Search

Abstract Fermenting Chinese medicinal herbs could enhance their bioactivities. We hypothesized probiotic-fermented gastrodia elata Blume (GE) with better potential to alleviate insomnia than that of unfermented, thus the changes in chemical composition and the insomnia-alleviating effects and mechanisms of fermented GE on pentylenetetrazole (PTZ)-induced insomnia zebrafish were explored via high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS), phenotypic, transcriptomic, and metabolomics analysis. The results demonstrated that probiotic fermented GE performed better than unfermented GE in increasing the content of chemical composition, reducing the displacement, average speed, and number of apoptotic cells in zebrafish with insomnia. Metabolomic investigation showed that the anti-insomnia effect was related to regulating the pathways of actin cytoskeleton and neuroactive ligand-receptor interactions. Transcriptomic and reverse transcription qPCR (RT-qPCR) analysis revealed that secondary fermentation liquid (SFL) significantly modulated the expression levels of neurod1, msh2, msh3, recql4, ercc5, rad5lc, and rev3l, which are mainly involved in neuron differentiation and DNA repair. Collectively, as a functional food, fermented GE possessed potential for insomnia alleviation.

Abstract A model is developed to establish the relationship between the critical gyration radius k of the primary component and the mass ratio (q) by considering the different dimensionless gyration radii of main-sequence stars with varying masses. The next step involves obtaining the low mass ratio limit ( $${q_{\text{min}}} = 0.038 \sim 0.041$$ q min = 0.038 ∼ 0.041 for overcontact degree $$f = 0$$ f = 0 ~ 1) of W UMa-type contact binaries. Furthermore, the radial density distributions are estimated within the range of $$0.3 M_{\odot } \sim 4.0 M_{\odot }$$ 0.3 M ⊙ ∼ 4.0 M ⊙ , based on the mass-radius relationship of main-sequence stars. Subsequently, the physical meaning of the minimum k value is proposed, which leads to an explanation for the cause of the minimum mass ratio. Finally, a stability criterion is proposed, which is based on both the mass ratio (q) and the total mass of the two components ( $$M_{tot}$$ M tot ).

Abstract There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.

ABSTRACTObjective To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK).Methods We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022.Results Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein–Barr virus (EBV) expression. The 5-years overall survival rate was 83%.Conclusion Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased β-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.

Abstract The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Abstract Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with an increasing number of new cases each year. Apolipoprotein (APOL) isoforms have been explored for their associations with HCC.The GSE14520 cohort was used for training data; The Cancer Genome Atlas (TCGA) database was used for validated data. Diagnostic, prognostic significance and mechanisms were explored using these cohorts. Risk score models and nomograms were constructed using prognosis-related isoforms and clinical factors for survival prediction. Oncomine and HCCDB databases were further used for validation of diagnostic, prognostic significance. APOL1, 3, and 6 were differentially expressed in two cohorts (all P ≤ 0.05). APOL1 and APOL6 had diagnostic capacity whereas APOL3 and APOL6 had prognostic capacity in two cohorts (areas under curves [AUCs] > 0.7, P ≤ 0.05). Mechanism studies demonstrated that APOL3 and APOL6 might be involved in humoral chemokine signaling pathways (all P ≤ 0.05). Risk score models and nomograms were constructed and validated for survival prediction of HCC. Moreover, diagnostic values of APOL1 and weak APOL6 were validated in Oncomine database (AUC > 0.700, 0.694); prognostic values of APOL3 and APOL6 were validated in HCCDB database (all P

Abstract Worldwide, cancer is a huge burden, and each year sees an increase in its incidence. RAB (Ras-related in brain) 13 is crucial for a number of tumor types. But more research on RAB13's tumor-related mechanism is still required. This study's goal was to investigate RAB13's function in human pan-cancer, and we have also preliminarily explored the relevant mechanisms. To investigate the differential expression, survival prognosis, immunological checkpoints, and pathological stage of RAB13 in human pan-cancer, respectively, databases of TIMER2.0, GEPIA 2, and UALCAN were employed. CBioPortal database was used to analyze the mutation level, meanwhile, PPI network was constructed based on STRING website. The putative functions of RAB13 in immunological infiltration were investigated using single sample gene set enrichment analysis (ssGSEA). The mechanism of RAB13 in hepatocellular cancer was also briefly investigated by us using gene set enrichment analysis (GSEA). RAB13 was differentially expressed in a number of different cancers, including liver hepatocellular carcinoma (LIHC), stomach adenocarcinoma (STAD), etc. Additionally, RAB13 overexpression in LGG and LIHC is associated with a worse prognosis, including overall survival (OS) and disease-free survival (DFS). Then, we observed that early in BLCA, BRAC, CHOL, ESCA, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, and STAD, the level of RAB13 expression was raised. Next, we found that “amplification” was the most common mutation in RAB13. The expression of SLC39A1, JTB, SSR2, SNAPIN, and RHOC was strongly positively linked with RAB13, according to a correlation study. RAB13 favorably regulated B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell in LIHC, according to immune infiltration analysis. Immune checkpoint study revealed a positive correlation between RAB13 expression and PD1, PDL1, and CTLA4 in LIHC. According to GSEA, RAB13 is involved in a number of processes in LIHC, including MTORC1 signaling, MYC targets v1, G2M checkpoint, MITOTIC spindle, DNA repair, P53 pathway, glycolysis, PI3K-AKT-MTOR signaling, etc. RAB13 is a possible therapeutic target in LIHC and can be used as a prognostic marker.

Background: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. Methods: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. Results: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486–2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697–1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361–2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126–1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490–1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357–1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn’t receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. Conclusions: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.

Abstract Background Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments. Methods LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts. Results LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P 0.700). Conclusions Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

Abstract Background Peripheral facial paralysis (PFP) results in functional disorder and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture methods have been reported to be potentially effective for shortening the disease course and reducing the occurrence of sequelae when they are applied at an early stage. Neuro edema is a common pathological feature in the acute phase, and many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and to assess the most suitable acupuncture method for the acute period. Methods and analysis All the RCTs and quasi-RCTs on acupuncture therapy for patients who is during acute stage of PFP will be included. The recovery rate of facial function, the time it takes to restore facial function and the odds of sequelae occurring will be the key parts we focus on. Psychological well-being and quality of life will also be evaluated. Literature searching will be conducted until December 31th, 2022 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software will be used for data analysis, and the version 2 of the Cochrane risk-of-bias tool (RoB 2) will be used to assess the certainty of evidence. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. Ethics and dissemination Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. Discussion This review will summarize the evidence on the different type of acupuncture therapy for acute Bell’s palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applied to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review. Systematic review registration International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127

Autoimmune encephalitis, a class of encephalitis, is clinically characterized by multifocal or diffuse brain injury, including aberrant mental behavior, convulsions, and near-event memory impairment. In this article, we describe a female patient with autoimmune encephalitis who tested positive for leucine-rich glioma inactivated 1 (LGI1) antibodies and had hippocampal inflammatory edema in the lesion area. During the first 3 months of her illness, the patient primarily experienced memory loss, the onset of rigid twitching in her extremities that lasted for 1 min while in remission, and incontinence. After gamma globulin administration, methylprednisolone shock, and other symptomatic therapies during hospitalization, the patient’s psychiatric symptoms and seizures improved considerably; however, she did not fully recover her memory. After receiving fire acupuncture for 6 months, the patient’s understanding, orientation, and calculation skills improved considerably. Her memory and mental state were also improved at the follow-up visit. In this case, the use of fire acupuncture for the treatment of autoimmune encephalitis resulted in favorable outcomes with important benefits for conditions affecting the central nervous system; however, more convincing data are required to support the effectiveness of this treatment method.

Abstract Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small‑sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow‑up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

Abstract Background China is the country with the largest elderly population. To actively respond to this ageing population, China has proposed the Community Aged Care Service Centre (CACSC) network as the major elderly care development policy. However, many residents resisted the development of the CACSC network, which affected its smooth implementation. Based on the theory of “Not in My Backyard” (NIMBY), this paper proposes a model of the influencing factors of community residents on the opposition to the construction of CACSCs. Methods Residents living in urban communities over the age of 20 in China are the target of this study. The questionnaires were collected in the form of electronic questionnaires created on a professional website, and hyperlinks to the questionnaires were distributed through social media. The descriptive statistical analysis, T-tests, ANOVA and structural equation modelling were performed on cross-sectional survey data from 509 questionnaires. Results The research results show that superstition, the NIMBY attitude, and perceived risk have a significant positive impact on the opposition to the construction of CACSCs, while the negative impact of perceived benefit on the opposition intention is not significant. Moreover, perceived knowledge has a significant positive impact on perceived benefit and a significant negative impact on superstition and perceived risk. Conclusions Strengthen policy advocacy on ageing, clarify the service content of CACSC and encourage young people to participate in public welfare activities for the elderly can reduce the opposition of community residents to the construction of a CACSC.

Abstract PCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.

The irreversible oxygen redox reaction during charging to the high-voltage region causes cathode structural degradation and Na-ion cell capacity fading. Here, the authors report a B-doped cathode active material to mitigate the irreversible oxygen oxidation and increase the cell capacity.

Abstract Background Substance use and adverse sexual and reproductive health (SRH) outcomes continue to be significant threats to female adolescents’ health and wellbeing, particularly to these marginalized subpopulations. Our research aimed to tackle knowledge gaps regarding the prevalence of concurrent substance use including alcohol, tobacco, illicit drug among Chinese adolescent female sex workers (AFSWs), while to assess the correlates between substance use and SRH risks; the needs for comprehensive SRH services were also examined in this study. Methods A cross-sectional study enrolled 310 AFSWs aged 15–19 years by using cluster sampling method in Kunming, China. Descriptive analysis was employed to characterize the participants who were regular-alcohol users, regular-tobacco users, illicit drug users and polysubstance users. Multivariable logistic regression analysis was performed to detect the SRH correlates of regular-alcohol use, regular-tobacco use, illicit drugs and polysubstance use respectively. Results There is a high prevalence of regular-alcohol drinking (83%, 257/310) among AFSWs, with 44% (136/310) smoking cigarettes regularly and 9% using illicit drug (27/310) in the past year. In multivariate analysis, AFSWs who had middle and high school education, had higher monthly income, experienced of sexual and gender based violence (SGBV) and prior abortion, and regular-tobacco smoking were associated with increased odds of regular-alcohol drinking; engaging in unprotected sex while drunk, having STIs symptoms and using illicit drugs were significantly associated with regular-tobacco smoking; while AFSWs who had an illicit drug using- intimate partner, experienced forced sexual initiation, accessed unsafe medical providers for STIs treatment were associate with increased odds of illicit drug use. Moreover, 35% (105/298) AFSWs sought unsafe medical care for STIs treatment, or no treatment at all, among them, majority were using polysubstance (87%; 91/105). Conclusions Our findings reveal combined threats of substance use to AFSWs’ SRH and wellbeing in China, this study emphasises that the coordinated efforts are needed to integrate SRH promotion and harm reduction service across sectors, and not only fragmented measures. An effective response should include an agreed framework, indicators and targets supported by political will, solid leadership and policy reform to deal with AFSWs’ overlapping vulnerabilities in a systematic way.

High-amylose maize starch has great potential for widespread industrial use due to its ability to form strong gels and film and in the food processing field, thus serving as a resistant starch source. However, there is still a substantial shortage of high-amylose maize due to the limitation of natural germplasm resources, although the well-known amylose extender (ae) gene mutants have been found to produce high-amylose maize lines since 1948. In this context, high-amylose maize lines (13 inbreds and 18 hybrids) originating from a natural amylose mutant in our testing field were utilized to study the correlation between amylose content (AC) and phenotypic traits (kernel morphology and endosperm glossiness), grain filling characteristics, gene expression, and amylose inheritance. Our results showed that AC was negatively correlated with total starch content but was not correlated with grain phenotypes, such as kernel fullness, kernel morphology and endosperm glossiness. Maize lines with higher amylose had a greater grain filling rate than that of the control (B73) during the first 20 days after pollination (DAP). Both starch debranching enzyme (DBE) groups and starch branching enzyme IIb (SBEIIb) groups showed a greater abundance in the control (B73) than in the high-amylose maize lines. Male parents directly predicted AC of F1, which was moderately positively correlated with the F2 generation.

Methamphetamine is one of the most prevalent drugs abused in the world. Methamphetamine abusers usually present with hyperpyrexia (39°C), hallucination and other psychiatric symptoms. However, the detailed mechanism underlying its neurotoxic action remains elusive. This study investigated the effects of methamphetamine + 39°C on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats. Primary cortex neurons were exposed to 1 mM methamphetamine + 39°C. Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39°C triggered obvious necrosis-like death in cultured primary cortical neurons, which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially. Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39°C for 3 hours. After pre-treatment with RIP3 inhibitor GSK’872, propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased; RIP3 and MLKL protein expression significantly decreased. Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse. Taken together, the above results suggest that methamphetamine + 39°C can induce RIP3/MLKL regulated necroptosis, thereby resulting in neurotoxicity. The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University, China (approval numbers: 2017-S026 and 2017-S033) on March 7, 2017.

Molten lithium cannot spread onto the lithiophobic substrate, hindering the production and application of lithium metal anodes. Here, the authors show a general chemical strategy to tune the wettability by forming new chemical bonds through the reactions with various organic coatings or elemental additives.

Abstract Background Natural Killer T–Cell Lymphoma (NKTCL) is a subtype of Non‐Hodgkin's Lymphoma, and its morbidity is ranked the first of T‐Cell Lymphoma. Hippo signaling pathway is involved in the pathogenesis of tumors. However, the role of Hippo signaling pathway in the oncogenesis of NKTCL still remains unclear. Methods The expressions of mammalian sterile 20‐like kinase 1 (MST1) and Yes‐associated protein (YAP) were investigated by RT‐PCR and Western blotting. Cell viability was detected by MTT assays. Cell cycle and cell apoptosis were determined by flow cytometry. Cell proliferative capacity was detected by colony formation assay. Nude mice xenograft models were established and the tumor sections were analyzed by immunohistochemistry (IHC) staining. Results The expression of MST1 was significantly down‐regulated in NKTCL tissues (n = 30) and cell lines, while the expression of YAP was significantly up‐regulated, and the phosphorylation of YAP was inhibited. Overexpression of MST1, knockdown of YAP, or verteporfin (VP) treatment could inhibit cell proliferation, and promote cell cycle arrest and apoptosis in NKTCL cells, while knockdown of MST1 and overexpression of YAP promoted cell proliferation. Additionally, Bcl‐2/Bax ratio and downstream effectors of Hippo signaling pathway (c‐myc, survivin, cyclinD1, CTGF, and TEAD) were significantly decreased when MST1 was overexpressed and YAP was knocked down or after VP treatment. Furthermore, our mice model demonstrated that activation of Hippo signal pathway suppressed the tumorigenesis of NKTCL. Conclusion The activation of Hippo signal pathway via overexpressing MST1 or down‐regulating YAP can inhibit the tumorigenesis of NKTCL.

There are two main molecules in asymmetric unit of the title compound, C27H21N3O6·0.5C2H5OH. In both, the indole ring systems are approximately perpendicular to each other, at dihedral angles of 69.3 (5) and 82.8(4)°. In the crystal, molecules are linked by N—H...O and O—H...O hydrogen bonds into a three-dimensional supramolecular architecture. The solvent ethanol molecule acts as a donor, forming an O—H...O hydrogen bond, reinforcing the structure.

Room temperature liquid metal (LM) showcases a great promise in the fields of flexible functional thin film due to its favorable characteristics of flexibility, inherent conductivity, and printability. Current fabrication strategies of liquid metal film are substrate structure specific and sustain from unanticipated smearing effects. Herein, this paper reported a facile fabrication of liquid metal composite film via sequentially regulating oxidation to change the adhesion characteristics, targeting the ability of electrical connection and electrothermal conversion. The composite film was then made of the electrically resistive layer (oxidizing liquid metal) and the insulating Polyimide film (PI film) substrate, which has the advantages of electrical insulation and ultra-wide temperature working range, and its thickness is only 50 μm. The electrical resistance of composite film can maintain constant for 6 h and could work normally. Additionally, the heating film exhibited excellent thermal switching characteristics that can reach temperature equilibrium within 100 s, and recovery to ambient temperature within 50 s. The maximum working temperature of the as-prepared film is 115 °C, which is consistent with the result of the theoretical calculation, demonstrating a good electrothermal conversion capability. Finally, the heating application under extreme low temperature (−196 °C) was achieved. This conceptual study showed the promising value of the prototype strategy to the specific application areas such as the field of smart homes, flexible electronics, wearable thermal management, and high-performance heating systems.

Abstract Spinel‐type LiMn2O4 cathode materials commonly suffer from manganese dissolution due to the severe interfacial side reactions especially at elevated temperature. Here, a 3D hollow fusiform LiMn2O4 cathode material is reported with preferentially exposed stable {111} facets and seamless outer structure, which is clearly confirmed by microfocused ion beam scanning electron microscopy, high‐resolution transmission electron microscopy as well as scanning transmission electron microscopy with atomic resolution. Owing to the optimal geometrical structure design and the preferentially exposed stable {111} facets, the electrode delivers excellent rate capability (107.6 mAh g−1 at 10 C), remarkable cycling stability (83.3% capacity retention after 1000 cycles at 1 C), and outstanding high‐temperature performance. Together with the analyses of electrochemical behaviors, in situ X‐ray diffraction at different temperatures, and ex situ X‐ray photoelectron spectra, the underlying working mechanism for suppressing manganese dissolution is clearly articulated. These findings could provide significant guidelines for precisely designing highly stable cathode materials for LIBs.

Objective To explore the relationship between mean arterial pressure (MAP) on admission and prognosis of patients with acute ischemic stroke. Methods A total of 342 patients on acute stage (< 24 h) of ischemic stroke were divided into 4 groups according to their MAP levels on admission: < 97 mm Hg, 97- mm Hg, 107- mm Hg and ≥ 117 mm Hg. Ninety days after onset, these patients were divided into 2 groups according to modified Rankin Scale (mRS): favorable prognosis (mRS < 3) and unfavorable prognosis (mRS 3-6). Logistic regression analysis was used to evaluate the effect of MAP at admission on the prognosis 90 d after onset. Results Patients with unfavorable prognosis in 4 MAP groups (< 97 mm Hg, 97- mm Hg, 107- mm Hg and ≥ 117 mm Hg) accounted for 34.78% (16/46), 14.29% (14/98), 15.32% (17/111) and 41.38% (36/87), respectively. Patients in 97- mm Hg and 107- mm Hg groups presented better prognosis (P < 0.01, for all). In Logistic regression analysis, by optimal modification of systolic blood pressure (SBP) and diastolic blood pressure (DBP), MAP from 97 mm Hg to 107 mm Hg and from 107 mm Hg to 117 mm Hg were independent protective factors for the prognosis 90 d after onset (P = 0.003, 0.011). Conclusions Too high or too low MAP in acute stage of ischemic stroke indicates an unfavorable progonsis of patients. Therefore, MAP can be used as predictive indicator of prognosis of patients with acute ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2015.05.013

Traditional agricultural systems have contributed to food and livelihood security. Rice-crab coculture (RC) is an important eco-agricultural process in rice production in northern China. Recognizing the soil fertility in RC may help develop novel sustainable agriculture. Soil carbohydrates are important factors in determining soil fertility in different culture modes. In this study, soil carbohydrates were analyzed under three different culture modes including rice monoculture (RM), conventional rice-crab coculture (CRC) and organic rice-crab coculture (ORC). Results showed that the contents of soil organic carbon and carbohydrates were significantly higher in the ORC than those in RM. The increasing effect was greater with increased organic manure. Similar tendency was found in CRC, but the overall effect was less pronounced compared with ORC. Carbohydrates were more sensitive to RC mode and manure amendment than soil organic carbon. Compare to RM, the (Gal+Man)/(Ara+Xyl) ratio decreased in all the RC modes, indicating a relative enrichment in plant-derived carbohydrates due to the input of crab feed and manure. While the increasing (Gal+Man)/(Ara+Xyl) ratio in ORC modes with increased organic manure suggested that crab activity and metabolism induced microbially derived carbohydrates accumulation. The lower GluN/MurA ratio in ORC indicated an enhancement of bacteria contribution to SOM turnover in a short term. The findings reveal that the ORC mode could improve the quantity and composition of soil carbohydrates, effectively, to ensure a sustainable use of paddy soil.

Objective To investigate operative efficacy, surgical complication rate and surgical strategy of microvascular decompression (MVD) for hemifacial spasm (HFS). Methods The clinical data of 46 patients with HFS were retrospectively analysed. All patients underwent MVD. Results During operation, it was found that the facial nerve root exit zone (RExZ) was compressed by arterial vessels, namely anterior inferior cerebellar artery (AICA) in 24 cases (52.17%), posterior inferior cerebellar artery (PICA) in 14 cases (30.43%), vertebral artery and small artery in 7 cases (15.22%), and vertebral artery in one case (2.18% ). Symptoms in 38 patients were completely remitted immediately after surgery, and symptoms of 8 cases were reduced significantly. The main complications included dizziness and tinnitus in 9 cases, hearing loss in 5 cases, cerebrospinal fluid leakage in one case, and infection in 2 cases. No patient died during operation. Conclusion Microvascular decompression is the first choice for treating idiopathic hemifacial spasm. Skilled microsurgical techniques, and identification and complete decompression of the responsible artery are the key to ensure success in microvascular decompression. DOI：10.3969/j.issn.1672-6731.2010.05.013

OBJECTIVE:In China, policy and social taboo prevent unmarried adolescents from accessing sexual and reproductive health (SRH) services. Research is needed to determine the SRH needs of highly disadvantaged groups, such as adolescent female sex workers (FSWs). This study describes SRH knowledge, contraception use, pregnancy, and factors associated with unmet need for modern contraception among adolescent FSWs in Kunming, China. METHODS:A cross-sectional study using a one-stage cluster sampling method was employed to recruit adolescents aged 15 to 20 years, and who self-reported having received money or gifts in exchange for sex in the past 6 months. A semi-structured questionnaire was administered by trained peer educators or health workers. Multivariable logistic regression was conducted to determine correlates of low knowledge and unmet need for modern contraception. RESULTS:SRH knowledge was poor among the 310 adolescents surveyed; only 39% had heard of any long-acting reversible contraception (implant, injection or IUD). Despite 98% reporting not wanting to get pregnant, just 43% reported consistent condom use and 28% currently used another form of modern contraception. Unmet need for modern contraception was found in 35% of adolescents, and was associated with having a current non-paying partner, regular alcohol use, and having poorer SRH knowledge. Past abortion was common (136, 44%). In the past year, 76% had reported a contraception consultation but only 27% reported ever receiving SRH information from a health service. CONCLUSIONS:This study demonstrated a low level of SRH knowledge, a high unmet need for modern contraception and a high prevalence of unintended pregnancy among adolescent FSWs in Kunming. Most girls relied on condoms, emergency contraception, or traditional methods, putting them at risk of unwanted pregnancy. This study identifies an urgent need for Chinese adolescent FSWs to be able to access quality SRH information and effective modern contraception.

OBJECTIVES: To assess sexual risk-taking of female sex workers (FSWs) with emotional partners (boyfriends and husbands), compared to regular and casual clients. Experiences of violence and the degree of relationship control that FSWs have with emotional partners are also described. DESIGN: Cohort study with quarterly follow-up visit over 12-months. METHODS: Four hundred HIV-uninfected FSWs older than 16 years were recruited from their homes and guesthouses in Mombasa, Kenya. A structured questionnaire assessed participant characteristics and study outcomes at each visit, and women received risk-reduction counselling, male and female condoms, and HIV testing. RESULTS: Four or more unprotected sex acts in the past week were reported by 21.3% of women during sex with emotional partners, compared to 5.8% with regular and 4.8% with casual clients (P

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and "NO-Astrocyte-Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.

The influences of cooling rate on the phase constitution, microstructural length scale, and microhardness of directionally solidified Galvalume (Zn-55Al-1.6Si) alloy were investigated by directional solidification experiments at different withdrawal speeds (5, 10, 20, 50, 100, 200, and 400 µm·s-1). The results show that the microstructure of directionally solidified Galvalume alloys is composed of primary Al dendrites, Si-rich phase and (Zn-Al-Si) ternary eutectics at the withdrawal speed ranging from 5 to 400 µm·s-1. As the withdrawal speed increases, the segregation of Si element intensifies, resulting in an increase in the area fraction of the Si-rich phase. In addition, the primary Al dendrites show significant refinement with an increase in the withdrawal speed. The relationship between the primary dendrite arm spacing (λ1) and the thermal parameters of solidification is obtained: λ1=127.3V-0.31. Moreover, as the withdrawal speed increases from 5 to 400 µm·s-1, the microhardness of the alloy increases from 90 HV to 151 HV. This is a combined effect of grain refinement and second-phase strengthening. [ABSTRACT FROM AUTHOR]

The Chinese tree shrew (Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used metatranscriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses — hepacivirus 1, parvovirus, and picornavirus — exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses — hepacivirus 2, hepatovirus A and hepevirus — exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for crossspecies transmission. [ABSTRACT FROM AUTHOR]