Wnt genes in colonic polyposis predisposition

Much of the genetic predisposition to polyposis,and particularly to serrated polyposis(SP),remains unknown.Only germline pathogenic variants in RNF43,a tumor suppressor that exerts negative feedback in the Wnt/β-catenin signaling pathway,have been causally linked to some SP cases(<2%),a disease associated with increased risk of colorectal cancer(CRC).^(1) Most known hereditary CRC and polyposis genes affect DNA repair,BMP/TGF-β,or Wnt signaling,being the latter associated with adenomatous and serrated polyposis phenotypes.2 Based on this observation,we evaluated the presence and role of germline variants in those pathways in unsolved polyposis patients.

Climate change,air pollution,and allergic respiratory diseases:a call to action for health professionals

Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality.The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes.Climate change and air pollution pose adverse impacts on respiratory allergies,and that the mechanisms are complex and interactive.Adverse weather conditions,such as extreme temperatures,can act directly on the respiratory tract to induce allergic respiratory illnesses.Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution,and therefore indirectly enhance health risks.Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation,and the rising temperatures and CO2 increase pollen,molds,and spores,which escalate the risk of allergic respiratory diseases.The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants,which in turn augment the allergenicity of aeroallergens.With the Earth’s climate change,migration of humans and plants shift the living environments and allergens of susceptible people.Urban residents are exposed to multiple factors while children are sensitive to environmental exposure.Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases,health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.

INMA-Sabadell队列中孕期双酚A及邻苯二甲酸酯暴露与胎儿发育的超声测量(续完)

暴露于ΣMWPm与任何胎儿大小或胎儿发育结局（见补充材料，表8）及所评估的出生结局（表2及补充材料表S7）都没有显著相关性。代谢物MnBP与12-20孕周HC增长降低有显著相关性（-4．88％；95％CI：-8．36，-1．36），且与EFW增长减低也有显著相关性（-4．32％；95％CI：-8．33，-0．27）（图3及补充材料表S8）。

A demonstration project of Global Alliance against Chronic Respiratory Diseases:Prediction of interactions between air pollution and allergen exposure—the Mobile Airways Sentinel NetworK-Impact of air POLLution on Asthma and Rhinitis approach

This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers.For decades,information available for the patients and allergologists consisted of pollen counts,which are vital but insufficient.New technology paves the way to substantial increase in amount and diversity of the data.This paper reviews old and newly suggested methods to predict pollen and air pollutant concentrations in the air and proposes an allergy risk concept,which combines the pollen and pollution information and transforms it into a qualitative risk index.This new index is available in an app(Mobile Airways Sentinel NetworK-air)that was developed in the frame of the European Union grant Impact of Air POLLution on sleep,Asthma and Rhinitis(a project of European Institute of Innovation and Technology-Health).On-going transformation of the pollen allergy information support is based on new technological solutions for pollen and air quality monitoring and predictions.The new information-technology and artificial-intelligence-based solutions help to convert this information into easy-to-use services for both medical practitioners and allergy sufferers.

The protective role of m A during stress-induced granulation

Post-transcriptional methylation of N6-adenine and Nl-adenine can affect transcriptome turnover and translation.Furthermore,the regulatory function of N6-methyladenine(m6A)during heat shock has been uncovered,including the enhancement of the phase separation potential of RNAs.In response to acute stress,e.g.heat shock,the orderly sequestration of mRNAs in stress granules(SGs)is considered important to protect transcripts from the irreversible aggregation.Until recently,the role of N1-methyladenine(m^(1)A)on mRNAs during acute stress response remains largely unknown.Here we show that the methyltransferase complex TRMT6/61A,which generates the tag,is involved in transcriptome protection during heat shock.Our bioinformatics analysis indicates that occurrence of the motif is increased in mRNAs known to be enriched in SGs.Accordingly,the m^(1)A-generating methyltransferase TRMT6/61A accumulated in SGs and mass spectrometry confirmed enrichment of in the SG RNAs.The insertion of a single methylation motif in the untranslated region of a reporter RNA leads to more efficient recovery of protein synthesis from that transcript after the return to normal temperature.Our results demonstrate far-reaching functional consequences of a minimal RNA modification on N1-adenine during acute proteostasis stress.

INMA-Sabadell队列中孕期双酚A及邻苯二甲酸酯暴露与胎儿发育的超声测量(待续)

[背景]产前暴露于双酚A（BPA）及邻苯二甲酸酯会影响胎儿发育；然而该类研究很少，且得出的结果不一致。[目的]对一个西班牙出生队列中488对母婴进行研究，评估产前暴露于BPA及邻苯二甲酸酯是否与胎儿发育相关。[方法]检测第一和第三孕期两次尿液样本中BPA及8种邻苯二甲酸酯[4种邻苯二甲酸二（2-乙基己基）酯代谢物（DEHPm），邻苯二甲酸单卞酯（MBzP）以及3种低分子量邻苯二甲酸酯代谢物（LMWPm）]。另外，估计股骨长度（FL）、头围（HC）、腹围（AC）、双顶径（BPD）的生长曲线，估计孕期（12—20周，20～34周）的胎儿体重，并测量出生体重、出生长度、出生头围以及胎盘重量。[结果]总体上，结果并不支持孕期暴露于BPA或DEHPm与胎儿发育参数相关。产前MBzP暴露与20～34孕周的FL呈正相关，MBzP浓度每增加一倍，平均FL增加3．7％（95％CI：0．75，6．63％）。MBzP与男婴出生体重呈正相关（48g；95％CI：6，90），但在女婴中没有相关性（-27g；95％CI：-79，25）（交互作用P=0．04）。LMWPm邻苯二甲酸单丁酯（MnBP）与12—20孕周的HC呈负相关[平均HC降低了4．88％（95％CI：-8．36，-1．36％）]。[结论]本研究首次将暴露生物标志重复测量值与胎儿期多种发育参数相结合，发现暴露于BPA或邻苯二甲酸酯与胎儿发育不相关。邻苯二甲酸酯代谢物MBzP与MnBP与部分胎儿发育参数相关，但这些结果还需要重复验证。

Attenuation artifacts in light sheet fluorescence microscopy corrected by OPTiSPIM

Light sheet fluorescence microscopy(LSFM)is rapidly becoming an essential technology for mesoscopic imaging of samples such as embryos and adult mouse organs.However,LSFM can suffer from optical artifacts for which there is no intrinsic solution.The attenuation of light due to absorbing material causes“shadow”artifacts along both the illumination and detection paths.Several approaches have been introduced to reduce this problem,including scanning illumination and multi-view imaging.However,neither of these approaches completely eliminates the problem.If the distribution of the absorbing material is complex,shadows cannot be avoided.We introduce a new approach that relies on multi-modal integration of two very different mesoscopic techniques.Unlike LSFM,optical projection tomography(OPT)can operate in transmission mode to create a voxel map of the 3D distribution of the sample’s optical attenuation.Here,we demonstrate a hybrid instrument(OPTiSPIM)that can quantify this attenuation and use the information to correct the shadow artifacts of LSFM.

人类生命早期暴露组(HELIX)：项目理念与设计(待续)

[背景]人类在生命早期的发育期间可能特别容易受到环境暴露的影响。有关这一主题的人体研究一般集中在单一暴露与健康效应之间的关系。而"暴露组"的概念涵盖了从受孕开始的的全部暴露,完善了基因组。[目的]人类生命早期暴露组(HELIX)项目是一个新的合作研究项目,目的是为了采用新的暴露评估和生物标志分析方法来描述生命早期多种环境因素的暴露,并将这些与生物标志组学和儿童健康结局相关联,从而刻画"生命早期暴露组"。本文描述了该项目的总体设计。[方法]HELIX将利用欧洲现有的6个出生队列研究来估计产前、产后暴露的一系列化学和物理暴露。建立全部队列中总共32 000对母亲和儿童的暴露模型,并在一个包含1 200对母亲和儿童的子队列中测量生物标志。嵌套重复采样的定组研究(n=150)将收集生物标志的变化数据,利用智能手机来评估流动性和体力活动,并监测个体暴露。采用组学技术确定与暴露相关的分子学特征(代谢组、蛋白质组、转录组和表观基因组)。对于多次暴露,采用统计方法估计胎儿和儿童的成长、肥胖、神经发育和呼吸系统结局中的暴露-效应关系。项目还将进行一项健康效应评估测试,以评价组合暴露的风险和收益。[结论]HELIX是描述欧洲人群生命早期暴露组并解开它与组学标志物和儿童健康之间关联的首次尝试之一。作为对暴露组学这一概念的验证,该项目向生命过程中暴露组迈出了重要的第一步。

人类生命早期暴露组(HELIX)：项目理念与设计(续完)

3．2研究2：室外暴露 传统h基于居住区评估的暴露，如室外空气污染、噪声、建筑环境，可以通过收集时间一空间活动以及（就空气污染而言）个人吸入空气量的信息，改善暴露评估和减小测量误差。例如，可替代吸入率（Kawahara等，2011）的体力活动方面的信息与个人空气污染测量结合来评估吸入剂量。基于暴露评估的新一代地理信息系统（GIS）（Beelen等，2013;Eeflens等，2012）、遥感（Dadvand等，2012）和智能手机技术（deNazelle等，2013）使评估室外暴露和整合个人活动范围及体力活动数据变得更容易。

SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Antigen-presenting cells(APCs)may be resistant to SARS-CoV-2 infection but still contribute to viral pathogenesis.Lectins such as sialic acid-binding Ig-like lectin 1(Siglec-1/CD169)mediate the attachment of viruses to APCs.Here,we show that APCs effectively capture SARS-CoV-2 within compartments via recognition of Siglec-1.This receptor interacts with sialylated gangliosides on membranes of SARS-CoV-2 variants.

Gene expression changes in blood RNA after swimming in a chlorinated pool

Exposure to disinfection by-products（DBP） such as trihalomethanes（THM） in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40 min in an indoor chlorinated pool. Blood samples were drawn and four THM（chloroform,bromodichloromethane, dibromochloromethane and bromoform） were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents（METs）. Gene expression in whole blood m RNA was evaluated using Illumina Human HT-12v3 Expression-Bead Chip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were： 0.7 to 2.3 for MET, and 1.4 to 7.1 μg/m^3 for exhaled total THM（sum of the four THM）.Exhaled THM increased on average 0.94 μg/m^3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate（Log-fold change range：-0.17 to 0.15）. In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies.