The mechanism and treatment strategies of GSDMD-mediated pyroptosis in myocardial infarction

Acute myocardial infarction(MI)is associated with high morbidity and mortality and poses a significant challenge to human health.Despite advances in medicine,effective treatment options for MI are still associated with adverse outcomes,such as heart failure.Consequently,identifying the pathogenesis of MI is a promising avenue for developing practical treatments.The inflammatory response plays a critical role in the pathogenesis of MI.Gasdermin D(GSDMD)-mediated pyroptosis regulates the inflammatory response,which is a pathogenic and potential therapeutic target for MI.Therefore,anti-pyroptosis treatment is emerging as a promising therapeutic approach for MI.Overall,this article reviews the mechanism and treatment strategies for GSDMD-mediated pyroptosis in MI,with the hope of providing insights into pathogenic interventions.

从知识图谱探析当代大学生自我发展的困境与变化

高效的大学生自我发展规划和实施对于高等教育本源和创新创业能力培养具有重要的内在意义。面对大学生自我发展规划过程中出现的困境和变化,本研究从教师角度出发,采用知识图谱的文献计量专业软件CiteSpace,可视化出当代大学生自我发展研究的客观与研究主题知识图谱,从客观数据和研究主题角度分析大学生自我发展规划时遇到的问题及发生的变化,根据研究主题的聚类结果探析发生困境的原因。基于分析所得结果,提出引导大学生走出困境规划自我发展的四条建议。

Genome sequencing and phylogenetic analysis of allotetraploid Salix matsudana Koidz

Polyploidy is a common phenomenon among willow species.In this study,genome sequencing was conducted for Salix matsudana Koidz(also named Chinese willow),an important greening and arbor tree species,and the genome of this species was compared with those of four other tree species in Salicaceae.The total genome sequence of S.matsudana was 655.72 Mb in size,with repeated sequences accounting for 45.97%of the total length.In total,531.43 Mb of the genome sequence could be mapped onto 38 chromosomes using the published genetic map as a reference.The genome of S.matsudana could be divided into two groups,the A and B genomes,through homology analysis with the genome of Populus trichocarpa,and the A and B genomes contained 23,985 and 25,107 genes,respectively.4DTv combined transposon analysis predicted that allotetraploidy in S.matsudana appeared~4 million years ago.The results from this study will help reveal the evolutionary history of S.matsudana and lay a genetic basis for its breeding.

The genetic architecture of growth traits in Salix matsudana under salt stress

Willow(Salix)is one of the most important ornamental tree species in landscape plants.One species,Salix matsudana,is widely used as a shade tree and border tree because of its soft branches and plump crown.Some varieties of S.matsudana were salt tolerant and could grow normally in coastal regions.However,the molecular mechanisms of salt tolerance for S.matsudana have been less clear.Here,we addressed this issue by performing a mapping experiment containing 195 intraspecific F1 progeny of S.matsudana,derived from salt-sensitive‘yanjiang’and salt-tolerant‘9901’,grown by cuttings in a 100 mM NaCl solution.Growth performance of these progeny under salt stress was investigated,displaying marked genotypic variability with the coefficients of variance of 28.64–86.11%in shoot and root growth traits.We further mapped specific QTLs contributing to these differences to the Salix genome.Of the 204 QTLs identified,a few were detected to explain a remarkably larger portion of the phenotypic variation than many others.Many detected QTLs were found to reside in the region of candidate genes of known biological function.The discovery of growth QTLs expressed under salt stress provides important information for marker-assisted breeding of salt tolerant Salix varieties and founds the basis for the application of S.matsudana in coastal afforestation.

Validated,Rapid and Sensitive HPLC-MS/MS Method for Determination of 7,4'-Dihydroxylflavone in Rat Plasma and Its Application to Preliminary Pharmacokinetics

A sensitive,specific and rapid high-performance liquid chromatography-electronic spray ionization-tandem mass spectrometric method was developed and validated for the determination of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma.Genistein(internal standard,IS)was added in the collected plasma samples and subsided together by a simple one-step protein precipitation using acetonitrile-methanol(1:1,v/v).Chromatographic separation was performed on an Agilent Zorbax XDB C18 chromatography column and gradient elution with the mobile phase consisting of methanol and 0.1%formic acid was used.The mass spectrometric detection was performed by negative ion electro-spray ionization in multiple selected reactions monitoring(MRM)mode,with the transitions of m/z 253.1→113.0 for 7,4'-DHF and m/z 268.9→158.8 for IS.The calibration curve has liner relationship over the concentration range of 0.1-50.ng/mL(r=0.995.4).The intra-and inter-day precision(RSD%)was less than 10%,and the accuracy(RE%,relative error)ranged from-5.2%to 8.0%.The fully validated method was applied to the pharmacokinetics(PK)of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma after oral administration(two doses:15 and 30.mg/kg)and intravenous injection(5.mg/kg).The result showed that Tmax and Cmax was 1.33±0.29.h and 0.12±0.02.ng/mL(15.mg/kg),and 1.17±0.29.h and 0.17±0.04.ng/mL(30.mg/kg),respectively.The bioavailability was 0.078%(15.mg/kg)and 0.070%(30.mg/kg),respectively.

Studies in Brain Functional Networks Based on Complex Networks

The purpose of the paper is to provide a way to model the brain functional network based on the complex networks with brain anatomical architecture. We introduce the brain structural and functional researches, and delineate the brain anatomical and functional networks based on complex networks, then we discuss the brain functional complex network models; at last we put forward the brain functional networks modeling process and the data processing with fMRI （functional magnetic resonance imaging） in detailed.

The variation of DOM during long distance water transport by the China South to North Water Diversion Scheme and impact on drinking water treatment

In this study,samples were taken from three locations,upstream to downstream,along the central route project of the China South to North Water Diversion(SNWD)scheme in summer and winter.These were used to reveal the variations of dissolved organic matter(DOM)during the water transfer process,and the effects of these variations on drinking water treatment and disinfection by-products formation potential(DBPs-FP).The results showed that polysaccharides accumulate in summer and reduce in winter with flow distance,which has an important effect on the overall properties of DOM,as well as on the performance of coagulation,ultrafiltration,and the formation of DBPs.Humic substances,and their hydrophilic content,also increased in summer and decreased in winter with flow distance.In contrast,the concentration of small organic substances(MW≤1000 Da)increased in both summer and winter with flow distance,which affected both nanofiltration(NF)membrane fouling and DBPs-FP.The results provide a useful case study of spatial and temporal changes in raw water DOM during long distance water transfer and their impact on the treatment and quality of drinking water from the SNWD.

Correlating particle impact condition with microstructure and properties of the cold-sprayed metallic deposits

Inter-particle bonding is an important factor affecting the property of cold sprayed metallic deposit.Because the interface bonding between particles in deposit is directly determined by plastic strain of particles during spraying,Cu deposits were made at series of impact velocities of 578 m s^-1 to 745 m s^-1 and 807 m s^-1 to correlate particle impact condition with microstructure and properties of the deposits.Results show that as the average particle impact velocity increases from 578 m s^-1 to 745 m s^-1 and 807 m s^-1,the deposition efficiency of feedstock powder increases from 58%to 84%and even to 95%.Although all three deposits reveal dense microstructure due to the high ductility of Cu,the deformation degree of the deposited particles remarkably increases with increasing impact velocity.The enhanced plastic deformation of the deposited particles leads to more dispersed oxide scale and thereby stronger interparticle bonding with the strength of the deposit along the deposition direction increasing from 25.8 MPa to 148.5 MPa.The electrical and thermal conductivities at through-thickness direction of the deposit at particle impact velocity of 807 m s^-1 are 78%IACS,295 W m^-1 K^-1,respectively.

Overview of the quality standard research of traditional Chinese medicine

Traditional Chinese medicine(TCM)has been widely used for the prevention and treatment of various diseases for a long time in China.Due to its proven efficacy,wide applications,and low side effect,TCM has increasingly attracted worldwide attention.However,one of the biggest challenges facing the clinical practice of TCM is the uncontrollable quality.In this review,the progress of the development and the current status of quality standard as well as new quality control techniques introduced in Chinese Pharmacopoeia(2010 edition),such as liquid chromatography hyphenated mass spectrometry(LC-MS),fingerprint,quantitative analysis of multi-components by single-marker(QAMS),thin layer chromatography bio-autographic assay(TLC-BAA),and DNA molecular marker technique,are briefly overviewed.

Long-term results of synovectomy in total knee arthroplasty:a prospective,randomized controlled trial

Background:Synovectomy has been introduced into total knee arthroplasty(TKA)with the aim of relieving pain and inflammation of the synovium.However,there are no long-term,comparative data to evaluate the effect of synovectomy in TKA.This study was aimed at assessing pain,function,and complications in patients undergoing synovectomy during TKA for osteoarthritis(OA)at long-term follow-up.Methods:This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA.Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA.The overall efficacy of both strategies was evaluated by determination of blood loss,the Knee Society score(KSS),and knee inflammation conditions during a 3-month postoperative period.The postoperative pain,range of motion(ROM),and complications were sequentially evaluated to compare the two groups until 10 years after surgery.Results:At the 10-year follow-up,both groups had a similarly significantly improved ROM(114.88±9.84°vs.114.02±9.43°,t=0.221,P=0.815)and pain relief with no differences between the two groups(1.0[1.0]vs.1.0[1.5],U=789.500,P=0.613).Similar changes in total blood loss,KSS,and knee inflammation were found in both groups during 3 months postoperatively(P>0.05).Additionally,there was no significant difference regarding complications and satisfaction between the two groups(P>0.05).Conclusions:Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain,ROM,and satisfaction during a 10-year follow-up.In addition,it may not result in more blood loss and increased incidence of long-term complications.Based on our long-term findings,it should not be performed routinely.Trial registration:Chinese Clinical Trial Registry,ChiCTR-INR-16008245;https://www.chictr.org.cn/showproj.aspx?proj=13334.

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Dragon’s Blood Protect Rat Blood-Brain Barrier Dysfunction Induced by Simulated Microgravity Effect

Dragon’s blood(DB)has shown a protective effect on neurological diseases.Microgravity(MG)or simulated MG(SMG)can induce blood-brain barrier(BBB)dysfunction,which is a characteristic feature of neurological disorders.This study’s purpose was to evaluate the effect of DB on SMG-induced BBB dysfunction and explore its signaling pathway.Both DB and vitamin C(Vc)were administered orally for tail-suspended rats within 3 weeks.DB and Vc solutions were added to human brain microvascular endothelial cells(HCMEC/D3)cells,which were then exposed to SMG for 24 h.The protective effect of DB was assessed by hematoxylin and eosin and Nissl staining,ultrastructure observation,and permeability in rats.Cell apoptosis and the distribution of tight junction(TJ)and adherens junction(AJ)proteins and filamentous actin(F-actin)were examined in HCMEC/D3.The oxidative stress and inflammation,and TJ and AJ protein expressions were determined in rat brain and HCMEC/D3.The focal adhesion kinase(FAK)signaling pathway proteins were determined.DB protected SMG-induced rat BBB disruption by improving neuronal apoptosis,repairing widened intercellular space,and decreasing BBB permeability.DB effectively relieved SMG-induced HCMEC/D3 damage by inhibiting cell apoptosis and restoring F-actin spindle distribution.High doses of DB upregulated TJ and AJ protein expressions and decreased oxidative stress and proinflammatory cytokine levels in rat brain and HCMEC/D3.DB enhanced the expressions of FAK signal transduction proteins and F-actin/globular actin(G-actin)ratio in rat brain and HCMEC/D3,suggesting that DB promotes actin cytoskeleton polymerization,benefits the endothelial cell-cell and cell-extracellular matrix adhesion,and,in consequence,contributes to BBB integrity.

Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression

MicroRNAs （miRNAs） are a class of small non-coding regulatory RNAs, and changes in miRNAs are involved in tumor origin and progression. Studies have shown that miR-20a is overexpressed in human ovarian cancer tissues and that this miRNA enhances long-term cellular proliferation and invasion capabilities. In this study, a positive correlation between serum miR-20a expression and ovarian cancer stage was observed. We found that miR-20a binds directly to the 3＇-untranslated region of MICA/B mRNA, resulting in its degradation and reducing its protein levels on the plasma membrane. Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D （NKG2D） receptor found on natural killer （NK） cells, y＋ T cells and CD8＋ T cells, allows tumor cells to evade immune-mediated killing. Notably, antagonizing miR-20a action enhanced the NKG2D-mediated killing of tumor cells in both in vitro and in vivo models of tumors. Taken together, our data indicate that increased levels of miR-20a in tumor cells may indirectly suppress NK cell cytotoxicity by downregulating MICA/B expression. These data provide a potential link between metastasis capability and immune escape of tumor cells from NK cells.

Investigation on P-Glycoprotein Function and Its Interacting Proteins under Simulated Microgravity

P-glycoprotein(P-gp)could maintain stability of the nerve system by effluxing toxins out of the blood-brain barrier.Whether it plays a very important role in drug brain distribution during space travel is not yet known.The present study was aimed at investigating P-gp function,expression,and its interacting proteins in a rat brain under simulated microgravity(SMG)by comparative proteomics approach.Rats were tail-suspended to induce short-(7-day)and long-term(21-day)microgravity.P-gp function was assessed by measuring the P-gp ATPase activity and the brain-to-plasma concentration ratio of rhodamine 123.P-gp expression was evaluated by Western blot.21d-SMG significantly enhanced P-gp efflux activity and expression in rats.Label-free proteomics strategy identified 26 common differentially expressed proteins(DEPs)interacting with P-gp in 7d-and 21d-SMG groups.Most of the DEPs mainly regulated ATP hydrolysis coupled transmembrane transport and so on.Interaction analysis showed that P-gp might potentially interact with heat shock proteins,sodium/potassium ATP enzyme,ATP synthase,microtubule-associated proteins,and vesicle fusion ATPase.The present study firstly reported P-gp function,expression,and its potentially interacting proteins exposed to simulated microgravity.These findings might be helpful not only for further study on nerve system stability but also for the safe and effective use of P-gp substrate drugs during space travel.

pSim6质粒与新型反选择kil系统联用在重组工程的应用

基因工程中,无痕修饰是一种很受欢迎的基因组操作技术。反选择系统的严谨性决定了无痕修饰的效率。近期有文献报道了一种新型的反选择系统kil,该系统与质粒pSim6联用后反选择严谨性较pKD46质粒更高,预示着kil与pSim6质粒联用可以更高效地选择出重组子。据此,对大肠杆菌菌株W3110、MG1655和DH10B中的4个不同的非必需基因位点(lacI、dbpa、ack和glk)进行了分析,将不同长度的外源基因片段对预先插入这些位点的tet/kil进行基因替换。结果表明kil与pSim6质粒联用较其与pKD46质粒联用,重组效率均有显著提高,并且随着外源片段的增长,效果更明显。外源片段为1 000 bp时,kil与pSim6质粒联用是其与pKD46联用的1.2–2倍;外源片段为2 000 bp时,则是pKD46的2.2–5倍。综上,kil与pSim6联用具有更高的重组效率,更有利于大肠杆菌基因组的无痕修饰操作,这为大肠杆菌重组工程提供了更多的选择。