中国仓鼠V79细胞对长波紫外辐射的应激反应

长波紫外线(UVA．320～400nm)在环境光生物学和光医学中具有重要意义,作者以指数生长期V79细胞为材料,用克隆形成和MTT分析法，实验证明：①UVA对V79细胞增殖有刺激作用,光源强度一定，在实验所用剂量范围内(5×10^3～2×10^5J／m^2),效应谱约在330～370nm波段之间，系单峰，效应峰值在350nm处．

中国仓鼠V79细胞对长波紫外辐射的应激反应

用MTT分析和克隆形成法,证明长波紫外线(UVA)可刺激指数生长期V79细胞增殖。效应谱在330～370nm,效应峰值位于350nm处。在此波长下,最佳刺激剂量为5×10~4J/m^2。UVA还能诱发细胞抗药性和耐热性,并强化热休克细胞的抗药性。这些效应与照射剂量和照射与药物暴露之间时间间隔有依赖关系。

The metabolome identity:basis for discovery of biomarkers in neurodegeneration

Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying protein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in response to these molecular malfunctions and treatment is often too late or restricted only to the slowing of further cell death. Important new strategies to identify early biomarkers with predictive value to intervene with disease progression at stages where cell dysfunction has not progressed irreversibly is of paramount importance. Thus, the identification of these markers presents an essential opportunity to identify and target disease pathways. This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways identified across different neurodegenerative diseases. Thus, having established some commonalities between various degenerative conditions, detectable metabolic changes may be of extreme value as an early diagnostic biomarker in disease.

Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs

Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negative breast cancers.Methods:Find Tar and miRanda were used to detect the manner in which potential micro RNAs are affected by the SNP rs4245739-flanking sequence.RNA sequencing data for ER-negative breast cancer from The Cancer Genome Atlas(TCGA)were used to compare the expression of miR-184,miR-191,miR-193a,miR-378,and MDM4 in different rs4245739 genotypes.Results:Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile micro RNAs(miR-184,miR-191,miR-193a and miR-378 altogether)can differentiate the expression of MDM4 among different rs4245739 genotypes.Although simple genotyping alone did not reveal significant clinical relationships,the combination of genotyping and micro RNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymph nodes(P<0.05)in the risk group(A allele).Conclusions:We present two novel methods to analyze SNPs within 3′UTRs that use:(i)a single miRNA marker expression and(ii)an expression profile of miRNAs predicted to bind to the SNP region.We demonstrate that the application of these two methods,in particular the miRNA profile approach,permits detection of new molecular and clinical features related to the rs4245739 variant in ER-negative breast cancer.

Optical diagnosis of colorectal polyps using convolutional neural networks

Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-malignant and neoplastic polyps.Although technologies for image-enhanced endoscopy are widely available,optical diagnosis has not been incorporated into routine clinical practice,mainly due to significant inter-operator variability.In recent years,there has been a growing number of studies demonstrating the potential of convolutional neural networks(CNN)to enhance optical diagnosis of polyps.Data suggest that the use of CNNs might mitigate the inter-operator variability amongst endoscopists,potentially enabling a“resect and discard”or“leave in”strategy to be adopted in real-time.This would have significant financial benefits for healthcare systems,avoid unnecessary polypectomies of non-neoplastic polyps and improve the efficiency of colonoscopy.Here,we review advances in CNN for the optical diagnosis of colorectal polyps,current limitations and future directions.

Heat dissipating upper body compression garment:Thermoregulatory,cardiovascular, and perceptual responses

Purpose:The aim of the present study was to determine the effects of an upper body compression garment(UBCG)on thermoregulatory responses during cycling in a controlled laboratory thermoneutral environment(~23℃).A secondary aim was to determine the cardiovascular and perceptual responses when wearing the garment.Methods:Sixteen untrained participants(age:21.3±5.7 years;peak oxygen consumption(V02 peak):50.88±8.00 mL/min/kg;mean±SD)performed 2 cycling trials in a thermoneutral environment(~23℃)wearing either UBCG or control(Con)garment.Testing consisted of a 5-min rest on a cycle ergometer,followed by 4 bouts of cycling for 14-min at ~50%VO2 peak,with 1-min rest between each bout.At the end of these bouts there was 10-min of passive recovery.During the entire protocol rectal temperature(Trec),skin temperature(Tskin),mean body temperature(Tbody),and heat storage(HS)were measured.Heart rate(HR),VO2,pH,hematocrit(Hct),plasma electrolytes,weight loss(Wloss),and perceptual responses were also measured.Results:There were no significant differences between garments for Tskin,HS,HR,VO2,pH,Hct,plasma electrolyte concentration,Wloss,and perceptual responses during the trial.Trec did not differ between garment conditions during rest,exercise,or recovery although a greater reduction in Trec wearing UBCG(p=0.01)was observed during recovery.Lower Tbody during recovery was found when wearing UBCG(36.82℃±0.30℃ vs.36.99℃±0.24℃).Conclusion:Wearing a UBCG did not benefit thermoregulatory,cardiovascular,and perceptual responses during exercise although it was found to lower Tbody during recovery,which suggests that it could be used as a recovery tool after exercise.

Investigation of the Anti-Mycobacterial Mechanism of Action of 7-Methyljuglone

Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been identified. The primary objective of the current study was to investigate the mycobacterial outer membrane as a potential target of 7-MJ by measuring the effects of this agent (0.023 - 1.5 mg/L) on microbial ATP levels and uptake of K+ . Methods: Bioluminescence and radiometric (uptake of 86Rb+) procedures were used to assay microbial ATP levels and K+ transport respectively. Results: Exposure of MTB (strain H37Rv) to 7-MJ for 60 min resulted in dose-related decreases in both microbial ATP levels and uptake of 86Rb+ which achieved statistical significance (P + transport.

Adolescents’ perspectives on a school-based physical activity intervention:A mixed method study

Purpose'. To examine adolescent experiences and perspectives of the GoActive intervention (ISRCTN31583496) using mixed methods processevaluation to determine satisfaction with intervention components and interpret a*dolescents experiences of the intervention process in order toprovide insights for future intervention design.Methods'. Participants (n = 1542;13.2 土 0.4 years, mean 土 SD) provided questionnaire data at baseline (shyness, activity level) and post-intervention(intervention acceptability, satisfaction with components). Between-group differences (boys vs. girls and shy/inactive vs. others) weretested with linear regression models, accounting for school clustering. Data from 16 individual interviews (shy/inactive) and 11 focus groupswith 48 participants (mean = 4;range 2—7) were thematically coded. Qualitative and quantitative data were merged in an integrative mixedmethods convergence matrix, which denoted convergence and dissonance across datasets.Results'. Effect sizes for quantitative results were small and may not represent substantial between-group differences. Boys (vs. girls) preferredclass-based sessions (0 = 0.2, 95% confidence interval (CI): 0.1—0.3);qualitative data suggested that this was because boys preferred competition,which was supported quantitatively (0 = 0.2, 95%CI: 0.1-0.3). Shy/inactive students did not enjoy the competition (0 = -0.3, 95%CI:—0.5 to —0.1). Boys enjoyed trying new activities more (0 = 0.1, 95%CI: 0.1 -0.2);qualitative data indicated a desire to try new activities acrossall subgroups but identified barriers to choosing unfamiliar activities with self-imposed choice restriction leading to boredom. Qualitative datahighlighted critique of mentorship;adolescents liked the idea, but older mentors did not meet expectations.Conclusion. We interpreted adolescent perspectives of intervention components and implementation to provide insights into future complexinterventions aimed at increasing young people's physical activity in school-based settings. The intervention component mentorship was liked inprinciple, but implementation issues undesirably impacted satisfaction;competition was disliked by girls and shy/inactive students. The resultshighlight the importance of considering gender differences in preference of competition and extensive mentorship training.

Implementing physically active learning:Future directions for research,policy,and practice

Purpose:To identify co-produced multi-stakeholder perspectives important for successful widespread physically active learning(PAL) adoption and implementation.Methods:A total of 35 stakeholders(policymakers n=9;commercial education sector,n=8;teachers,n=3;researchers,n=15) attended a design thinking PAL workshop.Participants formed 5 multi-disciplinary groups with at least 1 representative from each stakeholder group.Each group,facilitated by a researcher,undertook 2 tasks:(1) using Post-it Notes,the following question was answered:within the school day,what are the opportunities for learning combined with movement?and(2) structured as a washing-line task,the following question was answered:how can we establish PAL as the norm?All discussions were audio-recorded and transcribed.Inductive analyses were conducted by 4 authors.After the analyses were complete,the main themes and subthemes were assigned to 4 predetermined categories:(1) PAL design and implementation,(2) priorities for practice,(3) priorities for policy,and(4) priorities for research.Results:The following were the main themes for PAL implementation:opportunities for PAL within the school day,delivery environments,learning approaches,and the intensity of PAL.The main themes for the priorities for practice included teacher confidence and competence,resources to support delivery,and community of practice.The main themes for the policy for priorities included self-governance,the Office for Standards in Education,Children’s Services,and Skill,policy investment in initial teacher training,and curriculum reform.The main themes for the research priorities included establishing a strong evidence base,school-based PAL implementation,and a whole-systems approach.Conclusion:The present study is the first to identify PAL implementation factors using a combined multi-stakeholder perspective.To achieve wider PAL adoption and implementation,future interventions should be evidence based and address implementation factors at the classroom level(e.g.,approaches and delivery environments),school level(e.g.,communities of practice),and policy level(e.g.,initial teacher training).

Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early <i>erm</i>B Gene Expression, Metabolic Activity and Growth of an <i>erm</i>(B)-Expressing Macrolide-Resistant Strain of <i>Streptococcus pneumoniae</i>

Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

A classical function of Clq is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when Clq binds some other ligands. Besides complement activation, Clq also regulates cell differentiation, adhesion, migration, activation and survival. Clq deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of Clq, its expression, and classical and regulatory functions. Cellular ＆ Molecular Immunology.

State of the Art of Lifecourse Cohort Establishment

The global rise in non-communicable diseases(NCDs)presents significant public health challenges.Effectively managing and preventing NCDs necessitates a thorough understanding of their causes and progression,which can be achieved through a lifecourse approach to determine past exposures’impact before NCD onset.However,this approach requires robust backing from data,specifically lifecourse cohort data,which are generally insufficient.To overcome this obstacle,three primary strategies have been employed to establish such cohorts:active follow-up cohorts,registry-based datasets,and technology-based data collection and simulation methods.

心血管发病风险预测模型在降压疗效评价中的应用

目的:以缬沙坦/氨氯地平片对比氨氯地平的降压疗效,探讨心血管发病风险预测模型在降压疗效评价中的应用。方法:基于临床试验数据,采用缺血性心血管病(ICVD)发病风险预测模型进行平均发病风险值估计和敏感性分析,将估计的平均发病风险值作为指标进行降压疗效评价。结果:由模型估计可知:①相比用药前,缬沙坦/氨氯地平片和氨氯地平两组用药后的未来10年ICVD平均发病风险值均有所降低,且高血压Ⅱ期的风险降低百分比高于Ⅰ期,男性的风险降低百分比高于女性。②相比氨氯地平组,缬沙坦/氨氯地平片组的未来10年ICVD平均发病风险在高血压Ⅰ期中低0.009 7;在高血压Ⅱ期中低0.022 4;在男性中低0.021 4;在女性中低0.012 2。③敏感性分析显示结果稳定。结论:缬沙坦/氨氯地平片通过降低血压而减少心血管发病风险的疗效不逊于氨氯地平,甚至在某些情况下要优于氨氯地平;心血管发病风险预测模型可通过估计血压变化对心血管发病风险产生的作用而用于降压疗效评价。

Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D

Surfactant proteins A(SP-A)and D(SP-D),both members of the collectin family,play a well established role in apoptotic cell recognition and clearance.Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner.SP-A and SP-D bind in a Ca^(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca^(2+)-independent.Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules.Myeloperoxidase(MPO),a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis,was identified by affinity purification,mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D.To confirm its role in recognition,it was shown that purified immobilised MPO binds SP-A and SP-D,and that MPO is surface-exposed on late apoptotic neutrophils.SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells.Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils.Desmoplakin was identified as a further potential ligand for SP-A,and neutrophil defensin as a target for both proteins.

Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells

The role of surfactant protein A(SP-A)in the recognition and clearance of apoptotic cells is well established,but to date,it is still not clear which surface molecules of apoptotic cells are involved in the process.Here we present evidence that phosphatidylserine(PS)is a relevant binding molecule for human SP-A.The binding is Ca^(2+)-dependent and is not inhibited by mannose,suggesting that the sugar-binding site of the carbohydrate recognition domain(CRD)of SP-A is not involved.Flow cytometry studies on apoptotic Jurkat cells revealed apparent inhibition of annexin V binding by increasing concentrations of SP-A in late apoptotic but not early apoptotic cells,and this was consistent for Jurkat cells and neutrophils.Supporting these data,confocal microscopy results show a co-localisation of annexin V and SP-A in late apoptotic but not early apoptotic cells.However,we cannot conclude that this inhibition is exclusively due to the binding of SP-A to PS on the cell surface,as annexin V is not wholly specific for PS and SP-A also interacts with other phospholipids that might become exposed on the apoptotic cell surface.

Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon:cross-sectional study

Background:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy(ACT)partner drugs critical to elimination efforts.Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon.Methods:Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through crosssectional surveys from May 2013 to March 2014 along the slope of mount Cameroon.Plasmodium falciparum malaria parasitaemic blood,screened by light microscopy,was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform.Results:A total of 259 participants were enrolled in this study from three different altitudes.While some alleles associated with drug resistance in pfdhfr,pfmdr1 and pfcrt were highly prevalent,less than 3%of all samples carried mutations in the pfkelch13 gene,none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia.The most prevalent haplotypes were triple mutants PfdhfrI51R59N108I164(99%),pfcrt-C72V73I74E75T76(47.3%),and single mutants PfdhpsS_(436)G_(437)K_(540)A_(581)A_(613)(69%)and Pfmdr1 N_(86)F)(184)D_(1246)(53.2%).Conclusions:The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.

Complement activation by phospholipids: the interplay of factor H and C1q

Complement proteins in blood recognize charged particles.The anionic phospholipid(aPL)cardiolipin binds both complement proteins C1q and factor H.C1q is an activator of the complement classical pathway,while factor H is an inhibitor of the alternative pathway.To examine opposing effects of C1q and factor H on complement activation by aPL,we surveyed C1q and factor H binding,and complement activation by aPL,either coated on microtitre plates or in liposomes.Both C1q and factor H bound to all aPL tested,and competed directly with each other for binding.All the aPL activated the complement classical pathway,but negligibly the alternative pathway,consistent with accepted roles of C1q and factor H.However,in this system,factor H,by competing directly with C1q for binding to aPL,acts as a direct regulator of the complement classical pathway.This regulatory mechanism is distinct from its action on the alternative pathway.Regulation of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide range.Thus factor H,which is regarded as a down-regulator only of the alternative pathway,has a distinct role in downregulating activation of the classical complement pathway by aPL.A factor H homologue,β2-glycoprotein-1,also strongly inhibits C1q binding to cardiolipin.Recombinant globular domains of C1q A,B and C chains bound aPL similarly to native C1q,confirming that C1q binds aPL via its globular heads.

医学是终极的个体化技术

现代医学将科学与交流、照护个体患者的艺术相结合。临床医生通过与患者交谈来确定最佳治疗方案一直是各种临床照护情境的中心环节。由于巨大的技术进步，二十一世纪医学的科学成分与艺术成分不相上下。在分子水平上展现肿瘤特点的技术能力已经降低了治疗的副作用，提高了患者的生存率和生活质量。

膳食脂肪和心脏代谢健康:证据、争议和指导共识

Nita G Forouhi及其同事认为,尽管在营养研究和制定指南方面存在困难,但公众越来越能理解膳食脂肪和整体饮食的复杂性。

Breath Biopsy^(®) to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection

Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden.Breath is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease moni-toring.Having previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use.Methods:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)levels.Results:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test sets.The seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component analysis.Conclusions:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.