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Abstract Background Senior nursing students’ perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students’ perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. Methods This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students’ Questionnaire and the Professional Identity Scale for Nursing Students. Results Three latent profiles were identified and labeled as “low perceived professional preparedness” (n = 90, 28.2%), “low clinical competency-low EBP (Evidence-Based Practice)” (n = 190, 59.5%), and “high perceived professional preparedness” (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p

Microring resonators have been widely used in passive optical devices such as wavelength division multiplexers, differentiators, and integrators. Research on terahertz (THz) components has been accelerated by these photonics technologies. Compact and integrated time-domain differentiators that enable low-loss, high-speed THz signal processing are necessary for THz applications. In this study, an on-chip THz temporal differentiator based on all-silicon photonic technology was developed. This device primarily consisted of a microring waveguide resonator and was packaged with standard waveguide compatibility. It performed time-domain differentiation on input signals at a frequency of 405.45 GHz with an insertion loss of 2.5 dB and a working bandwidth of 0.36 GHz. Various periodic waveforms could be handled by this differentiator. This device could work as an edge detector, which detected step-like edges in high-speed input signals through differential effects. This development holds significant promise for future THz data processing technologies and THz communication systems.

Abstract Introduction The turnover and shortage of health care workers (HCWs) have been a worldwide problem for healthcare organizations. The primary aim of this study was to identify the factors influencing the intention of Chinese HCWs to leave their job, especially meaning in life and professional happiness. Methods This observational cross-sectional study, conducted among 1125 full-time HCWs, assessed demographic variables, meaning in life, professional happiness, and turnover intention by a survey. The survey was distributed to HCWs in three tertiary hospitals. The data were analyzed by T-tests, ANOVA, Kruskal–Wallis tests and hierarchical linear regression model. Results There were statistically significant differences in turnover intention of HCWs by gender, age, role, educational level, years in practice, and number of monthly night shifts. HCWs’ meaning in life and professional happiness were negatively associated with the turnover intention. Furthermore, after controlling for other factors, meaning in life explained 3.7% of the turnover intention and professional happiness explained 13.4%. Conclusion In our study, positive psychological factors were related to turnover intentions. Professional happiness was the strongest predictor. Thus, health human resource managers should foster positive psychology among HCWs to reduce their turnover.

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications.

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

In Chinese universities, most English majors are taught by teachers, and students attend classes and do homework. Students are often passive in their study, which can make them lose study interest, negatively affect their study and cause boredom in class. Although previous studies have studied the class-related boredom of some English courses, they have not compared the level of it between different English courses. Besides, in previous studies, study interest and perceived autonomy support, two factors that affect class-related boredom, have received a lot of attention, while student enthusiasm has not received enough attention. Based on Control Value Theory, this study examines the degree of class-related boredom experienced by English majors in various English courses from the three factors including study interest, perceived autonomy support and student enthusiasm in an effort to diminish it in a more focused manner. The respondents are 884 English majors (94.1% female) from a university in Shanxi Province, China. And SPSS 26.0 is used for descriptive statistics and multiple linear regression analysis. Studies show that Advanced English Listening has the lowest degree of class-related boredom, but Basic English has the highest one. This study also finds that study interest, perceived autonomy support and student enthusiasm in English major courses are significantly negatively correlated with class-related boredom.

Introduction: In order to promote the consumption of renewable energy, reduce carbon emissions, and take into account the uncertainty of renewable energy output and load fluctuations in the new power system that can affect the normal operation of market mechanism, a two-stage low-carbon optimization scheduling method for power system that considers demand response under multiple uncertainties is proposed in this paper.Methods: Uncertain scene sets are generated through Latin hypercube sampling and heuristic synchronous backpropagation method is used to reduce scenes to obtain typical scenes and their probabilities. Then, a one-stage optimization model is established with the goal of maximizing energy efficiency and corresponding demand response strategies are obtained. Green certificate carbon trading joint mechanism model consisting of tiered green certificate trading and time-sharing tiered carbon trading are established, and the output of two-stage units are optimized with the goal of minimizing comprehensive operating costs.Result: The simulation results show that the carbon emissions are decreased by 251.57 tons, the consumption rate of renewable energy is increased by 8.64%, and the total costs are decreased by 124.0612 million yuan.Discussion: From this, it can be seen that the dual layer low-carbon optimization scheduling strategy for power system considering demand response under multiple uncertainties can effectively reduce the operating costs and carbon emissions of the system, while balancing the economic and environmental aspects of power system operation.

IntroductionPatriotism, a positive emotional attachment to one’s country, has been associated with prosocial behavior, social responsibility, and gratitude. It plays a crucial role in promoting social harmony and national development. However, the factors influencing patriotism and their mechanisms remain unclear. This research consists of two studies exploring the internal mechanisms that connect gratitude and patriotism.MethodsStudy 1 conducted a cross-sectional analysis among 3,826 college students to investigate the influence of gratitude on patriotism, emphasizing the mediating role of general life satisfaction and the moderating impact of socioeconomic status. This approach aimed to elucidate the complex relationships between these variables within college students. Study 2 adopted a longitudinal approach, surveying 905 college students across three-time points. This study was designed to explore the temporal mediation of general life satisfaction in the gratitude-patriotism relationship, offering insights into the evolution of these constructs over time. The sequential surveys aimed to capture the dynamic nature of gratitude’s impact on patriotism, considering the continuous interplay with general life satisfaction among college students.ResultsStudy 1 reveals a noteworthy finding: Gratitude enables the direct prediction of patriotism, while additionally, general life satisfaction plays a role between them. Furthermore, the predictive effect of gratitude on patriotism is strengthened among individuals with higher levels of socioeconomic status. However, there is no significant moderating effect between general life satisfaction and patriotism by socioeconomic status. Study 2 demonstrates that general life satisfaction plays a significant mediating role in the relationship between gratitude and patriotism, over a period of three times. However, the moderating influence of socioeconomic status was not substantiated in the longitudinal mediation model.ConclusionThese two studies shed light on the complex relationship between gratitude and patriotism. They emphasize the significance of gratitude, general life satisfaction, and socioeconomic status in shaping patriotism, offering potential avenues for understanding the internal mechanisms that influence patriotism.

To improve the gel quality of chicken blood, a by-product of concentrated slaughter, the effects of different concentrations and formulations of xanthan gum (XG) and guar gum (GG) on the gel properties of chicken blood were investigated using the indices of water retention, texture, and rheological properties, as well as analysis of molecular interactions and sensory scores. The results showed that while individual treatment with either XG or GG improved the water-holding capacity of the chicken blood gel, the action of XG was superior. Addition of 4.0 g/L of XG resulted in a cooking loss rate of 10.02%, centrifugation loss of 12.73%, and syneresis rate of 10.96% (at 48 h), while the hardness, cohesiveness, gelation, mastication, and recovery of the gel were decreased. Addition of 6.0 g/L of GG significantly improved the textural properties of the gel, resulting in a hardness of 366.95 N, elasticity of 0.94 mm, cohesiveness of 0.77, adhesiveness of 281.94, masticatory value of 263.72 mJ, and recovery of 0.25. Analysis of dynamic rheology and intermolecular forces showed that the gelation transformation of the chicken blood gel system was mainly determined by the elastic response. The formulation of XG and GG had a synergistic effect in stabilizing the chicken blood gel, with strengthened ionic bonds (from 29.18% to 32.62%) and hydrogen bonds (from 2.48% to 6.43%), reduced hydrophobic force (from 22.68% to 16.28%), increased water-holding capacity of the gel, and enhanced gel stability. The addition of 4.0 g/L of formulated colloid (XG and GG in a ratio of 7:3) to chicken blood resulted in optimal water retention and texture, together with high sensory scores of the gel.

Abstract Background Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)—based quantitative proteomics analysis of skeletal muscle. Methods The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. Results After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE’s ingredients. Conclusions This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE. Graphical Abstract

Objective: To characterize the effects of Qingwei San (QWS) on diabetic oral ulcer (OU) mice with stomach heat pattern through metabolomic analysis. Methods: A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db (db/db) mice with dried Zingiber officinale Rosc. rhizome (Z. officinale, Gan Jiang) decoction by gavage. All model mice had blood glucose levels of ≥11.1 mM. Subsequently, OU was induced by NaOH cauterization. After 1 week of administration of QWS, non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS). Results: The non-targeted metabolomics results indicated that tryptophan metabolism, 2-oxocarboxylic acid metabolism, serotonergic synapses, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were involved in the therapeutic effects of QWS, with tryptophan metabolism playing a predominant role. Conclusion: QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern. QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.

Abstract Purpose The purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved. Methods Thirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose

Optimal carbohydrate level in diets could improve growth and feed efficiency，whereas HC (high carbohydrate) diets usually induce the liver injury in reared fish. While SA (sodium acetate) has demonstrated its potential to alleviate liver injury in mammals, the mechanism underlying its impact on liver health in fish remains elusive. This study aims to elucidate the effect of dietary SA on liver injury in the female Monopterus albus. In our study, groups of M. albus were fed with different diets: NC (normal, 20% carbohydrate), HC (high carbohydrate, 32% carbohydrate) and HC+A (HC supplemented with 0.2% SA) diets, in separate, for a consecutive period of 56 days. Our findings showed that HC+A diets improved growth (weight gain rate, from 263.27 ± 9.87–292.34 ± 6.18%) and FE (feed efficiency, from 67.28 ± 2.18–75.91 ± 1.90%) (P

ABSTRACTBackground The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension.Methods Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT1R signaling pathway was examined by Western blot.Results We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT1R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT1R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD+/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT1R promoter, which reversed enhanced AT1R expression and function, and lowered blood pressure in aged mice.Conclusions Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.

Abstract Background It is important to understand how the perception of death affects the competence to cope with death. Objectives To explore whether the perception of death has an indirect effect on competence to cope with death through the mediation of attitude toward death and meaning of life. Methods A total of 786 nurses from Hunan Province, China, selected by random sampling method and asked to complete an online electronic questionnaire between October and November 2021 were included in the study. Results The nurses’ scored 125.39 ± 23.88 on the competence to cope with death. There was a positive correlation among perception of death, competence to cope with death, the meaning of life, and attitude toward death. There were three mediating pathways: the separate mediating effect of natural acceptance and meaning of life, and the chain mediating effect of natural acceptance and meaning of life. Conclusion The nurses’ competence to cope with death was moderate. Perception of death could indirectly and positively predict nurses’ competence to cope with death by enhancing natural acceptance or sense of meaning in life. In addition, perception of death could improve natural acceptance and then enhance the sense of meaning in life to positively predict nurses’ competence to cope with death.

Abstract Analyses of several databases showed that the lncRNA RNF157 Antisense RNA 1 (RNF157-AS1) is overexpressed in epithelial ovarian cancer (EOC) tissues. In our study, suppressing RNF157-AS1 strikingly reduced the proliferation, invasion, and migration of EOC cells compared with control cells, while overexpressing RNF157-AS1 greatly increased these effects. By RNA pulldown assays, RNA binding protein immunoprecipitation (RIP) assays, and mass spectrometry, RNF157-AS1 was further found to be able to bind to the HMGA1 and EZH2 proteins. Chromatin immunoprecipitation (ChIP) assays showed that RNF157-AS1 and HMGA1 bound to the ULK1 promoter and prevented the expression of ULK1. Additionally, RNF157-AS1 interacted with EZH2 to bind to the DIRAS3 promoter and diminish DIRAS3 expression. ULK1 and DIRAS3 were found to be essential for autophagy. Combination autophagy inhibitor and RNF157-AS1 overexpression or knockdown, a change in the LC3 II/I ratio was found using immunofluorescence (IF) staining and western blot (WB) analysis. The autophagy level also was confirmed by autophagy/cytotoxicity dual staining. However, the majority of advanced EOC patients require platinum-based chemotherapy, since autophagy is a cellular catabolic response to cell stress. As a result, RNF157-AS1 increased EOC cell sensitivity to chemotherapy and death under cis-platinum (DDP) treatment by suppressing autophagy, as confirmed by cell count Kit-8 (CCK8) assays, flow cytometry, and autophagy/cytotoxicity dual staining. Therefore, the OS and PPS times were longer in EOC patients with elevated RNF157-AS1 expression. RNF157-AS1-mediated autophagy has potential clinical significance in DDP chemotherapy for EOC patients.

Environmentally cued hatching is prevalent, diverse, and crucial to many animals’ survival. Fish embryos use a variety of chemical cues to initiate hatching to avoid potential predators, yet the function of chemical cues released from the predatory consumption of heterospecific prey is largely unknown. Zebra cichlids (Metriaclima estherae) are ferocious predators that can feed on medaka (Oryzias latipes), though it is impossible for this to occur in their natural habitat. Zebrafish (Danio rerio) embryos have been employed as experimental subjects due to their sensitivity to a variety of chemical signals. In this study, zebrafish embryos were subjected to three types of chemical signals: predator cues (PCs, released from cichlids), heterospecific cues (HCs, released from medaka), and heterospecific dietary cues (HDCs, released from cichlids that have ingested medaka). As a result, the hatching times of zebrafish embryos were accelerated by 6.8% and 12.6% by PCs and HDCs, respectively. PCs and HDCs cause significantly reduced morphology in zebrafish embryos, including regarding total length, eye length, dorsal fin length, trunk height, caudal fin height, and body cavity, and increase yolk sac height. The PCs and HDCs diminished the larvae’s motion at 120 and 144 h post fertilization (hpf), which could be attributed to non-developmental embryogenesis. Overall, the impacts of HDCs on embryonic hatching, developmental morphology, and locomotor were more pronounced in comparison with PCs. Our findings demonstrate that predators’ dietary cues, even those released after predation on heterospecific prey, can modify embryogenesis, highlighting the critical functions of chemical signals in predation risk assessment using embryos.

The phase inversion tape casting has been widely used to fabricate open straight porous supports for solid oxide fuel cells (SOFCs), which can offer better gas transmission and minimize the concentration polarization. However, the overall weak strength of the macro-porous structure still limits the applications of these SOFCs. In this work, a novel SOFC supported by an ordered porous cathode membrane with a four-layer configuration containing a finger-like porous 3 mol% yttria- stabilized zirconia (3YSZ)-La0.8Sr0.2Co0.6Fe0.4O3−δ (LSCF) catalyst, porous 8 mol% yttria-stabilized zirconia (8YSZ)-LSCF catalyst, and dense 8YSZ porous 8YSZ-NiO catalyst is successfully prepared by the phase inversion tape casting, dip-coating, co-sintering, and impregnation process. The flexural strength of the open straight porous 3YSZ membrane is as high as 131.95 MPa, which meets the requirement for SOFCs. The cathode-supported single cell shows a peak power density of 540 mW cm−2 at 850 °C using H2 as the fuel. The degradation mechanism of the SOFC is investigated by the combination of microstructure characterization and distribution of relaxation times (DRT) analysis.

Tilmicosin is a semi-synthetic macrolide for veterinary use with strong antibacterial effect on respiratory bacteria. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) integration of tilmicosin against Pasteurella multocida (P. multocida) was evaluated by establishing a piglet tissue cage infection model. Concentration of tilmicosin and bacterial numbers of P. multocida in the tissue-cage fluid were monitered. After the population of P. multocida was equal to or greater than 107 CFU/mL in a tissue cage, piglets received an oral administration of tilmicosin at a dose of 30, 40, 50, and 60 mg/kg b.w., once daily for 3 days, respectively. Bacteria were counted every 24 h after drug administration and at 48 and 72 h after the last administration. A sigmoidal Emax model was used to fit the relationship between PK/PD parameters and the antibacterial effect. AUC24h/MIC was the best PK/PD index that correlated with effectiveness of tilmicosin against P. multocida. The magnitude of AUC24h/MIC required for continuous 1/3-log, 1/2-log, and 3/4-log reductions were 19.65 h, 23.86 h, and 35.77 h, respectively, during each 24 h treatment period. In this study, when the dosage was >50 mg/kg, the AUC24h/MIC was still >35.77 h in the period of 24–48 h after the last administration due to the slow elimination, that is, tilmicosin exhibited a potent antibacterial effect against P. multocida after three successive daily administrations. The data provide meaningful guidance to optimize regimens of tilmicosin to treat respiratory tract infections caused by P. multocida.

Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM2.5 exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N6-methyladenine (m6A) modification in PM2.5-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.

Rapid and cost-efficient antibiotic susceptibility testing (AST) is key to timely prescription-oriented diagnosis and precision treatment. However, current AST methods have limitations in throughput or cost effectiveness, and are impractical for microbial communities. Here, we developed a high-throughput micro-well array-based colorimetric AST (macAST) system equipped with a self-developed smartphone application that could efficiently test sixteen combinations of bacteria strains and antibiotics, achieving comparable AST results based on resazurin metabolism assay. For community samples, we integrated immunomagnetic separation into the macAST (imacAST) system to specifically enrich the target cells before testing, which shortened bacterial isolation time from days to only 45 min and achieved AST of the target bacteria with a low concentration (~103 CFU/mL). This proof-of-concept study developed a high-throughput AST system with an at least ten-fold reduction in cost compared with a system equipped with a microscope or Raman spectrum. Based on colorimetric readout, the antimicrobial susceptibility of the bacteria from microbial communities can be delivered within 6 h, compared to days being required based on standard procedures, bypassing the need for precise instrumentation in therapy to combat bacterial antibiotic resistance in resource-limited settings.

Objective FKBP prolyl isomerase 5 (FKBP5) has been shown to play an important role in metabolically active tissues such as skeletal muscle. However, the expression of FKBP5 in Muscovy duck tissues and its association with body weight are still unclear. Methods In this study, real-time quantitative polymerase chain reaction was used to detect the expression of FKBP5 in different tissues of Muscovy duck at different growth stages. Further, single nucleotide polymorphisms (SNPs) were detected in the exon region of FKBP5 and were combined analyzed with the body weight of 334 Muscovy ducks. Results FKBP5 was highly expressed in various tissues of Muscovy duck at days 17, 19, 21, 24, and 27 of embryonic development. In addition, the expression of FKBP5 in the tissues of female adult Muscovy ducks was higher than that of male Muscovy ducks. Besides, an association analysis indicated that 3 SNPs were related to body weight trait. At the g.4819252 A>G, the body weight of AG genotype was significantly higher than that of the AA and the GG genotype. At the g.4821390 G>A, the genotype GA was extremely significantly related to body weight. At the g.4830622 T>G, the body weight of TT was significantly higher than GG and TG. Conclusion These findings indicate the possible effects of expression levels in various tissues and the SNPs of FKBP5 on Muscovy duck body weight trait. FKBP5 could be used as molecular marker for muscle development trait using early marker-assisted selection of Muscovy ducks.

Abstract Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.

Abstract Background The COVID-19 pandemic called for a new ethical climate in the designated hospitals and imposed challenges on care quality for anti-pandemic nurses. Less was known about whether hospital ethical climate and nurses’ ethical sensitivity were associated with care quality. This study examined the association between the perceived hospital ethical climate and self-evaluated quality of care for COVID-19 patients among anti-pandemic nurses, and explored the mediating role of ethical sensitivity in this relationship. Methods A cross-sectional study was conducted through an online survey. A total of 399 anti-pandemic nurses from ten designated hospitals in three provinces of China were recruited to fill out an online survey. Multiple linear regression analysis and a bootstrap test were used to examine the relationships between ethical climate, ethical sensitivity and care quality. Results Nurses reported mean scores of 4.43 ± 0.577 (out of 5) for hospital ethical climate, 45.00 ± 7.085 (out of 54) for ethical sensitivity, and 5.35 ± 0.661 (out of 6) for self-evaluated care quality. After controlling for covariates, perceived hospital ethical climate was positively associated with self-evaluated care quality (direct effect = 0.710, 95% confidence interval [CI] 0.628, 0.792), and was partly mediated by ethical sensitivity (indirect effect = 0.078, 95% confidence interval [CI] 0.002, 0.145). Conclusions Chinese nurses who cared for COVID-19 patients perceived high levels of hospital ethical climate, ethical sensitivity, and self-evaluated care quality. Positive perceptions of hospital ethical climate were both directly associated with a higher level of self-evaluated care quality and indirectly associated, through the mediation effect of ethical sensitivity among anti-pandemic nurses.

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting “Warburg effect” compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H2O2 gradient towards deep tumor, with hypoxia successfully alleviated in the meantime. The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis. In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel (PTX@HSA) after pre-treated with NM-si for TME reconstruction. This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

Riemerella anatipestifer (RA) is an important pathogen found in poultry. RA infection can kill ducks and lead to significant economic losses. Seven RA strains with different susceptibility phenotypes were chosen to study the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) alone and in combination with doxycycline (DOX). The checkerboard assay indicated that synergy [fractional inhibitory concentration index (FICI) ≤ 0.5] was detected in the CVCC3952 strain of RA and that additivity (FICI >0.5 to ≤ 1) was observed in other strains. Static time–kill curves showed that the bactericidal effect of FF against RA was produced at a FF concentration ≥4 MIC, and the antibacterial activity of FF against RA was enhanced from the aspects of efficacy and efficacy in combination with DOX. Dynamic time–kill curves indicated that FF elicited bactericidal activity against the CVCC3857 strain with a reduction ≥4.88 log10CFU/ml when the dose was ≥8 mg/L. However, a bactericidal effect was not achieved at the maximum administered dose of FF monotherapy (20 mg/L) for isolates with a MIC ≥4 μg/ml. The effect of FF against RA was enhanced upon combination with DOX. The combination of FF with DOX reduced the bacterial burden ≥4.53 log10CFU/ml for all strains with a MIC ≥4 μg/ml. Data were fitted to a sigmoidal Emax model. The PK/PD parameters of AUC24h/MIC (the area under the concentration–time curve over 24 h divided by the MIC) and %T >MIC (the cumulative percentage of time over a 24-h period at which the concentration exceeded the MIC) of FF for eliciting a reduction of 3 log10CFU/ml was 40.10 h and 58.71, respectively. For strains with a MIC ≤ 16 μg/ml, the magnitude of the AUC24h/MIC and Cmax/MIC required for a 3 log10CFU/ml of bacterial killing was 34.84 h and 4.74 in the presence of DOX at 0.5 MIC, respectively. These data suggest that combination of FF with DOX enhanced the activity against RA strains with various susceptibilities to FF and DOX.

Abstract Supramolecular metal‐organic materials are considered as the ideal candidates for membrane fabrication due to their excellent film forming characteristics, diverse metal centers and ligand sources, and designable structure and function. However, it remains challenging to rapidly construct highly permeable supramolecular metal‐organic membranes with high salt rejection. Herein, a novel ultrafast interfacial self‐assembly strategy to prepare supramolecular metal‐organic films through the strong coordination interaction between highly active 1,3,5‐triformylphloroglucinol (TFP) ligands and Fe3+, Sc3+, or Cu2+ at the organic–aqueous interface is reported. Benefiting from the self‐completing and self‐limiting characteristics of this interfacial self‐assembly, the new kind of supramolecular membrane with optimized composition can be assembled within 3.5 min and exhibits ultrathin, dense, defect‐free features, and thus shows an excellent water permeance (21.5 L m–2 h–1 bar–1) with a high Na2SO4 rejection above 95%, which outperforms almost all of the non‐polyamide membranes and commercially available nanofiltration membranes. This strong‐coordination interfacial self‐assembly method will open up a new way for the development of functional metal‐organic supramolecular films for high‐performance membrane separation and beyond.

Technostress as an antecedent factor exploring knowledge hiding continues to be seldomly discussed in the digital era. Based on the job demand-resource theory, this article introduces work exhaustion as a mediator variable and constructs a model that the five sub-dimensions of technostress (i.e., overload, invasion, complexity, insecurity, and uncertainty) affect knowledge hiding for R&D employees. Similarly, this study analyzes the moderation of workplace friendship as the resource buffering effect. Based on data from the 254 questionnaires of the two-stage survey, empirical results show that: (1) Techno-invasion, techno-insecurity, and techno-complexity have significant positive effects on work exhaustion, and techno-invasion has the greatest effect. However, techno-overload and techno-uncertainty have no significant relationship with work exhaustion. (2) Work exhaustion plays a mediating role in the relationships between the three aspects of technostress (techno-invasion, techno-insecurity, techno-complexity) and knowledge hiding; However, its mediating effects are insignificant in the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and knowledge hiding. (3) Workplace friendship negatively moderates the relationships between the two aspects of technostress (techno-invasion and techno-insecurity) and work exhaustion, leading to less knowledge hiding. Nonetheless, its negative moderation for the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and work exhaustion are insignificant. Empirical results further show that workplace friendship positively moderates the relationship between techno-complexity and work exhaustion.

Many studies have investigated the molecular crosstalk between mastitis-pathogens and cows by either miRNA or mRNA profiles. Here, we employed both miRNA and mRNA profiles to understand the mechanisms of the response of bovine mammary epithelial cells (bMECs) to lipopolysaccharide (LPS) by RNA-Seq. The total expression level of miRNAs increased while mRNAs reduced after LPS treatment. About 41 differentially expressed mRNAs and 45 differentially expressed miRNAs involved in inflammation were screened out. We found the NFκB-dependent chemokine, CXCL1, CXCL3, CXCL6, IL8, and CX3CL1 to be strongly induced. The anti-apoptosis was active because BCL2A1 and BIRC3 significantly increased with a higher expression. The effects of anti-microbe and inflammation were weakly activated because TNF, IL1, CCL20, CFB, S100A, MMP9, and NOS2A significantly increased but with a low expression, IL6 and β-defensin decreased. These activities were supervised by the NFKBIA to avoid excessive damage to bMECs. The bta-let-7a-5p, bta-miR-30a-5p, bta-miR-125b, and bta-miR-100 were essential to regulate infection process in bMECs after LPS induction. Moreover, the lactation potential of bMECs was undermined due to significantly downregulated SOSTDC1, WNT7B, MSX1, and bta-miR-2425-5p. In summary, bMECs may not be good at going head-to-head with the pathogens; they seem to be mainly charged with sending out signals for help and anti-apoptosis for maintaining lives after LPS induction.

Background: Dyspnea is a multidimensional experience similar to pain and is one of the most common clinical presentations in patients with respiratory diseases. Accurately evaluating the experience of dyspnea allows nurses and physicians to deliver better medical services to patients. The multidimensional dyspnea profile emphasizes the psychosocial factors of dyspnea and assesses immediate discomfort, sensory qualities, and the emotional responses of patients with dyspnea. At present, the validity, reliability, and test–retest reliability of the multidimensional dyspnea profile in patients with respiratory diseases in China are unclear. Objectives: The aim of this study was to investigate the validity, reliability, and test–retest reliability of the Chinese version of the multidimensional dyspnea profile and to assess the convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale. Methods: The factorial construct, intraclass correlations, internal consistency, and convergent validity of the Chinese version of the multidimensional dyspnea profile was evaluated using data from 231 inpatients with dyspnea from the respiratory department of a hospital. In the principal component analysis stage, 131 inpatients were evaluated. In the test–retest reliability analysis stage, 50 out of the 131 patients responded to the questionnaire again. In the confirmatory factor analysis, 100 inpatients from an independent sample were assessed. Results: The principal component analysis showed that the Chinese version of the multidimensional dyspnea profile had a two-factor structure: the immediate perceptual-related problem factor (6 items) and the emotional response-related problem factor (5 items). The convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale was significant and acceptable based on the average variance extracted (r = .56, p

Objective: To evaluate the efficacy and safety of endoscopic variceal ligation + endoscopic injection sclerotherapy (EVL+EIS) to control acute variceal bleeding (AVB).Methods: Online databases, including Web of Science, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) disc, VIP, and Wanfang, were searched to identify the studies comparing the differences between EVB+EIS and EVB, EIS from the inception of the databases up to December 30, 2020. STATA 13.0 was used for the meta-analysis.Results: A total of eight studies involving 595 patients (317 patients in the EVL group and 278 patients in the EVL+EIS group) were included. The results of the meta-analysis did not reveal any statistically significant differences in the efficacy of acute bleeding control (P = 0.981), overall rebleeding (P = 0.415), variceal eradication (P = 0.960), and overall mortality (P = 0.314), but a significant difference was noted in the overall complications (P = 0.01).Conclusion: EVL is superior to the combination of EVL and EIS in safety, while no statistically significant differences were detected in efficacy. Further studies should be designed with a large sample size, multiple centers, and randomized controlled trials to assess both clinical interventions.

Objectives With about one-third of the population living below the poverty line, Jordan faces major healthcare, social and national development issues. Low insurance coverage among the poor and high out-of-pocket expenditure worsens the financial insecurity especially for the marginalised population. The Government of Jordan aims to achieve universal coverage of health insurance—a bold plan that requires research evidence for successful implementation. In this study, we aimed to assess the proportion of the population covered by any health insurance, and the determinants owing a health insurance.Design A population-based prospective cohort study.Setting Jordan.Methods Data for this study were derived from the Jordan Population and Family Health Survey, which was implemented by the Department of Statistics from early October 2017 to January 2018. Sample characteristics were described as percentages with 95% CIs. Binary logistic regression models were used to estimate OR of health insurance ownership. Parsimonious model was employed to assess the sex and geographical differences.Results Data revealed that in 2017–2018, 73.13% of the 12 992 men and women had health insurance. There was no indication of age of sex difference in health insurance ownership; however, marital status and socioeconomic factors such as wealth and education as well as internet access and geographical location appeared to be the important predictors of non-use of health insurance. The associations differed by sex and urbanicity for certain variables. Addressing these inequities may help achieve universal coverage in health insurance ownership in the population.Conclusions More than one-quarter of the population in Jordan were not insured. Efforts to decrease disparities in insurance coverage should focus on minimising socioeconomic and geographical disparities to promote equity in terms of healthcare services.

Ovarian cancer (OVCA) is the most lethal gynaecological cancer with a 5-year survival rate less than 50%. Despite new therapeutic strategies, such as immune checkpoint blockers (ICBs), tumor recurrence and drug resistance remain key obstacles in achieving long-term therapeutic success. Therefore, there is an urgent need to understand the cellular mechanisms of immune dysregulation in chemoresistant OVCA in order to harness the host’s immune system to improve survival. The over-expression of plasma gelsolin (pGSN) mRNA is associated with a poorer prognosis in OVCA patients; however, its immuno-modulatory role has not been elucidated. In this study, for the first time, we report pGSN as an inhibitor of M1 macrophage anti-tumor functions in OVCA chemoresistance. Increased epithelial pGSN expression was associated with the loss of chemoresponsiveness and poor survival. While patients with increased M1 macrophage infiltration exhibited better survival due to nitric-oxide-induced ROS accumulation in OVCA cells, cohorts with poor survival had a higher infiltration of M2 macrophages. Interestingly, increased epithelial pGSN expression was significantly associated with the reduced survival benefits of infiltrated M1 macrophages, through apoptosis via increased caspase-3 activation and reduced production of iNOS and TNFα. Additionally, epithelial pGSN expression was an independent prognostic marker in predicting progression-free survival. These findings support our hypothesis that pGSN is a modulator of inflammation and confers chemoresistance in OVCA, in part by resetting the relative abundance and function of macrophage subtypes in the ovarian tumor microenvironment. Our findings raise the possibility that pGSN may be a potential therapeutic target for immune-mediated chemoresistance in OVCA.

Background. Information regarding the impact of cardiovascular (CV) conditions on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. Methods. This study evaluated the association of underlying CV conditions with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to the designated hospital for intensive care due to COVID-19 disease progression. The patients were divided into with and without CV conditions as well as stable and intensive care groups. Results. Of the 332 patients with mild COVID-19, the median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of the 48 (14.5%) patients with CV conditions, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CV conditions, patients with CV conditions were older and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CV conditions than in patients without CV conditions (47.92% vs. 12.4%; P

Background: Over-expression of Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) in cancer cells has been reported in the context of several tumors (including ovarian cancer) and is associated with poor prognosis. The aim of this study was to construct a fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) and investigate its antitumor activity against ovarian cancer cells, bothin vitro and in vivo. Methods: A fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) eukaryotic expression vector was constructed and ROR1-IgG antibody was expressed in CHO cells. The characteristics of ROR1-IgG were investigated by ELISA, SPR, Western blotting, FACS and fluorescence staining analyses. CCK8 and wound healing assays were performed to determine inhibition and migration capacity of ovarian cancer cells after treatment with ROR1-IgGin vitro. Further, the antitumor activity of ROR1-IgG was assessed in vivo using tumor-mice xenograft model. Results: The results showed that ROR1-IgG could specifically bind to ROR1-positive cells (HO8910 and A2780) with a high affinity. Functional studies revealed that ROR1-IgG inhibited the malignant behavior of ROR1-positive cells (HO8910 and A2780) in a time- and dose-dependent manner. These effects were not observed in ROR1-negative lose386 cells. The tumor inhibition rates following treatment with low, medium, and high concentrations of ROR1-IgG were approximately 47.72%, 53.79%, and 60.51%, respectively. In addition, the expression of Bcl-2 was obviously reduced while that of Bax was distinctly elevated in xenografts. Conclusions: Collectively, our findings suggest that ROR1-IgG may be a novel therapeutic agent for patients with ROR1-positive ovarian cancer.

Doxycycline is a broad-spectrum antibacterial drug. It is used widely to treat diseases caused by Mycoplasma species. We investigated the antibacterial activity of doxycycline against the Mycoplasma hyopneumoniae strain ATCC25934. The minimum inhibitory concentration (MIC) of doxycycline against M. hyopneumoniae determined by a microdilution method was 0.125 μg/ml. Static time–kill curves with constant drug concentrations (0–64 MIC) showed that a bacteriostatic effect occurred if the doxycycline concentration reached 4 MIC. Doxycycline produced a maximum antimycoplasmal effect (reduction of 2.76 log10CFU/ml) at 64 MIC within 48 h. The effect of doxycycline against M. hyopneumoniae was analyzed by a sigmoid Emax model, and there was high correlation between the kill rate and doxycycline concentration (R2 = 0.986). A one-compartment open model with first-order absorption was adopted and was used to simulate doxycycline pharmacokinetics in porcine plasma. The dynamic time–concentration curve showed that the area under the curve at 24 h (AUC24 h) and Cmax (peak concentration) after each drug administration was 1.78–48.4 μg h/ml and 0.16–3.41 μg/ml, respectively. The reduction of M. hyopneumoniae (log10CFU/ml) for 1, 2.5, 5, 7.5, 10, 15, 20, and 30 mg/kg body weight was 0.16, 1.29, 1.75, 2.94, 3.35, 3.91, 4.35, and 5.77, respectively, during the entire experiment, respectively. When the dose was >10 mg/kg body weight, continuous administration for 3 days could achieve a bactericidal effect. The correlation coefficient of AUC24 h/MIC, Cmax/MIC, and %T > MIC (the cumulative percentage of time over a 24-h period that the drug concentration exceeds the MIC) with antibacterial effect was 0.917, 0.923, and 0.823, respectively. Doxycycline showed concentration-dependent activity, and the value of AUC24 h/MIC and Cmax/MIC required to produce a drop of 1 log10CFU/ml was 164 h and 9.89, respectively.

Pecking Opera Painted Faces (POPF) is a Chinese intangible cultural heritage full of aesthetic value. However, their cultural connotations become less known in modern society. It is therefor, necessary to make public easily understand unique cultural connotation and aesthetic value of POPF. In this project, we built a POPF image database based on the image classification model, with the aim to better showcase POPF. The images are classified into multiple categories according to the traditional connotation patterns. By using the MLP (Multilayer Perceptrons) algorithm classifier, the classification accuracy of model has approached 70%. Using those tools, the uncertainty of information about images of POPF can be reduced appreciably, and would benefit the innovation of derivatives around POPF.

Emergency triage is an important tool for prioritizing urgent or critical patients, and its effect needs to be investigated and evaluated. This observational study aimed to compare the reliability and validity of the Chinese four-level and three-district triage standard (CHT) and the Australasian Triage Scale (ATS) in an adult emergency department of a general hospital in China. From 2016-01 to 2017-01, twelve nurses independently performed on-site triage of 254 patients and 1552 patients to assess the scales’ reliability and validity, respectively. The interrater reliability, as assessed by the weighted k scores, was 0.686 (95% CI 0.608–0.757) for the CHT and 0.731 (95% CI 0.663–0.790) for the ATS, and the k scores between the CHT and the ATS were 0.630 (95% CI 0.594–0.669). Temperature, respiration, pulse, blood oxygen saturation, waiting time, treatment time, emergency disposition, hospitalization rate, and mortality were significantly associated with the triage levels of the CHT and ATS (p

Skeletal muscle, accounting for approximately 50% of body weight, is the largest and most important tissue. In this study, the gene expression profiles and pathways in skeletal muscle of Pekin duck were investigated and compared at embryonic day 17, 21, and 27 and postnatally at 6 months of age. An average of 49,555,936 reads in each sample was obtained from the transcriptome libraries. Over 70.0% of alternative splicing (AS) in each sample was mainly alternative 5′ first exon (transcription start site)—the first exon splicing (TSS) and alternative 3′ last exon (transcription terminal site)—the last exon splicing (TTS), indicating that TSS and TTS were the most common AS event in Pekin ducks, and these AS events were closely related to the regulation of muscle development at different growth stages. The results provided a valuable genomic resource for selective breeding and functional studies of genes. A total of 299 novel genes with ≥2 exons were obtained. There were 294 to 2806 differentially expressed genes (DEGs) in each pairwise comparison of Pekin duck. Notably, 90 DEGs in breast muscle and 9 DEGs in leg muscle were co-expressed at all developmental points. DEGs were validated by qPCR analysis, which confirmed the tendency of the expression. DEGs related to muscle development were involved in biological processes such as “endodermal cell differentiation”, “muscle cell cellular homeostasis”, “skeletal muscle tissue growth” and “skeletal muscle cell differentiation”, and were involved in pathways such as oxidative phosphorylation, ECM-receptor (extracellular matrix receptor) interaction, focal adhesion, carbon metabolism, and biosynthesis of amino acids. Some DEGs, including MYL4, IGF2BP1, CSRP3, SPP1 and KLHL31, as well as LAMB2, LAMA2, ITGB1 and OPN, played crucial roles in muscle growth and development. This study provides valuable information about the expression profile of mRNAs and pathways from duck skeletal muscle at different growth stages, and further functional study of these mRNAs and pathways could provide new ideas for studying the molecular networks of growth and development in duck skeletal muscle.

As one of the most important poultry worldwide, ducks (Anas platyrhynchos) are raised mainly for meat and egg products, and muscle development in ducks is important for meat production. Therefore, an investigation of gene expression in duck skeletal muscle would significantly contribute to our understanding of muscle development. In this study, twenty-four cDNA libraries were constructed from breast and leg muscles of Hanzhong Ma ducks at day 17, 21, 27 of the embryo and postnatal at 6-month-old. High-throughput sequencing and bioinformatics were used to determine the abundances and characteristics of transcripts. A total of 632,172,628 (average 52,681,052) and 637,213,938 (average 53,101,162) reads were obtained from the sequencing data of breast and leg muscles, respectively. Over 71.63% and 77.36% of the reads could be mapped to the Anas platyrhynchos genome. In the skeletal muscle of Hanzhong duck, intron variant (INTRON), synonymous variant (SYNONYMOUS_CODING), and prime 3′ UTR variant (UTR_3_PRIME) were the main single nucleotide polymorphisms (SNP) annotation information, and “INTRON”, “UTR_3_PRIME”, and downstream-gene variant (DOWNSTREAM) were the main insertion-deletion (InDel) annotation information. The predicted number of alternative splicing (AS) in all samples were mainly alternative 5′ first exon (transcription start site)-the first exon splicing (TSS) and alternative 3′ last exon (transcription terminal site)-the last exon splicing (TTS). Besides, there were 292 to 2801 annotated differentially expressed genes (DEGs) in breast muscle and 304 to 1950 annotated DEGs in leg muscle from different databases. It is worth noting that 75 DEGs in breast muscle and 49 DEGs in leg muscle were co-expressed at all developmental points of comparison, respectively. The RNA-Seq data were confirmed to be reliable by qPCR. The identified DEGs, such as CREBL2, RHEB, GDF6, SHISA2, MYLK2, ACTN3, RYR3, and STMN1, were specially highlighted, indicating their strong associations with muscle development in the Hanzhong Ma duck. KEGG pathway analysis suggested that regulation of actin cytoskeleton, oxidative phosphorylation, and focal adhesion were involved in the development of skeletal muscle. The findings from this study can contribute to future investigations of the growth and development mechanism in duck skeletal muscle.

In China, the production for duck meat is second only to that of chicken, and the demand for duck meat is also increasing. However, there is still unclear on the internal mechanism of regulating skeletal muscle growth and development in duck. This study aimed to identity candidate genes related to growth of duck skeletal muscle and explore the potential regulatory mechanism. RNA-seq technology was used to compare the transcriptome of skeletal muscles in black Muscovy ducks at different developmental stages (day 17, 21, 27, 31, and 34 of embryos and postnatal 6-month-olds). The SNPs and InDels of black Muscovy ducks at different growth stages were mainly in “INTRON”, “SYNONYMOUS_CODING”, “UTR_3_PRIME”, and “DOWNSTREAM”. The average number of AS in each sample was 37,267, mainly concentrated in TSS and TTS. Besides, a total of 19 to 5377 DEGs were detected in each pairwise comparison. Functional analysis showed that the DEGs were mainly involved in the processes of cell growth, muscle development, and cellular activities (junction, migration, assembly, differentiation, and proliferation). Many of DEGs were well known to be related to growth of skeletal muscle in black Muscovy duck, such as MyoG, FBXO1, MEF2A, and FoxN2. KEGG pathway analysis identified that the DEGs were significantly enriched in the pathways related to the focal adhesion, MAPK signaling pathway and regulation of the actin cytoskeleton. Some DEGs assigned to these pathways were potential candidate genes inducing the difference in muscle growth among the developmental stages, such as FAF1, RGS8, GRB10, SMYD3, and TNNI2. Our study identified several genes and pathways that may participate in the regulation of skeletal muscle growth in black Muscovy duck. These results should serve as an important resource revealing the molecular basis of muscle growth and development in duck.

Chemoresistance and metastasis are the main causes of treatment failure and unfavorable outcome in cancers. There is a pressing need to reveal their mechanisms and to discover novel therapy targets. Autophagy is composed of a cascade of steps controlled by different autophagy-related genes (ATGs). Accumulating evidence suggests that dysregulated autophagy contributes to chemoresistance and metastasis via competing endogenous RNA (ceRNA) networks including lncRNAs and circRNAs. ceRNAs sequester the targeted miRNA expression to indirectly upregulate ATGs expression, and thereof participate in autophagy-mediated chemoresistance and metastasis. Here, we attempt to summarize the roles of ceRNAs in cancer chemoresistance and metastasis through autophagy regulation.

Objectives: We aimed to determine the demographic characteristics of giant cell tumor around the knee in China. Methods: Between March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age. Results: 334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged ≤40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009). Conclusions: Giant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients ≤40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee.

Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin.

Resveratrol (trans-3,4,5'-trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

Microfluidic devices have attracted increasing attention in the fields of biomedical diagnostics, food safety control, environmental protection, and animal epidemic prevention. Micromixing has a considerable impact on the efficiency and sensitivity of microfluidic devices. This work reviews recent advances on the passive and active micromixers for the development of various microfluidic chips. Recently reported active micromixers driven by pressure fields, electrical fields, sound fields, magnetic fields, and thermal fields, etc. and passive micromixers, which owned two-dimensional obstacles, unbalanced collisions, spiral and convergence-divergence structures or three-dimensional lamination and spiral structures, were summarized and discussed. The future trends for micromixers to combine with 3D printing and paper channel were brought forth as well.

Understanding how individuals collaborate with others is a complex undertaking, because collaborative problem-solving (CPS) is an interactive and dynamic process. We attempt to identify distinct collaborative problem-solver profiles of Chinese 15-year-old students on a computer-based CPS task using process data from the 2015 Program for International Student Assessment (PISA, N = 1,677), and further to examine how these profiles may relate to student demographics (i.e., gender, socioeconomic status) and motivational characteristics (i.e., achieving motivation, attitudes toward collaboration), as well as CPS performance. The process indicators we used include time-on-task, actions-on-task, and three specific CPS process skills (i.e., establish and maintain shared understanding, take appropriate action to solve the problem, establish and maintain team organization). The results of latent profile analysis indicate four collaborative problem-solver profiles: "Disengaged," "Struggling," "Adaptive," and "Excellent." Gender, socioeconomic status, attitudes toward collaboration and CPS performance are shown to be significantly associated with profile membership, yet achieving motivation was not a significant predictor. These findings may contribute to better understanding of the way students interact with computer-based CPS tasks and inform educators of individualized and adaptive instructions to support student collaborative problem-solving.