhanghao, K, Guan, M, Chen, X, Li, M & Jin, D 2023, 'Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy (PAR-SIM)', Research Square Platform LLC.
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Xiang, M, Jiang, Y, zhou, J, Bao, G, Luo, X, Zhang, L, Jin, D, Xian, Y & Zhang, C 2023, 'NIR Light-Controlled DNA Nanodevice for Amplified mRNA Imaging and Precise Gene Therapy', Research Square Platform LLC.
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