Publications by authors named "Hui Yang"

2,565 Publications

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Upregulated LINC00319 aggravates neuronal injury induced by oxygen-glucose deprivation via modulating miR-200a-3p.

Exp Ther Med 2021 Aug 7;22(2):844. Epub 2021 Jun 7.

Department of Neurosurgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154001, P.R. China.

Ischemic stroke is one of the main causes of physical disability and mortality worldwide. Long non-coding RNAs (lncRNAs) are reported to be dysregulated in various biological progressions and serve important roles in pathological processes of cerebral ischemia. However, their biological actions and potential mechanisms in the progression of ischemic stroke remain unknown. The present study aimed to investigate the functions of LINC00319 on ischemic brain injury. It was identified that LINC00319 was significantly upregulated in the Gene Expression Omnibus profile of ischemic stroke. Furthermore, LINC00319 overexpression elevated caspase-3 activity and increased the apoptotic rate of neuronal cells, as well as decreased cell viability and glucose uptake. It was also demonstrated that LINC00319 participated in oxygen-glucose deprivation (OGD)-induced cerebral ischemic injury. LINC00319 could competitively bind with microRNA (miR)-200a-3p and decrease its expression. Moreover, miR-200a-3p could partly offset the negative effects of LINC00319 overexpression on neuronal injury caused by OGD. Collectively, the present results suggested that LINC00319 promoted apoptosis and aggravated neuronal injury induced by OGD by regulating miR-200a-3p, which may be important for ischemic stroke treatment.
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http://dx.doi.org/10.3892/etm.2021.10276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210224PMC
August 2021

Activation of Hippocampal IR/IRS-1 Signaling Contributes to the Treatment with Zuogui Jiangtang Jieyu Decoction on the Diabetes-Related Depression.

Evid Based Complement Alternat Med 2021 3;2021:6688723. Epub 2021 Jun 3.

Key Laboratory of Chinese Material Medical Power and Innovation Drugs Established By Provincial and Ministry, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Background: Zuogui Jiangtang Jieyu decoction (ZJJ) is mainly used for the treatment of diabetes-related depression in current clinical applications and research. This study aims to investigate whether the brain IR/IRS-1 signaling pathway is involved in the therapeutic effect of ZJJ on depression-like behavior in diabetic rats.

Methods: Sprague-Dawley rats were fed with high-fat diet and subjected to streptozotocin injection to establish the diabetes animal model. After treatment with different doses of ZJJ (20.530 g/kg or 10.265 g/kg) for 4 weeks, the blood glucose level and peripheral insulin resistance were measured. The forced-swimming test (FST) and Morris water maze test (MWMT) were applied for the mood and cognitive function assessment. Then, the Western blot method was used to analyze the protein levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylonositol-3-kinase (PI3K), and protein kinase B (PKB, also as known as AKT) in the hippocampus of diabetic rats. Meanwhile, the immunofluorescence method was performed to analyze the above proteins' expression in the neuron and astrocyte. At last, the levels of glycogen, lactate, and ATP were tested by the ELISA method. Additionally, the insulin-sensitive glucose transporter 4 (GLUT4) and the lactate transporter monocarboxylate transporter 4 (MCT4) were analyzed by the Western blot method.

Results: ZJJ administration significantly decreased the level of blood glucose and improved the peripheral insulin resistance in diabetic rats. Besides, ZJJ attenuated the depression-like behavior and the cognitive dysfunction in rats with diabetes. Furthermore, we found the upregulation of protein expression of phospho-IR, phospho-IRS-1, phospho-PI3K, and phospho-AKT in the hippocampus of diabetic rats after being treated with ZJJ. Moreover, the above proteins are increased not only in the neuron but also in the astrocyte after ZJJ administration. In addition, ZJJ increased the content of ATP, glycogen, and lactate, as well as the expression of GLUT4 and MCT4 in the hippocampus of diabetic rats.

Conclusions: These findings suggest that ZJJ improves the depression-like behavior of diabetic rats by activating the IR/IRS-1 signaling pathway in both hippocampal neuron and astrocyte. And the brain IR/IRS-1 signaling pathway plays an important role in astrocyte-neuron metabolic coupling, providing a potential mechanism by which the IR/IRS-1 signaling pathway may contribute to the treatment of ZJJ on diabetes-related depression.
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http://dx.doi.org/10.1155/2021/6688723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195672PMC
June 2021

Arachidonic Acid Metabolism Controls Macrophage Alternative Activation Through Regulating Oxidative Phosphorylation in PPARγ Dependent Manner.

Front Immunol 2021 3;12:618501. Epub 2021 Jun 3.

NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing, China.

Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophage polarization models, we revealed a pivotal role for arachidonic acid metabolism in determining the phenotype of M2 macrophages. We demonstrated that macrophage M2 polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting in the alternative activation of macrophages, which was counterweighted by the activation of PPARγ. This connection between PGE2 biosynthesis and macrophage M2 polarization also existed in human and mouse esophageal squamous cell carcinoma. Our results highlight the critical role of arachidonic acid and metabolic PGE2 as immune regulators in modulating tissue homeostasis and pathological process.
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http://dx.doi.org/10.3389/fimmu.2021.618501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211451PMC
June 2021

A Conjugative MDR pMG1-Like Plasmid Carrying the (E) Gene of With Potential Transmission to .

Front Microbiol 2021 4;12:667415. Epub 2021 Jun 4.

State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

(E) is a pleuromutilin, lincosamide, and streptogramin A (PLSA phenotype) resistance gene that was first described in and was thought to have been transferred from sp. This study aimed to elucidate the prevalence of the (E) gene among isolates at a tertiary teaching hospital and to evaluate the transferability of the (E) gene from to . A total of 96 strains isolated from one hospital in Beijing in 2013 were analysed for quinupristin-dalfopristin (QDA) resistance genes, and multilocus sequence typing (MLST) was performed. The transferability of QDA resistance between ten strains and four strains was determined by filter mating. Genome sequencing of the transconjugant was performed. A total of 46 isolates (46/96, 47.92%) tested positive for (E), while two isolates (2/96, 2.08%) tested positive for (A). Thirty-six (E)-positive strains (36/46, 78.3%) belonged to ST78. Among 40 mating tests, (E) was successfully transferred through one conjugation at a frequency of 1.125 × 10 transconjugants per donor. The QDA resistance of the transconjugant N7435-R3645 was expressed at a higher level (MIC = 16 mg/L) than that of the parent strain (MIC = 0.38 mg/L). Next-generation sequencing (NGS) analysis of the transconjugant N7435-R3645 showed that the complete sequence of the (E)-carrying plasmid pN7435-R3645 had a size of 92,396 bp and a G + C content of 33% (accession no. MT022086). The genetic map of pN7435-R3645 had high nucleotide similarity and shared the main open reading frame (ORF) features with two plasmids: pMG1 (AB206333.1) and LS170308 (CP025078.1). The gene of pN7435-R3645 showed 100% identity with that of pMG1, although it did not belong to the 1-19 family but instead a unique family. Multiple antibiotic resistance genes, including (E), and (B), (B), -Ia, and (B), were present on the plasmid. In conclusion, an (E)-carrying plasmid that can be transferred by conjugation from to was identified. This multidrug resistance (MDR) pMG1-like plasmid may act as a vector in the dissemination of antimicrobial resistance among species.
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http://dx.doi.org/10.3389/fmicb.2021.667415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212935PMC
June 2021

Rechargeable Aqueous Zinc-Ion Batteries in MgSO/ZnSO Hybrid Electrolytes.

Nanomicro Lett 2020 Feb 21;12(1):60. Epub 2020 Feb 21.

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372, Singapore.

MgSO is chosen as an additive to address the capacity fading issue in the rechargeable zinc-ion battery system of MgVO·nHO//ZnSO//zinc. Electrolytes with different concentration ratios of ZnSO and MgSO are investigated. The batteries measured in the 1 M ZnSO M MgSO electrolyte outplay other competitors, which deliver a high specific capacity of 374 mAh g at a current density of 100 mA g and exhibit a competitive rate performance with the reversible capacity of 175 mAh g at 5 A g. This study provides a promising route to improve the performance of vanadium-based cathodes for aqueous zinc-ion batteries with electrolyte optimization in cost-effective electrolytes.
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http://dx.doi.org/10.1007/s40820-020-0385-7DOI Listing
February 2020

Boosting Sodium Storage of FeS/MoS Composite via Heterointerface Engineering.

Nanomicro Lett 2019 Sep 23;11(1):80. Epub 2019 Sep 23.

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372, Singapore.

Improving the cycling stability of metal sulfide-based anode materials at high rate is of great significance for advanced sodium ion batteries. However, the sluggish reaction kinetics is a big obstacle for the development of high-performance sodium storage electrodes. Herein, we have rationally engineered the heterointerface by designing the FeS/MoS heterostructure with abundant "ion reservoir" to endow the electrode with excellent cycling stability and rate capability, which is proved by a series of in and ex situ electrochemical investigations. Density functional theory calculations further reveal that the heterointerface greatly decreases sodium ion diffusion barrier and facilitates charge-transfer kinetics. Our present findings not only provide a deep analysis on the correlation between the structure and performance, but also draw inspiration for rational heterointerface engineering toward the next-generation high-performance energy storage devices.
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http://dx.doi.org/10.1007/s40820-019-0311-zDOI Listing
September 2019

Herbicide atrazine exposure induce oxidative stress, immune dysfunction and WSSV proliferation in red swamp crayfish Procambarus clarkii.

Chemosphere 2021 Jun 15;283:131227. Epub 2021 Jun 15.

College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.

Atrazine is considered as a potential environmental endocrine disruptors and exhibits various toxic effects on animals. It has a great impact in the aquatic ecosystems, but there are few studies on its immunotoxicity in crustaceans. In the present study, the Procambarus clarkii were utilized to assess the immune toxicity after 0.5 mg/L and 5 mg/L atrazine exposure. A significant decrease in total hemocytes count (THC) was observed at 5 mg/L atrazine exposure throughout the experiment. The activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly inhibited, but the content of reactive oxygen species (ROS) and malondialdehyde (MDA) were up-regulated, indicating the potential oxidative stress. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants. After 5 mg/L atrazine exposure for 144 h, the integrity of crayfish hepatopancreas was destroyed with disappeared connections between tubules and increased liver tubules vacuoles. The relative expression levels of different immune genes in hepatopancreas after atrazine exposure were measured. Most of these genes were suppressed and exhibited a certain dose-dependent effect. The results of crayfish white spot syndrome virus (WSSV) replication shown the amount of virus in muscle was significantly higher and exhibited a higher mortality rate at 5 mg/L group than other groups. The present study determined the impact of atrazine exposure on WSSV outbreaks, and also provide an important basis for further assessing the occurrence of pesticides on diseases of P. clarkii.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131227DOI Listing
June 2021

Coordination of two enhancers drives expression of olfactory trace amine-associated receptors.

Nat Commun 2021 06 18;12(1):3798. Epub 2021 Jun 18.

Center for Brain Science of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.
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http://dx.doi.org/10.1038/s41467-021-23823-4DOI Listing
June 2021

Photoredox Catalytic Phosphite-Mediated Deoxygenation of 𝛼-Diketones Enables Wolff Rearrangement and Staudinger Synthesis of β-Lactams.

Angew Chem Int Ed Engl 2021 Jun 17. Epub 2021 Jun 17.

Henan University, Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Jinming Campus, 475004, Kaifeng, CHINA.

A novel visible light-driven catalytic activation of C=O bonds by exploiting the photoredox chemistry of 1,3,2-dioxaphospholes, readily accessible from 𝛼-diketones and trialkyl phosphites, is reported. This mild and environmentally friendly strategy provides an unprecedented and efficient access to the Wolff rearrangement reaction which traditionally entails 𝛼-diazoketones as the precursors. The resulting ketenes could be precisely trapped by alcohols/thiols to give 𝛼-aryl (thio)acetates and by imines to afford the valuable 𝛽-lactams in up to 99% yields.
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http://dx.doi.org/10.1002/anie.202107080DOI Listing
June 2021

Involvement of plasminogen activator inhibitor-1 and its related molecules in atrial fibrosis in patients with atrial fibrillation.

PeerJ 2021 2;9:e11488. Epub 2021 Jun 2.

School of Medicine, South China University of Technology, Guangzhou, China.

Atrial fibrillation is the most common form of cardiac arrhythmia. Atrial fibrosis is a significant feature of atrial fibrillation though its mechanism is not well understood. We searched the Gene Expression Omnibus database to compare mRNA expression patterns between atrial fibrillation and sinus rhythm samples; one hundred and forty eight differentially expressed genes were identified. Most of these genes were significantly enriched in the extracellular matrix organization process and collagen-activated tyrosine kinase receptor signaling pathway. To screen hub genes involved in atrial fibrosis, we constructed a protein-protein interaction network and found that three hub genes (SERPINE1/plasminogen activator inhibitor-1/PAI-1, TIMP Metallopeptidase Inhibitor 3/TIMP3 and decorin/DCN) play vital roles in atrial fibrosis, especially plasminogen activator inhibitor-1. Elevated plasminogen activator inhibitor-1 expression was positively correlated with the p53 signaling pathway. Plasminogen activator inhibitor-1 and p53 protein expression levels were verified in patients with sinus rhythm and atrial fibrillation by Western blot analysis. Compared with the sinus rhythm controls, p53 and plasminogen activator inhibitor-1 protein expressions were upregulated in the atrial tissues of patients with atrial fibrillation. p53 was also found to regulate plasminogen activator inhibitor-1 based on the results of cellular and molecular experiments. Thus, the p53/plasminogen activator inhibitor-1 signaling axis may participate in the pathophysiological processes of atrial fibrillation, and plasminogen activator inhibitor-1 may serve as a new therapeutic biomarker in atrial fibrillation.
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http://dx.doi.org/10.7717/peerj.11488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179226PMC
June 2021

Enhanced Reversible Zinc Ion Intercalation in Deficient Ammonium Vanadate for High-Performance Aqueous Zinc-Ion Battery.

Nanomicro Lett 2021 Apr 30;13(1):116. Epub 2021 Apr 30.

Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.

Ammonium vanadate with bronze structure (NHVO) is a promising cathode material for zinc-ion batteries due to its high specific capacity and low cost. However, the extraction of [Formula: see text] at a high voltage during charge/discharge processes leads to irreversible reaction and structure degradation. In this work, partial [Formula: see text] ions were pre-removed from NHVO through heat treatment; NHVO nanosheets were directly grown on carbon cloth through hydrothermal method. Deficient NHVO (denoted as NVO), with enlarged interlayer spacing, facilitated fast zinc ions transport and high storage capacity and ensured the highly reversible electrochemical reaction and the good stability of layered structure. The NVO nanosheets delivered a high specific capacity of 457 mAh g at a current density of 100 mA g and a capacity retention of 81% over 1000 cycles at 2 A g. The initial Coulombic efficiency of NVO could reach up to 97% compared to 85% of NHVO and maintain almost 100% during cycling, indicating the high reaction reversibility in NVO electrode.
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http://dx.doi.org/10.1007/s40820-021-00641-3DOI Listing
April 2021

Defect and Doping Co-Engineered Non-Metal Nanocarbon ORR Electrocatalyst.

Nanomicro Lett 2021 Feb 6;13(1):65. Epub 2021 Feb 6.

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372, Singapore.

Exploring low-cost and earth-abundant oxygen reduction reaction (ORR) electrocatalyst is essential for fuel cells and metal-air batteries. Among them, non-metal nanocarbon with multiple advantages of low cost, abundance, high conductivity, good durability, and competitive activity has attracted intense interest in recent years. The enhanced ORR activities of the nanocarbons are normally thought to originate from heteroatom (e.g., N, B, P, or S) doping or various induced defects. However, in practice, carbon-based materials usually contain both dopants and defects. In this regard, in terms of the co-engineering of heteroatom doping and defect inducing, we present an overview of recent advances in developing non-metal carbon-based electrocatalysts for the ORR. The characteristics, ORR performance, and the related mechanism of these functionalized nanocarbons by heteroatom doping, defect inducing, and in particular their synergistic promotion effect are emphatically analyzed and discussed. Finally, the current issues and perspectives in developing carbon-based electrocatalysts from both of heteroatom doping and defect engineering are proposed. This review will be beneficial for the rational design and manufacturing of highly efficient carbon-based materials for electrocatalysis.
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http://dx.doi.org/10.1007/s40820-020-00579-yDOI Listing
February 2021

Retrospective Analysis of Clinicopathological Features and Prognosis of Gynecological Small-Cell Carcinoma.

Cancer Manag Res 2021 8;13:4529-4540. Epub 2021 Jun 8.

Department of Chinese Journals of Practical Medicine, China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.

Purpose: Although rare, small-cell neuroendocrine carcinoma of the gynecologic tract (SCNCGT) is associated with poor prognosis. We analyzed the clinical characteristics, pathological features, treatment strategies, and prognosis in patients with SCNCGT.

Patients And Methods: We performed a retrospective data analysis of 34 patients with SCNCGT diagnosed and treated at our hospital between 2006 and 2018. Medical records were reviewed for pathological features, treatment methods, and outcomes of this disease.

Results: We included 34 patients who had small-cell neuroendocrine carcinoma of the endometrium (SCNCE; 7), ovary (SCNCO; 7), and cervix (SCNCC; 20). All patients with SCNCE underwent comprehensive surgery and six received postoperative chemotherapy. All patients with SCNCO received chemotherapy after surgery; six underwent comprehensive surgery and one underwent treatment only in the pelvic cavity. Sixteen patients with SCNCC underwent radical surgery and received chemotherapy, two of whom received simultaneous radiotherapy. The remaining four patients with SCNCC underwent comprehensive chemotherapy and radiation therapy. Among the 34 patients, 11 had vascular metastases, 15 had lymph node metastases, and seven exhibited positive margins. The median overall survival time among all patients was 23.18 months (range: 3-66 months). Death occurred in 18 cases (52.94%). Recurrence was observed in 13 cases (38.24%). The average time to recurrence was 15.78 months following treatment (range: 2-30 months). All 34 patients were evaluated for neuroendocrine markers. The immunohistochemical positive rates of synaptophysin, CD56, and chromogranin A were 73.5%, 64.7%, and 55.9%, respectively.

Conclusion: The rates of metastasis and recurrence are high, and prognosis remains poor, even among patients with early-stage SCNCGT. Our data may aid in the development of reference standards for diagnosis and treatment.
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http://dx.doi.org/10.2147/CMAR.S314686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197567PMC
June 2021

Correction: Crystal structure and metallization mechanism of the π-radical metal TED.

Chem Sci 2020 Oct 22;11(43):11945-11946. Epub 2020 Oct 22.

National Institute for Materials Science (NIMS) Sengen 1-2-1 Tsukuba Ibaraki Japan

[This corrects the article DOI: 10.1039/D0SC03521A.].
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http://dx.doi.org/10.1039/d0sc90231dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162466PMC
October 2020

Analysis of the Efficacy and Mechanism of Action of Xuebijing Injection on ARDS Using Meta-Analysis and Network Pharmacology.

Biomed Res Int 2021 22;2021:8824059. Epub 2021 May 22.

Immunology Research Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Objective: Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing.

Methods: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF- and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF- and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software.

Results: Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54-0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97--4.06)), reduced the TNF- ((MD), -1.23 (95% CrI, -1.38--1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52--0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing's action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-, and two components docked with IL-6 got the binding energies lower than -5.

Conclusion: Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF- is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.
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http://dx.doi.org/10.1155/2021/8824059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166476PMC
May 2021

Crystal structure and metallization mechanism of the π-radical metal .

Chem Sci 2020 Sep 11;11(43):11699-11704. Epub 2020 Sep 11.

National Institute for Materials Science (NIMS) Sengen 1-2-1 Tsukuba Ibaraki Japan

Radical electrons tend to localize on individual molecules, resulting in an insulating (Mott-Hubbard) bandgap in the solid state. Herein, we report the crystal structure and intrinsic electronic properties of the first single crystal of a π-radical metal, tetrathiafulvalene-extended dicarboxylate (). The electrical conductivity is up to 30 000 S cm at 2 K and 2300 S cm at room temperature. Temperature dependence of resistivity obeys a power-law above > 100 K, indicating a new type of metal. X-ray crystallographic analysis clarifies the planar molecule, with a symmetric intramolecular hydrogen bond, is stacked along longitudinal (the -axis) and transverse (the -axis) directions. The π-orbitals are distributed to avoid strong local interactions. First-principles electronic calculations reveal the origin of the metallization giving rise to a wide bandwidth exceeding 1 eV near the Fermi level. demonstrates the effect of two-dimensional stacking of π-orbitals on electron delocalization, where a high carrier mobility of 31.6 cm V s (113 K) is achieved.
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http://dx.doi.org/10.1039/d0sc03521aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162741PMC
September 2020

NUCOME: A comprehensive database of nucleosome organization referenced landscapes in mammalian genomes.

BMC Bioinformatics 2021 Jun 13;22(1):321. Epub 2021 Jun 13.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

Background: Nucleosome organization is involved in many regulatory activities in various organisms. However, studies integrating nucleosome organization in mammalian genomes are very limited mainly due to the lack of comprehensive data quality control (QC) assessment and uneven data quality of public data sets.

Results: The NUCOME is a database focused on filtering qualified nucleosome organization referenced landscapes covering various cell types in human and mouse based on QC metrics. The filtering strategy guarantees the quality of nucleosome organization referenced landscapes and exempts users from redundant data set selection and processing. The NUCOME database provides standardized, qualified data source and informative nucleosome organization features at a whole-genome scale and on the level of individual loci.

Conclusions: The NUCOME provides valuable data resources for integrative analyses focus on nucleosome organization. The NUCOME is freely available at http://compbio-zhanglab.org/NUCOME .
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http://dx.doi.org/10.1186/s12859-021-04239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201709PMC
June 2021

Neuroprotective Effects and Related Mechanisms of Echinacoside in MPTP-Induced PD Mice.

Neuropsychiatr Dis Treat 2021 3;17:1779-1792. Epub 2021 Jun 3.

Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, People's Republic of China.

Objective: To explore the neuroprotective effect and the related mechanisms of echinacoside (ECH) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice.

Methods: Parkinson's disease is induced in mice by MPTP and the neurobehaviors of mice in different groups are observed. Then, immunohistochemistry and Western blot analysis are adopted to measure the expression of tyrosine hydroxylase (TH) and α-synuclein in the substantia nigra (SN). The content of dopamine (DA) and other neurotransmitters in the brain is detected by high-performance liquid chromatography. The expression of nerve growth factors and inflammatory factors in SN in mice in each group is measured by quantitative polymerase chain reaction. Finally, the expression of oxidative stress-related parameters in each group is measured.

Results: Compared with the model group, the pole-climbing time among mice in the moderate and high-dose ECH groups is significantly reduced (P < 0.01). The rotarod staying time, as well as fore and hind-limb strides, shows a significant increase (P < 0.01), as does spontaneous activity (P < 0.01). Moreover, the expression levels of TH, DA, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor in SN in mice show significant increases in these two groups (P < 0.01). The content of superoxide dismutase, catalase, and glutathione peroxidase indicates significant increases in the low, moderate, and high-dose ECH groups (P < 0.01), and the content of MDA was reduced (P < 0.01). In the high-dose ECH group, the expression of interleukin (IL) 6 and tumor necrosis factor-α is significantly reduced (P < 0.01), while the expression of IL-10 shows a marked increase (P < 0.01) alongside a decrease in the expression of α-synuclein (P < 0.01).

Conclusion: Echinacoside improves neurobehavioral symptoms in PD mice and significantly increases the expression of TH and DA. The neuroprotective effect potentially correlates with anti-inflammation and anti-oxidation actions, promotes the expression of nerve growth factor, and reduces the accumulation of α-synuclein.
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http://dx.doi.org/10.2147/NDT.S299685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184243PMC
June 2021

Highly efficient electrocatalytic hydrogen evolution promoted by O-Mo-C interfaces of ultrafine β-MoC nanostructures.

Chem Sci 2020 Mar 12;11(13):3523-3530. Epub 2020 Mar 12.

Department of Chemistry, University of South Florida 4202 E. Fowler Avenue Tampa Florida 33620 USA

Optimizing interfacial contacts and thus electron transfer phenomena in heterogeneous electrocatalysts is an effective approach for enhancing electrocatalytic performance. Herein, we successfully synthesized ultrafine β-MoC nanoparticles confined within hollow capsules of nitrogen-doped porous carbon (β[email protected]) and found that the surface layer of molybdenum atoms was further oxidized to a single Mo-O surface layer, thus producing intimate O-Mo-C interfaces. An arsenal of complementary technologies, including XPS, atomic-resolution HAADF-STEM, and XAS analysis clearly reveals the existence of O-Mo-C interfaces for these surface-engineered ultrafine nanostructures. The β[email protected] electrocatalyst exhibited excellent electrocatalytic activity for the hydrogen evolution reaction (HER) in water. Theoretical studies indicate that the highly accessible ultrathin O-Mo-C interfaces serving as the active sites are crucial to the HER performance and underpinned the outstanding electrocatalytic performance of β[email protected] This proof-of-concept study opens a new avenue for the fabrication of highly efficient catalysts for HER and other applications, whilst further demonstrating the importance of exposed interfaces and interfacial contacts in efficient electrocatalysis.
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http://dx.doi.org/10.1039/d0sc00427hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152622PMC
March 2020

The Impact of hyperuricemia on long-term clinical outcomes of renal transplant recipients: a systematic review and meta-analysis.

J Pharm Pharm Sci 2021 ;24:292-307

Purpose: To evaluate the effect of hyperuricemia on clinical outcomes of renal transplant recipients (RTRs).

Methods: A literature search of PubMed, Cochrane, Embase was conducted up to March 20, 2020. The primary outcome was the estimated glomerular filtration rate (eGFR). The second outcomes were the risk of graft loss, death, cardiovascular event and the level of triglyceride. The following search terms were utilized: ((Hyperuricemic group) OR (Hyperuricaemia) OR (Hyperuric) OR (Urea acid) OR (Uric acid) OR (Acid urate) OR (Urate) OR (Gout)) and ((Transplantation) OR (Transplantations) OR (Transplant) OR (Transplants) OR (Graft)).

Results: 28 studies with 18224 patients were eligible for inclusion. There was no significant difference in eGFR (<12 months, p=0.07), the risk of graft loss (<60 months, p=0.07) and death (<60months, p=0.19) between the hyperuricemic and normouricemic group in the early post-transplantation period. But increased uric acid levels contributed to the long-term decline of eGFR, the risk of graft loss and death increased after transplantation. Hyperuricemia increased the risk of cardiovascular event with no significant difference in the level of triglyceride between the two groups.

Conclusions: Increased uric acid levels contributed to the long-term decline of eGFR, increased risk of graft loss and death after transplantation. Although there was no significant effect on triglyceride, hyperuricemia increased the risk of cardiovascular event.
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http://dx.doi.org/10.18433/jpps31620DOI Listing
January 2021

Trans-esophageal echocardiography guided closure of ventricular septal defect with 2 occluders from different incisions simultaneously: A case report.

Medicine (Baltimore) 2021 May;100(19):e23854

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu.

Introduction: Ventricular septal defect (VSD) accounts for up to 40% of all congenital cardiac malformations. Transthoracic closure of VSDs has been well described in literature. In the current report, we described a procedure to successfully close a VSD with 2 occluders from different incisions simultaneously under the guidance of trans-esophageal echocardiography (TEE), to save the patient from undergoing another surgery.

Patient Concerns: A 52-year-old man was referred to our clinic for repeating palpitations for 6 months without chest pain and polypnea after activity.

Diagnosis: The diagnosis of VSD was established due to the findings of a juxtatricuspid VSD with a left-to-right shunt at ventricular level and mild mitral regurgitation by TTE.

Interventions: A transcatheter VSD closure was firstly performed but failed to repair the VSD. After the failure of transcatheter VSD closure, the patient received transthoracic closure of VSD operated by a cardiac surgeon. The VSD was closed with 2 occluders from different incisions (median thoracic skin incision and subxiphoid incision) simultaneously under the TEE guidance.

Outcomes: The patient was extubated in intensive care unit and was discharged 4 days after the operation. During the follow up, there were no significant clinical nor laboratory side-effects of the procedure found as compared to the patient's condition before the procedure.

Conclusion: VSD can be closed with 2 occluders from different incisions simultaneously under the TEE guidance to save the patient from undergoing repeated surgeries. Meanwhile, TEE plays a significant role in cardiac surgery.
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http://dx.doi.org/10.1097/MD.0000000000023854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133107PMC
May 2021

MXene-Based Materials for Electrochemical Sodium-Ion Storage.

Adv Sci (Weinh) 2021 Jun 15;8(11):e2003185. Epub 2021 Mar 15.

Pillar of Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372, Singapore.

Advanced architecture and rational design of electrode materials for electrochemical sodium-ion storage are well developed by researchers worldwide. MXene-based materials are considered as one of the most potential electrode materials for sodium-ion-based devices, such as sodium-ion batteries (SIBs), sodium-sulfur batteries (SSBs), and sodium-ion capacitors (SICs), because of the excellent physicochemical characteristics of MXenes. Here, in this review, the recent research work and progress, both theoretical and experimental, on MXene-based materials including pure MXenes and MXene-based composites in application of SIBs, SSBs, and SICs are comprehensively summarized. The sodium storage mechanisms and the effective methods to enhance the electrochemical performance are also discussed. Finally, the current critical challenges and future research directions on the development of these MXene-based materials for electrochemical sodium-ion storage are presented.
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http://dx.doi.org/10.1002/advs.202003185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188191PMC
June 2021

A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau.

Cell Res 2021 Jun 7. Epub 2021 Jun 7.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

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http://dx.doi.org/10.1038/s41422-021-00517-6DOI Listing
June 2021

lncRNA MIR210HG promotes the progression of endometrial cancer by sponging miR-337-3p/137 via the HMGA2-TGF-β/Wnt pathway.

Mol Ther Nucleic Acids 2021 Jun 16;24:905-922. Epub 2021 Apr 16.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Epithelial-mesenchymal transition (EMT) promotes tumorigenesis and metastasis and increases tumor tolerance to treatment intervention. Abnormal activation of transforming growth factor β (TGF-β) and Wnt pathway induces EMT. Long non-coding RNAs (lncRNAs) significantly influence EMT regulation. Herein, we show that MIR210HG is overexpressed in endometrial cancer tissues, which is associated with poor prognosis. MIR210HG silencing significantly inhibited proliferation, migration, invasion, and EMT phenotype formation as well as tumorigenesis . Mechanistically, bioinformatics analyses, RNA binding protein immunoprecipitation (RIP) assays, and luciferase assays showed that MIR210HG acts as a molecular sponge of miR-337-3p and miR-137 to regulate the expression of HMGA2. Additionally, MIR210HG overexpression significantly enriched the Wnt/β-catenin and TGF-β/Smad3 signaling pathway genes, while MIR210HG or HMGA2 knockdown suppressed the Wnt/β-catenin and TGF-β/Smad3 signaling pathway. Our findings on the MIR210HG-miR-337-3p/137-HMGA2 axis illustrate its potential as a target for endometrial cancer therapeutic development.
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http://dx.doi.org/10.1016/j.omtn.2021.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141672PMC
June 2021

Dynamic monitoring of circulating tumor DNA to predict prognosis and efficacy of adjuvant chemotherapy after resection of colorectal liver metastases.

Theranostics 2021 12;11(14):7018-7028. Epub 2021 May 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.

Hepatectomy and adjuvant chemotherapy after resection of colorectal liver metastases (CRLM) may improve survival, however, patients which may benefit cannot currently be identified. Postoperative circulating tumor DNA (ctDNA) analysis can detect minimal residual disease (MRD) and predict the prognosis and efficacy of adjuvant chemotherapy. Our study aims to determine the impact of serial ctDNA analysis to predict the outcome among patients undergoing resection of CRLM. Between May 2018 and October 2019, 91 CRLM patients were prospectively enrolled. Whole exome sequencing was performed in 50 primary and 48 metastatic liver tissues. Targeted sequencing of 451 cancer relevant genes was performed in 50 baseline plasma to determine plasma-tissue concordance. We prospectively investigated changes in the amount and constitution of ctDNA in 271 serial plasma samples taken at different time points (baseline, pre-operation, post-operation, post-operative adjuvant chemotherapy (post-ACT) and recurrence) during the treatment of CRLM. Detected molecular alterations were highly consistent among baseline ctDNA, primary and liver metastases tissue. Patients with a higher variant allele frequency (VAF) level at baseline ctDNA represent a higher tumor burden, and decreased ctDNA during pre-operative chemotherapy predicted better tumor response. Patients with detectable post-operative and post-ACT ctDNA were associated with significantly shorter recurrence-free survival (RFS). ROC analysis showed that post-ACT ctDNA status was superior to post-operative ctDNA status in predicting RFS with an AUROC of 0.79. A significant difference in overall recurrence rate was observed in patients with detectable vs undetectable levels of ctDNA after resection of CRLM (79.4% vs 41.7%) and after completion of adjuvant chemotherapy (77.3% vs 40.7%). During adjuvant chemotherapy, patients with decreased ctDNA VAF after adjuvant chemotherapy had a recurrence rate of 63.6%, compared to 92.3% in patients with increased ctDNA VAF. We envision that dynamic ctDNA analysis, especially in a post-ACT setting, might be used to not only reflect MRD but also to determine rational personalized adjuvant therapy after the resection of CRLM.
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http://dx.doi.org/10.7150/thno.59644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171084PMC
May 2021

Piperine promotes autophagy flux by P2RX4 activation in /α-synuclein-induced Parkinson disease model.

Autophagy 2021 Jun 7. Epub 2021 Jun 7.

Department of Neurobiology School of Basic Medical Sciences, Capital Medical University, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Key Laboratory on Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, China.

Olfactory dysfunction, one of the earliest non-motor symptoms of Parkinson disease (PD), is accompanied by abnormal deposition of SNCA/α-synuclein in the olfactory bulb (OB). The macroautophagy/autophagy-lysosome pathway (ALP) plays an important role in degrading pathological SNCA and modulating this pathway may be a promising treatment strategy. P2RX4 (purinergic receptor P2X, ligand-gated ion channel 4), a member of the purinergic receptor X family, is a key molecule regulating ALP. Piperine (PIP) is a Chinese medicine with anti-inflammatory and anti-oxidant effects. The present study investigated the neuroprotective effects of PIP on SNCA overexpression-induced PD cell and mouse models. We found that PIP oral administration (25, 50 and 100 mg/kg) for 6 weeks attenuated olfactory deficits and delayed motor deficits in Thy 1- transgenic mice overexpressing human . This was accompanied by a degradation of pathological SNCA in OB. In addition, PIP improved cell viability and promoted degradation of human SNCA in SK-N-SH cells. These protective effects were exerted via autophagy flux promotion by enhancing autophagosome-lysosome membrane fusion. Furthermore, tandem mass tag proteomics analyses showed that P2RX4 plays an important role in PIP treatment-induced activation of autophagy flux. These findings demonstrate that PIP exerts neuroprotective effects in PD models via promotion of autophagy flux and may be an effective agent for PD treatment.
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http://dx.doi.org/10.1080/15548627.2021.1937897DOI Listing
June 2021

Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

J Hepatol 2021 Jun 3. Epub 2021 Jun 3.

Institute of Pharmaceutical Biotechnology and the First Affiliated Hospital Department of Radiation Oncology, Zhejiang University School of Medicine, Hangzhou, China; Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, China. Electronic address:

Background & Aims: The early prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to decrease its high mortality. This study aims to develop a new simplified prognostic score to accurately predict the outcome of these patients.

Methods: The prospective clinical data of 2409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated by an external group.

Results: A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to the 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of four other scores (COSSH-ACLFs, 0.793/0.784; CLIF-C ACLFs, 0.792/0.770; MELDs, 0.731/0.727; MELD-Nas, 0.730/0.726; all p<0.05). The prediction error rates of the new score for 28-day mortality were significantly lower than those of the COSSH-ACLFs (15.9%), CLIF-C ACLFs (16.3%), MELDs (35.3%) and MELD-Nas (35.6%). The probability density function evaluation and risk stratification of the new score also showed the highest predictive values for mortality. The external group further validated these results.

Conclusion: The new prognostic score based on six predictors without an assessment of organ failure can accurately predict and easily stratify the short-term mortality of patients with HBV-ACLF and might be used for early prognosis to decrease the high mortality.

Lay Summary: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome with a high short-term mortality rate. We developed a simplified prognostic score for these patients based on a prospective multicentre cohort that showed the best predictive performance compared with four other generic prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, MELDs and MELD-Nas).
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http://dx.doi.org/10.1016/j.jhep.2021.05.026DOI Listing
June 2021

Gemcitabine Plus Platinum versus Docetaxel Plus Platinum as First-Line Therapy for Metastatic Nasopharyngeal Carcinoma: A Randomized Clinical Study.

Saudi J Med Med Sci 2021 May-Aug;9(2):125-134. Epub 2021 Apr 29.

Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.

Background: A well-established first-line chemotherapy standard for metastatic nasopharyngeal carcinoma is yet lacking.

Objectives: To compare the efficacy and safety of gemcitabine plus platinum versus docetaxel plus platinum regimen as first-line therapies for distal metastatic nasopharyngeal carcinoma.

Study Design And Participants: A single center, randomized, open-label, parallel-arm study. The study included 120 patients with metastatic nasopharyngeal carcinoma who met the study requirements.

Interventions: Participants were randomized in a 1:1 ratio through a sealed envelope selection. Gemcitabine 1000 mg/m/d intravenously (IV) for >30 min (days 1 and 8) or docetaxel 75 mg/m/d IV for 1 h (day 1) were administered to the respective group participants. Nedaplatin 75 mg/m/d, IV (day 1), cisplatin 75 mg/m/d IV (day 1) or carboplatin (area under the curve set as 5) IV (day 1) were used in both groups. One cycle duration was 21 days, with 4-6 cycles for all participants.

Outcomes: The primary assessed outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were short-term efficacy [i.e., response rate (RR) and disease control rate (DCR)] and safety.

Results: Seven patients withdrew from the study, and efficacy and adverse reactions were obtained for 113 patients (gemcitabine: 56; docetaxel: 57). Compared with the docetaxel plus platinum group, the gemcitabine plus platinum group had significantly higher RR (71.4% vs. 52.6%, < 0.05); mPFS (9.7 vs. 7.8 months, < 0.05), and mOS (20.6 vs. 16.8 months, < 0.01). The significance was not associated with increased adverse reactions, as both groups showed similar Grades 3 and 4 adverse reactions ( > 0.05). DCR was non-significantly higher in the gemcitabine group (85.7% vs. 75.4%, > 0.05). Multivariable analysis revealed that time to disease progression, number of involved organs, liver metastasis, and grouping were associated with mPFS and mOS (all < 0.05).

Conclusion: The combination of gemcitabine with platinum is likely superior to that of docetaxel with platinum as first-line treatment for metastatic nasopharyngeal carcinoma.
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http://dx.doi.org/10.4103/sjmms.sjmms_471_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152382PMC
April 2021

Asymmetric Nucleophilic Allylation of α-Chloro Glycinate via Squaramide Anion-Abstraction Catalysis: S1 or S2 Mechanism, or Both?

J Org Chem 2021 Jun 3;86(12):8414-8424. Epub 2021 Jun 3.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543.

The nucleophilic substitution mechanism of enantioselective allylation of α-chloro glycinate catalyzed by squaramide organocatalysts was studied using density functional theory. Based on a comprehensive study of S1 and S2 pathways of a catalyst-free reaction, we found that the catalytic reaction slightly favors the S1 mechanism, instead of the previously proposed S2 mechanism. Further investigation of different leaving groups and nucleophiles revealed that this is not limited to the present reaction, and the S1 mechanism might have been generally overlooked. For the squaramide-catalyzed reactions, the S1 mechanism was predicted to be preferred. However, the rate-determining step of the S1 pathway has changed from the chloride-leaving step to the C-C bond-formation step. Therefore, a first-order dependence on both substrates was predicted, in agreement with the observed second-order kinetics. Intriguingly, the lowest-energy enantioselective transition states (TSs) originate from different pathways; -inducing TS corresponds to the S1 pathway, while -inducing TS corresponds to S2. The calculated enantiomeric excesses of two squaramide catalysts agree well with the experimental values. Given the ubiquity of nucleophilic substitution reactions in chemistry and biology, we believe that our finding will inspire more studies that will lead to an improved mechanistic understanding of important chemical reactions, and it may even lead to better catalysts.
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http://dx.doi.org/10.1021/acs.joc.1c00839DOI Listing
June 2021

The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas.

Front Cell Dev Biol 2021 17;9:670145. Epub 2021 May 17.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs "F-V-S/N-I/V" in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that is positively correlated with and by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG gliomas compared to 2-HG glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
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http://dx.doi.org/10.3389/fcell.2021.670145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165280PMC
May 2021