Chlorine disinfection to drinking water plays an important role in preventing and controlling waterborne disease outbreaks globally. Nevertheless, little is known about why it enriches the antibiotic ...resistance genes (ARGs) in bacteria after chlorination. Here, ARGs released from killed antibiotic-resistant bacteria (ARB), and culturable chlorine-injured bacteria produced in the chlorination process as the recipient, were investigated to determine their contribution to the horizontal transfer of ARGs during disinfection treatment. We discovered Escherichia coli, Salmonella aberdeen, Pseudomonas aeruginosa and Enterococcus faecalis showed diverse resistance to sodium hypochlorite, and transferable RP4 could be released from killed sensitive donor consistently. Meanwhile, the survival of chlorine-tolerant injured bacteria with enhanced cell membrane permeabilisation and a strong oxidative stress-response demonstrated that a physiologically competent cell could be transferred by RP4 with an improved transformation frequency of up to 550 times compared with the corresponding untreated bacteria. Furthermore, the water quality factors involving chemical oxygen demand (COD
), ammonium nitrogen and metal ions (Ca
and K
) could significantly promote above transformation frequency of released RP4 into injured E. faecalis. Our findings demonstrated that the chlorination process promoted the horizontal transfer of plasmids by natural transformation, which resulted in the exchange of ARGs across bacterial genera and the emergence of new ARB, as well as the transfer of chlorine-injured opportunistic pathogen from non-ARB to ARB. Considering that the transfer elements were quite resistant to degradation through disinfection, this situation poses a potential risk to public health.
Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act ...as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.
Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano‐sized vesicles released by a variety of cells. Emerging evidence shows that ...exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life‐threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome‐delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti‐cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti‐cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.
Exosomes are nano‐sized vesicles released by a variety of cells. Exosomes function as versatile promoters in the tumorigenesis, metastasis and drug resistance of breast cancer. In this review, we summarize the current knowledge about the functions of exosomes in the diagnosis, tumorigenesis, metastasis, microenvironment, drug resistance and therapy of breast cancer.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
The association between physical activity, sedentary behavior and health-related quality of life in children and adolescents has been mostly investigated in those young people with chronic disease ...conditions. No systematic review to date has synthesized the relationship between physical activity, sedentary behavior and health-related quality of life in the general healthy population of children and adolescents. The purpose of this study was to review systematically the existing literature that evaluated the relations between physical activity, sedentary behavior and health-related quality of life in the general population of children and adolescents.
We conducted a computer search for English language literature from databases of MEDLINE, EMBASE, PSYCINFO and PubMed-related articles as well as the reference lists of existing literature between 1946 and the second week of January 2017 to retrieve eligible studies. We included the studies that assessed associations between physical activity and/or sedentary behavior and health-related quality of life among the general population of children and adolescents aged between 3-18 years. The study design included cross-sectional, longitudinal and health intervention studies. We excluded the studies that examined associations between physical activity, sedentary behavior and health-related quality of life among children and adolescents with specific chronic diseases, and other studies and reports including reviews, meta-analyses, study protocols, comments, letters, case reports and guidelines. We followed up the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement in the reporting of this review. The risk of bias of the primary studies was assessed by the Newcastle-Ottawa Scale. We synthesized the difference in health-related quality of life scores between different levels of physical activity and sedentary time.
In total, 31 studies met the inclusion criteria and were synthesized in the review. Most of the included studies used a cross-sectional design (n = 21). There were six longitudinal studies and three school-based physical activity intervention studies. One study used both cross-sectional and longitudinal designs. We found that higher levels of physical activity were associated with better health-related quality of life and increased time of sedentary behavior was linked to lower health-related quality of life among children and adolescents. A dose-response relation between physical activity, sedentary behavior and health-related quality of life was observed in several studies suggesting that the higher frequency of physical activity or the less time being sedentary, the better the health-related quality of life.
The findings in this study suggest that school health programs promoting active lifestyles among children and adolescents may contribute to the improvement of health-related quality of life. Future research is needed to extend studies on longitudinal relationships between physical activity, sedentary behavior and health-related quality of life, and on effects of physical activity interventions on health-related quality of life among children and youth.
Anthracycline/taxane-based chemotherapy regimens are usually used as neoadjuvant chemotherapies to decrease tumour size and prevent metastasis of advanced breast cancer. However, patients have a high ...risk of developing chemo-resistance during treatment through still unknown mechanisms. Glutathione S-transferase P1 (GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione. Previous studies have identified GSTP1 as a predictor of prognosis and chemo-resistance in breast cancer patients, but the mechanisms governing GSTP1-dependent drug resistance are still unclear. We have found that GSTP1 expression is much higher in adriamycin-resistant cells and their corresponding exosomes. The role of GSTP1-containing exosomes in conferring drug resistance was analysed through cell apoptosis and immunofluorescence staining assays. Furthermore, we analysed 42 cases of paired breast cancer tissues collected before and after anthracycline/taxane-based neoadjuvant chemotherapy by immunohistochemistry. Higher GSTP1 expression was shown in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in the samples collected before and after the chemotherapy treatment. Interestingly, GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon treatment, and similar results were obtained for the exosomal marker Tumour susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. After analysing the serum exosomes of 30 patients treated with anthracycline/taxane-based neoadjuvant chemotherapy, we discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were significantly higher than those in the PR/CR group. Here, for the first time, we investigated a novel role for GSTP1-containing exosomes and their capability to transfer drug resistance and evaluated their clinical use in predicting chemo-resistance.
•Up-regulation of GSTP1 expression level was observed in Adriamycin-resistant cells and their corresponding exosomes.•GSTP1 can be transferred to sensitive cells through exosomes, thus resulting in a switch to drug-resistance.•GSTP1 expression is higher in chemo-resistant group from neoadjuvant chemo-resistant breast cancer tissues.•GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon chemotherapy.•Circulating GSTP1-containing exosomes predict clinical outcome of chemotherapy in breast cancer patients.
The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI ...symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.
COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.
Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m
A methylation and changed binding capacity with ACE2.
We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
Circular RNAs (circRNAs) are 3'-5' head-to-tail covalently closed non-coding RNA that have been proved to play essential roles in many cellular and developmental processes. However, no information ...relate to cucumber circRNAs is available currently, especially under salt stress condition.
In this study, we sequenced circRNAs in cucumber and a total of 2787 were identified, with 1934 in root and 44 in leaf being differentially regulated under salt stress. Characteristics analysis of these circRNAs revealed following features: most of them are exon circRNAs (79.51%) and they prefer to arise from middle exon(s) of parent genes (2035/2516); moreover, most of circularization events (88.3%) use non-canonical-GT/AG splicing signals; last but not least, pairing-driven circularization is not the major way to generate cucumber circRNAs since very few circRNAs (18) contain sufficient flanking complementary sequences. Annotation and enrichment analysis of both parental genes and target mRNAs were launched to uncover the functions of differentially expressed circRNAs induced by salt stress. The results showed that circRNAs may be paly roles in salt stress response by mediating transcription, signal transcription, cell cycle, metabolism adaptation, and ion homeostasis related pathways. Moreover, circRNAs may function to regulate proline metabolisms through regulating associated biosynthesis and degradation genes.
The present study identified large number of cucumber circRNAs and function annotation revealed their possible biological roles in response to salt stress. Our findings will lay a solid foundation for further structure and function studies of cucumber circRNAs.
Recently, a great deal of interest has been paid to polysaccharides isolated from natural sources due to their various beneficial health effects. Many of these special interested polysaccharides have ...a long history as part of herbal formulas that have been widely accepted in Asian countries. Lycium barbarum L. (L. barbarum), Zizyphus jujuba Mill (Z. jujuba), Plantago spp., and Morus spp. have been widely used in China as traditional herbal medicines and functional foods for millennia. Polysaccharides are bioactive constituents of these plants and are of interest because of their functional properties, which include immunomodulatory, antioxidant, antitumor, and hypoglycemic activity. This paper provides an overview of recent advances in understanding of the physiochemical, structural features and biological effects of these bioactive polysaccharides from L. barbarum, Z. jujuba, Plantago spp., and Morus spp. This review is to provide background and useful updated information for future research and application of these polysaccharides.
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•Interest in natural polysaccharides is increasing rapidly.•Polysaccharides from Lycium barbarum, Zizyphus jujuba, Plantago, Morus are reviewed.•Structural and bioactivities of these polysaccharides are lighted in this review.•Future perspective and challenges of these polysaccharides are presented.
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