Publications by authors named "Dan Zhou"

664 Publications

A transcriptome-wide association study identifies novel candidate susceptibility genes for prostate cancer risk.

Int J Cancer 2021 Sep 14. Epub 2021 Sep 14.

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.

A large proportion of heritability for prostate cancer risk remains unknown. Transcriptome-wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype-Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures, and Joint-Tissue Imputation. We applied these prediction models to the genetic data of 79,194 prostate cancer cases and 61,112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor versus normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor versus normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor versus normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor versus normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33808DOI Listing
September 2021

Coronavirus disease-19 and the gut-lung axis.

Int J Infect Dis 2021 Sep 10. Epub 2021 Sep 10.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education. Electronic address:

Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the "gut-lung axis," in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has triggered the global pandemic of coronavirus disease 2019 (COVID-19), in which respiratory symptoms of fever, cough, and dyspnea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea. Besides the gut-lung axis, it should be noted that the gut participates in numerous axes, which may affect lung function and consequently COVID-19 severity through several pathways. However, in this article, we mainly pay attention to the latest evidence and the mechanisms that drive the operation of the gut-lung axis, as well as discuss the interaction between the gut-lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II (ACE2). Raising hypotheses and providing methods to guide future research on this new disease and its treatments.
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http://dx.doi.org/10.1016/j.ijid.2021.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431834PMC
September 2021

A transcriptome-wide association study of Alzheimer's disease using prediction models of relevant tissues identifies novel candidate susceptibility genes.

Genome Med 2021 Sep 1;13(1):141. Epub 2021 Sep 1.

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 96813, USA.

Background: Genome-wide association studies (GWAS) have identified over 56 susceptibility loci associated with Alzheimer's disease (AD), but the genes responsible for these associations remain largely unknown.

Methods: We performed a large transcriptome-wide association study (TWAS) leveraging modified UTMOST (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues that are potentially related to AD to discover novel AD genetic loci and putative target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European ancestry.

Results: We identified 53 genes with predicted expression associations with AD risk at Bonferroni correction threshold (P value < 3.38 × 10). Based on fine-mapping analyses, 21 genes at nine loci showed strong support for being causal.

Conclusions: Our study provides new insights into the etiology and underlying genetic architecture of AD.
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http://dx.doi.org/10.1186/s13073-021-00959-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408990PMC
September 2021

Dynamic Behavior of Single-Atom Catalysts in Electrocatalysis: Identification of Cu-N as an Active Site for the Oxygen Reduction Reaction.

J Am Chem Soc 2021 Sep 31;143(36):14530-14539. Epub 2021 Aug 31.

Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.

Atomically dispersed M-N-C (M refers to transition metals) materials represent the most promising catalyst alternatives to the precious metal Pt for the electrochemical reduction of oxygen (ORR), yet the genuine active sites in M-N-C remain elusive. Here, we develop a two-step approach to fabricate Cu-N-C single-atom catalysts with a uniform and well-defined Cu-N structure that exhibits comparable activity and superior durability in comparison to Pt/C. By combining X-ray absorption spectroscopy with theoretical calculations, we unambiguously identify the dynamic evolution of Cu-N to Cu-N and further to HO-Cu-N under ORR working conditions, which concurrently occurs with reduction of Cu to Cu and is driven by the applied potential. The increase in the Cu/Cu ratio with the reduced potential indicates that the low-coordinated Cu-N is the real active site, which is further supported by DFT calculations showing the lower free energy in each elemental step of the ORR on Cu-N than on Cu-N. These findings provide a new understanding of the dynamic electrochemistry on M-N-C catalysts and may guide the design of more efficient low-cost catalysts.
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http://dx.doi.org/10.1021/jacs.1c03788DOI Listing
September 2021

Fingerprinting vanadium in soils based on speciation characteristics and isotope compositions.

Sci Total Environ 2021 Oct 9;791:148240. Epub 2021 Jun 9.

CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026, Anhui, China; CAS Center for Excellence in Comparative Planetology, China. Electronic address:

Vanadium (V) can have toxic effects on human organs and physiological systems, yet tracing V sources remains challenging. Here, two methods were used for V source tracing in soil based on speciation characteristics and isotope compositions. According to the sequential extraction method of the European Communities Bureau of Reference (BCR), the analysis of speciation distributions offers a possible means of distinguishing V sources. Here, the isotope compositions of polluted soils around a coal-fired power plant and smelter in China were used to identify the sources of V. Significant V isotope variation (δV range = -0.74 ± 0.07; mean ± 2SD = -0.52 ± 0.05‰) was observed in the soil samples, attributed to coal-burning (ΔV = -0.31 ± 0.05‰; mean ± 2SD; n = 1) and smelting processes (ΔV = -0.31 ± 0.07‰; mean ± 2SD; n = 1). All of the soil V isotope ratios plotted within the range of end-member components corresponding to potential V contributors in the environment. Among these, δV ranged from -0.74 ± 0.07 to -0.55 ± 0.02‰ in topsoil, the average δV was -0.52 ± 0.05‰ in the deep soils, and the δV of the end-member components ranged from -0.52 ± 0.05 to -0.94 ± 0.11‰. The primary anthropogenic source of V in the topsoil was fly ash from coal-burning that was consistent with the BCR method results. Furthermore, the downward migration of V was identified in the soil profile adjacent to the smelting plant, and V in the deep soils was dominated by natural sources relative to anthropogenic sources in the surface soils.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148240DOI Listing
October 2021

Thickness-Insensitive Anode Interface Layer for High-Efficiency Organic Solar Cells.

ACS Appl Mater Interfaces 2021 Aug 13;13(33):39844-39853. Epub 2021 Aug 13.

Institute of Advanced Scientific Research (iASR), Key Laboratory of Functional Small Molecules for Ministry of Education, Jiangxi Normal University, Nanchang 330022, Jiangxi, China.

Thickness-insensitive anode interface layer materials are extremely crucial for commercial applications of organic solar cells (OSCs). Here, we have demonstrated a solution-processed and thickness-insensitive anode interfacial layer PCPDT-2Ph-H and employed it in large-area OSCs. The power conversion efficiency (PCE) of a PM6:Y6 device with a 0.04 cm area using PCPDT-2Ph-H as the anode interface layer can reach 16.5%. More importantly, when the thickness of PCPDT-2Ph-H reaches 100 nm, a device with a 1.0 cm effective area can still achieve a high efficiency of 10.3%, which is highly favorable to large-area printing of OSCs. Due to its advantages of thickness insensitivity and solution processing, PCPDT-2Ph-H would be a promising anode interface layer for large-area OSCs.
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http://dx.doi.org/10.1021/acsami.1c09474DOI Listing
August 2021

A transcriptome-wide association study identifies novel blood-based gene biomarker candidates for Alzheimer's disease risk.

Hum Mol Genet 2021 Aug 13. Epub 2021 Aug 13.

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 96813, USA.

Alzheimer's disease (ad) adversely affects the health, quality of life and independence of patients. There is a critical need to identify novel blood gene biomarkers for ad risk assessment. We performed a transcriptome-wide association study to identify biomarker candidates for ad risk. We leveraged two sets of gene expression prediction models of blood developed using different reference panels and modelling strategies. By applying the prediction models to a meta-GWAS including 71 880 (proxy) cases and 383 378 (proxy) controls, we identified significant associations of genetically determined expression of 108 genes in blood with ad risk. Of these, 15 genes were differentially expressed between ad patients and controls with concordant directions in measured expression data. With evidence from the analyses based on both genetic instruments and directly measured expression levels, this study identifies 15 genes with strong support as biomarkers in blood for ad risk, which may enhance ad risk assessment and mechanism-focused studies.
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http://dx.doi.org/10.1093/hmg/ddab229DOI Listing
August 2021

Efficacy of Yun-Type Optimized Pelvic Floor Training Therapy for Middle-Aged Women With Severe Overactive Bladder: A Randomized Clinical Trial.

Front Surg 2021 14;8:670123. Epub 2021 Jul 14.

Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.

This study aimed to evaluate the clinical efficacy of Yun-type optimized pelvic floor training therapy for middle-aged women with severe overactive bladder (OAB). This randomized, observer-blinded, parallel-group controlled clinical trial included 108 middle-age women with severe OAB and assigned them to the intervention group (treated with combination of Yun-type optimized pelvic floor training with solifenacin for 12 weeks) and control group (treated with solifenacin for 6 weeks and, after 2 weeks of elution, received the combination of Yun-type optimized pelvic floor training and solifenacin for 6 weeks). The outcomes associated with OAB, pelvic floor muscle (PFM) function, and sexual function were compared after 6 and 12/14 weeks of treatment. The primary variables were OAB-associated outcomes, including overactive bladder symptom score (OABSS), urgent urination, urine, nocturia, urge urinary incontinence, patient's perception of bladder condition, urogenital distress inventory-6, incontinence impact questionnaire-7, voiding volume, average flow rate, and maximum flow rate. The secondary variables were indicators related to PFM function and sexual function. These indicators were significantly improved in both groups after interventions. Notably, the improvements in most of these indicators were superior in the intervention group than in the control group after 6 weeks and 12/14 weeks of treatment. The use of Yun-type optimized pelvic floor training adds to the benefits of solifenacin regarding severe OAB-associated outcomes, PMF function, and sexual function in middle-aged women with severe OAB. Combining Yun-type optimized pelvic floor training with traditional drug therapies may improve clinical outcomes in patients with severe OAB. ChiCTR-INR-17012189.
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http://dx.doi.org/10.3389/fsurg.2021.670123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316598PMC
July 2021

Release and Actions of Inflammatory Exosomes in Pulmonary Emphysema: Potential Therapeutic Target of Acupuncture.

J Inflamm Res 2021 24;14:3501-3521. Epub 2021 Jul 24.

Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.

Background: Exosomes have been reported to mediate activation of the inflammatory response by secretion of inflammasome products such as IL-1β or IL-18 and that changes in exosomes production or secretion may be a therapeutic target for treatment of a variety of different chronic diseases. The present study tested the hypothesis that exosome-mediated release of NLRP3 inflammasome products instigates the inflammatory response in the lung during emphysema, a type of chronic obstructive pulmonary disease (COPD) and that electroacupuncture (EA) may attenuate emphysema by inhibition of NLRP3 inflammasome activation and consequent inflammation.

Methods: The COPD mice model was developed by injecting porcine pancreatic elastase (PPE) via puncture tracheotomy and instillation. EA (4 Hz/20 Hz, 1 to 3 mA) was applied to the bilateral BL13 and ST36 for 30 min, once every other day for 2 weeks. Micro computed tomography (micro-CT) was performed to measure lung function. Histopathological changes in the lungs were displayed by HE staining.

Results: In a mouse model of porcine pancreatic elastase (PPE)-induced emphysema, the lung tissue was found to display several key features of emphysema, including alveolar septal thickening, enlarged alveoli, interstitial edema, and inflammatory cells infiltration. Lungs of mice receiving PPE exhibited substantially increased low attenuation area (LAA) in micro-CT images. The colocalization of NLRP3 vs ASC or caspase-1 detected by confocal microscopy was shown to increase in both bronchial and alveolar walls, indicating the increased formation of NLRP3 inflammasomes. IL-1β, a prototype NLRP3 inflammasome activating product, was also found to have increased in the lung during emphysema, which was colocalized with CD63 (an exosome marker), an indicative of inflammatory exosome formation. By nanoparticle tracking analysis (NTA), IL-1β-containing exosomes were shown to significantly increase in the bronchoalveolar lavage (BAL) from mice with emphysema. Therapeutically, IL-1β production in the lung during emphysema was significantly reduced by EA at the acupoint Feishu (BL13) and Zusanli (ST36), accompanied by decreased colocalization of NLRP3 vs ASC or caspase-1. Increased exosome release into BAL during emphysema was shown to be significantly attenuated in EA-treated mice compared to their controls. However, EA of non-specific BL23 together with ST36 acupoint had no effects on NLRP3 inflammasome activation, exosome release and associated lung pathology during emphysema.

Conclusion: NLRP3 inflammasome activation in concert with increased release of exosomes containing IL-1β or other inflammasome products contributes to the development of lung inflammation and injury during PPE-induced emphysema and that EA of lung-specific acupoints attenuates inflammasome activation and exosome release, thereby reducing inflammatory response in the lung of mice with emphysema.
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http://dx.doi.org/10.2147/JIR.S312385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318722PMC
July 2021

Secretory lipid transfer protein OsLTPL94 acts as a target of EAT1 and is required for rice pollen wall development.

Plant J 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Chengdu, 611130, China.

The plant pollen wall protects the male gametophyte from various biotic and abiotic stresses. The formation of a unique pollen wall structure and elaborate exine pattern is a well-organized process, which needs coordination between reproductive cells and the neighboring somatic cells. However, molecular mechanisms underlying this process remain largely unknown. Here, we report a rice male-sterile mutant (l94) that exhibits defective pollen exine patterning and abnormal tapetal cell development. MutMap and knockout analyses demonstrated that the causal gene encodes a type-G non-specific lipid transfer protein (OsLTPL94). Histological and cellular analyses established that OsLTPL94 is strongly expressed in the developing microspores and tapetal cells, and its protein is secreted to the plasma membrane. The l94 mutation impeded the secretory ability of OsLTPL94 protein. Further in vivo and in vitro investigations supported the hypothesis that ETERNAL TAPETUM 1 (EAT1), a basic helix-loop-helix transcription factor (bHLH TF), activated OsLTPL94 expression through direct binding to the E-box motif of the OsLTPL94 promoter, which was supported by the positive correlation between the expression of EAT1 and OsLTPL94 in two independent eat1 mutants. Our findings suggest that the secretory OsLTPL94 plays a key role in the coordinated development of tapetum and microspores with the regulation of EAT1.
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http://dx.doi.org/10.1111/tpj.15443DOI Listing
July 2021

Morphology-controllable amphiphilic cellulose microgels made from self-assembly of hydrophobic long-chain bromide-alkylated-cellulose/gelatin copolymer.

Carbohydr Polym 2021 Oct 29;269:118265. Epub 2021 May 29.

College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science and Technology, Xi'an, Shaanxi Province 710021, China.

A cellulose-based microgel is firstly synthesized via chemically coupling gelatin and cellulose, and then amphiphilic cellulose copolymers (HMGC) are prepared by alkylated cellulose-based microgel from different long-chain alkyl groups. The long-chain alkyl group is mainly bonded onto the residual hydroxyl group at C from the AGU of cellulose and the imino groups of gelatin, respectively. The results of self-assembly behavior of HMGC demonstrate that the critical aggregation concentrations of the microgels are in the range from 0.628 to 0.075 mg/mL, and the corresponding hydrodynamic diameters are between 104-1000 nm. Besides, the HMGC can self-assemble into microgels of various morphologies including cotton flocculence, sphere, rod-like, vesicle, flower-like cluster, snowflake-like, urchin-like, and coral shapes. These novel morphologies can be controlled by adjusting the degree of alkylation, the length of the alkyl chain, and the concentration of microgel. Furthermore, the possible formation mechanism of the multiform microgels is proposed from the chain conformation.
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http://dx.doi.org/10.1016/j.carbpol.2021.118265DOI Listing
October 2021

Contextualizing genetic risk score for disease screening and rare variant discovery.

Nat Commun 2021 07 20;12(1):4418. Epub 2021 Jul 20.

Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Studies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making.
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http://dx.doi.org/10.1038/s41467-021-24387-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292385PMC
July 2021

Transcriptomic landscape of persistent diarrhoea in rhesus macaques and comparison with humans and mouse models with inflammatory bowel disease.

Gene 2021 Oct 16;800:145837. Epub 2021 Jul 16.

Key Laboratory of Bioresources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, Sichuan, China; Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu 610064, Sichuan, China. Electronic address:

Diarrhoea is a widespread disease in captive rhesus macaques (Macaca mulatta) and a small proportion of individuals may experience persistent diarrhoea. Persistent diarrhoea can lead to a compromised immune system, intestinal inflammation and malnutrition. We analyzed the blood transcriptomes of 10 persistent diarrhoeal and 12 healthy rhesus macaques to investigate the gene expression differences between the two groups. We identified 330 DEGs between persistent diarrhoeal and healthy rhesus macaques. The 211 up-regulated DEGs in the diarrhoeal group were mainly enriched in immune-related and interleukin-related categories. Among them, three interleukin (IL) 18 related DEGs (IL18, IL18R1, and IL18BP) played important roles in actively regulating pro-inflammatory responses. Interestingly, the up- and down-regulated DEGs were both enriched in the same immune-related categories. Thus, we applied a new method to examine the distribution of DEGs in all child categories. We found that interleukin and T cell related categories were mainly occupied by up-regulated DEGs, while immunoglobulin production and B cell related categories were enriched by down-regulated DEGs. We also compared rhesus macaque DEGs with the DEGs of inflammatory bowel disease (IBD) humans and IBD mouse models and found that 30-40% of macaque DEGs were shared with IBD humans and mouse models. In conclusion, our results showed that there were significant immune differences between persistent diarrhoeal rhesus macaques and healthy macaques, which was similar to the expression differences in IBD patients and mouse models.
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http://dx.doi.org/10.1016/j.gene.2021.145837DOI Listing
October 2021

Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies.

J Nanobiotechnology 2021 Jul 15;19(1):211. Epub 2021 Jul 15.

Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.
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http://dx.doi.org/10.1186/s12951-021-00902-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281664PMC
July 2021

Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia.

Front Physiol 2021 25;12:680275. Epub 2021 Jun 25.

Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, United States.

The microbiota plays a critical role in regulating organismal health and response to environmental stresses. Intermittent hypoxia and hypercapnia, a condition that represents the main hallmark of obstructive sleep apnea in humans, is known to induce significant alterations in the gut microbiome and metabolism, and promotes the progression of atherosclerosis in mouse models. To further understand the role of the microbiome in the cardiovascular response to intermittent hypoxia and hypercapnia, we developed a new rodent cage system that allows exposure of mice to controlled levels of O and CO under gnotobiotic conditions. Using this experimental setup, we determined the impact of the microbiome on the transcriptional response to intermittent hypoxia and hypercapnia in the left ventricle of the mouse heart. We identified significant changes in gene expression in both conventionally reared and germ-free mice. Following intermittent hypoxia and hypercapnia exposure, we detected 192 significant changes in conventionally reared mice (96 upregulated and 96 downregulated) and 161 significant changes (70 upregulated and 91 downregulated) in germ-free mice. Only 19 of these differentially expressed transcripts (∼10%) were common to conventionally reared and germ-free mice. Such distinct transcriptional responses imply that the host microbiota plays an important role in regulating the host transcriptional response to intermittent hypoxia and hypercapnia in the mouse heart.
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http://dx.doi.org/10.3389/fphys.2021.680275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267877PMC
June 2021

Kondo effect and superconductivity in niobium with iron impurities.

Sci Rep 2021 Jul 9;11(1):14256. Epub 2021 Jul 9.

Department of Physics, Brown University, Providence, RI, 02912, USA.

Kondo effect is an interesting phenomenon in quantum many-body physics. Niobium (Nb) is a conventional superconductor important for many superconducting device applications. It was long thought that the Kondo effect cannot be observed in Nb because the magnetic moment of a magnetic impurity, e.g. iron (Fe), would have been quenched in Nb. Here we report an observation of the Kondo effect in a Nb thin film structure. We found that by co-annealing Nb films with Fe in Argon gas at above 400 [Formula: see text]C for an hour, one can induce a Kondo effect in Nb. The Kondo effect is more pronounced at higher annealing temperature. The temperature dependence of the resistance suggests existence of remnant superconductivity at low temperatures even though the system never becomes superconducting. We find that the Hamann theory for the Kondo resistivity gives a satisfactory fitting to the result. The Hamann analysis gives a Kondo temperature for this Nb-Fe system at [Formula: see text] 16 K, well above the superconducting transition onset temperature 9 K of the starting Nb film, suggesting that the screening of the impurity spins is effective to allow Cooper pairs to form at low temperatures. We suggest that the mechanism by which the Fe impurities retain partially their magnetic moment is that they are located at the grain boundaries, not fully dissolved into the bcc lattice of Nb.
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http://dx.doi.org/10.1038/s41598-021-93731-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270948PMC
July 2021

Identification of a novel HLA-A*11 allele, HLA-A*11:399, in a Chinese Individual.

HLA 2021 Sep 12;98(3):223-224. Epub 2021 Jul 12.

Shenzhen Blood Center, Shenzhen, Guangdong, China.

One nucleotide substitution in codon 90 of HLA-A*11:01:01:01 results in a novel allele, HLA-A*11:399.
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http://dx.doi.org/10.1111/tan.14357DOI Listing
September 2021

Electronic Structure and -Band Center Control Engineering over Ni-Doped CoP Nanowall Arrays for Boosting Hydrogen Production.

Nanomaterials (Basel) 2021 Jun 17;11(6). Epub 2021 Jun 17.

Henan Key Laboratory of Photovoltaic Materials, Henan University, Kaifeng 475004, China.

To address the challenge of highly efficient water splitting into H, successful fabrication of novel porous three-dimensional Ni-doped CoP nanowall arrays on carbon cloth was realized, resulting in an effective self-supported electrode for the electrocatalytic hydrogen-evolution reaction. The synthesized samples exhibit rough, curly, and porous structures, which are beneficial for gaseous transfer and diffusion during the electrocatalytic process. As expected, the obtained Ni-doped CoP nanowall arrays with a doping concentration of 7% exhibit the promoted electrocatalytic activity. The achieved overpotentials of 176 mV for the hydrogen-evolution reaction afford a current density of 100 mA cm, which indicates that electrocatalytic performance can be dramatically enhanced via Ni doping. The Ni-doped CoP electrocatalysts with increasing catalytic activity should have significant potential in the field of water splitting into H. This study also opens an avenue for further enhancement of electrocatalytic performance through tuning of electronic structure and -band center by doping.
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http://dx.doi.org/10.3390/nano11061595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233895PMC
June 2021

Intermittent Hypoxia and Hypercapnia Alter Diurnal Rhythms of Luminal Gut Microbiome and Metabolome.

mSystems 2021 Jun 29:e0011621. Epub 2021 Jun 29.

Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia and hypercapnia (IHC), affects the composition of the gut microbiome and metabolome. The gut microbiome has diurnal oscillations that play a crucial role in regulating circadian and overall metabolic homeostasis. Thus, we hypothesized that IHC adversely alters the gut luminal dynamics of key microbial families and metabolites. The objective of this study was to determine the diurnal dynamics of the fecal microbiome and metabolome of mice after a week of IHC exposure. Individually housed, 10-week-old mice on an atherogenic diet were split into two groups. One group was exposed to daily IHC conditions for 10 h (Zeitgeber time 2 [ZT2] to ZT12), while the other was maintained in room air. Six days after the initiation of the IHC conditions, fecal samples were collected every 4 h for 24 h (6 time points). We performed 16S rRNA gene amplicon sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) to assess changes in the microbiome and metabolome. IHC induced global changes in the cyclical dynamics of the gut microbiome and metabolome. , , S24-7, and had the greatest shifts in their diurnal oscillations. In the metabolome, bile acids, glycerolipids (phosphocholines and phosphoethanolamines), and acylcarnitines were greatly affected. Multi-omic analysis of these results demonstrated that and tauro-β-muricholic acid (TβMCA) cooccur and are associated with IHC conditions and that and chenodeoxycholic acid (CDCA) cooccur and are associated with control conditions. IHC significantly change the diurnal dynamics of the fecal microbiome and metabolome, increasing members and metabolites that are proinflammatory and proatherogenic while decreasing protective ones. People with obstructive sleep apnea are at a higher risk of high blood pressure, type 2 diabetes, cardiac arrhythmias, stroke, and sudden cardiac death. We wanted to understand whether the gut microbiome changes induced by obstructive sleep apnea could potentially explain some of these medical problems. By collecting stool from a mouse model of this disease at multiple time points during the day, we studied how obstructive sleep apnea changed the day-night patterns of microbes and metabolites of the gut. Since the oscillations of the gut microbiome play a crucial role in regulating metabolism, changes in these oscillations can explain why these patients can develop so many metabolic problems. We found changes in microbial families and metabolites that regulate many metabolic pathways contributing to the increased risk for heart disease seen in patients with obstructive sleep apnea.
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http://dx.doi.org/10.1128/mSystems.00116-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269208PMC
June 2021

Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway.

Cancer Manag Res 2021 17;13:4829-4840. Epub 2021 Jun 17.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China.

Introduction: Oral squamous cell carcinoma (OSCC) means oral epithelial cell injury caused by multiple genetic mutations of the cells. Dysregulation of microRNAs (miRs) can disrupt the progression of OSCC. This study explored the mechanism of miR-130a in OSCC progression.

Methods: miR-130a expression in OSCC cell lines was analyzed. Functional assays were utilized to test the alterations of OSCC cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) with downregulated miR-130a, shRNA-PTEN or/and YAP inhibitor verteporfin. Then, dual-luciferase reporter gene assay was performed to clarify the targeting relation between miR-130a and PTEN. After that, Hippo-YAP pathway-related protein levels were tested. Moreover, xenograft transplantation was applied to confirm the in vitro experiments.

Results: Highly expressed miR-130a was observed in OSCC cell lines. Silenced miR-130a reduced OSCC proliferation, metastasis, invasion and EMT while propelled apoptosis. Furthermore, miR-130a targeted PTEN to promote the OSCC progression. Downregulation of PTEN reversed the inhibition of silencing miR-130a on proliferation and migration of SCC-4 cells. miR-130a targeted PTEN to inactivate the Hippo-YAP axis. OSCC progression was notably promoted by a combination of YAP inhibitor verteporfin and miR-130a inhibitor. Additionally, silenced miR-130a inhibited OSCC progression in vivo.

Discussion: Silencing miR-130a inhibited OSCC progression by targeting PTEN and activating the Hippo-YAP axis. This investigation may provide novel insight for OSCC treatment.
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http://dx.doi.org/10.2147/CMAR.S287575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216666PMC
June 2021

Role of nonspherical DLVO and capillary forces in the transport of 2D delaminated TiCT MXene in saturated and unsaturated porous media.

Environ Res 2021 09 5;200:111451. Epub 2021 Jun 5.

Department of Soil and Water Sciences, China Agricultural University, Beijing, 100193, China.

The transport and retention of two-dimensional (2D) nanomaterials, such as graphene oxide, in porous media have attracted lots of attention. However, previous studies often simplified these 2D colloids as equivalent spheres for numerical simulations, which ignored the influence of particle shape on colloid retention at multiple interfaces. In this study, a novel 2D nanomaterial delaminated TiCT (d-TiCT) was adopted to fill this knowledge gap. Comprehensive analyses of the 2D colloid retention mechanisms were conducted based on colloid characterization, saturated and unsaturated column experiments, reactive transport modeling, 2D-based DLVO and nonspherical capillary energy simulations. Results show that d-TiCT mobility in both saturated and unsaturated conditions enhanced with the increase in pH and decrease in ionic strength. The DLVO interaction energy of d-TiCT at the sand-water-interface (SWI) decreased with the orientation angle of the colloidal major axis to the sand surface from 0° to 90°. The primary mechanism under saturated flow conditions was the irreversible attachment in the deep secondary minimum at the SWI with the major axis of d-TiCT parallel to the sand surface. The attachment in the primary minimum at 0° was impossible due to the extremely high energy barrier, and the attachment in the primary and secondary minimum at other orientation angles were negligible. d-TiCT only experienced repulsive electrostatic force when approaching the air-water-interface (AWI) no matter the particle orientation. The detaching capillary potential energy was 3 orders of magnitude larger than the attractive DLVO interaction energy of the SWI in the secondary minimum at 0°, suggesting that the capillary force-induced irreversible attachment at the AWI was the primary mechanism under unsaturated flow conditions. This study shows that the DLVO and capillary potential energies were significantly dependent on the particle-interface orientation and colloidal shape. A simplification of 2D colloids as spheres is not recommended.
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http://dx.doi.org/10.1016/j.envres.2021.111451DOI Listing
September 2021

Correlation of left ventricular longitudinal strain and E/e' ratio in primary hypertension patients.

Clin Exp Hypertens 2021 Oct 6;43(7):653-660. Epub 2021 Jun 6.

The First Affiliated Hospital of South China University of Technology, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Hypertension Research Laboratory, Guangzhou, China.

: The aim of this study is to explore and compare the relationships of both global longitudinal strain (GLS) and strain (SR) with E/e' ratio in a population of asymptomatic patients with systemic hypertension.: Retrospectively included 210 cases of essential hypertension patients. Dynamic images were analyzed for left ventricular myocardial systolic global longitudinal strain (GLS), left ventricular longitudinal peak systolic strain rate (SRs), early diastolic peak strain rate (SRe), late diastolic peak strain rate (SRa). According to the 2012 baseline E/e' ratio, the population was divided into three groups, group A (E/e'<8), group B (8 ≤ E/e'≤14), and group C (E/e'>14).: Systolic function parameters left ventricular ejection fraction (LVEF) remained at normal rage and no different, but patients with elevated E/e' ratio had significantly lower GLS, lower early diastolic strain rate(SRe), lower ratio of early diastolic strain rate to late diastolic strain rate (SRe/a) and higher E/SRe. Positive relationships were observed between GLS, E/SRe and E/e' ratio, inverse relationships were observed between SRe, SRe/a and E/e' ratio. E/SRe >0.73 had a sensitivity of 87.7% and a specificity of 38.2% for predicting an elevated E/e' ratio (E/e'>14). In multivariable analysis, IVS-e' <7 cm/s showed almost 2.5-fold increased risk for decreased GLS (OR 2.48[95% CI 1.36-4.53]; p = 003).: Our current study demonstrated that hypertensive patients with preserved LVEF and elevated E/e' ratio have systolic and diastolic abnormalities in longitudinal directions as detected by speckle imaging. E/SRe correlates well with E/e' and predicted elevated left ventricular filling pressure.
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http://dx.doi.org/10.1080/10641963.2021.1937201DOI Listing
October 2021

The Calcium-Sensing Receptor Is Involved in Follicle-Stimulating Hormone-Induced Cumulus Expansion in Cultured Porcine Cumulus-Oocyte Complexes.

Front Cell Dev Biol 2021 20;9:625036. Epub 2021 May 20.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

The Calcium-Sensing Receptor (CASR) is a G protein-coupled receptor of the C family that reportedly promotes maturation of porcine oocytes. However, its role in cumulus expansion of cumulus-oocyte complexes (COCs) is not well known. This study was conducted to determine the role of CASR and potential mechanisms involved during maturation (IVM) of porcine COCs. After culture of COCs in follicle-stimulating hormone (FSH)-supplement maturation medium for 24 h, the time of breakdown of the germinal vesicle (GVBD), indicative of initiation of meiotic maturation, resulted in an increased ( < 0.05) mRNA expression level in cumulus cells. Moreover, IVM of COCs in 10 μM of the CASR agonist NPS R-568 promoted ( < 0.05) cumulus expansion but only in FSH-containing medium. Conversely, 20 μM of the CASR inhibitor NPS2390 precluded cumulus expansion. We next tested the effect of the CASR agonist/inhibitor on the expression of cumulus expansion-related genes. The CASR agonist significantly upregulated the expression of hyaluronan acid synthase 2 (), whereas the CASR inhibitor downregulated the expression of all , prostaglandin-endoperoxide synthase 2 (), and tumor necrosis factor a-induced protein 6 (). Altogether, these results suggest that CASR activity is involved in FSH-stimulated porcine cumulus expansion.
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http://dx.doi.org/10.3389/fcell.2021.625036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173154PMC
May 2021

The patterns of left ventricular alteration by adipose tissue distribution: implication for heart failure prevention.

ESC Heart Fail 2021 Aug 26;8(4):3093-3105. Epub 2021 May 26.

Department of Cardiology, Guangdong Cardiovascular Institute, Hypertension Research Laboratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Aims: The current study aimed to evaluate the associations between general and abdominal obesity with left ventricular (LV) structure and function and whether these associations differed by sex.

Methods And Results: This is a community-based cross-sectional study, and 971 hypertensive individuals without overt cardiovascular disease were included. General obesity was defined as body mass index (BMI) ≥ 28 kg/m , and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm for men and ≥85 cm for women. The associations between general and abdominal obesity with LV structure and function were examined using linear regression analysis, and the interaction by sex was performed. The mean age was 66.5 ± 11.4 years, and women accounted for 62%. General obese individuals (n = 205) were more likely to have concentric remodelling, LV hypertrophy, and worse diastolic function. Similar differences were observed in abdominal obese individuals (n = 593). General obesity was associated with LV end-diastolic volume, LV mass, left atrial volume, and septal E/e' ratio after adjusting for WC and clinical covariates; and abdominal obesity was associated with septal e' velocity after adjusting for BMI and clinical covariates. The associations between general obesity with LV structure and function did not differ by sex, while the magnitudes of the associations between abdominal obesity with LV mass and septal e' velocity were greater in men.

Conclusions: General and abdominal obesity were associated with different patterns of LV structural and functional alterations, stressing the importance of incorporating BMI and WC measurements into assessing obesity-related LV alterations.
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http://dx.doi.org/10.1002/ehf2.13415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318514PMC
August 2021

Preoperative Ultrasound-Guided Trigeminal Nerve Block in Orthognathic Surgery: A Prospective Study About Its Efficacy of Intraoperative Anesthetic Dosage and Postoperative Analgesia.

J Oral Maxillofac Surg 2021 Apr 18. Epub 2021 Apr 18.

Attending, Department of Anesthesiology, Peking University Hospital of Stomatology, Beijing, China.

Purpose: Ultrasound-guided trigeminal nerve block is rarely used in orthognathic surgery, and its impact of postoperative analgesia and the auxiliary effect on hypotensive anesthesia have not been fully reported. The purpose of this study is to measure the efficacy of ultrasound-guided trigeminal nerve block on intraoperative anesthetic dosage and postoperative analgesia.

Patients And Methods: In this single-blind, prospective, controlled trial, all patients were randomly assigned to 2 groups (n = 21/group): GEA group (general anesthesia) and TNB group (ultrasound-guided trigeminal nerve block [UGTNB] with general anesthesia). The primary variable was postoperative pain (visual analog scale scores, VAS scores) at postoperative 2, 4, 6, 12, and 24 hours. Satisfaction with postoperative pain management during postoperative 24 hours; the number of patients with moderate-to-severe pain (VAS score: >3) at postoperative 2, 4, 6, 12, 24 hours; and the consumption of opioids and nicardipine intraoperatively, etc. were secondary variables. Data were analyzed using the unpaired t, χ2, and Wilcoxon nonparametric tests.

Results: In this study, 40 patients at the Peking University School and Hospital of Stomatology between January 2019 to March 2019 were included with a mean age of 24.13 ± 5.07 for statistical analysis and 37.5% were male. Compared to GEA group, the TNB group had a significantly lower VAS scores at postoperative 6 hours and 12 hours, which were 2[0,2] and 0[0,2], respectively. Furthermore, patients in TNB group were more satisfied with pain management at postoperative 24 hours than patients in GEA group (5[4,5] vs 4[3,5]; P = .03). Statistically less amount of opioids and nicardipine in TNB group were used intraoperatively (P < .01).

Conclusion: UGTNB use in orthognathic surgery may improve analgesia in the 24 hours after the operation, additionally, facilitate hypotensive anesthesia with fewer agents and fewer adverse effects postoperatively.
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http://dx.doi.org/10.1016/j.joms.2021.04.011DOI Listing
April 2021

Na1.7 target modulation and efficacy can be measured in nonhuman primate assays.

Sci Transl Med 2021 05;13(594)

Merck & Co. Inc., WP-14, 770 Sumneytown Pike, P.O. Box 4, West Point, PA 19486, USA.

Humans with loss-of-function mutations in the Na1.7 channel gene (SCN9A) show profound insensitivity to pain, whereas those with gain-of-function mutations can have inherited pain syndromes. Therefore, inhibition of the Na1.7 channel with a small molecule has been considered a promising approach for the treatment of various human pain conditions. To date, clinical studies conducted using selective Na1.7 inhibitors have not provided analgesic efficacy sufficient to warrant further investment. Clinical studies to date used multiples of in vitro IC values derived from electrophysiological studies to calculate anticipated human doses. To increase the chance of clinical success, we developed rhesus macaque models of action potential propagation, nociception, and olfaction, to measure Na1.7 target modulation in vivo. The potent and selective Na1.7 inhibitors SSCI-1 and SSCI-2 dose-dependently blocked C-fiber nociceptor conduction in microneurography studies and inhibited withdrawal responses to noxious heat in rhesus monkeys. Pharmacological Na1.7 inhibition also reduced odor-induced activation of the olfactory bulb (OB), measured by functional magnetic resonance imaging (fMRI) studies consistent with the anosmia reported in Na1.7 loss-of-function patients. These data demonstrate that it is possible to measure Na1.7 target modulation in rhesus macaques and determine the plasma concentration required to produce a predetermined level of inhibition. The calculated plasma concentration for preclinical efficacy could be used to guide human efficacious exposure estimates. Given the translatable nature of the assays used, it is anticipated that they can be also used in phase 1 clinical studies to measure target modulation and aid in the interpretation of phase 1 clinical data.
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http://dx.doi.org/10.1126/scitranslmed.aay1050DOI Listing
May 2021

Clinical outcomes of bivalirudin versus heparin in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion.

Ann Transl Med 2021 Apr;9(8):629

Department of Cardiology, Zhongshan Hospital, Fudan University, Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.

Background: Prior studies have suggested that patients with atrial fibrillation (AF) referred for left atrial appendage occlusion (LAAO) are confronted with considerable risk of periprocedural thromboembolism and hemmorhagic events. The purpose of this study was to evaluate the safety and feasibility of bivalirudin during LAAO.

Methods: This retrospective, observational study included 420 AF patients who were evaluated as being at high risk of stroke or bleeding and indicated for LAAO at our center between June 2018 and June 2019 (158 with bivalirudin and 262 with heparin). The primary outcome was the incidence of any bleeding within 48 hours of LAAO. Secondary outcomes were major adverse cardiac events (MACE) between 48 hours and 60 days post-procedure and overall bleeding events during follow up.

Results: No significant difference was observed between bivalirudin and heparin for major periprocedural bleeding (1.27% for bivalirudin 2.29% for heparin, P=0.716) or minor bleeding (1.27% 1.15%, P>0.9). At 48 hours post-procedure, strokes occurred at a rate of 0.63% in the bivalirudin group and 1.15% in the heparin group (P>0.9), and one case treated with bivalirudin developed systemic embolization. At 60 days, the rates of MACE (1.90% 2.29%, P>0.9), a device-related thrombus (DRT) (1.27% 1.52%, P>0.9), and overall bleeding events (5.06% 4.96%, P=0.963) were comparable between the 2 cohorts. Upon Kaplan-Meier survival analysis, early safety during the 60-day follow-up was 93.67% in the bivalirudin group and 91.60% in the heparin group (P=0.570).

Conclusions: Bivalirudin has a comparable safety and efficacy profile to heparin as an intraprocedural anticoagulant, but currently, it should still be reserved for patients in which heparin is contraindicated.
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http://dx.doi.org/10.21037/atm-20-4755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106030PMC
April 2021

Age-related alterations in cardiac and arterial structure and function in hypertensive women and men.

J Clin Hypertens (Greenwich) 2021 07 7;23(7):1322-1334. Epub 2021 May 7.

Department of Cardiology, Hypertension Research Laboratory, Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.

The study was to compare age-related alterations in cardiac and arterial structure and function by sex and to explore the impacts of achieved systolic blood pressure (SBP; <130 mm Hg vs. <140 mm Hg) level on age-related alterations in cardiac and arterial structure and function in hypertensive women and men. Community hypertensive individuals without cardiovascular disease who had echocardiographic examination were included. Age-related alterations in cardiac and arterial structure and function were compared by sex, and interplay between age and sex was analyzed according to achieved SBP level. The mean age of the cohort was 66.5 years, and women accounted for 62% (n = 602) of the cohort (n = 971). Compared to men, women had worse left ventricular (LV) diastolic function and greater LV and arterial stiffness. After adjusting for covariates, the magnitude of the associations between age with septal E/e' ratio, septal S' velocity, effective arterial elastance (Ea) and LV end-diastolic elastance (Eed) were greater in women. Sex differences in the magnitude of association between age with these four indices varied according to achieved SBP level. When achieved SBP <130 mm Hg, the magnitude of the associations between age with septal E/e' ratio, septal S' velocity, Ea and Eed did not differ by sex. Since age and sex are non-modifiable, achieving SBP target, especially at a lower level, might be beneficial to attenuate sex differences in age-related alterations in cardiac and arterial structure and function.
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http://dx.doi.org/10.1111/jch.14262DOI Listing
July 2021

Physiological characterization of chitin synthase A responsible for the biosynthesis of cuticle chitin in Culex pipiens pallens (Diptera: Culicidae).

Parasit Vectors 2021 May 1;14(1):234. Epub 2021 May 1.

Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.

Background: The pathogens transmitted by mosquitoes to humans and animals cause several emerging and resurgent infectious diseases. Increasing insecticide resistance requires rational action to control the target vector population. Chitin is indispensable for insect growth and development and absent from vertebrates and higher plants. Chitin synthase A (CHSA) is a crucial enzyme in chitin synthesis; therefore, identifying and characterizing how CHSA determines chitin content may contribute to the development of novel vector control strategies.

Results: The injection of small interfering RNA targeting CHSA (siCHSA) to knockdown CHSA transcripts in larval, pupal and adult stages of Culex pipiens pallens resulted in the appearance of different lethal phenotypes. When larval and pupal stages were injected with siCHSA, CHSA knockdown prevented larval molting, pupation and adult eclosion, and affected the production of chitin and chitin degradation, which resulted in an ecdysis defect phenotype of mosquitoes. When siCHSA was injected into mosquitoes in the adult stage, CHSA knockdown also affected the laminar organization of the mesoderm and the formation of pseudo-orthogonal patterns of the large fibers of the endoderm.

Conclusion: We provide a systematic and comprehensive description of the effects of CHSA on morphogenesis and metamorphosis. The results show that CHSA not only affects chitin synthesis during molting, but also might be involved in chitin degradation. Our results further show that CHSA is important for the structural integrity of the adult mosquito cuticle.
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http://dx.doi.org/10.1186/s13071-021-04741-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088658PMC
May 2021

Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome.

Front Physiol 2021 8;12:663950. Epub 2021 Apr 8.

Department of Pediatrics, University of California, San Diego, San Diego, CA, United States.

Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice ( ), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, < 0.05 vs. Air 8.1 ± 0.8%, < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, < 0.05). The most differentially abundant microbial families ( < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites ( < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.
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http://dx.doi.org/10.3389/fphys.2021.663950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060652PMC
April 2021
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