Single-cell RNA sequencing and cell-cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer.

BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

Ensemble learning model identifies adaptation classification and turning points of river microbial communities in response to heatwaves.

Heatwaves are a global issue that threaten microbial populations and deteriorate ecosystems. However, how river microbial communities respond to heatwaves and whether and how high temperatures exceed microbial adaptation remain unclear. In this study, we proposed four types of pulse temperature-induced microbial responses and predicted the possibility of microbial adaptation to high temperature in global rivers using ensemble machine learning models. Our findings suggest that microbial communities in parts of South American (e.g., Brazil and Chile) and Southeast Asian (e.g., Vietnam) countries are likely to change due to heatwave disturbance from 25 to 37°C for consecutive days. Furthermore, the microbial communities in approximately 48.4% of the global river gauge stations are prone to fast stress inadaptation, with approximately 76.9% of these stations expected to exceed microbial adaptation after heatwave disturbances. If emissions of particulate matter with sizes not more than 2.5 µm (PM2.5, an indicator of human activities) increase by twofold, the number of global rivers associated with the fast stress adaptation type will decrease by ~13.7% after heatwave disturbances. Understanding microbial responses is crucially important for effective ecosystem management, especially for fragile and sensitive rivers facing heatwave events.

The immunogenic involvement of miRNA-492 in mycoplasma pneumoniae infection in pediatric patients

Abstract Objective: This study aimed to evaluate the role of miRNA-492 in the progression of mycoplasma pneumoniae (MP) infection in pediatric patients. Methods: Forty-six children admitted to the present study's hospital and diagnosed with mycoplasma pneumonia were recruited as the study group from March 2018 to August 2019, and 40 healthy children were selected as the control group. Results: The expression levels of miRNA-492, TNF-α, IL-6 and IL-18 in the study group were significantly higher than those in the control group (p < 0.05). There was no significant correlation between miRNA-492 and most of the immune-correlated indicators in the study group, except for IL-6, IL-18 and HMGB1. Meanwhile, overexpression of miRNA-492 increased IL-6 secretion in PMA-activated monocytes (p < 0.01). Conclusion: The present study's results suggested that miRNA-492 might play a role in the pathogenesis of mycoplasma pneumoniae pneumonia in children by regulating the secretion of immune-inflammatory factors such as IL-6 and IL-18 in the mononuclear macrophages.

The immunogenic involvement of miRNA-492 in mycoplasma pneumoniae infection in pediatric patients.

OBJECTIVE: This study aimed to evaluate the role of miRNA-492 in the progression of mycoplasma pneumoniae (MP) infection in pediatric patients. METHODS: Forty-six children admitted to the present study's hospital and diagnosed with mycoplasma pneumonia were recruited as the study group from March 2018 to August 2019, and 40 healthy children were selected as the control group. RESULTS: The expression levels of miRNA-492, TNF-α, IL-6 and IL-18 in the study group were significantly higher than those in the control group (p < 0.05). There was no significant correlation between miRNA-492 and most of the immune-correlated indicators in the study group, except for IL-6, IL-18 and HMGB1. Meanwhile, overexpression of miRNA-492 increased IL-6 secretion in PMA-activated monocytes (p < 0.01). CONCLUSION: The present study's results suggested that miRNA-492 might play a role in the pathogenesis of mycoplasma pneumoniae pneumonia in children by regulating the secretion of immune-inflammatory factors such as IL-6 and IL-18 in the mononuclear macrophages.

Neuroprotection of Triptolide against Amyloid-Beta1-42-induced toxicity via the Akt/mTOR/p70S6K-mediated Autophagy Pathway.

Triptolide is a natural active compound that has significant neuroprotective properties and shows promising effects in the treatment of Alzheimer's disease (AD). Recent studies have shown that autophagy occurs in AD. In this study, we determined whether autophagy regulated by triptolide ameliorates neuronal death caused by amyloid-Beta1-42 (Aß1-42). We examined the effects of triptolide on cell viability, autophagy, apoptosis, and the protein kinase B/mammalian target of the rapamysin/70 kDa ribosomal protein S6 kinase (Akt/mTOR/p70S6K) signaling pathway in PC12 cells. The results indicated that triptolide treatment exhibited a cytoprotective effect against cell injury induced by Aß1-42. Triptolide also reduced apoptosis and enhanced cell survival by decreasing autophagosome accumulation and inducing autophagic degradation. Furthermore, our results also showed that activating the Akt/mTOR/p70S6K mechanism was one reason for the protection of triptolide. Triptolide treatment protected against Aß1-42-induced cytotoxicity by decreasing autophagosome accumulation, and inducing autophagic degradation in PC12 cells. These findings also suggest that the reduction of autophagosome accumulation observed in triptolide-treated cells was Akt/mTOR/p70S6K pathway dependent. Overall, triptolide exhibits a neuron protective effect and this study provides new insight into AD prevention and treatment.

Effects of physical activity on heart rate variability in children and adolescents: a systematic review and meta-analysis.

The aim of the study was to investigate the effects of physical activity (PA) on heart rate variability (HRV) in children and adolescents. We conducted a research of Web of Science, PubMed, ScienceDirect, Springer-Link and EBSCO-host. The revised Newcastle-Ottawa Scale was used in an investigative analysis to assess bias risk. A total of 21 studies were included. Overall, medium-sized associations were found between PA and low frequency and high frequency in children and adolescents. High PA level had significantly higher standard deviation of RR intervals and root of the mean of the sum of the squares of differences between adjacent RR intervals in children and adolescents. The effects of PA on HRV were consistent in children and adolescents. Our systematic review and meta-analysis revealed medium-sized between PA and HRV in children and adolescents. Promoting children's and adolescents' participation in moderate-to-vigorous physical activity (MVPA) will increase parasympathetic nerve activity and decreased sympathetic nerve activity. Our findings support motivating children and adolescents to engage in more MVPA in their daily lives to improve autonomic nervous system function and promote cardiovascular safety.

Effects of physical activity on heart rate variability in children and adolescents: a systematic review and meta-analysis / Efeitos da atividade física na variabilidade da frequência cardíaca em crianças e adolescentes: uma revisão sistemática e meta-análise

Abstract The aim of the study was to investigate the effects of physical activity (PA) on heart rate variability (HRV) in children and adolescents. We conducted a research of Web of Science, PubMed, ScienceDirect, Springer-Link and EBSCO-host. The revised Newcastle-Ottawa Scale was used in an investigative analysis to assess bias risk. A total of 21 studies were included. Overall, medium-sized associations were found between PA and low frequency and high frequency in children and adolescents. High PA level had significantly higher standard deviation of RR intervals and root of the mean of the sum of the squares of differences between adjacent RR intervals in children and adolescents. The effects of PA on HRV were consistent in children and adolescents. Our systematic review and meta-analysis revealed medium-sized between PA and HRV in children and adolescents. Promoting children's and adolescents' participation in moderate-to-vigorous physical activity (MVPA) will increase parasympathetic nerve activity and decreased sympathetic nerve activity. Our findings support motivating children and adolescents to engage in more MVPA in their daily lives to improve autonomic nervous system function and promote cardiovascular safety.

Resumo O objetivo do estudo foi investigar os efeitos da atividade física (AF) na variabilidade da frequência cardíaca (VFC) em crianças e adolescentes. Realizamos uma pesquisa nas bases Web of Science, PubMed, ScienceDirect, Springer-Link e EBSCO-host. A Escala Newcastle-Ottawa revisada foi utilizada para avaliar o risco de enviesamento. Um total de 21 estudos foi incluído. De forma geral, foram encontradas associações de médio porte entre AF e baixa frequência e alta frequência em crianças e adolescentes. O alto nível de AF teve um desvio padrão significativamente maior dos intervalos e raiz da média da soma dos quadrados de diferenças entre os intervalos RR adjacentes em crianças e adolescentes. Os efeitos de AF sobre VFC foram consistentes em crianças e adolescentes. Nossa revisão sistemática e meta-análise revelou que AF e VFC em crianças e adolescentes são de médio porte. Promover a participação de crianças e adolescentes em atividade física de moderada à vigorosa (AFMV) aumentará a atividade nervosa parassimpática e diminuirá a atividade nervosa simpática. Nossas descobertas apoiam a motivação de crianças e adolescentes a se envolverem mais na AFMV em suas vidas diárias para melhorar o funcionamento do sistema nervoso autônomo e promover a segurança cardiovascular.

Chromosomal Microarray Reinterpretation: Applications to Pediatric Practice.

Chromosomal microarray analysis (CMA) frequently yields inconclusive results. We reexamined inconclusive CMA results from 33 previously tested patients and reached a definitive diagnosis in 3 (9.1%) and identified the need for additional testing in 4 (12.1%). Reinterpretation may resolve inconclusive CMA results.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway.

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

Prevalence and genotype distribution of human papillomavirus: implications for cancer screening and vaccination in Henan province, China.

INTRODUCTION: To provide information for cervical cancer screening and vaccination in Henan province, China, the distribution of human papillomavirus (HPV) was analyzed. METHODS: The HPV genotypes were detected using gene array and flow-through hybridization. RESULTS: Overall, 38.1% (1,536/4,033) of the women were human papillomavirus deoxyribonucleic acid (HPV DNA) positive. The prevalence of high-risk HPV types was 32.4%. HPV 16 was the most prevalent genotype (8.9%), followed by HPV 52 (5.8%) and HPV 58 (4.4%). CONCLUSIONS: The data support close surveillance of women for cervical cancer screening, and HPV prophylactic vaccines including HPV16, HPV 52, and HPV 58 might offer greater protection in this area.

HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood. In the present study, full-length human HER2 cDNA was introduced to the NSCLC cell lines H1975 and H1299, which have a low endogenous expression level of HER2. In addition, it was observed in the present study that the H1975 cell line harbored the L858R and T790M mutations in the EGFR kinase domain. Western blot analysis and MTT assay were used to evaluate the TKI sensitivity of HER2 expression status, and the activation of HER3 and HER2 downstream effectors. The results indicated that the sensitivity of H1975 cells to gefitinib was restored by the overexpression of HER2, which stimulated HER2-driven signaling cascades accompanied by the activation of protein kinase B. By contrast, ectopic HER2 overexpression in H1299 cells did not significantly alter the sensitivity to gefitinib treatment. In conclusion, the current study results suggested that the relatively resistance of the H1975 cell line to gefitinib could be reversed by the overexpression of HER2. Therefore, the expression of HER2 could also be considered when evaluate the patients' potential response to gefitinib, particularly in the subgroup of lung cancer patients who harbor an EGFR mutation.

Isolation and molecular characterization of 1-aminocyclopropane-1-carboxylic acid synthase genes in Hevea brasiliensis.

Ethylene is an important factor that stimulates Hevea brasiliensis to produce natural rubber. 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is a rate-limiting enzyme in ethylene biosynthesis. However, knowledge of the ACS gene family of H. brasiliensis is limited. In this study, nine ACS-like genes were identified in H. brasiliensis. Sequence and phylogenetic analysis results confirmed that seven isozymes (HbACS1-7) of these nine ACS-like genes were similar to ACS isozymes with ACS activity in other plants. Expression analysis results showed that seven ACS genes were differentially expressed in roots, barks, flowers, and leaves of H. brasiliensis. However, no or low ACS gene expression was detected in the latex of H. brasiliensis. Moreover, seven genes were differentially up-regulated by ethylene treatment. These results provided relevant information to help determine the functions of the ACS gene in H. brasiliensis, particularly the functions in regulating ethylene stimulation of latex production.

Cloning and molecular characterization of HbCOI1 from Hevea brasiliensis.

The full-length cDNA encoding a coronatine insensitive-1 (COI1) protein, designated HbCOI1, was isolated for the first time from Hevea brasiliensis by the rapid amplification of cDNA ends (RACE) method. HbCOI1 contained a 2,187 bp open reading frame encoding 597 amino acids. The deduced HbCOI1 protein, which showed high identity to COI1 protein of other plant species, was predicted to possess F-box and LRRs domains. The promoter region of HbCOI1 was isolated by the PCR-based DNA walking method. TATA box and other core configurations were found in the promoter. Several sequences similar to the eukaryotic cis regulatory element were found in the 5'-untranslated region (UTR) proximal 5' flanking sequence of HbCOI1. Southern blot analysis indicated that the HbCOI1 is present as a single copy in Hevea brasiliensis. Transcription pattern analysis revealed that HbCOI1 had high transcription in laticifer, low in barks and leaf. Transcription of HbCOI1 in latex was induced by jasmonate and tapping.