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Skeletal muscle development is closely related with the amount of meat production and its quality in chickens. Natriuretic peptides (NPs) play an important role in myotube formation and fat oxidation of skeletal muscle in animals. The effect of C-type natriuretic peptide (CNP), an important member of the NPs, and its underlying molecular mechanisms in skeletal muscle are incompletely understood. Treatment of myoblasts with CNP led to enhanced proliferation/differentiation and significantly upregulated (P

Abstract We investigate the gauge invariance and localization of vector KK modes for a bulk U(1) gauge field under three kinds of localization mechanism on a brane with one extra dimension. By a general KK decomposition for the bulk U(1) gauge field, there are both vector and scalar KK modes on the brane, which couple with each other. We demonstrate that for a localization mechanism with a gauge invariant bulk action of the U(1) gauge field, the effective action of the KK modes on the brane can be formalized to gauge invariant form. However, only the massive vector KK modes and their accompanying scalar ones can be both localized on the brane, which depends on the solution of the brane, the gauge invariance of the massive vector field is finally preserved. For a localization mechanism with a broken gauge invariant bulk action of the field, it is impossible to rebuild the gauge invariance on the brane.

Objective To investigate the effects of eukaryotic elongation factor-2 kinase (eEF2K) gene transfection and sodium tanshinone Ⅱ A sulfonate (STS) on proliferation, invasion and migration of lung adenocarcinoma cell line A549 and its mechanism. Methods The optimal concentration of STS was screened out by preliminary experiment. A549 cells were divided into siRNA-NC group (transfected with siRNA-NC), siRNA-eEF2K group (transfected with siRNA-eEF2K), siRNA-NC+STS group (treated with 10 μg/mL STS after siRNA-NC) and siRNA-eEF2K+STS group (treated with 10 μg/mL STS after siRNA-eEF2K).The survival rate, clone formation, cell counting of transmembrane cells, migration and apoptosis of A549 cells were detected by CCK-8 method, clone formation test, Transwell chamber test, scratch test and flow cytometry. The protein expression levels of protein kinase B (AKT), phosphorylation (p)-AKT, Ki67, matrix metalloproteinase-2 (MMP-2) and B-cell lymphoma-2 genes (Bcl-2) were detected by Western blot. Results Compared with those in siRNA-NC group, the cell survival rate, clone formation rate, number of transmembrane cells, migration rate and p-AKT, Ki67, MMP-2 and Bcl-2 in proteins siRNA-eEF2K+STS group were significantly lower, while the apoptosis rate was significantly higher (P＜0.05). The siRNA-eEF2K+STS group had the largest range of changes in the above indexes. Conclusions Silencing eEF2K combined with STS can synergistically inhibit the proliferation, invasion and migration of A549 cells and promote cell apoptosis. The mechanism is potentially related to the inhibition of protein expression of p-AKT, Ki67, MMP-2 and Bcl-2.

Atmospheric and room temperature plasma(ARTP) Bacillus cereus was used to screen the strains with increased enzyme activity. The results showed that culturing Bacillus cereus in the seed solution for 6 hours could reach the middle and late logarithmic phase. When the mutagenesis time of normal temperature and atmospheric pressure plasma was 60 s, the lethality of Bacillus cereus reached 85%. A mutant strain with a 13.19% increase in chitosanase activity was screened. Then the stability of the enzyme activity was verified. The average enzyme activity after six generations of culture was 9.643367 U/mL, and the fluctuation was within 5%, indicating that its enzyme production was high and the stability was strong, and it could be used for subsequent starting strains. After the mutagenesis, the strain was observed by electron microscope, and it was found that the morphology of the colony did not change significantly, but the individual morphology of the strain had changed, and it was slenderer than the original strain, which proved that the increase in enzyme activity was the effect of ARTP mutagenesis.

Organoid modeling is a powerful, robust and efficient technology faithfully preserving physiological and pathological characteristics of tissues of origin. Recently, substantial advances have been made in applying genetically engineered organoid models to study early tumorigenesis and premalignant biology. These efforts promise to identify novel avenues for early cancer detection, intervention and prevention. Here, we highlight significant advancements in the functional characterization of early genomic and epigenomic events during neoplastic evolution using organoid modeling, discuss the application of the lineage-tracing methodology in organoids to study cancer cells-of-origin, and review future opportunities for further development and improvement of organoid modeling of cancer precursors.

The soil-borne necrotrophic fungus Rhizoctonia solani is one of destructive fungi causing severe yield losses in various important crops. However, the host defense mechanisms against the invasion of this pathogen are poorly understood. In this study, we employed an iTRAQ-based quantitative proteomic approach to investigate host proteins responsive to R. solani using the resistant rice cultivar YSBR1. As a whole, we identified 319 differentially accumulated proteins (DAPs) after inoculation of rice plants with R. solani. Functional categorization analysis indicates that these DAPs cover a broad range of functions. Notably, a substantial portion of the DAPs are involved in cell redox homeostasis, carbohydrate metabolism, and phenylpropanoid biosynthesis, or belong to pathogenesis-related proteins, indicating that these processes/proteins play important roles in host defense against R. solani. Interestingly, all of the DAPs involved in photosynthesis and chlorophyll biosynthetic processes, and part of the DAPs involved in phenylpropanoid biosynthesis, show reduced accumulation after R. solani infection, suggesting that R. solani probably inhibits host photosynthetic system and phenylpropanoid biosynthesis to facilitate infection and colonization. In conclusion, our results provide both valuable resources and new insights into the molecular mechanisms underlying rice and R. solani interaction.

Genetic linkage maps are important for quantitative trait locus (QTL) and marker-assisted selection breeding. The wolfberry (Lycium spp.) is an important food and traditional medicine in China. However, few construction genetic linkage maps have been reported because of the lack of genomic and genetic resources. In this study, a population of 89 F1 seedings was derived from a cross between two heterozygous parents, L. chinense var. potaninii ‘BF-01’ (female) and L. barbarum var. auranticarpum ‘NH-01’ (male), in order to construct a genetic linkage map using simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers based on the double pseudo-test cross mapping strategy. The resulting genetic map consisted of 165 markers (74 AFLPs and 91 SSRs) distributed across 12 linkage groups and spanned a total length of 557.6 cM with an average distance of 3.38 cM between adjacent markers. The 12 linkage groups contained 3 to 21 markers and ranged in length from 8.6 to 58.3 cM. Twenty-nine segregated markers distributed in the map were mainly located on LG4 and LG9 linkage groups at P

Abstract Background Body composition alterations may participate in the pathophysiological processes of type 2 diabetes (T2D). A sedentary lifestyle may be responsible for alterations of body composition and adverse consequences, but on which body composition of patients with T2D and to what extent the sedentary lifestyle has an effect have been poorly investigated. Methods We recruited 402 patients with T2D for this cross-sectional study. All patients received questionnaires to evaluate sedentary time and were further divided into three subgroups: low sedentary time (LST, 8 h, n = 164). Each patient underwent a dual energy X-ray absorptiometry (DXA) scan to detect body composition, which included body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD) and total BMD (T-BMD). Other relevant clinical data were also collected. Results With increasing sedentary time (from the LST to HST group), B-FAT and T-FAT were notably increased, while ASMI, LS-BMD, FN-BMD, H-BMD and T-BMD were decreased (p for trend

Abstract Background Diabetic kidney disease (DKD) is a significant complication of diabetes and has garnered considerable attention. Our previous retrospective study indicated that Shenzhuo formula (SZF) potentially reduces macroalbuminuria secondary to DKD. Methods This trial is a 24-week, randomized, multicentric, double-blinded, double-dummy clinical trial. A total of 120 patients with DKD will be equally and randomly divided into two groups: SZF+ irbesartan simulator or irbesartan + SZF simulator. The 24-h urinary protein change from baseline to week 24 is the primary outcome measure. The secondary outcome measures include serum creatinine, estimated glomerular filtration rate, urinary albumin excretion rate, improvement in traditional Chinese medicine symptoms, fasting blood glucose, 2-h postprandial plasma glucose, hemoglobin A1c, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, blood pressure, albumin to creatinine ratio, and the Audit of Diabetes-Dependent Quality of Life 19. Our recruitment began in May 2015; currently, we have recruited 100 participants, with a designed maximum sample size of 120. The interim results were reviewed at N = 60, and continuing recruitment was recommended. This statistical analysis plan includes our approach to missing data imputation, primary and secondary outcomes analyses, and safety endpoints. Discussion This statistical analysis plan will standardize the clinical trial’s statistical analysis and avoid outcome selective reporting bias and data-driven analysis. This trial will provide further clinical evidence regarding the effectiveness of SZF in managing macroalbuminuria secondary to DKD. Trial registration Chinese Clinical Trial Registry ChiCTR-ICR-15006311. Registered on 26 May 2013. http://www.chictr.org.cn/showproj.aspx?proj=10862

Abstract Background Plasma 1,5-anhydro-d-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia. Methods We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c

Background & Aims: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. Methods: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii–derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. Results: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid β-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii–derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. Conclusions: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.

BackgroundSuicide is the fourth leading cause of death for adolescents, and globally, over 75% of completed suicides occur in low- and middle-income countries (LMICs). Bullying has been proven to be closely related to suicide attempts. However, further understanding of the mechanisms underlying the relationship between bullying and adolescents' suicide attempts is urgently needed.MethodsWe used data from the Global School-based Student Health Survey (GSHS) (2010–2017) from 41 LMICs or regions. This study was based on questions assessing bullying victimization, suicide attempts, sleep deprivation, and body mass. Chi-square tests were used to explore the correlations among the main variables. The mediating role of sleep deprivation and the moderating role of body mass index (BMI) were analyzed using PROCESS.ResultsThe results showed a positive association between bullying victimization and suicide attempts. Sleep deprivation partially mediated the relationship between the frequency of being bullied and suicide attempts. In addition, sleep deprivation played a full or partial mediating role in the relationship between different types of bullying and suicide attempts. BMI moderated the relationships between the frequency of being bullied and suicide attempts, between being made fun of about one's body and sleep deprivation, and between sleep deprivation and suicide attempts.ConclusionBeing bullied has a positive effect on suicide attempts, which is mediated by sleep deprivation and moderated by body mass. The results of this study are consistent with the stress-diathesis model of suicide, suggesting that being bullied is one of the stressors of suicide in adolescents, while sleep deprivation and body mass are susceptibility diatheses of suicide. The results are conducive to identifying adolescents at a high risk of suicide, suggesting that there is a need to pay more attention to bullied adolescents, especially their sleep quality and body mass, and design effective intervention measures to improve the current situation of adolescent suicide in LMICs.

The failure mode of cement-augmented pedicle screw (CAPS) was different from common pedicle screw. No biomechanical study of this failure mode named as “reversed windshield-wiper effect” was reported. To investigate the mechanisms underlying this failure mode, a series of finite element models of CAPS and PS were modified on L4 osseous model. Nine models were created according to the cement volume at 0.5 mL interval (range: 1–5 mL). Pullout load and cranio-caudal loads were applied on the screws. Stress and instantaneous rotation center (IRC) of the vertebra were observed. Under cranio-caudal load, the stress concentrated on the screw tip and pedicle region. The maximal stress (MS) at the screw tip region was +2.143 MPa higher than pedicle region. With cement volume increasing, the maximal stress (MS) at the screw tip region decreased dramatically, while MS at pedicle region was not obviously affected. As dose increased to 1.5 mL, the MS at pedicle region became higher than screw tip region and the maximal stress difference was observed at 3.5 mL. IRC of the vertebra located at the facet joint region in PS model. While IRC in CAPS models shifted anteriorly closer to the vertebral body with the increasing of cement volume. Under axial pull-out load, the maximal stress (MS) of cancellous bone in CAPS models was 29.53–50.04% lower than that 2.228 MPa in PS model. MS in the screw-bone interface did not change significantly with cement volume increasing. Therefore, the possible mechanism is that anterior shift of IRC and the negative difference value of MS between screw tip and pedicle region due to cement augmentation, leading to the screw rotate around the cement-screw complex as the fulcrum point.

Though numerous empirical and theoretical studies have been conducted on the determinants and effects of executive compensation, empirical evidence regarding the bargaining effect on the monetary compensation decisions of executives, especially in a large emerging economy such as China, remains scarce. In this study, a two-tier stochastic frontier and endogenous correction model was developed to quantitatively estimate the bargaining effect on the monetary compensation decisions of investment bank executives. Our study is the first to provide comprehensive empirical evidence that bargaining between investment banks and executives in China significantly affects the compensation decisions of executives. In the bargaining process, investment banks are more proficient than executives, and the comprehensive bargaining effect tends to lower the negotiated compensation of executives. The bargaining effect exhibited obvious heterogeneity in the characteristics of executives and investment banks. When these characteristics tend to augment the bargaining power of executives, the negotiated compensation exhibits a limited decrease; when these characteristics augment the bargaining power of investment banks, the negotiated compensation decreases substantially. Our results provide deep insight into factors that determine executive compensation and help compensation designers of investment banks better understand and design executive pay packages.

L-theanine, a characteristic non-protein amino acid first extracted from green tea leaves, has multiple biological functions, including antioxidant, immune and anti-inflammatory functions. However, the effect of L-theanine on intestinal barrier function of piglets remains unclear. This study aimed to investigate the role and underlying molecular mechanism of L-theanine in tight junction protein expression and intestinal mucosa inflammation in weaned piglets. Our data showed that L-theanine increased the expression of zonula occludens 1, claudin 1 and occludin in jejunum and ileum of piglets. In addition, L-theanine inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6 and Toll-like receptor 4 (TLR4) and the protein expressions of TNF-α, phospho-p38 MAPK (mitogen-activated protein kinase), phospho-IĸB and nuclear NF-ĸB (nuclear factor-ĸB) p65. Taken together, our results indicated that L-theanine could improve intestinal barrier function in weaned piglets, and the effect might be mediated through inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway.

ABSTRACTIonic liquids (ILs) have been widely explored as alternative solvents for carbon dioxide (CO2) capture and utilization. However, most of these processes are under pressures significantly higher than atmospheric level, which not only levies additional equipment and operation costs, but also makes the large-scale CO2 capture and conversion less practical. In this study, we rationally designed glycol ether-functionalized imidazolium, phosphonium and ammonium ILs containing acetate (OAc–) or Tf2N– anions, and found these task-specific ILs could solubilize up to 0.55 mol CO2 per mole of IL (or 5.9 wt% CO2) at room temperature and atmospheric pressure. Although acetate anions enabled a better capture of CO2, Tf2N– anions are more compatible with alcohol dehydrogenase (ADH), which is a key enzyme involved in the cascade enzymatic conversion of CO2 to methanol. Our promising results indicate the possibility of CO2 capture under ambient pressure and its enzymatic conversion to valuable commodity.

Oil and gas pipelines are one of the main means for oil and gas transportation over the world, and the development trend of their planning and construction is mainly affected by the development of oil and gas resources, as well as the national and regional energy policies. By quantitative and qualitative information mining, the global energy consumption structure and pipeline construction development in 2020 were sorted out, the current operation status of global oil and gas pipelines was analyzed, and the construction and development trend of global oil and gas pipelines in major regions of the world under the new situation was predicted. In the future, the construction of global oil and gas pipelines will be mainly affected by three factors: economy, politics and environment. It is predicted that the overall construction of global oil and gas pipelines will tend to be stable in recent years. Affected by the international environment, the construction progress of transnational pipelines is uncertain to a large extent, and fewer transnational pipelines can be completed and put into service on schedule. Besides, the pipeline construction in each country mainly depends on the economic development situation thereof. However, due to the dual impact of the economic downturn under the global COVID-19 pandemic and the energy transition under the guidance of "carbon peaking and carbon neutrality", it is expected that the local pipeline construction in the world will be concentrated in Asia-Pacific Region in the future. Meanwhile, the European and American countries and regions will explore to construct new hydrogen-mixed natural gas transportation pipelines or reconstruct existing gas pipelines for hydrogen-mixed natural gas transportation.(5 Figures, 3 Tables, 31 References)

Dipteris shenzhenensis, a new species of ferns from Shenzhen, Guangdong, southern China, is identified and described. It closely resembles D. chinensis but possesses several unique traits, such as long rhizome scales, castaneous stipe, and abaxially pale fronds with two fan-shaped fronds connected by a broad wing. Molecular evidence showed that D. shenzhenensis is allied to D. conjugata, whereas it has morphologically significant differences (P < 0.05) on the basis of quantitative trait statistical analysis. Overall, the morphological evidence, taken together with the result of cpDNA indicated that D. shenzhenensis is a distinct species.

Abstract Background Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. Methods We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff) was used to estimate the transmission interaction in different age groups. Results A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff = 4.28), followed by group 2 to 3 (R eff = 2.61), and group 2 to 4 (R eff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45–64 years old. Conclusions Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15–64 years should first be vaccinated to prevent transmission in China. Graphical Abstract

Abstract Background Management of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remains a clinical challenge. Currently, riociguat, a soluble guanylate-cyclase stimulator is recommended by international guidelines. More recently, balloon pulmonary angioplasty (BPA) develops as an alternative treatment for inoperable CTEPH. Method This study is a single-center randomized controlled trial. Subjects with inoperable CTEPH are randomized into either a BPA combined with riociguat or riociguat monotherapy group (2:1) and observed for 12 months after initiation of treatment. The primary endpoint is the change in pulmonary vascular resistance from baseline to 12 months after initiation of treatment. The secondary endpoints include 6-min walk distance (6MWD), WHO-FC, NT-proBNP, SF-36, and other hemodynamic parameters. Safety endpoints are analyzed too. Discussion This study aims to compare the efficacy and safety of BPA combined with riociguat and riociguat monotherapy for inoperable CTEPH. Trial registration Chinese Clinical Trial Registry ChiCTR2000032403 . Registered on 27 April 2020.

With the development of network virtualization technology,the deployment of service function chain in multi-domain network brings new challenges to the optimization of service function chain.The traditional deployment method usually optimizes a single target,which is not suitable for multi-objective optimization,and cannot measure and balance the weight among optimization targets.Therefore,in order to optimize the delay,network load balancing and acceptance rate of large-scale service function chain deployment requests synchronously,a data normalization processing scheme is proposed,and a two-step SFC deployment algorithm based on reinforcement learning is designed.The algorithm takes transmission delay and load balancing as feedback parameters and balances the weight relationship between them,and the SFC acceptance rate is optimized by using reinforcement learning framework simultaneously.The experimental results show that,the delay of the algorithm is reduced by 71.8% compared with LASP method,the acceptance rate is increased by 4.6% compared with MDSP method,and the average load balancing is increased by 39.1% compared with GREEDY method under the large-scale requests.The multi-objective optimization effect is guaranteed.

Introduction: MicroRNA (miR)-185-3p functions in multiple cancers, while the underlying function of miR-185-3p in hyperlipidemia remained obscure. This research was conducted to unravel its function in hyperlipidemia development via modulating mastermind-like 1 (MAML1). Methods: The hyperlipidemia rat model was established by feeding with high fat diet. MiR-185-3p and MAML1 levels in hyperlipidemia rats were detected. Adenoviral vectors altering miR-185-3p and MAML1 levels were injected into hyperlipidemia rats to examine the levels of serum lipids, oxidative stress, inflammatory cytokine, lipid accumulation and cellular morphology in liver tissues of hyperlipidemia rats. The targeting relation between miR-185-3p and MAML1 was manifested. Results: MiR-185-3p expressed at a low level while MAML1 expressed at high level in hyperlipidemia rats. MiR-185-3p overexpression or MAML1 silencing reduced levels of serum lipids, mitigated oxidative stress and inflammatory response, relieved lipid accumulation and pathological morphology in liver tissues in hyperlipidemia rats; while up-regulated MAML1 reversed the effects of augmented miR-185-3p in hyperlipidemia rats. Mechanically, miR-185-3p targeted MAML1. Conclusion: Up-regulated miR-185-3p represses hyperlipidemia development via modulating MAML1 expression. This research provides novel therapeutic candidates for the treatment of hyperlipidemia.

ObjectiveWhether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS.MethodsWe conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients.ResultsExercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival.ConclusionExercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.

BackgroundThere is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan.MethodsWe retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival.ResultsNine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, P < 0.00001, I2 = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, P = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated.ConclusionThe switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].

In this work, we investigate the radiation damage of 6H-SiC crystals by phosphorus (P) ion implantation. The 6H-SiC samples were implanted at different energy with the same fluence of 5.0 × 1014 ions/cm2 at room temperature, one of which was subsequently annealed. Raman and absorption spectra were obtained to probe the structure and optical properties of 6H-SiC crystals after P ion implantation. In addition, Rutherford backscattering/channeling spectroscopy and transmission electron microscopy were used to explore further the damage behavior at different implantation energy and damage evolution with post-annealing treatment. It was found that the damage of the 200 keV implanted sample partially recovered after annealing at 600 °C for 60 min and disappeared at an annealing temperature of 800 °C. The damage evolution behavior of phosphorus ions implantation into 6H-SiC crystals with different implantation and annealing conditions is presented in our work.

Purpose: To investigate the prognostic value and function of six-transmembrane epithelial antigen of prostate 1 (STEAP1) in osteosarcoma and determine whether EFEMP1 mediates its effects. Methods: IHC (immunohistochemistry)/ICC (immunocytochemistry) in conjunction with RT-qPCR (quantitative real-time polymerase chain reaction) were employed to assess the expression of STEAP1 in paratumoral tissues, osteosarcoma, benign fibrous dysplasia, osteosarcoma cells, normal osteoblastic hFOB cells, as well as various invasive subclones. The association of STEAP1 with outcome was examined with Kaplan–Meier graph among the osteosarcoma population. The effects of the down-regulation and up-regulation of STEAP1 on the biological behavior of osteosarcoma cells were studied through in-vitro and in-vivo functional tests. Results: Up-regulation of STEAP1 in the osteosarcoma tissues, whose correlations with the malignant osteosarcoma phenotype and the poor patient outcome were positive. In addition, STEAP1 induced the epithelial–mesenchymal transition (EMT) via the Wnt/β-catenin and TGF-β/Smad2/3 pathways and facilitated the osteosarcoma cell infiltration and migration. An increase or decrease in EFEMP1 expression directly promoted or inhibited the expression of STEAP1. In osteosarcoma cells overexpressing EFEMP1, STEAP1 knockdown significantly inhibited cell invasion, EMT process, and increased activity of Wnt/β-catenin and TGF-β/Smad2/3 signaling pathways. Although exogenous EFEMP1 could stimulate the Wnt/β-catenin and TGF-β/Smad2/3 pathways to promote the EMT, it had not effect on osteosarcoma cells with STEAP1 knockdown. Collectively, similar to EFEMP1, STEAP1 acted like an oncogene in the osteosarcoma progression. Conclusion: EFEMP1 enabled the Wnt/β-catenin and TGF-β/Smad2/3 axises initiation and EMT elicitation by targeting STEAP1, thereby facilitating the osteosarcoma cell infiltration and migration. These results are expected to contribute to the search for new targeted drugs able to effectively inhibit invasion and metastasis and improve prognosis in osteosarcoma.

Abstract. Staphylococcus hominis is a component of the normal human microflora and is considered to be an opportunistic pathogen that may cause a variety of infections. It has been reported to cause bacteremia, endocarditis and endophthalmitis. However, abscesses caused by S. hominis are rarely documented. Here, we describe a case of pyogenic liver abscesses caused by S. hominis. Laboratory tests, imaging examinations, and abscess puncture fluid culture were used to identify the etiology and pathogenic bacterium. This case suggests that percutaneous drainage and targeted antibiotic treatment according to the results of antimicrobial susceptibility tests are effective therapeutic approaches for pyogenic liver abscesses caused by S. hominis.

Abstract Mesenchymal stem/stromal cell (MSC)-based therapeutics is already available for treatment of a range of diseases or medical conditions. Autologous or allogeneic MSCs obtained from self or donors have their own advantages and disadvantages in their medical practice. Therapeutic benefits of using autologous vs. allogeneic MSCs are inconclusive. Transplanted MSCs within the body interact with their physical microenvironment or niche, physiologically or pathologically, and such cells in a newly established tissue microenvironment may be impacted by the pathological harmful environmental factors to alter their unique biological behaviors. Meanwhile, a temporary microenvironment/niche may be also altered by the resident or niche-surrounding MSCs. Therefore, the functional plasticity and heterogeneity of MSCs caused by different donors and subpopulations of MSCs may result in potential uncertainty in their safe and efficacious medical practice. Acknowledging a connection between MSCs’ biology and their existing microenvironment, donor-controlled clinical practice for the long-term therapeutic benefit is suggested to further consider minimizing MSCs potential harm for MSC-based individual therapies. In this review, we summarize the advantages and disadvantages of autologous vs. allogeneic MSCs in their therapeutic applications. Among other issues, we highlight the importance of better understanding of the various microenvironments that may affect the properties of niche-surrounding MSCs and discuss the clinical applications of MSCs within different contexts for treatment of different diseases including cardiomyopathy, lupus and lupus nephritis, diabetes and diabetic complications, bone and cartilage repair, cancer and tissue fibrosis.

Tertiary lymphoid structures (TLSs) are ectopic immune cell aggregations that develop in peripheral tissues in response to a wide range of chronic inflammatory conditions, including infection, autoimmune disease, and cancer. In the tumor microenvironment (TME), the structures of TLSs, including B-cell- and T-cell-enriched areas indicate that the TLSs might be the local site during the initiation and maintenance of humoral and cellular immune responses against cancers. Numerous studies have evaluated the expression of TLSs in different cancer patients and their association with prognoses of cancer patients. It was shown that well-developed TLSs characterized by mature B cells synthesized tumor specific antibodies, which were considered as specific markers for a good prognosis. However, there are still some immunosuppressive factors existing in the TLSs that may affect anti-tumor responses. These factors include dysfunctional B cells, regulatory T cells, and T follicular regulatory cells. The complexity and heterogeneity of the TLS composition may affect the function and activity of TLSs; it is therefore essential to fully understand the function and influencing factors in TLSs. It has been reported that checkpoint inhibitors and vaccines are currently being developed to reprogram the TME by establishing mature TLSs to improve cancer immunotherapies. In this review, we focused on recent advances in TLSs in human solid tumors, including structural characteristics and classes, antitumor mechanisms, immunosuppressive factors, and TLS-based therapeutic approaches.

Background Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. Methods Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR

Abstract In this paper, we consider the imbedding of the popular and well-motivated trimaximal mixing and μ–τ reflection symmetry (which can help us shape the forms of the neutrino mass matrix) in the minimal seesaw model (which contains much fewer parameters than the general seesaw model) with two TeV-scale right-handed neutrinos (for realizing a low-scale seesaw) of nearly degenerate masses (for realizing a resonant leptogenesis). However, either for the trimaximal mixing scenario (which is realized through the Form Dominance approach here) or for the μ–τ reflection symmetry scenario, leptogenesis cannot proceed. To address this issue, we consider the possibility that the special forms of the neutrino mass matrix for the trimaximal mixing and μ–τ reflection symmetry are slightly broken by the renormalization group evolution effect, thus allowing leptogenesis to proceed. It is found that in the normal case of the neutrino mass ordering, the baryon asymmetry thus generated can reproduce the observed value. For completeness, we have also extended our analysis to the scenario that two right-handed neutrinos are not nearly degenerate any more. Unfortunately, in this scenario the final baryon asymmetry is smaller than the observed value by several orders of magnitude.

Abstract. Background:. Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). Methods:. One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran–Mantel–Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. Results:. At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [−4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P 0.05). Conclusions:. The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

In order to solve the traditional A* algorithm is not taken into account when planning path obstacle distribution on the influence of the path selection,this paper puts forward an improved A* algorithm,the artificial potential field of thought and the traditional A* algorithm,the combination of the obstacles in grid map gives repulsive force function and the repulsive force around the grid size calculation,in order to improve the searching ability of A* algorithm,the repulsive force of the grid is introduced into the evaluation function of A* algorithm.The results of MATLAB simulation and Turtlebot experiments show that,compared with the traditional A* algorithm,the new improved algorithm combined with artificial potential field algorithm can plan a better path,improve the efficiency of path planning,and increase the search speed by 13.40%~29.68%.The path length is shortened by 10.56%~24.38%,and the number of path nodes is reduced by 6.89%~27.27%.The experimental results show that the improved A* algorithm has obvious optimization effect and is effective and feasible.

Sugar is an important material basis in fruit development, and strawberry fruit flavour and sweetness largely depend on the sugar content and variety. Invertases (INVs) play an important role in the regulation of sugar accumulation because they irreversibly catalyse the hydrolysis of sucrose into the corresponding nucleoside diphosphate-glucose, glucose or fructose in fruit. In this work, we provided a comprehensive analysis of the INV gene family in octoploid strawberry (Fragaria×ananassa), including the gene structure, chromosomal locations, conserved domains, and gene evolution and expression profiles during strawberry fruit development. Our study revealed that polyploid events resulted in the abundant amplification (almost three- or four-fold) of the INV gene in the F.×ananassa genome, and these amplified INV genes showed dominant expression in strawberry fruit. More than half of the FaINVs transcripts with low expression had incomplete coding sequences by alternative splicing. Previous studies have shown that cell wall invertases (CWINV) are involved in the regulation of phloem unloading and sink strength establishment. The expression of FaCWINV1 was markedly upregulated during fruit development and strongly expressed in ripe fruit. Moreover, a significant correlation was observed between the total sugar content and the FaCWINV1 expression level. These findings suggest that FaCWINV1 may be involved in sugar accumulation in strawberry fruit. Taken together, the results of our study will be beneficial for further research into the functions of INVs in the regulation of fruit ripening.

AIM: To evaluate the efficacy of pars plana vitrectomy combined with internal limiting membrane(ILM)insertion for the treatment of refractory macular holes(MH)by spectral-domain optical coherence tomography(SD-OCT). METHODS: Retrospective analysis was conducted in 17 patients(17 eyes)with refractory MH from July 2019 to December 2020. All patients were treated with pars plana vitrectomy combined with ILM insertion. Preoperative and postoperative best corrected visual acuity(BCVA)were compared. Quantified evaluation of the postoperative macular restoration was performed by SD-OCT. RESULTS: The widths of ellipsoid zone disruption were 839.00-1577.50μm, with an average of 1182.90±226.68μm. During the follow-up period(3-12mo), 17 cases achieved successful closure(100%), and no recurrence was seen. Postoperative BCVA was significantly improved compared with preoperative(P

Abstract Remarkable spots and lines were clearly observed at the two interfaces of indium-tin-oxide coated Z-cut Fe-doped lithium noibate plates under illumination by milliwatt continuous-wave laser light; this occurred because of the visible surface plasmons (SPs) supported by the promising non-metal plasmonic system. The intriguing observations are here explained via the SP-strengthened nonlinear effect, through consideration of the electrostatic field (which is comparable to the atomic field) and its large gradient; this hints at a promising, highly sensitive plasmonic system. The gigantic nonlinear effect discussed in this paper should be ubiquitously existed in many oxide ferroelectric/semiconductor combinations and is promising for visible plasmonic applications.

Abstract It has been well-known that built environment features influence the risk of chronic diseases. However, the existing data of its relationship with telomere length, a biomarker of biological aging, is still limited, with no study available for Mexican Americans. This study investigates the relationship between several factors of the built environment with leukocyte telomere length among 5508 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the quartile levels of telomere length, the study population was categorized into four groups, from the lowest (1st quartile) to the highest telomere length group (4th quartile). For individual built environment factors, their levels did not differ significantly across four groups. However, in the multinominal logistic regression analysis, increased Rundle’s land use mixture (LUM) and Frank’s LUM were found statistically significantly associated with increased odds of having high levels of telomere length (Rundle’s LUM: 2nd quartile: Odds ratio (OR) 1.26, 95% Confidence interval (CI) 1.07, 1.48; 3rd quartile: OR 1.25, 95% CI 1.06, 1.46; 4th quartile: OR 1.19, 95% CI 1.01, 1.41; Frank’s LUM: 2nd quartile: OR 1.34, 95% CI 1.02, 2.63; 3rd quartile: OR 1.55, 95% CI 1.04, 2.91; 4th quartile: OR 1.36, 95% CI 1.05, 2.72, respectively). The associations for Rundle’s LUM remained significant after further adjusting other non-redundant built environment factors. Finally, in stratified analysis, we found the association between Rundle’s LUM and telomere length was more evident among younger individuals (

Cardiopulmonary exercise testing and pulmonary function test are important methods for detecting human cardio‐pulmonary function. Whether they could screen vasoresponsiveness in idiopathic pulmonary artery hypertension (IPAH) patients remains undefined. One hundred thirty‐two IPAH patients with complete data were retrospectively enrolled. Patients were classified as vasodilator‐responsive (VR) group and vasodilator‐nonresponsive (VNR) group on the basis of the acute vasodilator test. Pulmonary function test and cardiopulmonary exercise testing were assessed subsequently and all patients were confirmed by right heart catheterization. We analyzed cardiopulmonary exercise testing and pulmonary function test data and derived a prediction rule to screen vasodilator‐responsive patients in IPAH. Nineteen of VR‐IPAH and 113 of VNR‐IPAH patients were retrospectively enrolled. Compared with VNR‐IPAH patients, VR‐IPAH patients had less severe hemodynamic effects (lower RAP, m PAP, PAWP, and PVR). And VR‐IPAH patients had higher anaerobic threshold (AT), peak partial pressure of end‐tidal carbon dioxide (PETCO2), oxygen uptake efficiency (OUEP), and FEV1/FVC (P all

The service performance of magnesium alloy wheel hub was simulated by studying the effect of surface defect size on the corrosion resistance of a calcium phosphate conversion coated AZ80 magnesium alloy. The surface defects were produced with different sizes using a Film Impactor. The corrosion behaviour was studied using electrochemical, hydrogen evolution and immersion tests. The microstructures were characterized using a scanning electron microscope and a laser confocal microscope. Phases and the corrosion products were analyzed using XRD and XPS. The size of the surface defects influenced the corrosion resistance of the coating and the corrosion initiation area. The coating provided no protection for an indentation larger than 2.7 mm. The corrosion mechanism of the coating was also clarified.

Abstract Background Deterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D). Methods We recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9–10 mmol/L (TIR3.9–10). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose. Results HbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR3.9–10 was decreased (p for trend

Abstract Background The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

BackgroundAlong with the rapid growth of the global aging society, the mobile and health digital market has expanded greatly. Countless mobile medical apps (mmApps) have sprung up in the internet market, aiming to help patients with chronic diseases achieve medication safety. ObjectiveBased on the medication safety action plans proposed by the World Health Organization, we aimed to explore the effectiveness of mmApps in ensuring the medication safety of patients with chronic diseases, including whether mmApps can improve the willingness to report adverse drug events (ADEs), improve patients' medication adherence, and reduce medication errors. We hoped to verify our hypothesis through a systematic review and meta-analysis. MethodsThe meta-analysis was performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included literature searched from 7 databases—PubMed, Web Of Science, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, and SinoMed. The publication time was limited to the time of database establishment to April 30, 2022. Studies were screened based on inclusion and exclusion criteria. The data extracted included authors, years of publication, countries or regions, participants’ characteristics, intervention groups, and control groups, among others. Our quality assessment followed the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions, Version 6.3. RevMan 5.2 software (Cochrane Collaboration) was used to analyze the statistical data, and a sensitivity analysis was performed to assess data stability. The degree of stability was calculated by using a different statistical method and excluding large-sample studies from the analysis. ResultsWe included 8 studies from 5 countries (China, the United States, France, Canada, and Spain) that were published from January 1, 2014, to December 31, 2021. The total number of participants was 1355, and we analyzed the characteristics of included studies, each app’s features, the risk of bias, and quality. The results showed that mmApps could increase ADE reporting willingness (relative risk [RR] 2.59, 95% CI 1.26-5.30; P=.009) and significantly improve medication adherence (RR 1.17, 95% CI 1.04-1.31; P=.007), but they had little effect on reducing medication errors (RR 1.54, 95% CI 0.33-7.29; P=.58). ConclusionsWe analyzed the following three merits of mmApps, with regard to facilitating the willingness to report ADEs: mmApps facilitate more communication between patients and physicians, patients attach more importance to ADE reporting, and the processing of results is transparent. The use of mmApps improved medication adherence among patients with chronic diseases by conveying medical solutions, providing educational support, tracking medications, and allowing for remote consultations. Finally, we found 3 potential reasons for why our medication error results differed from those of other studies. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42022322072; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=322072