Inhibitory effect and mechanism of chuanxiongzine on multiplication of VSMC

Objective： To study the inhibitory effect of chuanxiongzine on vascular smooth muscle cell （VSMC） proliferation and explore its molecular biology basis. Methods： we selected the VSMC cultured 4～8 generation from rat aorta thoracalis as research object. The objects were divided into four groups （ Ⅰ ）control group, （ Ⅱ ）chuanxiongzine （50 μg/ml）group, （Ⅲ）chuanxiongzine （100 μg/ ml） group and （Ⅳ） chuanxiongzine （200 μg/ml ） group. The inhib.itory effect of chuanxiongzine on VSMC proliferation was investigated by cell counting, MTT and ^3H-TdR incorporation assay. In order to illuminate the molecular biology mechanism of chuanxiongzine inhibiting VSMCs proliferation, the expression of proliferating cell nuclear antigen （PCNA） and C-myc were detected. Results ： Chuanxiongzine could inhibit the proliferation of VSMC significantly in a dose- and time-dependent manner, compared with control group （P 〈 0.05 ）. The expression of PCNA and c-myc were inhibited obviously and correlated with the concentration of chuanxiongzine （P 〈 0.05）. Conclusion： Chuanxiongzine may play a considerable role in VSMC proliferation process. The inhibitory effect of chuanxiongzine in a dose- and time-dependent manner can be realized via down regulating the expression of PCNA and c-myc. In this study, The great theoretical fundament about Chinese medicine, which is used to treat atherosclerosis （AS）, has been obtained.

热浸镀铝钢的性能及用途

为了便于研究人员和用户了解、掌握热浸镀铝钢的性能及其用途，进一步推动我国在这方面的大力发展，作者综述了热浸镀铝钢镀层的机械性能、耐腐蚀性能、抗高温氧化性能和其他性能及其在各工程领域上的应用情况，列出了部分性能指标。

Prognostic Value of D-Dimer in Patients with Diffuse Large B-cell Lymphoma:A Retrospective Study

This study evaluated the significance of serum D-Dimer for predicting survival of patients with diffuse large B-cell lymphoma(DLBCL).We analyzed the clinical data from 113 patients who were newly diagnosed with DLBCL at Tongji Hospital from January 2012 to January 2016.The results indicated that there were higher levels of D-Dimer in DLBCL patients with the following characteristics:stage HI/IV,lymphocyte monocyte ratio(LMR)<2.27,lactate dehydrogenase(LDH)>upper limit of normal(ULN),albumin(ALB)<35 g/L,and anemia.After the first chemotherapeutic regimen,D-Dimer was significantly decreased concomitantly with LDH.Cox univariate regression analysis showed that the overall survival(OS)was negatively affected by the following factors:age>60 years,stage m/IV,LDH>ULN,LMR<2.27,anemia and D-Dimer>0.92.Multivariate analysis showed that only LDH>ULN(P=0.038)and age>60 years(P=0.047)were independent adverse prognostic factors.However,it was suggested that D-Dimer could be regarded as a marker of high tumor burden and a potential prognostic screening tool for patients with DLBCL,not otherwise specified(NOS).

Newly developed vacuum differential pressure casting of thin-walled complicated Al-alloy castings

The newly designed vacuum differential pressure casting (VDPC) unit was introduced, by which the capabilityof the VDPC process to produce thin-walled complicated Al-alloy castings, that are free from oxides, gas pore andshrinkage cavity and thus enhance overall part quality, was studied. Experimental results were compared with those oftraditional gravity pouring and vacuum suction casting. The first series of experiments were focused on investigating thecastability of thin section Al-alloy casting. In the second series of experiments the metallographic evidence, castingstrength and soundness were examined. Finally, case studies of very interesting thin walled complicated casting applicationswere described. The advantages of the described technique have made possible to produce thin walled complicatedAl-alloy casting (up to a section thickness of 1 mm), which is not practical for gravity pouring and vacuum suction casting.

Berberine Inhibits Gluconeogenesis in Skeletal Muscles and Adipose Tissues in Streptozotocin-induced Diabetic Rats via LKB1-AMPK-TORC2 Signaling Pathway

The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.

A novel incompressible finite-difference lattice Boltzmann equation for particle-laden flow

In this paper, we propose a novel incompressible finite-difference lattice Boltzmann Equation （FDLBE）. Because source terms that reflect the interaction between phases can be accurately described, the new model is suitable for simulating two-way coupling incompressible multiphase flow The 2-D particle-laden flow over a backward-facing step is chosen as a test case to validate the present method. Favorable results are obtained and the present scheme is shown to have good prospects in practical applications.

Turbine speed control system based on a fuzzy-PID

The flexibility demand of marine nuclear power plant is very high,the multiple parameters of the marine nuclear power plant with the once-through steam generator are strongly coupled,and the normal PID control of the turbine speed can't meet the control demand.This paper introduces a turbine speed Fuzzy-PID controller to coordinately control the steam pressure and thus realize the demand for quick tracking and steady state control over the turbine speed by using the Fuzzy control's quick dynamic response and PID control's steady state performance.The simulation shows the improvement of the response time and steady state performance of the control system.

Effects of processing parameters on microstructure of semi-solid magnesium alloy

In this paper, the effects of pouring temperature of magnesium melt, preheating temperature of the barrel of the screw mixer, and shear rate on the solidified microstructures of semi-solid slurry were investigated by a mechanical stirring semi-solid process. The appropriate processing parameters of slurry preparation were obtained, and the mold filling ability of semi-solid slurry for thin-walled casting was examined. Results indicate that the solid volume fraction of non-dendritic microstructure increases with a decrease in pouring temperature of magnesium melt and the barrel preheating temperature of the screw mixer. Also the grain size of primary α-phase is reduced. Furthermore, the solid volume fraction of semi-solid nondendritic structure decreases with an increase of shear rate. The fine and round granular microstructure with 30～50 μm in size of semi-solid AZ91D magnesium alloy was presented. Finally, a 1.0 mm thin-walled casting with a clear contour and good soundness was successfully made by semi-solid rheo-diecasting.

IN VITRO ANALYSIS OFτPHOSPHORYLATION SITES AND ITS BIOLOGICAL ACTIVITY

To explore the association between the abnormal phosphorylation sites found in Alzheimer disease (AD) 蚲 and the inhibition of its biological activit y. Methods. Ultracentrifugation, chromatography, manual Edman degradation and autos equence techniques were used to prepare and phosphorylate human recombinant 蚲, isolate and purify 32P 蚲 peptides and determine phosphorylation sites. Results. Phosphorylation of 蚲 by casein kinase 1 (CK 1), cyclic AMP dependent protein kinase (PKA) and glycogen synthetase kinase 3 (GSK 3) separately inhi bited its biological activity and the inhibition of this activity by GSK 3 was significantly increased if 蚲 was prephosphorylated by CK 1 or PKA. The most po tent inhibition was seen by a combined phosphorylation of 蚲 with PKA and GSK 3 . The treatment of 蚲 by PKA and GSK 3 combination induced phosphorylation of 蚲 at Ser 195, Ser 198, Ser 199, Ser 202, Thr 205, Thr 231, Ser 235, Ser 262, Ser 356, Ser 404, whereas Thr 181, Ser 184, Ser 262, Ser 356 and Se r 400 were phosphorylated by GSK 3 alone under the same condition. Conclusion. Phosphorylation of 蚲 by PKA plus GSK 3 at Thr 205 might play a ke y role in 蚲 pathology in AD.

Gender difference of transmural heterogeneity of calcium current in rabbit ventricle

Objective: To study the distribution of I_ Ca,L in endomyocardium(Endo), mid-myocardium(Mid) and epicardium(Epi) in female and male rabbit ventricle and to elucidate the mechanism of sex difference in drug-associated torsade de pointes. Methods: Whole-cell patch clamp technique was used to record action potential and I_Ca,L. Results: Action potential duration ofMidinfemale rabbit heart waslonger thanthat in male and transmural dispersion of repolarization in female was largerthan thatinmale. The densities of I_ Ca,L in Endo, Mid and Epi of female rabbits were (7.1±0.6), (10.4±0.9) and (9.6±1.1) pA/pF and they were (9.1±0.9), (10.5±1.0) and (9.8±0.9) pA/pF in male respectively. Transmural heterogeneity of I_ Ca,L in female ventricle was more significant than that in male rabbit.Conclusion:Female rabbitspossessmoresignificant transmural heterogeneityof I_Ca,L,whichmaybe responsiblefor largertransmuraldispersion of repolarization and more drug-associated torsade de pointes in female.

Inhibiting NF-κB increases cholesterol efflux from THP-1 derived-foam cells treated with AngⅡ via up-regulating the expression of ATP-binding cassette transporter A1

Objective： To study the role of nuclear factor-kappa B（NF- κB） in cholesterol efflux from THP-1 derived-foam cells treated with Angiotensin Ⅱ（Ang Ⅱ ）. Methods：Cultured THP-1 derived-foam cells were treated with Ang Ⅱ or preincubated with tosyl-phenylalanine chloromethyl-ketone（TPCK） NF- κB inhibitor. The levels of activated NF- κB in the cells were examined by sandwich ELISA, Cellular cholesterol content was studied by electron microscopy scanning and zymochemistry via fluorospectrophotometer and cholesterol effiux was detected by scintillation counting technique. ABCA1 mRNA and protein were quantified by RT-PCR and Western blotting. Results：Addition of TPCK to the cells before Ang Ⅱ stimulation attenuated the response of NF- κB p65 nuclear translocation induced by Ang Ⅱ and showed no peak in foam cells group and caused a reduction in cholesterol content and an increase in cholesterol efflux by 24.1%（P〈 0.05） and 41.1%（P〈 0.05） respectively, when compared with Ang Ⅱ group. In accordance, the ABCA1 mRNA and protein were increased by 30% and 19%（P 〈 0.05） respectively, when compared with Ang Ⅱ group. Conclusion：Ang Ⅱ can downregulate ABCA1 in THP-1 derived-foam cells via NF- K B, which leads to less cholesterol effiux and the increase of cholesterol content with the consequence of the promotion of atherosclerosis.

Depressive Effect of the Antisense Oligonucleotides of C-myc and PCNA on the Proliferation of VSMC

Objectives To study the depressive effect of the antisense oligonuceotides （ASODN） of c-myc and proliferating cell nuclear antigen （PCNA） on the proliferation of VSMC. Methods Taking the VSMC obtained from rat aorta tho- racalis cultured 4 - 8 generation as research object. The objects were divided into three groups to carry out control study： control group, PCNA ASODN group and c-myc ASODN group. The ASODNs＇ working concentration all were 1 ： 50. The depressive effect of ASODN on VSMC proliferation was investigated by cell counting, MTT and ^3H-TdR incorporation assay; PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC. Results ① PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly, compared with control group （ P 〈 0. 05）. ②Transferring PCNA and c-myc ASODN into VSMC obtained successfully ; the corresponding gene was inhibited obviously ; compared with control group （ P 〈 0. 05 ）. Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process. The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC, and then the proliferation of VSMC was slowed down. This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.

The rise of intelligent fabric agent from mass-produced advanced fiber materials

Artificial intelligence(AI)is crucial in driving scientific,technological,and industrial advancements,and it has given rise to an ambient intelligence that can potentially improve the physical execution of healthcare delivery[1,2].Among diverse advanced AI technologies,an intelligent agent with multi-parameter perception,decision-making,and execution capabilities demonstrates the potential for facilitating the development of next-generation optoelectronic devices.The intelligent agent is a physical or abstract entity that acts autonomously,perceives and interacts with its environment,and communicates with other agents[3].It could perceive dynamic environmental conditions,execute actions,and make appropriate decisions.Fabric emerges as an ideal carrier for human-centered intelligent agents,providing various properties such as perceptibility,adaptability,and wearability.Intelligent fabric,known for its unique functionality,has attracted considerable attention from academia and industry.In 2014,Germany proposed a national strategy called FutureTEX to upgrade the entire textile industry by promoting integration between textiles and other fields.Two years later,the United States announced the establishment of the Revolutionary Fibers and Textiles Manufacturing Innovation Institute,which intends to accelerate the revival of fabric manufacturing.Compared with conventional fibers,revolutionary fibers focus on the design of multiple materials and structures,enabling the integration of various functionalities into a single fiber.Particularly in the United States,the advent of the digital revolution,advancements in Internet of Things technology,and mature fiber technology significantly boost the development of the intelligent fiber industry.Notable commercial applications of intelligent fibers are gradually emerging.Project Jacquard,a collaborative effort by Google and Levi’s,presents an intelligent jacket that combines the washability and texture of standard fabrics with the interactive functionalities of electronic products.Apple Inc.has developed intelligent garments,accessories,and household items with capabilities to“read”physiological indicators such as weight,body temperature,and sedentary duration on sofas.

Transcriptional landscape of cotton roots in response to salt stress at single-cell resolution

Increasing soil salinization has led to severe reductions in plant yield and quality,and investigating the mo-lecular mechanism of salt stress response is therefore an urgent priority.In this study,we systematically analyzed the response of cotton roots to salt stress using single-cell transcriptomics technology;56281 high-quality cells were obtained from 5-day-old lateral root tips of Gossypium arboreum under natural growth conditions and different salt treatments.Ten cell types with an array of novel marker genes were identified and confirmed by in situ RNA hybridization,and pseudotime analysis of some specific cell types revealed their potential differentiation trajectories.Prominent changes in cell numbers under salt stress were observed for outer epidermal and inner endodermal cells,which were significantly enriched in response to stress,amide biosynthetic process,glutathione metabolism,and glycolysis/gluconeogenesis.Analysis of differentially expressed genes identified in multiple comparisons revealed other functional ag-gregations concentrated on plant-type primary cell wall biogenesis,defense response,phenylpropanoid biosynthesis,and metabolic pathways.Some candidate differentially expressed genes encoding transcrip-tion factors or associated with plant hormones also responsive to salt stress were identified,and the func-tion of Ga03G2153,annotated as auxin-responsive GH3.6,was confirmed by virus-induced gene silencing.The GaGH3.6-silenced plants showed a severe stress-susceptible phenotype,and physiological and biochemical measurements indicated that they suffered more significant oxidative damage.These results suggest that GaGH3.6 might participate in cotton salt tolerance by regulating redox processes.We thus construct a transcriptional atlas of salt-stressed cotton roots at single-cell resolution,enabling us to explore cellular heterogeneity and differentiation trajectories and providing valuable insights into the mo-lecular mechanisms that underlie plant stress tolerance.

Synthesis,disorder and Ising anisotropy in a new spin liquid candidate PrMgAl_(11)O_(19)

Here we report the successful synthesis of large single crystals of triangular frustrated PrMgAl_(11)O_(19)using the optical floating zone technique.Single crystal x-ray diffraction(XRD)measurements unveiled the presence of quenched disorder within the mirror plane,specifically~7%of Pr ions deviating from the ideal 2d site towards the 6h site.Magnetic susceptibility measurements revealed an Ising anisotropy with the c-axis being the easy axis.Despite a large spin–spin interaction that develops below~10 K and considerable site disorder,the spins do not order or freeze down to at least 50 mK.The availability of large single crystals offers a distinct opportunity to investigate the exotic magnetic state on a triangular lattice with an easy axis out of the plane.

Styrene and ethylbenzene exposure and type 2 diabetes mellitus:A longitudinal gene-environment interaction study

Styrene and ethylbenzene(S/EB)are identified as hazardous air contaminants that raise significant concerns.The association between S/EB exposure and the incidence of type 2 diabetes mellitus(T2DM),and the interaction between genes and environment,remains poorly understood.Our study consisted of 2219 Chinese adults who were part of the Wuhan-Zhuhai cohort.A follow-up assessment was conducted after six years.Exposure to S/EB was quantified by determining the concentrations of urinary biomarkers of exposure to S/EB(UBE-S/EB;urinary phenylglyoxylic acid level plus urinary mandelic acid level).Logistic regression models were constructed to investigate the relations of UBE-S/EB and genetic risk score(GRS)with T2DM prevalence and incidence.The interaction effects of UBE-S/EB and GRS on T2DM were investigated on multiplicative and additive scales.UBE-S/EB was dose-dependently and positively related to T2DM prevalence and incidence.Participants with high levels of UBE-S/EB[relative risk(RR)=1.930,95%confidence interval(CI):1.157-3.309]or GRS(1.943,1.110-3.462)demonstrated the highest risk of incident T2DM,in comparison to those with low levels of UBE-S/EB or GRS.Significant additive interaction between UBE-S/EB and GRS on T2DM incidence was discovered with relative excess risk due to interaction(95%CI)of 0.178(0.065-0.292).The RR(95%CI)of T2DM incidence was 2.602(1.238-6.140)for individuals with high UBE-S/EB and high GRS,compared to those with low UBE-S/EB and low GRS.This study presented the initial evidence that S/EB exposure was significantly related to increased risk of T2DM incidence,and the relationship was interactively aggravated by genetic predisposition.

Isolation,characterization,and phylogenic analysis of three new severe fever with thrombocytopenia syndrome bunyavirus strains derived from Hubei Province,China

Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.

SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria

Autophagy plays an important role in the interaction between viruses and host cells.SARS-CoV-2 infection can disrupt the autophagy process in target cells.However,the precise molecular mechanism is still unknown.In this study,we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes.From further investigation,we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy.The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy.Moreover,both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy,in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy.This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy,which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.

Role of C-type natriuretic peptide in the function of normal human sperm

C-type natriuretic peptide （CNP） is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B （NPR-B）. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods （such as immunolocalization, real time polymerase chain reaction and Western Blot）, and then to evaluate the influence of CNP on sperm function in vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

Drying-rewetting cycles reduce bacterial diversity and carbon loss in soil on the Loess Plateau of China

With global climate change, soil drying-rewetting(DRW) events have intensified and occurred frequently on the Loess Plateau of China. However, the extent to which the DRW cycles with different wetting intensities and cycle numbers alter microbial community and respiration is barely understood. Here,indoor DRW one and four cycles treatments were implemented on soil samples obtained from the Loess Plateau, involving increase of soil moisture from10% water-holding capacity(WHC) to 60% and 90% WHC(i.e., 10%–60% and 10%–90% WHC, respectively). Constant soil moistures of 10%, 60%,and 90% WHC were used as the controls. The results showed that bacterial diversity and richness decreased and those of fungi remained unchanged under DRW treatments compared to the controls. Under all moisture levels, Actinobacteriota and Ascomycota were the most dominant bacterial and fungal phyla,respectively. The bacterial network was more complex than that of fungi, indicating that bacteria had a greater potential for interaction and niche sharing under DRW treatments. The pulse of respiration rate declined as the DRW cycle increased under 10%–60% WHC, but remained similar for different cycles under 10%–90% WHC. Moreover, the DRW treatments reduced the overall carbon loss, and the direct carbon release under 10%–60% WHC was larger than that under 10%–90% WHC. The cumulative CO_(2) emissions after four DRW cycles were significantly positively correlated with microbial biomass carbon and negatively correlated with fungal richness(Chao 1).