Publications by authors named "Jing Cao"

683 Publications

Unsupervised Clustering Reveals Distinct Subtypes of Biliary Atresia Based on Immune Cell Types and Gene Expression.

Front Immunol 2021 27;12:720841. Epub 2021 Sep 27.

Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Biliary atresia (BA) is a severe cholangiopathy of early infancy that destroys cholangiocytes, obstructs ductular pathways and if left untreated, culminates to liver cirrhosis. Mechanisms underlying the etiological heterogeneity remain elusive and few studies have attempted phenotyping BA. We applied machine learning to identify distinct subtypes of BA which correlate with the underlying pathogenesis.

Methods: The BA microarray dataset GSE46995 was downloaded from the Gene Expression Omnibus (GEO) database. Unsupervised hierarchical cluster analysis was performed to identify BA subtypes. Then, functional enrichment analysis was applied and hub genes identified to explore molecular mechanisms associated with each subtype. An independent dataset GSE15235 was used for validation process.

Results: Based on unsupervised cluster analysis, BA patients can be classified into three distinct subtypes: Autoimmune, Viral and Embryonic subtypes. Functional analysis of Subtype 1 correlated with Fc Gamma Receptor (FCGR) activation and hub gene , suggesting an autoimmune response targeting bile ducts. Subtype 2 was associated with immune receptor activity, cytokine receptor, signaling by interleukins, viral protein interaction, suggesting BA is associated with viral infection. Subtype 3 was associated with signaling and regulation of expression of Robo receptors and hub gene , corresponding to embryonic BA. Moreover, Reactome pathway analysis showed Neutrophil degranulation pathway enrichment in all subtypes, suggesting it may result from an early insult that leads to biliary stasis.

Conclusions: The classification of BA into different subtypes improves our current understanding of the underlying pathogenesis of BA and provides new insights for future studies.
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http://dx.doi.org/10.3389/fimmu.2021.720841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502897PMC
September 2021

Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation.

Cell Rep 2021 Oct;37(2):109821

State Key Laboratory of Genetic Engineering, Zhongshan Hospital of Fudan University, School of Life Sciences, Children's Hospital of Fudan University, Fudan University Shanghai Cancer Center, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200438, P.R. China; Department of Anatomy and Neuroscience Research Institute, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.
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http://dx.doi.org/10.1016/j.celrep.2021.109821DOI Listing
October 2021

Intrinsic nucleus-targeted ultra-small metal-organic framework for the type I sonodynamic treatment of orthotopic pancreatic carcinoma.

J Nanobiotechnology 2021 Oct 12;19(1):315. Epub 2021 Oct 12.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jiefang Road, Shangcheng District,, Hangzhou, 310009, People's Republic of China.

Background: Sonodynamic therapy (SDT) strategies exhibit a high tissue penetration depth and can achieve therapeutic efficacy by facilitating the intertumoral release of reactive oxygen species (ROS) with a short lifespan and limited diffusion capabilities. The majority of SDT systems developed to date are of the highly O-dependent type II variety, limiting their therapeutic utility in pancreatic cancer and other hypoxic solid tumor types.

Results: Herein, a nucleus-targeted ultra-small Ti-tetrakis(4-carboxyphenyl)porphyrin (TCPP) metal-organic framework (MOF) platform was synthesized and shown to be an effective mediator of SDT. This MOF was capable of generating large quantities of ROS in an oxygen-independent manner in response to low-intensity ultrasound (US) irradiation (0.5 W cm), thereby facilitating both type I and type II SDT. This approach thus holds great promise for the treatment of highly hypoxic orthotopic pancreatic carcinoma solid tumors. This Ti-TCPP MOF was able to induce in vitro cellular apoptosis by directly destroying DNA and inducing S phase cell cycle arrest following US irradiation. The prolonged circulation, high intratumoral accumulation, and nucleus-targeting attributes of these MOF preparations significantly also served to significantly inhibit orthotopic pancreatic tumor growth and prolong the survival of tumor-bearing mice following Ti-TCPP + US treatment. Moreover, this Ti-TCPP MOF was almost completely cleared from mice within 7 days of treatment, and no apparent treatment-associated toxicity was observed.

Conclusion: The nucleus-targeted ultra-small Ti-TCPP MOF developed herein represents an effective approach to the enhanced SDT treatment of tumors in response to low-intensity US irradiation.
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http://dx.doi.org/10.1186/s12951-021-01060-7DOI Listing
October 2021

The kinase CIPK14 functions as a negative regulator of plant immune responses to Pseudomonas syringae in Arabidopsis.

Plant Sci 2021 Nov 12;312:111017. Epub 2021 Aug 12.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China. Electronic address:

As a critical second messenger in plants, Ca is involved in numerous biological processes including biotic and abiotic stress responses. The CBL-interacting protein kinases, known as CIPKs, are essential components in Ca-mediated signal transduction pathways. Here, we found that CIPK14 plays a role in the process of regulating immune response in Arabidopsis. The CIPK14 loss-of-function mutants exhibited enhanced resistance to the P. syringae, whereas CIPK14 overexpression plants were more susceptible to bacterial pathogen. Enhanced resistance in cipk14 mutants were accompanied by increased accumulation of SA and elevated expression of defense marker genes (PR1, EDS1, EDS5, ICS1). Overexpression of CIPK14 suppressed Pst DC3000, Pst DC3000 hrcC and flg22 induced generation of ROS and callose deposition. As compared with wild type plants, the expression levels of MPK3/6-dependent PTI marker genes (FRK1, CYP81F2, WAK2, FOX) were up-regulated in cipk14 mutants but down-regulated in CIPK14 overexpression plants after flg22 and elf18 treatment. Additionally, both loss-of-function and gain-of-function of CIPK14 significantly altered the phosphorylation status of MPK3/6 under flg22 treatment, suggesting that CIPK14 is a general modulator of plant immunity at both transcriptional and post-transcriptional level. Taken together, our results uncover that CIPK14 acts as a negative regulator in plant immune response.
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http://dx.doi.org/10.1016/j.plantsci.2021.111017DOI Listing
November 2021

Corrigendum to Vascular peroxidase 1 is a novel regulator of cardiac fibrosis after myocardial infarction [Redox Biol. 22, (2019), 101151].

Redox Biol 2021 Sep 27:102146. Epub 2021 Sep 27.

Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

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http://dx.doi.org/10.1016/j.redox.2021.102146DOI Listing
September 2021

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy.

Int J Gen Med 2021 21;14:5927-5937. Epub 2021 Sep 21.

Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Purpose: Ischemic cardiomyopathy (ICM) is considered to be the most common cause of heart failure, with high prevalence and mortality. This study aimed to investigate the different expressed genes (DEGs) and pathways in the pathogenesis of ICM using bioinformatics analysis.

Methods: The control and ICM datasets GSE116250, GSE46224 and GSE5406 were collected from the gene expression omnibus (GEO) database. DEGs were identified using limma package of R software, and co-expressed genes were identified using Venn diagrams. Then, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the biological functions and signaling pathways. Protein-protein interaction (PPI) networks were assembled with Cytoscape software to identify hub genes related to the pathogenesis of ICM. RT-PCR of Heart tissues (n=2 for non-failing controls and n=4 for ischemic cardiomyopathy patients) was used to validate the bioinformatic results.

Results: A total of 844 DEGs were screened from GSE116250, of which 447 were up-regulated genes and 397 were down-regulated genes, respectively. A total of 99 DEGs were singled out from GSE46224, of which 58 were up-regulated genes and 41 were down-regulated genes, respectively. Thirty DEGs were screened from GSE5406, including 10 genes with up-regulated expression and 20 genes with down-regulated expression. Five up-regulated and 3 down-regulated co-expressed DEGs were intersected in three datasets. GO and KEGG pathway analyses revealed that DEGs are mainly enriched in collagen fibril organization, protein digestion and absorption, AGE-RAGE signaling pathway and other related pathways. Collagen alpha-1(III) chain (COL3A1), collagen alpha-2(I) chain (COL1A2) and lumican (LUM) are the three hub genes in all three datasets through PPI network analysis. The expression of 5 DEGs (SERPINA3, FCN3, COL3A1, HBB, MXRA5) in heart tissues by qRT-PCR results was consistent with our GEO analysis, while expression of 3 DEGs (ASPN, LUM, COL1A2) was opposite with GEO analysis.

Conclusion: These findings from this bioinformatics network analysis investigated key hub genes, which contributed to better understanding the mechanism and new therapeutic targets of ICM.
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http://dx.doi.org/10.2147/IJGM.S329980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464396PMC
September 2021

Ferroptosis Mechanisms Involved in Hippocampal-Related Diseases.

Int J Mol Sci 2021 Sep 14;22(18). Epub 2021 Sep 14.

Neurobiology Laboratory, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.

Ferroptosis is a newly recognized type of cell death that is different from traditional forms of cell death, such as apoptosis, autophagy, and necrosis. It is caused by the accumulation of intracellular iron, promoting lipid peroxidation and leading to cell death. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. An increased concentration of iron in the central nervous system has been associated with oxidative stress, lipid peroxidation of proteins, and cell death. The hippocampus is an important brain region for learning, memory, and emotional responses, and is also a sensitive part of the brain to the dysfunctional homeostasis of transition metals. Damage of hippocampal structure and function are intimately involved in the pathogenic mechanisms underlying neurodegenerative diseases. Currently, ferroptosis is playing an increasingly important role in treatment areas of central nervous system diseases. Thus, we provide an overview of ferroptosis regulatory mechanisms, such as lipid metabolism, glutathione metabolism, and iron metabolism in this review. We also highlight the role of ferroptosis in hippocampal-related diseases and investigate a theoretical basis for further research on the role of ferroptosis in nervous system disease treatment.
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http://dx.doi.org/10.3390/ijms22189902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472822PMC
September 2021

Effects of konjac glucomannan with different molecular weights on gut microflora with antibiotic perturbance in in vitro fecal fermentation.

Carbohydr Polym 2021 Dec 18;273:118546. Epub 2021 Aug 18.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

This study investigated the effect of konjac glucomannan (KGM) of different molecular weight on fecal microflora against antibiotic disturbance. KGM (~1.8 × 10 Da) was partially hydrolysed with trifluoroacetic acid (TFA) for 10 and 60 min to KGM1 (~2.1 × 10 Da) and KGM2 (7413 Da), respectively. The acid treatment caused significant reduction of intrinsic viscosity, average molecular weight (MW) and particle size of KGM, but brought limited change to the molecular structure. Low-MW KGM2 showed the most significant effect on fecal microflora in the presence of two common antibiotics (ampicillin and clindamycin), by increasing the relative abundance of Bifidobacteriaceae while decreasing the proportion of Enterobacteriaceae. Additionally, both the native and acid-treated KGM counteracted the adverse influence of antibiotics on the production of short chain fatty acids. The results have demonstrated the effect of KGM on gut microbiota with antibiotic disturbance.
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http://dx.doi.org/10.1016/j.carbpol.2021.118546DOI Listing
December 2021

Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis.

Biochem Biophys Res Commun 2021 Nov 16;578:77-83. Epub 2021 Sep 16.

Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Key Laboratory of Cellular Physiology of Shanxi Province, And the Department of Physiology, Shanxi Medical University, Taiyuan, China. Electronic address:

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.
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http://dx.doi.org/10.1016/j.bbrc.2021.09.027DOI Listing
November 2021

Genome-Wide Identification and Analysis of the Phosphoenolpyruvate Carboxylase Gene Family in , an Annual Halophyte With Single-Cellular C Anatomy.

Front Plant Sci 2021 30;12:665279. Epub 2021 Aug 30.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.

Phosphoenolpyruvate carboxylase (PEPC) plays pivotal roles in the carbon fixation of photosynthesis and a variety of metabolic and stress pathways. belongs to a single-cellular C species and carries out a photosynthetic pathway in an unusually elongated chlorenchyma cell, which is expected to have PEPCs with different characteristics. To identify the different isoforms of genes in and comparatively analyze their expression and regulation patterns as well as the biochemical and enzymatic properties in this study, we characterized a bacterial-type PEPC (BTPC; SaPEPC-4) in addition to the two plant-type PEPCs (PTPCs; SaPEPC-1 and SaPEPC-2) using a genome-wide identification. presented a lower expression level in all test combinations with an unknown function; two SaPTPCs showed distinct subcellular localizations and different spatiotemporal expression patterns but positively responded to abiotic stresses. Compared to , the expression of specifically in chlorenchyma cell tissues was much more active with the progression of development and under various stresses, particularly sensitive to light, implying the involvement of in a C photosynthetic pathway. In contrast, was more like a non-photosynthetic PEPC. The expression trends of two SaPTPCs in response to light, development, and abiotic stresses were also matched with the changes in PEPC activity (native) or (recombinant), and the biochemical properties of the two recombinant SaPTPCs were similar in response to various effectors while the catalytic efficiency, substrate affinity, and enzyme activity of SaPEPC-2 were higher than that of SaPEPC-1 All the different properties between these two SaPTPCs might be involved in transcriptional (e.g., specific -elements), posttranscriptional [e.g., 5'-untranslated region (5'-UTR) secondary structure], or translational (e.g., PEPC phosphorylation/dephosphorylation) regulatory events. The comparative studies on the different isoforms of the PEPC gene family in may help to decipher their exact role in C photosynthesis, plant growth/development, and stress resistance.
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http://dx.doi.org/10.3389/fpls.2021.665279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435749PMC
August 2021

U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis.

Front Cardiovasc Med 2021 24;8:604736. Epub 2021 Aug 24.

Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group ( = 460) and the severe group (severe and critical cases) ( = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a -shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12-4.68; = 0.023) and 2.02 (1.04-3.94; = 0.039), respectively, compared to those with LDL-C of 2.81-3.40 mmol/L (108.6-131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07-6.37; = 0.035) and 2.36 (1.09-5.14; = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.
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http://dx.doi.org/10.3389/fcvm.2021.604736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421675PMC
August 2021

Risk factor for 31-day unplanned readmission to hospital in patients with pulmonary tuberculosis in China.

Saudi Med J 2021 Sep;42(9):1017-1023

From the Department of Statistical Office, Changsha Central Hospital (Cao), Changsha; from the Pediatric Department, Shenzhen People's Hospital (Lie), Shenzhen; and from the Chronic Disease Prevention and Treatment Department, Loudi Center For Disease Control And Prevention (Huang), Loudi, China.

Objectives: To evaluate risk factors associated with 31-day unplanned readmission(s) for pulmonary tuberculosis (TB) in China.

Methods: This retrospective study enrolled patients (age, >14 years) with pulmonary TB who experienced 31-day unplanned readmissions to a specialized hospital for TB between January 2018 and December 2019. For each confirmed readmission, 2 control subjects were randomly selected from among patients with pulmonary TB but did not experience an unplanned readmission within 31 days.

Results: A total of 402 pulmonary TB patients (5.9%) experienced unplanned readmission within 31 days after discharge. In univariate analysis, readmission was associated with gender, age, insurance coverage, residing in a rural area, active smoking, chronic obstructive pulmonary disease (COPD), drug-induced hepatitis, and leaving hospital against medical advice. The final logistic regression model revealed that higher risks for unplanned readmissions were associated with male gender (odds ratio [OR] 1.44, [95% confidence interval (CI) : 1.06-1.95]), age >65 years (OR 2.94, 95%CI: 2.03-4.27), rural residence (OR 8.86, 95%CI: 6.61-11.87), active smoking (OR 2.15, 95% CI 1.37-3.40), COPD (OR 2.77, 95%CI: 1.59-4.81), and leaving hospital against physician advice (OR 4.11, 95%CI: 1.43-11.83). The median time to 31-day unplanned readmission was 24 days. Major reasons for unplanned readmission included fever, exacerbation of dyspnea, and hemoptysis.

Conclusion: Unplanned readmission for pulmonary TB within 31 days of discharge was higher among older males residing in rural areas, active smokers, and those leaving hospital against medical advice.
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http://dx.doi.org/10.15537/smj.2021.42.9.20210281DOI Listing
September 2021

Psychological impact on COVID-19 patients during the outbreak in China: A case-control study.

Psychiatry Res 2021 Aug 23;305:114180. Epub 2021 Aug 23.

Department of Neurology, Hanyang Hospital of Wuhan, Hubei, China. Electronic address:

Background: The coronavirus disease 2019 (COVID-19) has caused widespread panic due to its highly infectious and pandemic transmission. We aimed to evaluate the psychological impact of the COVID-19 outbreak on infected subjects in China.

Methods: This case-control, survey-based study assessed the psychological status of COVID-19 patients and non-infected controls from February 10 to March 18, 2020, in China. Sex, age, education years, marital status, jobs, annual household income, living status, and geographic origin were matched between the two groups. The main outcome measures included anxiety, depression, insomnia, help-seeking behaviors, and treatment for mental problems.

Results: A total of 326 patients and 1304 (1:4 ratio) matched non-infected controls were enrolled. Compared with controls, patients had higher scores on the Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), and Insomnia Severity Index (ISI) (all p<0.01). Patients had higher rate of any mental problems (62.6% vs 42.5%, p<0.01), anxiety (27.3% vs 12.2%, p<0.01), depression (26.7% vs 14.6%, p<0.01), suicidal ideation (16.0% vs 10.7%, p<0.01), and insomnia (57.7% vs 36.7%, p<0.01). Among the subjects with mental problems, the proportion of seeking help (15.2% vs 6.9%, p<0.01) and receiving treatment (11.3% vs 4.3%, p<0.01) was higher in patients than controls.

Conclusions: Our study showed a higher prevalence of mental problems in COVID-19 patients compared to controls, suggesting a great psychological impact of COVID-19 infection. Our findings highlighted the urgent need for psychological assistance for COVID-19 patients.
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http://dx.doi.org/10.1016/j.psychres.2021.114180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381686PMC
August 2021

A flexible sample size solution for longitudinal and crossover cluster randomized trials with continuous outcomes.

Contemp Clin Trials 2021 Aug 25;109:106543. Epub 2021 Aug 25.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States of America.

Longitudinal cluster randomized trial (LCRT) and crossover cluster randomized trial (CCRT) are two variants of cluster randomized trials. In LCRTs, clusters of subjects are randomly assigned to different treatment groups and each subject has repeated measurements over the study period. In CCRTs, clusters of subjects are randomly assigned to different sequences. Within each sequence, clusters receive all treatments in a particular order. Both LCRTs and CCRTs lead to complicated correlation structures that involve longitudinal and intracluster correlations. Generalized linear mixed model (GLMM) and generalized estimating equation (GEE) approaches have been frequently employed in data analysis and sample size estimation. In this study we propose closed-form sample size and power formulas for LCRTs and CCRTs based on the GEE approach. These formulas are flexible to incorporate unbalanced randomization, different missing patterns, arbitrary correlation structures, and randomly varying cluster sizes, providing a practical yet robust sample size solution. Simulation studies show that the proposed methods achieve good performance with empirical powers and type I errors close to their nominal values.
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http://dx.doi.org/10.1016/j.cct.2021.106543DOI Listing
August 2021

Effect of Arylmethylene Substitutions on Molecular Structure, Optoelectronic Properties and Photovoltaic Performance of Dithienocyclopentafluorene-Based Small-Molecule Acceptors.

Chemistry 2021 Oct 24;27(58):14508-14519. Epub 2021 Sep 24.

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, P. R. China.

Two dithienocyclopentafluorene-based small-molecule acceptors (SMAs) were developed that feature methylene-functionalized conjugated side chains, to study the effect of arylmethylene substitution and its number on structure, optoelectronic properties and device performance. Results showed that two SMAs have better absorption properties and planarity, lower bandgaps and higher LUMOs compared with the control SMA without conjugated side chains. The synthesized SMAs were tested in polymer solar cells for examples of their applicability. This work argues that the introduction of methylene-functionalized conjugated side chains has great potential in tuning molecular structure, optoelectronic properties, device physics and photovoltaic performance of SMAs.
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http://dx.doi.org/10.1002/chem.202102252DOI Listing
October 2021

Effect of Minor Er Additions on the Microstructures and Mechanical Properties of Cast Al-Cu-Mg-Ag Alloys.

Materials (Basel) 2021 Jul 28;14(15). Epub 2021 Jul 28.

School of Material Science and Engineering, Central South University, Changsha 410083, China.

The microstructures and mechanical properties of novel cast Al-Cu-Mg-Ag alloys with and without minor additions of Er (0.09 and 0.2 wt %) are investigated by Vickers hardness tests, tensile tests, optical metallographic examination, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results reveal that the Er addition decreases the hardness value of peak-aged Al-Cu-Mg-Ag alloy but has little influence on the time required for achieving the peak aging condition. Meanwhile, the Ω phase is suppressed in Er-added alloys, leading to a lower tensile strength at room temperature, which causes the (Mg, Ag, Er, V, Ti)-rich phase in the matrix in Er-added alloys. This blocky phase consumes available Mg and Ag atoms for Ω nucleation, leading to the low number density of Ω plates. The strength properties of Er-added alloys at 300 °C are found to be enhanced, which benefits from the pinning effect of the AlCuEr phase on grain boundaries. Meanwhile, the brittle fracture of Er-added alloys at room temperature is directly associated with the AlCuEr phase and the blocky (Mg, Ag, Er, V, Ti)-rich phase, which acts as the source of microcracks during deformation. In addition, no obvious grain refinement effect can be observed in Er-added alloys.
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http://dx.doi.org/10.3390/ma14154212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348178PMC
July 2021

Hypoxia-Adapted Sono-chemodynamic Treatment of Orthotopic Pancreatic Carcinoma Using Copper Metal-Organic Frameworks Loaded with an Ultrasound-Induced Free Radical Initiator.

ACS Appl Mater Interfaces 2021 Aug 6;13(32):38114-38126. Epub 2021 Aug 6.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jiefang Road, Shangcheng District, Hangzhou 310009, P.R. China.

The efficacy of sonodynamic therapy (SDT) is largely dependent upon oxygen availability to generate deleterious reactive oxygen species, and as such, hypoxic microenvironments greatly constrain the efficacy of SDT. Development of free radical generators that are not dependent on oxygen and related combination treatment strategies thus have the potential to enhance the antitumor potential of SDT. Combined treatment strategies are expected to improve the efficacy of sonodynamic antitumor therapy. As metal-organic framework (MOF) platforms are highly amenable to integration with other therapeutic approaches, we herein report the development of tumor microenvironment (TME)-responsive nanoparticles constructed by embedding the azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH) into hypoxia-triggered copper metal-organic framework (Cu-MOF) nanovectors to achieve synergistic sono-chemodynamic therapy in an orthotopic murine pancreatic carcinoma model system. When exposed to hypoxic conditions within the TME, this Cu-MOF structure underwent degradation, leading to the release of Cu and AIPH. Cu was then able to deplete local glutathione stores, resulting in the reduction of Cu to Cu, which then reacts with endogenous HO in a Fenton-like reaction to yield cytotoxic hydroxyl radicals (OH) for chemodynamic therapy. When exposed to ultrasound irradiation, AIPH further degraded in an oxygen-independent manner to yield nitrogen bubbles and alkyl radicals, the former of which enhanced the ability of these nanoparticles to penetrate deeply into the tumor. The resultant radicals induced substantial DNA damage and apoptotic cell death within target tumors under different levels of oxygen availability. As such, this hypoxic TME-responsive synergistic sono-chemodynamic approach offers an ideal means of achieving oxygen-independent free radical generation and enhanced treatment efficacy.
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http://dx.doi.org/10.1021/acsami.1c11017DOI Listing
August 2021

Effects of a fully enclosed hollow-fiber centrifugal ultrafiltration technique for laboratory biosafety improvement.

Biotechniques 2021 Sep 5;71(3):465-472. Epub 2021 Aug 5.

Hebei Provincial Center for Clinical Laboratories, Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, Hebei Province, 050051, China.

Laboratory biosafety has become a core focus in biological analysis, owing to the frequent occurrence of laboratory-acquired infections caused by the leakage of pathogenic microorganisms. For this purpose, the authors developed a safe pretreatment device combining a sealing technique with a direct injection technique. In this study, several bacteria and viruses were used to validate the filtration effect of the invention. Data show that the new device can completely filter bacteria and that the filtration rates for hepatitis B virus and hepatitis C virus reached 94% and 96%, respectively. The results show that the new preparation device can effectively block these pathogens and can improve biological safety and provide powerful protection for technicians.
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http://dx.doi.org/10.2144/btn-2021-0029DOI Listing
September 2021

Glucocorticoid Receptor Contributes to Electroacupuncture-Induced Analgesia by Inhibiting Nav1.7 Expression in Rats With Inflammatory Pain Induced by Complete Freund's Adjuvant.

Neuromodulation 2021 Aug 2. Epub 2021 Aug 2.

Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, Guangzhou, China.

Background: While electroacupuncture (EA) has been used traditionally for the treatment of chronic pain, its analgesic mechanisms have not been fully clarified. We observed in an earlier study that EA could reverse inflammatory pain and suppress high Nav1.7 expression. However, the molecular mechanism underlying Nav1.7 expression regulation is unclear. In this study, we studied the relationship between the glucocorticoid receptor (GR) and Nav1.7 and the role of these molecules in EA analgesia.

Materials And Methods: In this study, we established an inflammatory pain model by intraplantar injection of complete Freund's adjuvant (CFA) in rats. EA stimulation was applied to the ipsilateral "Huantiao" (GB30) and "Zusanli" (ST36) acupoints in the rat model. Western blotting, real-time polymerase chain reaction, immunostaining, intrathecal injection, and chromatin immunoprecipitation (ChIP) assay were performed to determine whether the sodium channel protein Nav1.7 plays a role in CFA-induced pain and whether GR regulates Nav1.7 expression during analgesia following EA stimulation.

Results: EA application significantly decreased the paw withdrawal threshold thresholds and thermal paw withdrawal latency and suppressed GR and Nav1.7 expression in the dorsal root ganglion. Moreover, treatment with a GR sense oligonucleotide (OND) markedly reversed these alterations. In contrast, treatment with a GR antisense OND along with EA application exerted a better analgesic effect, which was accompanied by the suppression of Nav1.7 and GR protein expression. The ChIP assay showed that the binding activity of GR to the Nav1.7 promoter was enhanced in CFA injected rats and suppressed in EA-treated rats.

Conclusions: The present study demonstrated that EA exerted anti-hyperalgesic effects by inhibiting GR expression, which led to Nav1.7 expression modulation in the rat model of CFA-induced inflammatory pain.
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http://dx.doi.org/10.1111/ner.13499DOI Listing
August 2021

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis.

Front Pharmacol 2021 16;12:708645. Epub 2021 Jul 16.

Neurobiology Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Memory decline caused by insufficient sleep is a critical public health issues and currently lacks effective treatments. This study objective was to explore alleviative effect of melatonin on sleep deprivation (SD)-induced deficiencies in learning and memory. A continuous 72 h SD mouse model, with or without melatonin or Fer-1 supplementation were established. The changes of cognitive function, iron homeostasis, lipid peroxidation and intracellular signal pathways in mice were detected by Morris water maze, antioxidant assay, immunohistochemistry, western blot, RT-PCR and Prussian blue staining. , we treated HT-22 cells with ferroptosis inducer (Erastin) to further explore the specific mechanism of melatonin in ferroptosis. Mice subjected to SD had significantly elevated latency and path length to reach hidden platform, as well as a decrease in number of entries and time spent in the target zone when the hidden platform was removed ( < 0.05). Nevertheless, supplementation with ferroptosis inhibitor (Fer-1) mitigated the memory impairment associated with SD. Further evaluation revealed an up-regulation of intracellular iron accumulation, transferrin receptor 1 and divalent metal transporter 1 expression and ROS and MDA production, and a down-regulation of ferroportin and antioxidant enzyme (GPX4 and SOD) expression in SD mice. SD decreased expression of MT2 receptor rather than of MT1, and inhibited ERK/Nrf2 signaling activation in the hippocampus ( < 0.05). In contrast, the aforementioned SD-inductions were reversed by supplementation using 20 and 40 mg/kg melatonin in SD mice. , melatonin pretreatment reversed Erastin-induced ferroptosis, abnormalities in iron transporter protein and antioxidant enzyme expression and suppression of ERK/Nrf2 signaling in HT-22 cells, however this protective effect of melatonin was blocked by MT2-, ERK- and Nrf2-specific antagonists ( < 0.05). Our finding suggested SD may induce ferroptosis, in turn leading to cognitive deficits. Melatonin alleviated memory loss and hippocampal ferroptosis caused by acute SD through binding to the MT2 receptor to activate ERK/Nrf2 signaling.
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http://dx.doi.org/10.3389/fphar.2021.708645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322577PMC
July 2021

Heat shock protein 70 attenuates hypoxia‑induced apoptosis of pulmonary microvascular endothelial cells isolated from neonatal rats.

Mol Med Rep 2021 10 30;24(4). Epub 2021 Jul 30.

Department of Echocardiography, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830054, P.R. China.

Pulmonary microvascular endothelial cell (PMVEC) apoptosis is the initial stage of adult pulmonary hypertension (PH), which involves high pulmonary arterial pressure and pulmonary vascular remodeling. However, the mechanism regulating PMVEC apoptosis and its involvement in the early stages of neonatal hypoxic PH (HPH) pathogenesis are currently unclear. The present study aimed to investigate the effects of heat shock protein 70 (HSP70) on hypoxia‑induced apoptosis in PMVECs. PMVECs isolated from neonatal Sprague‑Dawley rats were transfected with lentivirus with or without HSP70, or treated with the synthetic HSP70 inhibitor N‑formyl‑3,4‑methylenedioxy‑benzylidene-g-butyrolactam under hypoxic conditions (5% O) for 24, 48 or 72 h. PMVEC apoptosis was evaluated by performing flow cytometry and mitochondrial membrane potential (MMP) assays. The expression levels of HSP70, hypoxia‑inducible factor‑1α (HIF‑1α) and apoptosis‑associated proteins were determined by conducting reverse transcription‑quantitative PCR and western blotting. Following 24, 48 or 72 h of hypoxia, the apoptotic rates of PMVECs were significantly elevated compared with cells under normoxic conditions. The MMP was significantly reduced, whereas the mRNA and protein expression levels of HIF‑1α, cytochrome (cyt C), caspase‑3 and HSP70 were enhanced by hypoxia compared with those under normoxic conditions. Additionally, the mRNA and protein expression levels of B‑cell lymphoma 2 (Bcl‑2) were significantly downregulated in the hypoxia group compared with those in the normoxia group. In hypoxic PMVECs, HSP70 overexpression decreased the apoptotic rate and the expression levels of cyt C, downregulated the expression levels of caspase‑3 and HIF‑1α, and increased the MMP and the expression levels of Bcl‑2. HSP70 inhibition resulted in the opposite outcomes compared with those of HSP70 overexpression. Therefore, the results of the present study suggested that HSP70 may inhibit mitochondrial pathway‑mediated apoptosis in isolated neonatal rat PMVECs in early‑stage hypoxia, which may be associated with HSP70‑mediated HIF‑1α downregulation. Overall, HSP70 may be protective against neonatal HPH through the HSP70/HIF‑1α pathway.
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http://dx.doi.org/10.3892/mmr.2021.12327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365595PMC
October 2021

Ultra-Fast Label-Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer.

Adv Sci (Weinh) 2021 09 29;8(18):e2101333. Epub 2021 Jul 29.

State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.

Although mass spectrometry (MS) of metabolites has the potential to provide real-time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra-fast, label-free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle-assisted laser desorption/ionization-MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high-quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high-throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label-free, ultra-fast, and stabilized platform for future protocol development in clinics.
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http://dx.doi.org/10.1002/advs.202101333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456274PMC
September 2021

A Nomogram Based on Combining Clinical Features and Contrast Enhanced Ultrasound LI-RADS Improves Prediction of Microvascular Invasion in Hepatocellular Carcinoma.

Front Oncol 2021 8;11:699290. Epub 2021 Jul 8.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Purposes: To establish a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging and reporting and data system (CEUS LI-RADS) for estimation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients.

Methods: In the retrospective study, 127 HCC patients from two hospitals were allocated as training cohort (n=98) and test cohorts (n=29) based on cutoff time-point, June 2020. Multivariate regression analysis was performed to identify independent indicators for developing predictive nomogram models. The area under receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. Corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared.

Results: In the training cohort, clinical information (larger tumor size, higher AFP level) and CEUS LR-M were significantly correlated with the presence of MVI (all p<0.05). By incorporating clinical information and CEUS LR-M, the predictive model (LR-M+Clin) achieved a desirable diagnostic performance (AUC=0.80 and 0.84) in both cohorts at nomogram cutoff score value of 89. The sensitivity of LR-M+Clin when predicting MVI in HCC patients was higher than that of the clinical model alone (86.7% vs. 46.7%, p=0.027), while specificities were 78.6% and 85.7% (p=0.06), respectively, in the test cohort. In addition, LR-M+Clin exhibited similar AUC and specificity, but a significantly higher sensitivity (86.7%) than those of LR-M alone and LR-5(No)+Clin (both sensitivities=73.3%, both p=0.048).

Conclusion: The predictive model incorporating CEUS LR-M and clinical features was able to predict the MVI status of HCC and is a potential reliable preoperative tool for informing treatment.
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http://dx.doi.org/10.3389/fonc.2021.699290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297520PMC
July 2021

Liposome-mediated detection of SARS-CoV-2 RNA-positive extracellular vesicles in plasma.

Nat Nanotechnol 2021 09 22;16(9):1039-1044. Epub 2021 Jul 22.

Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA.

Plasma SARS-CoV-2 RNA may represent a viable diagnostic alternative to respiratory RNA levels, which rapidly decline after infection. Quantitative PCR with reverse transcription (RT-qPCR) reference assays exhibit poor performance with plasma, probably reflecting the dilution and degradation of viral RNA released into the circulation, but these issues could be addressed by analysing viral RNA packaged into extracellular vesicles. Here we describe an assay approach in which extracellular vesicles directly captured from plasma are fused with reagent-loaded liposomes to sensitively amplify and detect a SARS-CoV-2 gene target. This approach accurately identified patients with COVID-19, including challenging cases missed by RT-qPCR. SARS-CoV-2-positive extracellular vesicles were detected at day 1 post-infection, and plateaued from day 6 to the day 28 endpoint in a non-human primate model, while signal durations for 20-60 days were observed in young children. This nanotechnology approach uses a non-infectious sample and extends virus detection windows, offering a tool to support COVID-19 diagnosis in patients without SARS-CoV-2 RNA detectable in the respiratory tract.
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http://dx.doi.org/10.1038/s41565-021-00939-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440422PMC
September 2021

Physiological and Expressional Regulation on Photosynthesis, Starch and Sucrose Metabolism Response to Waterlogging Stress in Peanut.

Front Plant Sci 2021 2;12:601771. Epub 2021 Jul 2.

Bio-Tech Research Center, Shandong Academy of Agricultural Science, Jinan, China.

Waterlogging has negative effects on crop yield. Physiological and transcriptome data of two peanut cultivars [Zhongkaihua 1 (ZKH 1) and Huayu 39 (HY 39)] were studied under normal water supply and waterlogging stress for 5 or 10 days at the flowering stage. The results showed that the main stem height, the number of lateral branches, lateral branch length, and the stem diameter increased under waterlogging stress, followed by an increase in dry matter accumulation, which was correlated with the increase in the soil and plant analysis development (SPAD) and net photosynthetic rate (Pn) and the upregulation of genes related to porphyrin and chlorophyll metabolism and photosynthesis. However, the imbalance of the source-sink relationship under waterlogging was the main cause of yield loss, and waterlogging caused an increase in the sucrose and soluble sugar contents and a decrease in the starch content; it also decreased the activities of sucrose synthetase (SS) and sucrose phosphate synthetase (SPS), which may be due to the changes in the expression of genes related to starch and sucrose metabolism. However, the imbalance of the source-sink relationship led to the accumulation of photosynthate in the stems and leaves, which resulted in the decrease of the ratio of pod dry weight to total dry weight (PDW/TDW) and yield. Compared with ZKH 1, the PDW of HY 39 decreased more probably because more photosynthate accumulated in the stem and leaves of HY 39 and could not be effectively transported to the pod.
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http://dx.doi.org/10.3389/fpls.2021.601771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283264PMC
July 2021

Plaque Elasticity and Intraplaque Neovascularisation on Carotid Artery Ultrasound: A Comparative Histological Study.

Eur J Vasc Endovasc Surg 2021 09;62(3):358-366

Department of Ultrasound in Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China. Electronic address:

Objective: Plaque elasticity and intraplaque neovascularisation are strongly suggestive of vulnerable plaque. This study aimed to investigate the relationship between intraplaque neovascularisation and plaque elasticity, and to compare the ultrasound findings with histopathological changes.

Methods: Patients enrolled in this study presented with symptomatic carotid stenosis (> 70%) and later underwent both pre-operative ultrasonography and endarterectomy. Contrast enhanced ultrasound (CEUS) and shear wave elastography (SWE) were used to measure the neovascularisation and elasticity of the plaque, respectively. After removal, plaques were histologically assessed to determine the microvessel density (MVD), matrix metalloproteinase (MMP)-9 expression, and type I/type III collagen ratio using immunohistochemistry staining and morphometry. A correlation analysis was used to establish the relationship among the aforementioned quantitative parameters. Inter- and intra-observer consistency evaluations were performed using the intraclass correlation coefficient and Bland-Altman plots.

Results: Ninety-four symptomatic patients with 98 plaques were included. The area under the curve (AUC) of the carotid plaque detected using CEUS correlated with its shear wave velocity (SWV) (r = -.714; p < .001), MVD (r = .842; p < .001), collagen type I/III ratio (r = -.833; p < .001), and MMP-9 (r = .738; p < .001). SWE was positively correlated with the type I/III collagen ratio (r = .805; p < .001). The overall interexaminer consistency of the SWE was acceptable (r = .638; p < .001). The interobserver correlation coefficient of the AUC, time to peak (TP), mean transit time (MTT), and SWV were .719, .756, .733, and .686, respectively. The intra-observer variability values of the AUC, TP, MTT, and SWV were .826, .845, .633, and .748, respectively.

Conclusion: SWE and CEUS can comprehensively evaluate the vulnerability of the carotid plaque by assessing the elasticity of the plaque and neovascularisation within it. The negative correlation between the intraplaque neovascularisation and elasticity, further validated by histological findings, suggests that the more abundant the neovascularisation, the less elasticity.
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http://dx.doi.org/10.1016/j.ejvs.2021.05.026DOI Listing
September 2021

Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota.

Oxid Med Cell Longev 2021 23;2021:9981480. Epub 2021 Jun 23.

College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.

Background: Inflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis.

Methods: A 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin.

Results: SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-B pathway-induced inflammatory response in vivo and in vitro.

Conclusions: We revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.
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http://dx.doi.org/10.1155/2021/9981480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246302PMC
June 2021

Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer.

Front Pharmacol 2021 24;12:692454. Epub 2021 Jun 24.

Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

The pathogenesis of heterogeneity in gastric cancer (GC) is not clear and presents as a significant obstacle in providing effective drug treatment. We aimed to identify subtypes of GC and explore the underlying pathogenesis. We collected two microarray datasets from GEO (GSE84433 and GSE84426), performed an unsupervised cluster analysis based on gene expression patterns, and identified related immune and stromal cells. Then, we explored the possible molecular mechanisms of each subtype by functional enrichment analysis and identified related hub genes. First, we identified three clusters of GC by unsupervised hierarchical clustering, with average silhouette width of 0.96, and also identified their related representative genes and immune cells. We validated our findings using dataset GSE84426. Subtypes associated with the highest mortality (subtype 2 in the training group and subtype C in the validation group) showed high expression of SPARC, COL3A1, and CCN. Both subtypes also showed high infiltration of fibroblasts, endothelial cells, hematopoietic stem cells, and a high stromal score. Furthermore, subtypes with the best prognosis (subtype 3 in the training group and subtype A in the validation group) showed high expression of FGL2, DLGAP1-AS5, and so on. Both subtypes also showed high infiltration of CD4 T cells, CD8 T cells, NK cells, pDC, macrophages, and CD4 T effector memory cells. We found that GC can be classified into three subtypes based on gene expression patterns and cell composition. Findings of this study help us better understand the tumor microenvironment and immune milieu associated with heterogeneity in GC and provide practical information to guide personalized treatment.
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http://dx.doi.org/10.3389/fphar.2021.692454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264374PMC
June 2021

High forest stand density exacerbates growth decline of conifers driven by warming but not broad-leaved trees in temperate mixed forest in northeast Asia.

Sci Total Environ 2021 Nov 5;795:148875. Epub 2021 Jul 5.

Geography, College of Life & Environmental Sciences, University of Exeter, Exeter EX4 4RJ, United Kingdom.

Increasing temperature over recent decades is expected to positively impact tree growth in humid regions. However, high stand density could increase the negative effects of warming-induced drought through inter-tree competition. How neighborhood competition impacts tree growth responding to climate change remains unclear. Here, we utilized the Changbai Mountain region in northeastern Asia as our study area. We quantified individual tree growth using tree-ring samples collected from three dominant tree species growing in three forest stand density levels. We estimated the effects of climate warming and forest stand density on growth processes and tested for a species-specific response to climate. Our results demonstrated that overall 25% of Korean pine, but only ~3% of Mongolian oak and ~ 4% of Manchurian ash experienced growth reduction. Increased forest density can also exacerbate growth reduction. We identified a climate turning point in 1984, where warming rapidly increased, and defined two groups, "enhance group" (EG) and "decline group" (DG), according to the individual tree growth trend after 1984. For the EG, climate warming increased temperature sensitivity, but the temperature sensitivity declined with increasing stand density for the whole study period. For the DG, tree growth sensitivity shifted from temperature to precipitation after 1984, driven by increased competition pressure under climate warming. Our study concludes that growth decline from warming-induced drought might be amplified by high forest stand density, was especially pronounced in conifer trees.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148875DOI Listing
November 2021
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