焦虑对急性心肌梗死患者院前延误时间的影响

背景急性心肌梗死(AMI)患者院前延误时间(PHT)延长是影响救治效果的主要因素。现关于PHT的研究越来越多,但多集中在社会人口学因素、AMI临床症状、发病情景、认知等层面,而缺乏对社会心理因素的系统研究。焦虑是AMI患者常见心理问题,但在中国人群中其是否影响AMI患者PHT尚未见相关报道。目的探究焦虑对AMI患者PHT的影响,以期为AMI伴焦虑患者院前延误干预策略的制订提供依据。方法本研究为多中心横断面研究,连续选取2016年4月-2017年2月于上海市4家医院(同济大学附属同济医院、同济大学附属第十人民医院、上海市杨浦区中心医院和解放军第411医院)就诊的AMI住院患者265例为研究对象。收集患者一般资料、AMI发病时症状、决定时间、转运时间、PHT(患者发病至到达医院的时间),采用广泛性焦虑障碍量表(GAD-7)评估患者焦虑情况。结果 265例患者的PHT为150.0(70.0,501.0)min;焦虑评估结果:无焦虑161例,有焦虑104例(其中轻度焦虑81例,中度焦虑16例,重度焦虑7例)。有焦虑患者抑郁、心脏否认发生率及怕死程度得分高于无焦虑患者(P<0.05)。有焦虑患者濒死感、头晕发生率高于无焦虑患者(P<0.05)。无焦虑与有焦虑患者决定时间、转运时间、PHT比较,差异无统计学意义(P>0.05)。重度焦虑患者决定时间、PHT长于轻度焦虑患者(P<0.05);不同焦虑程度患者转运时间比较,差异无统计学意义(P>0.05)。结论 AMI伴焦虑患者更易发生抑郁、心脏否认,重度焦虑患者较轻度焦虑患者决定时间、PHT更长,从而更可能错过最佳再灌注治疗时间,影响预后。

Systems Biology of Plant-Microbiome Interactions

In natural environments,plants are exposed to diverse microbiota that they interact with in complex ways.While plant-pathogen interactions have been intensely studied to understand defense mechanisms in plants,many microbes and microbial communities can have substantial beneficial effects on their plant host.Such beneficial effects include improved acquisition of nutrients,accelerated growth,resilience against pathogens,and improved resistance against abiotic stress conditions such as heat,drought,and salinity.However,the beneficial effects of bacterial strains or consortia on their host are often cultivar and species specific,posing an obstacle to their general application.Remarkably,many of the signals that trigger plant immune responses are molecularly highly similar and often identical in pathogenic and beneficial microbes.Thus,it is unclear what determines the outcome of a particular microbe-host interaction and which factors enable plants to distinguish beneficials from pathogens.To unravel the complex network of genetic,microbial,and metabolic interactions,including the signaling events mediating microbe-host interactions,comprehensive quantitative systems biology approaches will be needed.

Looking at sound: optoacoustics with all-optical ultrasound detection

Originally developed for diagnostic ultrasound imaging,piezoelectric transducers are the most widespread technology employed in optoacoustic(photoacoustic)signal detection.However,the detection requirements of optoacoustic sensing and imaging differ from those of conventional ultrasonography and lead to specifications not sufficiently addressed by piezoelectric detectors.Consequently,interest has shifted to utilizing entirely optical methods for measuring optoacoustic waves.All-optical sound detectors yield a higher signal-to-noise ratio per unit area than piezoelectric detectors and feature wide detection bandwidths that may be more appropriate for optoacoustic applications,enabling several biomedical or industrial applications.Additionally,optical sensing of sound is less sensitive to electromagnetic noise,making it appropriate for a greater spectrum of environments.In this review,we categorize different methods of optical ultrasound detection and discuss key technology trends geared towards the development of all-optical optoacoustic systems.We also review application areas that are enabled by all-optical sound detectors,including interventional imaging,non-contact measurements,magnetoacoustics,and nondestructive testing.

Functional impacts of non-coding RNA processing on enhancer activity and target gene expression

Tight regulation of gene expression is orchestrated by enhancers.Through recent research advancements,it is becoming clear that enhancers are not solely distal regulatory elements harboring transcription factor binding sites and decorated with specific histone marks,but they rather display sign atures of active transcription,showingdistinct degrees oftranscription unit organization.Thereby,a substantial fraction of enhancers give rise to different species of non-coding RNA transcripts with an unprecedented range of potential functions.In this review,we bring together data from recent studies indicating that non-coding RNA transcription from active enhancers,as well as enhancer-produced long non-coding RNA transcripts,may modulate or define the functional regulatory potential ofthe cognate enhancer.In addition,we summarize supporting evidence that RNA processing ofthe enhancer-associated long non-coding RNA transcripts may constitute an additional layer of regulation of enhancer activity,which contributes to the control and final outcome of enhancer-targeted gene expression.

Challenges and perspectives for structural biology of IncRNAs-the example of the Xist IncRNA A-repeats

Following the discovery of numerous long non-coding RNA(IncRNA)transcripts in the human genome,their important roles in biology and human disease are emerging.Recent progress in experimental methods has enabled the identification of structural features of IncRNAs.However,determining high-resolution structures is challenging as IncRNAs are expected to be dynamic and adopt multiple conformations,which may be modulated by interaction with protein binding partners.The X-inactive specific transcript(Xist)is necessary for X inactivation during dosage compensation in female placental mammals and one of the beststudied IncRNAs.Recent progress has provided new insights into the domain organization,molecular features,and RNA binding proteins that interact with distinct regions of Xist.The A-repeats located at the 5'end of the transcript are of particular interest as they are essential for mediating silencing ofthe inactive X chromosome.Here,we discuss recent progress with elucidating structural features of the Xist IncRNA,focusing on the A-repeats.We discuss the experimental and computational approaches employed that have led to distinct structural models,likely reflecting the intrinsic dynamics of this RNA.The presence of multiple dynamic conformations may also play an important role in the formation ofthe associated RNPs,thus influencing the molecular mechanism underlying the biological function of the Xist A-repeats.We propose that integrative approaches that combine biochemical experiments and high-resolution structural biology in vitro with chemical probing and functional studies in vivo are required to unravel the molecular mechanisms of IncRNAs.

Opening a window to skin biomarkers for diabetes stage with optoacoustic mesoscopy

Being the largest and most accessible organ of the human body,the skin could offer a window to diabetes-related complications on the microvasculature.However,skin microvasculature is typically assessed by histological analysis,which is not suited for applications to large populations or longitudinal studies.We introduce ultra-wideband rasterscan optoacoustic mesoscopy(RSOM)for precise,non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy,resolved with unprecedented sensitivity and detail without the need for contrast agents.Providing unique imaging contrast,we explored a possible role for RSOM as an investigational tool in diabetes healthcare and offer the first comprehensive study investigating the relationship between different diabetes complications and microvascular features in vivo.We applied RSOM to scan the pretibial area of 95 participants with diabetes mellitus and 48 age-matched volunteers without diabetes,grouped according to disease complications,and extracted six label-free optoacoustic biomarkers of human skin,including dermal microvasculature density and epidermal parameters,based on a novel image-processing pipeline.We then correlated these biomarkers to disease severity and found statistically significant effects on microvasculature parameters as a function of diabetes complications.We discuss how label-free RSOM biomarkers can lead to a quantitative assessment of the systemic effects of diabetes and its complications,complementing the qualitative assessment allowed by current clinical metrics,possibly leading to a precise scoring system that captures the gradual evolution of the disease.

Optoacoustic microscopy at multiple discrete frequencies

Optoacoustic(photoacoustic)sensing employs illumination of transient energy and is typically implemented in the time domain using nanosecond photon pulses.However,the generation of high-energy short photon pulses requires complex laser technology that imposes a low pulse repetition frequency(PRF)and limits the number of wavelengths that are concurrently available for spectral imaging.To avoid the limitations of working in the time domain,we have developed frequency-domain optoacoustic microscopy(FDOM),in which light intensity is modulated at multiple discrete frequencies.We integrated FDOM into a hybrid system with multiphoton microscopy,and we examine the relationship between image formation and modulation frequency,showcase high-fidelity images with increasing numbers of modulation frequencies from phantoms and in vivo,and identify a redundancy in optoacoustic measurements performed at multiple frequencies.We demonstrate that due to high repetition rates,FDOM achieves signal-to-noise ratios similar to those obtained by time-domain methods,using commonly available laser diodes.Moreover,we experimentally confirm various advantages of the frequency-domain implementation at discrete modulation frequencies,including concurrent illumination at two wavelengths that are carried out at different modulation frequencies as well as flow measurements in microfluidic chips and in vivo based on the optoacoustic Doppler effect.Furthermore,we discuss how FDOM redefines possibilities for optoacoustic imaging by capitalizing on the advantages of working in the frequency domain.

Meta-Analysis of Retrograde Signaling in Arabidopsis thaliana Reveals a Core Module of Genes Embedded in Complex Cellular Signaling Networks

Plastid-to-nucleus signaling is essential for the coordination and adjustment of cellular metabolism in response to environmental and developmental cues of plant cells. A variety of operational retrograde signaling path- ways have been described that are thought to be triggered by reactive oxygen species, photosynthesis redox imbalance, tetrapyrrole intermediates, and other metabolic traits. Here we report a meta-analysis based on transcriptome and pro- tein interaction data. Comparing the output of these pathways reveals the commonalities and peculiarities stimulated by six different sources impinging on operational retrograde signaling. Our study provides novel insights into the interplay of these pathways, supporting the existence of an as-yet unknown core response module of genes being regulated under all conditions tested. Our analysis further highlights affiliated regulatory cis-elements and classifies abscisic acid and auxin-based signaling as secondary components involved in the response cascades following a plastidial signal. Our study provides a global analysis of structure and interfaces of different pathways involved in plastid-to-nucleus signaling and a new view on this complex cellular communication network.

Spatial heterogeneity of oxygenation and haemodynamics in breast cancer resolved in vivo by conical multispectral optoacoustic mesoscopy

The characteristics of tumour development and metastasis relate not only to genomic heterogeneity but also to spatial heterogeneity,associated with variations in the intratumoural arrangement of cell populations,vascular morphology and oxygen and nutrient supply.While optical(photonic)microscopy is commonly employed to visualize the tumour microenvironment,it assesses only a few hundred cubic microns of tissue.Therefore,it is not suitable for investigating biological processes at the level of the entire tumour,which can be at least four orders of magnitude larger.In this study,we aimed to extend optical visualization and resolve spatial heterogeneity throughout the entire tumour volume.We developed an optoacoustic(photoacoustic)mesoscope adapted to solid tumour imaging and,in a pilot study,offer the first insights into cancer optical contrast heterogeneity in vivo at an unprecedented resolution of<50μm throughout the entire tumour mass.Using spectral methods,we resolve unknown patterns of oxygenation,vasculature and perfusion in three types of breast cancer and showcase different levels of structural and functional organization.To our knowledge,these results are the most detailed insights of optical signatures reported throughout entire tumours in vivo,and they position optoacoustic mesoscopy as a unique investigational tool linking microscopic and macroscopic observations.

Immunomodulatory Nanosystems:Advanced Delivery Tools for Treating Chronic Wounds

The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.

Cell type specificity of signaling:view from membrane receptors distribution and their downstream transduction networks

Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.

Local tissue development of type 1 innate lymphoid cells:guided by interferon-gamma

A recent article published in Science by Bai et a I.1 identified interferon-Y(IFN-y)secreted by type 1 innate lymphoid cells(ILCIs)self-perpetuated their own local development from resident hematopoietic stem cells(HSCs)in adult liver.

iPlant Systems Biology (iPSB): An International Network Hub in the Plant Community

sequenced genome of a multicellular organism (Arabidopsis Genome, 2000) completed just after those of the nematode Caenorhabditis elegans (C. elegans Sequencing Consortium, 1998) and the fruit fly Drosophila melanogaster (Adams et al., 2000). Availability of a full whole-genome sequence for the reference plant opened to plant biologists what is commonly called the post-genomic era.

Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events

Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including （i） full model using all available predictors and estimated by standard techniques, （ii） backward elimination （BE）, （iii） ridge regression, （iv） least absolute shrinkage and selection operator （lasso）, and （v） elastic net. Based on a prospective cohort of patients with manifest coronary artery disease （CAD）, we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches, Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.

Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review

Background:Continuing progress in the global pediatric human immunodeficiency virus(HIV)response depends on timely identification and care of infants with HIV.As countries scale-out improvements to HIV early infant diagnosis(EID),economic evaluations are needed to inform program design and implementation.This scoping review aimed to summarize the available evidence and discuss practical implications of cost and cost-effectiveness analyses of HIV EID.Methods:We systematically searched bibliographic databases(Embase,MEDLINE and EconLit)and grey literature for economic analyses of HIV EID in low-and middle-income countries published between January 2008 and June 2021.We extracted data on unit costs,cost savings,and incremental cost-effectiveness ratios as well as outcomes related to health and the HIV EID care process and summarized results in narrative and tabular formats.We converted unit costs to 2021 USD for easier comparison of costs across studies.Results:After title and abstract screening of 1278 records and full-text review of 99 records,we included 29 studies:17 cost analyses and 12 model-based cost-effectiveness analyses.Unit costs were 21.46-51.80 USD for point-of-care EID tests and 16.21-42.73 USD for laboratory-based EID tests.All cost-effectiveness analyses stated at least one of the interventions evaluated to be cost-effective.Most studies reported costs of EID testing strategies;however,few studies assessed the same intervention or reported costs in the same way,making comparison of costs across studies challenging.Limited data availability of context-appropriate costs and outcomes of children with HIV as well as structural heterogeneity of cost-effectiveness modelling studies limits generalizability of economic analyses of HIV EID.Conclusions:The available cost and cost-effectiveness evidence for EID of HIV,while not directly comparable across studies,covers a broad range of interventions and suggests most interventions designed to improve EID are cost-effective or cost-saving.Further studies capturing costs and benefits of EID services as they are delivered in real-world settings are needed.

Nature：大规模研究揭示生命所必需的基因

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。