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Abstract Endoplasmic reticulum (ER) is an enclosed three-dimensional eukaryotic membrane network composed of flattened sacs. Fusion of homologous membranes to the ER membrane is essential for the maintenance of this network structure. In yeast, ER membrane fusion is mediated by Sey1p, whose paralogues function distinctly in different species. In this study, we investigated the biological functions of MoSEY1 in the devastating rice blast fungus Magnaporthe oryzae by functional genomic approach. Compared to wild type, deletion of MoSEY1 considerably decreased the growth and conidia production of M. oryzae. Additionally, the absence of MoSEY1 delayed appressorium formation and invasive hyphae growth. The appressorium function was also impaired in ΔMosey1 mutant. Subcellular localization analysis revealed that MoSey1 is localized at the ER. The ΔMosey1 mutant showed augmented sensitivity to ER stress. Additionally, we found that MoSey1 regulated the unfolded protein response, autophagy, and protein secretion in M. oryzae. In conclusion, our study unveiled the involvement of MoSey1 in the development, pathogenesis, and ER functions in M. oryzae.

Purpose This study aimed to compare the efficacies of Femoston and Dydrogesterone therapy in patients with incomplete abortions.Methods Patients with incomplete abortions were included if they preferred medication over surgical intervention. The participants were categorized into three groups: the Femoston group received Femoston, the Dydrogesterone group was administered Dydrogesterone, and the control group was followed up without treatment. Basic clinical information, complete abortion success rate, and menstrual recovery rate were collected to evaluate the efficacy of Femoston and Dydrogesterone in patients with incomplete abortions.Results We analyzed 332 patients with incomplete abortions. The success rate of complete abortion was significantly higher in the Femoston group than in the control group (relative risk (RR)=1.708, 95% CI 1.304–2.237, p = .001) and the Dydrogesterone group (RR = 1.200, 95% CI 1.015–1.418, p = .023). The effectiveness of Dydrogesterone was also significantly higher than that in the control group (RR = 1.439, 95% CI 1.068–1.938, p = .015). After 60 days, the rate of menstrual recovery in the Femoston group was significantly higher than that in the control group (RR =1.322, 95% CI 1.103–1.609, p = .001), while the rate in the Dydrogesterone group was significantly lower than that in the Femoston group (RR =1.200, 95% CI 1.035–1.391, p = .009).Conclusions Femoston and Dydrogesterone were effective in treating incomplete abortions, with Femoston being more effective. Patients receiving Femoston had shorter menstrual recovery times than those receiving dydrogesterone. Therefore, Femoston and Dydrogesterone are potential treatment options for incomplete abortion, with Femoston being the more effective.

The rice blast disease, caused by the fungus Magnaporthe oryzae, is a significant agricultural problem that adversely impacts rice production and food security. Understanding the precise molecular pathways involved in the interaction between the pathogen and its host is crucial for developing effective disease management strategies. This study examines the crucial function of the nucleolin MoNsr1 in regulating M. oryzae physiological functions. ΔMoNsr1 deletion mutants showed reduced fungal growth, asexual sporulation, and pathogenicity compared to the wild-type. Mutants exhibited impaired conidial germination and appressoria formation, reducing infection progression. Additionally, ΔMoNsr1 deletion mutant had less turgor pressure, confirming that MoNsr1 is essential for cell wall biogenesis and resistant to external stresses. Furthermore, ΔMoNsr1 deletion mutant showed enhanced sensitivity to oxidative stress, reactive oxygen species, and cold tolerance. Our results offer a thorough understanding of the function of MoNsr1 in the virulence and stress-resilient capability in M. oryzae. These findings provide insights into the novel targets and contribute to the emergence of innovative approaches for managing rice blast disease.

Abstract Compared to transition metal dichalcogenide (TMD) monolayers, rhombohedral-stacked (R-stacked) TMD bilayers exhibit remarkable electrical performance, enhanced nonlinear optical response, giant piezo-photovoltaic effect and intrinsic interfacial ferroelectricity. However, from a thermodynamics perspective, the formation energies of R-stacked and hexagonal-stacked (H-stacked) TMD bilayers are nearly identical, leading to mixed stacking of both H- and R-stacked bilayers in epitaxial films. Here, we report the remote epitaxy of centimetre-scale single-crystal R-stacked WS2 bilayer films on sapphire substrates. The bilayer growth is realized by a high flux feeding of the tungsten source at high temperature on substrates. The R-stacked configuration is achieved by the symmetry breaking in a-plane sapphire, where the influence of atomic steps passes through the lower TMD layer and controls the R-stacking of the upper layer. The as-grown R-stacked bilayers show up-to-30-fold enhancements in carrier mobility (34 cm2V−1s−1), nearly doubled circular helicity (61%) and interfacial ferroelectricity, in contrast to monolayer films. Our work reveals a growth mechanism to obtain stacking-controlled bilayer TMD single crystals, and promotes large-scale applications of R-stacked TMD.

Abstract Background Parenting is both a complex and stressful endeavor, so parents sometimes experience parenting burnout. The main objective of this study was to provide an overview of factors related to general parental burnout (PB) among parents with at least one child based on the Ecological Systems Theory (EST). Methods PubMed, Web of Science, EBSCO, CNKI and WanFang were systematically searched for studies published from 2010 to July 2023 for peer-reviewed articles using keywords extracted from Medical Subject Headings such as “parenting”, “parental”, “burnout”, “psychological burnout”, “burn-out syndrome”. Studies were included if they described associations between factors and PB among parents of children aged 0-18 years old in the general population, and published in an English or Chinese language peer-reviewed journal. The Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was employed to assess the risk of bias of included studies. Results Of 2037 articles, 26 articles met the inclusion criteria. Based on the Ecological Systems Theory (EST), we found that microsystem-individual factors such as gender, educational level, income, parental personality, internalization of maternal parental motivation, unmitigated communion, self-compassion and concern for others, alexithymia, anxiety and depressive symptoms, parental perfectionism, resilience, low self-esteem and high need for control, mother's attachment style were identified as being associated with parenting burnout. Mesosystem-interpersonal factors involve parent-child relationship and marital satisfaction. The exosystem-organizational or community factors include the number of children in the household, neighborhood and the number of hours spent with children, child's illness, child's behavior problems and social support. The macrosystem-society/policy or culture factors are mainly personal values and cultural values. Conclusions This systematic review found several factors that have been investigated in relation to PB. However, the majority of the factors were reported by one or two studies often implementing a cross-sectional design. Nevertheless, we still recommend that health policymakers and administrators relieve parenting burnout among parents with children by adjusting these modifiable factors.

In this paper, we explore and analyze the network subculture in the youth and actively explore the new path of socialist core values to cultivate the values of college students. Through the effective questionnaire survey of college students, the prediction model of decision support is established by improving the metaheuristic algorithms. Hunger games search (HGS) is a metaheuristic algorithm widely used in many fields. However, the method converges slowly and veers toward the local optimum when presented with challenging problems. Therefore, there is room for HGS to develop. We introduce a brand-new HGS variant, denoted as SDHGS. This variant combines the directional crossover mechanism with an adaptive Lévy diversity strategy. The directed crossover mechanism endeavors to harmonize the interplay between exploration and exploitation, while the adaptive Lévy diversity facet enhances the range of variations within the population. The cooperation of these mechanisms within SDHGS concludes in an augmented convergence rate and heightened precision. SDHGS is compared to HGS, seven classic algorithms, and enhanced algorithms on the benchmark function set to evaluate and demonstrate the performance. Besides, various analytical techniques, such as the Friedman test and the Wilcoxon signed-rank test, are considered when analyzing the experimental results. The findings demonstrate that SDHGS with two techniques greatly enhances HGS performance. Finally, SDHGS is applied to discuss the internal relationship that affects the existence of youth subculture and establish a prediction model of decision support.

Isomorphism holds that, ideally, a single meaning is expressed by a single form. However, despite long-standing support, the theoretical viability of the isomorphic principle has been called into question. There is widespread recognition that the coexistence of (near-) synonymous expressions—variation—is actually very common in language. In this study, we explore a possible path toward reconciling the theoretical notion of isomorphism with the observable fact of variation. To this end, we adopt an analogy to tool use inspired by Zipf (1949). Tools largely monopolize their core functional domains (e.g., for cutting, knives are overwhelmingly preferred over screwdrivers) but compete over more peripheral functions (for puncturing, knives and screwdrivers have more equal chances of selection). In the same way, we hypothesize forms can code a prototypically organized network of senses, whereby they largely monopolize the core but are more likely to come into competition with other forms in the periphery. To test this hypothesis, a case study is conducted on variation in the use of two prepositions: at and with. For each, a semantic core and periphery are established. Using a corpus consisting of parallel translations of the same source text, it is then tested whether translators are more likely to converge on the same preposition to express one of that preposition’s core senses than to express one of its peripheral senses. This is the pattern one would expect if isomorphic pressure is stronger for semantic cores than for peripheries. The results are promising but inconclusive. They confirm that the sense most prone to competition is arguably the most peripheral but also reveal a surprisingly high level of competition for the spatial core use of at.

Abstract Objective Our present study utilized case–control research to explore the relationship between specific circRNAs and pediatric obesity through a literature review and bioinformatics and to predict their possible biological functions, providing ideas for epigenetic mechanism studies of pediatric obesity. Methods CircRNAs related to pediatric obesity were preliminarily screened by a literature review and qRT–PCR. CircRNA expression in children with obesity (n = 75) and control individuals (n = 75) was confirmed with qRT–PCR in a case–control study. This was followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and ceRNA network construction. Multivariate logistic regression was utilized to analyze the effects of circRNAs on obesity. A receiver operating characteristic (ROC) curve was also drawn to explore the clinical application value of circRNAs in pediatric obesity. Results Has_circ_0046367 and hsa_circ_0000284 were separately validated to be statistically downregulated and upregulated, respectively, in the peripheral blood mononuclear cells of children with obesity and revealed as independent indicators of increased CHD risk [hsa_circ_0046367 (OR = 0.681, 95% CI: 0.480 ~ 0.967) and hsa_circ_0000284 (OR = 1.218, 95% CI: 1.041 ~ 1.424)]. The area under the ROC curve in the combined analysis of hsa_circ_0046367 and hsa_circ_0000284 was 0.706 (95% CI: 0.623 ~ 0.789). Enrichment analyses revealed that these circRNAs were actively involved in neural plasticity mechanisms, cell secretion and signal regulation. Conclusion The present research revealed that low expression of hsa_circ_0046367 and high expression of hsa_circ_0000284 are risk factors for pediatric obesity and that neural plasticity mechanisms are closely related to obesity.

Abstract Background To study the value of shear wave elasticity and shear wave dispersion imaging to evaluate the viscoelasticity of renal parenchyma in children with glomerular diseases. Methods Forty-three children with glomerular diseases were prospectively evaluated by shear wave elasticity (SWE) and shear wave dispersion imaging (SWD); 43 healthy volunteers served as the control group. The shear wave velocities (SWV) and the dispersion slopes were measured at the upper, middle, and lower poles of both kidneys. The analysis of mean SWV and mean dispersion slope in control and patient groups was used to further evaluate the value of SWE and SWD in the viscoelasticity of renal parenchyma in children with glomerular disease. Results The mean SWV in children with glomerular disease was higher than that in the healthy control group (1.61 ± 0.09 m/s vs. 1.43 ± 0.07 m/s, p

Objectives To explore the impact of the triglyceride-glucose (TyG) index on the severity of coronary stenosis and the risk of in-hospital mortality in patients with acute ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Design A multicentre retrospective cohort study.Setting Patients with STEMI undergoing PCI from three centres in China from 2015 to 2019.Participants A total of 1491 individuals presenting with STEMI were enrolled.Primary outcome measure The degree of coronary stenosis was quantified by the Gensini score (GS). The association between the TyG index and the severity of coronary stenosis was explored by using a logistic regression analysis. Cox proportional hazards regression analyses were used to investigate the associations between the variables and in-hospital mortality.Results We found a significant correlation between the TyG index and the degree of coronary stenosis in the present study. The TyG index was an independent risk factor for the severity of coronary stenosis (OR 2.003, p

Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.

The purpose of this work was to ameliorate the yield of polysaccharides from Kangxian flowers (PKFs) using ultrasonic-assisted extraction (UAE) and to explore the structural features and cosmetic potential of PKFs obtained under the optimized UAE. According to response surface methodology, the optimal UAE for PKFs were liquid-to-solid ratio of 59: 1 mL/g, ultrasonic power of 404 W, time of 48 min, and temperature of 66℃, under which the yield of PKFs reached 26.8 ± 1.76 %, 2.6-folds higher than hot-water extraction. By comparing the microstructures, it can be seen that ultrasonication exerted great damage on Kangxian flowers to promote the outflow of PKFs. Various analyses revealed that the PKFs extracted with UAE were acidic polysaccharides with relatively lower molecular weights of 0.92 – 76.9 kDa, negatively charged potential of −16.3 mV, and arabinose the dominant monosaccharide followed by galactose. These structural features conferred PKFs pronounced antioxidant, moisture absorption and retention properties, showing great potential for cosmetic application.

Food production security (FPS) and agricultural ecological protection (AEP) are both among the paramount issues affecting the country. There are multiple nonlinear interactions between the two systems, while fewer studies have focused on the interaction patterns between them. To realize China's national strategic goals of food security and ecological protection, the interaction between FPS and AEP needs to be analyzed. Based on the evaluation index system of the coupling and coordination between the two systems, this article analyzes the spatio-temporal differentiation and influencing factors in 13 main food-producing regions in China from 2009 to 2021 using the state-space method and spatial econometric model. The following three conclusions were found: First, the overall development levels of both FPS and AEP show an increasing trend, but regional differences are obvious. Second, the coupling coordination degree and stage of the two systems present an upward trend, but the overall development level remains low, with obvious regional differences: Liaoning is still on the imminent disorder stage, while Heilongjiang has taken the lead into the intermediate coordination stage. Third, the total power of grain machinery and the soybean corn planting ratio have a significant positive impact on the coupling and coordination between FPS and AEP. The results make up for the lack of research on coupling and coordination between FPS and AEP, and provide a feasible development path for exploring coordinated development of FPS and AEP in China's main food-producing areas.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are commonly used in regenerative medicine. However, it is not clear whether transplantation of BMSCs can improve cardiac function of the X-Linked Muscular Dystrophy Mice (mdx) and how to detect it. We aimed to investigate the role of speckle tracking echocardiography (STE) in detecting cardiac function of the BMSCs-transplanted mdx in comparison with the untreated mdx. Methods The experimental mice were divided into the BMSCs-transplanted mdx, untreated mdx, and control mice groups (n = 6 per group). The BMSCs were transplanted via tail vein injections into a subset of mdx at 20 weeks of age. After four weeks, the cardiac functional parameters of all the mice in the 3 groups were analyzed by echocardiography. Then, all the mice were sacrificed, and the cardiac tissues were harvested and analyzed by immunofluorescence. The serum biochemical parameters were also analyzed to determine the beneficial effects of BMSCs transplantation. Results Traditional echocardiography parameters did not show statistically significant differences after BMSCs transplantation for the three groups of mice. In comparison with the control group, mdx showed significantly lower left ventricular (LV) STE parameters in both the long-axis and short-axis LV images (P

ObjectiveMetagenomic next-generation sequencing (mNGS) technology has the potential to detect a wide range of pathogenic microorganisms. However, reports on the diagnostic value and clinical significance of different platforms of mNGS for patients with lower respiratory tract infections (LRTIs) remain scarce.MethodsA total of 306 patients with suspected LRTIs were enrolled from January 2019 to December 2021. The diagnostic performance of conventional methods and mNGS on bronchoalveolar lavage fluid (BALF) were compared. BALF mNGS was performed using a commercial and an in-house laboratory. The diagnostic value and the clinical implications of mNGS for LRTIs were analyzed for the different platforms.ResultsThe positive rate of mNGS in the in-house group was higher than that in the commercial group (85.26% vs. 70.67%, p < 0.001). mNGS significantly increased the pathogen detection rate compared with conventional methods [from 70.67% vs. 22.67% (p < 0.001) to 85.26% vs. 30.77% (p < 0.001)]. The pathogens detected using mNGS included bacteria, fungi, viruses, and atypical pathogens. The in-house platform performed well on a wider spectrum of microbial distribution. Furthermore, it showed an advantage in detecting mixed pathogens in immunocompromised patients. Among the mNGS positive cases, 34 (32.0%) cases had their antibiotics adjusted in the commercial group, while 51 (38.3%) cases had a change of treatment in the in-house group. Moreover, the turnaround time of mNGS and the time from mNGS to discharge in the in-house group were significantly shorter than those in the commercial group.ConclusionIn-house mNGS had a higher detection rate and can show a wider spectrum of pathogens, with potential benefits for the clinic by shortening the turnaround time and hospitalization, and it may be more suitable for clinical microbiology laboratories.

BackgroundThis current study set out to investigate the status of sleep health in 7–20-year-old students in Fuzhou and explore the related influencing factors of sleep health.MethodsA total of 38,467 children and adolescents in Fuzhou were included in the study through a random stratified cluster sampling. Data were collected from May to June 2019, in 18 primary schools and 18 middle schools from nine districts, Fuzhou. Children's parents and adolescents of sampled classes were invited to fill out a series of questionnaires about the performance of the last 6 months (sociodemographic characteristics, sleep-related lifestyle behaviors, and electronic-products usage). Multiple linear regression was carried out to analyze data.ResultsOf the total 40,888 questionnaires we released, 38,467 were valid and effective with the response rate was 94.08%. The age of the surveyed participants was 11.85 ± 3.1, including 20,013 boys and 18,454 girls. The multiple linear regression analysis identified factors associated with sleep health (p < 0.05): Boy (coef = 0.073, 95% CI: 0.030–0.115), age (coef = 1.797, 95% CI: 0.224–0.243), key school (coef = 2.069, 95% CI: 0.105–0.193), urban (coef = 0.096, 95% CI: 0.054–0.139), excessive daytime sleepiness (coef = 0.535, 95% CI: 0.432–0.639), unhealthy sleep habits (coef = 0.363, 95% CI: 0.307–0.419), eating before sleep (coef = 0.578, 95% CI: 0.527–0.630), using electronic products in bedroom (coef = 0.074, 95% CI: 0.028–0.121), screen time per day during school (coef = 0.260, 95% CI: 0.235–0.284), frequency of using electronics 30 min before bedtime (coef = 0.150, 95% CI: 0.134–0.166), strained relationship with parents (coef = 0.361, 95% CI: 0.270–0.452), strained relationship with peers (coef = 0.267, 95% CI: 0.171–0.363), excessive homework or learning (coef = 0.189, 95% CI: 0.141–0.237), time for doing homework (coef = 0.266, 95% CI: 0.245–0.287), and mood swings frequently (coef = 1.174, 95% CI: 1.127–1.221) negatively impact sleep health. Sleep alone (coef = −0.204, 95% CI: −0.262–0.147) were the risk factors for sleep health. Furthermore, frequent mood swings was considered the most influential factor on overall variables.ConclusionsSleep health is associated with factors covered sociodemographic characteristics, family sleep habits, and routine activities before bedtime. Multiple measures should be taken to improve sleep quality in a targeted manner.

Objectives: Globally, informal caregivers caring for cancer patients meet challenges within their caregiving role, which significantly influence their quality of life. This qualitative systematic review aimed to analyze how cancer caregiving influence the quality of life of informal caregivers and the management strategies of informal caregivers for their role as cancer caregivers. Methods: Following the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement, Wanfang database, the China National Knowledge Infrastructure (CNKI), CINAHL, MEDLINE, PubMed, Cochrane Library, PsycARTICLES and PsycINFO, and grey literature in English and Chinese from 1 May 2009 to 31 December 2019 were searched. Quality of included studies was assessed by the Critical Appraisal Skills Programme (2018) Qualitative Checklist and thematic synthesis was conducted. Results: Of the 8,945 studies identified, 6 studies met the inclusion criteria. One analytical theme relating to the QoL of informal caregivers following cancer caregiving was identified: “challenges of caregiving”. In terms of the management strategies to the role of cancer caregivers, two analytical themes were identified: “self-adjustment” and “seeking for formal and informal support”. Conclusions: Cancer caregiving influences informal caregivers’ QoL significantly and informal caregivers develop diverse coping strategies to deal with the difficulties occurred while balancing the relationship between their own lives and caregiving. However, professional and policy support remain inadequate for informal caregivers that require the need for improvement in terms of health care professionals and policymakers.

Existing text sentiment analysis methods mostly rely on a large number of language knowledge and sentiment resources. This paper proposes the Multi-channel convolution and bidirectional GRU multi-head attention capsule (AT-MC-BiGRU-Capsule), which uses vector neurons to replace scalar neurons to model text emotions, and uses capsules to characterize text emotions. In addition, traditional methods cannot extract the multi-level features of text sequence well. Multi-head attention can encode the dependencies between words, capture sentiment words in text, and using Convolutional Neural Network (CNN) and Bidirectional gated recurrent unit network (Bi-GRU) to extract local features and global semantic features of text respectively, the global average pooling layer is introduced to obtain the multi-level feature representation of the text sequence more comprehensively. This paper selects three English datasets and one Chinese dataset in the general corpus of sentiment classification to conduct experiments, and achieves better results than other baseline models.

Abstract Background The present study aims to investigate the complete long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in Intracranial aneurysm (IA) patients and controls by RNA sequencing, which reveals the lncRNA with predictive value for IA risk. Methods The comprehensive lncRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs), followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and CNC network construction. Subsequently, qRT-PCR was used to profile the expression levels of selected lncRNA (lncRNA ENST000000576153, lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1, lncRNA ENST00000508090 and lncRNA ENST00000579688) in 30 (small) or 130 (large) peripheral blood leukocytes, respectively. Multivariate logistic regression was utilized to analyze the effects of lncRNA on IA. Receiver operating characteristic (ROC) curve was further drawn to explore the value of lncRNA in predicting IA. Results Totally 900 up-regulated and 293 down-regulated lncRNAs, as well as 1297 up-regulated and 831 down-regulated mRNAs were discovered in sequencing. Enrichment analyses revealed that they were actively involved in immune/inflammatory response and cell adhesion/extracellular matrix. Co-expression analysis and further enrichment analyses showed that five candidate lncRNAs might participate in IA’s inflammatory response. Besides, after controlling other conventional risk factors, multivariate logistic regression analysis disclosed that low expression of lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1 in peripheral blood leukocytes were independent risk factors for IA. LncRNA ENST00000607042 has superior diagnostic value for IA. Conclusions This study reveals the complete lncRNAs expression profiles in IA. The inflammatory response was closely related to IA. Besides, lncRNA ENST00000607042 might be a novel biomarker for IA risk.

MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.

Nonalcoholic fatty liver disease (NAFLD), main cause of liver damage, is inextricably linked to diabetes. However, there is no specific means to improve the pathology of fatty liver in diabetic patients. Brown adipose tissue (BAT) is an important endocrine organ that secretes adipokines and microRNAs (miRNAs) involved in systemic metabolic regulation. To investigate the effects of BAT transplantation on liver lipid metabolism in diabetic mice, we transplanted BAT from male donor mice into diabetic mice induced by streptozotocin (STZ) combined with high-fat diet (HFD). At 10 weeks after transplantation, BAT transplantation significantly decreased the blood glucose and lipid, downregulated FAS, CD36, Scd1, ACCα, NOX2, NOX4, TGF-β1, FN and COL-1, up-regulated Nrf2, reversed the pathological changes of liver and increased the circulating miR-99a in diabetic mice. To verify whether circulating miR-99a improves oxidative stress by targeting inhibition of NOX4, we used 0.4mM palmitic acid (PA) to treat the LO2 cells. The expression of NOX4 protein was significantly decreased after transfection with miR-99a mimic, and increased after transfection with miR-99a inhibitor. Luciferase reporter assay confirmed that miR-99a could target NOX4 mRNA. These findings clarify the role of miR-99a and NOX4 in liver beneficial effect of BAT transplantation in diabetic mice.

Background: Residential surrounding greenness may be protective of dyslipidemia are often theorized but remain poorly quantified. In particular, the underlying biological mechanisms of blood lipid changes with green spaces remain unclear. Methods: Our observational epidemiology study included a residentially stable sample of 1035 coronary heart disease patients, and proteomics study included 16 participants. Normalized Difference Vegetation Index (NDVI) was used to evaluate residential greenness exposures. Proteomics technology was used to identify plasma greenness-related proteome disturbance, and the pathway analysis was employed to evaluate the potential biological mechanisms of greenness decreasing dyslipidemia risk. Result: Higher residential surrounding greenness in the 500-m area was associated with lower risks of dyslipidemia (odds ratio (OR) = 0.871, 95% confidence interval (CI): 0.763, 0.994 for per one-quartile NDVI increase). Lymphocytes mediated 18.7% of the association between greenness and dyslipidemia. Greenness related proteins (including PLXDC1, IGFBP2 and LY6D) may regulate the biological functions of lipid metabolism and transport-related proteins (including ADIPOQ and CES1) through a series of biological processes. Conclusion: People in greener surroundings have a lower risk of dyslipidemia, which may be due to their lower inflammation, stronger lipid transporter activity, and normal cholesterol metabolism.

The evaluation of the learning process is an effective way to realize personalized online learning. Real-time evaluation of learners’ cognitive level during online learning helps to monitor learners’ cognitive state and adjust learning strategies to improve the quality of online learning. However, most of the existing cognitive level evaluation methods use manual coding or traditional machine learning methods, which are time-consuming and laborious. They cannot fully mine the implicit cognitive semantic information in unstructured text data, making the cognitive level evaluation inefficient. Therefore, this study proposed the bidirectional gated recurrent convolutional neural network combined with an attention mechanism (AM-BiGRU-CNN) deep neural network cognitive level evaluation method, and based on Bloom’s taxonomy of cognition objectives, taking the unstructured interactive text data released by 9167 learners in the massive open online course (MOOC) forum as an empirical study to support the method. The study found that the AM-BiGRU-CNN method has the best evaluation effect, with the overall accuracy of the evaluation of the six cognitive levels reaching 84.21%, of which the F1-Score at the creating level is 91.77%. The experimental results show that the deep neural network method can effectively identify the cognitive features implicit in the text and can be better applied to the automatic evaluation of the cognitive level of online learners. This study provides a technical reference for the evaluation of the cognitive level of the students in the online learning environment, and automatic evaluation in the realization of personalized learning strategies, teaching intervention, and resources recommended have higher application value.

Antibacterial hand sanitizers could play a prominent role in slowing down the spread and infection of hand bacterial pathogens; luteolin (LUT) is potentially useful as an antibacterial component. Therefore, this study elucidated the antibacterial mechanism of LUT against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and developed an antibacterial hand sanitizer. The results showed that LUT had excellent antibacterial activity against both E. coli (minimum inhibitory concentration (MIC) = 312.5 μg/mL, minimal bactericidal concentration (MBC) = 625 μg/mL), and S. aureus (MIC = 312.5 μg/mL, MBC = 625 μg/mL). Furthermore, LUT induced cell dysfunction in E. coli and S. aureus, changed membrane permeability, and promoted the leakage of cellular contents. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) analysis showed that LUT treatment affected cell structure and disrupted cell membrane integrity. The Fourier transform infrared analysis (FTIR) also confirmed that the LUT acted on the cell membranes of both E. coli and S. aureus. Overall, the application of LUT in hand sanitizer had better inhibition effects. Therefore, this study could provide insight into expanding the application of LUT in the hand sanitizer markets.

Foodborne disease caused by Listeria monocytogenes is a major global food safety problem. A potential solution is the antimicrobial development of the highly bioactive natural product juglone, yet few studies exist on its antibacterial mechanism against L. monocytogenes. Thus, we aimed to elucidate the antibacterial mechanism of action of juglone against L. monocytogenes by determining the resultant cell morphology, membrane permeability, membrane integrity, and proteome changes. The minimum inhibitory concentration of juglone against L. monocytogenes was 50 μg/mL, and L. monocytogenes treated with juglone had longer lag phases compared to controls. Juglone induced L. monocytogenes cell dysfunction, leakage of potassium ions, and membrane potential hyperpolarization. Confocal laser scanning microscopy and field-emission-gun scanning electron microscope assays revealed clear membrane damage due to juglone treatment. Fourier transform infrared analyses showed that L. monocytogenes responded to juglone by some conformational and compositional changes in the molecular makeup of the cell membrane. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that juglone either destroyed proteins or inhibited proteins synthesis in L. monocytogenes. Therefore, our findings established juglone as a natural antibacterial agent with potential to control foodborne L. monocytogenes infections.

Introduction: To study the association between specific circular RNAs and rupture of intracranial aneurysm. To explore its clinical diagnostic significance and synergistic effects with individual environmental influencing factors.Methods: Three hundred and forty seven cases and controls were included in this study. Multivariate analysis was used to explore the main individual environmental factors. Intracranial aneurysm rupture related circular RNAs screened based on sequencing was verified in peripheral blood by PCR. ROC curve, logistic regression model and fork analysis were used to study the association, diagnostic values, and synergistic effects of circular RNA with intracranial aneurysms and individual environmental factors.Results: Smoking, hair dyeing, sitting time ≥6 h/day, single animal oil intake and hypertension are the main risk factors for intracranial aneurysm rupture; People with higher education, sleeping time ≥7 h/day, tea drinking, diabetes, higher levels of (hemoglobin, low density lipoprotein, serum calcium, and apolipoprotein-A1) have a low risk of intracranial aneurysm rupture. Hsa_circ_0008433 and hsa_circ_0001946 are closely related to intracranial aneurysm rupture and have certain clinical diagnostic significance (AUC = 0.726; 95% CI: 0.668~0.784). Hsa_circ_0008433 (OR = 0.497, 95% CI: 0.338~0.731), hsa_circ_0001946 (OR = 0.682, 95% CI: 0.509~0.914) were independent epigenetic factors affecting intracranial aneurysm rupture, and have a multiplicative interaction with age (OR = 3.052, 95% CI: 1.006~9.258).Conclusions: Low expressions of hsa_circ_0008433 and hsa_circ_0001946 are risk factors for intracranial aneurysms rupture and have good clinical diagnostic value. There was a multiplicative interaction between epigenetic score and age. The older and the higher the epigenetic score was, the more likely to have intracranial aneurysm rupture.

Background: Parkinson's disease (PD) and sarcopenia are two common diseases in aging people. To date, the prevalence of sarcopenia in PD patients and the relationship between clinical features and sarcopenia in PD patients are not clear. The aim of the study was to (1) assess the prevalence of sarcopenia in PD patients and (2) reveal the clinical features between PD patients with and without sarcopenia.Method: A systematic review was carried out through screening PubMed, EMBASE, and Cochrane database in May 2020. All study designs (case–control, cohort, and cross-sectional studies) were eligible for meta-analysis. Data of patients' characteristics, sarcopenia criteria, sarcopenia prevalence, and sarcopenia measures were retrieved. The primary outcome was estimated prevalence of sarcopenia by a pooled prevalence (%) and its 95% confidence interval (CI), using a random-effects model. The secondary outcome was the differences in clinical features between PD patients with and without sarcopenia by meta-analysis. Included articles were assessed for risk of bias. Potential sources of variation were investigated by using subgroup analyses and meta-regression.Result: Ten studies were included in the review. Among them, nine were cross-sectional studies, and one was a prospective cohort study. Age of participants with PD in the studies ranged from 51.1 to 80.7 years. The estimated prevalence of sarcopenia ranged from 6 to 55.5%. The random-effects pooled prevalence was 29% (95% CIs: 0.18–0.40). When only studies at low risk of bias were considered, pooled prevalence decreased to 17% (95% CIs: 0.02–0.33), with still high heterogeneity. The incidence of falls in PD patients with sarcopenia was higher than that in PD patients without sarcopenia. There was no difference in sex ratio between PD patients with and without sarcopenia.Conclusion: Sarcopenia seems to be common in patients with PD. Early assessment of sarcopenia should be implemented in PD to avoid fall and disability.

Vanilla produces aroma after curing. There were a few reports about the possible involvement of microorganisms during the curing process. Bacterial and fungal community was analyzed to explore the distinct roles. Alpha diversity analysis indicated that the abundance and diversity of microorganisms did not increase regularly as the curing progressed. Weighted and unweighted principal coordinates analysis (PCoA) showed that the fungal community of blanching beans was significantly different from those of the vanilla beans of other stages, respectively. Bacillus and Aspergillus were the dominant genus during the curing process. Correlation analysis indicated that the bacterial and fungal structure was positively related to the vanillin formation, respectively. The study was conducive to reveal the formation of flavor components and the biosynthesis of vanillin. Furthermore, it proposed the possible curing methods of regulating the bacterial and fungal community to increase vanillin formation.

Rab7, an important member of the Rab family, is closely related to autophagy, endocytosis, apoptosis, and tumor suppression but few studies have described its association with renal fibrosis. In the early stage, our group studied the effects of Rab7 on production and degradation of extracellular matrix in hypoxic renal tubular epithelial cells. Because cell culture in vitro is different from the environment in vivo, it is urgent to understand the effects in vivo. In our current study, we established a renal fibrosis model in Rab7-knock-in mice (prepared by CRISPR/Cas9 technology) and wild type (WT) C57BL/6 mice using unilateral ureteral obstruction (UUO). Seven and 14 days after UUO, the expression of the Rab7 protein in WT mice, as well as the autophagic activity, renal function, and the degree of renal fibrosis in WT and Rab7-knock-in mice were examined by blood biochemical assay, hematoxylin-eosin and Masson staining, immunohistochemistry, and western blotting. We found that the Rab7 expression in WT mice increased over time. Furthermore, the autophagic activity constantly increased in both groups, although it was higher in the Rab7-knock-in mice than in the WT mice at the same time point. Seven days after UUO, the degree of renal fibrosis was milder in the Rab7-knock-in mice than in the WT mice, but it became more severe 14 days after surgery. Similar results were found for renal function. Therefore, Rab7 suppressed renal fibrosis in mice initially, but eventually it aggravated fibrosis with the activation of autophagy.

Background. The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. Results. The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. Conclusions. Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.

Genetic individualization based on non-invasive sampling is crucial for estimating the numbers of individuals in endangered mammalian populations. In sable (Martes zibellina)-poaching cases, identifying the number of animals involved is critical for determining the penalty. In addition, investigating animal numbers for wild sable populations requires genetic individualization when collecting several samples in neighboring regions. Microsatellites have been demonstrated to be reliable markers for individual identification. Thirty-three microsatellite loci derived from Mustelidae were selected to develop a genetic individualization method for sable. Three reference populations containing 54 unrelated sables were used to calculate allele number, allelic frequencies, and the polymorphic information content of each locus. The data were subsequently used to assess the validity of a combination of twelve loci for sable individualization. We defined twelve polymorphic loci that were easy to be amplified and genotyped. Four significant deviations from Hardy-Weinberg equilibrium were observed among the 12 loci in the three populations. The match probability of an individual from the reference populations with a random individual based on the 12 loci was 1.37 × 10−13. Using the combination of the twelve loci provides sufficient power to individualize sables considering the levels of microsatellite polymorphism observed. These loci were successfully applied to a case of sable poaching and provided valid evidence to determine the penalty. The genetic individualization of sable based on these loci might also be useful to investigate the numbers of animals in wild populations.

Abstract Background As a very important coenzyme in the cell metabolism, Vitamin B12 (cobalamin, VB12) has been widely used in food and medicine fields. The complete biosynthesis of VB12 requires approximately 30 genes, but overexpression of these genes did not result in expected increase of VB12 production. High-yield VB12-producing strains are usually obtained by mutagenesis treatments, thus developing an efficient screening approach is urgently needed. Result By the help of engineered strains with varied capacities of VB12 production, a riboswitch library was constructed and screened, and the btuB element from Salmonella typhimurium was identified as the best regulatory device. A flow cytometry high-throughput screening system was developed based on the btuB riboswitch with high efficiency to identify positive mutants. Mutation of Sinorhizobium meliloti (S. meliloti) was optimized using the novel mutation technique of atmospheric and room temperature plasma (ARTP). Finally, the mutant S. meliloti MC5–2 was obtained and considered as a candidate for industrial applications. After 7 d’s cultivation on a rotary shaker at 30 °C, the VB12 titer of S. meliloti MC5–2 reached 156 ± 4.2 mg/L, which was 21.9% higher than that of the wild type strain S. meliloti 320 (128 ± 3.2 mg/L). The genome of S. meliloti MC5–2 was sequenced, and gene mutations were identified and analyzed. Conclusion To our knowledge, it is the first time that a riboswitch element was used in S. meliloti. The flow cytometry high-throughput screening system was successfully developed and a high-yield VB12 producing strain was obtained. The identified and analyzed gene mutations gave useful information for developing high-yield strains by metabolic engineering. Overall, this work provides a useful high-throughput screening method for developing high VB12-yield strains.

Background: Limited studies have explored the impact of arthritis, other medical illnesses on morale in the elderly. Our study is aim to assess the association between arthritis and morale among Chinese nonagenarians and centenarians. Methods: This work was conducted as a cross-sectional study. The presence of arthritis, other medical illnesses was based on the subjects' report of diagnoses as told by their doctors and medical records from the investigation. The 17-item Philadelphia Geriatric Center Morale Scale (PGCMS) was used to measure morale. Low morale was defined as PGCMS score

Current treatments of multiple sclerosis are aimed at immunosuppression. Here the authors show that kappa opioid receptor is important for oligodendrocyte differentiation and myelination and the receptor agonists are protective in a mouse model of multiple sclerosis.

Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

This paper compares the differences in metabolites of vanilla beans at five different curing stages. Key vanilla flavors, vanillin precursors and main enzymes during the curing process of Hainan vanilla beans were also analyzed. Hundreds of metabolites were detected based on metabolic analyses of a widely targeted metabolome technique, compared with blanched vanilla beans (BVB), sweating vanilla beans (SVB) and drying vanilla beans (DVB), the total peak intensity of cured vanilla beans (CVB) is on the rise. The score plots of principal component analysis indicated that the metabolites were generally similar at the same curing stages, but for the different curing stages, they varied substantially. During processing, vanillin content increased while glucovanillin content decreased, and vanillic acid was present in sweating beans, but its content was reduced in drying beans. Both p-hydroxybenzaldehyde and p-hydroxybenzoic acid showed the maximum contents in cured beans. Ferulic acid was mainly produced in drying beans and reduced in cured beans. p-coumaric acid increased during the curing process. Vanillyl alcohol in drying beans (0.22%) may be formed by the hydrolysis of glucoside, whose conversion into vanillin may explain its decrease during the curing stage. β-Glucosidase enzymatic activity was not detected in blanched and sweating beans, but was observed after drying. Peroxidase activity decreased during curing by 94% in cured beans. Polyphenol oxidase activity was low in earlier stages, whereas cellulase activity in processed beans was higher than in green beans, except for cured beans. This study contributes to revealing the formation of flavor components and the biosynthesis pathway of vanillin.

BACKGROUND: Little is known so far on the lipid profile in polymyositis (PM) patients. Our aim is to identify lipid profiles in untreated patients with early PM, to assess the association between lipid profiles and C-reactive protein (a sensitive marker of inflammation) in these patients. METHODS AND FINDINGS: This work was conducted as a case-control study. Sixty untreated patients with PM and 60 age- and sex-matched healthy controls were included. The duration of PM was less than six months, and none of them had received intermittent or regular corticosteroids or disease-modifying antirheumatic drugs or biological agents prior to the study. Triglyceride (TG), total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C), and C-reactive protein (CRP) were assessed using standard techniques. Thirty patients (50%) had a decreased level of HDL-C and 47% had an increased level of TG. The levels of HDL-C, LDL-C, and TC in PM were significantly lower than in controls (P