Publications by authors named "Qian Cheng"

817 Publications

Comprehensive analysis of dysregulated genes associated with atherosclerotic plaque destabilization.

Exp Biol Med (Maywood) 2021 Jul 25:15353702211033247. Epub 2021 Jul 25.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

Atherosclerotic plaque destabilization is a dominating cause of acute cardiovascular events such as myocardial infarction and stroke. This study aims to identify genetic biomarkers related to atherosclerotic plaque destabilization using bioinformatics. Three transcriptome datasets of human carotid atherosclerotic plaque samples were downloaded from ArrayExpress and Gene Expression Omnibus databases, including E-MATB-2055, E-TABM-190, and GSE120521. With Robust Rank Aggregation analysis, we documented 46 differentially expressed genes between stable and unstable/ruptured plaques. Functional enrichment analysis using DAVID tool demonstrated that these genes were mainly related to biological functions such as extracellular matrix disassembly, collagen catabolic process, response to mechanical stimulus, and PPAR signaling pathway. A protein-protein interaction network for the differentially expressed genes was constructed, and eight pivotal genes (, , , , , , , and ) were obtained from the network with a connective degree > 5. The expression patterns of these hub differentially expressed genes could be verified in atherosclerotic plaque samples with intraplaque hemorrhage. Using gene set variation analysis, the eight genes were integrated to generate an atherosclerotic plaque destabilization score, which showed a high performance in not only discriminating individuals with myocardial infarction from those with stable coronary illness, but also in predicting future acute cardiovascular events in atherosclerotic patients. In conclusion, the findings of this study will enhance our knowledge on the pathological mechanisms involved in atherosclerotic plaque destabilization, and provide potential gene biomarkers for risk stratification of patients with atherosclerotic cardiovascular disease.
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http://dx.doi.org/10.1177/15353702211033247DOI Listing
July 2021

Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose.

Elife 2021 Jul 16;10. Epub 2021 Jul 16.

State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.

Vesicular neurotransmitter transporters (VNTs) mediate the selective uptake and enrichment of small molecule neurotransmitters into synaptic vesicles (SVs) and are therefore a major determinant of the synaptic output of specific neurons. To identify novel VNTs expressed on SVs (thus identifying new neurotransmitters and/or neuromodulators), we conducted localization profiling of 361 solute carrier (SLC) transporters tagging with a fluorescent protein in neurons, which revealed 40 possible candidates through comparison with a known SV marker. We parallelly performed proteomics analysis of immunoisolated SVs and identified 7 transporters in overlap. Ultrastructural analysis confirmed one of the transporters, SLC35D3, localized to SVs. Finally, by combining metabolite profiling with a radiolabeled substrate transport assay, we identified UDP-glucose as the principal substrate for SLC35D3. These results provide new insights into the functional role of SLC transporters in neurotransmission and improve our understanding of the molecular diversity of chemical transmitters.
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http://dx.doi.org/10.7554/eLife.65417DOI Listing
July 2021

Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy.

Acta Biomater 2021 Jul 12. Epub 2021 Jul 12.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, and MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau 999078, China. Electronic address:

Photodynamic therapy (PDT), where a photosensitizer (under light irradiation) converts molecular oxygen to singlet oxygen to elicit programmed cell death, is a promising cancer treatment modality with a high temporal and spatial resolution. However, only limited cancer treatment efficacy has been achieved in clinical PDT due to the hypoxic conditions of solid tumor microenvironment that limits the generation of singlet oxygen, and PDT process often leads to even more hypoxic microenvironment due to the consumption of oxygens during therapy. Herein, we designed novel supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles (CPC) were derived from a polyethylene glycol (PEG) system dually tagged with hydrophilic cucurbit[7]uril (CB[7]) and hydrophobic Chlorin e6 (Ce6) respectively on each end, for synergistic antitumor therapy via PDT of Ce6 and chemotherapy of a hypoxia-responsive prodrug, banoxantrone (AQ4N), loaded into the cavity of CB[7]. In addition, CPC was further modularly functionalized by folate (FA) via strong host-guest interaction between folate-amantadine (FA-ADA) and CB[7] to produce a novel nanoplatform, [email protected], for targeted delivery. [email protected] exhibited enhanced cellular uptake, negligible cytotoxicity and good biocompatibility, and improved intracellular reactive oxygen species (ROS) generation efficiency. More importantly, in vivo evaluation of [email protected] revealed a synergistic antitumor efficacy between PDT of Ce6 and hypoxia-activated chemotherapy of AQ4N (that can be converted to chemotherapeutic AQ4 for tumor chemotherapy in response to the strengthened hypoxic tumor microenvironment during PDT treatment). This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment, but also offers important new insights to design and development of multifunctional supramolecular drug delivery system.
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http://dx.doi.org/10.1016/j.actbio.2021.07.014DOI Listing
July 2021

Self-Propelled Asymmetrical Nanomotor for Self-Reported Gas Therapy.

Small 2021 Jul 14:e2102286. Epub 2021 Jul 14.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, 999078, P. R. China.

Gas therapy has emerged as a new therapeutic strategy in combating cancer owing to its high therapeutic efficacy and biosafety. However, the clinical translation of gas therapy remains challenging due to the rapid diffusion and limited tissue penetration of therapeutic gases. Herein, a self-propelled, asymmetrical [email protected] nanomotor for efficient delivery of therapeutic gas to deep-seated cancer tissue for enhanced efficacy of gas therapy, is reported. The [email protected] nanoparticles (NPs) catalyze endogenous H O into O that propels NPs into deep solid tumors, where SO prodrug is released from the hollow NPs owing to the degradation of MnO shells. Fluorescein isothiocyanate (FITC) is conjugated onto the surface of Au via caspase-3 responsive peptide (DEVD) and the therapeutic process of gas therapy can be optically self-reported by the fluorescence of FITC that is turned on in the presence of overexpressed caspase-3 as an apoptosis indicator. [email protected] nanomotors show self-reported therapeutic efficacy and high biocompatibility both in vitro and in vivo, offering important new insights to the design and development of novel nanomotors for efficient payload delivery into deep tumor tissue and in situ monitoring of the therapeutic process.
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http://dx.doi.org/10.1002/smll.202102286DOI Listing
July 2021

Redox environment metabolomic evaluation (REME) of the heart after myocardial ischemia/reperfusion injury.

Free Radic Biol Med 2021 Jul 9;173:7-18. Epub 2021 Jul 9.

Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China. Electronic address:

Myocardial ischemia/reperfusion injury (MIRI) is closely related to oxidative stress. However, the redox environment of the heart has not been evaluated thoroughly after MIRI, which limits precise redox intervention. In this study, we developed the redox environment metabolomic evaluation (REME) method to analyze the redox metabolites of the heart after MIRI. Based on the targeted metabolomics strategy, we established a detection panel for 22 redox-related molecules, including the major redox couples nicotinamide adenine dinucleotide (NADH/NAD+), nicotinamide adenine dinucleotide phosphate (NADPH/NADP+), and glutathione/glutathione disulfide (GSH/GSSG), reactive oxygen and nitrogen species-related molecules, and some lipid peroxidation products. The high sensitivity and specificity of the method make it suitable for evaluating the endogenous redox environment. The REME method showed that the heart tissue in a MIRI mouse model had a different redox profile from that in the control group. Different redox species changed in different ways. The ratios of GSSG/GSH and NADP+/NADPH increased, but the levels of both NAD+ and NADH decreased in the risk area of the infarcted heart after reperfusion. In addition, some reactive nitrogen species-related metabolites (tetrahydrobiopterin, arginine, and S-nitrosoglutathione) decreased and some lipid peroxides (4-hydroxy-2-nonenal, 4-hydroxy-2-hexenal, and benzaldehyde) increased. The redox metabolites GSH, GSSG, NADPH, NAD+, S-nitrosoglutathione, arginine, and tetrahydrobiopterin had a positive correlation with the ejection fraction and a negative correlation with the level of lactate dehydrogenase in plasma. In summary, we achieved a comprehensive, systemic understanding of the changes in the redox environment after MIRI. Our REME method could be used to evaluate the redox environment in other processes.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.06.033DOI Listing
July 2021

The development of a wash-free homogeneous immunoassay method for the detection of tetracycline in environmental samples.

Analyst 2021 Jul;146(15):4918-4926

Research Center of Analytical Instrumentation, Northwest University, Xi'an, Shaanxi 710069, China. and Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, Shaanxi 710069, China.

Antibiotic residues have become the major source of environmental pollutants. In order to monitor tetracycline (TC) in the environment, we have established a highly sensitive and wash-free homogeneous time-resolved immunoassay. This analytical method was based on a rare earth chelate with excellent fluorescence properties. The cryptate organic ligand had good stability and acted as an antenna for Eu3+ excitation. In a homogeneous system, the Eu3+ cryptate complex was used as a label to bind to antibodies. Under the action of immunoaffinity, fluorescent donors and acceptors were close to each other, which induced the FRET effect to produce proportional fluorescence. Under the optimal parameters, the half-inhibitory concentration (IC50) and limit of detection (LOD, IC10) of TC were 0.4188 ng mL-1 and 0.0106 ng mL-1, respectively. The linear range (IC20-IC80) was 0.0273-9.2645 ng mL-1. With the environmental samples, the recovery rate of TC was 84.3-107.2%, and the standard deviation (RSD) was 4.6-12.9%. The results showed the good sensitivity and reliability of the method. Compared with the traditional ELISA, our method has less background interference, only one step was required without the washing procedure, and the detection result can be obtained by 30 min incubation, which improves the detection efficiency. Because of the characteristics of immunoassays, different pollutants can be monitored by changing the antibodies. This method provides an alternative path for detecting environmental pollutants and has the potential to develop into an on-site detection kit.
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http://dx.doi.org/10.1039/d1an00929jDOI Listing
July 2021

IDH Mutation Subgroup Status Associates with Intratumor Heterogeneity and the Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.

Adv Sci (Weinh) 2021 Jul 11:e2101230. Epub 2021 Jul 11.

Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China.

Intrahepatic cholangiocarcinoma (ICC) is highly heterogeneous. Here, the authors perform exome sequencing and bulk RNA sequencing on 73 tumor regions from 14 ICC patients to portray the multi-faceted intratumor heterogeneity (ITH) landscape of ICC. The authors show that ITH is highly concordant across genomic, transcriptomic, and immune levels. Comparison of these data to 8 published datasets reveals significantly higher degrees of ITH in ICC than hepatocellular carcinoma. Remarkably, the authors find that high-ITH tumors highly overlap with the IDH (isocitrate dehydrogenase)-mutant subgroup (IDH-SG), comprising of IDH-mutated tumors and IDH-like tumors, that is, those IDH-wildtype tumors that exhibit similar molecular profiles to the IDH-mutated ones. Furthermore, IDH-SG exhibits less T cell infiltration and lower T cell cytotoxicity, indicating a colder tumor microenvironment (TME). The higher ITH and colder TME of IDH-SG are successfully validated by single-cell RNA sequencing on 17 503 cells from 4 patients. Collectively, the study shows that IDH mutant subgroup status, rather than IDH mutation alone, is associated with ITH and the TME of ICC tumors. The results highlight that IDH-like patients may also benefit from IDH targeted therapies and provide important implications for the diagnosis and treatment of ICC.
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http://dx.doi.org/10.1002/advs.202101230DOI Listing
July 2021

Fuxin Granules ameliorate diabetic nephropathy in db/db mice through TGF-β1/Smad and VEGF/VEGFR2 signaling pathways.

Biomed Pharmacother 2021 Jul 7;141:111806. Epub 2021 Jul 7.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for Traditional Chinese Medicine(TCM) Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine(TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Diabetic nephropathy (DN) is a common disease, and patients often do not have satisfactory treatments. We investigated therapeutic effects of Fuxin Granules(FX) on DN and potential molecular mechanisms. We orally administered doses of FX to db/db mice for 10 weeks and measured total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol. H&E, PAS, Masson, and Oil Red O staining were used to observe the structure of kidneys and calculate indices of kidney function. We used pharmacological analysis to investigate potential mechanisms of FX. Relative mRNA and protein levels in the TGF-β1/Smad, TGF-β1/Smad, and VEGF/VEGFR2 pathways were examined. TC, TG, and LDL-C were markedly reduced, lipid accumulation was low, fibrosis reduced, kidney atrophy improved, kidney lipid droplet number significantly reduced, and glomerular filtration function improved by FX treatment. Multi-channel therapeutic effects in DN through the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways occurred, and FX substantially reduced expression of TGF-β1 in the glomeruli. FX significantly inhibited TGF-β1, Smad2/3 total protein levels, Smad2/3 phosphorylation mRNA levels of TGF-β1, Smad2, and Smad3. eNOS, VEGFA, and VEGFR2 expression was regulated, levels of VEGFA and VEGFR2 were decreased, and FX increased eNOS. FX ameliorated symptoms of DN, resulting in marked improvement in hyperglycemia and hyperlipidemia and optimized structure and function of kidneys in db/db mice. FX efficacy was associated with the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways. We verified this potential mechanism and hope that this study will provide benefits for the clinical treatment of DN.
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http://dx.doi.org/10.1016/j.biopha.2021.111806DOI Listing
July 2021

NKG2D Enhances Double-Negative T Cell Regulation of B Cells.

Front Immunol 2021 16;12:650788. Epub 2021 Jun 16.

Department of Hepatobiliary Surgery, Peking University Organ Transplantation Institute, Peking University People's Hospital, Beijing, China.

Numerous studies reported a small subpopulation of TCRαβCD4CD8 (double-negative) T cells that exert regulatory functions in the peripheral lymphocyte population. However, the origin of these double-negative T (DNT) cells is controversial. Some researchers reported that DNT cells originated from the thymus, and others argued that these cells are derived from peripheral immune induction. We report a possible mechanism for the induction of nonregulatory CD4 T cells to become regulatory double-negative T (iDNT) cells . We found that immature bone marrow dendritic cells (CD86MHC-II DCs), rather than mature DCs (CD86MHC-II), induced high levels of iDNT cells. The addition of an anti-MHC-II antibody to the CD86MHC-II DC group significantly increased induction. These iDNT cells promoted B cell apoptosis and inhibited B cell proliferation and plasma cell formation. A subgroup of iDNT cells expressed NKG2D. Compared to NKG2D iDNT cells, NKG2D iDNT cells released more granzyme B to enhance B cell regulation. This enhancement may function NKG2D ligands expressed on B cells following lipopolysaccharide stimulation. These results demonstrate that MHC-II impedes induction, and iDNT cells may be MHC independent. NKG2D expression on iDNT cells enhanced the regulatory function of these cells. Our findings elucidate one possible mechanism of the induction of peripheral immune tolerance and provide a potential treatment for chronic allograft rejection in the future.
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http://dx.doi.org/10.3389/fimmu.2021.650788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242353PMC
June 2021

An analysis of delay-constrained consensus-based optimal algorithms in virtual power plants.

ISA Trans 2021 Jun 28. Epub 2021 Jun 28.

State Key Laboratory of Power Transmission Equipment and System Security at Chongqing University, Chongqing 400044, China. Electronic address:

In virtual power plants (VPPs), consensus-based distributed optimal dispatch algorithms aim to collectively minimize the operating cost. As ubiquitous latency on communication networks may lead to divergence, convergence to a nonoptimal solution, or a longer convergence time, mitigating the impacts of arbitrarily large but bounded time-varying delays is significant both in theory and in practice. To modify a typical consensus-based optimal dispatch algorithm under time-varying delays, this paper designs new update rules and introduces a reduction approach to evaluate the performance of the algorithm. The results reveal that the modified algorithm can always converge to the optimal solution with a tactical initial setup in a distributed manner if the undirected interaction topology is connected and the gain parameter is sufficiently small. The analytical expression of the gain is also given. Furthermore, we show that the convergence time is determined by the maximum time delays, the number of generators, and the convergence accuracy. Several numerical simulation studies validate our theory.
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http://dx.doi.org/10.1016/j.isatra.2021.06.035DOI Listing
June 2021

Methylphenidate and atomoxetine treatment negatively affect physical growth indexes of school-age children and adolescents with attention-deficit/hyperactivity disorder.

Pharmacol Biochem Behav 2021 Jul 1;208:173225. Epub 2021 Jul 1.

Growth, Development, and Mental Health Center of Children and Adolescents, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400014, China; Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing 400014, China; China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing 400014, China; National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China. Electronic address:

Aim: To determine the effects of drug therapy on the physical growth of school-age children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

Method: The medical records of 86 participants (average age: 8.9 ± 2.2 years) with ADHD prescribed methylphenidate (MPH) or atomoxetine (ATX) for ≥24 weeks from the Children's Hospital of Chongqing Medical University were analysed.

Results: The Z-scores of height, weight and body mass index (BMI) of children with ADHD decreased significantly over the first six months of MPH treatment (P < 0.001). The slopes of the fitting lines after the first six months of MPH (-0.18, -0.58 and -0.69, respectively) returned over the entire treatment (the slopes changed to -0.027, -0.26 and -0.20, respectively). For ATX, the Z-scores of height of children decreased significantly over the first six months (P < 0.001), but the Z-scores of weight and BMI did not (P > 0.05). The slopes of the fitting lines after the first six months of ATX (-0.058, -0.032 and 0.0094, respectively) changed over the entire treatment (slopes were 0.16, 0.52 and 0.26, respectively). Children taking MPH were more likely to report decreased appetite (P < 0.05). The weight and BMI of the children receiving MPH were significantly correlated with decreased appetite (P < 0.01).

Conclusion: The physical growth indexes (PGIs) of school-age children and adolescents with ADHD were negatively affected while taking MPH, and these effects were gradually mitigated with continued treatment. ATX hardly had negative effects on weight and BMI. Neither MPH nor ATX had a significant negative effect on the height of children in long-term ADHD treatment. It is necessary for clinicians to consider children's diet during treatment.
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http://dx.doi.org/10.1016/j.pbb.2021.173225DOI Listing
July 2021

Hollow performances quenching label of Au [email protected] nanoboxes-based sandwich photoelectrochemical immunosensor for sensitive CYFRA 21-1 detection.

Talanta 2021 Oct 27;233:122552. Epub 2021 May 27.

Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, PR China. Electronic address:

In this work, a fire-new "signal-off" type photoelectrochemical (PEC) immunosensor based on bismuth sulfide/iodine doped bismuth oxychloride (BiS/I:BiOCl) heterostructure as a platform and Au nanoparticles loaded hollow CoSnO nanoboxes (Au [email protected]) as quenching label was designed, for sensitive detection of CYFRA 21-1. The I:BiOCl with flower-like structure could supply high specific surface area for loading nanometer materials. Then, BiS was formed in-situ by S adsorption on the surface of I:BiOCl by dangling bond of Bi, but did not change the flower-like structure of I:BiOCl. Then, n-type BiS and p-type I:BiOCl heterostructure showed good photoelectric behavior by providing an additional electric field to accelerate electron-hole separation. Furthermore, the production process of the heterostructure was simple, fast, low temperature, and without complex raw materials. The Au [email protected] with good photocatalytic activity could strongly compete with BiS/I:BiOCl for electron donor of ascorbic acid (AA). Meanwhile, the CoSnO with hollow structure made the quenching effect more significant by the light-scattering effect that enhanced the light absorption capacity and shorten distance of carrier transport. Under optimal conditions, this proposed strategy displayed the low detection limit of 30 fg/mL, with a high linearity range from 100 fg/mL to 100 ng/mL for tumor markers CYFRA 21-1. Simultaneously, it also exhibited excellent specificity and acceptable stability, which might provide a new perspective for the fabrication of other PEC immunosensors with heterostructure simple synthesis and hollow materials.
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http://dx.doi.org/10.1016/j.talanta.2021.122552DOI Listing
October 2021

Prevalence of Mycobacterium tuberculosis resistant to Bedaquiline and Delamanid in China.

J Glob Antimicrob Resist 2021 Jun 29. Epub 2021 Jun 29.

National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address:

Objectives: New anti-TB drugs delamanid and bedaquiline appear as the last line to defense drug-resistant tuberculosis. Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs' effectiveness and inform regimen design.

Methods: TB strains without prior exposure to novel anti-TB drugs were analyzed retrospectively. Drug susceptibility testing was conducted for TB strains with bedaquiline, delamanid, linezolid, clofazimine, and widely-used first- and second-line anti-TB drugs. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore molecular characteristics of resistance and perform the phylogenetic analysis.

Results: Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine were observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of strains, respectively. Moreover, 1.0% (1/102) and 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of MDR-TB strains were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.22% (2/9) of XDR-TB strains were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB strains with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four strains with cross-resistance between bedaquiline and clofazimine were identified with a related gene mutation in Rv0678. Three out of five strains with linezolid resistance were detected gene mutation in rplC.

Conclusions: The detection of resistance to new anti-TB drugs emphasizes the pressing need for intensive surveillance for such resistance before wide-usage.
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http://dx.doi.org/10.1016/j.jgar.2021.06.007DOI Listing
June 2021

A plasmonic route for the integrated wireless communication of subdiffraction-limited signals.

Light Sci Appl 2020 Jul 2;9(1):113. Epub 2020 Jul 2.

State Key Laboratory of Millimeter Waves, Southeast University, 210096, Nanjing, China.

Perfect lenses, superlenses and time-reversal mirrors can support and spatially separate evanescent waves, which is the basis for detecting subwavelength information in the far field. However, the inherent limitations of these methods have prevented the development of systems to dynamically distinguish subdiffraction-limited signals. Utilizing the physical merits of spoof surface plasmon polaritons (SPPs), we demonstrate that subdiffraction-limited signals can be transmitted on planar integrated SPP channels with low loss, low channel interference, and high gain and can be radiated with a very low environmental sensitivity. Furthermore, we show how deep subdiffraction-limited signals that are spatially coupled can be distinguished after line-of-sight wireless transmission. For a visualized demonstration, we realize the high-quality wireless communication of two movies on subwavelength channels over the line of sight in real time using our plasmonic scheme, showing significant advantages over the conventional methods.
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http://dx.doi.org/10.1038/s41377-020-00355-yDOI Listing
July 2020

Varying contributions of three ryanodine receptor point mutations to diamide insecticide resistance in Plutella xylostella.

Pest Manag Sci 2021 Jun 27. Epub 2021 Jun 27.

Key Laboratory of Plant Immunity and College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

Background: Although decoding the molecular mechanisms underlying insecticide resistance has often proven difficult, recent progress has revealed that specific mutations in the ryanodine receptor (RyR) of the diamondback moth, Plutella xylostella, can confer resistance to diamide insecticides. The extent to which specific RyR mutations contribute to the diamide resistance phenotype, the associated genetic traits and fitness costs remain limited.

Results: Three field-evolved PxRyR mutations (G4946E, I4790 M, and I4790 K) were respectively introgressed into a common susceptible background strain (IPP-S) of P. xylostella with marker-assisted backcrossing. The mutations alone can result in moderate to high levels of resistance to five commercial diamides (flubendiamide, chlorantraniliprole, cyantraniliprole, tetraniliprole, and cyclaniliprole), and the resistance intensity mediated by the three mutations was hierarchical in order of I4790 K (1199- to >2778-fold) > G4946E (39- to 739-fold) > I4790 M (16- to 57-fold). Flubendiamide resistance was autosomal and incompletely recessive, and was significantly linked with the introgressed mutations in the three constructed strains. In addition, the resistance levels to flubendiamide of hybrid progeny from any two resistant strains fell in between the status of their parents. Furthermore, by comparing the net replacement rate, the fitness of 4946E, 4790 M and 4790 K strains were 0.77, 0.93 and 0.92 relative to the IPP-S strain, respectively.

Conclusion: Three independent PxRyR mutations confer varying degrees of resistance to diamides in P. xylostella. Among the three mutations, I4790 K confers highest levels of resistance (> 1000-fold) to all five commercial diamides. The findings can guide resistance management practices for diamides in P. xylostella and other arthropods.
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http://dx.doi.org/10.1002/ps.6534DOI Listing
June 2021

Prostate cancer identification via photoacoustic spectroscopy and machine learning.

Photoacoustics 2021 Sep 6;23:100280. Epub 2021 Jun 6.

Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, China.

Photoacoustic spectroscopy can generate abundant chemical and physical information about biological tissues. However, this abundance of information makes it difficult to compare these tissues directly. Data mining methods can circumvent this problem. We describe the application of machine-learning methods (including unsupervised hierarchical clustering and supervised classification) to the diagnosis of prostate cancer by photoacoustic spectrum analysis. We focus on the content and distribution of hemoglobin, collagen, and lipids, because these molecules change during the development of prostate cancer. A higher correlation among the ultrasonic power spectra of these chemical components is observed in cancerous than in normal tissues, indicating that the microstructural distributions in cancerous tissues are more consistent. Different classifiers applied in cancer-tissue diagnoses achieved an accuracy of 82 % (better than that of standard clinical methods). The technique thus exhibits great potential for painless early diagnosis of aggressive prostate cancer.
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http://dx.doi.org/10.1016/j.pacs.2021.100280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209684PMC
September 2021

Cyclooxygenase-2 expressed hepatocellular carcinoma induces cytotoxic T lymphocytes exhaustion through M2 macrophage polarization.

Am J Transl Res 2021 15;13(5):4360-4375. Epub 2021 May 15.

Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Laboratory of Basic Research on Liver Cirrhosis and Cancer, UMHS-PUHSC Joint Institute for Translational and Clinical Research Beijing, China.

Objective: Due to the tumor immune microenvironment (TIME) complexity and cancer heterogeneity, the clinical outcomes of hepatocellular carcinoma (HCC) are barely elicited from the conventional treatment options, even from the promising anti-cancer immunotherapy. As a suppressive TIME-related marker, the role played by cyclooxygenase-2 (COX-2) in HCC TIME, and its potential effects on anti-cancer T cell immune response remains unknown. In our study, to investigate the COX-2-dependent immune regulation pathway, we verified that the macrophages phenotypes were correlated to COX-2/PGE2 expressions among HCC patients. A multi-cellular co-culture platform containing HCC cells, macrophages, and T cells were established to mimic HCC TIME in vitro and in animal model. M2 macrophage polarization and activated CD8 T cells exhaustion were observed under high COX-2 levels in HCC cells, with further evaluation using CRISPR/Cas9-based PTGS2 knocking out and COX-2 blockade (celecoxib) treatment controls. PGE2, TGF-β, Granzyme B, and IFN-γ levels were testified by flow cytometry and ELISA to fully understand the mechanism of COX-2 suppressive effects on T cell-based anti-HCC responses. The activation of the TGF-β pathway evaluated by auto-western blot in T cells was confirmed which increased the level of phosphorylated Smad3, phosphorylated Samd2, and FoxP1, leading to T cell de-lymphotoxin. In conclusion, high COX-2-expressing HCC cell lines can induce anti-tumor abilities exhaustion in activated CD8 T cell through M2 TAMs polarization and TGF beta pathway. COX-2 inhibitors may reduce the inhibitory effect on CD8 T cells through regulating TAMs in TIME, thus enhance the T cell-based cytotoxicity and improve the prognosis of HCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205841PMC
May 2021

Adjuvant effects of vitamin A and vitamin D supplementation on treatment of children with attention-deficit/hyperactivity disorder: a study protocol for a randomised, double-blinded, placebo-controlled, multicentric trial in China.

BMJ Open 2021 06 16;11(6):e050541. Epub 2021 Jun 16.

Division of Growth, Development and Mental health of Children and Adolescence, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China

Introduction: Approximately 7.2% of children in the world suffer from attention-deficit/hyperactivity disorder (ADHD). Due to the availability of the osmotic-release oral-system methylphenidate, ADHD currently has a remission rate of up to 30.72%. Nevertheless, it has been reported that patients with ADHD tend to exhibit vitamin A and vitamin D deficiency, which may aggravate the symptoms of ADHD. This study aims to determine the effect of vitamin A and vitamin D supplementation as adjunctive therapy to methylphenidate on the symptoms of ADHD.

Methods And Analysis: This is a parallel, prospective, interventional multicentric study. Patients will be enrolled from the southern, central and northern parts of China. A target of 504 patients will be followed for 8 weeks. They will be allocated into three groups (vitamin AD, vitamin D and placebo) and administered the interventions accordingly. Data on changes in the symptoms of ADHD as well as changes in the serum concentrations of vitamin A and vitamin D will be recorded. Both responders and nonresponders based on the sociodemographic and clinical data will also be described to mitigate selection bias.

Ethics And Dissemination: This study is performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Children's Hospital of Chongqing Medical University, China (approval number: (2019) IRB (STUDY) number 262). The results of the trial will be reported in peer-reviewed scientific journals and academic conferences regardless of the outcomes.

Trial Registration Number: NCT04284059.
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http://dx.doi.org/10.1136/bmjopen-2021-050541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211063PMC
June 2021

Research progress of adsorption and removal of heavy metals by chitosan and its derivatives: A review.

Chemosphere 2021 Sep 17;279:130927. Epub 2021 May 17.

School of Environmental and Safety Engineering, Changzhou University, Changzhou, 213164, China; Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou, 213164, China; Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou University, Changzhou, 213164, China. Electronic address:

Chitosan has received widespread attention as an adsorbent for pollutants because of its low cost and great adsorption potentials. Chitosan has abundant hydroxyl and amino groups that can bind heavy metal ions. However, it has defects such as sensitivity to pH, low thermal stability, and low mechanical strength, which limit the application of chitosan in wastewater treatment. The functional groups of chitosan can be modified to improve its performance via crosslinking and graft modification. The porosity and specific surface area of chitosan in powder form are not ideal, therefore, physical modification has been attempted to generate chitosan nanoparticles and hydrogel. Chitosan has also been integrated with other materials (e.g. graphene, zeolite) resulting in composite materials with improved adsorption performance. This review mainly focuses on reports about the application of chitosan and its derivatives to remove different heavy metals. The preparation strategy, adsorption mechanism, and factors affecting the adsorption performance of adsorbents for each type of heavy metal are discussed in detail. Recent reports on important organic pollutants (dyes and phenol) removal by chitosan and its derivatives are also briefly discussed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130927DOI Listing
September 2021

The Therapeutic Effect of Traditional Chinese Medicine on Inflammatory Diseases Caused by Virus, Especially on Those Caused by COVID-19.

Front Pharmacol 2021 26;12:650425. Epub 2021 May 26.

National Drug Clinical Trial Institution, The First Affiliated Hospital of Bengbu Medical College, Hefei, China.

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 β (IL-1β). IL-1β was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1β is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.650425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187915PMC
May 2021

Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells.

Small 2021 Jun 10:e2101139. Epub 2021 Jun 10.

State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, 999078, China.

The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host-guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form β-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive "nanoparticle-to-microfiber" transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.
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http://dx.doi.org/10.1002/smll.202101139DOI Listing
June 2021

Reversing the mitochondrial stress-induced exhaustion of CD8 T cells for improving cancer immunotherapy.

Cell Mol Immunol 2021 Jul 7;18(7):1634-1637. Epub 2021 Jun 7.

National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai, China.

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http://dx.doi.org/10.1038/s41423-021-00709-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245517PMC
July 2021

Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis.

Front Cardiovasc Med 2021 20;8:661709. Epub 2021 May 20.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Regulatory T cells (Tregs) have shown to be protective against the development of atherosclerosis, a major pathological cause for cardiovascular events. Here, we aim to explore the roles of Tregs-related genes in atherosclerosis deterioration. We downloaded the gene expression profile of 29 atherosclerotic samples from the Gene Expression Omnibus database with an accession number of GSE28829. The abundance of Tregs estimated by the CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using the limma test and correlation analysis, a total of 159 differentially expressed Tregs-related genes (DETregRGs) between early and advanced atherosclerotic plaques were documented. Functional annotation analysis using the DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory responses, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte trans-endothelial migration, vascular smooth muscle contraction, and so on. A protein-protein interaction network of the DETregRGs was then constructed, and five hub genes (, and ) were derived from the network with node degrees ≥20. The expression patterns of these hub DETregRGs were further validated in several independent datasets. Finally, a single sample scoring method was used to build a gene signature for the five DETregRGs, which could distinguish patients with myocardial infarction from those with stable coronary disease. The results of this study will improve our understanding about the Tregs-associated molecular mechanisms in the progression of atherosclerosis and facilitate the discovery of novel biomarkers for acute cardiovascular events.
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http://dx.doi.org/10.3389/fcvm.2021.661709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172618PMC
May 2021

Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis.

Microb Pathog 2021 Jun 2;158:105020. Epub 2021 Jun 2.

Department of Child Health Care, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. Electronic address:

Gut microbial dysbiosis is closely associated with cow's milk protein allergy (CMPA) during infancy. Recent research has highlighted the crucial role of the commensal microbiota-induced intestinal regulatory T (Treg) cell response in the development of oral tolerance and protection against IgE-mediated food allergies. However, the influences of CMPA (particularly non-IgE-mediated CMPA)-associated microbial dysbiosis on Treg cell-mediated intestinal immune tolerance and homeostasis remain poorly characterized. To investigate this issue, fecal microbiota from infant donors with food protein-induced allergic proctocolitis (FPIAP) associated with cow's milk, which is the most frequent clinical type of non-IgE-mediated gastrointestinal CMPA, and from age-matched healthy controls were transplanted into germ-free mice in this study. Two weeks post fecal microbiota transplantation, the gut microbiome of the recipient mice was analyzed by 16S rRNA gene sequencing, and the intestinal immunological alterations associated with the Treg cell compartment and intestinal immune homeostasis were detected. The specific gut microbial phylotypes that were potentially responsible for the disruption of intestinal immune homeostasis were also analyzed. We observed that the main characteristics of the gut microbiome in infant donors could be stably maintained in recipient mice. We also found that mice colonized with the gut microbiome from infants with cow's milk-induced FPIAP showed significant deficiencies in the accumulation and function of intestinal Treg cells. Furthermore, these mice showed disrupted intestinal immune homeostasis, which was characterized by an overactivated Th2 biased immune response. We further identified two potentially pathogenic genera that contribute to this disruption. Overall, our results highlight a destructive effect of non-IgE-mediated CMPA-associated microbial dysbiosis on intestinal immune tolerance and homeostasis. We believe these findings will help improve our understanding of the gut microbiota-mediated pathogenesis of non-IgE-mediated CMPA in the future.
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http://dx.doi.org/10.1016/j.micpath.2021.105020DOI Listing
June 2021

Effects of S24-7 on the weight of progeny rats after exposure to ceftriaxone sodium during pregnancy.

BMC Microbiol 2021 Jun 3;21(1):166. Epub 2021 Jun 3.

Department of Primary Child Health Care, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.

Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old. To determine the role of the gut microbiota and its metabolites in the growth of offspring, we collected feces for sequencing and further established that the experimental group has a different composition ratio of dominant bacteria at 6 week old, among which S24-7 correlated negatively with body weight and the metabolites that correlated with body weight-related unique flora were L-Valine, L-Leucine, Glutaric acid, N-Acetyl-L-glutamate, and 5-Methylcytosine. To further explore how they affect the growth of offspring, we submitted these data to Kyoto Encyclopedia of Genes and Genomes website for relevant pathway analysis. The results showed that compared with the control, the following metabolic pathways changed significantly: Valine, leucine, and isoleucine biosynthesis; Protein digestion and absorption; and Mineral absorption. Therefore, we believe that our findings support the conclusion that ceftriaxone sodium exposure in pregnancy has a long-lasting adverse effect on the growth of offspring because of an imbalance of gut microbiota, especially S24-7, via different metabolic pathways.
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http://dx.doi.org/10.1186/s12866-021-02231-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176729PMC
June 2021

M2 macrophage-derived exosomes carry miR-1271-5p to alleviate cardiac injury in acute myocardial infarction through down-regulating SOX6.

Mol Immunol 2021 Aug 28;136:26-35. Epub 2021 May 28.

Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

Background: Emerging evidence has indicated that exosomes serve as key regulators in acute myocardial infarction (AMI). This study was determined to investigate the effect of M2 macrophage-derived exosomes (M2-Exos) in AMI and the further mechanism.

Methods: M2 macrophages were induced and M2-exos were isolated and verified. The AMI mouse model was prepared by ligation of the left anterior descending coronary artery (LAD) and then intravenously injected with the isolated M2-exos. The mouse cardiac function was assessed by echocardiography. Hematoxylin and eosin (HE) staining and TUNEL assay were conducted to examine myocardial lesion and apoptosis in cardiac tissues. The expressions of associated molecules were detected by quantitative real time-PCR (qRT-PCR) and western blot. MTT assay, Flow cytometry and Dual-luciferase reporter assay were carried out to detect cell viability, apoptosis and the interaction of miRNA and the target.

Result: M2-Exos could promote cardiac repair in AMI mice. M2-Exos suppressed apoptosis and enhanced viability of hypoxia-induced cardiomyocytes through delivery of miR-1271-5p. SOX6 is a direct target of miR-1271-5p. miR-1271-5p decreased cardiomyocyte apoptosis induced by hypoxia and alleviated cardiac injury in AMI via down-regulating SOX6 expression.

Conclusion: We identified that M2-Exos could carry miR-1271-5p to reduce apoptosis of cardiomyocytes and promote cardiac repair via down-regulating SOX6.
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http://dx.doi.org/10.1016/j.molimm.2021.05.006DOI Listing
August 2021

Inflammatory Immune Cytokine TNF-α Modulates Ezrin Protein Activation FAK/RhoA Signaling Pathway in PMVECs Hyperpermeability.

Front Pharmacol 2021 12;12:676817. Epub 2021 May 12.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

One of the important pathogenesis of acute respiratory distress syndrome (ARDS) is the dysfunction of pulmonary microvascular endothelial barrier induced by a hyperinflammatory immune response. However, the potential mechanisms of such an imbalance in pulmonary microvascular endothelial cells (PMVECs) are not yet understood. Explore the molecular mechanism of endothelial barrier dysfunction induced by inflammatory immune cytokines in ARDS, and find a therapeutic target for this syndrome. Rat PMVECs were cultured to form a monolayer. Immunofluorescence, flow cytometry, and Western blotting were selected to detect the distribution and the expression level of phosphorylated Ezrin protein and Ezrin protein. Transendothelial electrical resistance (TER) and transendothelial fluxes of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) were utilized to measure the permeability of the cell monolayer. Ezrin short hairpin RNA (shRNA) and Ezrin 567-site threonine mutant (Ezrin) were used to examine the role of Ezrin protein and phosphorylated Ezrin protein in endothelial response induced by tumor necrosis factor-alpha (TNF-α), respectively. The function of focal adhesion kinase (FAK) and Ras homolog gene family, member A (RhoA) signaling pathways were estimated by inhibitors and RhoA/FAK shRNA in TNF-α-stimulated rat PMVECs. The activation of FAK and RhoA was assessed by Western blotting or pull-down assay plus Western blotting. The TER was decreased after TNF-α treatment, while the Ezrin protein phosphorylation was increased in a time- and dose-dependent manner. The phosphorylated Ezrin protein was localized primarily at the cell periphery, resulting in filamentous actin (F-actin) rearrangement, followed by a significant decrease in TER and increase in fluxes of FITC-BSA. Moreover, FAK and RhoA signaling pathways were required in the phosphorylation of Ezrin protein, and the former positively regulated the latter. The phosphorylated Ezrin protein was induced by TNF-α the FAK/RhoA signaling pathway leading to endothelial hyperpermeability in PMVECs.
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http://dx.doi.org/10.3389/fphar.2021.676817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152434PMC
May 2021

Pathogenesis and Function of Interleukin-35 in Rheumatoid Arthritis.

Front Pharmacol 2021 13;12:655114. Epub 2021 May 13.

Second Hospital of Anhui Medical University, Hefei, China.

It is well known that RA (Rheumatoid arthritis) is an autoimmune disease characterized by multiple and symmetric arthropathy. The main pathological features of RA are synovial hyperplasia, angiogenesis, pannus formation, inflammatory cell infiltration, articular cartilage, bone destruction, and ultimately joint dysfunction, even deformity. IL-35 (Interleukin-35) is a new member of the IL-12 (Interleukin-12) family, which is an immunosuppressive and anti-inflammatory cytokine secreted mainly by Treg (T regulatory cells). There is evidence suggested that IL-35 can attenuate the progression of RA through influencing the immune and pathological process. It suggests that IL-35 played an important role in the pathogenesis of RA, and can be used as a potential target for the future treatment of RA. This review summarizes the recent advances of IL-35 in the pathological roles and the therapeutic potential roles in RA.
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http://dx.doi.org/10.3389/fphar.2021.655114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155723PMC
May 2021

Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus.

Diabetes Metab Syndr Obes 2021 20;14:2269-2280. Epub 2021 May 20.

Department of Endocrinology, Yixing People's Hospital, Yixing, 214200, Jiangsu, People's Republic of China.

Background: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for type 2 diabetes mellitus (T2DM). Previous studies have reported that silent information regulator 1 (Sirt1) closely relates to many pathological processes of glucose metabolism and insulin resistance (IR). However, it is unclear whether Sirt1 is involved in the hepatic glucose metabolism of T2DM after RYGB.

Methods: T2DM rats were randomly divided into four groups: Control, DM, Diet and RYGB. Normal rats were served as the control group. Hematoxylin and eosin (H&E) staining and Masson staining assays were performed to explore the changes of liver fibrous tissue after RYGB. The effect of RYGB on the protein expression of Sirt1 was detected by the Western blotting assay and immunohistochemical assay. Next, we built the insulin resistance model of human hepatocyte cell lines (FL62891 and HHL5) using the human recombinant insulin. Western blotting assay was applied to determine the expression of Sirt1 and the expression change of IRS1/mTOR2 /PKB pathway-related proteins in FL62891 and HHL5 cells. Additionally, the effects of Sirt1 on the expression of PTP1B and FGF-21 in insulin-resistant FL62891 and HHL5 cells were investigated using Western blotting and immunofluorescence assay.

Results: Our results showed that following RYGB improved the pathological changes of liver and increased the expression of Sirt1 in rats with T2DM compared with the diabetic rats. In experiments in vitro, the expression of Sirt1 was downregulated in insulin-resistance FL62891 and HHL5 cells. Moreover, overexpression of Sirt1 significantly increased the expression of FGF-21 whereas decreased the expression of PTP1B in insulin-resistance FL62891 and HHL5 cells. These above changes were alleviated in RYGB and Diet groups. Furthermore, RYGB could improve the glucose metabolism through activating IRS1/mTOR2/PKB pathways by regulating Sirt1 in rats with T2DM.

Conclusion: RYGB could significantly improve hepatic glucose metabolism and increase the expression of Sirt1 in T2DM rats, which is related to the IRS1/mTOR2 /PKB pathway.
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http://dx.doi.org/10.2147/DMSO.S298897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145911PMC
May 2021
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