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1.
Nucleic Acids Res ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570230

RESUMO

To date, only some cancer patients can benefit from chemotherapy and targeted therapy. Drug resistance continues to be a major and challenging problem facing current cancer research. Rapidly accumulated patient-derived clinical transcriptomic data with cancer drug response bring opportunities for exploring molecular determinants of drug response, but meanwhile pose challenges for data management, integration, and reuse. Here we present the Cancer Treatment Response gene signature DataBase (CTR-DB, http://ctrdb.ncpsb.org.cn/), a unique database for basic and clinical researchers to access, integrate, and reuse clinical transcriptomes with cancer drug response. CTR-DB has collected and uniformly reprocessed 83 patient-derived pre-treatment transcriptomic source datasets with manually curated cancer drug response information, involving 28 histological cancer types, 123 drugs, and 5139 patient samples. These data are browsable, searchable, and downloadable. Moreover, CTR-DB supports single-dataset exploration (including differential gene expression, receiver operating characteristic curve, functional enrichment, sensitizing drug search, and tumor microenvironment analyses), and multiple-dataset combination and comparison, as well as biomarker validation function, which provide insights into the drug resistance mechanism, predictive biomarker discovery and validation, drug combination, and resistance mechanism heterogeneity.

2.
Int J Biol Macromol ; 190: 11-18, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478791

RESUMO

The development of advanced energy storage systems, such as rechargeable batteries and supercapacitors (SCs), is one of the great challenges related to energy demand with the rapid development of world economy. Herein, a three-dimensional hierarchical porous lignin-derived carbon/WO3 (HPC/WO3) was prepared by carbonization and solvothermal process. This electrode material for supercapacitor can be operated at a wide voltage window range of -0.4 V to 1.0 V. More importantly, 3HPC/WO3 with ultrahigh mass loading (~3.56 mg cm-2) has excellent specific capacitance of 432 F g-1 at 0.5 A g-1 and cycling stability of 86.6% after 10,000 cycles at 10 A g-1. The as-assembled asymmetrical supercapacitor shows an energy density of 34.2 W h kg-1 at a power density of 237 W kg-1 and energy density of 16 W h kg-1 at a power density is 14,300 W kg-1. A solid-state planar micro-supercapacitor (MSC) was fabricated using HPC/WO3 nanocomposites. Moreover, the calculated specific capacity of MSC was 20 mF cm-2 in polyvinyl alcohol-sulfuric acid gel electrolyte. Overall, through the reasonable design of HPC/WO3 nanocomposite materials and the efficient assembly of MSCs, the performance of the device was greatly improved, thus providing a clear strategy for the development of energy storage devices.

3.
J Org Chem ; 86(17): 12386-12393, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34378932

RESUMO

In this paper, visible-light-induced deoxyalkynylation of activated tertiary alcohols has been successfully performed under mild reaction conditions with ethynylbenziodoxole as the readily available alkynylation reagent. The desired C(sp3)-C(sp) coupling can smoothly occur with 4-CzIPN as a photocatalyst, affording a wide range of valuable alkynylation products bearing quaternary carbon centers in 37-84% yields.

4.
Inorg Chem ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34352170

RESUMO

Manufacturing heteroatom-doped porous C with controllable N species is an important issue for supercapacitors. Herein, we report a low-cost and simplified strategy for synthesizing B,N-codoped porous C (BNPC) by a freeze-drying chitosan-boric acid aerogel beads and subsequent carbonization treatment. The BNPC samples were studied using various characterization technologies. The introduction of boric acid to chitosan successfully induced the formation of B,N-codoped C with a well-developed 3D interconnected porous structure. The B doping had a significant impact on the distribution of N species in the samples. Moreover, the good wettability of the sample resulting from B doping is favorable for electrolyte diffusion and ion transport. As a consequence, the optimal BNPC sample showed an excellent specific capacitance of 240 F g-1 at 0.5 A g-1 and an outstanding capacitance retention of 95.1% after 10000 cycles at 5 A g-1. An assembled symmetrical supercapacitor displayed an energy density of 11.4 Wh kg-1 at a power density of 250 W kg-1. The proposed work provides a simple and effective method to obtain B,N-codoped C-based materials with high electrochemical performance.

5.
Ecotoxicology ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379244

RESUMO

Microzooplanton play a crucial role in marine ecosystems, as they transfer matter and energy from pico- and nano-phytoplankton to mesozooplankton. In this study, we explored the seasonal variations of microzooplankton grazing derived from dilution experiments in a typical eutrophic coast of Southern China, as well as the abundance and biodiversity of its key group (ciliate), to further understand its function in the subtropical coastal food web associated with potential regulation factors. A total of 29 ciliate species belonging to 18 genera were identified, with the dominating species of Mesodinium rubrum, Strombidium globosaneum and Strombidium conicum. The spatial difference of ciliates abundance was attributed by the changes of temperature and salinity. Phytoplankton growth rate (µ) and microzooplankton grazing rate (m) ranged from 0.03 to 1.36 d-1 and 0.10 to 1.57 d-1, respectively, and both µ and m showed the highest values in summer and the lowest in winter. Moreover, microzooplankton grazing pressure on the phytoplankton standing stocks and potential primary production ranged from 10% to 79% and 58% to 471%, respectively. Our results indicated that temperature is the main environmental driving force for the seasonal changes of µ and m, and that the impacts of run-offs from the Pearl River and offshore seawater intrusion from the South China Sea are responsible for the spatial-temporal variations of phytoplankton growth and microzooplankton grazing.

6.
J Cell Mol Med ; 25(18): 8645-8661, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347392

RESUMO

Myocardin-related transcription factor-A/serum response factor (MRTF-A/SRF), a well-known transcriptional programme, has been proposed to play crucial roles in skeletal muscle development and function. However, whether MRTF-A participates in muscle regeneration and the molecular mechanisms are not completely understood. Here, we show that MRTF-A levels are highly correlated with myogenic genes using a RNA-seq assay, which reveal that MRTF-A knockdown in C2C12 cells significantly reduces PAX7 expression. Subsequent in vitro and in vivo data show that MRTF-A and PAX7 present identical expression patterns during myoblast differentiation and CTX-induced muscle injury and repair. Remarkably, MRTF-A overexpression promotes myoblast proliferation, while inhibiting cell differentiation and the expression of MyoD and MyoG. MRTF-A loss of function produces the opposite effect. Moreover, mice with lentivirus (MRTF-A) injection possesses more PAX7+ satellite cells, but less differentiating MyoD+ and MyoG+ cells, leading subsequently to diminished muscle regeneration. Our mechanistic results reveal that MRTF-A contributes to PAX7-mediated myoblast self-renewal, proliferation, and differentiation by binding to its distal CArG box. Overall, we propose that MRTF-A functions as a novel PAX7 regulator upon myoblast commitment to differentiation, which could provide pathways for dictating muscle stem cell fate and open new avenues to explore stem cell-based therapy for muscle degenerative diseases.

7.
Vaccines (Basel) ; 9(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34452016

RESUMO

The need for a cold chain system during storage and transport substantially increases the cost of vaccines. Virus-like particles (VLPs) are among the best countermeasures against foot and mouth disease virus (FMDV). However, VLPs are composed of pure proteins, and thus, are susceptible to heat. To address this problem, four simple biomimetic mineralization methods with the use of calcium phosphate were developed to improve heat tolerance via biomineralization. The results showed that biomineralization can significantly improve the heat resistance of VLPs. The biomineralized VLPs can be stored at low as 25 °C for eight days, and 37 °C for four days. Animal experiments showed that biomineralization had no effect on the immunogenicity of VLPs or the expression of specific antibodies (Abs) and neutralizing Abs. Even after heat treatment at 37 °C for four days, the biomineralized VLPs remained immunogenic and produced highly specific and neutralizing Abs with a high rate of protection. These results suggest that these biomineralization approaches can promote the thermal stability of VLPs against and significantly reduce dependence on cold storage and delivery systems.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34322817

RESUMO

This study focused on the removal of organic matter and nitrogen and explored the feasible operation strategies to achieve short-cut nitrification and denitrification in two constructed wetlands (CWs), which were designed to treat the actual landfill leachate from a small county in parallel. The two CWs were horizontal sub-surface flow constructed wetlands (HFCW) with partial-area aeration and vertical sub-surface flow constructed wetlands (VFCW) with full-area aeration. The experimental results showed that both CWs could achieve an excellent organic matter and nitrogen removal performance under the conditions of intermittent aeration with high frequency and medium intensity (2 h of aeration and 4 h of rest). The removal efficiencies of COD and total nitrogen by HFCW were 89.08% and 73.22%, and the corresponding values of VFCW were 84.51% and 71.44%, respectively. Meanwhile, the inhibition kinetics model indicated that HFCW with partial-area aeration could enhance the free ammonium (FA) tolerance of ammonium-oxidizing bacteria (AOB) and reduce the conversion percentage of ammonia nitrogen. In addition, the intermittent aeration mode with high frequency and medium intensity could keep the DO concentration below under 0.60 mg L-1 in HFCW, which helped to achieve stable short-cut nitrification and ensure the average nitrite accumulation rate (NAR) reach 50.96%. These results suggested that the intermittent aeration in partial-area could achieve successful short-cut nitrification in HFCW, thereby improving the removal efficiency of nitrogen in landfill leachate.

9.
J Am Chem Soc ; 143(28): 10735-10742, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34242004

RESUMO

Fluorescence anisotropy (FA) holds great potential for multiplexed analysis and imaging of biomolecules since it can effectively discriminate fluorophores with overlapping emission spectra. Nevertheless, its susceptibility to environmental variation hampers its widespread applications in biology and biotechnology. In this study, we design FA DNA frameworks (FAFs) by scaffolding fluorophores in a fluorescent protein-like microenvironment. We find that the FA stability of the fluorophores is remarkably improved due to the sequestration effects of FAFs. The FA level of the fluorophores can be finely tuned when placed at different locations on an FAF, analogous to spectral shifts of protein-bound fluorophores. The high programmability of FAFs further enables the design of a spectrum of encoded FA barcodes for multiplexed sensing of nucleic acids and multiplexed labeling of live cells. This FAF system thus establishes a new paradigm for designing multiplexing FA probes for cellular imaging and other biological applications.

10.
J Org Chem ; 86(17): 12443-12451, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34324330

RESUMO

Deconstructive functionalization of cyclic amines can provide access to chemicals with diverse skeletons. We report the conversion of tertiary amines to thiocarbamoyl fluorides, a reaction enabled by photoredox catalysis and tolerating different functional groups while avoiding strong oxidants. A one-pot synthetic method from tertiary amines and AgF has been developed to get access to trifluoromethylamines. The synthesized thiocarbamoyl fluorides can be further transferred into esters.

11.
Dalton Trans ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231593

RESUMO

In recent years, smart windows have been gradually applied and developed in the fields of environmental protection, energy management, smart camouflage and display. With the continuous upgrading of market demand, smart windows with both visible and infrared band modulation functions are the future development trends. However, the optical modulation of smart windows is usually limited in the visible light band (380-780 nm). In this paper, we report a novel smart window by doping antimony doped tin oxide (ATO) nanoparticles (NPs) into polymer stabilized liquid crystal (PSLC) films. These films have the widest waveband modulation function among those reported so far, covering the visible and infrared regions (380-5500 nm). The transmittance of the as-prepared smart films can be changed reversibly from highly transparent (78.5%) state to a strong light scattering (10%) state in the visible region. In addition, due to the localized surface plasmon resonance of ATO NPs, up to 80.7% of the infrared invisible light can be effectively shielded. The significance of this research is to provide theoretical and technical support for the broadband optical modulation of novel smart windows.

12.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 988-996, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34133712

RESUMO

The ubiquitin-proteasome system (UPS) plays a central role in regulating protein homeostasis in tumor progression. The proteasome subunit Rpn10 is associated with the progression of several tumor types. However, little is known regarding the role of Rpn10 in clear cell renal cell carcinoma (ccRCC). In this study, we found that overexpression of Rpn10 increased ccRCC cell proliferation, migration, and invasion. Silencing Rpn10 expression resulted in decreased cell proli-feration, migration, and invasion in ccRCC cells. Knockdown of Rpn10 inhibits tumor growth and cell proliferation in vivo. Furthermore, we demonstrated that Rpn10 increased cell proliferation, migration, and invasion via regulation of the nuclear factor kappa B (NF-κB) pathway. Rpn10 directly promoted inhibitor of nuclear factor-kappa B alpha (IκBα) degradation through the UPS. Moreover, we observed that upregulation of Rpn10 or downregulation of IκBα in ccRCC was associated with poor prognosis. We found that the combination of these two parameters was a more powerful predictor of poor prognosis than either parameter alone. Collectively, these findings provide evidence that Rpn10 promotes the progression of ccRCC by regulation of the NF-κB pathways and is a prognostic indicator for patients with ccRCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , NF-kappa B/metabolismo , Proteínas de Ligação a RNA/biossíntese , Transdução de Sinais , Regulação para Cima , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Células HEK293 , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , NF-kappa B/genética , Proteínas de Ligação a RNA/genética
13.
Diagn Interv Radiol ; 27(3): 315-322, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34003119

RESUMO

PURPOSE: We aimed to compare the diagnostic performance and interobserver variability in breast tumor classification with or without the aid of an innovative dual-mode artificial intelligence (AI) architecture, which can automatically integrate information from ultrasonography (US) and shear-wave elastography (SWE). METHODS: Diagnostic performance assessment was performed with a test subset, containing 599 images (from September 2018 to February 2019) from 91 patients including 64 benign and 27 malignant breast tumors. Six radiologists (three inexperienced, three experienced) were assigned to read images independently (independent diagnosis) and then make a secondary diagnosis with the knowledge of AI results. Sensitivity, specificity, accuracy, receiver-operator characteristics (ROC) curve analysis and Cohen's κ statistics were calculated. RESULTS: In the inexperienced radiologists' group, the average area under the ROC curve (AUC) for diagnostic performance increased from 0.722 to 0.765 (p = 0.050) with secondary diagnosis using US-mode and from 0.794 to 0.834 (p = 0.019) with secondary diagnosis using dual-mode compared with independent diagnosis. In the experienced radiologists' group, the average AUC for diagnostic performance was significantly higher with AI system using the US-mode (0.812 vs. 0.833, p = 0.039), but not for dual-mode (0.858 vs. 0.866, p = 0.458). Using the US-mode, interobserver agreement among all radiologists improved from fair to moderate (p = 0.003). Using the dual-mode, substantial agreement was seen among the experienced radiologists (0.65 to 0.74, p = 0.017) and all radiologists (0.62 to 0.73, p = 0.001). CONCLUSION: AI assistance provides a more pronounced improvement in diagnostic performance for the inexperienced radiologists; meanwhile, the experienced radiologists benefit more from AI in reducing interobserver variability.


Assuntos
Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Radiologistas , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassom , Ultrassonografia Mamária
14.
Anal Chim Acta ; 1168: 338621, 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34051991

RESUMO

Leucine aminopeptidase (LAP) as an important proteolytic enzyme, has been mainly found in hepatobiliary cells, and overexpressed in hepatoma cells. Herein, a new highly selective red-emitting fluorescent probe (DCDHF-Ala) for LAP has been synthesized based on 2-dicyanomethyldiene-3-cyano-2, 5-dihydrofuran (DCDHF) as fluorophore, and alanine (Ala) as the detection group. More importantly, it's the first time to use Ala as a reactive group for LAP. DCDHF-Ala has a low detection limit (0.20 U/L), excellent water solubility and cell membrane permeability. In addition, the probe has been successfully applied to fluorescent imaging in cells and zebrafish. It's especially worth mentioning that, DCDHF-Ala has a high biosafety and enables a real-time detection of LAP levels in mice model. What's the most important is that DCDHF-Ala may be an effective tool to qualitatively monitor the upregulation of LAP induced by liver injury and liver cancer.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Neoplasias Hepáticas , Animais , Corantes Fluorescentes , Neoplasias Hepáticas/diagnóstico por imagem , Camundongos , Imagem Óptica , Peixe-Zebra
15.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 395-403, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33645143

RESUMO

Breast cancer is the most common cancer in women. At present, the in vivo model and traditional cell culture are mainly used in breast cancer researches. However, as high as 90% clinical trials are failed for drugs explored by the above two methods, due to the inherent species differences between humans and animals, as well as the differences in the tissue structure between organs and cells. Therefore, organoid three-dimensional culture is emerging. As a new tumor research model, organoid, a three-dimensional cell complex with spatial structure, has broad application prospects, such as precision medicine, organ transplantation, establishment of refractory disease model, gene therapy and drug research and development. Therefore, organoid is considered as one of the ideal carriers for life science research in the future. Breast cancer, a heterogeneous disease with complex phenotypes, has a low survival rate. Breast cancer organoid can reproduce many key features of human breast cancer, thus, the construction of organoid biological library of breast cancer will provide a new platform for studying the occurrence, development, metastasis and drug resistance mechanism of breast cancer. In this review, we systematically introduce the culture conditions of organoids and their application in breast cancer related research, and the application prospect of organoids.


Assuntos
Neoplasias da Mama , Organoides , Animais , Técnicas de Cultura de Células , Feminino , Humanos , Medicina de Precisão , Pesquisa
16.
Opt Lett ; 46(6): 1369-1372, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720189

RESUMO

Plasmonic hollow fibers are fabricated by coating silver-/ gold-alloyed nanoparticles (Ag-Au-ANPs) onto the inner walls of hollow fibers. In this Letter, the Ag-Au-ANPs were synthesized chemically and dissolved in acetone to prepare a colloidal solution, flowed subsequently through the hollow fiber multiple times so that a thin layer of colloidal Ag-Au-ANPs was produced on the inner wall. Annealing at 400°C enabled melting/aggregation of the metallic nanoparticles and consequent formation of closely arranged plasmonic nanostructures fixed solidly on the inner wall. A surface-enhanced Raman scattering (SERS) mechanism was thus established for the liquids flowing through the hollows. The SERS measurements show an enhancement factor >104 for such plasmonic hollow fibers in the direct detection of R6G/ethanol solutions. Confinement of the excitation laser energy inside the hollow space represents an additional contribution to the enhancement mechanism. This is a promising design for the direct on-site SERS detection of molecules in flowing liquids with low concentrations.

17.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33432986

RESUMO

OBJECTIVE: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches. MATERIALS AND METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets. RESULTS: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways. CONCLUSION: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.

18.
Nanotheranostics ; 5(1): 73-89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391976

RESUMO

Microfluidic chip is not a chip in the traditional sense. It is technologies that control fluids at the micro level. As a burgeoning biochip, microfluidic chips integrate multiple disciplines, including physiology, pathology, cell biology, biophysics, engineering mechanics, mechanical design, materials science, and so on. The application of microfluidic chip has shown tremendous promise in the field of cancer therapy in the past three decades. Various types of cell and tissue cultures, including 2D cell culture, 3D cell culture and tissue organoid culture could be performed on microfluidic chips. Patient-derived cancer cells and tissues can be cultured on microfluidic chips in a visible, controllable, and high-throughput manner, which greatly advances the process of personalized medicine. Moreover, the functionality of microfluidic chip is greatly expanding due to the customizable nature. In this review, we introduce its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs. We highlight the functions and recent development of microfluidic chip to provide references for advancing cancer diagnosis and treatment.


Assuntos
Técnicas Analíticas Microfluídicas/instrumentação , Neoplasias/diagnóstico , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico
20.
Endocr J ; 68(2): 153-162, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32938833

RESUMO

Type 2 diabetes (T2D) is a chronic endocrine disorder with rapidly increasing prevalence worldwide. Genetic instability leading to metabolic dysfunction plays an important role in T2D susceptibility and progression. Structural alteration in genome, that is, copy number variation (CNV) is emerging as the inherent marker for disease identification. Previous genomic CNV array revealed that protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene was overlapped with a CNV region, however, whether this CNV affected T2D risk remains to be further elucidated. In this study, we first identified divergent distributions of the PTPN22 copy number (CN) between T2D patients and healthy controls in Chinese population (p < 0.01). Risk assessment analysis revealed that the CN gain (OR = 3.28, p < 0.001) was the promising risk factor for T2D. Also, significantly positive correlations of the PTPN22 CNV with fasting plasma glucose and glycated hemoglobin were demonstrated in T2D patients. Statistical association analysis investigated that the T2D individuals carrying CN gain showed higher plasma glucose and lower insulin levels than those carrying CN normal and loss at 60 min/120 min/180 min during an OGTT test. In addition, the PTPN22 CNV had an effect on total cholesterol, and the CN gain presented higher values than the other two CN types. These results suggested that the CN gain types of the PTPN22 gene accompany with the glycometabolism dysregulation, and finally predispose their carriers to T2D; therefore, the PTPN22 CNV may be a promising biomarker for predicting T2D risk, or a clinical target for T2D diagnosis and therapy.

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