Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Characteristics of long-distance mobile mRNAs from shoot to root in grafted plant species

Thousands of long-distance mobile mRNAs were identified from different grafting systems,based on high-throughput sequencing technology.Moreover,the long-distance delivery of RNAs was proved to involve multiple mechanisms.Here,we analyzed the homology,motif,and tRNA-like structure(TLS)of long-distance mobile mRNAs identified by RNA-seq as well as the RNA-binding protein(RBP)in nine grafting combinations including Arabidopsis thaliana,Vitis vinifera,Cucumis sativus,Citrullus lanatus,Nicotiana benthamiana,Malus domestica,Pyrus spp.,Glycine max and Phaseolus vulgaris.Although several mRNAs were found to be shared in herbaceous,woody,and related species,the vast majority of long-distance mobile mRNAs were species-specific.Four non-specific movement-related motifs were identified,while the TLS was not necessary for mRNA long distance mobility.In addition,we found that RBPs were conserved among herbaceous and woody plants as well as related species.This paper reports a further in-depth analysis of the endogenous mechanisms by which the species-specific transportable m RNAs were selected by bioinformatics,in order to provide insights for future research on long-distance mobile mRNAs.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

越南非洲猪瘟疫苗AVAC ASF LIVE(ASFV-G-ΔMGF)研究工作分析与思考

非洲猪瘟(Afcrian swine fever,ASF)是由非洲猪瘟病毒(African swine fever virus,ASFV)感染引起的烈性传染病。近日,越南正式将经临床试验验证的非洲猪瘟弱毒疫苗AVAC ASF LIVE(ASFV-G-ΔMGF)在其全国推广使用。本文对越南非洲猪瘟弱毒疫苗ASFV-G-ΔMGF相关研究数据进行了总结分析,分别从ASFVG-ΔMGF株攻毒保护能力评价、传代细胞培养株临床动物实验、野猪口服接种试验、毒力返强验证等方面,结合国内相关ASFV基因缺失株试验数据进行了分析。总结分析发现:越南上市的ASFV-G-ΔMGF疫苗株,二次免疫接种后攻毒保护效果更好,但在对野猪的口服接种评价中,其口鼻接种效果存在不确定性;随着疫苗株在动物体内的不断传代,其存在毒力返强和毒株变异风险,导致接种猪只临床症状明显;ASFV-G-ΔMGF株虽然有较好的攻毒保护能力和可靠的生产优势,但仍缺乏相关研究数据,特别是在垂直传播、交叉保护、基因突变等方面。后续仍需对ASFV-G-ΔMGF株的临床应用效果进一步评价。

基于LIVE2D技术的博物馆动态形象设计实践研究

探索以Live2D技术作为新的设计手段,进一步提升二维平面形象设计的表现力和影响力,寻找塑造新颖的博物馆动态形象的可行性,为博物馆提供适应现代多种媒体渠道传播形式的动态形象设计。以Live2D技术为核心,从文化传承与发展的角度出发,结合博物馆实地调研与文物设计转化,拓宽博物馆形象设计在其馆内的应用范围,将传统平面原画通过2D建模,进而增强二维形象的可动性和真实感,结合符号学语义,实现以山东博物馆“亚丑钺”为例的动态形象设计实践。围绕博物馆藏品为原型,从平面设计图实现二维建模,实现文物藏品转化为角色形象,设计出基于Live2D技术的动态博物馆形象,为观展流程增添吸引力和沉浸感。促进博物馆以文物为原型的形象良性发展,丰富与观众的交互形式,帮助藏品达成创造性转化、创新性发展,从而为山东博物馆以及其他文化机构提供关于形象设计多元化创新的可借鉴新形式。

Water hammer protection for diversion systems in front of pumps in long-distance water supply projects

For a water supply system with long-distance diversion pipelines, in addition to the water hammer problems that occur beyond pumps, the safety of the water diversion pipeline in front of pumps also deserves attention. In this study, a water hammer protection scheme combined with an overflow surge tank and a regulating valve was developed. A mathematical model of the overflow surge tank was developed, and an analytical formula for the height of the overflow surge tank was derived. Furthermore, a practical water supply project was used to evaluate the feasibility of the combined protection scheme and analyze the sensitivity of valve regulation rules. The results showed that the combined protection scheme effectively reduced the height of the surge tank, lessened the difficulties related to construction, and reduced the necessary financial investment for the project. The two-stage closing rule articulated as fast first and then slow could minimize the overflow volume of the surge tank when the power failure occurred, while the two-stage opening rule articulated as slow first and then fast could be more conducive to the safety of the water supply system when the pump started up.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

The impact of the Rural Minimum Living Standard Guarantee(Rural Dibao)Program on child nutrition outcomes

The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.

Outcome of split liver transplantation vs living donor liver transplantation:A systematic review and meta-analysis

BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT(DD-SLT)and living donor LT(LDLT).AIM To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.METHODS This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.The following databases were searched for articles comparing outcomes of DD-SLT and LDLT:PubMed;Google Scholar;Embase;Cochrane Central Register of Controlled Trials;the Cochrane Database of Systematic Reviews;and Reference Citation Analysis(https://www.referencecitationanalysis.com/).The search terms used were:“liver transplantation;”“liver transplant;”“split liver transplant;”“living donor liver transplant;”“partial liver transplant;”“partial liver graft;”“ex vivo splitting;”and“in vivo splitting.”RESULTS Ten studies were included for the data synthesis and meta-analysis.There were a total of 4836 patients.The overall survival rate at 1 year,3 years and 5 years was superior in patients that received LDLT compared to DD-SLT.At 1 year,the hazard ratios was 1.44(95%confidence interval:1.16-1.78;P=0.001).The graft survival rate at 3 years and 5 years was superior in the LDLT group(3 year hazard ratio:1.28;95%confidence interval:1.01-1.63;P=0.04).CONCLUSION This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.

Significance of Live Streaming in Shaping Business: A Critical Review and Analytical Study

With the rise of live streaming on social media, platforms like Facebook, Instagram, and YouTube have become powerful business tools. They enable users to share live videos, fostering direct connections between businesses and their customers. This critical literature review paper explores the impact of live streaming on businesses, focusing on its role in attracting and satisfying consumers by promoting products tailored to their needs and wants. It emphasizes live streaming’s crucial role in engaging customers, a key to business growth. The study also provides viable strategies for businesses to leverage live streaming for growth and customer engagement, underscoring its importance in the business landscape.

Individual alcohol consumption by the population of Russia versus regional living conditions

Background:There are substantial regional differences in drinking alcohol in Russia,both at the population and individual levels.However,the causes of these differences have not been studied yet.Objective:The goal of our study was to examine the effect of regional living conditions on individual alcohol consumption by the population of Russia.Methods:For the analysis,we used data from a cross-sectional epidemiological study conducted in 2013-2014.The final analytical sample included 18,130 people aged 25-64 years.We conducted the interviews face to face,based on which any drinking in the last year,as well as alcohol abuse,were considered as a response.Alcohol abuse was recorded when the respondent consumed 5.75 or more grams of pure ethanol per day(75th percentile of average daily alcohol consumption among alcohol drinkers).The assessment of the regional living conditions was accomplished via integral indexing,which was previously performed based on publicly available data for 2010-2014.Associations were assessed using generalized scoring equations with unchanging standard errors.The associations were expressed by odds ratios(OR)and 95%confidence intervals(C).Results:Deterioration of social conditions and increase in demographic depression in the region of residence increased the odds of any drinking(OR 1.51,95%CI:1.33 to 1.72,P<0.001 and OR 1.22,95%CI:1.05 to 1.41,P=0.oo9,respectively).The odds of alcohol abuse increased with the deterioration of social living conditions and the growth of the industrial development in the region:OR 1.35,95%CI:1.14 to 1.59,P<0.001 and OR 1.16,95%CI:1.05 to 1.28,P=0.002,respectively.Conclusion:Our analysis allowed assessing the impact of the regional living conditions on individual drinking alcohol in the population of Russia.

Study on Distribution of Four Pseudomonas Species in Living Environment Using Multiplex PCR

Purpose: The genus Pseudomonas is a ubiquitous microorganism frequently detected from immunocompromised patients. The inherent resistance to numerous antimicrobial agents contributes to the opportunistic character of this pathogen exhaustive monitoring of this pathogen is considered of critical importance to public health organizations. The reliable identification method able to distinguish genetic close Pseudomonas species is needed, because these organisms are difficult to differentiate by phenotypic or biochemical methods. The purpose of the present study was to design species-specific primers in order to identify and detect four Pseudomonas species which are frequently detected from the human oral cavities, and to investigate the distribution of these organisms in the living environment using a multiplex PCR. Methods: Polymerase chain reaction (PCR) primers were designed based on partial sequences of the rpoD gene of four Pseudomonas species. Swab samples were collected from fifty washstands, and the distribution of Pseudomonas species was investigated using a conventional PCR at genus level and a multiplex PCR at species level. Results: Multiplex PCR method developed in this study was able to distinguish four Pseudomonas species clearly. The genus Pseudomonas was detected from all samples (100%), whereas P. putida, P, aeruginosa, P. stutzeri and P. fluorescens were detected at 44%, 8%, 4% and 2% in fifty swab samples, respectively. Conclusion: Our developed one-step multiplex PCR method is accurate, specific, cost-effective, time-saving, and works without requiring DNA extraction. It was indicated that washstands were the uninhabitable environment for P. putida, P, aeruginosa, P. stutzeri and P. fluorescens.

Live2D制作立体感的优化——以物理模拟系统和OpenGL渲染技术为例

Live2D作为一种创新的2.5D(半三维)技术,已经在动漫、游戏和虚拟角色领域展现出了巨大的潜力。它的出现为二维图像注入了更多的动态和立体感,使得角色在屏幕上呈现出更为生动逼真的表现。本文重点探讨Live2D制作技术中如何通过物理模拟使用和对渲染技术进行调整,使Live2D能够实现更加精细的变形和纹理映射,从而增强二维画面的立体感和真实感。进一步研究和优化Live2D制作技术对于提升二维动画质量和表现力具有重要意义。它有助于动漫、游戏和虚拟角色行业创造更具吸引力和沉浸式的用户体验,扩展二维动画的创作可能性。

Evaluation of the Living Conditions and Health Perceptions of Waste Electrical and Electronic Equipment Handlers in the Informal Sector in Dakar

Electrical and electronic devices are becoming an increasingly important part of our society. In Africa, and in Senegal in particular, the handling and management of electronic and electrical equipment (EEE) that has reached the end of its life is mainly informal. This professional environment is characterized by the disintegration of the sector and the social heterogeneity that can be found there. The objective of this study is to assess the standard of living of electrical and electronic equipment waste handlers in the Dakar region, as well as their perception of their health. A survey was used to obtain information on sociodemographic background, living arrangements, perception of health status, and good practices to be implemented in case of work-related health problems. Life style, perception of general health and health problems were ranged as excellent, very good, good, average and poor. Informal recyclers in the Dakar region lived mainly in rooms and buildings as tenants (49.1%), or in family homes (48.4%) before starting this activity, and 51.2% continue to live in rooms and buildings as tenants compared to 41.4% who still live in a family home. The perception of health status ranged from poor to excellent, and 4.9% believe that they are limited in work due to a disability or health problem. Informal work is a heterogeneous phenomenon that makes research and policymaking particularly complex. There are several external factors within informal WEEE re-cyclers that can cause health problems or functional disability. However, the living conditions and the perception they have of their state of health are contradictory to the working conditions and the social environment to which they belong. A biomedical approach would consolidate these achievements by confirming or invalidating them.

Multiplexed stimulated emission depletion nanoscopy(mSTED)for 5-color live-cell long-term imaging of organelle interactome

Stimulated emission depletion microscopy(STED)holds great potential in biological science applications,especially in studying nanoscale subcellular structures.However,multi-color STED imaging in live-cell remains challenging due to the limited excitation wavelengths and large amount of laser radiation.Here,we develop a multiplexed live-cell STED method to observe more structures simultaneously with limited photo-bleaching and photo-cytotoxicity.By separating live-cell fluorescent probes with similar spectral properties using phasor analysis,our method enables five-color live-cell STED imaging and reveals long-term interactions between different subcellular structures.The results here provide an avenue for understanding the complex and delicate interactome of subcellular structures in live-cell.

某旅游商业综合体开发Live House音乐街区项目的可行性分析

音乐产业作为实现文旅赋能商业的重要元素,已成为各地政府及市场的重点打造对象。本文针对某城市旅游商业综合体提质增效、文旅赋能转型的发展需要,提出开发Live House音乐街区项目,从市场环境出发,基于SWOT分析理论对项目开发可行性进行分析理论及项目效益分析,并就项目运营发展策略提出思考建议。

Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.

Effect of solvent on the initiation mechanism of living anionic polymerization of styrene:A computational study

For living anionic polymerization(LAP),solvent has a great influence on both reaction mechanism and kinetics.In this work,by using the classical butyl lithium-styrene polymerization as a model system,the effect of solvent on the mechanism and kinetics of LAP was revealed through a strategy combining density functional theory(DFT)calculations and kinetic modeling.In terms of mechanism,it is found that the stronger the solvent polarity,the more electrons transfer from initiator to solvent through detailed energy decomposition analysis of electrostatic interactions between initiator and solvent molecules.Furthermore,we also found that the stronger the solvent polarity,the higher the monomer initiation energy barrier and the smaller the initiation rate coefficient.Counterintuitively,initiation is more favorable at lower temperatures based on the calculated results ofΔG_(TS).Finally,the kinetic characteristics in different solvents were further examined by kinetic modeling.It is found that in benzene and n-pentane,the polymerization rate exhibits first-order kinetics.While,slow initiation and fast propagation were observed in tetrahydrofuran(THF)due to the slow free ion formation rate,leading to a deviation from first-order kinetics.

Non-Deterministic Liveness-Enforcing Supervisor Tolerant to Sensor-Reading Modification Attacks

In this paper, we study the supervisory control problem of discrete event systems assuming that cyber-attacks might occur. In particular, we focus on the problem of liveness enforcement and consider a sensor-reading modification attack(SM-attack) that may disguise the occurrence of an event as that of another event by intruding sensor communication channels. To solve the problem, we introduce non-deterministic supervisors in the paper, which associate to every observed sequence a set of possible control actions offline and choose a control action from the set randomly online to control the system. Specifically, given a bounded Petri net(PN) as the reference formalism and an SMattack, an algorithm that synthesizes a liveness-enforcing nondeterministic supervisor tolerant to the SM-attack is proposed for the first time.

Launching Ceremony of the International Living Water Project Held in Nairobi,Kenya

Jointly hosted by Jiangsu People's Association for Friendship with Foreign Countries and the Amity Foundation,the launching ceremony of the International Living Water Project was held in Nairobi,Kenya on the afternoon of April 18.Ma Xin,member of the Standing Committee of the CPC Jiangsu Provincial Committee and Executive Vice-Governor,and Pasalis,member of the Kenyan National Assembly,attended the event and delivered speeches.