Publications by authors named "Yue Ding"

246 Publications

A polytherapy based approach to combat antimicrobial resistance using cubosomes.

Nat Commun 2022 Jan 17;13(1):343. Epub 2022 Jan 17.

Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC, 3800, Australia.

A depleted antimicrobial drug pipeline combined with an increasing prevalence of Gram-negative 'superbugs' has increased interest in nano therapies to treat antibiotic resistance. As cubosomes and polymyxins disrupt the outer membrane of Gram-negative bacteria via different mechanisms, we herein examine the antimicrobial activity of polymyxin-loaded cubosomes and explore an alternative strategy via the polytherapy treatment of pathogens with cubosomes in combination with polymyxin. The polytherapy treatment substantially increases antimicrobial activity compared to polymyxin B-loaded cubosomes or polymyxin and cubosomes alone. Confocal microscopy and neutron reflectometry suggest the superior polytherapy activity is achieved via a two-step process. Firstly, electrostatic interactions between polymyxin and lipid A initially destabilize the outer membrane. Subsequently, an influx of cubosomes results in further membrane disruption via a lipid exchange process. These findings demonstrate that nanoparticle-based polytherapy treatments may potentially serve as improved alternatives to the conventional use of drug-loaded lipid nanoparticles for the treatment of "superbugs".
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http://dx.doi.org/10.1038/s41467-022-28012-5DOI Listing
January 2022

INCloud: integrated neuroimaging cloud for data collection, management, analysis and clinical translations.

Gen Psychiatr 2021 23;34(6):e100651. Epub 2021 Dec 23.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Neuroimaging techniques provide rich and accurate measures of brain structure and function, and have become one of the most popular methods in mental health and neuroscience research. Rapidly growing neuroimaging research generates massive amounts of data, bringing new challenges in data collection, large-scale data management, efficient computing requirements and data mining and analyses.

Aims: To tackle the challenges and promote the application of neuroimaging technology in clinical practice, we developed an integrated neuroimaging cloud (INCloud). INCloud provides a full-stack solution for the entire process of large-scale neuroimaging data collection, management, analysis and clinical applications.

Methods: INCloud consists of data acquisition systems, a data warehouse, automatic multimodal image quality check and processing systems, a brain feature library, a high-performance computing cluster and computer-aided diagnosis systems (CADS) for mental disorders. A unique design of INCloud is the brain feature library that converts the unit of data management from image to image features such as hippocampal volume. Connecting the CADS to the scientific database, INCloud allows the accumulation of scientific data to continuously improve the accuracy of objective diagnosis of mental disorders.

Results: Users can manage and analyze neuroimaging data on INCloud, without the need to download them to the local device. INCloud users can query, manage, analyze and share image features based on customized criteria. Several examples of 'mega-analyses' based on the brain feature library are shown.

Conclusions: Compared with traditional neuroimaging acquisition and analysis workflow, INCloud features safe and convenient data management and sharing, reduced technical requirements for researchers, high-efficiency computing and data mining, and straightforward translations to clinical service. The design and implementation of the system are also applicable to imaging research platforms in other fields.
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http://dx.doi.org/10.1136/gpsych-2021-100651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705204PMC
December 2021

NLRP3 promotes immune escape by regulating immune checkpoints: A pan-cancer analysis.

Int Immunopharmacol 2022 Jan 10;104:108512. Epub 2022 Jan 10.

Department of Hepatobiliary Pancreatic Surgery, the First Hospital of Ningbo City, Ningbo 315010, China. Electronic address:

NLRP3 plays a pathogenic role in tumorigenesis by regulating innate and acquired immunity, apoptosis, differentiation, and intestinal microbes in tumors. Our research aimed to investigate the role of NLRP3 in pan-cancers based on multi-omics data in the TCGA database. Most types of tumors showed increased expression of NLRP3. Among them, the overexpressed NLRP3 in liver hepatocellular carcinoma (LIHC) and ovarian cancer (OV) indicated worse overall survival (OS). Further analysis also confirmed overexpressed NLRP3 in colon cancer (COAD) indicated a high probability of microsatellite instability (MSI) and low tumor mutational burden (TMB), which indicated a better response to immune checkpoint inhibitors (ICIs). Interestingly, overexpression of NLRP3 was closely related to high infiltration of immune cells (T cells, B cells, etc.) and overexpressed immune checkpoints (PD-1, PD-L1, LAG3, etc.). These results demonstrated NLRP3 promoted immune escape in cancers. Finally, we investigated the expression of various immune checkpoints by treating NLRP3 inhibitor MCC950 during the co-culture of peripheral blood mononuclear cells (PBMC) and LIHC cell line Hep3B. MCC950 significantly repressed the expression of PD-L1 and LAG3, and promoted the apoptosis rate of Hep3B. In conclusion, our research demonstrated the role of NLRP3 in pan-cancer, especially in LIHC. Inhibition of NLRP3 promoted the killing effect of T cells to cancer cells by repressing the expression of immune checkpoints.
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http://dx.doi.org/10.1016/j.intimp.2021.108512DOI Listing
January 2022

Pillar[5]arene-derived covalent organic materials with pre-encoded molecular recognition for targeted and synergistic cancer photo- and chemotherapy.

Chem Commun (Camb) 2022 Jan 13. Epub 2022 Jan 13.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu, 226019, P. R. China.

An efficient targeted and synergistic cancer photo- and chemotherapy platform was constructed from aldehyde-modified pillar[5]arene and tetra-(4-aminophenyl)porphyrin successfully.
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http://dx.doi.org/10.1039/d1cc07072jDOI Listing
January 2022

Increased expression of osteopontin in subchondral bone promotes bone turnover and remodeling, and accelerates the progression of OA in a mouse model.

Aging (Albany NY) 2022 Jan 4;13(undefined). Epub 2022 Jan 4.

Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.

Osteopontin (OPN) has been proved to be closely related to the pathogenesis of osteoarthritis (OA), but the role of OPN in the pathogenesis of OA has not been fully clarified. Current studies on OPN in OA mostly focus on articular cartilage, synovial membrane and articular fluid, while ignoring its role in OA subchondral bone turnover and remodeling. In this study, we used a destabilization OA mouse model to investigate the role of OPN in OA subchondral bone changes. Our results indicate that increased expression of OPN accelerates the turnover and remodeling of OA subchondral bone, promotes the formation of h-type vessels in subchondral bone, and mediates articular cartilage degeneration induced by subchondral bone metabolism. In addition, our results confirmed that inhibition of PI3K/AKT signaling pathway inhibits OPN-mediated OA subchondral bone remodeling and cartilage degeneration. This study revealed the role and mechanism of OPN in OA subchondral bone, which is of great significance for exploring specific biological indicators for early diagnosis of OA and monitoring disease progression, as well as for developing drugs to regulate the metabolism and turnover of subchondral bone and alleviate the subchondral bone sclerosis of OA.
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http://dx.doi.org/10.18632/aging.203707DOI Listing
January 2022

Hierarchical cortical networks of "voice patches" for processing voices in human brain.

Proc Natl Acad Sci U S A 2021 Dec;118(52)

Tsinghua Laboratory of Brain and Intelligence (THBI), Tsinghua University, Beijing 100084, China;

Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as "voice patches." Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices.
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http://dx.doi.org/10.1073/pnas.2113887118DOI Listing
December 2021

Polydopamine-drug conjugate nanocomposites based on ZIF-8 for targeted cancer photothermal-chemotherapy.

J Biomed Mater Res A 2021 Dec 15. Epub 2021 Dec 15.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, China.

Stimuli-responsive prodrug-based nanoplatform with synergistic antitumor activity is of central importance to the development of promising nanomedicines for cancer therapy. Here, we describe a polydopamine-drug conjugate nanocomposite (ZP-PDA-DOX) with targeted cancer photothermal-chemotherapy (PTT-CT), which constructed by a gradual copolymerization of dopamine (DA) and pH-sensitive dopamine-derived prodrug (DA-DOX) into the porous channels of zeolite imidazolate frameworks-8 (ZIF-8), followed by PEGylation with amino-terminated folic acid-polyethylene glycol (NH -PEG-FA) to acquire the high biocompatibility, specificity, and excellent tumor-targeting property. The incorporation of polydopamine strengthened the stability and dispersion of ZIF-8, and also conferred photothermal conversion effect. In the tumor acidic microenvironment, the acid-labile hydrazone linker of DA-DOX and ZIF-8 promptly degraded to release activated DOX. Moreover, the generated hyperthermia due to the high photothermal conversion efficiency of PDA component could accelerate drug release, and simultaneously thermally ablate tumor tissue to maximize the DOX-induced CT, which could also assist PTT to eradicate tumor cells. This study provides a promising strategy for targeted cancer PTT-CT with synergistic anti-tumor effect.
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http://dx.doi.org/10.1002/jbm.a.37344DOI Listing
December 2021

Osteoporosis Diagnosis Based on Ultrasound Radio Frequency Signal via Multi-channel Convolutional Neural Network.

Annu Int Conf IEEE Eng Med Biol Soc 2021 11;2021:832-835

Osteoporosis is a metabolic osteopathy syndrome, and the incidence of osteoporosis increases significantly with age. Currently, bone quantitative ultrasound (QUS) has been considered as a potential method for screening and diagnosing osteoporosis. However, its diagnostic accuracy is quite low. By contrast, deep learning based methods have shown the great power for extracting the most discriminative features from complex data. To improve the osteoporosis diagnostic accuracy and take advantages of QUS, we devise a deep learning method based on ultrasound radio frequency (RF) signal. Specifically, we construct a multi-channel convolutional neural network (MCNN) combined with a sliding window scheme, which can enhance the number of data as well. By using speed of sound (SOS), the quantitative experimental results of our preliminary study indicate that our proposed osteoporosis diagnosis method outperforms the conventional ultrasound methods, which may assist the clinician for osteoporosis screening.
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http://dx.doi.org/10.1109/EMBC46164.2021.9629546DOI Listing
November 2021

Insights into N-Coordinated Bimetallic Site Synergy during NO Selective Catalytic Reduction by CO.

ACS Appl Mater Interfaces 2021 Dec 22;13(48):57182-57192. Epub 2021 Nov 22.

Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.

The nature of the synergistic effect in bimetallic catalysts remains a challenging issue, due to the difficulty in understanding the adjacent interaction between dual metals at the atomic level. Herein, a CuFe-N/C catalyst featuring diatomic metal-nitrogen sites was prepared through a sequential ion exchange strategy and applied for NO selective catalytic reduction by CO (CO-SCR). The bimetallic CuFe-N/C catalyst exhibits high N selectivity with a NO conversion efficiency of nearly 100% over a wide temperature range from 225 to 400 °C, significantly higher than that of its single-component counterparts. The synergistic effect of bimetallic Cu-Fe sites is well revealed using the combined FTIR technique and DFT calculations. Bifunctional Cu-Fe sites are demonstrated not only to provide two different preferential adsorption centers for the CO molecule and ONNO intermediate but also to achieve a complete electron cycle for efficient interfacial electron transfer upon ONNO uptake. The unique electron transfer mechanism stemmed from 4s-3d-type electron coupling, and different 3d shell fillings of Cu (3d) and Fe (3d) atoms are presented. These fundamental insights pave the way for the understanding of N-coordinated bimetallic site synergy and rational design of highly active atomic-scale metal catalysts for SCR applications.
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http://dx.doi.org/10.1021/acsami.1c17352DOI Listing
December 2021

Vasculitic Tibial Mononeuropathy Associated with Inherited Immune Dysregulation: A Review of Tibial Mononeuropathies with Electrodiagnostic Considerations.

Case Rep Neurol Med 2021 12;2021:7161757. Epub 2021 Nov 12.

University of Michigan, Ann Arbor, USA.

Compressive tibial mononeuropathies are uncommon and can be caused by conditions including posterior compartment syndrome, soleal sling syndrome, and tarsal tunnel syndrome. Therefore, it is critical to consider noncompressive etiologies when a tibial mononeuropathy is suspected. This is a patient with a history of rare inherited immune dysregulation that presented to the electrodiagnostic laboratory with severe neuropathic pain in the right foot associated with plantarflexion weakness, concerning for a tibial mononeuropathy. However, the patient's clinical presentation and results on electrodiagnostic testing were not consistent with any of the above entities. Therefore, noncompressive etiologies of tibial mononeuropathies such as vasculitis had to be considered. The patient subsequently underwent sural nerve biopsy which confirmed small-vessel vasculitis as the cause of the tibial mononeuropathy. She was then started on appropriate immunosuppressive treatment which resulted in significant pain relief and was discharged home. This case highlights the importance of considering noncompressive causes of tibial nerve injury. Compressive and vasculitic tibial mononeuropathies along with their electrodiagnostic considerations are reviewed. Furthermore, this case highlights the critical role of the electromyographer and ability to maximize the impact on patient care through a solid foundation in anatomy, pathophysiology, and electrodiagnosis blended with clinical acumen.
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http://dx.doi.org/10.1155/2021/7161757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604612PMC
November 2021

Enhancing the Stability and Photothermal Conversion Efficiency of ICG by Pillar[5]arene-Based Host-Guest Interaction.

Front Chem 2021 29;9:775436. Epub 2021 Oct 29.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, China.

Indocyanine green (ICG) is a classical near-infrared (NIR) photothermal reagent that can be employed in clinical medical detection. Under neutral conditions, ICG can adsorb NIR light effectively for photothermal (PTT) and photodynamic (PDT) therapy. However, ICG is easily degraded in weak acid environments, which seriously restricts its application. In this work, a cationic water-soluble pillar[5]arene (WP5) was selected as the stabilizing agent for ICG. Thanks to the host-guest interaction between WP5 and alkyl sulfonate, the stability and the photothermal conversion efficiency of ICG increased remarkably upon addition of WP5 as investigated by UV-vis spectrum and photothermal studies. Furthermore, an study showed higher efficiency of WP5&ICG in killing cancer cells in a shorter treatment time than the free ICG. Hence, it is hopeful that WP5 can be a new type of supramolecular host in enhancing the stability and photothermal conversion efficiency of photosensitizers.
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http://dx.doi.org/10.3389/fchem.2021.775436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586498PMC
October 2021

BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm.

Biochem Biophys Res Commun 2021 Nov 1;583:169-177. Epub 2021 Nov 1.

State Key Laboratory of Reproductive Medicine, Center for Reproduction and Genetics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, China. Electronic address:

Spermatogonia are accountable for spermatogenesis and male fertility, but the underlying mechanisms involved in spermatogonia maintenance are not clear. B lymphoma Mo-MLV insertion region 1 (BMI1) is a key component of epigenetic silencers. BMI1 is essential for stem-cell maintenance. Here, we attempted to uncover the role of BMI1 in spermatogonia maintenance using a mouse spermatogonia cell line (GC-1) and Bmi1-knockout (KO) mouse model. We showed that BMI1 promoted the proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, we present in vitro and in vivo evidence to show that BMI1 binds to the promoter region of the Protein tyrosine phosphatase receptor type M (PTPRM) gene, thereby driving chromatin remodeling and gene silencing. Knockdown of Ptprm expression significantly improved spermatogonia proliferation in BMI1-deficient GC-1 cells. Collectively, our data show, for the first time, an epigenetic mechanism involving in BMI1-mediated gene silencing in spermatogonia maintenance, and provide potential targets for the treatment of male infertility.
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http://dx.doi.org/10.1016/j.bbrc.2021.10.074DOI Listing
November 2021

Porcine uterine luminal fluid-derived extracellular vesicles improve conceptus-endometrial interaction during implantation.

Theriogenology 2022 Jan 23;178:8-17. Epub 2021 Oct 23.

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China; Lingnan Guangdong Laboratory of Modern Agriculture, Guangzhou, China. Electronic address:

Successful implantation of porcine conceptus requires synergistic interaction with various signal molecules in the maternal uterus. Extracellular vesicles (EVs) in uterine luminal fluid (ULF) of mice play important roles in conceptus development. However, studies have not explored the roles of extracellular vesicles (EV) in ULF of pigs. The aim of this study was to identify characteristics, origin, and roles of ULF-derived EVs on day 9 of the estrous cycle and on day 9,12 and 15 of pregnancy in pigs. Western blot, BCA assay and HE staining analysis showed increase in EVs concentration in ULF began from day 12 of pregnancy. Immunofluorescence staining and transmission electron microscopy analysis showed that EVs were mainly derived from endometrial epithelial cells. Fluorescent labeling, CCK-8 and transwell migration assays showed that these EVs were delivered to the trophoblast or parthenogenetic activation embryos to regulate proliferation and migration of trophoblast cells. A total of 305 miRNAs were identified using small RNA sequencing analysis. Functional enrichment analysis showed that miRNAs in these EVs potentially play vital regulatory functions in EV transportation or conceptus implantation. QRT-PCR analysis was used to further verify the RNA-seq data. The findings of this study provide information on the functions of porcine ULF-derived EVs and provide a reference dataset for future translational studies on porcine ULF-derived EVs.
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http://dx.doi.org/10.1016/j.theriogenology.2021.10.021DOI Listing
January 2022

A-DA'D-A fused-ring small molecule-based nanoparticles for combined photothermal and photodynamic therapy of cancer.

Chem Commun (Camb) 2021 Nov 11;57(90):12020-12023. Epub 2021 Nov 11.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu, 226019, P. R. China.

New nanoparticles (Y6 NPs) based on the A-DA'D-A fused-ring conjugated small molecule Y6 have been prepared for the combined photothermal and photodynamic therapy of cancer. Y6 NPs show excellent light absorption from 300 to 900 nm, a good photothermal conversion efficiency of 57% and reactive oxygen species generation capability. The high photothermal conversion ability and superior photodynamic activity of Y6 NPs endow them with great potential for cancer therapy.
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http://dx.doi.org/10.1039/d1cc04629bDOI Listing
November 2021

Identification of Prognosis-Related RNA-Binding Proteins to Reveal the Role of RNA-Binding Proteins in the Progression and Prognosis of Colon Cancer.

Int J Gen Med 2021 14;14:6795-6805. Epub 2021 Oct 14.

Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People's Republic of China.

Background: RNA binding proteins (RBPs) are now under discussion as novel promising bio-markers for patients with colon cancer. The purpose of our study is to identify several RBPs related to the progression and prognosis of colon cancer and to further investigate the mechanism of their influence on tumor progression.

Methods: The transcriptome data of colon cancer and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to elucidate the gene functions and relative pathways. Cox and Lasso regression analyses were used to analyze the effect of immune genes on the prognosis of colon cancer. An immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate Cox regression analysis was utilized to investigate whether the immune gene risk score model was an independent factor for predicting the prognosis of colon cancer. A nomogram was constructed to comprehensively predict the survival rate of colon cancer. P < 0.05 was considered statistically significant.

Results: The results showed that 473 RBPs exhibited differential expression between normal and colon cancer tissues (P < 0.05). Univariate Cox regression analysis revealed 25 RBPs statistically correlated with colon cancer-related survival risk (P < 0.05). In addition, a 10-RBPs based risk scoring model was constructed through multivariate Cox regression analysis. A K-M curve indicated that high-risk patients were associated with poor outcomes (P < 0.001). A ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year overall survival (OS), area under curve (AUC) = 0.782). Our model showed satisfying AUC and survival correlation in the validation dataset (5-year OS, AUC = 0.744). Furthermore, multivariate Cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer. Finally, we found that 10-RBPs and risk scores were significantly associated with clinical factors and prognosis and were involved in multiple oncogenic pathways.

Conclusion: Collectively, RBPs play an essential role in the progression and prognosis of colon cancer by regulating multiple biological pathways. Furthermore, the RBP risk score was an independent predictive factor of colon cancer, indicating poor survival.
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http://dx.doi.org/10.2147/IJGM.S330863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523907PMC
October 2021

All-in-one: Accurate quantification, on-site detection, and bioimaging of sulfite using a colorimetric and ratiometric fluorescent probe in vitro and in vivo.

J Hazard Mater 2022 Feb 14;424(Pt B):127229. Epub 2021 Sep 14.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

SO and its derivatives (SO/HSO) are used widely in food, beverages, and pharmaceutical production. However, they could induce multiple diseases in respiratory, nervous, and cardiovascular systems. Although several fluorescent probes have been developed for detecting SO/HSO, reports on rapid fluorescent probes for the on-site detection of SO derivatives are scarce. Herein, a colorimetric and ratiometric fluorescent probe 1 based on the intramolecular charge transfer (ICT) was reported. Probe 1 resulted in a 122 nm blue-shift in fluorescent emission and decrement of absorbance at 500 nm upon the addition of sulfite. Therefore, probe 1 could quantify SO/HSO using both UV-Vis and fluorescent methods (LOD: UV-Vis method 34 nM; fluorescent method 51 nM). Importantly, probe 1 was used for a rapid (60 s) and convenient (1 step, on-site) measurement of the SO derivatives in real samples (LOD: 0.47 µM) using smartphone based on the colorimetric method. The SO/HSO-sensing mechanism was confirmed as the Michael addition reaction. Furthermore, the probe was used for the real-time monitoring of SO/HSO in A549 cells and zebrafish. In summary, an all-in-one fluorescent probe was successfully developed for the accurate quantification, on-site detection, and bioimaging of SO/HSO.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127229DOI Listing
February 2022

Novel Timosaponin AIII-Based Multifunctional Liposomal Delivery System for Synergistic Therapy Against Hepatocellular Carcinoma Cancer.

Int J Nanomedicine 2021 16;16:5531-5550. Epub 2021 Aug 16.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Introduction: As high cholesterol level has been reported to be associated with cancer cell growth and cholesterol is vulnerable to oxidation, the conventional liposomes including cholesterol in the formulation seem to be challenged. Timosaponin AIII (TAIII), as a steroid saponin from Bunge, possesses a similar structure with cholesterol and exhibits a wide range of antitumor activities, making it possible to develop a TAIII-based liposome where TAIII could potentially stabilize the phospholipid bilayer as a substitution of cholesterol and work as a chemotherapeutic drug as well. Meanwhile, TAIII could enhance the uptake of doxorubicin hydrochloride (DOX) in human hepatocellular carcinoma (HCC) cells and exhibit synergistic effect. Thus, we designed a novel thermally sensitive multifunctional liposomal system composed of TAIII and lipids to deliver DOX for enhanced HCC treatment.

Methods: The synergistic effects of DOX and TAIII were explored on HCC cells and the tumor inhibition rate of TAIII-based liposomes carrying DOX was evaluated on both subcutaneous and orthotopic transplantation tumor models. TAIII-based multifunctional liposomes were characterized.

Results: Synergistic HCC cytotoxicity was achieved at molar ratios of 1:1, 1:2 and 1:4 of DOX/TAIII. TAIII-based liposomes carrying a low DOX dose of 2 mg/kg exhibited significantly enhanced antitumor activity than 5 mg/kg of DOX without detected cardiotoxicity on both subcutaneous and orthotopic transplantation tumor models. TAIII-based liposomes were characterized with smaller size than cholesterol liposomes but exhibited favorable stability. Mild hyperthermia generated by laser irradiation accelerated the release of DOX and TAIII from liposomes at tumor site, and cell permeability of TAIII enhanced uptake of DOX in HCC cells.

Conclusion: The innovative application of TAIII working as bilayer stabilizer and chemotherapeutic drug affords a stable multifunctional liposomal delivery system for synergistic therapy against HCC, which may be referred for the development of other types of saponins with similar property.
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http://dx.doi.org/10.2147/IJN.S313759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379713PMC
October 2021

Inhibition of ultraviolet-induced sea cucumber (Stichopus japonicus) autolysis by maintaining coelomocyte intracellular calcium homeostasis.

Food Chem 2022 Jan 5;368:130768. Epub 2021 Aug 5.

Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, The North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA. Electronic address:

Apoptosis plays a critical role in sea cucumber autolysis. To investigate the ultraviolet (UV)-induced apoptosis, sea cucumbers with and without injection of BAPTA-AM (cytosolic calcium chelator) were exposed to UV (15 W/m) for 30 min. The results showed that UV irradiation caused several changes in sea cucumber coelomocytes, including calcium imbalance, abnormal morphology of endoplasmic reticulum, upregulation of pro-apoptotic proteins CRT, CHOP, and caspases 9 and 3, and downregulation of anti-apoptotic protein Bcl-2. A comparison between the two groups showed that injection of the calcium chelator into sea cucumbers helped maintain coelomocyte intracellular calcium homeostasis and suppressed other abnormal changes caused by ER stress, indicating apoptosis in sea cucumbers is mediated by calcium imbalance and follows the activation of the ER stress pathway. Therefore, this study broadens understanding of the apoptotic mechanism involved in sea cucumber autolysis, which is helpful in developing preservative agents for sea cucumbers.
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http://dx.doi.org/10.1016/j.foodchem.2021.130768DOI Listing
January 2022

Pandemic Risk Management for Public Health Care Schemes.

Front Public Health 2021 27;9:700021. Epub 2021 Jul 27.

Faculty of Finance and Accounting, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam.

The coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, has caused a large death, a range of serious health problems, and significant economic costs in many countries around the world. This study analyzes statistical characteristics of pandemic disasters using historical records since the Middle Ages. Compared to literature which studies the effect of the COVID- 19 pandemic on the financial market, this paper attempts to find two financial instruments in the financial market to hedge pandemic risks. Two instruments could be useful for public health care schemes to increase their assets or decrease their liabilities during the pandemic period, namely, assets in the form of a biotechnology investment portfolio and liabilities in the form of pandemic bonds. Empirical results show the feasibility of such instruments and the informational efficiency of the U.S. stock market.
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http://dx.doi.org/10.3389/fpubh.2021.700021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353108PMC
August 2021

The / Quorum Sensing System Effects on Pathogenicity in .

Front Microbiol 2021 12;12:679241. Epub 2021 Jul 12.

Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.

is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for healthcare institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion, and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic bases of virulence remains poorly understood. Therefore, the contribution of the / QS system to growth characteristics, morphology, biofilm formation, resistance, motility, and virulence of was studied in detail. RNA sequencing (RNA-seq) analysis indicated that genes involved in various aspects of energy production and conversion; valine, leucine, and isoleucine degradation; and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into the / QS system effects on pathogenicity in . We propose that targeting the acyl homoserine lactone (AHL) synthase enzyme could provide an effective strategy for attenuating virulence. On the contrary, interdicting the AI synthase receptor elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
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http://dx.doi.org/10.3389/fmicb.2021.679241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312687PMC
July 2021

Stimuli-responsive polypeptide nanoassemblies: Recent progress and applications in cancer nanomedicine.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2021 Jul 26:e1742. Epub 2021 Jul 26.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai, China.

Stimuli-responsive polypeptide nanoassemblies exhibit great potentials for cancer nanomedicines because of desirable biocompatibility and biodegradability, unique secondary conformations, varying functionalities, and especially the stimuli-enhanced therapeutic efficacy and reduced side effect. This review introduces the design and fabrication of stimuli-responsive polypeptide nanoassemblies that exhibit endogenous stimuli (e.g., pH, reduction, reactive oxygen species, adenosine triphosphate and enzyme, etc.) and exogenous light stimuli (e.g., UV and near-infrared light), which are biologically related or applied in the clinic. We also discuss the applications and prospects of those stimuli-responsive polypeptide nanoassemblies that might overcome the biological barriers of cancer nanomedicines for in vivo administration. Much more effort is needed to accelerate the second-generation stimuli-responsive polypeptide nanomedicines for clinical transition and applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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http://dx.doi.org/10.1002/wnan.1742DOI Listing
July 2021

Comparative Studies on Multi-Component Pharmacokinetics of Thunb Extract After Oral Administration in Different Rat Models.

Front Pharmacol 2021 17;12:655332. Epub 2021 Jun 17.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The clinical use of Thunb (PM) has been restricted or banned in many countries, due to its hepatotoxic adverse effects. Its toxicity research has become a hot topic. So far, the pharmacokinetic studies of PM, focusing on prototype compounds such as 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin, and physcion, have been considered the main basis of pharmacodynamic material or of toxic effect. However, pharmacokinetic studies of its phase II metabolites have not yet been reported, mainly because the quantifications of such metabolites are difficult to do without the reference substance. In addition, pharmacokinetic studies on different pathological models treated with PM have also not been reported. On the other hand, toxic effects of PM have been reported in patients diagnosed with different liver pathologies. In the present work, a simultaneous quantitation method for eight prototypes components of PM and their five phase II metabolites has been performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and used for the pharmacokinetic study of PM in two different liver pathological models in rats (normal, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl)). The results showed that the main blood-entering components of PM are TSG, emodin, physcion, emodin-8-O-β⁃D⁃glucoside (E-Glu), physcion-8-O-β⁃D⁃glucoside (P-Glu), aloe-emodin, gallic acid, resveratrol and catechin, among which TSG, emodin, and catechin were primary metabolized in phase II, while resveratrol was converted to all phase II metabolites, and the others were metabolized as drug prototypes. Meanwhile, their pharmacokinetic parameters in the different models also exhibited significant differences. For instance, the AUC (0-∞) values of the TSG prototype and its phase II metabolites were higher in the ANIT group, followed by CCl group and the normal group, while the AUC (0-∞) values of the emodin prototype and its phase II metabolites were higher in the CCl group. To further illustrate the reasons for the pharmacokinetic differences, bilirubin metabolizing enzymes and transporters in the liver were measured, and the correlations with the AUC of the main compounds were analyzed. TSG and aloe-emodin have significant negative correlations with UGT1A1, BSEP, OATP1A4, OCT1, NTCP, MRP2 and MDR1 ( < 0.01). These data suggest that when the expression of metabolic enzymes and transporters in the liver is inhibited, the exposure levels of some components of PM might be promoted .
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http://dx.doi.org/10.3389/fphar.2021.655332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245786PMC
June 2021

Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs.

Int J Mol Sci 2021 Jun 21;22(12). Epub 2021 Jun 21.

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal-fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.
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http://dx.doi.org/10.3390/ijms22126644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235555PMC
June 2021

RIPK3-Mediated Necroptosis in Diabetic Cardiomyopathy Requires CaMKII Activation.

Oxid Med Cell Longev 2021 7;2021:6617816. Epub 2021 Jun 7.

Department of Pharmacology, School of Pharmacy, Nantong University, Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong, 226001 Jiangsu, China.

Activation of Ca/calmodulin-dependent protein kinase (CaMKII) has been proved to play a vital role in cardiovascular diseases. Receptor-interaction protein kinase 3- (RIPK3-) mediated necroptosis has crucially participated in cardiac dysfunction. The study is aimed at investigating the effect as well as the mechanism of CaMKII activation and necroptosis on diabetic cardiomyopathy (DCM). Wild-type (WT) and the RIPK3 gene knockout (RIPK3) mice were intraperitoneally injected with 60 mg/kg/d streptozotocin (STZ) for 5 consecutive days. After 12 w of feeding, 100 L recombinant adenovirus solution carrying inhibitor 1 of protein phosphatase 1 (I1PP1) gene was injected into the caudal vein of mice. Echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK1 expression, mixed lineage kinase domain-like protein (MLKL) phosphorylation, and mitochondrial ultrastructure were measured. The results showed that cardiac dysfunction, CaMKII activation, and necroptosis were aggravated in streptozotocin- (STZ-) stimulated mice, as well as in (Lepr) KO/KO (db/db) mice. RIPK3 deficiency alleviated cardiac dysfunction, CaMKII activation, and necroptosis in DCM. Furthermore, I1PP1 overexpression reversed cardiac dysfunction, myocardial injury and necroptosis augment, and CaMKII activity enhancement in WT mice with DCM but not in RIPK3 mice with DCM. The present study demonstrated that CaMKII activation and necroptosis augment in DCM via a RIPK3-dependent manner, which may provide therapeutic strategies for DCM.
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http://dx.doi.org/10.1155/2021/6617816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203407PMC
January 2022

Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation.

Biochem Pharmacol 2021 10 25;192:114665. Epub 2021 Jun 25.

Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China. Electronic address:

Sirtuin3 (SIRT3) is involved in reactive oxygen species (ROS), cell metabolism, apoptosis and inflammation. However, the exact role of SIRT3 in macrophages during pathophysiological process of atherosclerosis remains unclear. The present study was to investigate the possible effects and mechanisms of SIRT3 on lipid uptake and foam cells transforming in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Compared with wild-type (WT) mice, SIRT3 deficiency further increased foam cell formation and cellular cholesterol accumulation, exacerbated oxidative stress, impaired mitochondrial permeability potential, decreased optic atrophy 1 (OPA1) but enhanced dynamin-related protein 1 (DRP1) expression, and promoted NLR family pyrin domain-containing protein 3 (NLRP3) activation in ox-LDL-stimulated macrophages from SIRT3 knockout (KO) mice. Dihydromyricetin (DMY), a potential compound to enhance SIRT3 expression, significantly inhibited cellular cholesterol accumulation, suppressed foam cell formation, improved mitochondrial function, attenuated oxidative stress, and alleviated NLRP3 activation in ox-LDL-stimulated macrophages. Moreover, above protective effects of DMY was unavailable in macrophages from SIRT3 KO mice. Collectively, the study demonstrated the protective role of SIRT3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation, which is beneficial to provide novel strategy for atherosclerosis prevention and treatment.
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http://dx.doi.org/10.1016/j.bcp.2021.114665DOI Listing
October 2021

Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis.

Stem Cell Res Ther 2021 05 20;12(1):295. Epub 2021 May 20.

Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.

Background: Mesenchymal stem cells (MSCs) can improve cutaneous wound healing via the secretion of growth factors. However, the therapeutic efficacy of MSCs varies depending upon their source. Induced pluripotent stem cells are emerging as a promising source of MSCs with the potential to overcome several limitations of adult MSCs. This study compared the effectiveness of conditioned medium of MSCs derived from induced pluripotent stem cells (iMSC-CdM) with that derived from umbilical cord MSCs (uMSC-CdM) in a mouse cutaneous wound healing model. We also investigated the mechanisms of protection.

Methods: The iMSC-CdM or uMSC-CdM were topically applied to mice cutaneous wound model. The recovery rate, scar formation, inflammation and angiogenesis were measured. We compared angiogenesis cytokine expression between iMSC-CdM and uMSC-CdM and their protective effects on human umbilical vein endothelial cells (HUVECs) under HO-induced injury. The effects of iMSC-CdM on energy metabolism, mitochondria fragmentation and apoptosis were measured.

Results: Topical application of iMSC-CdM was superior to the uMSC-CdM in accelerating wound closure and enhancing angiogenesis. Expression levels of angiogenetic cytokines were higher in iMSC-CdM than they were in uMSC-CdM. The iMSC-CdM protected HUVECs from HO induced injury more effectively than uMSC-CdM did. Administration of iMSC-CdM stimulated HUVEC proliferation, tube formation and energy metabolism via the ERK pathway. Mechanistically, iMSC-CdM inhibited HO-induced mitochondrial fragmentation and apoptosis of HUVECs.

Conclusion: Collectively, these findings indicate that iMSC-CdM is more effective than uMSC-CdM in treating cutaneous wounds, and in this way, iMSC-CdM may serve as a more constant and sustainable source for cell-free therapeutic approach.
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http://dx.doi.org/10.1186/s13287-021-02366-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139053PMC
May 2021

Platinum(II) Metallatriangle: Construction, Coassembly with Polypeptide, and Application in Combined Cancer Photodynamic and Chemotherapy.

Inorg Chem 2021 Jun 11;60(11):7627-7631. Epub 2021 May 11.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu 226019, P.R. China.

The development of the supramolecular coordination complex with different shapes and dimensionalities lays the basis for its application in different areas. In this study, a porphyrin-based 3D organo-Pt(II) metallatriangle () was fabricated through the reported method termed as "coordination driven self-assembly". P NMR, H NMR, HR-MS, and theoretical calculation were employed to characterize the resultant fully. Furthermore, the fabricated nanocomposite through coassembly of and an amphiphilic polypeptide () could generate singlet oxygen (O) under the NIR irradiation and release a Pt drug under a low-pH microenvironment. O and the Pt drug can both damage the cancer cells, which improves the efficiency of cancer therapies. The fabrication of a Pt-porphyrin metallatriangle expands the topological structures, and the Pt-porphyrin metallatriangle can be applied to the combined cancer therapies. Moreover, various stimuli-responsive groups can be modified to the triangle, so a new method is created to develop high-performance biosupramolecular materials.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00962DOI Listing
June 2021

Realizing ultra-stable TiC-MXene in aqueous solution surface grafting with ionomers.

Soft Matter 2021 May;17(18):4703-4706

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, 30 South PuZhu Road, Nanjing, Jiangsu 211816, China.

MXenes are the first class of 2D materials with the combination of metallic conductivity and hydrophilicity. However, degradation forms a key drawback limiting their long-term applications. This work for the first time demonstrates a strategy for designing a hydrophilic yet ultra-stable MXene via surface grafting with ionomers.
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http://dx.doi.org/10.1039/d1sm00508aDOI Listing
May 2021

Social Support and Mortality in Community-Dwelling Chinese Older Adults: The Mediating Role of Frailty.

Risk Manag Healthc Policy 2021 16;14:1583-1593. Epub 2021 Apr 16.

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China.

Purpose: Population ageing is posing an unprecedented challenge globally, necessitating a better understanding of modifiable factors and underlying pathways that could contribute to health and longevity in older age. We thus aim to investigate how the modifiable social support (and its various sources) is related to mortality among older adults, as well as whether and to what extent geriatric frailty plays a role in mediating the relationship.

Methods: We included 11,934 community-dwelling adults (≥65) from four waves of the Chinese Longitudinal Healthy Longevity Survey (2008-2018). Frailty was constructed by 44 health deficits, following a validated frailty index scale. Social support was measured using a sum score of three dimensions (family support, social service and social security) with 22 items. The outcome was all-cause mortality. Multivariate logistic or linear regression models were employed when appropriate to assess the associations among social support, frailty and mortality. Mediation analysis was applied to examine the role of frailty underlying the pathway between social support and mortality risk.

Results: A higher sum score of social support at baseline reduced mortality risk during the 10-year follow-up period (AOR=0.947, 95% CI=0.917~0.977). Amongst three sources of social support, family support and social security availability showed significantly protective effect against mortality, while social service revealed only non-significant effect. A higher level in the overall social support (β=-0.066, 95% CI=-0.113~-0.020) or family support (β=-0.121, 95% CI=-0.202~-0.039) was also significantly associated with decreased frailty. Meanwhile, frailty partially mediated the relationship of mortality with the overall social support and family support, where the proportion of mediation equaled to 17.1% and 20.5%, respectively.

Conclusion: Social support could be associated with reduced risks for frailty and mortality, and such protective influences are especially manifested in its family support component among Chinese older adults. Frailty functions as potential mediator underlying the association of mortality with social support and family support. Our findings indicate the importance of social support as an integral part of geriatric care and underline the potential benefits of frailty assessment and intervention.
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http://dx.doi.org/10.2147/RMHP.S296018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057827PMC
April 2021

An optic-fiber graphene field effect transistor biosensor for the detection of single-stranded DNA.

Anal Methods 2021 04;13(15):1839-1846

School of Physics and Electronics, Shandong Normal University, Jinan 250014, P. R. China.

Herein, a graphene field effect transistor (GFET) was constructed on an optic fiber end face to develop an integrated optical/electrical double read-out biosensor, which was used to detect target single-stranded DNA (tDNA). Two isolated Au electrodes were, respectively, prepared as the drain and source at the ends of an optic fiber and coated with a graphene film to construct a field effect transistor (FET). Probe aptamers modified with fluorophore 6'-carboxy-fluorescein (6'-FAM) were immobilized on the graphene for specific capture of tDNA. Graphene oxide (GO) was introduced to quench 6'-FAM and construct a fluorescence biosensor. Thus, a dual GFET and fluorescence biosensor was integrated on the end-face of an optic fiber. Following synchronous detection by fluorescence and FET methods, results showed satisfactory sensitivity for DNA detection. Compared with conventional biosensors using a single sensing technology, these dual sensing integrated biosensors significantly improved the reliability and accuracy of DNA detection. Furthermore, this proposed technique provides both a new biosensor for single-stranded DNA detection and a strategy for designing multi-sensing integrated biosensors.
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http://dx.doi.org/10.1039/d1ay00101aDOI Listing
April 2021
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