One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mechanisms of bacterial infection in the dissemination of lung cancer cells. A series of studies have indicated that certain Gram-negative bacteria are able to hijack antigen-presenting cells (APCs) via interaction with DC-SIGN (CD209) receptors to facilitate the dissemination of pathogens, including viruses, bacteria, fungi, and parasites. Therefore, in the present work, it was hypothesized that bacterial infection may promote the dissemination of cancer cells via the utilization of a similar mechanism. It was first discovered that human lung cancer tissues contain a very high diversity of bacterial DNAs, indicating the co-existence of lung cancer tissues and microbial organisms. It was then found that lung cancer tissues express DC-SIGN, leading to binding with a Gram-negative bacterium, Shigella sonnei. Further, this bacterium was found to be able not only to induce the expression of DC-SIGN on macrophages but also to enhance the migration ability of lung cancer cells in vitro. The in vivo experiments supported these observations, showing that in wild-type (WT) mice, Shigella sonnei infection significantly increased tumor size, weight, and metastatic nodules compared to SIGNR1 knockout (KO) mice. These observations were associated with increasing DC-SIGN expression in WT mice. Finally, these results suggest that bacterial infections could play a significant role in promoting lung cancer progression and metastasis via DC-SIGN-mediated mechanisms.

BACKGROUND AND AIMS:High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes. METHODS:We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD. RESULTS:During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32-1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73-0.86), but higher risks among diabetics (1.38, 1.02-1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics. CONCLUSIONS:Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes.

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (+/- 5 +/- 5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin ( P interaction =0.04) and deltamethrin ( P interaction =0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], P interaction =0.03 and 3.23 [95 % CI: 1.78-5.87], P interaction = 0 . 05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

BACKGROUND:Evidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common. OBJECTIVES:This study aimed to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks. METHODS:Observational analyses were performed among 15,226 T2D participants aged 40-72 y from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants. RESULTS:The mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 y, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0-74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99). CONCLUSIONS:Higher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D.

实验分别采取持续升温(大间隔5 ℃)、持续升温(小间隔2 ℃)、设定升温(大间隔5 ℃)和设定升温(小间隔2 ℃)4种方法测定金属Al的线胀系数.从实验结果可知,持续升温法比设定升温法测定的金属Al线胀系数误差大,因为本实验加热系统具有热惯性和PID温控仪传感器滞后性,导致瞬时温度并不是实际温度.小间隔设定升温法获得的线胀系数比大间隔设定升温法测出的线胀系数要更精确,小间隔设定升温法的相对误差仅为0.25％,用最小二乘法拟合曲线与实验数据的拟合相似度为0.999 8,拟合度非常高、耗时较短.故小间隔设定升温法适合本实验教学.

新课标指出利用现代信息技术引导学生理解物理学本质,强调突出学生的主体地位,促进学生核心素养的全面发展.借助GeoGebra软件深入剖析带电粒子在有界磁场中的运动,使几种常见的磁场边界问题动态化,促进学生构建清晰的物理模型,从而突破难点,对磁场动态问题有更深入的理解.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

Abstract Background: Despite the developments in diagnosis and treatment of HER2-positive metastatic breast cancer, there is a high likelihood in the development of resistance to trastuzumab. In general, HER2-positive patients with deteriorated health face negative clinical outcomes. The present study is conducted to systematically explore the medicinal properties of trastuzumab in HER2-positive breast cancer patients. Methods: Randomized controlled trials investigating the clinical properties of including trastuzumab to treat HER2-positive breast cancer cases will be sourced by exploring these online-based databases: MEDLINE, BIOSIS, China National Knowledge Infrastructure (CNKI), Cochrane Library, EMBASE, Central Register of Controlled Trials, and WanFang. Two independent authors will screen the literature, gather data, and assess the quality of selected studies. The significance of the relationship between the medical properties of trastuzumab when incorporated to treat HER2-positive breast cancer cases will be evaluated according to the relative risk, mean differences or standardized mean differences, and 95% confidence interval. Results: The outcomes from this review shall be issued in a journal that will be reviewed by peers. Conclusion: The conclusions presented in this review will serve as a reference for clinical practitioners and scholars to determine whether trastuzumab is an effective and safety intervention for treating HER2-positive breast cancer patients. Ethics and dissemination: Since this study is a systematic review of published studies, an ethical approval is not needed. Systematic review registration number: March 31, 2021.osf.io/wvqkf (https://osf.io/wvqkf/).

利用Algodoo软件探究“摩擦振子”实验中两轮轴内转和外转时杆的运动规律,并运用控制变量法和数理方法进行原理分析,推出运动方程及验证其运动参数与轮轴间距、摩擦因数以及轮轴转速有关.通过将虚拟软件应用于实验探究,培养学生的科学思维能力.

通过仿真软件Algodoo来探究两轮轴内转时"摩擦振子"的运动规律,并运用控制变量法进行理论分析和模拟验证,得出其所依赖的运动参数与轮轴间距 、摩擦系数及初始位置有关.通过融合仿真技术手段进行模拟探究,不仅使师生的仿真技术应用能力得到锻炼,而且提升学生科学思维的高阶能力.

The objective of this study was to investigate macrophage polarization during the early stages of secondary Echinococcus granulosus sensu lato (E. granulosus s.l.) infection. We observed an early initial increase in inflammatory genes (peaking at 5-10 days) and a later rise in M (IL-4)-like genes (still rising by day 15). In addition, we showed that the induction of M (IL-4)-like genes was paralleled by an increase in expression of the transcription factor KLF4. Most of the changes observed in vivo were reproduced in vitro upon the culture of normal peritoneal macrophages with live E. granulosus s.l. protoscoleces (PSC), and that knockdown of KLF4 in this system attenuates M (IL-4) differentiation. Our results suggest that KLF4 pathway contributes to the differentiation of macrophages towards M (IL-4)-like phenotype during early stages of secondary E. granulosus s.l. infection.

Yersinia pseudotuberculosisis a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals.

医学介于科学与人文之间,高等医学教育肩负着培养具有人文精神的高素质医学人才的重任.当前,医学人文教育面临缺乏医学人文课程体系设计 、医学人文教育认知错位 、医学人文校内外实践活动力度不足等问题.通过设计搭建医学人文教育体系,从课堂主渠道教育 、校内外专家医学人文讲座和引导示范 、校内外医学人文社会实践活动三个途径,探索构建医学生人文教育体系,从而增强医学人文教育的广度 、深度和效度.

Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, can cause infectious diseases ranging from gastroenteritis to systemic dissemination and infection. However, the molecular mechanisms underlying this bacterial dissemination have yet to be elucidated. A study indicated that using the lipopolysaccharide (LPS) core as a ligand, S Typhimurium was able to bind human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (hCD209a), an HIV receptor that promotes viral dissemination by hijacking antigen-presenting cells (APCs). In this study, we showed that S Typhimurium interacted with CD209s, leading to the invasion of APCs and potentially the dissemination to regional lymph nodes, spleen, and liver in mice. Shielding of the exposed LPS core through the expression of O-antigen reduces dissemination and infection. Thus, we propose that similar to HIV, S Typhimurium may also utilize APCs via interactions with CD209s as a way to disseminate to the lymph nodes, spleen, and liver to initiate host infection.

The electron impact excitation (EIE) collision strengths of Ne-like Fe16+,Xe44+ and U82+ ions form the ground state 1 s22s22p61 S0 to all of excited states 1 s22s22p53s are calculated systematically by using the fully relativistic distorted-wave program REIE06.Based on these calculations,the influence of the electron correlation and the Breit interaction on the EIE collision strengths are discussed systematically.The EIE collision strengths versus different energies of incident electron are studied,and some important conclusions are summarized.Because of the configuration interaction and Breit interaction are considered in detail,the part of present results are compared with the existing theoretical results,and the relative error of the experimental values is relatively small.

针对扭摆法测物体转动惯量系统误差较大的缺点,提出了实验中3种塑料圆柱选取周期值N=5,并采取3组周期平均值,从而最大程度上降低系统误差.发现当N不是很大时,粘性阻力对转动惯量起主要作用,此时转动惯量的大小与空气的接触面积大小有很大关系.增加空气接触面积,非线性阻尼效果增强.表面积S越大,转动惯量理论值I和实验值I′之间的差异就越大,不确定度也随之变大,非线性阻尼导致的实验值与理论值之间的差异越来越明显.

翻转课堂颠覆了传统教学模式,利用信息技术和网路教学环境在课前进行课堂知识的学习,在课堂教学中通过教师的指导完成知识的内化,这种教学模式在提高学生的学习兴趣、提高课堂教学效果方面都有促进作用.将翻转课堂融合进大学物理教学中,可以弥补实验教学资源有限、课时不足、简单模仿等缺点,因此根据大学物理实验教学的特点,进行基于翻转课堂教学模式的探究,以期能够切实提高大学物理实验教学质量.

Plague is a zoonotic disease caused by the bacterium Yersinia pestis. This pathogen can be transmitted by fleas and has an enzootic cycle, circulating among small mammals, and occasionally epizootic cycles, infecting other species. In China, infected wild rodents are primarily reservoirs of Y.Pestis and are related to human infection (Int. J. Infect. Dis., 33, 2015 and 67; BMC Microbiol., 9, 2009 and 205). Because shepherd dogs prey on and eat rodents (e.g. marmots and mice), they are valuable sentinel animals for plague serosurveillance in endemic disease foci, although their infections are usually asymptomatic (Vet. Microbiol., 172, 2014 and 339).

Base on the 《Theoretical study on sym metry of the Stark effect of Hydrogen atom》work , We discusses the hydrogen atomic electrostatic field induced forbidden transition 2s → 1s transition probability .Due to the superposition of States , the forbidden transitions are realization ,which cannot be achieved in the general approximation ,in under the action of electrostatic field .In this case ,the forbidden transition 2s → 1s the transition probability and 2p → 1s the transition probability is proportional to .