人类发育细胞蓝图的现状和挑战

阐明人类胚胎发育的分子调控机制一直是科学家们努力攻克的重大生物学问题之一。然而,由于人类胚胎样本稀少、样本解剖困难、器官结构复杂等因素,解析人类胚胎发育机制面临重重挑战。近年来,随着单细胞组学技术的迅猛发展,人们可以在中心法则的各个环节,系统地解析细胞分化过程中的动态变化,并在空间维度上进行观测与研究,加快了构建人类发育细胞图谱的进程,最终实现对人类发育的细胞分类体系、命运轨迹和三维动态变化的刻画。本文首先介绍了绘制人类发育细胞图谱所使用的单细胞组学技术,然后总结了胚胎发育图谱的最新进展并提出了该领域目前面临的主要问题和挑战,最后对如何利用人类胚胎发育图谱解决生物学和医学的关键问题进行了探讨,以期为利用单细胞组学技术构建并应用人类发育细胞蓝图提供更好的指导。

Ice-Induced Vibrational Response of Single-Pile Offshore Wind-Turbine Foundations

Important challenges must be addressed to make wind turbines sustainable renewable energy sources.A typical problem concerns the design of the foundation.If the pile diameter is larger than that of the jacket platform,traditional mechanical models cannot be used.In this study,relying on the seabed soil data of an offshore wind farm,the m-method and the equivalent embedded method are used to address the single-pile wind turbine foundation problem for different pile diameters.An approach to determine the equivalent pile length is also proposed accordingly.The results provide evidence for the effectiveness and reliability of the model based on the equivalent embedded method.

新型冠状病毒感染核酸/抗原转阴后常见症中医诊断与疗效评价专家共识

部分新冠康复患者在核酸/抗原检测转阴后,仍然存在一系列持续、反复或新发症状,这已成为需要关注的新公共卫生问题。中医药在新冠病毒感染的预防、治疗和康复阶段均发挥了重要作用。为进一步规范临床医生对中医药治疗新冠核酸/抗原转阴后常见症的诊疗行为,特邀请一线临床专家就新冠感染核酸/抗原转阴后常见症的概念、病因病机、临床表现、中医治疗及注意事项等进行讨论,形成专家共识。中医、西医、中西医结合医师在临床实践和研究中可参考本文件。

宣肺败毒颗粒临床应用专家共识

宣肺败毒颗粒是在经典名方基础上化裁而成的用于治疗新型冠状病毒感染的有效方药。为进一步规范临床医师对宣肺败毒颗粒的合理使用,提高临床疗效,提高合理用药水平,发挥更大作用,特邀请来自临床一线专家,针对宣肺败毒颗粒的功能主治、用法用量、不良反应及注意事项等进行讨论,形成共识。共识认为:宣肺败毒颗粒具有宣肺化湿、清热透邪、泻肺解毒的功效;可用于治疗新冠病毒感染轻型、普通型、重型患者及流感等其他常见上呼吸道感染性疾病;急性气管炎-支气管炎及社区获得性下呼吸道感染性疾病等属湿毒郁肺者;可缓解慢性阻塞性肺疾病急性加重所引发的咳嗽、咯痰等症状,临床疗效确切,安全性好。按照循证医学原则,该专家共识将会定期进行更新。

Animal models for anti-neutrophil cytoplasmic antibody-associated vasculitis:Are current models good enough?

Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.

TPX2 knockdown suppressed hepatocellular carcinoma cell invasion via inactivating AKT signaling and inhibiting MMP2 and MMP9 expression

Objective： Targeting protein for Xenopus kinesin-like protein 2 （TPX2） is a nuclear proliferation-related protein that plays a critical role in the formation of mitotic spindle. High expression of TPX2 has been observed in several types of tumors. However, the role of TPX2 in hepatocellular carcinoma （HCC） remains unclear. Our study aimed to investigate the effect of TPX2 on HCC cell invasion. Methods： The immortalized normal human liver cell line L02 and six HCC cell lines including SMMC- 7721, BEL-7402, Huh-7, HepG2, Hep3B and SKHepl were subjected to qRT-PCR and western blot for TPX2 mRNA and protein, respectively. Furthermore, TPX2 small interfering RNA （siRNA） was used to knock down TPX2 expression in SMMC-7721 and HepG2 cells. Cell proliferation and invasion were determined by MTT and transwell assays. Otherwise, expression of p-AKT, MMP2 and MMP9 were evaluated by western blot in SMMC-7721 cells. Results： The expression of TPX2 in HCC cell lines was markedly higher than that in normal human liver cell line. TPX2 knockdown using a specific TPX2-siP, NA reduced the number of invaded cells and inhibited cell proliferation in SMMC-7721 and HepG2 cells. Furthermore, TPX2 knockdown resulted in inactivation of AKT signaling and down-regulation of MMP2 and MMP9 expression in SMMC-7721 cells. Conclusions： Our study identified that TPX2 might contribute to tumor cell invasion through activating AKT signaling and subsequently increasing MMP2 and MMP9 in HCC.

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019(COS-COVID)

自2019年12月新型冠状病毒肺炎(Coronavirus Disease 2019, COVID-19)暴发以来,已有大量相关临床研究完成注册或已启动。然而,不同研究间临床结局指标存在显著的异质性,同时一些不关键的指标会造成研究资源的浪费。本研究旨在构建COVID-19临床试验核心结局指标集(core outcome set, COS),为相关临床研究方案设计、开展和证据转化提供参考。本研究的实施参照《有效性试验核心结局指标(COMET)手册》(1.0版),研究组成员包括呼吸系统和危重医学、中医学、循证医学、临床药理学、统计学专家以及医学杂志编辑等。通过检索临床试验注册网站(chictr.org.cn和clinicaltrials.gov)中COVID-19相关临床研究方案,提取方案中的结局指标,形成指标池。78个COVID-19临床试验方案纳入研究,收集结局指标259个,合并规范后确定132个结局指标,涉及7个指标域。经遴选,形成了包括58个结局指标在内的初始指标清单。经过两轮德尔菲调查和一轮共识会议,最终确立针对COVID-19不同临床分型的核心指标集(COS-COVID)。COS-COVID包括1个轻型指标(病毒核酸检测转阴时间)、4个普通型指标(住院时间、复合事件发生率、临床症状积分和病毒核酸检测转阴时间)、5个重型指标(复合事件发生率、住院时间、PaO2/FiO2、机械通气时间和病毒核酸检测转阴时间)、1个危重型指标(全因死亡率)及1个康复期指标(肺功能)。COS-COVID作为目前临床评价COVID-19干预效果最具临床价值及操作性的指标集合,对证据评估和决策具有重要意义。随着对疾病认知的不断深入和COS-COVID应用的反馈,课题组将对本核心指标集进行进一步完善并更新。

Reference Gene Selection for qRT-PCR Normalization in Iris germanica L.

Quantitative real-time PCR(qPCR)is an effective and widely used method to analyze expression patterns of target genes.Selection of stable reference genes is a prerequisite for accurate normalization of target gene expression by qRT-PCR.In Iris germanica L.,no studies have yet been published regarding the evaluation of potential reference genes.In this study,nine candidate reference genes were assessed at different flower developmental stages and in different tissues by four different algorithms(GeNorm,NormFinder,BestKeeper,and RefFinder).The results revealed that ACT11(Actin 11)and EF1α(Elongation factor 1 alpha)were the most stable reference genes in different tissues,whereas TUA(Tubulin alpha)and UBC9(Ubiquitin-protein ligase 9)were the most stable ones in different flower developmental stages.UBC9 and ACT11 were the most stable reference genes in all of the tested samples,while the SAMDC(S-Adenosylmethionine decarboxylase)showed the least stability.Finally,to validate the suitability of the selected reference genes,the relative expression level of IgTPS(beta-caryophyllene synthase)was assessed and highlighted the importance of suitable reference gene selection.This work constitutes the first systematic evaluation of potential reference genes in I.germanica and provides guidelines for future research on gene function and molecular mechanisms on I.germanica and related species.

Expert consensus guidelines on clinical use of Xiyanping injection for acute infectious diseases

Xiyanping injection,a traditional Chinese medicine injection made of andrographolide sulfonate,consisting of well-defined ingredients with antiviral,antibacterial,anti-inflammatory and antipyretic efficacy,has been widely used for treating infectious diseases of respiratory and digestive systems.However,its wide applications may easily lead to unreasonable clinical medication.In order to guide the precise clinical application and rational use of Xiyanping injection,experts in related fields conducted systematically literature review,evaluated and deliberated the application of Xiyanping injection in treating acute infectious diseases using evidence-based medicine method,and jointly drafted the consensus to summarize types of acute infectious diseases in children and adults that can be treated with Xiyanping injection,and recommend the intervention time,usage and dosage,course of treatment and combined medication of the injection.Besides,the consensus elucidates the safety,precautions and contraindications of the injection,so as to provide guidance for clinical use.

The chromosome-level Stevia genome provides insights into steviol glycoside biosynthesis

Stevia(Stevia rebaudiana Bertoni)is well known for its very sweet steviol glycosides(SGs)consisting of a common tetracyclic diterpenoid steviol backbone and a variable glycone.Steviol glycosides are 150–300 times sweeter than sucrose and are used as natural zero-calorie sweeteners.However,the most promising compounds are biosynthesized in small amounts.Based on Illumina,PacBio,and Hi-C sequencing,we constructed a chromosome-level assembly of Stevia covering 1416 Mb with a contig N50 value of 616.85 kb and a scaffold N50 value of 106.55 Mb.More than four-fifths of the Stevia genome consisted of repetitive elements.We annotated 44,143 high-confidence protein-coding genes in the high-quality genome.Genome evolution analysis suggested that Stevia and sunflower diverged~29.4 million years ago(Mya),shortly after the whole-genome duplication(WGD)event(WGD-2,~32.1 Mya)that occurred in their common ancestor.Comparative genomic analysis revealed that the expanded genes in Stevia were mainly enriched for biosynthesis of specialized metabolites,especially biosynthesis of terpenoid backbones,and for further oxidation and glycosylation of these compounds.We further identified all candidate genes involved in SG biosynthesis.Collectively,our current findings on the Stevia reference genome will be very helpful for dissecting the evolutionary history of Stevia and for discovering novel genes contributing to SG biosynthesis and other important agronomic traits in future breeding programs.

Method for designing the optimal sealing depth in methane drainage boreholes to realize efficient drainage

The purpose of underground methane drainage technology is to prevent methane disasters and enable the efficient use of coal mine methane(CMM),and the sealing depth is a key factor that affects the performance of underground methane drainage.In this work,the layouts of in-seam and crossing boreholes are considered to analyze the stress distribution and failure characteristics of roadway surrounding rock through a numerical simulation and field stress investigation to determine a reasonable sealing depth.The results show that the depths of the plastic and elastic zones in two experimental coal mines are 16 and 20 m respectively.Borehole sealing minimizes the air leakage through the fractures around the roadway when the sealing material covers the failure and plastic zones,and the field test results for CMM drainage at different sealing depths indicate that the CMM drainage efficiency increases with increasing sealing depth but does not change once the sealing depth exceeds the plastic zone.Moreover,sealing in the high-permeability roadway surrounding rock does not have a strong influence on the borehole sealing performance.Considering these findings,a new CMM drainage system for key sealing in the low-permeability zone was developed that is effective for improving the CMM drainage efficiency and prolonging the high-concentration CMM drainage period.The proposed approach offers a valuable quantitative analysis method for selecting the optimum sealing parameters for underground methane drainage,thereby improving considerably the drainage and utilization rates of CMM.

An E-type Temperature Sensor for Upper Air Meteorology

An E-type high-precision temperature sensor, which is adopted for upper air meteorology, was proposed in this paper. A computational fluid dynamics(CFD) method was implemented to analyze temperature rise induced by solar radiation at different altitudes and solar radiation intensities. A temperature rise correction equation was obtained by fitting the CFD results using a Broyden-Fletcher-Goldfarb-Shanno(BFGS) method. To verify the performance of the temperature sensor, an experimental platform was constructed. Through simulations and experiments, the relationship among the altitude, solar radiation intensity and radiation temperature rise was obtaned. The root-mean-square error(RMSE) between the temperature rise derived from the correction equation and that derived from the experiments is 0.013 K. The sample determination coefficient r2 of the solar radiation error correction equation is 0.9975.

Clinical practice guideline on traditional Chinese medicine in the treatment of influenza (2021)

Influenza is a serious public health problem that endangers the health of the global human population.Traditional Chinese medicine(TCM)is rich in theory and practical experience regarding the treatment of influenza,and TCM treatments have shown good curative effects,but there is a dearth of standardized clinical guidance.It is necessary to formulate a clinical practice guide based on evidence-based medicine.To this end,the Specialty Committee of Emergency,China Association of Chinese Medicine(Beijing,China)organized a team of clinical experts,methodological experts,and other multidisciplinary experts to develop a guideline with integrated research methods in the first place of TCM.This guide includes 23 recommendations.The prescription section contains 16 recommendations,including 5 recommendations for mild cases,5 recommendations for severe cases,3 recommendations for critical cases,and 4 recommendations for the recovery period;the portion covering proprietary Chinese medicines forms a total of 7 recommendations.This guide aims to provide the best evidence for clinicians and related practitioners to make decisions about influenza diagnosis and treatment in Chinese medicine.

Post COVID-19 burden:focus on the short-term condition

The catastrophic pandemic of the coronavirus disease 2019(COVID-19)has caused serious harm to human life and global social economy.As of June 13,2022,there were more than 530 million confirmed cases of COVID-19 and over 6.3 million deaths[1].During the past 2 years,global studies on prevention and therapies for COVID-19 have achieved a series of promising findings,including antiviral drugs(Remdesivir,Molnupiravir,Paxlovid)and monoclonal antibodies(Bamlanivimab and Etesevimab,Sotrovimab,Casirivimab and Imdevimab)[2].

Effect of viscosity on motion of splashing crown in high speed drop impact

A splashing crown is commonly observed when a high-speed drop impacts a liquid film. The influence of the liquid viscosity on the crown＇s evolution is not yet clear. We review several existing theories of this problem, and carry out a series of numerical simulations. We find that a three-segment model can describe the crown＇s motion. In the very early stage when the crown is barely visible, the influence of viscosity is small. Later, a shallow water approach used in most existing models is applicable as long as the initial conditions are formulated properly. They depend on viscous dissipation in the intermediate period. Preliminary estimation based on a dissipation function is proposed to characterize the influence of viscosity in this problem.

Dynamic criterion for the formation of surface water-blooms

Surface water-blooms （SWBs） is usually explained as a buoyant migration of blue-green algae to the water surface under the conditions of reduced turbulence. Wind-induced turbulent mixing can cause considerable heterogeneity in the vertical concentration distribution of algal cells. There exists a criterion below which cell buoyancy can overcome the turbulent mixing. Former researchers regarded a certain wind speed as this criterion, but this wind speed differs in value. In this research, we propose a new criterion, nondimensional entrainment number （En）, which represents the ratio of the intrinsic velocity of algal cells relative to the characteristic velocity of wind-induced mixing. Observation in Taihu Lake demonstrates that this new criterion is more suitable for the description of hydrodynamic effect on the formation of surface water-blooms.

A Design of 220 kV Line Protection Action Deduction System Based on Numerical Simulation

Accurate conditions monitoring and early wrong action warnings of relay protection in the Smart Substation is the basic guarantee to realize the normal operation of primary and secondary system of the power grid.At present,the traditional operation and maintenance monitoring methods of relay protections have poor timeliness,while some automatic monitoring methods have insufficient early warning performance,and lack the online action deduction function independent of the actual device.In this paper,a design method of integrated action deduction system including protection logic reasoning and software and hardware operation condition is proposed.The system can receive real-time operation information of protection online,simulate different types of faults,and output the recording information of sub modules belongs to the action deduction system.It can realize the online monitoring of device faults such as deducing the correctness of setting values at a certain time in the future,giving the wrong action warnings and predicting the probability of them as well,which effectively improves the operation and maintenance efficiency of the secondary system in the intelligent substation.

Research Advance in the Efficacy and Mechanism of Qing Fei Xiao Yan Wan for the Treatment of Respiratory Diseases

Qing Fei Xiao Yan Wan had been incorporated into the existing “Chinese Pharmacopoeia”, protected by patents. The manufacturing process of it was scientific and its compatibility was reasonable. It was also shown by clinical trials that the efficacy is exact. Clinical trials and experiment studies had confirmed the efficacy and some mechanism for the treatment of respiratory diseases, which were summaried in this paper. Combined with the experimental results (published in another paper), the other prospect application was further discussed.

登月舱尺度陨石坑对羽流-月表相互作用影响的数值研究

登月舱着陆期间,陨石坑和其他复杂地形可能会加剧发动机羽流引起的月尘扩散,给探月任务带来干扰和威胁.本文采用direct simulationMonteCarlo(DSMC)方法,研究了嫦娥五号发动机羽流与登月舱尺度陨石坑的相互作用.结果表明,陡峭陨石坑显著改变了近场流动结构,在喷管下方形成明显的回流区.回流区增加了坑壁的风化层侵蚀,将月尘吹入喷管,容易对发动机等设备造成结构损坏。同时,随着陨石坑变陡,羽流被陨石坑所偏转的角度明显增加,从而显著增加了登月舱受到的气动力和气动热;最大扬尘角也显著增大,严重干扰了着陆能见度.对于比较平坦的陨石坑,虽然羽流偏转和扬尘的角度较小,但根据Roberts侵蚀模型计算的总侵蚀通量较大,也意味着对登月舱的严重威胁。这些结果揭示了登月舱尺度陨石坑对羽流-月表相互作用的显著影响,为预测和减轻复杂地形对探月任务的威胁提供了有效参考.

Wet‑Spinning Knittable Hygroscopic Organogel Fibers Toward Moisture‑Capture‑Enabled Multifunctional Devices

Atmospheric moisture exploitation is emerging as a promising alternative to relieve the shortage of freshwater and energy.Efforts to exploit hygroscopic materials featuring flexibility,programmability,and accessibility are crucial to portable and adaptable devices.However,current two-dimensional(2D)or three-dimensional(3D)-based hygroscopic materials are dif-ficult to adapt to diverse irregular surfaces and meet breathability,which severely hinders their wide applications in wearable and programmable devices.Herein,hygroscopic organogel fibers(HOGFs)were designed via a wet-spinning strategy.The achieved fibers were composed of the hydrophilic polymeric network,hygroscopic solvent,and photothermal/antibacterial Ag nanoparticles(AgNPs),enabling hygroscopic capacity,photothermal conversion,and antibacterial.Owing to the good knittable feature,the HOGFs can be readily woven to adjusted 2D textiles to function as an efficient self-sustained solar evaporator of 4-layer woven HOGF device with a saturated moisture capacity of 1.63 kg m^(-2) and water-releasing rate of 1.46 kg m^(-2) h^(-1).Furthermore,the 2D textile can be applied as a wearable dehumidification device to efficiently remove the evaporative moisture from human skin to maintain a comfortable environment.It can reduce the humidity from 90 to 33.4%within 12.5 min.In addition,the introduction of AgNPs can also endow the HOGFs with antibacterial features,demonstrat-ing significant potential in personal healthcare.