Publications by authors named "Wenwen Li"

201 Publications

Spatiotemporal occurrence, sources and risk assessment of polycyclic aromatic hydrocarbons in a typical mariculture ecosystem.

Water Res 2021 Sep 4;204:117632. Epub 2021 Sep 4.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Marine Sciences, Ningbo University, 818 Fenghua Road, Ningbo 315211, PR China; School of Marine Sciences, Ningbo University, Ningbo 315211, PR China. Electronic address:

The spatiotemporal variations, influencing factors and potential sources, as well as the ecological/health risks of polycyclic aromatic hydrocarbons (PAHs) were systematically investigated in seawater, sediment, and fish from Xiangshan Bay, China, one of the most important and oldest domestic marine aquaculture bases. The average concentrations of Σ in seawater, sediment and fish were 150 ± 70.0 ng/L, 276 ± 271 μg/kg (dry weight, dw), and 434 ± 151 μg/kg (dw), respectively. Naphthalene, phenanthrene, fluoranthene, benzo(b)fluoranthene and pyrene were the dominant contaminants in all samples. The highest PAH concentrations in the seawater and sediment samples occurred in the inner bay where the mariculture and industry are clustered. Seasonal differences were observed in the seawater samples but not in the sediment samples. Among all 15 fish species, large yellow croaker (Larimichthys crocea) (775 μg/kg (dw)), red drum (Sciaenops ocellatus) (749 μg/kg (dw)), and flathead grey mullet (Mugil cephalus) (637 μg/kg (dw)) had relatively high PAH accumulation concentrations in muscle tissue. According to the molecular diagnostic ratio method, the PAHs in seawater mainly originated from a mixed source of petroleum and combustion, whereas biomass/coal combustion sources were identified for sediment. The results obtained from the risk quotient (for seawater), sediment quality guidelines and toxic equivalence quotients (for seawater and sediment) methods showed that the ecological risks posed by PAHs were generally at a low to moderate level. Potentially toxic effects existed from PAH-contaminated fish consumption, and the resulting potential carcinogenic risk was also slightly higher than the recommended guidelines (10).
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http://dx.doi.org/10.1016/j.watres.2021.117632DOI Listing
September 2021

A -mutant patient with late-stage duodenal adenocarcinoma benefited from anti-HER2 therapy and PD-1 inhibition: a case report.

J Gastrointest Oncol 2021 Aug;12(4):1939-1943

Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, China.

Duodenal adenocarcinoma (DA) is a subtype of small bowel adenocarcinoma (SBA). Compared with gastrointestinal cancers such as colorectal cancer and gastric cancer, SBA is less common. For patients with advanced and metastatic DA, chemotherapies are usually extrapolated from colorectal cancer and gastric cancer but the therapeutic effects remain undefined. Herein, we reported a 50-year-old female patient whom was diagnosed as stage IV DA with metastasis to both lungs and retroperitoneal lymph nodes. The next generation sequencing (NGS) using a panel consisting of 168 cancer related genes revealed amplification of the gene which has been a well-recognized therapeutic target among various tumor types. The anti-HER2 targeted therapy trastuzumab was used in combination with XELOX (oxaliplatin and capecitabine) as the first line treatment. The patient achieved partial response (PR) and had progression-free survival (PFS) of six months. After progressive disease (PD), the patient started the second line treatment with trastuzumab and PD1 inhibitors and remained stable disease (SD) with PFS for three months. The use of trastuzumab in neoadjuvant and adjuvant settings have been reported in sporadic cases. To the best of our knowledge, it is the first report to use anti-HER2 therapy and PD-1 inhibition as systemic therapy for advanced DA patients.
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http://dx.doi.org/10.21037/jgo-21-311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421918PMC
August 2021

Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aβ catabolic enzyme Neprilysin.

Theranostics 2021 11;11(18):8797-8812. Epub 2021 Aug 11.

Sir Run run Hospital, Nanjing Medical University, Nanjing, China.

Neprilysin (NEP) is a major endogenous catabolic enzyme of amyloid β (Aβ). Previous studies have suggested that increasing NEP expression in animal models of Alzheimer's disease had an ameliorative effect. However, the underlying signaling pathway that regulates NEP expression remains unclear. The aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor. Recent studies have shown that AhR plays essential roles in the central nervous system (CNS), but its physiological and pathological roles in regulating NEP are not entirely known. Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay were used to verify the effects of AhR agonists on NEP in a cell model (N2a) and a mouse model (APP/PS1). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the roles of AhR in regulating NEP transcription. Object recognition test and the Morris water maze task were performed to assess the cognitive capacity of the mice. Activating AhR by the endogenous ligand L-Kynurenine (L-KN) or FICZ, or by the exogenous ligand diosmin or indole-3-carbinol (I3C) significantly increases NEP expression and enzyme activity in N2a cells and APP/PS1 mice. We also found that AhR is a direct transcription factor of NEP. Diosmin treatment effectively ameliorated the cognitive disorder and memory deficit of APP/PS1 transgenic mice. By knocking down AhR or using a small molecular inhibitor targeting AhR or NEP, we found that diosmin enhanced Aβ degradation through activated AhR and increased NEP expression. These results indicate a novel pathway for regulating NEP expression in neurons and that AhR may be a potential therapeutic target for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.7150/thno.61601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419060PMC
August 2021

Excitation-transcription coupling via synapto-nuclear signaling triggers autophagy for synaptic turnover and long-lasting synaptic depression.

Autophagy 2021 Aug 30:1-2. Epub 2021 Aug 30.

Department of Neurobiology, Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

For network rewiring and information storage in the brain, late phase long-term synaptic depression (L-LTD) requires the long-lasting reorganization of cellular resources. We found that activation of GRIN/NMDAR recruits transcription-dependent autophagy for synaptic turnover to support L-LTD. Activity-dependent CRTC1 synapto-nuclear translocation increases nuclear CRTC1 that competes with FXR for binding to CREB; this in turn enhances the direct binding between CRTC1-CREB and macroautophagy/autophagy gene promoters. Synergistic actions of CRTC1-CREB are preferentially turned on by LTD-inducing stimuli and switched off by genetic knockdown of CREB or CRTC1, or acutely activating FXR. Disrupted CRTC1-CREB signaling impairs activity-driven loss of surface GRIA/AMPARs and DLG4/PSD-95, and selectively prevents GRIN/NMDAR-dependent L-LTD, which are rescued by enhancing MTOR-regulated autophagy. These findings suggest a novel mechanism in L-LTD, in which brief synaptic activities recruit long-lasting autophagy through excitation-transcription coupling for ensuing synaptic remodeling.
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http://dx.doi.org/10.1080/15548627.2021.1964888DOI Listing
August 2021

Cerebral blood flow in mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.

Ageing Res Rev 2021 Aug 19;71:101450. Epub 2021 Aug 19.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China; Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China; Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. Electronic address:

Background: Reduced cerebral blood flow (CBF) contributes to the pathophysiology of Alzheimer's disease (AD). However, it is unclear whether there is a spatial-temporal-specific pattern of changed CBF in AD progression.

Methods: We systematically screened literature databases for cross-sectional and longitudinal studies reporting resting CBF or CBF velocity (CBFv) among patients with AD, mild cognitive impairment (MCI), and healthy controls (HCs). Standardised mean differences (SMDs) for CBF and mean differences (MDs) for CBFv were calculated. Quality assessments, meta-analysis, subgroup analysis, and meta-regression were subsequently performed (PROSPERO: CRD42020207548).

Results: Overall, 244 studies comprising 13,644 participants and 60 regions were included. Compared with HCs, AD subjects had decreased resting CBF throughout the brain (SMD range: -1.87 to -0.32), especially within the posterior cingulate and temporal-parietal regions. However, MCI subjects presented decreased CBF in ten regions with modest effects (SMD range: -0.86 to -0.25), especially in the precuneus. We identified the decreased CBF in the temporal, parietal, and hippocampal regions was associated with the lower AD Mini-Mental State Examination scores.

Conclusions: Our findings suggest that the spatial-temporal pattern of CBF decreased from the precuneus, posterior cingulate and temporal-parietal regions to broader areas with progression from HC to MCI to AD, supporting the incorporation of CBF into the AD research framework.
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http://dx.doi.org/10.1016/j.arr.2021.101450DOI Listing
August 2021

Replication across space and time must be weak in the social and environmental sciences.

Proc Natl Acad Sci U S A 2021 Aug;118(35)

School of Geographical Sciences and Urban Planning, Arizona State University, Tempe, AZ 85287-5302

Replicability takes on special meaning when researching phenomena that are embedded in space and time, including phenomena distributed on the surface and near surface of the Earth. Two principles, spatial dependence and spatial heterogeneity, are generally characteristic of such phenomena. Various practices have evolved in dealing with spatial heterogeneity, including the use of place-based models. We review the rapidly emerging applications of artificial intelligence to phenomena distributed in space and time and speculate on how the principle of spatial heterogeneity might be addressed. We introduce a concept of weak replicability and discuss possible approaches to its measurement.
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http://dx.doi.org/10.1073/pnas.2015759118DOI Listing
August 2021

Transcriptome Variations in in Response to Two Different Inorganic Nitrogen Sources.

Front Microbiol 2021 28;12:712701. Epub 2021 Jul 28.

Beijing Key Laboratory for Forest Pest Control, College of Forestry, Beijing Forestry University, Beijing, China.

The fungus causes vascular wilt disease on hundreds of plant species. The main focus of the research to control this fungus has been aimed at infection processes such as penetration peg formation and effector secretion, but the ability of the fungus to acquire and utilize nutrients are often overlooked and may hold additional potential to formulate new disease control approaches. Little is known about the molecular mechanisms of nitrogen acquisition and assimilation processes in . In this present study, RNA sequencing and gene expression analysis were used to examine differentially expressed genes in response to the different nitrogen sources, nitrate and ammonium, in . A total of 3244 and 2528 differentially expressed genes were identified in response to nitrate and ammonium treatments, respectively. The data indicated nitrate metabolism requires additional energy input while ammonium metabolism is accompanied by reductions in particular cellular processes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of DEGs during nitrate metabolism revealed that many of the genes encoded those involved in protein biosynthetic and metabolic processes, especially ribosome and RNA polymerase biosynthesis, but also other processes including transport and organonitrogen compound metabolism. Analysis of DEGs in the ammonium treatment indicated that cell cycle, oxidoreductase, and certain metabolic activities were reduced. In addition, DEGs participating in the utilization of both nitrate and ammonium were related to L-serine biosynthesis, energy-dependent multidrug efflux pump activity, and glycerol transport. We further showed that the mutants of three differentially expressed transcription factors (, , and ) exhibited abnormal phenotypes under nitrate and ammonium treatment compared with the wild type strain. Deletion of displayed slower growth when utilizing both nitrogen sources, while deletion of and only affected nitrate metabolism, inferring that nitrogen assimilation required regulation of bZIP transcription factor family and participation of cell cycle. Taken together, our findings illustrate the convergent and distinctive regulatory mechanisms between preferred (ammonium) and alternative nitrogen (nitrate) metabolism at the transcriptome level, leading to better understanding of inorganic nitrogen metabolism in .
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http://dx.doi.org/10.3389/fmicb.2021.712701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355529PMC
July 2021

Characterization the structural property and degradation behavior of corn starch in KOH/thiourea aqueous solution.

Carbohydr Polym 2021 Oct 22;270:118363. Epub 2021 Jun 22.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Wuxi 214122, Jiangsu Province, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, China; Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, Jiangsu Province, China. Electronic address:

Finding an efficient and eco-friendly solution for starch dissolution has attracted considerable attentions in recent years. This study investigated the structural characteristics, and degradation behavior of corn starch in KOH/thiourea aqueous solution by the comparison with DMSO/LiBr and 1-allyl-3-methylimidazolium chloride (AMIMCl). Results showed that KOH/thiourea solution was an effective solvent for corn starch dissolution (30 min with 97.01% solubility). X-ray diffraction (XRD) and C CP-MAS NMR spectroscopy revealed that native crystallinity of the corn starch was altered by all tested solvents, especially DMSO/LiBr and AMIMCl. Conversely, this new solvent did not change the primary molecular structure, chain-length distribution, or thermal stability of starch, compared with the native starch. Furthermore, KOH/thiourea solution was more suitable for measuring the molecular weight of corn starch, with a weight-average molecular weight (M) of 7.18 × 10 g/mol. Therefore, KOH/thiourea solution is a promising novel solvent for starch dissolution and structural exploration.
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http://dx.doi.org/10.1016/j.carbpol.2021.118363DOI Listing
October 2021

Race-Related Association between APOE Genotype and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

J Alzheimers Dis 2021 ;83(2):897-906

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations.

Objective: This study aims to determine how race and APOE genotype affect the risks for AD.

Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes.

Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOEɛ4 was a risk factor for AD, whereas APOEɛ2 protected against it. The effects of APOEɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOEɛ4/ɛ4 and lower frequency of APOEɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races.

Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.
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http://dx.doi.org/10.3233/JAD-210549DOI Listing
January 2021

Analgesic effect of the main components of Corydalis yanhusuo (yanhusuo in Chinese) is caused by inhibition of voltage gated sodium channels.

J Ethnopharmacol 2021 Nov 27;280:114457. Epub 2021 Jul 27.

School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China. Electronic address:

Ethnopharmacology Relevance: Pain often causes a series of abnormal changes in physiology and psychology, which can lead to disease and even death. Drug therapy is the most basic and commonly used method for pain relief and management. Interestingly, at present, hundreds of traditional Chinese medicines have been reported to be used for pain relief, most of which are monomer preparations, which have been developed into new painkillers. Corydalis yanhusuo is a representative of one of these medicines and is available for pain relief.

Aim Of The Study: This study aims to determine the analgesic effect and the potential targets of the monomers derived from Corydalis yanhusuo, and to explore any possible associated cardiac risk factors.

Materials And Methods: In this study, four monomers derived from Corydalis yanhusuo (tetrahydropalmatine, corydaline, protopine, dehydrocorydaline) were tested in vivo, using the formalin-induced pain model to determine their analgesic properties. Their potential targets were also determined using whole cell patch clamp recordings and myocardial enzyme assays.

Results: The results showed that all monomers showed analgesic activity and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.7, which indicating that Nav1.7 might be involved in the analgesic mechanism of Corydalis yanhusuo. Protopine increased the level of creatine kinase-MB (CK-MB) and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.5, indicating that Nav1.5 might be involved in the cardiac risk associated with protopine treatment.

Conclusion: These data showed that tetrahydropalmatine produced the best analgesic effect and the lowest cardiac risk. Thus, voltage gated sodium channels (VGSCs) might be the main targets associated with Corydalis yanhusuo. This study, therefore, provides valuable information for future studies and use of traditional Chines medicines for the alleviation of pain.
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http://dx.doi.org/10.1016/j.jep.2021.114457DOI Listing
November 2021

Neuronal activity recruits the CRTC1/CREB axis to drive transcription-dependent autophagy for maintaining late-phase LTD.

Cell Rep 2021 Jul;36(3):109398

Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Affiliated Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China; Research Units for Emotion and Emotion Disorders, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Cellular resources must be reorganized for long-term synaptic plasticity during brain information processing, in which coordinated gene transcription and protein turnover are required. However, the mechanism underlying this process remains elusive. Here, we report that activating N-methyl-d-aspartate receptors (NMDARs) induce transcription-dependent autophagy for synaptic turnover and late-phase long-term synaptic depression (L-LTD), which invokes cytoplasm-to-nucleus signaling mechanisms known to be required for late-phase long-term synaptic potentiation (L-LTP). Mechanistically, LTD-inducing stimuli specifically dephosphorylate CRTC1 (CREB-regulated transcription coactivator 1) at Ser-151 and are advantaged in recruiting CRTC1 from cytoplasm to the nucleus, where it competes with FXR (fed-state sensing nuclear receptor) for binding to CREB (cAMP response element-binding protein) and drives autophagy gene expression. Disrupting synergistic actions of CREB and CRTC1 (two essential L-LTP transcription factors) impairs transcription-dependent autophagy induction and prevents NMDAR-dependent L-LTD, which can be rescued by constitutively inducing mechanistic target of rapamycin (mTOR)-dependent autophagy. Together, these findings uncover mechanistic commonalities between L-LTP and L-LTD, suggesting that synaptic activity can tune excitation-transcription coupling for distinct long-lasting synaptic remodeling.
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http://dx.doi.org/10.1016/j.celrep.2021.109398DOI Listing
July 2021

The mechanism and candidate compounds of aged citrus peel () preventing chronic obstructive pulmonary disease and its progression to lung cancer.

Food Nutr Res 2021 17;65. Epub 2021 May 17.

Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng, China.

Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for developing lung cancer. Aged citrus peel () has been used as a dietary supplement for respiratory diseases in China.

Objective: To explore the mechanism and candidate compounds of preventing COPD and its progression to lung cancer.

Methods: The active components and potential targets of were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease-associated targets of COPD and lung cancer were collected in the Gene Cards and TTD database. The component-target network and PPI network were constructed using the Cytoscape 3.8.0 software. David database was used for GO and KEGG enrichment analysis. The main active components were verified by using the autodock Vina 1.1.2 software. Mouse lung cancer with COPD was induced by cigarette smoking (CS) combined with urethane injection to confirm preventing the effect of hesperetin (the candidate compound of ) on COPD progression to lung cancer and its underlying mechanisms.

Results: The network analysis revealed that the key active components of (nobiletin, naringenin, hesperetin) regulate five core targets (AKT1, TP53, IL6, VEGFA, MMP9). In addition, 103 potential pathways of were identified. can prevent COPD and its progression to lung cancer by getting involved in the PI3K-Akt signaling pathway and MAPK signaling pathway. Molecular docking indicated that hesperetin had better binding activity for core targets. In mouse lung cancer with COPD, treatment with hesperetin dose-dependently improved not only lung tissue injury in COPD but also carcinoma lesions in lung cancer. Meanwhile, hesperetin could suppress the protein expression of AKT1, IL6, VEGFA, MMP9 and up-regulate the protein expression of TP53, and thus reduced the risk of COPD progression to lung cancer.

Conclusion: Hesperetin is a candidate compound of that helps in preventing COPD and its progression to lung cancer by regulating AKT1, IL6, VEGFA, MMP9 and TP53.
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http://dx.doi.org/10.29219/fnr.v65.7526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254466PMC
May 2021

The Clinical Efficiency and the Mechanism of Sanzi Yangqin Decoction for Chronic Obstructive Pulmonary Disease.

Evid Based Complement Alternat Med 2021 10;2021:5565562. Epub 2021 Jun 10.

School of Pharmacy and Chemical Engineering, Zhengzhou University of Industry Technology, Xinzheng, Henan Province 451150, China.

This work is carried out to evaluate the clinical efficacy of Sanzi Yangqin decoction (SZYQD) treating chronic obstructive pulmonary disease (COPD) and to analyze its mechanism. The clinical efficacy of SZYQD treating COPD was evaluated by meta-analysis, and its mechanism was analyzed by network pharmacology. Molecular docking validation of the main active compounds and the core targets was performed by AutoDock vina software. A cigarette smoke (CS) and LPS-induced COPD model in ICR mice was constructed to confirm the effects of luteolin on COPD. Results showed that SZYQD has a greater benefit on the total effect (OR = 3.85, 95% CI [3.07, 4.83], =1) in the trial group compared with the control group. The percentage of forced expiratory volume in one second (FEV1%) (MD = 0.5, 95% CI [0.41, 0.59], < 0.00001) and first seconds breathing volume percentage of forced vital capacity (FEV1%/FVC) were improved (MD = 5.97, 95% CI [3.23, 8.71], < 0.00001). There are 27 compounds in SZYQD targeting 104 disease targets related to COPD. PPI network analysis indicated that EGFR, MMP9, PTGS2, MMP2, APP, and ERBB2 may be the core targets for the treatment of COPD. Molecular docking demonstrated that luteolin in SZYQD showed the strongest binding activity to core targets. Experimental results revealed that the expression of COPD-related targets in lung tissue was significantly increased in the COPD group and was improved in the luteolin group. Our data indicated that SZYQD has a curative effect on COPD and luteolin is a candidate compound for COPD treatment by regulating EGFR, MMP9, PTGS2, MMP2, APP, and ERBB2.
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http://dx.doi.org/10.1155/2021/5565562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213503PMC
June 2021

The structure of exopolyphosphatase (PPX) from Porphyromonas gingivalis in complex with substrate analogs and magnesium ions reveals the basis for polyphosphate processivity.

J Struct Biol 2021 09 30;213(3):107767. Epub 2021 Jun 30.

Food and Pharmacy College, Xuchang University, China; Key Laboratory of Biomarker Based Rapid-detection Technology for Food Safety of Henan Province, Xuchang University, China.

The enzymes exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) play important roles in the bacterial stringent response. PPX degrades inorganic polyphosphate (polyP), a polymer composed of a few to hundreds of phosphate residues supporting cell survival in the stationary phase. The crystal structure of PPX from Porphyromonas gingivalis (PgPPX) in complex with catalytic magnesium ions and several sulfate ions was solved. PgPPX contained two domains and represented a "closed" configuration. Four sulfate ions forming a linear dispersed chain were observed in the aqueduct of the PPX dimer, which the long polyP chain most likely occupied. The side chain of R255 stretched into the cavity where polyP could be located, obstructing the entrance of larger substrates such as NTP and NDP. This study provided the first view into the structure of the PPX/GppA homolog in complex with magnesium ions and substrate analogs and explained how PgPPX implemented its functionality.
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http://dx.doi.org/10.1016/j.jsb.2021.107767DOI Listing
September 2021

Soil Nutrient Estimation and Mapping in Farmland Based on UAV Imaging Spectrometry.

Sensors (Basel) 2021 Jun 6;21(11). Epub 2021 Jun 6.

College of Resources and Civil Engineering, Northeastern University, Shenyang 110819, China.

Soil nutrient is one of the most important properties for improving farmland quality and product. Imaging spectrometry has the potential for rapid acquisition and real-time monitoring of soil characteristics. This study aims to explore the preprocessing and modeling methods of hyperspectral images obtained from an unmanned aerial vehicle (UAV) platform for estimating the soil organic matter (SOM) and soil total nitrogen (STN) in farmland. The results showed that: (1) Multiplicative Scattering Correction (MSC) performed better in reducing image scattering noise than Standard Normal Variate (SNV) transformation or spectral derivatives, and it yielded a result with higher correlation and lower signal-to-noise ratio; (2) The proposed feature selection method combining Successive Projections Algorithm (SPA) and Competitive Adaptive Reweighted Sampling algorithm (CARS), could provide selective preference for hyperspectral bands. Exploiting this method, 24 and 22 feature bands were selected for SOM and STN estimation, respectively; (3) The particle swarm optimization (PSO) algorithm was employed to obtain optimized input weights and bias values of the extreme learning machine (ELM) model for more accurate prediction of SOM and STN. The improved PSO-ELM model based on the selected preference bands achieved higher prediction accuracy (R of 0.73 and RPD of 1.91 for SOM, R of 0.63, and RPD of 1.53 for STN) than support vector machine (SVM), partial least squares regression (PLSR), and the ELM model. This study provides an important guideline for monitoring soil nutrient for precision agriculture with imaging spectrometry.
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http://dx.doi.org/10.3390/s21113919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201019PMC
June 2021

Nucleoprotein (P40) Binding to 5HT2C Receptors (5HT2CR) is the Key Point in the Pathogenesis of BoDV-1-Infected Hosts.

Neurochem Res 2021 Sep 24;46(9):2427-2438. Epub 2021 Jun 24.

NHC Key Laboratory of Diagnosis and Treatment On Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, China.

Nucleoprotein (P40) is one of the most important proteins of Borna disease virus 1 (BoDV-1), but which proteins it would bind to in the pathogenesis of BoDV-1-infected hosts is unknown. We used lentivirus LV5-P40 overexpressing P40 to infect primary hippocampal neurons and characterized the interactome of P40 with co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS) analysis. These interacting protein partners revealed the pathogenesis of BoDV-1-infected hosts. We also show for the first time that P40 interacts with 5HT2CR in rat neurons, which may be the molecular basis leading to neuropsychiatric diseases such as anxiety disorders and behavioral abnormalities after BoDV-1 infection of hosts.
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http://dx.doi.org/10.1007/s11064-021-03385-zDOI Listing
September 2021

Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.

J Alzheimers Dis 2021 ;82(4):1475-1485

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

Background: Dysfunction of microglia has been increasingly recognized as a causative factor in Alzheimer's disease (AD); thus, developing medicines capable of restoring microglial functions is critically important and constitutes a promising therapeutic strategy. Honokiol is a natural neuroprotective compound extracted from Magnolia officinalis, which may play roles in AD therapy.

Objective: This study aimed to evaluate the role and the underlying mechanisms of honokiol in microglial phagocytosis.

Methods: MTT and flow cytometry were used to assess the cell viability and apoptosis, respectively. Phagocytic capacity, mitochondrial reactive oxygen species production, and membrane potential were evaluated using fluorescence microscopy. Seahorse XF24 extracellular flux analyzer was for cell glycolysis and oxidative phosphorylation detection. Mass spectrometry was applied for metabolites measurement. Quantitative real-time polymerase chain reaction and western blotting were performed to detect the mRNA and protein level of PPARγ and PGC1α, respectively.

Results: Honokiol alleviated Aβ42-induced BV2 neurotoxicity. Honokiol promoted phagocytic efficiency of BV2 cells through reversing a metabolic switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production. Meanwhile, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential. Moreover, honokiol increased the expression of PPARγ and PGC1α, which might play positive roles in energy metabolism and microglial phagocytosis.

Conclusion: In this study, honokiol was identified as an effect natural product capable of enhancing mitochondrial function thus promoting microglial phagocytic function.
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http://dx.doi.org/10.3233/JAD-210177DOI Listing
January 2021

Preparation of sludge-based activated carbon for adsorption of dimethyl sulfide and dimethyl disulfide during sludge aerobic composting.

Chemosphere 2021 Sep 17;279:130924. Epub 2021 May 17.

Beijing Key Lab for Source Control Technology of Water Pollution, Engineering Research Center for Water Pollution Source Control & Eco-remediation, College of Environmental Science & Engineering, Beijing Forestry University, Beijing, 100083, China. Electronic address:

Emission of dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) during sludge aerobic composting has limited the use and development of this economical sludge treatment process. In this study, cheap and easily available sludge was used as raw material for the preparation of adsorbents to eliminate DMS and DMDS. A series of sludge-based activated carbons (SACs) were prepared by acid or base activation, and coconut shell mix was also assessed. The results revealed that SAC preparation by KOH activation without coconut shell mix could significantly enhance the surface area and pore volume of SAC, and showed the maximum adsorption capacity for DMS (53.45 mg g) and DMDS (151.28 mg g). In addition, SAC had a good adsorption effect on a mixture of DMS and DMDS. The SAC adsorbents could efficiently adsorb DMS and DMDS after four cycles of regeneration. Thermodynamic and kinetic analyses demonstrated that adsorption between the SAC and DMS/DMDS was via physical adsorption. The SAC developed in this study utilized waste in a useful way that could significantly reduce the cost of adsorbents and use them for odor elimination during sludge aerobic composting.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130924DOI Listing
September 2021

[Prenatal diagnosis of a fetus with chromosome 18p deletion and duplication].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jun;38(6):569-572

Prenatal Diagnosis Center, Huzhou Women and Children's Health Care Hospital, Huzhou, Zhejiang 313000, China.

Objective: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing.

Methods: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan.

Results: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent.

Conclusion: Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200713-00509DOI Listing
June 2021

A Small Molecule Antagonist of PD-1/PD-L1 Interactions Acts as an Immune Checkpoint Inhibitor for NSCLC and Melanoma Immunotherapy.

Front Immunol 2021 14;12:654463. Epub 2021 May 14.

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Immune checkpoint inhibitors, such as monoclonal antibodies targeting programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1), have achieved enormous success in the treatment of several cancers. However, monoclonal antibodies are expensive to produce, have poor tumor penetration, and may induce autoimmune side effects, all of which limit their application. Here, we demonstrate that PDI-1 (also name PD1/PD-L1 inhibitor 1), a small molecule antagonist of PD-1/PD-L1 interactions, shows potent anti-tumor activity and and acts by relieving PD-1/PD-L1-induced T cell exhaustion. We show that PDI-1 binds with high affinity to purified human and mouse PD-1 and PD-L1 proteins and is a competitive inhibitor of human PD-1/PD-L1 binding . Incubation of activated human T cells with PDI-1 enhanced their cytotoxicity towards human lung cancer and melanoma cells, and concomitantly increased the production of granzyme B, perforin, and inflammatory cytokines. Luciferase reporter assays showed that PDI-1 directly increases TCR-mediated activation of NFAT in a PD-1/PD-L1-dependent manner. In two syngeneic mouse tumor models, the intraperitoneal administration of PDI-1 reduced the growth of tumors derived from human PD-L1-transfected mouse lung cancer and melanoma cells; increased and decreased the abundance of tumor-infiltrating CD8+ and FoxP3+ CD4+ T cells, respectively; decreased the abundance of PD-L1-expressing tumor cells, and increased the production of inflammatory cytokines. The anti-tumor effect of PDI-1 was comparable to that of the anti-PD-L1 antibody atezolizumab. These results suggest that the small molecule inhibitors of PD-1/PD-L1 may be effective as an alternative or complementary immune checkpoint inhibitor to monoclonal antibodies.
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http://dx.doi.org/10.3389/fimmu.2021.654463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160380PMC
May 2021

Genetic diversity, population structure, and relationships of apricot (Prunus) based on restriction site-associated DNA sequencing.

Hortic Res 2020 May 1;7(1):69. Epub 2020 May 1.

College of Horticulture and Forestry, Xinjiang Agricultural University, Urumqi, Xinjiang, 830052, China.

Single-nucleotide polymorphisms (SNPs) are the most abundant form of genomic polymorphisms and are widely used in population genetics research. Here, high-throughput sequencing was used to examine the genome-level diversity, population structure, and relationships of apricot, which are important for germplasm conservation and molecular breeding. Restriction site-associated DNA sequencing (RAD-seq) was adopted to sequence 168 Prunus spp. accessions distributed in five ecological groups, including 74 accessions of cultivated Prunus armeniaca L. and 94 accessions of wild apricots (P. armeniaca L. and Prunus sibirica L.), which generated 417,961 high-quality SNPs. We used cluster, genetic structure, and principal component analyses to examine the genetic diversities and genetic relationships of the 168 accessions. The Dzhungar-Ili ecological group accessions showed the highest genetic diversity in terms of private allele number, observed heterozygosity, and nucleotide diversity. We speculate that the Central Asian ecological group accessions were domesticated from the Dzhungar-Ili ecological group accessions. The population structure and gene flow of the North China and European ecological group accessions suggested a genetic background of P. sibirica. We argue that the two groups should be considered hybrid swarms connected to P. sibirica by continuous and extensive gene flow. P. armeniaca originated in Northwest China (Ili Valley), subsequently spread throughout Central Asia, and eventually spread to Europe. In addition, selective sweep signatures in P. armeniaca during domestication from wild to cultivated apricots, combined with differentially expressed genes, underlie distinct fruit traits, including sugars, aromas, organic acids, and carotenoids. This study provides substantive and valuable genomic resources that will significantly advance apricot improvement and effective utilization.
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http://dx.doi.org/10.1038/s41438-020-0284-6DOI Listing
May 2020

Frequent inappropriate implantable cardioverter defibrillator therapy was determined to be dual atrioventricular nodal non-reentrant tachycardia: A case report.

Medicine (Baltimore) 2021 Apr;100(14):e25370

Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China.

Rationale: Dual atrioventricular node non-reentrant tachycardia (DAVNNRT) is a rare arrhythmia. We present a case of inappropriate implantable cardioverter defibrillator (ICD) therapy caused by DAVNNRT. DAVNNRT is easily misdiagnosed as atrial fibrillation and is often identified as ventricular tachycardia (VT) by the supraventricular tachycardia-ventricular tachycardia (SVT-VT) discriminator of the ICD.

Patient Concerns: A 73-year-old man with ischemic heart disease (IHD) presented with palpitations accompanied by dyspnea and syncope. Frequent multifocal premature ventricular beats and non-sustained ventricular tachycardia were observed on ambulatory electrocardiography. The left ventricular ejection fraction decreased to 32%.

Diagnosis: He was diagnosed with IHD, heart failure with reduced ejection fraction (HFrEF), and VT.

Interventions: : Initially, the patient received a single-chamber ICD implantation for secondary prevention of sudden death. He then suffered from inappropriate anti-tachycardia pacing (ATP)/shock therapy many times after the procedure. DAVNNRT was confirmed in an electrophysiology study (EPS), and radiofrequency ablation of the slow pathway successfully terminated this tachycardia.

Outcomes: No episode of inappropriate ICD therapy or tachycardia occurred during the follow-up.

Lessons: In conclusion, it is essential to have a full understanding of DAVNNRT and eliminate slow pathways for patients with DAVNNRT and be prepared to implant an ICD.
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http://dx.doi.org/10.1097/MD.0000000000025370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036121PMC
April 2021

Lipid Phase Influences the Dynamic Interactions between Graphene Oxide Nanosheets and a Phospholipid Membrane.

J Phys Chem B 2021 04 6;125(14):3589-3597. Epub 2021 Apr 6.

Center for Soft Condensed Matter Physics and Interdisciplinary Research and School of Physical Science and Technology, Soochow University, Suzhou 215006 Jiangsu China.

To understand the possible perturbations of graphene oxide (GO) nanosheets on cell membranes is the first step to evaluate their cytotoxicity, while the membrane heterogeneity such like lipid phase separation complicates such interactions. Using the dynamic giant unilamellar vesicle leakage assays, atomic force microscopy characterizations, and molecular dynamics simulations, we demonstrated the structural and property disturbance of GO on a lipid bilayer membrane in a low ionic strength and neutral pH condition, specifically the influence of lipid phase on this process. GO tends to obliquely insert into and even be sandwiched between leaflets of a liquid-phase membrane, inducing formidable flaw in lipid packing states and fast transmembrane leakage. However, GO adopts parallel adsorption or vertical insertion on/into a gel-phase bilayer, while permeabilization occurs only when the disturbance is strong enough. Our results are helpful to understand the fundamental interaction mechanism between GO nanosheets and cells.
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http://dx.doi.org/10.1021/acs.jpcb.1c02500DOI Listing
April 2021

Effect of dipeptidyl peptidase-4 inhibitors on the progression of atherosclerosis in patients with type 2 diabetes mellitus: A meta-analysis of randomised controlled trials.

Int J Clin Pract 2021 Apr 5:e14213. Epub 2021 Apr 5.

Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Objectives: Type 2 diabetes mellitus (T2DM) can accelerate the clinical process of atherosclerosis (AS). Dipeptidyl peptidase-4 inhibitors (DPP-4Is) have potential anti-AS effects. And, we completed a meta-analysis of the changes in carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) and pulse wave velocity (PWV) of DPP-4Is to research the effect of DPP-4Is in the progression of AS in T2DM patients.

Materials And Methods: We included RCTs that evaluated the impact of DPP-4Is on CIMT, FMD and PWV compared to other treatments from PubMed, Cochrane trials and Embase database before October 31, 2020. We selected the random-effect model and calculated the weighted mean difference (WMD) to evaluate the effect of CIMT, FMD and PWV in T2DM patients.

Results: Through the meta-analysis, we found that DPP-4Is can significantly reduce CIMT in T2DM patients (WMD = -0.036, 95% CI:-0.055 to-0.017; P ≤ .001). Based on the subgroup analysis, we found that CIMT was significantly decreased in patients with greater than 12 months of intervention and without cardiovascular diseases. Besides, we also found that DPP-4Is had a no significant efficacy on the improvement of FMD in T2DM patients (WMD = 0.635, 95% CI: -0.112 to 1.383, P = .097). Our subgroup analysis showed that for T2DM patients who have cardiovascular diseases, DPP-4Is can significantly increase their FMD. In addition, we also found that DPP-4Is had an insignificant influence on PWV in T2DM patients (WMD = 0.424, 95% CI: -0.198 to 1.046, P = .18), but SGLT2 inhibitors may reduce the PWV of T2DM patients.

Conclusions: DPP-4Is can alleviate the development of AS in T2DM patients to a certain extent by reducing CIMT. And, we believe that long-term use of DPP-4Is may be more helpful to alleviate the atherosclerotic development of T2DM without obvious cardiovascular history.
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http://dx.doi.org/10.1111/ijcp.14213DOI Listing
April 2021

Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function.

Stem Cells Transl Med 2021 Jul 4;10(7):956-967. Epub 2021 Mar 4.

Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Mesenchymal stem cells (MSCs) hold great potential in treating patients with diabetes, but the therapeutic effects are not always achieved. Particularly, the clinical factors regulating MSC therapy in this setting are largely unknown. In this study, 24 patients with type 2 diabetes mellitus (T2DM) treated with insulin were selected to receive three intravenous infusions of stem cells from human exfoliated deciduous teeth (SHED) over the course of 6 weeks and were followed up for 12 months. We observed a significant reduction of glycosylated serum albumin level (P < .05) and glycosylated hemoglobin level (P < .05) after SHED transplantation. The total effective rate was 86.36% and 68.18%, respectively, at the end of treatment and follow-up periods. Three patients ceased insulin injections after SHED transplantation. A steamed bread meal test showed that the serum levels of postprandial C-peptide at 2 hours were significantly higher than those at the baseline (P < .05). Further analysis showed that patients with a high level of blood cholesterol and a low baseline level of C-peptide had poor response to SHED transplantation. Some patients experienced a transient fever (11.11%), fatigue (4.17%), or rash (1.39%) after SHED transplantation, which were easily resolved. In summary, SHED infusion is a safe and effective therapy to improve glucose metabolism and islet function in patients with T2DM. Blood lipid levels and baseline islet function may serve as key factors contributing to the therapeutic outcome of MSC transplantation in patients with T2DM.
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http://dx.doi.org/10.1002/sctm.20-0303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235136PMC
July 2021

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology.

Evid Based Complement Alternat Med 2021 13;2021:9473531. Epub 2021 Feb 13.

Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan 475004, China.

Xuefu Zhuyu Decoction (XFZY) is an ancient compound widely used in the treatment of coronary heart disease. However, its efficacy evaluation is not complete and its mechanism of action is not clear enough. In an attempt to address these problems, the efficacy was evaluated by meta-analysis and the mechanism was elucidated by the network pharmacology method. We systematically searched relevant studies in PubMed, Chinese National Knowledge Infrastructure Database (CNKI), Cochrane Library, Wanfang Data, and other databases from 2007 to 2019. The association between XFZY treatment and CHD was estimated by risk ratio (RR) and corresponding 95% confidence intervals (95% CIs). The compounds and the potential protein targets of XFZY were obtained from TCMSP, and active compounds were selected according to their oral bioavailability and drug similarity. The potential genes of coronary heart disease were obtained from TTD, OMIM, and GeneCards. The potential pathways related to genes were determined by GO and KEGG pathway enrichment analyses. The compound-target and compound-target-pathway networks were constructed. Molecular docking validates the component and the target. A total of 21 studies including 1844 patients were enrolled in the present meta-analysis, indicating that XFZY has a greater beneficial on total effect (fixed effect RR = 1.30; 95% Cl: 1.24-1.36; =0.82;  = 0.0%) and electrocardiogram efficacy (fixed effect RR = 1.40; 95% Cl: 1.26-1.56; =0.96;  = 0.0%) compared with the control group. A total of 1342 components in XFZY were obtained, among which, 241 were chosen as bioactive components. GO and KEGG analyses got top 10 significantly enriched terms and 10 enriched pathways. The C-T network included 192 compounds and 3085 targets, whereas the C-T-P network included 10 compounds, 109 targets, and 5 pathways. There was a good binding activity between the components and the targets. XFZY has the curative effect on coronary heart disease, and its mechanism is related to 10 compounds, 10 core targets, and 5 pathways.
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http://dx.doi.org/10.1155/2021/9473531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896852PMC
February 2021

Regulatory effects of non-steroidal anti-inflammatory drugs on cardiac ion channels Nav1.5 and Kv11.1.

Chem Biol Interact 2021 Apr 19;338:109425. Epub 2021 Feb 19.

School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China. Electronic address:

Non-steroidal Anti-inflammatory Drugs (NSAIDs) are widely used because of their excellent anti-inflammatory and analgesic effects. However, NSAIDs could cause certain cardiac side effects, such as myocardial infarction, heart failure, atrial fibrillation, arrhythmia and sudden cardiac death. Therefore, meloxicam, nimesulide, piroxicam, and diclofenac were selected and the whole cell patch clamp technique was used to investigate the electrophysiological regulatory effects of them on the sodium channel hNav1.5 and potassium channel hKv11.1, which were closely associated to the biotoxicity of cardiac, and to explore the potential cardiac risk mechanism. The results showed that the four NSAIDs could inhibit the peak currents of hNav1.5 and hKv11.1. Furthermore, the four NSAIDs could affect both the activation and inactivation processes of hNav1.5 with I-V curves left-shifted to hyperpolarized direction in activation phase. These data indicate that the inhibition effects of Nav1.5 and Kv11.1 by meloxicam, nimesulide, piroxicam, and diclofenac might contribute to their potential cardiac risk. These findings provide a basis for the discovery of other potential cardiac risk targets for NSAIDs.
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http://dx.doi.org/10.1016/j.cbi.2021.109425DOI Listing
April 2021

High performance exhaled breath biomarkers for diagnosis of lung cancer and potential biomarkers for classification of lung cancer.

J Breath Res 2021 02 13;15(1):016017. Epub 2021 Feb 13.

Research Center of Analytical Instrumentation, Key Laboratory of Bio-source and Eco-environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, People's Republic of China.

Exhaled breath analysis has emerged as a promising non-invasive method for diagnosing lung cancer (LC), whereas reliable biomarkers are lacking. Herein, a standardized and systematic study was presented for LC diagnosis, classification and metabolism exploration. To improve the reliability of biomarkers, a validation group was included, and quality control for breath sampling and analysis, comprehensive pollutants analysis, and strict biomarker screening were performed. The performance of exhaled breath biomarkers was shown to be excellent in diagnosing LC even in early stages (stage I and II) with surpassing 0.930 area under the receiver operating characteristic (ROC) curve (AUC), 90% of sensitivity and 88% of specificity both in the discovery and validation analyses. Meanwhile, in these two groups, diagnosing subtypes of LC attained AUCs over 0.930 and reached 1.00 in the two subtypes of adenocarcinomas. It is demonstrated that the metabolism changes in LC are possibly related to lipid oxidation, gut microbial, cytochrome P450 and glutathione S-transferase, and glutathione pathways change in LC progression. Overall, the reliable biomarkers contribute to the clinical application of breath analysis in screening LC patients as well as those in early stages.
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http://dx.doi.org/10.1088/1752-7163/abaecbDOI Listing
February 2021

Gating of hippocampal rhythms and memory by synaptic plasticity in inhibitory interneurons.

Neuron 2021 03 5;109(6):1013-1028.e9. Epub 2021 Feb 5.

Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China; Research Units for Emotion and Emotion Disorders, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Mental experiences can become long-term memories if the hippocampal activity patterns that encode them are broadcast during network oscillations. The activity of inhibitory neurons is essential for generating these neural oscillations, but molecular control of this dynamic process during learning remains unknown. Here, we show that hippocampal oscillatory strength positively correlates with excitatory monosynaptic drive onto inhibitory neurons (E→I) in freely behaving mice. To establish a causal relationship between them, we identified γCaMKII as the long-sought mediator of long-term potentiation for E→I synapses (LTP), which enabled the genetic manipulation of experience-dependent E→I synaptic input/plasticity. Deleting γCaMKII in parvalbumin interneurons selectively eliminated LTP and disrupted experience-driven strengthening in theta and gamma rhythmicity. Behaviorally, this manipulation impaired long-term memory, for which the kinase activity of γCaMKII was required. Taken together, our data suggest that E→I synaptic plasticity, exemplified by LTP, plays a gatekeeping role in tuning experience-dependent brain rhythms and mnemonic function.
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http://dx.doi.org/10.1016/j.neuron.2021.01.014DOI Listing
March 2021
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