电针预处理通过抑制NF-kB/NLRP3信号通路介导炎症和凋亡改善大鼠脑卒中后痉挛

目的探讨电针预处理诱导NF-κB/NLRP3信号通路及炎症和凋亡在脑卒中后挛治疗中的潜在机制。方法SPF级雄性SD大鼠18只随机分为:假手术组(sham),模型组(I/R),电针治疗组(I/R+EP),每组6只。假手术组仅暴露不做阻塞,模型组进行中动脉闭塞模型,电针组使用电针治疗曲鬓穴和百会穴,持续治疗3 d。采用HE、Nissl、TUNEL染色检测大鼠脑组织病理变化情况。ELISA法检测各组IL-4、IL-6、TNF-α、TMAO的水平变化情况。采用qRT-PCR、Western blotting和免疫组化检测NF-κB p65、NLRP3、caspase-3、caspase-9 mRNA和蛋白水平。结果与假手术组相比,模型组的神经功能评分增加(P<0.05),肌张力增增加(P<0.05),新事物识别时间减少(P<0.05),海马细胞排列不均、松散和轮廓不清晰(P<0.05),细胞凋亡数量显着增加(P<0.05),促炎因子IL-6和TNF-α,NF-B p65、NLRP3、caspase-3和caspase-9水平上升(P<0.05)。与模型组相比,电针治疗组神经功能评分下降,肌张力评分下降,新事物识别时间增加(P>0.05),海马细胞排列紧密规则,染色均匀,轮廓清晰(P<0.05),活神经元数量增加(P<0.05),细胞凋亡明显减少(P<0.05),促炎因子IL-6和TNF-α水平下降,抑炎因子IL-4水平上升(P<0.05)。此外,电针治疗抑制了脑组织中NLRP3、caspase-3、caspase-9和NF-B p65的表达(P<0.05)。结论电针预处理有助于缓解大鼠脑卒中后痉挛,这是因为它阻断了NF-B/NLRP3通路,抑制炎症反应和细胞凋亡。

Mapping of fruit apex shape related QTLs across multi-genetic backgrounds in cucumber(Cucumis sativus L.)

The shape of fruit apex is critical to appearance quality in cucumber(Cucumis sativus L.),of which the genetic basis was poorly understood,and the use of marker-assisted breeding for fruit apex improvement is not available yet.In this study,the variation of fruit apex in different cucumber ecotypes was evaluated by fruit apex angle(variation coefficient from 7.1%to 15.7%)and fruit apex index(variation coefficient from 8.8%to 22.6%).Fruit apex associated QTLs were mapped by using 145 F_(2:3) families and 155 F_(2:6) population that were derived from the cross of different ecotype cucumbers.Phenotyping of the mapping populations were conducted in four experiments in 2 years.Four majoreffect QTLs,Bfal4.1,Bfai4.1,Bfad6.1 and Bfai6.1 were consistently and reliably detected across two environments which could explain 11.6%-33.6%phenotypic variations(R^(2))in the F_(2:3) families.Three major-effect QTLs,Ofai4.1(R^(2)=13.4%-15.5%),Ofal4.1(R^(2)=10.7%-12.8%),and Ofad6.1(R^(2)=11.6%-12.4%)were stably detected in the F_(2:6) population in two experiments.Bfai4.1,Bfal4.1,Ofai4.1 and Ofal4.1 were integrated to be consensus QTL fa4.1,within which 11 candidate genes were predicted.Bfai6.1 and Bfad6.1 were integrated to be consensus QTL fa6.1.QTL interaction analysis showed that Bfai6.1 has epistatic effect with Bfai4.1.This study revealed two reliable major-effect fruit apex related QTLs across multi-genetic backgrounds and environments in cucumber.The possible candidate genes regulating the shape of fruit apex,and the relationship between cell division and fruit apex morphogenesis were discussed.

Chromosome-scale genome assembly of Cucumis hystrix-a wild species interspecifically cross-compatible with cultivated cucumber

Cucumis hystrix Chakr.(2n=2x=24)is a wild species that can hybridize with cultivated cucumber(C.sativus L.,2n=2x=14),a globally important vegetable crop.However,cucumber breeding is hindered by its narrow genetic base.Therefore,introgression from C.hystrix has been anticipated to bring a breakthrough in cucumber improvement.Here,we report the chromosome-scale assembly of C.hystrix genome(289 Mb).Scaffold N50 reached 14.1 Mb.Over 90%of the sequences were anchored onto 12 chromosomes.A total of 23,864 genes were annotated using a hybrid method.Further,we conducted a comprehensive comparative genomic analysis of cucumber,C.hystrix,and melon(C.melo L.,2n=2x=24).Whole-genome comparisons revealed that C.hystrix is phylogenetically closer to cucumber than to melon,providing a molecular basis for the success of its hybridization with cucumber.Moreover,expanded gene families of C.hystrix were significantly enriched in“defense response,”and C.hystrix harbored 104 nucleotide-binding site-encoding disease resistance gene analogs.Furthermore,121 genes were positively selected,and 12(9.9%)of these were involved in responses to biotic stimuli,which might explain the high disease resistance of C.hystrix.The alignment of whole C.hystrix genome with cucumber genome and self-alignment revealed 45,417 chromosome-specific sequences evenly distributed on C.hystrix chromosomes.Finally,we developed four cucumber-C.hystrix alien addition lines and identified the exact introgressed chromosome using molecular and cytological methods.The assembled C.hystrix genome can serve as a valuable resource for studies on Cucumis evolution and interspecific introgression breeding of cucumber.

Mutational screening of affected cardiac tissues and peripheral blood cells identified novel somatic mutations in GATA4 in patients with ventricular septal defect

The aim of this study was to examine how somatic mutations of the GATA4 gene contributed to the genesis of ventricular septal defect （VSD）. The coding and intron-exon boundary regions of GATA4 were sequenced of DNA samples from peripheral blood cells and cardiac tissues of twenty surgically treated probands with VSD. Seven novel heterozygous variants were detected in cardiac tissues from VSD patients, but they were not detected in the peripheral blood cells of VSD patients or in 500 healthy control samples. We replicated 14 single nucleotide polymorphisms （SNPs） reported in NCBI. Bioinformatics analysis was performed to analyze the possible mechanism by which mutations were linked to VSD. Among those variants, c. 1004C〉A （p.S335X） occurred in the highly conserved domain of GATA4 and generated a termination codon, which led to the production of truncated GATA4. The seven novel heterozygous GATA4 mutations were only identified in cardiac tissues with VSD, suggesting that they are of somatic origin. A higher mutation rate in cardiac tissues than in peripheral blood cells implies that the genetic contribution to VSD may have been underestimated.

A Study of Domestic and Foreign Mango Research Progress during 2013-2014: Based on Literature Analysis

The scientific literature retrieval and analysis is of great significance to promoting scientific research and technological progress.Based on the related literature included in SCI-EXPANDED and EI database,we make a comparative analysis of the main domestic and foreign mango research literature information during 2013-2014,and carry out the comparative study of the mango research countries and main research progress about the articles included in domestic and foreign mango literature as well as main research disciplines and fields during 2013-2014,so as to provide a reference for the Chinese mango research.

高水平临床研究推动肺动脉高压危险分层内涵发展

肺动脉高压是一种疑难危重罕见病,一直以来被视为“心血管系统的癌症”,患者预后极差.对疾病进行危险分层可以帮助临床医生判断患者病情、指导治疗、评价疗效和预测预后,这需要大量的临床研究作为依据.高水平临床研究是解决临床实践问题的重要手段,我国肺动脉高压队列有着独特的特点,学习和借鉴国外肺动脉高压危险分层发展经验,对建立符合我国肺动脉高压人群的危险分层具有重要意义.本文以肺动脉高压危险分层发展为例,旨在深入剖析通过高水平临床研究解决临床问题的过程与方法.文章概述了肺动脉高压的发现与流行,明确了定义与深入开展临床研究的全过程;重点围绕靶向药治疗时代下肺动脉高压危险分层的建立与更新,总结临床研究推动肺动脉高压诊疗指南和治疗理念不断发展的方式方法;最后通过分析肺动脉高压危险分层在我国的应用现状和问题,希望国外研究肺动脉高压危险分层的思维方式对我国开展临床研究、解决临床实践中的问题有所启示.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism:A case-control study

Background:The potential impact of pre-existing coronary artery stenosis(CAS)on acute pulmonary embolism(PE)episodes remains underexplored.This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I(hs-cTnI)levels in patients with PE.Methods:In this multicenter,prospective case-control study,88 cases and 163 controls matched for age,sex,and study center were enrolled.Cases were patients with PE with elevated hs-cTnI.Controls were patients with PE with normal hs-cTnI.Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography.CAS was defined as≥50%stenosis of the lumen diameter in any coronary vessel>2.0 mm in diameter.Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results:The percentage of CAS was higher in the case group compared to the control group(44.3%[39/88]vs.30.1%[49/163];P=0.024).In multivariable conditional logistic regression model 1,CAS(adjusted odds ratio[OR],2.680;95%confidence interval[CI],1.243-5.779),heart rate>75 beats/min(OR,2.306;95%CI,1.056-5.036)and N-terminal pro-B type natriuretic peptide(NT-proBNP)>420 pg/mL(OR,12.169;95%CI,4.792-30.900)were independently associated with elevated hs-cTnI.In model 2,right CAS(OR,3.615;95%CI,1.467-8.909)and NT-proBNP>420 pg/mL(OR,13.890;95%CI,5.288-36.484)were independently associated with elevated hs-cTnI.Conclusions:CAS was independently associated with myocardial injury in patients with PE.Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension:A national prospective cohort study

Background:Coronavirus disease 2019(COVID-19)has potential risks for both clinically worsening pulmonary hypertension(PH)and increasing mortality.However,the data regarding the protective role of vaccination in this population are still lacking.This study aimed to assess the safety of approved vaccination for patients with PH.Methods:In this national prospective cohort study,patients diagnosed with PH(World Health Organization[WHO]groups 1 and 4)were enrolled from October 2021 to April 2022.The primary outcome was the composite of PH-related major adverse events.We used an inverse probability weighting(IPW)approach to control for possible confounding factors in the baseline characteristics of patients.Results:In total,706 patients with PH participated in this study(mean age,40.3 years;mean duration after diagnosis of PH,8.2 years).All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China.Among them,278 patients did not receive vaccination,whereas 428 patients completed the vaccination series.None of the participants were infected with COVID-19 during our study period.Overall,398 patients received inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine,whereas 30 received recombinant protein subunit vaccine.After adjusting for baseline covariates using the IPW approach,the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase(27/428[6.3%]vs.24/278[8.6%],odds ratio=0.72,P=0.302).Approximately half of the vaccinated patients reported at least one post-vaccination side effects,most of which were mild,including pain at the injection site(159/428,37.1%),fever(11/428,2.6%),and fatigue(26/428,6.1%).Conclusions:COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH,although there were some tolerable side effects.A large-scale randomized controlled trial is warranted to confirm this finding.The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Role of T Cells in Viral and Immune-mediated Myocarditis

Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.

Size, phase-controlled synthesis,the nucleation and growth mechanisms of NaYF_4:Yb/Er nanocrystals

Near-monodisperse NaYF4：Yb/Er nanoparticles（NPs） with controlled size, phases（α,β） and shapes（sphere, and hexagonal plate） were synthesized by adjusting the NaF to RE（RE = Y, Yb, Er） ratios, the reaction temperature and time in the hot surfactant solutions（oleic acid, 1-octadecene） from the improved one-pot thermal decomposition metal trifluoroacetate, and the precursors were prepared via hydrothermal route. The growth kinetics of β-NaYF4 NPs includes several stages： nucleation, growth of aNaYF4, Ostwald ripening, size shrinkage and growth. The results prove that the temperatures are preferred to the phase transformation compared with the NaF content when other experimental conditions are unchanged. Our work will further facilitate the comprehension of the nucleation and growth mechanisms of the NPs, and provide guidance for their controlled synthesis.

Comparative Cyto-molecular Analysis of Repetitive DNA Provides Insights into the Differential Genome Structure and Evolution of Five Cucumis Species

The genus Cucumis, includes the cucumber(2n = 14), melon(2n = 24), and other wild species, which is a good model for studying genome organization and evolution due to their variation in genome size and basic chromosome number. In this study, five Cucumis species with different geographical origins and basic chromosome numbers(i.e., C. sativus, C. hystrix, C. melo, C. anguria, and C. metuliferus) were used to identify and characterize the repetitive DNA in detail using a phylogenetic method. Comparative cyto-molecular genetic analysis of repetitive DNA was carried out using a graph-based clustering method, construction of Neighbor-Joining tree and fluorescence in situ hybridization(FISH).The results revealed that the five Cucumis species had differences in the repeat content of their genome, as well as in the composition of repetitive DNA and their genomic proportions. Three species from subgenus Melo showed a decreased tendency in both repeat types and genomic proportions, while two species from subgenus Cucumis also showed a decreased tendency in repeat types, but an increased tendency in genomic proportions. Phylogenic analysis of Cucumis Ty1/Copia, Ty3/Gypsy, and 45 S rDNA ITS regions revealed that C. sativus, C. hystrix, and C. melo were closely related species, which C. sativus and C. hystrix were closer, while C. anguria and C. metuliferus were closer to each other and further from the other three species. Differential accumulation and elimination of different repeat types divergently shaped the genomic architecture of these five Cucumis species, contributing to the genome’s evolution and diversification. Overall, these results enhance our understanding of the genomes of these five Cucumis species, and contribute to a more holistic view of genome evolution and phylogenetics of this genus.

Balancing charge injection in quantum dot light-emitting diodes to achieve high efficienciy of over 21%

Quantum dot light-emitting diodes(QLEDs)have attracted considerable attention in displays owing to their high color purity,wide gamut,narrow emission band,and solution-processed characteristics.However,a major problem of the unbalanced carrier(electrons and holes)injection in QLEDs deteriorates their performance.Here,we balanced the charge injection in QLEDs by optimizing the carrier transport layers.Different organic hole transport layers(HTLs)with a suitable thickness were employed to match the electron transport layer(ETL)of ZnO.Mg^(2+) was doped into the ZnO(MZO)ETL to decrease the electron mobility and match the hole mobility of the HTL.Consequently,the QLEDs exhibited an excellent external quantum efficiency(EQE)of 21.10%at a luminance of 4661 cd m^(-2).In the luminance range of 100–30,000 cd m^(-2),EQE roll-off was considerably low,and more than 80%of the initial EQE value could be maintained,indicating less Auger recombination because of the balanced carrier injection.This work reveals that compared with energy level matching,the charge transfer capability of the transport layers is more instrumental in the charge balance regulation of QLED devices.

Standard:Human intestinal cancer organoids

Intestinal cancer is one of the most frequent and lethal types of cancer.Modeling intestinal cancer using organoids has emerged in the last decade.Human intestinal cancer organoids are physiologically relevant in vitro models,which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer.“Human intestinal cancer organoids”is the first set of guidelines on human intestinal organoids in China,jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society:the Chinese Society for Stem Cell Research.This standard specifies terms and definitions,technical requirements,test methods for human intestinal cancer organoids,which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids.It was released by the Chinese Society for Cell Biology on 24 September 2022.We hope that the publication of this standard will guide institutional establishment,acceptance and execution of proper practocal protocols,and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.

Efficient solution-processed InP quantum-dots light-emitting diodes enabled by suppressing hole injection loss

Solution-processed cadmium-based quantum dots(QDs)light-emitting diodes(QLEDs)have shown promising for high-definition display panels due to their high colour purity and low-cost fabrication,but the toxicity still is a big threat.InP is considered as the most promising cadmium-free material to achieve high performance QLEDs,however,the performance of the InP-based QLEDs is far behind of the cadmium-based counterparts.Here,we report high efficiency InP-based QLEDs with more than 20%of external quantum efficiency(EQE)by suppressing hole injection loss.This suppression is achieved by doping a strong Lewis acid into a Lewis base poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine)to form a Lewis acid-base adduct hole-transport layer(HTL),which improves the hole mobility of the HTL,reduces the hole transfer barrier between HTL and QDs layer to increase hole transport capability.This eventually leads to a more balanced carrier-injection through accelerating hole-injection to match well with the rate of electron-injection,thus suppressing the hole injection loss in the QLED.The InP-based QLED shows EQE of 20.4%,current efficiency of 25.3 cd·A^(−1),turn-on voltage of 2.0 V,luminance of 24,000 cd·m^(−2).This strategy would be a constructive approach to reduce hole loss for p-n junction optoelectronics.