Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

Bifunctional flexible electrochromic energy storage devices based on silver nanowire flexible transparent electrodes

Flexible electrochromic energy storage devices(FECESDs)for powering flexible electronics have attracted considerable attention.Silver nanowires(AgNWs)are one kind of the most promising flexible transparent electrodes(FTEs)materials for the emerging flexible devices.Currently,fabricating FECESD based on AgNWs FTEs is still hindered by their intrinsic poor electrochemical stability.To address this issue,a hybrid AgNWs/Co(OH)_(2)/PEDOT:PSS electrode is proposed.The PEDOT:PSS could not only improve the resistance against electrochemical corrosion of AgNWs,but also work as functional layer to realize the color-changing and energy storage properties.Moreover,the Co(OH)_(2)interlayer further improved the color-changing and energy storage performance.Based on the improvement,we assembled the symmetrical FECESDs.Under the same condition,the areal capacitance(0.8 mF cm^(−2))and coloration efficiency(269.80 cm^(2)C−1)of AgNWs/Co(OH)_(2)/PEDOT:PSS FECESDs were obviously higher than AgNWs/PEDOT:PSS FECESDs.Furthermore,the obtained FECESDs exhibited excellent stability against the mechanical deformation.The areal capacitance remained stable during 1000 times cyclic bending with a 25 mm curvature radius.These results demonstrated the broad application potential of the AgNWs/Co(OH)_(2)/PEDOT:PSS FECESD for the emerging portable and multifunctional electronics.

The role of prolactin/vasoinhibins in cardiovascular diseases

Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including 5.6–18 kDa fragments).Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization,including endothelial cell proliferation and migration,protease production,and apoptosis.However,their effects on vascular function and cardiovascular diseases are different or even contrary.In addition to the structure,secretion regulation,and signal transduction of PRL/vasoinhibins,this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Mechanism and Method of Testing Fracture Toughness and Impact Absorbed Energy of Ductile Metals by Spherical Indentation Tests

To address the problem of conventional approaches for mechanical property determination requiring destructive sampling, which may be unsuitable for in-service structures, the authors proposed a method for determining the quasi-static fracture toughness and impact absorbed energy of ductile metals from spherical indentation tests (SITs). The stress status and damage mechanism of SIT, mode I fracture, Charpy impact tests, and related tests were frst investigated through fnite element (FE) calculations and scanning electron microscopy (SEM) observations, respectively. It was found that the damage mechanism of SITs is diferent from that of mode I fractures, while mode I fractures and Charpy impact tests share the same damage mechanism. Considering the diference between SIT and mode I fractures, uniaxial tension and pure shear were introduced to correlate SIT with mode I fractures. Based on this, the widely used critical indentation energy (CIE) model for fracture toughness determination using SITs was modifed. The quasi-static fracture toughness determined from the modifed CIE model was used to evaluate the impact absorbed energy using the dynamic fracture toughness and energy for crack initiation. The efectiveness of the newly proposed method was verifed through experiments on four types of steels: Q345R, SA508-3, 18MnMoNbR, and S30408.

Biology and function of pericytes in the vascular microcirculation

Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Research on the Cultivation of Craftsmanship in Huang Yanpei’s Education Thought

Skilled talents are the main support for the strategic development of science and technology in China.The quality of talents is an important guarantee for the transformation and upgrading of national industries.By analyzing and studying Huang Yanpei’s thought on vocational education,this paper focuses on the cultivation of students’craftsmanship in vocational schools.First,we analyze the results of previous research and then elaborate on the connotations of Huang Yanpei’s education thought and craftsmanship spirit.Lastly,we propose five suggestions for the cultivation of craftsmanship.Our research work carries certain reference value to the study of craftsmanship cultivation in Huang Yanpei’s education thought.

Study on the Career Development of Young Teachers in Vocational Colleges

The quality of the teaching staff is crucial to the development of vocational education.Skilled and knowledgeable teachers can provide students with specialized technical knowledge and practical skills.In addition to teaching,teachers also act as mentors in providing guidance and support in all areas to students.However,the development of young teachers faces many problems,such as unclear career plans and a lack of attention to operational skills.This paper analyzes the research findings of past scholars and uses a questionnaire to analyze the problems faced by young teachers in their career development.Based on this,this paper puts forward some targeted suggestions,which can provide guidelines for the career development of young teachers.

Reflections on the Construction of“Double-Qualified”Teachers in Higher Vocational Colleges

Vocational education is an important part of the overall education system.The development of higher vocational education is one of the guiding principles of education in China.The development of teachers is an important support for the development of vocational education.Teachers who can teach theoretically and guide students in practical work are known as“double-qualified”teachers.Building a highly qualified and professional double-qualified teaching team is the fundamental task in modernizing vocational education.Firstly,this paper discusses the importance of“double-qualified”teachers by describing the relevant policies of the Ministry of Education in China.Secondly,it reviews the research works of early scholars.Thirdly,it analyzes the main problems of teacher training in higher education institutions.Fourthly,it proposes five suggestions for the development of a“double-qualified”teaching team in higher education institutions.A high level and professional teaching team is an important support for the high-quality development of vocational institutions.School leaders must attach great importance to the construction of a“double-qualified”teaching team and increase the support in terms of policies,institutional protection,and financial investment.

Enhancing Vocational Education through Innovative Skills Competitions: Challenges and Solutions

This study investigates the challenges encountered by vocational colleges when preparing for innovative skills competitions and proposes effective countermeasures.It highlights issues concerning students’motivation,limited financial resources and hardware,teacher capacity limitations,inadequate reward systems,and curriculum misalignment.Through meticulous research and analysis,this paper presents practical recommendations to mitigate these challenges.Suggestions encompass strategies to enhance students’motivation,increase financial support,provide professional development opportunities for teachers,revamp the reward system,and align the curriculum with competition requirements.By implementing these measures,vocational colleges can cultivate active student participation,elevate teaching quality,bridge the gap between education and industry demands,and equip students for success in innovative skills competitions.

Research on the Cultivation Path of Craftsmanship Spirit in Vocational Colleges: from the Perspective of Skills Competition

The spirit of craftsmanship is gaining increasing attention from both society and the education community.Along with professional knowledge,continuous research,and innovation have become decisive factors in determining the quality of products.In this context,vocational colleges strive to cultivate high-quality skilled talents,making the cultivation of craftsmanship spirit a crucial component of vocational education.This study explores the cultivation path of craftsmanship spirit through the lens of skills competitions,with a special emphasis on developing students’perseverance.The research conclusions of this article hold significant reference value for the implementation of vocational education policies.

The Role of Skills Competitions in Improving the Practical Ability of Vocational College Students

Vocational education and general education are two different types of education that are equally important.The orientation of talent training in vocational education is to nurture skilled talents to serve the society.The practical ability of students is both the focus of teaching in vocational colleges and the requirement of enterprise posts.The various types of skills competitions provide a“stage”for students to showcase their abilities.First,this paper explores students’problem-solving ability while preparing for these competitions,expounding the importance of vocational education and skills competitions.Second,this paper summarizes the views of different scholars.Third,based on a specific case,this paper describes the improvement in students’ability while preparing for these competitions.Fourth,this paper analyzes the results of the questionnaire survey conducted to investigate the improvement in students’ability.Lastly,this paper puts forward several suggestions that appeal for vocational colleges to pay more attention to skills competitions.

Challenges and Countermeasures in the Teaching of Engineering Mechanics in Vocational Colleges

Engineering mechanics is as a basic course,and the learning effect of this course directly affects the learning of subsequent professional courses.However,the teaching quality of engineering mechanics in vocational colleges has been subpar for a long time.In this study,we explored the teaching situation of engineering mechanics by using questionnaires,pointing out the challenges faced in the teaching of engineering mechanics and putting forward four targeted suggestions,which include stimulating students’interest and increasing the investment in laboratory equipment,to improve the teaching quality.The findings of this study may provide some reference for the teaching reform of engineering mechanics.

Research on the Cultivation Path of Craftsmanship Spirit Among Vocational College Students

With the continuous progress of science and technology,the speed of technology iteration in enterprise production line and the demand for comprehensive quality among workers are increasing.Companies not only require their employees to have excellent skills,but also require them to be rigorous and meticulous,possess excellence,and carry out continuous innovation of the craftsman spirit.The talent training goal in vocational colleges is to supply high-quality skilled talents to the society.Vocational colleges have an important duty to cultivate the spirit of craftsmanship in students through multiple paths.Through in-depth analysis of previous research results,we carried out a study on the cultivation path of craftsmanship spirit.The results of this study may provide reference for the development of moral education in vocational colleges.

Combined detection and subclass characteristics analysis of CTCs and CTECs by SE-iFISH in ovarian cancer

Objective:Hematogenous metastasis is essential for the progression of ovarian cancer(OC),and circulating tumor cells(CTCs)are part of the metastatic cascade.However,the detection rate of CTC is low due to the use of less sensitive detection methods.Therefore,this study aimed to detect CTCs and circulating tumorigenic endothelial cells(CTECs)in patients with OC using subtraction enrichment and immunostaining and fluorescence in situ hybridization(SE-iFISH).Methods:We enrolled a total of 56 subjects,including 20 OC patients and 36 ovarian benign tumor patients.CTCs and CTECs were captured by subtraction enrichment(SE)and counted and classified according to immunofluorescence staining of tumor markers(TMs)carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)combined with fluorescence in situ hybridization(iFISH)of chromosome 8(Chr8)aneuploidy.The diagnostic value and subtype characteristics of CTCs and CTECs were investigated.Results:The detection rate of CTCs by SE-iFISH was high.Compared with CA125 and HE4,Chr8 aneuploidy was the major identification feature of CTC.CTC counts in OC were statistically higher than those in benign groups.CTC and CTEC with≥pentaploidy were detected in both groups,illustrating the poor diagnostic value of CTC or CTEC.Distributions of triploid and tetraploid CTC subtypes were significantly different,and combined detection of triploid and tetraploid CTCs showed the best diagnostic value.In contrast,the distribution of CTECs in the OC and benign groups had no statistically significant difference.Small CTCs accounted for over 1/3 of the total CTC count.We also found that small CTCs and CTECs primarily comprised triploid cells,while large CTCs and CTECs mainly comprised pentaploidy and beyond.Conclusions:The application of SE-iFISH offered a more comprehensive understanding of heterogeneous CTCs and CTECs in OC.Analysis of subclass characteristics of the CTCs and CTECs according to Chr8 aneuploidy and cell size may broaden their potential clinical utility and deepen mechanistic studies in OC.

Circular RNA circStag1 promotes bone regeneration by interacting with HuR

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of BMSCs.Furthermore,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized rats.Collectively,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

Diversity of microbial plankton across the Three Gorges Dam of the Yangtze River,China

The Three Gorges Dam （TGD） of the Yangtze River, China, is one of the largest irrigation and hydroelectric engineering projects in the world. The effects of huge man-made projects like TGD on fauna and macrophyte are obvious, mainly through changes of water dynamics and flow pattern; however, it is less clear how microorganisms respond to such changes. This research was aimed to examine differences in microbial diversity at different seasons and locations （in front of and behind the TGD）. In addition, differences between particle-attached and free-living communities were also examined. The community structures of total and potentially active microorganisms in the water columns behind and in front of the TGD were analyzed with the DNA- and RNA-based 16S rRNA gene phylogenetic approaches over three different seasons. Clone libraries of 16S rRNA genes were prepared after ampli- fication from extracted DNA and, for some samples, after preparing cDNA from extracted rRNA. Differ- ences were observed between sites at different seasons and between free-living and particle-attached communities. Both bacterial and archaeal communities were more diverse in summer than in winter, due to higher nutrient levels and warmer temperature in summer than in winter. Particle-attached micro- organisms were more diverse than free-living communities, possibly because of higher nutrient levels and heterogeneous geochemical micro-environments in particles. Spatial variations in bacterial community structure were observed, i.e., the water reservoir behind the TGD （upstream） hosted more diverse bacte- rial populations than in front of the dam （downstream）, because of diverse sources of sediments and waters from upstream to the reservoir. These results have important implications for our understanding of responses of microbial communities to environmental changes in river ecosystems affected by dam construction.

Arterial and venous thromboembolism risk associated with blood eosinophils: A systematic review and meta-analysis

The association between blood eosinophil(EOS)counts and arterial/venous throm-bosis is unclear.We aim to explore whether EOS count is a risk factor for throm-bosis.We searched several databases and preprint platforms using core terms‘eosinophil’,‘myocardial infarction’,‘ischemic stroke’,and‘venous thromboembo-lism’(VTE),among others.Studies comparing the odds ratios(ORs)or risk ratios(RRs)of EOSs with the abovementioned diseases were eligible.Overall,22 studies were included.A high EOS count was associated with acute coronary artery throm-bosis events(OR:1.23,95%CI:1.15-1.32),short-term cerebral infarction and mor-tality(RR:2.87,95%CI:1.49-5.51).The short-term risk of VTE was more common in patients with EOS-related diseases(RR:6.52,95%CI:2.42-17.54).For coronary artery disease,a high EOS count was a protective factor against 6-month to 1-year mortality(RR:0.56,95%CI:0.45-0.69)but was associated with long-term mortal-ity(RR:1.64,95%CI:1.25-2.14).Therefore,we conclude that for coronary artery thrombosis,EOS count is not associated with AMI events in general population.It may be associated with NSTEMI and STEMI in CAD patients,but more studies are needed to confirm this.In addition,EOS count is associated with an increased risk of both short-and long-term mortality but is not predictive of the composite end-points.For cerebral artery thrombosis,EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short-term prognosis.For VTEs,EOS count was a risk factor for some patients,especially those with acute-phase EOS-related diseases.

High-efficiency extraction synthesis for high-purity copper nanowires and their applications in flexible transparent electrodes

Copper nanowires(Cu NWs)are considered an excellent alternative to indium tin oxide(ITO)in flexible transparency electrodes(FTEs).However,the mixed particles and surface oxidation of Cu NWs degrade the transmittance and conductivity of the electrodes.Therefore,highly purified Cu NWs without oxidation are vital for high-performance FTEs.Herein,a facile and effective purification process is introduced to purify Cu NWs in a water and n-hexane system,which takes advantage of the differences in hydrophilicity between Cu NWs and Cu NPs caused by their different adsorption affinities to octadecylamine(ODA).At the same sheet resistance,the transmittance of the purified Cu NW-based FTEs improved approximately 2%compared to that of non-purified Cu NW-based FTEs.Immersion of the electrode in glacial acetic acid removed the surface organics and oxides.After only 40 s of treatment,the sheet resistance dramatically decreased from 10^5 Ohm/sq to 31 Ohm/sq with a transmittance of 85%.In addition,the Cu NW-based FTE conductors showed excellent flexibility(remaining stable after 1000 bending cycles).The Cu NW-based FTEs were further applied to fabricate a flexible transparent heater.At a voltage of 10 V,the temperature of the heater reached 73℃,demonstrating the potential applications of this material in various fields.