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Abstract High‐nickel cathode materials are widely used in lithium‐ion batteries because of their advantages of high energy density and high safety. High‐nickel cathode materials need to further improve cycling stability because they are prone to structural changes and capacity degradation. This paper proposes a method to improve high‐nickel cathode materials by Mg doping. XRD proves that Mg‐doped high‐nickel materials still have R‐3 m spatial structural characteristics; Rietveld refinement confirms that the c‐axis gradually increases with the increase of Mg content. Combined with DFT calculations, the presence of Mg can inhibit structural collapse during charge and discharge, reduce Li/Ni antisite defects, improve the electronic conductivity of the material, and improve the cyclic stability of the material. The 0.6 mol % Mg‐doped sample has an initial discharge capacity of 233 mAh g−1 at 0.1 C in the range of 2.7–4.3 V, a capacity retention rate of 91.0 % after 50 cycles at 1 C, still retains 79.9 % after 100 cycles. The dQ/dV curves further indicate that the presence of Mg improves the structural stability of the material.

ABSTRACT The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic Lactococcus garvieae strain LG1 (L. garvieae strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne Clostridium perfringens (C. perfringens) infection. L. garvieae was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a C. perfringens enterocolitis model, L. garvieae-pretreated mice were less susceptible to C. perfringens infection compared with Phosphate buffered solution (PBS)-pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that L. garvieae could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover, L. garvieae was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by C. perfringens. Together, these findings highlight the prospect of immunomodulatory potentially probiotic L. garvieae and might offer valuable strategies for prophylaxis and/or treatment of pathogenic C. perfringens mucosal infection.IMPORTANCEC. perfringens necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that C. perfringens causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for C. perfringens infection may provide important insights into the intervention. L. garvieae originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit C. perfringens enterocolitis and pathogenic colonization. Importantly, we found that L. garvieae limits C. perfringens invasion via improving intestinal mucosal barrier function. Also, L. garvieae alleviates C. perfringens-induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance.

Background/Objective: Resistance training (RT) and protein supplementation have beneficial effects on the human body. However, it is unknown if RT's health-promoting benefits are enhanced by food-borne protein, such as cheese supplements. This study investigated at how the body composition, lipid profile, muscle strength and intestinal microbiota changed following four weeks of RT combined with cheese supplementation. Methods: Thirty-five male and untrained adults were divided into 4 groups [control group (CON), low-dose group (LG), medium-dose group (MG), and high-dose group (HG)] and underwent a 4-week RT (3 times/week) in combination with cheese supplementation. Participants received 108 g (LG), 216 g (MG), or 324 g (HG) of cheese on the day of RT, and each serving (108 g) of cheese contained 6.7 g of food-borne protein. The RT program was a whole-body program with movements such as chest presses, leg presses, seated rowing, knee extensions and triceps pushdown. The exercise consisted of 3 sets of 8–12 repetitions at 70%RM, with a 120-s break in between. Body parameters (body composition, lipid profile and muscle strength) were assessed at baseline and after the 4 weeks of the intervention. The feces sample was taken every weekend. A two-way (group × time) mixed-design ANOVA was used to examine the body parameters. Independent one-way ANOVA was used to analyze the differences between groups in baseline characteristics and different values of each parameter. Results: HDL-C level was higher in MG than in LG. In comparison to LG, MG had lower levels of total cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, body fat mass and body fat percentage. However, there was no difference in muscle strength between in the four groups. The abundance of Actinobacteria was higher in LG and Erysipelotrichaceae was lower in MG and HG. Conclusion: The findings suggest that cheese could be a readily available food-borne protein supplement to enhance the beneficial effects of RT on health. It may improve body composition and lipid profile by altering the proportion of intestinal microbiota. During the 4-week RT intervention, 13.4 g of foodborne protein in the form of cheese 3 times per week was the ideal dosage.

Abstract The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development. Graphical Abstract

Multiphoton dynamics beyond linear optical materials are of significant fundamental and technological importance in quantum information processing. However, it remains largely unexplored in nonlinear waveguide QED. In this work, we theoretically propose a structured nonlinear waveguide in the presence of staggered photon-photon interactions, which supports two branches of gaped bands for doublons (i.e., spatially bound-photon-pair states). In contrast to linear waveguide QED systems, we identify two important contributions to its dynamical evolution, i.e., single-photon bound states (SPBSs) and doublon bound states (DBSs). Most remarkably, the nonlinear waveguide can mediate the long-range four-body interactions between two emitter pairs, even in the presence of disturbance from SPBSs. By appropriately designing system's parameters, we can achieve high-fidelity four-body Rabi oscillations mediated only by virtual doublons in DBSs. Our findings pave the way for applying structured nonlinear waveguide QED in multi-body quantum information processing and quantum simulations among remote sites.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. Methods: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. Results: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). Conclusion: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Background: The ability to hang for a long time before forearm muscle fatigue is a crucial element of successful rock climbing. Electromyography (EMG) and near-infrared spectroscopy (NIRS) are also useful for measuring hemoglobin oxygenation for determining muscle endurance. In the present study, we aimed to evaluate the reliability and validity of muscle endurance indices derived using EMG and NIRS during a hanging task. Methods: A bilateral hanging task was designed to compare rock climbers and non-climbers in terms of the slopes of changes in the median frequency (MDF) and tissue oxygenation index (TOI) of forearm muscles. Results: A total of 17 participants were included in each of the two groups. The intraclass correlation coefficient (3,1) values derived for the MDF slope, TOI slope, ΔTOI, percentage change in oxygen concentration, and ΔHbt were 0.85, 0.73, 0.65, 0.75, and 0.65, respectively. The MDF slope, TOI slope, and ΔHbt differed significantly between the groups (p < 0.05). The MDF slope, TOI slopes, and ΔHbt were significantly correlated with V-scale levels for climbing (p < 0.05). Conclusions: The satisfactory reliability and observed distinctions between climbers and non-climbers imply that these indices are a valuable tool for assessing muscle endurance.

Objective: The objective of the study was to observe and analyze the characteristics of negative emotions and quality of life (QoL) in patients with nonsmall cell lung cancer (NSCLC) from 1 to 3 months after surgery, and summarize their population characteristics after surgery. Materials and Methods: The consolidation rehabilitation period was defined as 1 to 3 months after surgery. The main observation indicators were the general Hospital Anxiety and Depression Scale, the European Organization for the Research and Treatment of Cancer Core QoL Questionnaire (EORTC QLQ-C30), and EORTC QLQ-Lung Cancer-13. The secondary observation indicators were peripheral blood cytokines and immune function indicators. Statistical methods such as one-way analysis of variance and logistic regression were used to analyze the characteristics of this part of the population. Results: Among patients who underwent lung surgery, the overall incidence of anxiety during consolidation recovery was 13.66%, and that of depression was 10.38%. The scores of fatigue, pain, dyspnea, insomnia, and loss of appetite were significantly higher than those of other symptoms (P = 0.000). The presence of anxiety was associated with the site of surgery (P < 0.05) and the presence of depression was associated with emotional functioning and dyspnea (P < 0.05). Conclusions: The occurrence of negative emotions in the postoperative NSCLC population is related to gender, and the degree of emotions is negatively correlated with QoL and positively correlated with the degree of symptoms. The main relevant syndromes are the pulmonary and meridian categories.

Abstract Selenium (Se) maintains soil-plant homeostasis in the rhizosphere and regulates signaling molecules to mitigate cadmium (Cd) toxicity. However, there has been no systematic investigation of the effects of nano-selenium (nano-Se) on the regulation of non-target metabolites and nutritional components in pepper plants under Cd stress. This study investigated the effects of Cd-contaminated soil stress and nano-Se (1, 5, and 20 mg/L) on the metabolic mechanism, fruit nutritional quality, and volatile organic compounds (VOCs) composition of pepper plants. The screening of differential metabolites in roots and fruit showed that most were involved in amino acid metabolism and capsaicin production. Amino acids in roots (Pro, Trp, Arg, and Gln) and fruits (Phe, Glu, Pro, Arg, Trp, and Gln) were dramatically elevated by nano-Se biofortification. The expression of genes of the phenylpropane-branched fatty acid pathway (BCAT, Fat, AT3, HCT, and Kas) was induced by nano-Se (5 mg/L), increasing the levels of capsaicin (29.6%), nordihydrocapsaicin (44.2%), and dihydrocapsaicin (45.3%). VOCs (amyl alcohol, linalool oxide, E-2-heptaldehyde, 2-hexenal, ethyl crotonate, and 2-butanone) related to crop resistance and quality were markedly increased in correspondence with the nano-Se concentration. Therefore, nano-Se can improve the health of pepper plants by regulating the capsaicin metabolic pathway and modulating both amino acid and VOC contents. Graphical Abstract

Japanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus Flavivirus of the family Flaviviridae and has caused huge threat to public health. It is still obscure regarding the functions of stem-loop (SL) and dumbbell (DB) domains of JEV 3′ UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3′ UTR to investigate their effects on virus replication. The results showed that partial deletions within SL or DB domain had no apparent effects on virus replication in both mammalian (BHK-21) and mosquito (C6/36) cells, suggesting that they were not involved in viral host-specific replication. However, the entire SL domain deletion (ΔVR) significantly reduced virus replication in both cell lines, indicating the important role of the complete SL domain in virus replication. The revertant of ΔVR mutant virus was obtained by serial passage in BHK-21 cells that acquired a duplication of DB domain (DB-dup) in the 3′ UTR, which greatly restored virus replication as well as the capability to produce the subgenomic flavivirus RNAs (sfRNAs). Interestingly, the DB-dup mutant virus was highly attenuated in C57BL/6 mice despite replicating similar to WT JEV. These findings demonstrate the significant roles of the duplicated structures in 3′ UTR in JEV replication and provide a novel strategy for the design of live-attenuated vaccines.

Polygonatum odoratum has been known as having therapeutic effects on diabetes. However, due to its complex composition, it is difficult to elucidate the molecular mechanisms of its functions. In this study, we investigated the material basis and molecular mechanisms underlying the antidiabetic activities of methanol extract of P. odoratum (Mill.) Druce by ultra-performance liquid chromatography orbitrap mass spectrometry (UPLC-Orbitrap-MS) and network pharmacology. In specificity, we first constructed a compound-protein interaction network for type 2 diabetes mellitus (T2DM) to identify potential drug targets. Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then conducted to discover the pathways involved in the antidiabetic activities of P. odoratum. Among the 334 compounds detected in P. odoratum, 277 active constituents and 897 corresponding targets were identified to be associated with antidiabetic activities. Five compounds and five targets were consequently obtained by analyzing the compound-target-pathway network. The five compounds were 9-Aminocamptothecin, 9-Methoxycamptothecin, 5-Hydroxy-1-tetralone, 5,7,3′-Trihydroxy-6,4′,5′-trimethoxyflavone, and Diacerein, while the five targets were ACTB, JUN, STAT3, HIF1A, and MMP9. In addition, 30 antidiabetic-related pathways were recognized by using KEGG pathway analysis. Moreover, molecular docking was performed with the five essential compounds and the top five targets based on degree ranking. Our study confirms that active components in P. odoratum can exert antidiabetic activities via multi-component, multi-target, and multi-pathway mechanisms of action, which serves as a practical guidance for further experimental investigations into the biological functions of the methanol extract of P. odoratum in the treatment of T2DM.

DGUOK deficiency has primarily been associated with lethal hepatic failure with or without hypotonia, nystagmus, and psychomotor retardation, features typical of mitochondrial disease. A study in 3 Turkish children identified homozygosity for a variant in DGUOK as associated with idiopathic non-cirrhotic portal hypertension (INCPH). However, no further instances of INCPH associated with DGUOK variants have been reported. We here describe a fourth patient with DGUOK variants and childhood-onset INCPH, a 12-year-old Han Chinese boy, reporting clinical manifestations, histopathologic findings, and results of genetic studies. The child presented with hepatosplenomegaly; portal hypertension and hypersplenism were found. Vascular changes with hepatic fibrosis (Scheuer score 3) were observed on liver biopsy. Whole-exome sequencing and family analyses revealed compound heterozygosity for the DGUOK (NM_080916.3) variants c.778_781dup, (p.Thr261Serfs*28) and c.831_832del, (p.*278Thrfs*9) in the proband. These observations support ascription of instances of INCPH in children to variation in DGUOK.

Abstract In this paper, [Ni0.9Co0.1](OH)2 precursor is used to dope H3BO3 to synthesize positive electrode material when mixing lithium in wet method, and to explore the best doping by testing the microscopic morphology and electrochemical performance of the positive electrode material amount and calcination temperature. After doping with B, the microstructure of the material is improved, and the primary crystal grains are oriented and agglomerated into a needle shape. This good crystal structure can slow down the generation of grain microcracks and mechanical fracture, and improve the cycle stability of the positive electrode material. After doping B, the discharge specific capacity was slightly improved. When the calcination temperature is 750 °C and the doping amount of B is 1.0 mol%, the first discharge specific capacity reaches 223 mAh g−1. More importantly, the capacity retention rate of the battery after 100 cycles has been greatly improved, from 74 % without doping B to 87 %.

Single-step genomic best linear unbiased prediction (ssGBLUP) is now intensively investigated and widely used in livestock breeding due to its beneficial feature of combining information from both genotyped and ungenotyped individuals in the single model. With the increasing accessibility of whole-genome sequence (WGS) data at the population level, more attention is being paid to the usage of WGS data in ssGBLUP. The predictive ability of ssGBLUP using WGS data might be improved by incorporating biological knowledge from public databases. Thus, we extended ssGBLUP, incorporated genomic annotation information into the model, and evaluated them using a yellow-feathered chicken population as the examples. The chicken population consisted of 1 338 birds with 23 traits, where imputed WGS data including 5 127 612 single nucleotide polymorphisms (SNPs) are available for 895 birds. Considering different combinations of annotation information and models, original ssGBLUP, haplotype-based ssGHBLUP, and four extended ssGBLUP incorporating genomic annotation models were evaluated. Based on the genomic annotation (GRCg6a) of chickens, 3 155 524 and 94 837 SNPs were mapped to genic and exonic regions, respectively. Extended ssGBLUP using genic/exonic SNPs outperformed other models with respect to predictive ability in 15 out of 23 traits, and their advantages ranged from 2.5 to 6.1% compared with original ssGBLUP. In addition, to further enhance the performance of genomic prediction with imputed WGS data, we investigated the genotyping strategies of reference population on ssGBLUP in the chicken population. Comparing two strategies of individual selection for genotyping in the reference population, the strategy of evenly selection by family (SBF) performed slightly better than random selection in most situations. Overall, we extended genomic prediction models that can comprehensively utilize WGS data and genomic annotation information in the framework of ssGBLUP, and validated the idea that properly handling the genomic annotation information and WGS data increased the predictive ability of ssGBLUP. Moreover, while using WGS data, the genotyping strategy of maximizing the expected genetic relationship between the reference and candidate population could further improve the predictive ability of ssGBLUP. The results from this study shed light on the comprehensive usage of genomic annotation information in WGS-based single-step genomic prediction.

Objective To assess and compare the therapeutic effects of Anterior Cervical Discectomy and Fusion (ACDF) and Cervical Laminectomy and Fusion (CLF) in the treatment of 4‐level cervical. Methods We performed a retrospective review on 39 patients with 4‐level CSM who underwent ACDF or CLF in the Third Hospital of Hebei Medical University from January 2010 to December 2018. The patients were divided into ACDF group and CLF group according to the treatment. The operative index was evaluated based on intraoperative blood loss and operation time. The functional outcomes including Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) of axial pain were compared. The Cobb angle, Cobb angle improvement rate, range of motion (ROM) and ROM loss ratio were measured for radiographic evaluation. Results No major complications or deaths occurred. The average age at baseline was 55 years. There was no significant difference between the ACDF and CLF group in follow‐up time (26.29 months, 25.39 months, P > 0.05). The intraoperative blood loss was higher in the CLF group than in the ACDF group (692.67 ± 38.68 vs 392.14 ± 128.06, P

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected “rapid progressors” (RPs) have severe damage to the immune system early in HIV infection, which provides a “magnified” opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 “normal progressors” (NPs; CD4+ T-cell count > 500 cells/μl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.

Abstract The lung is the prophylaxis target against SARS-CoV-2 infection, and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen. In this study, we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle (VRP) delivery system, to prevent SARS-CoV-2 infections. First, a modified VEEV replicon with two subgenomic (sg) promoters was engineered to translate the light and heavy chains of antibody simultaneously, for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6. Second, the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays. The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice. Overall, our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.

Abstract Selenium (Se) can promote the growth and resistance of agricultural crops as fertilizers, while the role of nano-selenium (nano-Se) against Cd remains unclear in pepper plants (Capsicum annuum L.). Biofortification with nano-Se observably restored Cd stress by decreasing the level of Cd in plant tissues and boosting the accumulation in biomass. The Se compounds transformed by nano-Se were primarily in the form of SeMet and MeSeCys in pepper tissues. Differential metabolites and the genes of plant signal transduction and lignin biosynthesis were measured by employing transcriptomics and determining target metabolites. The number of lignin-related genes (PAL, CAD, 4CL, and COMT) and contents of metabolites (sinapyl alcohol, phenylalanine, p-coumaryl alcohol, caffeyl alcohol, and coniferaldehyde) were remarkably enhanced by treatment with Cd1Se0.2, thus, maintaining the integrity of cell walls in the roots. It also enhanced signal transduction by plant hormones and responsive resistance by inducing the biosynthesis of genes (BZR1, LOX3, and NCDE1) and metabolites (brassinolide, abscisic acid, and jasmonic acid) in the roots and leaves. In general, this study can enable a better understanding of the protective mechanism of nano-Se in improving the capacity of plants to resist environmental stress.

To meet special requirements and respond to control problems of surface micromorphology of different strips in skin rolling process, a rolling transfer generation model of the surface micromorphology contact between work roll and actual rough surface of strip was established on the basis of batch tracing the surface micromorphology of electric discharge textured roll, grinding roll and cold rolled strip. The inheritance and evolution of surface micromorphology of the strip was analyzed based on the generation model and the accuracy of the generation model was verified by industrial experiments. The concepts of negative transfer and transfer saturation were proposed, and the descriptive indicators for two extreme rolling transfer status (the maximum negative transfer and transfer saturation) were defined. When strip surface roughness is equal to or less than that of roll, a maximum negative transfer point and transfer saturation point exist, while when strip surface roughness is greater than that of roll, the maximum negative transfer point is in superposition with the transfer saturation point. Under the above precondition, through the rolling force of critical strip width, which corresponds to the maximum negative transfer point and transfer saturation point, the inheritance and evolution of surface micromorphology of the strip were characterized. The effect of strip yield strength, strip surface roughness, and roll surface roughness on the rolling force of critical strip width corresponding to maximum negative transfer point and transfer saturation point were also analyzed. Results show that with the increase of strip yield strength and roll surface roughness, the rolling force of critical strip width corresponding to maximum negative transfer point and transfer saturation point increases. With the increase of strip surface roughness, the rolling force of critical strip width corresponding to maximum negative transfer point increases, and the rolling force of critical strip width corresponding to transfer saturation point decreases.

Based on the theory of rack-gear common-tangential conjugate generating, the constructing of ease-off surface has been done by means of the topology modification of polynomial surface. By analyzing topological structure characteristics of ease-off surface, the meshing characteristics such as the contact area, the contact line, and transmission error are determined. By using the geometric analysis of ease-off surface and the potential energy method, the calculation methods of gear tooth stiffness and loaded transmission error are given, and a series of results for the tooth meshing stiffness, loaded transmission error, and load distribution map under varied loads are obtained. In order to solve the stress problem of tooth surface edge contact, the calculation method of quasi-Hertz contact is proposed by subdividing finite contact elements. Taking the second-order parabolic topological modification as an example, the time-varying history characteristics of tooth surface meshing are analyzed. The simulation results of the maximum contact stress and contact area are in good agreement with those calculated by MASTA software. Based on the integration of the geometric analysis of ease-off surface, the tooth stiffness calculation of potential energy method and the quasi-Hertz contact, it provides a convenient method for loaded tooth contact analysis.

BackgroundSubcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.Materials and methodsA total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.ResultsFor males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.ConclusionH-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.

In modern pig breeding programs, growth and fatness are vital economic traits that significantly influence porcine production. To identify underlying variants and candidate genes associated with growth and fatness traits, a total of 1 067 genotyped Duroc pigs with de-regressed estimated breeding values (DEBV) records were analyzed in a genome wide association study (GWAS) by using a single marker regression model. In total, 28 potential single nucleotide polymorphisms (SNPs) were associated with these traits of interest. Moreover, VPS4B, PHLPP1, and some other genes were highlighted as functionally plausible candidate genes that compose the underlying genetic architecture of porcine growth and fatness traits. Our findings contribute to a better understanding of the genetic architectures underlying swine growth and fatness traits that can be potentially used in pig breeding programs.

To explore the genetic features and signatures of selection in indigenous pigs from South China and Duroc pigs, 259 pigs from six populations were genotyped using single-nucleotide polymorphism (SNP) BeadChips. Principal component analysis (PCA), effective population size (Ne), linkage disequilibrium (LD), and signatures of selection were explored and investigated among the six pig populations. The results showed the Ne of five South China indigenous pig populations has been decreasing rapidly since 100 generations ago. The LD between pairwise SNP distance at 100 kb ranged from 0.16 to 0.20 for the five indigenous pig populations, while it was 0.32 for the Duroc population. However, the LD of all six pig populations showed the opposite order at long distances (>5 Mb). Furthermore, 15 potential signatures of selection associated with meat quality and age at puberty were exclusively detected in South China indigenous pigs, while eight potential signatures of selection associated with growth traits were detected in Duroc pigs. Our work provides valuable insights for the utilization and conservation of South China indigenous pigs.

Abstract Sorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot–Marie–Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.

Abstract. Objective:. To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin. Methods:. The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot. Results:. Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated (P 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 (P > 0.05). Conclusion:. Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.

Abstract The current study investigated the effects of shoes of different weights on calf individual muscle contributions during a running cycle. Twenty male runners ran on a force platform with shoes of four different weights (175 g, 255 g, 335 g, and 415 g). The study evaluated runners’ lower extremity muscle forces under the four shoe weight conditions using a musculoskeletal modeling system. The system generates equality and inequality constraint equations to simulate muscle forces. The individual muscle contributions in each calf were determined using these muscle forces. Data were compared using one-way repeated-measure ANOVA. The results revealed significant differences in the contributions of the gastrocnemius lateralis. Post hoc comparisons revealed that running in the 175 g shoes resulted in a larger contribution of the gastrocnemius lateralis than running in the 415 g shoes during the braking phase. Therefore, wearing lightweight shoes while running may promote fatigue in the gastrocnemius muscle during the braking phase. The calf muscle activation results may indicate that an adaptation period is warranted when changing from heavy to lightweight shoes.

Abstract Background The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated. Materials and method NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay. Results The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cells, and DZNep inhibited mTORC1 and mTORC2 activity and aggravated cell apoptosis. Conclusions These data suggested that EZH2 inhibition increased the transcription of Deptor by modifying H3K27me3 in its promoter region, subsequently inhibited mTORC1 and mTORC2 activities, downregulated the expression of apoptosis suppressor genes, and finally led to apoptosis in renal tubular cells. The inhibition of EZH2 aggravated the cisplatin-induced injury in renal tubular cells by inactivating the mTOR complexes. The present study provides new insight into renal protection and suggests that EZH2 might be a target.

Background: The new coronavirus (SARS-CoV-2), which has been responsible for the recent coronavirus disease 2019 (COVID-19) pandemic, uses the cell receptor angiotensin converting enzyme-2 (ACE2) for entry and the serine protease TMPRSS2 for spike (S) protein priming. Meanwhile, the presence of B0AT1 (SLC6A19) may prevent TMPRSS2 from accessing the cutting position on ACE2. Identifying the expression of these cell receptor-related genes of SARS-CoV-2 is critical for understanding the pathogenesis of SARS-CoV-2 in various tissues, especially in the kidney. Methods: The single-cell transcription datasets of the human cell landscape (HCL) and other relevant single-cell transcription databases were used to analyze the expression of ACE2, TMPRSS2, and SLC6A19 in various organs and tissues, but mainly in the kidney. Results: ACE2 was significantly expressed in the S1, S2, and S3 segments of proximal tubule (PT) cells. TMPRSS2 was widely expressed in several renal tubule populations extending from the PT cells to the collection system cell type, of which intercalated cells and the distal convoluted tubule cells showed more significant expression than PT cells. Unexpectedly, although expressed on various renal tubule populations, SLC6A19 was mainly enriched in PT cells, in line with ACE2 expression. Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells. Conclusions: ACE2 was widely expressed in specific cell subgroups of various human tissues, especially in intestinal epithelial cells, kidney PT cells, and also AT 2 cells of the lung. These 3 types of cells demonstrated significant differences in the distribution of the cell receptor-related genes of SARS-CoV-2, which may indicate the diversity of cell surface structures and differences in the affinity between SARS-CoV-2 and cells.

With its low-cost, label-free and non-destructive features, Raman spectroscopy is becoming an attractive technique with high potential to discriminate the causative agent of bacterial infections and bacterial infections per se. However, it is challenging to achieve consistency and accuracy of Raman spectra from numerous bacterial species and phenotypes, which significantly hinders the practical application of the technique. In this study, we analyzed surfaced enhanced Raman spectra (SERS) through machine learning algorithms in order to discriminate bacterial pathogens quickly and accurately. Two unsupervised machine learning methods, K-means Clustering (K-Means) and Agglomerative Nesting (AGNES) were performed for clustering analysis. In addition, eight supervised machine learning methods were compared in terms of bacterial predictions via Raman spectra, which showed that convolutional neural network (CNN) achieved the best prediction accuracy (99.86%) with the highest area (0.9996) under receiver operating characteristic curve (ROC). In sum, machine learning methods can be potentially applied to classify and predict bacterial pathogens via Raman spectra at general level.

BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.MethodsA total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.ResultsExpression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.ConclusionWe established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.

Abstract. Objective:. To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11 (KCNJ11) with gestational diabetes mellitus (GDM). Methods:. Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018, in which 241 pregnant women were identified as GDM, and 391 were non-GDM. All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn, and DNA in the blood was extracted. rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses. Results:. After adjusting age and body mass index, the variant genotypes of rs5210 in genotype models were as follows: P for dominant model was 0.945, (odd ratio: 0.987, 95% confidence intervals (CI): 0.681–1.430); P for recessive model: 0.556, (odd ratio: 1.217, 95% CI: 0.633–2.343) and P for addictive model was 0.098 (genotype AA vs. GG), (odds ratio: 1.435, 95% CI: 0.936–2.201). Weight-gain during pregnancy and total cholesterol were significantly different in recessive model (P = 0.015, P = 0.022, respectively) of all participants. Conclusion:. No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women. But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels. However, more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.

Manipulating droplet dynamics is of great importance in condensation heat transfer enhancement. Cavity topography was believed to be able to regulate droplet merging and self-removal via Laplace force imbalance by the cavity wall and the effect of spatial confinement and isolation. However, the size effect of the microcavity on the droplet dynamics behavior, droplet size distribution and condensation heat transfer performance are not sufficiently understood. In this paper, hierarchical microcavity-arrayed superhydrophobic surfaces with a nominal cavity diameter of 20, 35, 50 and 70 μm were fabricated. Condensation experiments were first carried out in the atmosphere under an optical microscope, and then in pure steam in a self-designed environmental chamber at 4000 Pa. Local dynamic behaviors and time-lapsed evolutions of droplets during condensation were observed. Droplet size distribution and jumping rate were statistically analyzed using ImageJ software. It was proved the smaller cavity size of 20 μm is beneficial to facilitate condensate droplet jumping and increase the density of small droplets. The surface coverage ratio on the microcavity-arrayed superhydrophobic surfaces was only half of that on the hydrophobic surface at steady state. Enhancement of pure steam condensation heat transfer can be realized by effectively regulating droplet dynamics using microcavity topographies at limited subcooling degrees.

Background: Both obstructive sleep apnea-hypopnea syndrome (OSAHS) and obesity are related to cognitive deficits, but the interaction effects of OSAHS and abdominal obesity on cognitive function are unclear. Thus, we performed this study to investigate this issue. Methods: We recruited subjects who received polysomnography test, anthropometric measurements and cognitive function assessment and/or blood protein test. Correlations between apnea-hypopnea index (AHI) and cognitive function were assessed. Analysis of covariance was used to compare the differences in cognitive function between groups and detect the interactions of OSAHS and obesity on cognitive function. Multiple linear regression models were used to determine the associations between OSAHS and cognitive function. Results: In total, 196 subjects with Montreal Cognitive Assessment (MoCA), 161 subjects with Symbol Digit Modalities Test (SDMT) and Trail making test, and 44 subjects with blood protein test were enrolled. Significant negative correlations between AHI and visuo-spatial and executive, language, delayed recall and total score of MoCA were observed. After adjusting for multiple confounding factors, subjects with severe OSAHS had significant lower delayed recall score and total score of MoCA, SDMT index, and Aβ40 protein level than those with non-severe OSAHS group. Severe OSAHS was independently negatively associated with delayed recall score and total score of MoCA, SDMT index, and Aβ40 protein level. An interactive effect of severe OSAHS and abdominal obesity on language score of MoCA was found. Conclusions: Severe OSAHS increased the risk of cognitive deficits. Interaction effect of severe OSAHS and abdominal obesity on language was seen.

Background: Non-specific low back pain (LBP) is highly prevalent today. Disc degeneration could be one of the causes of non-specific LBP, and increased intradiscal pressure (IDP) can potentially induce disc degeneration. The differences in vivo IDP in sitting and standing postures have been studied, but inconsistent results have been reported. The primary objective of this systematic review is to compare the differences in vivo IDP between sitting and standing postures. The secondary objective of this review is to compare effect size estimates between (1) dated and more recent studies and (2) healthy and degenerated intervertebral discs. Methods: An exhaustive search of six electronic databases for studies published before November 2021 was conducted. Articles measuring in vivo IDP in sitting and standing postures were included. Two independent researchers conducted the screening and data extraction. Results: Ten studies that met the inclusion criteria were included in the systematic review, and seven studies with nine independent groups were included in meta-analyses. The sitting posture induces a significantly higher IDP on the lumbar spine (SMD: 0.87; 95% CI = [0.33, 1.41]) than the standing posture. In studies published after 1990 and subjects with degenerated discs, there are no differences in vivo IDP between both postures. Conclusions: Sitting causes higher loads on the lumbar spine than standing in the normal discs, but recent studies do not support this conclusion. Furthermore, the degenerated discs showed no difference in IDP in both postures.

The Duroc pig has high adaptability and feeding efficiency, making it one of the most popular pig breeds worldwide. Over long periods of natural and artificial selection, genetic footprints, i.e., selective signatures, were left in the genome. In this study, a Duroc pig population (n=715) was genotyped with the Porcine SNP60K Bead Chip and the GeneSeek Genomic Profiler (GGP) Porcine Chip. The relative extended haplotype homozygosity (REHH) method was used for selective signature detection in a subset of the population (n=368), selected to represent a balanced family structure. In total, 154 significant core regions were detected as selective signatures (P

Abstract Background Transient infantile hypertriglyceridemia (HTGTI) is an autosomal recessive disorder caused by mutations in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene. Case presentation We report a case of HTGTI in a Chinese female infant. She presented with hepatomegaly, hypertriglyceridemia, moderately elevated transaminases, and hepatic steatosis at 3.5 months of age. A novel mutation c.523C>T, p. (Q175*) was identified in GPD1. The patient was a homozygote and her parents were heterozygous for the mutation. Ultrastructural study showed intrahepatocytic lipid droplets. Conclusions This is the first reported case of HTGTI in Chinese, expanding the worldwide distribution of HTGTI and the mutation spectrum of GPD1.

Superconducting metamaterials, which are designed and fabricated with structured fundamental circuit elements, have motivated recent developments of exploring unconventional quantum phenomena in circuit quantum electrodynamics (circuit-QEDs). We propose a method to engineer 1D Josephson metamaterial as a chiral waveguide by considering a programmed spatiotemporal modulation on its effective impedance. The modulation currents are in the form of travelling waves which phase velocities are much slower than the propagation speed of microwave photons. Due to the Brillouin-scattering process, non-trivial spectrum regimes where photons can propagate unidirectionally emerge. Considering superconducting qubits coupling with this metamaterial waveguide, we analyze both Markovian and non-Markovian quantum dynamics, and find that superconducting qubits can dissipate photons unidirectionally. Moreover, we show that our proposal can be extended a cascaded quantum network with multiple nodes, where chiral photon transport between remote qubits can be realized. Our work might open the possibilities to exploit SQUID metamaterials for realizing unidirectional photon transport in circuit-QED platforms.

Granulosa cells (GCs) are somatic cells of ovary, the behaviors of GCs are important for ovarian function. MicroRNAs (miRNAs) are a class of endogenous 18–24 nucleotide (nt) non-coding RNAs, some of which have been shown to be important regulators of GCs function. miR-34c involved in the regulation of various biological processes and was identified to be a pro-apoptotic and anti-proliferative factor in many cell types. However, the roles of miR-34c in GCs function remain unknown. In this study, we used Annexin V-FITC and EdU assays to demonstrate that miR-34c exerted pro-apoptotic and anti-proliferative effects in porcine GCs. Dual-luciferase reporter assays, quantitative real-time PCR (qRT-PCR) and Western blotting identified Forkhead box O3a (FoxO3a) as a direct target gene of miR-34c. The overexpression of FoxO3a rescued the phenotypic change caused by miR-34c in porcine GCs. In conclusion, miR-34c regulate the function of porcine GCs by targeting FoxO3a.

Abstract Previous studies have suggested that DNA methylation in both CpG and CpH (where H = C, T or A) contexts plays a critical role in biological functions of different tissues. However, the genome-wide DNA methylation patterns of porcine hypothalamus-pituitary-ovary (HPO) tissues remain virtually unexplored. In this study, methylomes of HPO tissues were profiled to investigate their differences and similarities. We found that HPO methylomes displayed tissue-specific methylation patterns in both CpG and CpH contexts. At gene locations, the methylation and density of CpGs was negatively linked at transcription start sites but positively linked at transcription end sites. The densities of CpGs and CpHs at CpG island (CGI) locations were negatively correlated with their methylation. Moreover, the methylation interactions between CGIs and genes showed similar pattern in the CpG context but tissue-specific pattern in the CpH context. CpGs located in CGIs, upstream regions and exons were protected from methylation dynamics, whereas CGI shores, CGI shelves and intergenic regions were more likely to be targets of methylation changes. The methylation dynamics enriching in a tissue-specific manner appeared to maintain and establish the biological functions of HPO tissues. Our analyses provided valuable insights into the tissue-specific methylomes of porcine HPO tissues.

Abstract Background Underlying causes in Chinese children with recurrent acute liver failure (RALF), including liver crises less than full acute liver failure, are incompletely understood. We sought to address this by searching for genes mutated in such children. Methods Five unrelated Chinese boys presenting between 2012 and 2015 with RALF of unexplained etiology were studied. Results of whole exome sequencing were screened for mutations in candidate genes. Mutations were verified in patients and their family members by Sanger sequencing. All 5 boys underwent liver biopsy. Results NBAS was the only candidate gene mutated in more than one patient (biallelic mutations, 3 of 5 patients; 5 separate mutations). All NBAS mutations were novel and predictedly pathogenic (frameshift insertion mutation c.6611_6612insCA, missense mutations c.2407G > A and c.3596G > A, nonsense mutation c.586C > T, and splicing-site mutation c.5389 + 1G > T). Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution. Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related RALF), with markedly elevated alanine aminotransferase and aspartate aminotransferase activities 24-72 h after elevation of body temperature, succeeded by severe coagulopathy and mild to moderate jaundice. Conclusions As in other countries, so too in China; NBAS disease is a major cause of fever-related RALF in children. The mutation spectrum of NBAS in Chinese children seems different from that described in other populations.

Coalescence-induced jumping of condensate droplets has been studied as an emerging mode for enhanced condensation heat transfer. However, the spontaneous droplet jumping phenomenon usually disappears at relatively higher degrees of subcooling due to the increase of nucleation density of condensate droplets. In this Letter, we show that self-propelled droplet jumping condensation can be realized surprisingly on a hierarchical porous superhydrophobic surface, having pores of the size of ∼20 μm with nanoscale dendritic structures, which was fabricated via a facile electrochemical deposition method. Droplet jumping condensation was always able to be sustained on this surface, making it never flooded even at elevated subcooling up to ∼20 K, although the intensity of droplet jumping degraded gradually with increasing the subcooling. It was hypothesized that the presence of microscale ridges among the pores, where nucleating droplets tended to appear and grow over the nano-structures on the ridge tips, serve as spatial separation barriers that prevent the surfaces from nucleation-density-modulated flooding at relatively high degrees of subcooling. As compared to conventional dropwise condensation on a smooth hydrophobic surface, significant heat transfer enhancement was able to attain for subcooling up to ∼7 K. The fabrication of this hierarchical porous superhydrophobic surface was deemed to be rapid, scalable, and highly-adaptive for curved surfaces on metallic bulk materials, e.g., copper tubes, with a great potential for industrial condensation applications.

Given that the venom system in sea snakes has a role in enhancing their secondary adaption to the marine environment, it follows that elucidating the diversity and function of venom toxins will help to understand the adaptive radiation of sea snakes. We performed proteomic and de novo NGS analyses to explore the diversity of venom toxins in the annulated sea snake (Hydrophis cyanocinctus) and estimated the adaptive molecular evolution of the toxin-coding unigenes and the toxicity of the major components. We found three-finger toxins (3-FTxs), phospholipase A2 (PLA2) and cysteine-rich secretory protein (CRISP) in the venom proteome and 59 toxin-coding unigenes belonging to 24 protein families in the venom-gland transcriptome; 3-FTx and PLA2 were the most abundant families. Nearly half of the toxin-coding unigenes had undergone positive selection. The short- (i.p. 0.09 μg/g) and long-chain neurotoxin (i.p. 0.14 μg/g) presented fairly high toxicity, whereas both basic and acidic PLA2s expressed low toxicity. The toxicity of H. cyanocinctus venom was largely determined by the 3-FTxs. Our data show the venom is used by H. cyanocinctus as a biochemically simple but genetically complex weapon and venom evolution in H. cyanocinctus is presumably driven by natural selection to deal with fast-moving prey and enemies in the marine environment.

MicroRNAs (miRNAs) are endogenous 18–24 nucleotide (nt) non-coding RNAs, some of which have been indicated to play key roles in granulosa cells (GCs) function. However, little is known about how the miRNA gene expression itself is regulated in the GCs. Our previous study showed that miR-34c, identified to be a pro-apoptotic and anti-proliferative factor in many cell types, exerted the same effects in porcine GCs. Here, the transcriptional regulation of miR-34c expression in GCs was further investigated. 5′ rapid amplification of cDNA ends (RACE) assay indicated that the pri-miR-34c transcription start site was located in 1 556 bp upstream of pre-miR-34c. With dual-luciferase reporter assay, we confirmed a 69 bp core promoter region (–1 799 bp/–1 730 bp) was indispensable for the transcription of miR-34c. Chromatin immunoprecipitation (ChIP) assay demonstrated that p53, p50, and p65 could bind to the transcription factor binding sites within the 69 bp core promoter region. In addition, deletion of transcripition factor binding sites resulted in obvious change of the miR-34c promoter activity. Finally, using overexpression and knockdown of p53, p50, and p65 strategies, we showed that p53 and p50 could positively regulated miR-34c expression, whereas p65 neletively regulated miR-34c expression in GCs. Our results provide new data about the transcription regulatory mechanism of miRNA genes in GCs.

The objectives of this study were to estimate the genetic parameters and the breeding progress in a Landrace herd in China, and to predict the potential benefits by applying new breeding technology. Hereby, the performance records from a Landrace swine herd in China, composing over 33 000 pigs born between 2001 and 2013, were collected on six economically important traits, i.e., average daily gain between 30–100 kg (ADG), adjusted backfat thickness at 100 kg (BF), adjusted days to 30 kg (D30), adjusted days to 100 kg (D100), number born alive (NBA), and total number born (TNB). The genetic parameters were estimated by restricted maximum likelihood via DMU, and realized genetic trends were analyzed. Based on the real population structure and genetic parameters obtained from this herd, the potential genetic trends by applying genomic selection (GS) were predicted via a computer simulation study. Results showed that the heritability estimates in this Landrace herd were 0.55 (0.02), 0.42 (0.01), and 0.12 (0.01), for BF, D100, and TNB, respectively. Favorable genetic trends were obtained for D100, BF, and TNB due to direct selection, for ADG and NBA due to indirect selection. Long-term selection against D100 did not improve D30, though they are highly genetically correlated (0.64). Appling GS in such a swine herd, the genetic gain can be increased by 25%, or even larger for traits with low heritability or individuals without phenotypes before selection. It can be concluded that conventional breeding strategy was effective in the herd studied, while applying GS is promising and hence the road ahead in swine breeding.

The purpose of this study is to investigate the influence of alloy composition on the evolvement rule of microstructure for ZL201 cast aluminium alloy. The ZL201 casting samples with different components were prepared by gravity diecasting process, the phase composition was characterized and calculated by x-ray diffraction (XRD) and thermo-calc (TC) software respectively, the evolvement rule of microstructures was observed by metallographic microscope (OM) and scanning electron microscope (SEM), and simulated by ProCAST software. The results show that the Al _2 Cu ( θ ) formed by Cu and Al matrix, which increased the free energy and reduced the precipitation temperature for the alloy system. For the microstructure of ZL201, the nucleation direction of Al-Cu was along the positive direction of z -axis, the morphology was a regular ribbed morphology; Al-Mn and Al-Ti were along the negative directions of x - and y -axis and morphologies were columnar. Besides, the nucleation mode of casting center was dominated by the growth pattern of Al-Cu, and that of casting surface was dominated by Al-Ti and Al-Mn.

Objective This study aimed to identify the risk factors for vertebral compression fractures in patients with osteoporosis. Methods A total of 864 patients with osteoporosis were enrolled in a retrospective study from February 2010 to June 2016. Patients with diseases, such as pathological fractures, high-energy direct injury to the thoracic or lumbar vertebrae, and severe spinal deformity, were excluded. The patients were divided into two groups: those with vertebral compression fractures (288) and those with no vertebral compression fractures (576). Information on the patients’ age, sex, lumbar bone mineral density (BMD), trauma, body mass index, previous history of vertebral compression fractures, and spondylolisthesis was recorded. Logistic regression analysis and the chi-square test were applied for comparisons. Results Univariate logistic regression analysis and chi-square test results showed no significant differences in age, sex, body mass index, type 2 diabetes, previous history of vertebral fracture, and trivial trauma between the groups. Multivariate analysis showed significant associations between spondylolisthesis and BMD. Logistic regression analysis showed that spondylolisthesis and BMD were risk factors for vertebral compression fractures. Conclusions Lumbar spondylolisthesis is an independent risk factor for vertebral compression fractures in patients with osteoporosis. Therefore, patients with osteoporosis and lumbar spondylolisthesis require more attention.

The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 < 26 μM. DC1 was found to be the best inhibitor of ImiS (IC50 < 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 µM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.

BACKGROUND AIMS: We previously demonstrated the pro-metastasis effect of sorafenib in hepatocellular carcinoma (HCC), which is mediated by down-regulation of tumor suppressor HTATIP2. The aim of the present study was to determine whether aspirin minimizes this effect and improves survival. METHODS: The effects of sorafenib, aspirin, and combined sorafenib and aspirin were observed in HCCLM3 and HepG2 xenograft nude mice. Tumor growth, intrahepatic metastasis (IHM), lung metastasis, and survival were assessed. Polymerase chain reaction (PCR) array, real-time (RT)-PCR, and Western blotting were used to examine gene expression. The anti-invasion and anti-metastasis effects of aspirin were studied in HTATIP2-knockdown and HTATIP2-overexpressing HCC cell lines. The molecular mechanism of HTATIP2 regulation by aspirin was explored. RESULTS: Aspirin suppressed the pro-invasion and pro-metastasis effects of sorafenib in HCC and up-regulated HTATIP2 expression. Aspirin did not inhibit the proliferation of HCC cells, but it decreased the invasiveness of HCC with lower expression of HTATIP2 and increased expression of a set of markers, indicating a mesenchymal-to-epithelial transition in tumor cells. The up-regulation of HTATPI2 expression by aspirin is most likely mediated through inhibition of cyclooxygenase (COX) 2 expression. CONCLUSIONS: Aspirin minimized the pro-metastasis effect of sorafenib by up-regulating the tumor suppressor HTATIP2; this mechanism is mediated through inhibition of COX2.