Publications by authors named "Tao Wang"

6,181 Publications

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A critical review on the distribution and ecological risk assessment of steroid hormones in the environment in China.

Sci Total Environ 2021 Apr 30;786:147452. Epub 2021 Apr 30.

Chair of Ecological Systems Design, Institute of Environmental Engineering, ETH Zürich, 8093 Zürich, Switzerland.

During past two decades, steroid hormones have raised significant public concerns due to their potential adverse effects on the hormonal functions of aquatic organisms and humans. Considering China being a big producer and consumer of steroid hormones, we summarize the current contamination status of steroid hormones in different environmental compartments in China, and preliminarily assess the associated risks to ecological systems. The results show that steroid hormones are ubiquitously present in Chinese surface waters where estrogens are the most studied steroids compared with androgens, progestogens and glucocorticoids. Estrone (E1), 17β-estradiol (17β-E2) and estriol (E3) are generally the dominant steroid estrogens in Chinese surface waters, whereas for the other steroids, androsterone (ADR), epi-androsterone (EADR), progesterone (PGT), cortisol (CRL) and cortisone (CRN) have relatively large contributions. Meanwhile, the investigations for the other environmental media such as particles, sediments, soils and groundwater have been limited, as well as for steroid conjugates and metabolites. The median risk quotients of most steroid hormones in surface waters and sediments are lower than 1, indicating low to moderate risks to local organisms. This review provides a full picture of steroid distribution and ecological risks in China, which may be useful for future monitoring and risk assessment. More studies may focus on the analysis of steroid conjugates, metabolites, solid phase fractions, analytical method development and acute/chronic toxicities in different matrices to pursue a more precise and holistic risk assessment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147452DOI Listing
April 2021

Bilayer and three dimensional conductive network composed by SnCl reduced rGO with CNTs and GO applied in transparent conductive films.

Sci Rep 2021 May 10;11(1):9891. Epub 2021 May 10.

Tianjin Key Laboratory of Advanced Fibers and Energy Storage, School of Material Science and Engineering, Tiangong University, Tianjin, 300387, China.

Graphene oxide (GO), reduced graphene oxide (rGO) and carbon nanotubes (CNTs) have their own advantages in electrical, optical, thermal and mechanical properties. An effective combination of these materials is ideal for preparing transparent conductive films to replace the traditional indium tin oxide films. At present, the preparation conditions of rGO are usually harsh and some of them have toxic effects. In this paper, an SnCl/ethanol solution was selected as the reductant because it requires mild reaction conditions and no harmful products are produced. The whole process of rGO preparation was convenient, fast and environmentally friendly. Then, SEM, XPS, Raman, and XRD were used to verify the high reduction efficiency. CNTs were introduced to improve the film conductive property. The transmittance and sheet resistance were the criteria used to choose the reduction time and the content ratios of GO/CNT. Thanks to the post-treatment of nitric acid, not only the by-product (SnO) and dispersant in the film are removed, but also the doping effect occurs, which are all conducive to reducing the sheet resistances of films. Ultimately, by combining rGO, GO and CNTs, transparent conductive films with a bilayer and three-dimensional structure were prepared, and they exhibited high transmittance and low sheet resistance (58.8 Ω/sq. at 83.45 T%, 47.5 Ω/sq. at 79.07 T%), with corresponding [Formula: see text] values of 33.8 and 31.8, respectively. In addition, GO and rGO can modify the surface and reduce the film surface roughness. The transparent conductive films are expected to be used in photoelectric devices.
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http://dx.doi.org/10.1038/s41598-021-89305-1DOI Listing
May 2021

Efficient inverse design and spectrum prediction for nanophotonic devices based on deep recurrent neural networks.

Nanotechnology 2021 May 10. Epub 2021 May 10.

Wuhan National Lab for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei, CHINA.

The development of nanophotonic devices has presented a revolutionary means to manipulate light at nanoscale. How to efficiently design these devices is an active area of research. Recently, artificial neural networks (ANNs) have displayed powerful ability in the inverse design of nanophotonic devices. However, there is limited research on the inverse design for modeling and learning the sequence characteristics of a spectrum. In this work, we propose a deep learning method based on an improved recurrent neural network to extract the sequence characteristics of a spectrum and achieve inverse design and spectrum prediction. A key feature of the network is that the memory or feedback loops it comprises allow it to effectively recognize time series data. In the context of nanorods hyperbolic metamaterials, we demonstrated the high consistency between the target spectrum and the predicted spectrum, and the network learned the deep physical relationship concerning the structural parameter changes reflected on the spectrum. The effectiveness of our approach is also tested by user-drawn spectra. Moreover, the proposed model is capable of predicting an unknown spectrum based on a known spectrum with only 0.32% mean relative error. The prediction model may be helpful to predict data beyond the detection limit. We propose this versatile method as an effective and accurate alternative to the application of ANNs in nanophotonics, paving way for fast and accurate design of desired devices.
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http://dx.doi.org/10.1088/1361-6528/abff8dDOI Listing
May 2021

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

Aging (Albany NY) 2021 May 7;13. Epub 2021 May 7.

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.

Background: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited.

Results: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV.

Conclusions: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV.

Materials And Methods: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.
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http://dx.doi.org/10.18632/aging.202987DOI Listing
May 2021

Nasopharyngeal Microbiomes in Donkeys Shedding Subspecies in Comparison to Healthy Donkeys.

Front Vet Sci 2021 22;8:645627. Epub 2021 Apr 22.

Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China.

subsp. equi () is the pathogen causing strangles, a highly infectious disease that can affect equids including donkeys of all ages. It can persistently colonize the upper respiratory tract of animals asymptomatically for years, which serves as a source of infection. Several strangles outbreaks have been reported in the donkey industry in China in the last few years and pose a great threat to health, production, and the welfare of donkeys. Nasopharyngeal swab samples for culture and PCR are used widely in strangles diagnosis. Additionally, microbiomes within and on the body are essential to host homoeostasis and health. Therefore, the microbiome of the equid nasopharynx may provide insights into the health of the upper respiratory tract in animals. There has been no study investigating the nasopharyngeal microbiome in healthy donkeys, nor in donkeys shedding . This study aimed to compare nasopharyngeal microbiomes in healthy and carrier donkeys using 16S rRNA gene sequencing. Nasopharyngeal samples were obtained from 16 donkeys recovered from strangles (group S) and 14 healthy donkeys with no history of strangles exposure (group H). Of those sampled, 7 donkeys were determined to be carriers with positive PCR and culture results in group S. In group H, all 14 donkeys were considered free of strangles based on the history of negative exposure, negative results of PCR and culture. Samples from these 21 donkeys were used for microbial analysis. The nasopharyngeal microbiome composition was compared between the two groups. At the phylum level, relative abundance of Proteobacteria was predominantly higher in the carrier donkeys than in healthy donkeys ( < 0.01), while Firmicutes and Actinobacteria were significantly less abundant in the carrier donkeys than in healthy donkeys ( < 0.05). At the genus level, was detected in the upper respiratory tract of donkeys for the first time and dominated in carrier donkeys. It is suspected to suppress other normal flora of URT microbiota including spp., spp., and spp. We concluded that the nasopharyngeal microbiome in carrier donkeys still exhibited microbial dysbiosis, which might predispose them to other airway diseases.
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http://dx.doi.org/10.3389/fvets.2021.645627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100518PMC
April 2021

A partial loss-of-function variant in gene in a Chinese cohort with idiopathic hypogonadotropic hypogonadism.

Transl Androl Urol 2021 Apr;10(4):1676-1687

Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease attributed to the disorder of hypothalamic-pituitary-gonadal axis. Mutations in the gene are one of the most common genetic causes of IHH. Herein, we aimed to investigate variants in a Chinese cohort with IHH, and to characterize them at the molecular level.

Methods: A total of 153 IHH patients were recruited, and variants were detected using a tailored next-generation sequencing panel. rare sequencing variant (RSV) was verified using Sanger sequencing. Phenotypic features and therapeutic outcomes of patients were followed up. In order to examine the pathogenicity of the RSV, we performed conservative analysis, crystal structure prediction, expression analysis as well as the assessment of ERK1/2 activation and IP3/Ca response.

Results: The same heterozygous RSV (p.R240Q) in was identified in four sporadic IHH patients. These patients exhibited different severity of testicular development and hormone profile. hCG treatment was effective in improving gonadal development, serum testosterone, and semen quality. The RSV has no effect on the expression of mRNA and protein, whereas damaged ERK1/2 activation and inositol triphosphate/calcium signaling.

Conclusions: The study expands mutation spectrum in IHH patients, and reveals that the RSV is a partial loss-of-function mutation. Although this heterozygous RSV may not have a significant influence on the pathogenesis of IHH, but its homozygous/ compound status should be paid attention in this research field.
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http://dx.doi.org/10.21037/tau-20-1390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100836PMC
April 2021

Integrated Analysis to Identify a Redox-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Oxid Med Cell Longev 2021 21;2021:6648093. Epub 2021 Apr 21.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.

The imbalance of the redox system has been shown to be closely related to the occurrence and progression of many cancers. However, the biological function and clinical significance of redox-related genes (RRGs) in clear cell renal cell carcinoma (ccRCC) are unclear. In our current study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database of ccRCC patients and identified the differential expression of RRGs in tumor and normal kidney tissues. Then, we identified a total of 344 differentially expressed RRGs, including 234 upregulated and 110 downregulated RRGs. Fourteen prognosis-related RRGs (, , , , , , , , , , , , , and ) were selected out, and a prognosis-related signature was constructed based on these RRGs. Survival analysis showed that overall survival was lower in the high-risk group than in the low-risk group. The area under the receiver operating characteristic curve of the risk score signature was 0.728 at three years and 0.759 at five years in the TCGA cohort and 0.804 at three years and 0.829 at five years in the E-MTAB-1980 cohort, showing good predictive performance. In addition, we explored the regulatory relationships of these RRGs with upstream miRNA, their biological functions and molecular mechanisms, and their relationship with immune cell infiltration. We also established a nomogram based on these prognostic RRGs and performed internal and external validation in the TCGA and E-MTAB-1980 cohorts, respectively, showing an accurate prediction of ccRCC prognosis. Moreover, a stratified analysis showed a significant correlation between the prognostic signature and ccRCC progression.
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http://dx.doi.org/10.1155/2021/6648093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084660PMC
April 2021

Transcriptomic and Physiological Analysis Reveal That α-Linolenic Acid Biosynthesis Responds to Early Chilling Tolerance in Pumpkin Rootstock Varieties.

Front Plant Sci 2021 23;12:669565. Epub 2021 Apr 23.

Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, China Agricultural University, Beijing, China.

Climate changes especially chilling stress affects cucurbit crops during winter seasonal production. Grafting to pumpkin rootstocks is widely used to improve the vigor of cucurbits, especially cucumber ( L.) plants, in the face of chilling stress. In our study, multi-disciplinary aspect approaches were used to investigate growth changes of pumpkin under chilling stress. Firstly, the morphological and physiological characteristics of 14 pumpkin () varieties following different periods of chilling stress was analyzed by using physiological means. Mathematical results of principal component analysis (PCA) with chlorophyll-a, chlorophyll-b, carotenoid contents, chilling injury index and relative electrolyte permeability indicated that relative electrolyte permeability as the primary judgment index was best associated with the comparison of chilling tolerance in pumpkin rootstock varieties. Then, transcriptomic and DCMU (Diuron) application and chlorophyll fluorescence examination analysis of pumpkin leaves revealed that 390 differentially expressed genes (CmoDEGs) that affect photosynthesis were upregulated in leaves. 127 CmoDEGs both in leaves and roots were enriched for genes involved in unsaturated fatty acid metabolism, suggesting that plasma membrane lipids are involved in chilling perception. The results of increased composition of unsaturated fatty acid in leaves and qRT-PCR analysis of relative mRNA abundance confirmed that α-linolenic acid biosynthesis was responding to pumpkin chilling tolerance. The integration of physiological, mathematical bioinformatical and biological analysis results contributes to our understanding of the molecular mechanisms underlying chilling tolerance and its improvement in cucumber grafted on pumpkin rootstocks. It provided an important theoretical basis and reference for further understanding on the impact of climate change on plant physiological changes.
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http://dx.doi.org/10.3389/fpls.2021.669565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104029PMC
April 2021

Late-life sleep duration associated with amnestic mild cognitive impairment.

Int Psychogeriatr 2021 May 10:1-10. Epub 2021 May 10.

Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and Alzheimer's Disease and Related Disorders Center, Shanghai Jiao Tong University, Shanghai, China.

Objective: To examine the association between sleep duration in different stages of life and amnestic mild cognitive impairment (aMCI).

Design, Setting, And Participants: A total of 2472 healthy elderly and 505 patients with aMCI in China were included in this study. The study analyzed the association between aMCI and sleep duration in different stages of life.

Measurements: We compared sleep duration in different stages of life and analyzed the association between Montreal Cognitive Assessment scores and sleep duration by curve estimation. Logistic regression was used to evaluate the association between aMCI and sleep duration.

Results: In the analysis, there were no results proving that sleep duration in youth (P = 0.719, sleep duration < 10 hours; P = 0.999, sleep duration ≥ 10 hours) or midlife (P = 0.898, sleep duration < 9 hours; P = 0.504, sleep duration ≥ 9 hours) had a significant association with aMCI. In the group sleeping less than 7 hours in late life, each hour more of sleep duration was associated with approximately 0.80 of the original risk of aMCI (P = 0.011, odds ratio = 0.80, 95% confidence interval = 0.68-0.95).

Conclusions: Among the elderly sleeping less than 7 hours, there is a decreased risk of aMCI for every additional hour of sleep.
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http://dx.doi.org/10.1017/S1041610221000466DOI Listing
May 2021

The application of steel slag in a multistage pond constructed wetland to purify low-phosphorus polluted river water.

J Environ Manage 2021 May 7;292:112578. Epub 2021 May 7.

National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Scientific Observation and Research Station for Lake Dongtinghu(SEPSORSLD), State Environmental Protection Key Laboratory for Lake Pollution Control, State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, PR China; School of Civil Engineering, Liaoning Technical University, Fuxin, 123000, China.

To investigate the effect of a constructed wetland (CW) with steel slag as the filler on water contaminated by low phosphorus levels, a multistage pond CW system was designed in this study. Low-phosphorus polluted river water was used as the research object. This study explored the effects of using steel slag as a CW filler on phosphorus removal and the total phosphorus (TP) purification effect of the wetland system. The results showed that the TP removal rates in the ecological pond, oxidation pond, surface flow wetlands and submerged plant pond were 5.17%, 8.02%, 21.56%, and 16.31%, respectively. Intermittent increases in phosphorus concentration were observed in the reactors and were caused by the decay of plant tissues, which released pollutants. Because steel slag was added to the filler, the TP concentrations in the effluent of the first- and second-level horizontal subsurface CWs increased by 151.13% and 16.29%, respectively, compared to the influent concentration. The 20th to 40th days of the test run was a period of rapid phosphorus release of the system. The use of steel slag has a potential risk of phosphorus release when applied in CWs used to purify low-phosphorus contaminated water bodies.
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http://dx.doi.org/10.1016/j.jenvman.2021.112578DOI Listing
May 2021

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.

Nat Commun 2021 05 5;12(1):2547. Epub 2021 May 5.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.

Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 10-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.
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http://dx.doi.org/10.1038/s41467-021-22810-zDOI Listing
May 2021

Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments.

Cancer Cell Int 2021 Apr 6;21(1):193. Epub 2021 Apr 6.

Department of Pathology, Shenyang KingMed Center for Clinical Laboratory Co., Ltd, Shenyang, 110164, China.

Background: Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers.

Methods: GSE18520 and GSE26712 were downloaded from the GEO database. The "limma" and "WGCNA" packages were used to explore hub genes. The Kaplan-Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples.

Results: In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients.

Conclusions: In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
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http://dx.doi.org/10.1186/s12935-021-01854-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097951PMC
April 2021

Weight gain from early to middle adulthood increases the risk of incident asthma later in life in the United States: a retrospective cohort study.

Respir Res 2021 May 5;22(1):139. Epub 2021 May 5.

School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, Shandong, People's Republic of China.

Background: Data describing the effects of weight change across adulthood on asthma are important for the prevention of asthma. This study aimed to investigate the association between weight change from early to middle adulthood and risk of incident asthma.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES), we performed a nationally retrospective cohort study of the U.S. general population. A total of 20,771 people aged 40-74 years with recalled weight at young and middle adulthood were included in the cohort. Four weight change groups were categorized: stable non-obesity, non-obesity to obesity, obesity to non-obesity, and stable obesity. Hazard ratios (HRs) and 95% confidence intervals (CIs) relating weight change to incident asthma over 10 years of follow-up were calculated using Cox models adjusting for covariates.

Results: Compared with the stable non-obesity group, the HRs of incident asthma were 1.63 (95% CI = 1.29 to 2.07, P < 0.001) for the non-obesity to obesity group, 1.41 (95% CI = 0.97 to 2.05, P = 0.075) for stable obesity group, and 1.21 (95% CI = 0.41 to 3.62, P = 0.730) for the obesity to non-obesity group. In addition, participants who gained more than 20 kg from young to middle adulthood had a HR of 1.53 (95% CI = 1.15 to 2.03, P = 0.004), compared with those whose weight remained stable (weight change within 2.5 kg).

Conclusions: Weight gain from early to middle adulthood was associated with higher risk of incident asthma as compared to those who maintained normal weight. Thus, maintaining normal weight throughout adulthood might be important for the primary prevention of adult-onset asthma.
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http://dx.doi.org/10.1186/s12931-021-01735-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097961PMC
May 2021

Carotid endarterectomy with stent graft removal and end to end bypass in the treatment of in-stent occlusion after endovascular therapy of carotid gunshot injury.

Ann Vasc Surg 2021 May 2. Epub 2021 May 2.

Cardiac Surgery, Peking University Third Hospital, Beijing, China.

Carotid jugular fistula and pseudoaneurysm are easy to form after gunshot injury of carotid artery. Endovascular therapy, such as stent graft implantation, can successfully block the fistula and pseudoaneurysm cavity. However, the possibility of in-stent restenosis or occlusion will lead to treatment failure. The authors describe the case of a 30-year-old man with carotid jugular fistula and pseudoaneurysm after gunshot injury of left carotid artery who had received stent graft placement. However, two years after stent graft, the stenosis of proximal carotid artery near stent was found and gradually aggravated. During the follow-up, transient amaurosis of his left eye occurred intermittently and in-stent occlusion and severe stenosis of proximal carotid artery were found by computed tomography angiography(CTA) in our centre. Carotid endarterectomy (CEA)with stent graft removal and end to end bypass using vascular graft was performed to reconstruct the blood flow of left carotid artery. To the extent of the authors' knowledge, this case illustrates a rare CEA and vascular graft bypass in the treatment of in-stent occlusion following the gunshot injury to the carotid artery. The successful treatment of this rare case provides an option to deal with this kind of tricky problem.
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http://dx.doi.org/10.1016/j.avsg.2021.04.013DOI Listing
May 2021

Rediscovering potential molecular targets for glioma therapy through the analysis of the cell of origin, microenvironment, and metabolism.

Curr Cancer Drug Targets 2021 May 3. Epub 2021 May 3.

Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd, Guangming Dist., Shenzhen 518107. China.

Gliomas are the most common type of malignant brain tumors. Despite significant medical advances, gliomas remain incurable and are associated with high mortality. Although numerous biomarkers of diagnostic value have been identified and significant progress in the prognosis of the outcome has been made, the treatment has not been parallelly improved during the last three decades. This review summarizes and discusses three aspects of recent discoveries related to glioma, with the objective to highlight the advantages of glioma-specific drugs targeting the cell of origin, microenvironment, and metabolism. Given the heterogeneous nature of gliomas, various cell populations have been implicated as likely sources of the tumor. Depending on the mutation(s) acquired by the cells, it is believed that neuronal stem/progenitor cells, oligodendrocyte progenitor cells, mature neurons, and glial cells can initiate cell transformation into a malignant phenotype. The level of tumorigenicity appears to be inversely correlated with the maturation of a given cell population. The microenvironment of gliomas includes non-cancer cells such as immune cells, fibroblasts, and cells of blood vessels, as well as secreted molecules and the extracellular matrix, and all these components play a vital role during tumor initiation and progression. We will discuss in detail how the tumor microenvironment can stimulate and drive the transformation of non-tumor cell populations into tumor-supporting cells or glioma cells. Metabolic reprogramming is a key feature of gliomas and is thought to reflect the adaptation to the increased nutritional requirements of tumor cell proliferation, growth, and survival. Mutations in the IDH gene can shape metabolic reprogramming and may generate some vulnerabilities in glioma cells, such as abnormal lipid metabolism and sensitivity to endoplasmic reticulum stress (ERS). We will analyze the prominent metabolic features of malignant gliomas and the key pathways regulating glioma metabolism. This review is intended to provide a conceptual background for the development of glioma therapies based on the properties of tumor cell populations, microenvironment, and metabolism.
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http://dx.doi.org/10.2174/1568009621666210504091722DOI Listing
May 2021

Safety and efficacy of transcarotid artery revascularisation versus carotid endarterectomy: protocol for a systematic review and meta-analysis study.

BMJ Open 2021 May 4;11(5):e043039. Epub 2021 May 4.

China International Neuroscience Institute (China-INI), Beijing, China

Introduction: In recent years, the transcarotid artery revascularisation (TCAR) with flow reversal technique has been developed to treat carotid artery stenosis. The superiority of TCAR over transfemoral carotid artery stenting has been demonstrated. However, the safety and efficacy of TCAR and carotid endarterectomy remain unclear. This study aims to introduce a protocol for a systematic review and meta-analysis to compare the morbidity and mortality rates between TCAR and carotid endarterectomy in the treatment of atherosclerotic carotid artery stenosis.

Methods And Analysis: This protocol was drafted using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. Herein, major databases will be searched, including Medline, Web of Science, Embase and the Cochrane Library, and randomised controlled trials and high-quality observational studies will be included. We will screen all studies published from January 2000 to March 2021. Bias risk will be evaluated using the Cochrane Collaboration criteria or Methodological Index for Non-randomised Studies criteria, depending on the study type. Two reviewers will select eligible studies and extract the data independently. The primary outcome will include stroke or death during the perioperative period and follow-up. Subgroup and sensitivity analyses will be performed to explore any potential sources of heterogeneity. Specific results will be described in a narrative form when available eligible studies are insufficient for meta-analysis. Publication bias will be assessed using a funnel plot.

Ethics And Dissemination: This study will summarise and analyse the existing literature; hence, ethics approval will not be required. The final results may be published at a relevant academic conference or in a journal.

Prospero Registration Number: CRD42020178691.
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http://dx.doi.org/10.1136/bmjopen-2020-043039DOI Listing
May 2021

Emerging functions of piwi-interacting RNAs in diseases.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.

PIWI-interacting RNAs (piRNAs) are recently discovered small non-coding RNAs consisting of 24-35 nucleotides, usually including a characteristic 5-terminal uridine and an adenosine at position 10. PIWI proteins can specifically bind to the unique structure of the 3' end of piRNAs. In the past, it was thought that piRNAs existed only in the reproductive system, but recently, it was reported that piRNAs are also expressed in several other human tissues with tissue specificity. Growing evidence shows that piRNAs and PIWI proteins are abnormally expressed in various diseases, including cancers, neurodegenerative diseases and ageing, and may be potential biomarkers and therapeutic targets. This review aims to discuss the current research status regarding piRNA biogenetic processes, functions, mechanisms and emerging roles in various diseases.
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http://dx.doi.org/10.1111/jcmm.16466DOI Listing
May 2021

Predictors of fatal outcomes of hospitalized COVID-19 patients with pre-existing hypertension in China.

Clin Respir J 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Background: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one third of the adult population are hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension.

Methods And Results: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/mL (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/mL (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg for more than once (≥ 2 times) during hospitalization, were more likely to have ICU admission (P=0.037), invasive mechanical ventilation (P=0.028), and renal injury (P=0.005). A stricter BP control with the threshold of 130/80 mmHg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB) and spironolactone, was associated with lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) Vs. 25 (43.1%), P=0.048).

Conclusion: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need of ICU admission.
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http://dx.doi.org/10.1111/crj.13382DOI Listing
May 2021

Long noncoding RNA CTD-2245E15.3 promotes anabolic enzymes ACC1 and PC to support non-small cell lung cancer growth.

Cancer Res 2021 May 3. Epub 2021 May 3.

Biochemistry, Nanjing University

Long noncoding RNAs (lncRNA) have been shown to play critical regulatory roles in the onset and progression of human cancers. However, the functions of a large proportion of lncRNAs are still unexplored. Here we describe a novel lncRNA, CTD-2245E15.3, that promotes lung tumorigenesis by regulating the anabolic enzymes acetyl-CoA carboxylase 1 (ACC1) and pyruvate carboxylase (PC). Differentially expressed lncRNAs between non-small cell lung cancer (NSCLC) and paired adjacent nontumor tissues were identified by a microarray and validated using quantitative real-time polymerase chain reaction. CTD-2245E15.3 was significantly upregulated in NSCLC and was mainly located in the cytoplasm. Knockdown of CTD-2245E15.3 by specific antisense oligonucleotides suppressed cell growth in vitro and in vivo, largely due to cell cycle arrest and induction of apoptosis. Overexpression of CTD-2245E15.3 in an orthotopic model of lung cancer led to a significant increase in total tumor burden. CTD-2245E15.3 exerted its oncogenic function by binding ACC1 and PC, which are key anabolic factors for biomolecule synthesis in rapidly proliferating tumor cells. Knockdown of CTD-2245E15.3 increased phosphorylation of ACC1 at an inhibitory site for enzymatic activity and promoted PC degradation via ubiquitination. Supplements of palmitate or oxaloacetate, products of ACC1 and PC, alleviated the suppression of cell growth caused by loss of CTD-2245E15.3. These findings reveal the important role of CTD-2245E15.3 as an oncogenic lncRNA in the anabolic process for tumor growth.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3806DOI Listing
May 2021

Super-Assembled Hierarchical CoO Nanosheets-Cu Foam Composites as Multi-Level Hosts for High-Performance Lithium Metal Anodes.

Small 2021 May 3:e2101301. Epub 2021 May 3.

Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200433, P. R. China.

Achieving uniform lithium (Li) deposition is the key to tackle uncontrollable dendrite growth, which hinders the application of Li metal anodes. In this study, molten Li is thermally injected into a 3D framework by growing lithiophilic CoO nanosheets on Cu foam (CF). The CoO layer grown on the CF surface physically adsorbs molten Li, which makes it possible to spontaneously wet the framework. The morphology of CoO nanosheets does not change during the Li injection process and formed a multi-level structure with the CF, which is difficult to be achieved previously, as most lithiophilic oxides undergo serious chemical changes due to chemical reaction with Li and cannot provide a stable submicron structure for the subsequent Li stripping/plating process. The super-assembled multi-level structure provides abundant Li nucleation sites and electrolyte/electrode contact areas for rapid charge transfer in the composite anode. Therefore, the prolonged lifespan of symmetrical cells for 300 cycles at 10 and 10 mAh cm with lower polarization is achieved, which further renders the LiFePO and Li Ti O based full cells with improved capacity retention up to 87.3% and 80.1% after 500 cycles at 1 C. These results suggest that the composite anode has a great application prospect.
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http://dx.doi.org/10.1002/smll.202101301DOI Listing
May 2021

Data mining of an acoustic biomarker in tongue cancers and its clinical validation.

Cancer Med 2021 May 2. Epub 2021 May 2.

Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.

The promise of speech disorders as biomarkers in clinical examination has been identified in a broad spectrum of neurodegenerative diseases. However, to the best of our knowledge, a validated acoustic marker with established discriminative and evaluative properties has not yet been developed for oral tongue cancers. Here we cross-sectionally collected a screening dataset that included acoustic parameters extracted from 3 sustained vowels /ɑ/, /i/, /u/ and binary perceptual outcomes from 12 consonant-vowel syllables. We used a support vector machine with linear kernel function within this dataset to identify the formant centralization ratio (FCR) as a dominant predictor of different perceptual outcomes across gender and syllable. The Acoustic analysis, Perceptual evaluation and Quality of Life assessment (APeQoL) was used to validate the FCR in 33 patients with primary resectable oral tongue cancers. Measurements were taken before (pre-op) and four to six weeks after (post-op) surgery. The speech handicap index (SHI), a speech-specific questionnaire, was also administrated at these time points. Pre-op correlation analysis within the APeQoL revealed overall consistency and a strong correlation between FCR and SHI scores. FCRs also increased significantly with increasing T classification pre-operatively, especially for women. Longitudinally, the main effects of T classification, the extent of resection, and their interaction effects with time (pre-op vs. post-op) on FCRs were all significant. For pre-operative FCR, after merging the two datasets, a cut-off value of 0.970 produced an AUC of 0.861 (95% confidence interval: 0.785-0.938) for T patients. In sum, this study determined that FCR is an acoustic marker with the potential to detect disease and related speech function in oral tongue cancers. These are preliminary findings that need to be replicated in longitudinal studies and/or larger cohorts.
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http://dx.doi.org/10.1002/cam4.3872DOI Listing
May 2021

, a Key Regulator of a Transitive Triplet, Acts on the TGF-β Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs.

Front Genet 2021 15;12:628192. Epub 2021 Apr 15.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, China.

Tibetan pigs are native mammalian species on the Tibetan Plateau that have evolved distinct physiological traits that allow them to tolerate high-altitude hypoxic environments. However, the genetic mechanism underlying this adaptation remains elusive. Here, based on multitissue transcriptional data from high-altitude Tibetan pigs and low-altitude Rongchang pigs, we performed a weighted correlation network analysis (WGCNA) and identified key modules related to these tissues. Complex network analysis and bioinformatics analysis were integrated to identify key genes and three-node network motifs. We found that among the six tissues (muscle, liver, heart, spleen, kidneys, and lungs), lung tissue may be the key organs for Tibetan pigs to adapt to hypoxic environment. In the lung tissue of Tibetan pigs, we identified , , , , , , , , and genes as potential regulators of hypoxia adaption. We found that and genes might simultaneously regulate the gene, forming a complex. This complex, dominated by , may enhance the hypoxia tolerance of Tibetan pigs by mediating the TGF-β signaling pathway. The complex may also affect the PI3K-Akt signaling pathway, which plays an important role in angiogenesis caused by hypoxia. Therefore, we postulate that the complex may be beneficial for Tibetan pigs to survive better in the hypoxia environments. Although further molecular experiments and independent large-scale studies are needed to verify our findings, these findings may provide new details of the regulatory architecture of hypoxia-adaptive genes and are valuable for understanding the genetic mechanism of hypoxic adaptation in mammals.
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http://dx.doi.org/10.3389/fgene.2021.628192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082500PMC
April 2021

Puerarin Restores Autophagosome-Lysosome Fusion to Alleviate Cadmium-Induced Autophagy Blockade via Restoring the Expression of Rab7 in Hepatocytes.

Front Pharmacol 2021 14;12:632825. Epub 2021 Apr 14.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Autophagic dysfunction is one of the main mechanisms by which the environmental pollutant cadmium (Cd) induces cell injury. Puerarin (Pue, a monomeric Chinese herbal medicine extract) has been reported to alleviate Cd-induced cell injury by regulating autophagy pathways; however, its detailed mechanisms are unclear. In the present study, to investigate the detailed mechanisms by which Pue targets autophagy to alleviate Cd hepatotoxicity, alpha mouse liver 12 (AML12) cells were used to construct a model of Cd-induced hepatocyte injury . First, the protective effect of Pue on Cd-induced cell injury was confirmed by changes in cell proliferation, cell morphology, and cell ultrastructure. Next, we found that Pue activated autophagy and mitigated Cd-induced autophagy blockade. In this process, the lysosome was further activated and the lysosomal degradation capacity was strengthened. We also found that Pue restored the autophagosome-lysosome fusion and the expression of Rab7 in Cd-exposed hepatocytes. However, the fusion of autophagosomes with lysosomes and autophagic flux were inhibited after knocking down , and were further inhibited after combined treatment with Cd. In addition, after knocking down , the protective effects of Pue on restoring autophagosome-lysosome fusion and alleviating autophagy blockade in Cd-exposed cells were inhibited. In conclusion, Pue-mediated alleviation of Cd-induced hepatocyte injury was related to the activation of autophagy and the alleviation of autophagy blockade. Pue also restored the fusion of autophagosomes and lysosomes by restoring the protein expression of Rab7, thereby alleviating Cd-induced autophagy blockade in hepatocytes.
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http://dx.doi.org/10.3389/fphar.2021.632825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079953PMC
April 2021

Nasal Delivery of D-Penicillamine Hydrogel Upregulates a Disintegrin and Metalloprotease 10 Expression via Melatonin Receptor 1 in Alzheimer's Disease Models.

Front Aging Neurosci 2021 15;13:660249. Epub 2021 Apr 15.

College of Life and Health Sciences, Northeastern University, Shenyang, China.

Alzheimer's disease (AD) is a type of neurodegenerative disease that is associated with the accumulation of amyloid plaques. Increasing non-amyloidogenic processing and/or manipulating amyloid precursor protein signaling could reduce AD amyloid pathology and cognitive impairment. D-penicillamine (D-Pen) is a water-soluble metal chelator and can reduce the aggregation of amyloid-β (Aβ) with metals . However, the potential mechanism of D-Pen for treating neurodegenerative disorders remains unexplored. In here, a novel type of chitosan-based hydrogel to carry D-Pen was designed and the D-Pen-CS/β-glycerophosphate hydrogel were characterized by scanning electron microscopy and HPLC. Behavior tests investigated the learning and memory levels of APP/PS1 mice treated through the D-Pen hydrogel nasal delivery. and findings showed that nasal delivery of D-Pen-CS/β-GP hydrogel had properly chelated metal ions that reduced Aβ deposition. Furthermore, D-Pen mainly regulated A disintegrin and metalloprotease 10 (ADAM10) expression via melatonin receptor 1 (MTNR1α) and the downstream PKA/ERK/CREB pathway. The present data demonstrated D-Pen significantly improved the cognitive ability of APP/PS1 mice and reduced Aβ generation through activating ADAM10 and accelerating non-amyloidogenic processing. Hence, these findings indicate the potential of D-Pen as a promising agent for treating AD.
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http://dx.doi.org/10.3389/fnagi.2021.660249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081912PMC
April 2021

Phosphorylation of the androgen receptor at Ser81 is co-sustained by CDK1 and CDK9 and leads to AR-mediated transactivation in prostate cancer.

Mol Oncol 2021 May 1. Epub 2021 May 1.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re-activation still remains a major challenge during treatment of castration-resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81-phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR-mediated transactivation with the chromatin locus openness. Moreover, pS81-specific ChIP-Seq showed a disproportional occupancy of pS81 on AR-activated promoters, while 3C-ChIP assays further indicated an enrichment of pS81 at the PSA enhancer-promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re-ChIP assays also confirmed that AR-dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin-bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.
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http://dx.doi.org/10.1002/1878-0261.12968DOI Listing
May 2021

Clinical use of machine learning-based pathomics signature for diagnosis and survival prediction of bladder cancer.

Cancer Sci 2021 May 1. Epub 2021 May 1.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Traditional histopathology performed by pathologists by the naked eye is insufficient for accurate and efficient diagnosis of bladder cancer (BCa). We collected 643 H&E-stained BCa images from Shanghai General Hospital and The Cancer Genome Atlas (TCGA). We constructed and cross-verified automatic diagnosis and prognosis models by performing a machine learning algorithm based on pathomics data. Our study indicated that high diagnostic efficiency of the machine learning-based diagnosis model was observed in patients with BCa, with area under the curve (AUC) values of 96.3%, 89.2%, and 94.1% in the training cohort, test cohort, and external validation cohort, respectively. Our diagnosis model also performed well in distinguishing patients with BCa from patients with glandular cystitis, with an AUC value of 93.4% in the General cohort. Significant differences were found in overall survival in TCGA cohort (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.56-2.81, P < .0001) and the General cohort (HR = 5.32, 95% CI: 2.95-9.59, P < .0001) comparing patients with BCa of high risk vs low risk stratified by risk score, which was proved to be an independent prognostic factor for BCa. The integration nomogram based on our risk score and clinicopathologic characters displayed higher prediction accuracy than current tumor stage/grade systems, with AUC values of 77.7%, 83.8%, and 81.3% for 1-, 3-, and 5-y overall survival prediction of patients with BCa. However, prospective studies are still needed for further verifications.
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http://dx.doi.org/10.1111/cas.14927DOI Listing
May 2021

Evaluation of left ventricular myocardial mechanics in patients with normally functioning bicuspid aortic valves: A systematic review and meta-analysis.

Echocardiography 2021 Apr 30. Epub 2021 Apr 30.

Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Background: Studies have found conflicting results concerning the left ventricular (LV) myocardial deformation properties in patients with normally functioning bicuspid aortic valves (BAVs). Whether the remodeling process of LV occurs independently in patients with BAV is a matter of debate.

Method: We searched PubMed, Embase, Cochrane library, and Web of Science for cohort studies aiming to assess LV function in adults with isolated BAV compared with tricuspid aortic valve (TAV) controls. Standard mean difference (SMD) was calculated from random-effects meta-analyses.

Results: Eight cohort studies were included. There were significantly lower global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS) in BAV than in TAV controls (GLS: SMD = 0.64, 95% CI: 0.35 to 0.92, P < .0001; GRS: SMD = -0.71, 95% CI: -1.09 to -0.32, P = .0003; GCS: SMD = 0.70, 95% CI: 0.41 to 0.98, P < .00001) and significantly higher left atrial volume index (LAVI) and E/e' in BAV than in TAV controls (LAVI: SMD = 0.50, 95% Cl: 0.12 to 0.88, P = .01; E/e': SMD = 0.54, 95% CI: 0.30 to 0.77, P < .00001). There was significantly higher Left ventricular mass index(LVMI) in BAV than in TAV controls (SMD = 0.51, 95% CI: 0.24 to 0.79, P = .0003). Left ventricular ejection fraction (LVEF) was not significantly different between BAV patients and TAV controls (SMD = 0.05, 95% CI: -0.16 to 0.26, P = .63).

Conclusion: The impairment of LV myocardial mechanics, including LV systolic, diastolic dysfunction and LV hypertrophy, is present in patients with normally functioning BAV. This might support the hypothesis that BAV is not only a valvular disease but also a myocardial disease.
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http://dx.doi.org/10.1111/echo.15042DOI Listing
April 2021

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BMC Infect Dis 2021 Apr 29;21(1):398. Epub 2021 Apr 29.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Rui Jin 2nd road, Shanghai, 200025, China.

Background: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors.

Method: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data.

Results: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 10/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19.

Conclusions: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.
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http://dx.doi.org/10.1186/s12879-021-06094-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084265PMC
April 2021

Autophagy in Plant Abiotic Stress Management.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Plants can be considered an open system. Throughout their life cycle, plants need to exchange material, energy and information with the outside world. To improve their survival and complete their life cycle, plants have developed sophisticated mechanisms to maintain cellular homeostasis during development and in response to environmental changes. Autophagy is an evolutionarily conserved self-degradative process that occurs ubiquitously in all eukaryotic cells and plays many physiological roles in maintaining cellular homeostasis. In recent years, an increasing number of studies have shown that autophagy can be induced not only by starvation but also as a cellular response to various abiotic stresses, including oxidative, salt, drought, cold and heat stresses. This review focuses mainly on the role of autophagy in plant abiotic stress management.
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http://dx.doi.org/10.3390/ijms22084075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071135PMC
April 2021

Simultaneous gene editing of three homoeoalleles in self-incompatible allohexaploid grasses.

J Integr Plant Biol 2021 Apr 29. Epub 2021 Apr 29.

CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Wuhan, 430074, China.

CRISPR/Cas system has been widely used for precise gene editing in plants. However, simultaneous gene editing of multiple homoeoalleles remains challenging, especially in self-incompatible polyploid plants. Here, we simultaneously introduced targeted mutations in all three homoeoalleles of two genes in the self-incompatible allohexaploid tall fescue, using both CRISPR/Cas9 and LbCas12a (LbCpf1) systems. Loss-of-function mutants of FaPDS exhibited albino leaves, while knockout of FaHSP17.9 resulted in impaired heat resistance in T0 generation of tall fescue. Moreover, these mutations were inheritable. Our findings demonstrate the feasibility of generating loss-of-function mutants in a T0 generation polyploid perennial grasses using CRISPR/Cas systems. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13101DOI Listing
April 2021