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  • 简介:AbstractAcute pancreatitis (AP) is a common and potentially life-threatening pancreatic inflammatory disease. Although it is usually self-limiting, up to 20% of patients will develop into severe AP. It may lead to systemic inflammatory response syndrome and multiple organ dysfunction, affecting the lungs, kidneys, liver, heart, etc. Surviving patients usually have sequelae of varying degrees, such as chronic hyperglycemia after AP (CHAP), pancreatic exocrine insufficiency, and chronic pancreatitis. Lacking specific target treatments is the main reason for high mortality and morbidity, which means that more research on the pathogenesis of AP is needed. Ferroptosis is a newly discovered regulated cell death (RCD), originally described in cancer cells, involving the accumulation of iron and the depletion of plasma membrane polyunsaturated fatty acids, and a caspase-independent RCD. It is closely related to neurological diseases, myocardial infarction, ischemia/reperfusion injury, cancer, etc. Research in the past years has also found the effects of ferroptosis in AP, pancreatic cancer, and AP complications, such as acute lung injury and acute kidney injury. This article reviews the research progress of ferroptosis and its association with the pathophysiological mechanisms of AP, trying to provide new insight into the pathogenesis and treatment of AP, facilitating the development of better-targeted drugs.

  • 标签: Acute pancreatitis Ferroptosis RCD Autophagy GPX4 PUFAs Regulated cell death
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  • 简介:AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.

  • 标签: SARS-CoV-2 Delta variant Omicron variant Trifluoperazine 2HCl Thioridazine HCl Antiviral therapy
  • 简介:AbstractFibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly.

  • 标签: dual agonists fibroblast growth factor 21 lipid metabolism metabolic diseases
  • 简介:AbstractThe recently emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread around the world. Although many consensus mutations of the Omicron variant have been recognized, little is known about its genetic variation during its transmission in the population. Here, we comprehensively analyzed the genetic differentiation and diversity of the Omicron variant during its early outbreak. We found that Omicron achieved more structural variations, especially deletions, on the SARS-CoV-2 genome than the other four variants of concern (Alpha, Beta, Gamma, and Delta) in the same timescale. In addition, the Omicron variant acquired, except for 50 consensus mutations, seven great new non-synonymous nucleotide substitutions during its spread. Three of them are on the S protein, including S_A701V, S_L1081V, and S_R346K, which belong to the receptor-binding domain (RBD). The Omicron BA.1 branch could be divided into five divergent groups spreading across different countries and regions based on these seven novel mutations. Furthermore, we found that the Omicron variant possesses more mutations related to a faster transmission rate than the other SARS-CoV-2 variants by assessing the relationship between the genetic diversity and transmission rate. The findings indicated that more attention should be paid to the significant genetic differentiation and diversity of the Omicron variant for better disease prevention and control.

  • 标签: SARS-CoV-2 Omicron Genetic diversity
  • 简介:AbstractBackground:Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM.Methods:Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography–mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM.Results:The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75–0.91) in the training set and 0.79 (0.65–0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74–0.93) and 0.82 (0.66–0.98), respectively.Conclusions:The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.

  • 标签: Hypertrophic cardiomyopathy Amino acids Targeted metabolomics Biomarkers Algorithm
  • 简介:AbstractBackgrounds:Cardiovascular disease (CVD) remains the leading cause of deaths nationwide. However, little is understood about its temporal trend and corresponding influence on longevity improvements. We aimed to describe the updated tendency in CVD mortality and to quantify its impact on life expectancy (LE) increase in China.Methods:All-cause mortality rates were calculated with population sizes from the National Bureau of Statistics and death counts from the National Health Commission. We estimated CVD mortality rates by allocating age- and sex-based mortality envelopes to each CVD subtype based on its proportion derived from the Disease Surveillance Points system. The probability of CVD premature deaths and LE were calculated with life tables and we adopted Arriaga’s method to quantitate age- and cause-specific contributions to LE gains.Results:During 2013 to 2018, the age-standardized mortality rate of CVD decreased from 289.69 (95% confidence interval [CI]: 289.03, 290.35)/100,000 to 272.37 (95%CI: 271.81, 272.94)/100,000, along with a decline in probability of CVD premature deaths from 9.05% (95%CI: 9.02%, 9.09%) to 8.13% (95%CI: 8.10%, 8.16%). The gap in CVD mortality across sexes expanded with more remarkable declines in females, especially for those aged 15 to 64 years. Among major subtypes, the probability of premature deaths from hemorrhage stroke declined fastest, while improvements of ischemic stroke and ischemic heart disease were limited, and there was an increase in stroke sequelae. LE in China reached 77.04 (95%CI: 76.96, 77.12) years in 2018 with an increase of 1.38 years from 2013. Of the total LE gains, 21.15% (0.29 years) were attributed to reductions of CVD mortality in the overall population, mostly driven by those aged >65 years.Conclusions:The general process in reducing CVD mortality has contributed to longevity improvements in China. More attention should be paid to prevention and control of atherosclerotic CVD and stroke sequelae, especially for the elderly. Working-age males also deserve additional attention due to inadequate improvements.

  • 标签: Aged Cardiovascular diseases Causes of death Hemorrhagic stroke Ischemic stroke Longevity Mortality premature Myocardial ischemia Life expectancy China
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  • 简介:AbstractThe novel betacoronavirus (Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2) is a pathogen that causes deadly respiratory disease named coronavirus disease 2019 (COVID-19). The incidence of this disease has increased in the last few months affecting 257,832,881 people in 221 countries and 51,68,069 deaths worldwide according to Worldometer at 04:03 GMT on November 22, 2021. Thus, the emergence of this disease creates a challenge for health care providers in handling this pathogen and reducing its risk of transmission. In developing countries, this virus is treated in biosafety level 2 laboratories, where a high concentration of pathogen can easily affect the laboratory staff and cause the spread of this disease. Based on the epidemiology and characteristics of the SARS-CoV-2 virus already discussed in recent studies, we will provide biosafety guidelines and suggestions for safe handling and transportation of the SARS-CoV-2 virus in dealing with the current pandemic situation with a focus on increased infectivity of emerging new variants.

  • 标签: SARS-CoV-2 Biosafety guidelines COVID-19 PPE Laboratory acquired infections
  • 简介:AbstractCell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.

  • 标签: Cell-cell communication Ligand-receptor pair Single-cell RNA sequencing Carcinogenesis COVID-19
  • 简介:AbstractThere is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.

  • 标签: Cell-free DNA Embryo culture medium Genomic DNA Non-invasive Pre-implantation genetic testing
  • 作者: Ran Wang Zhengde Xie
  • 学科: 医药卫生 >
  • 创建时间:2022-12-13
  • 出处:《儿科学研究(英文)》 2022年第03期
  • 机构:Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children’s Hospita
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  • 简介:AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused many deaths and contributed to a tremendous public health concern worldwide since 2020. Angiotensin-converting enzyme 2 (ACE2) binds to the SARS-CoV-2 virus as a receptor. The challenge of different nonhuman primate (NHP) species by SARS-CoV-2 virus demonstrated different effects on virus replication and disease pathology. This study characterizes differences between host ACE2 sequences of three NHP species: Macaca mulatta, Macaca fascicularis, and Chlorocebus sabaeus. In addition, the binding affinity between the ACE2 ectodomain and the SARS-CoV-2 S receptor-binding domain (RBD) was analyzed. Variation of ACE2 sequence among NHP species and the binding affinity may account for different susceptibility and responses to SARS-CoV-2 infection.

  • 标签: SARS-CoV-2 Angiotensin-converting enzyme 2 Receptor binding domain Surface plasmon resonance African green monkey
  • 简介:摘要:中国传统的文化,认为植物都是具有灵性的,对人的各方面都能起到一定的作用,所以也就延伸出了植物风水学一说。直到今天,风水学说依然可以作为选择绿化植物的标准之一。许多植物在风水学说中有自己的特殊的含义,同时风水学说也有其独特的植物配置理论。当然风水理论是中国古人通过实践积累而形成的空间环境优化方法理论,与现代生态学环境评价理论有异曲同工的模型概念。这其中的植物配置原理不仅符合植物的生态特性、美化居住环境,同时对人心理和生理方面产生影响,从而产生疗愈的效果。

  • 标签: 风水 植物风水学 植物造景 植物的征象性
  • 简介:摘要:通过对2629名中职生进行课堂环境感知调查,利用SPSSAU软件对问卷进行统计分析,发现参加职业技能竞赛的学生和未参加职业技能竞赛的学生对中职专业课课堂环境感知在3个维度、5个因子、14个题项上有显著的差异,为依托职业技能竞赛改善中职专业课课堂环境找到切入点,也为职业技能竞赛促进教学改革也提供了新的方向。

  • 标签: 职业技能竞赛 中职专业课 课堂环境 优化策略
  • 简介:摘要:近年来,我国航空情报部门一直致力于由AIS向AIM转变,提高航空情报数据发布质量。系统的更迭,上位文件的修订都是为了从数据用户的焦虑点出发,提高航空情报部门的运行效率,提供可靠的数字化产品。European control的EAD系统作为全球最大的一体化航空信息中央存储库,有不少方面值得我们借鉴。本文从航空情报原始资料上报的现状出发,结合EAD系统的动静态数据融合特点,浅谈航空情报原始资料上报的发展方向。

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  • 简介:摘要:蓝藻水华是水体藻类开始大量生长繁殖聚集到一定浓度的现象,会造成水质恶化产生恶臭,使水体丧失饮用、养殖、景观功能,直接危害居民的生活和生产。为了给武汉市某湖水生态修复提供经验,针对施工区域的环境特征,在水生态修复区域安装喷泉式曝气机,探索喷泉式曝气机在武汉某湖蓝藻水华处理中的应用效果,结果表明喷泉式曝气机扰动及曝气能够降低水体中有机物含量,加快[1]沉淀,抑制蓝藻水华,改善水环境。

  • 标签: 曝气机 蓝藻水华 浮游植物 透明度