Redundant and Distinct Roles of Two 14-3-3 Proteins in Fusarium sacchari, Pathogen of Sugarcane Pokkah Boeng Disease.

Fusarium sacchari, a key pathogen of sugarcane, is responsible for the Pokkah boeng disease (PBD) in China. The 14-3-3 proteins have been implicated in critical developmental processes, including dimorphic transition, signal transduction, and carbon metabolism in various phytopathogenic fungi. However, their roles are poorly understood in F. sacchari. This study focused on the characterization of two 14-3-3 protein-encoding genes, FsBmh1 and FsBmh2, within F. sacchari. Both genes were found to be expressed during the vegetative growth stage, yet FsBmh1 was repressed at the sporulation stage in vitro. To elucidate the functions of these genes, the deletion mutants ΔFsBmh1 and ΔFsBmh2 were generated. The ΔFsBmh2 exhibited more pronounced phenotypic defects, such as impaired hyphal branching, septation, conidiation, spore germination, and colony growth, compared to the ΔFsBmh1. Notably, both knockout mutants showed a reduction in virulence, with transcriptome analysis revealing changes associated with the observed phenotypes. To further investigate the functional interplay between FsBmh1 and FsBmh2, we constructed and analyzed mutants with combined deletion and silencing (ΔFsBmh/siFsBmh) as well as overexpression (O-FsBmh). The combinations of ΔFsBmh1/siFsBmh2 or ΔFsBmh2/siFsBmh1 displayed more severe phenotypes than those with single allele deletions, suggesting a functional redundancy between the two 14-3-3 proteins. Yeast two-hybrid (Y2H) assays identified 20 proteins with pivotal roles in primary metabolism or diverse biological functions, 12 of which interacted with both FsBmh1 and FsBmh2. Three proteins were specifically associated with FsBmh1, while five interacted exclusively with FsBmh2. In summary, this research provides novel insights into the roles of FsBmh1 and FsBmh2 in F. sacchari and highlights potential targets for PBD management through the modulation of FsBmh functions.

Whole genome sequencing in high-grade cervical intraepithelial neoplasia patients from different ethnic groups in China.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. It develops through precancerous lesions (cervical intraepithelial neoplasia (CIN), graded from low-grade (CIN1) to high-grade (CIN2-3)). It is well established that precancerous and cancerous cervical lesions are caused by a persistent infection with high-risk types of the human papilloma virus (hrHPV). To have a deeper understanding of the pathogenesis of CIN and CC, we systematically analyzed the landscape of genomic alterations and HPV integration profiles in high-grade CIN2/3. We performed deep whole genome sequencing on exfoliated cervical cells and matched peripheral blood samples from a cohort of 51 Chinese patients (of whom 35 were HPV+) with high-grade CIN from 3 ethnic groups and constructed strict integrated workflow of genomic analysis. In addition, the HPV types and integration breakpoints in the exfoliated cervical cells from these patients were examined. Genomic analysis identified 6 significantly mutated genes (SMGs), including CDKN2A, PIK3CB, FAM20A, RABEP1, TMPRSS2 and SS18L1, in 51 CIN2/3 samples. As none of them had previously been identified as SMGs in the Cancer Genome Atlas cervical squamous cell carcinoma and endocervical adenocarcinoma (TCGA-CESC) cohort, future studies with larger sample size of CINs may be needed to validate our findings. Mutational signature analysis showed that mutational signatures of CINs were dramatically different from CCs, highlighting their different mutational processes and etiologies. Moreover, non-silent somatic mutations were detected in all of the CIN2/3 samples, and 88% of these mutations occurred in genes that also mutated in CCs of TCGA cohort. CIN2 samples had significantly less non-silent mutations than CIN3 samples (P = .0006). Gene ontology and pathway level analysis revealed that functions of mutated genes were significantly associated with tumorigenesis, thus these genes may be involved in the development and progression of CC. HPV integration breakpoints occurred in 28.6% of the CIN2/3 samples with HPV infection. Integrations of common high risk HPV types in CCs, including HPV16, 52, 58 and 68, also occurred in the CIN samples. Our results lay the groundwork for a deeper understanding of the molecular mechanisms underlying the pathogenesis of CC and pave the way for new tools for screening, diagnosis and treatment of cervical precancerous and cancerous lesions.

Resveratrol alleviates salivary gland dysfunction induced by ovariectomy in rats.

Resveratrol (Res), found abundant in many medicinal plants, exerts multiple biological functions in the body, including anti-inflammatory, antioxidant, and anti-aging properties. Xerostomia is a major symptom of salivary gland dysfunction in menopausal women, which significantly compromises the quality of life. Here, we investigated the effect of Res on estrogen deficiency-induced salivary gland dysfunction in rats. We found that Res administration could reduce body weight and water consumption, and increase salivary fluid secretion and blood flow of the submandibular gland. Furthermore, Res therapy alleviated histological lesions, increased AQP5 expression, and inhibited cell apoptosis in submandibular gland tissue. Meanwhile, the action of antioxidants was restored and the levels of inflammatory cytokines were attenuated by Res supplementation. Collectively, Res effectively improved estrogen deficiency-induced hyposalivation, which may provide a novel, safe, and practical approach to protect the salivary glands of estrogen-deficient females against xerostomia.

Subacute combined degeneration induced by nitrous oxide inhalation: Two case reports.

RATIONALE: Nitrous oxide (N2O), commonly known as "laughing gas," is being increasingly abused by young people as a recreational drug; this can subsequently result in myelopathy and peripheral neuropathy, however, in China, few cases of neurologic deterioration by N2O abuse have been reported. PATIENT CONCERNS: Herein, we present 2 patients who developed progressive limb weakness, numbness, and ataxia. Both of them had recreationally inhaled N2O intermittently for a long time. DIAGNOSIS: Subacute combined degeneration (SCD) based on myelopathy and polyneuropathy after N2O abuse. INTERVENTIONS: The 2 patients were treated with cessation of N2O inhalation, methylcobalamin capsule 500 µg tid (ter in die, which means 3 times a day), and compound vitamin B 1 tablet tid p.o.(per os, which means taken orally) for 1 month. OUTCOMES: The symptoms of altered sensation and the patients' gait improved significantly. LESSONS: The 2 cases raise awareness of the important mechanisms of N2O neurotoxicity, and clinicians should be made fully aware of such substance-related diseases. The incidence of N2O -induced neurotoxicity is insufficiently recognized and should be considered as an important cause of SCD, especially in adolescents with undifferentiated weakness and abnormal sensation; this is essential because serious complications such as irreversible paralysis can result from the absence of early diagnosis and treatment.

Overexpression of EZH2/NSD2 Histone Methyltransferase Axis Predicts Poor Prognosis and Accelerates Tumor Progression in Triple-Negative Breast Cancer.

Two histone methyltransferases, enhancer of zeste homolog 2 (EZH2) and nuclear SET domain-containing 2 (NSD2), are aberrantly expressed in several types of human cancers. However, the regulatory relationship between EZH2 and NSD2 and their prognostic values in breast cancer (BC) have not been fully elucidated. In this study, we demonstrated that EZH2 and NSD2 were overexpressed in BC compared with benign lesions and normal tissues using tissue microarray, immunohistochemistry, and bioinformatic databases. Both EZH2 and NSD2 expression were associated with pathological grade of tumor and lymph node metastasis. A comprehensive survival analysis using Kaplan-Meier Plotter database indicated that EZH2 expression was negatively correlated with relapse-free survival (RFS), overall survival (OS), distant metastasis-free survival (DMFS), and postprogression survival (PPS) in 3951 BC patients, and NSD2 expression was negatively correlated with RFS and DMFS. Notably, EZH2 and NSD2 expression were coordinately higher in triple-negative breast cancer (TNBC) than that in other subtypes. Stable knockdown of EZH2 using lentiviral shRNA vector significantly reduced the proliferation, migration and invasion abilities of TNBC cell line MDA-MB-231 and MDA-MB-468, and downregulated NSD2 expression as well as the levels of H3K27me3 and H3K36me2, two histone methylation markers catalyzed by EZH2 and NSD2, respectively. By contrast, overexpression of EZH2 using adenovirus vector displayed an inverse phenotype. Furthermore, knockdown of NSD2 in EZH2-overexpressing cells could dramatically attenuate EZH2-mediated oncogenic effects. Bioinformatic analysis further revealed the function and pathway enrichments of co-expressed genes and interactive genes of EZH2/NSD2 axis, suggesting that EZH2/NSD2 axis was associated with cell division, mitotic nuclear division and transition of mitotic cell cycle in TNBC. Taken together, EZH2/NSD2 axis may act as a predictive marker for poor prognosis and accelerate the progression of TNBC.

Self-reported Rates of Abuse, Neglect, and Bullying Experienced by Transgender and Gender-Nonbinary Adolescents in China.

Importance: This is the first comprehensive national study reporting the rates of abuse, neglect, and bullying from family and classmates or teachers among Chinese transgender and gender-nonbinary adolescents and identifying risk factors associated with poor mental health in this population. Objective: To assess the rates of abuse, neglect, and bullying and their association with poor mental health among Chinese transgender and gender nonbinary adolescents. Design, Setting, and Participants: This national survey study used an online self-selecting survey conducted between January 1, 2017, and September 29, 2017, in China. Eligibility criteria included reporting being aged 12 to 18 years and being transgender or gender nonbinary. Data analysis was performed from March 25 to 28, 2019. Main Outcomes and Measures: The main outcome was self-reported poor mental health, including depressive symptoms, anxiety symptoms, and suicidal ideation. Depressive symptoms were measured using the Center for Epidemiological Studies Depression 9-item scale. Anxiety symptoms were measured using the 7-item General Anxiety Disorder scale. Suicidal ideation was measured using standardized questions adapted from previous Chinese studies. Abuse, neglect, and bullying were measured using specifically designed questions. Results: Of 564 responses collected, 385 respondents (mean [SD] age, 16.7 [1.2] years) met inclusion criteria, including 109 (28.3%) transgender adolescent boys, 167 (43.4%) transgender adolescent girls, and 109 (28.3%) gender-nonbinary adolescents. Among 319 respondents who reported that their parents were aware of their gender identity, 296 (92.8%) reported having experienced parental abuse or neglect. Among the full cohort, 295 respondents (76.6%) reported having experienced abuse or bullying owing to being transgender or gender nonbinary in school from classmates or teachers. There were 173 respondents (44.9%) with Center for Epidemiological Studies Depression 9-item scale scores indicating they were at risk of major depressive disorder, and 148 respondents (38.4%) had 7-item General Anxiety Disorder scale scores indicating they were at risk of an anxiety disorder. In univariate analysis, reporting experiences of bullying from a classmate or teacher was significantly associated with suicidal ideation (odds ratio, 1.68 [95% CI, 1.04-2.70]; P = .03), but the association was no longer statistically significant after controlling for level of educational attainment, aversion to assigned sex, and depressed mood at the onset of puberty (odds ratio, 1.63 [95% CI, 0.97-2.73]; P = .06). Conclusions and Relevance: In this survey study, transgender and gender-nonbinary adolescents in China reported high rates of abuse, neglect, and bullying at home and in school and high rates of symptoms associated with poor mental health. This study highlights the importance of reducing home- and school-based abuse, neglect, and bullying of transgender and gender-nonbinary adolescents in China to improve mental health outcomes; however, broader change in the social environment may be required to address the prejudice and stigma aimed at gender minorities.

Chinese Herbal Medicines for Restenosis After Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

Objectives: This study evaluates the efficacy of Chinese herbal medicines after percutaneous coronary intervention (PCI). Background: PCI is the primary treatment for coronary atherosclerotic heart disease (CHD). However, many patients experience restenosis within 6 months after PCI. Chinese herbal medicines are widely used in patients after PCI. Clinical studies have found that Chinese herbal medicines may prevent restenosis. Methods: Eight databases were searched for randomized controlled trials (RCTs) investigating the use of Chinese herbal medicines after PCI. The search period was from the date of database inception to June 2017. We used the Cochrane risk of bias tool to estimate the methodological quality of the studies. The primary outcome was the restenosis rate, and secondary outcomes were the angina recurrence rate and major adverse cardiac events (MACEs). Data were analyzed with RevMan 5.3, and the quality of evidence was assessed with the GRAD approach. Results: Eleven RCTs with a total of 1,383 patients were included. The major outcome was the restenosis rate, and the results showed a significant effect of Chinese herbal medicines on reduction in the rate of restenosis (risk ratio [RR] = 0.46, 95% CI: 0.35-0.60, p < 0.00001, I2 = 0%). Chinese herbal medicine treatment also decreased the angina recurrence rate (RR = 0.41, 95% CI: 0.29-0.57, p < 0.00001, I2 = 0%). The results revealed a lower rate of MACEs in the Chinese medicine group than in the control group (RR = 0.49, 95% CI: 0.34-0.71, p = 0.0001, I2 = 0%). We evaluated the quality of evidence with the GRADE system; the quality of evidence for the restenosis rate and angina was low, and the quality of evidence for MACEs was estimated to be moderate. Conclusion: According to existing research evidence, the use of Chinese herbal medicines may reduce the incidence of MACEs. Chinese herbal medicines may reduce restenosis and angina recurrence rates after PCI, but the evidence is limited.

Traditional Chinese Medicine Preparation Combined Therapy May Improve Chemotherapy Efficacy: A Systematic Review and Meta-Analysis.

BACKGROUND: Whether traditional Chinese medicine preparation combined therapy can improve the efficacy of chemotherapy is controversial. This meta-analysis evaluates the efficacy of traditional Chinese medicine preparation combined with chemotherapy. METHOD: Three databases were searched from inception through August 2018. Eligible randomized controlled trials (RCTs) involving the combined treatment of chemotherapy and traditional Chinese medicine preparation compared to chemotherapy alone for treating cancer were retrieved. The methodological quality of the included RCTs was assessed with Cochrane Collaboration's risk of bias assessment tool. Meta-analysis was adopted to make comprehensive comparisons between the experimental and control groups. RESULTS: Four RCTs were included in this review, comprising 256 subjects. The majority of the RCTs were judged as being of poor methodological quality. Meta-analysis showed that the combination of traditional Chinese medicine preparation and chemotherapy appeared to be more effective than chemotherapy alone, for the treatment of cancer, as assessed by the disease control rate (RR: 1.41, 95% CI: 1.11 to 1.79) and the objective response rate (RR: 2.71, 95% CI: 1.28 to 5.77). There were no statistically significant differences between the groups in terms of bone marrow suppression (RR: 0.88, 95% CI: 0.57 to 1.37) or gastrointestinal reaction (RR: 1.12, 95% CI 0.75 to 1.69). CONCLUSIONS: Traditional Chinese medicine preparation combined with chemotherapy may improve objective response rates and disease control rates more than chemotherapy alone. The evidence that combined traditional Chinese medicine preparation can reduce the side effects of chemotherapy is insufficient. More rigorous randomized controlled trials are needed to confirm these conclusions.

RNA-Seq Analysis Identified XLOC_009190 as Potential Therapeutic Target for Lung Adenocarcinoma.

BACKGROUND: The abnormal regulation on the expression of lncRNAs had been linked to multiple kinds of cancers, including lung adenocarcinoma. METHODS: In this study, we carried out RNA-Seq on the three tumors and their paired normal samples from Chinese patients with lung adenocarcinoma. All the transcripts were de novo assembled, among which all the possible lncRNAs were predicted by tools including PLEK, CNCI, CPC, Blastp, hmmscan, and so forth. Their expression levels, altogether with the annotated mRNAs, were quantified. The weighted correlation network analysis and analysis of differential expression were carried out to explain the biological function of these novel lncRNAs. RESULTS: The weighted correlation network analysis showed that the lncRNAs, which were highly correlated with protein-coding genes, participated in various pathways, including PI3K kinase pathways. These lncRNAs were important regulators in biological processes. Next, the differentially expressed lncRNAs were identified, including four known lncRNAs and one novel lncRNA (XLOC_009190). The cis-regulation of this novel lncRNA might act on MGST1, which protected cells by conjugation and glutathione peroxidase functions. The trans-regulation of this lncRNA was investigated by its correlated mRNAs. The results showed that it possibly played a role in transmembrane receptors like G protein-coupled receptors and potassium channels. CONCLUSION: We proposed the potential biological function of XLOC_009190, but further experiments are needed to elucidate its roles and its potential to be the therapeutic target.

Mapping Urban Extent Using Luojia 1-01 Nighttime Light Imagery.

Luojia 1-01 satellite, launched on 2 June 2018, provides a new data source of nighttime light at 130 m resolution and shows potential for mapping urban extent. In this paper, using Luojia 1-01 and VIIRS nighttime light imagery, we compared several methods for extracting urban areas, including Human Settlement Index (HSI), Simple Thresholding Segmentation (STS) and SVM supervised classification. According to the accuracy assessment, the HSI method using LJ1-01 data had the best performance in urban extent extraction, which presented the largest Kappa Coefficient value, 0.834, among all the results. For the urban areas extracted by VIIRS based HSI method, the largest Kappa Coefficient value was 0.772. In contrast, the largest Kappa Coefficient values obtained by STS method were 0.79 and 0.7512 respectively when using LJ1-01 and VIIRS data, while for SVM method the values were 0.7829 and 0.7486 when using Landsat-LJ and Landsat-VIIRS composite data respectively. The experimented results demonstrated that the utilization of nighttime light imagery can largely improve the accuracy of urban extent extraction and LJ1-01 data, with a higher resolution and more abundant spatial information, can lead to better identification results than its predecessors.

Cystic tumour of the atrioventricular node: a case report and review of the literature.

Cystic tumour of the atrioventricular node is a rare primary cardiac tumour that can cause complete heart block and sudden death. Here, we describe a male case aged 42 years who suddenly died without a medical and family history of cardiac illnesses. After detailed macroscopic and microscopic examinations, a cystic mass was found in the atrioventricular nodal region. The small lesion was less than 1 cm in diameter, and consisted of small and large cystic spaces and tubular structures lined by flat, cuboidal or squamous epithelium. Immunohistochemical staining revealed the tumour epithelium positive for epithelial membrane antigen, carcinoembryonic antigen, antigen epitopes AE1/AE3, cytokeratins CK5/6 and CK7, but negative for calretinin, HBME-1, Wilms' tumor 1, factor VIII, chromogranin, synaptophysin or smooth muscle actin, suggesting an endodermal rather than mesothelial origin.