Publications by authors named "Xuan Zhou"

844 Publications

ProbResist: a database for drug-resistant probiotic bacteria.

Database (Oxford) 2022 Aug;2022

Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang 325060, China.

Drug resistance remains a global threat, and the rising trend of consuming probiotic-containing foods, many of which harbor antibiotic resistant determinants, has raised serious health concerns. Currently, the lack of accessibility to location-, drug- and species-specific information of drug-resistant probiotics has hampered efforts to combat the global spread of drug resistance. Here, we describe the development of ProbResist, which is a manually curated online database that catalogs reports of probiotic bacteria that have been experimentally proven to be resistant to antibiotics. ProbResist allows users to search for information of drug resistance in probiotics by querying with the names of the bacteria, antibiotic or location. Retrieved results are presented in a downloadable table format containing the names of the antibiotic, probiotic species, resistant determinants, region where the study was conducted and digital article identifiers (PubMed Identifier and Digital Object Identifier) hyperlinked to the original sources. The webserver also presents a simple analysis of information stored in the database. Given the increasing reports of drug-resistant probiotics, an exclusive database is necessary to catalog them in one platform. It will enable medical practitioners and experts involved in policy making to access this information quickly and conveniently, thus contributing toward the broader goal of combating drug resistance.

Database Url: https://probresist.com.
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http://dx.doi.org/10.1093/database/baac064DOI Listing
August 2022

Effect of Wearable Sensor-Based Exercise on Musculoskeletal Disorders in Individuals With Neurodegenerative Diseases: A Systematic Review and Meta-Analysis.

Front Aging Neurosci 2022 26;14:934844. Epub 2022 Jul 26.

Department of Rehabilitation, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The application of wearable sensor technology in an exercise intervention provides a new method for the standardization and accuracy of intervention. Considering that the deterioration of musculoskeletal conditions is of serious concern in patients with neurodegenerative diseases, it is worthwhile to clarify the effect of wearable sensor-based exercise on musculoskeletal disorders in such patients compared with traditional exercise.

Methods: Five health science-related databases, including PubMed, Cochrane Library, Embase, Web of Science, and Ebsco Cumulative Index to Nursing and Allied Health, were systematically searched. The protocol number of the study is PROSPERO CRD42022319763. Randomized controlled trials (RCTs) that were published up to March 2022 and written in English were included. Balance was the primary outcome measure, comprising questionnaires on postural stability and computerized dynamic posturography. The secondary outcome measures are motor symptoms, mobility ability, functional gait abilities, fall-associated self-efficacy, and adverse events. Stata version 16.0 was used for statistical analysis, and the weighted mean difference (WMD) was selected as the effect size with a 95% confidence interval (CI).

Results: Fifteen RCTs involving 488 participants with mean ages ranging from 58.6 to 81.6 years were included in this review, with 14 of them being pooled in a quantitative meta-analysis. Only five included studies showed a low risk of bias. The Berg balance scale (BBS) was used in nine studies, and the pooled data showed a significant improvement in the wearable sensor-based exercise group compared with the traditional exercise group after 3-12-week intervention (WMD = 1.43; 95% CI, 0.50 to 2.36, = 0.003). A significant change in visual score was found both post-assessment and at 1-month follow-up assessment (WMD = 4.38; 95% CI, 1.69 to 7.07, = 0.001; I2 = 0.0%). However, no significant differences were found between the two groups in the secondary outcome measures (all > 0.05). No major adverse events were reported.

Conclusion: The wearable sensor-based exercise had advantages in improving balance in patients with neurodegenerative diseases, while there was a lack of evidence in motor symptoms, mobility, and functional gait ability enhancement. Future studies are recommended to construct a comprehensive rehabilitation treatment system for the improvement in both postural control and quality of life.

Systematic Review Registration: http://www.crd.york.ac.uk/prospero/, identifier CRD42022319763.
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http://dx.doi.org/10.3389/fnagi.2022.934844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360755PMC
July 2022

Repetitive Transcranial Magnetic Stimulation for Neuropathic Pain and Neuropsychiatric Symptoms in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Neural Plast 2022 30;2022:2036736. Epub 2022 Jul 30.

Department of Rehabilitation, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has indicated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the management of neurological and psychiatric disorders, little evidence has been presented to support the effects of rTMS on neuropathic pain and neuropsychiatric symptoms in patients with TBI in all age groups. In addition, a better understanding of the potential factors that might influence the therapeutic effect of rTMS is necessary. The objective of this preregistered systematic review and meta-analysis was to quantify the effects of rTMS on physical and psychological symptoms in individuals with TBI. We systematically searched six databases for randomized controlled trials (RCTs) of rTMS in TBI patients reporting pain and neuropsychiatric outcomes published until March 20, 2022. The mean difference (MD) with 95% confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. Twelve RCTs with 276 TBI patients were ultimately selected from 1605 records for systematic review, and 11 of the studies were included in the meta-analysis. Overall, five of the included studies showed a low risk of bias. The effects of rTMS on neuropathic pain were statistically significant (MD = -1.00, 95% CI -1.76 to -0.25, = 0.009), with high heterogeneity ( = 76%). A significant advantage of 1 Hz rTMS over the right dorsolateral prefrontal cortex (DLPFC) in improving depression (MD = -6.52, 95% CI -11.58 to -1.46, = 0.01) was shown, and a significant improvement was noted in the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) scores of mild TBI patients after rTMS (MD = -5.87, 95% CI -10.63 to -1.11, = 0.02). However, no significance was found in cognition measurement. No major adverse events related to rTMS were reported. Moderate evidence suggests that rTMS can effectively and safely improve neuropathic pain, while its effectiveness on depression, postconcussion symptoms, and cognition is limited. More trials with a larger number of participants are needed to draw firm conclusions. This trial is registered with PROSPERO (PROSPERO registration number: CRD42021242364.
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http://dx.doi.org/10.1155/2022/2036736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357260PMC
August 2022

Intelligent Three-Dimensional Reconstruction Algorithm-Based Ultrasound-Guided Nerve Block in Intraoperative Anesthesia and Postoperative Analgesia of Orthopedic Surgery.

Comput Math Methods Med 2022 22;2022:9447649. Epub 2022 Jul 22.

Department of Anesthesiology, Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, 157011 Heilongjiang, China.

This research was aimed at analyzing the role of ultrasound-guided nerve block based on intelligent three-dimensional (3D) reconstruction algorithm in intraoperative anesthesia and postoperative analgesia of orthopedic surgery. 68 elderly patients were undergoing orthopedic surgery on the lower extremities, and they were randomly rolled into two groups with 34 patients in each group. The patients in control group received sciatic nerve block anesthesia (SNBA), and the patients in the experimental group received ultrasound-guided SNBA (UG-SNBA) under 3D reconstruction algorithm to analyze and compare the anesthesia effect and the postoperative analgesia effect. The results showed that compared with other algorithms, the evaluation index of ultrasound images processed by the 3D reconstruction algorithm was better. In terms of anesthesia effect, there was no significant difference in systolic blood pressure, diastolic blood pressure, and heart rate between the two groups before surgery ( > 0.05). Intraoperative and postoperative indicators of the experimental group were significantly better than those of the control group; the drug dosage (61 mg) was less than that of the control group (78 mg). In addition, the onset time of anesthesia, the time of pain blockade, and the postoperative awake time (5 minutes, 8 minutes, and 8 minutes, respectively) were shorter than those in the control group (13 minutes, 15 minutes, and 15 minutes, respectively). The visual analogue scale (VAS) scores of the experimental group were better than those of the control group on the day after surgery, one day after surgery, two days after surgery, and three days after surgery, with significant differences ( < 0.05). In summary, 3D reconstruction algorithm-based ultrasound image effect was clearer, the effect of UG-SNBA was more stable, and the postoperative analgesic effect was better. This work provided a higher reference for the selection of safe and effective anesthesia options in orthopedic surgery.
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http://dx.doi.org/10.1155/2022/9447649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337952PMC
August 2022

Bioinformatics analysis and experimental verification of Notch signalling pathway-related miRNA-mRNA subnetwork in extracellular vesicles during Echinococcus granulosus encystation.

Parasit Vectors 2022 Jul 30;15(1):272. Epub 2022 Jul 30.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, 200025, China.

Background: Encystation of the protoscoleces (PSCs) of Echinococcus granulosus is the main cause of secondary hydatid dissemination in the intermediate host. Extracellular vesicles (EVs) can transfer miRNAs into parasite cells to regulate mRNA expression. However, loading of developmental pathway-related miRNAs, such as those related to the Notch signalling pathway in EVs is unclear. Thus, we screened the miRNA-mRNA subnetwork involved in the Notch pathway during E. granulosus encystation in vitro and assessed changes in expression in the parasite and EVs.

Methods: mRNAs and miRNAs differentially expressed (DE) between PSCs and microcysts (MCs) were screened using high-throughput sequencing. DE mRNAs obtained from transcriptome analysis were intersected with mRNAs predicted to be targets of the conserved DE miRNAs of a small RNA library. DE miRNA functions were analysed using public databases, and a miRNA-mRNA subnetwork related to the Notch pathway was established. Notch pathway-related mRNA and miRNA expression of worms and EVs at different times was verified.

Results: In total, 1445 DE mRNAs between MCs and PSCs were screened after the intersection between 1586 DE mRNAs from the transcriptome and 9439 target mRNAs predicted using 39 DE miRNAs from the small RNA library. The DE mRNAs were clustered into 94 metabolic pathways, including the Notch pathway. Five DE miRNAs, including the most significantly expressed new DE miRNA, egr-new-mir0694-3p, corresponding to four target mRNAs (EgrG_000892700, EgrG_001029400, EgrG_001081400 and EgrG_000465800) were all enriched in the Notch pathway. The expression of the above mRNAs and miRNAs was consistent with the results of high-throughput sequencing, and the expression of each miRNA in EVs was verified. Annotated as ADAM17/TACE in the Notch pathway, EgrG_000892700 was down-regulated during PSC encystation. egr-miR-4989-3p and egr-miR-277a-3p expression in EVs after encystation was nearly five times that in EVs before encystation, which might regulate the expression of EgrG_000892700.

Conclusions: Five miRNAs corresponding to four target mRNAs may be involved in regulating the Notch pathway during the PSC encystation. EVs may regulate the expression of EgrG_000892700 in PSCs because of continuous targeting of egr-miR-4989-3p and egr-miR-277a-3p and participate in the regulation the Notch pathway. The study might expand new ideas for blocking the secondary infection of E. granulosus PSCs via EVs miRNAs.
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http://dx.doi.org/10.1186/s13071-022-05391-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338502PMC
July 2022

Comparative Transcriptome Analyses of Geriatric Rats Associate Age-Related Erectile Dysfunction With a lncRNA-miRNA-mRNA Regulatory Network.

Front Endocrinol (Lausanne) 2022 11;13:887486. Epub 2022 Jul 11.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: The key regulatory roles of long non-coding RNAs (lncRNAs) in age-related erectile dysfunction (A-ED) are unknown.

Aim: This study aimed to identify putative lncRNAs that regulate age-related erectile dysfunction transcriptome analyses, and to predict their specific regulatory routes bioinformatics methods.

Methods: 22 geriatric male SD rats were divided into age-related erectile dysfunction (A-ED) and negative control (NC) groups after evaluations of intracavernous pressure (ICP). By comparative analysis of transcriptomes of cavernosal tissues from both groups, we identified differentially expressed lncRNAs, miRNAs, and mRNAs. Seven differentially expressed lncRNAs were selected and further verified by quantitative real-time polymerase chain reactions (RT-qPCR). The construction of the lncRNA-miRNA-mRNA network, the Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in Cytoscape.

Results: From comparative transcriptome analyses of A-ED and NC groups, 69, 29, and 364 differentially expressed lncRNAs, miRNAs, and mRNAs were identified respectively. Differentially expressed lncRNAs were culled to seven, which were all verified by qPCR. Three of these lncRNAs (ENSRNOT00000090050, ENSRNOT00000076482, and ENSRNOT00000029245) were used to build regulatory networks, of which only ENSRNOT00000029245 was successful. Moreover, GO and KEGG analyses demonstrated that these lncRNAs possibly regulated muscle myosin complex, muscle cell cellular homeostasis, and ultimately erectile function in rats through PI3K-Akt, fluid shear stress, and atherosclerosis pathways.

Conclusion: Our study identified differentially expressed lncRNAs, miRNAs, and mRNAs through comparisons of transcriptomes of geriatric rats. An identified lncRNA verified by qPCR, was used to construct a lncRNA-miRNA-mRNA regulatory network. LncRNA ENSRNOT00000029245 possibly regulated downstream mRNAs through this regulatory network, leading to apoptosis in the cavernous tissue, fibrosis, and endothelial dysfunction, which ultimately caused ED. These findings provide seminal insights into the molecular biology of aging-related ED, which could spur the development of effective therapeutics.
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http://dx.doi.org/10.3389/fendo.2022.887486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309694PMC
July 2022

Characterization of Field-Evolved Resistance to Afidopyropen, a Novel Insecticidal Toxin Developed from Microbial Secondary Metabolites, in .

Toxins (Basel) 2022 Jul 1;14(7). Epub 2022 Jul 1.

Institute of Plant Protection, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.

Afidopyropen, a newly identified chemical, is a derivative of pyripyropene A, which is produced by the filamentous fungus . It is a promising novel pesticide applied against whiteflies in agriculture. In this study, the reversion and selection, cross-resistance patterns, synergistic effects, and fitness costs of afidopyropen resistance were studied in a field-developed resistant population of . Compared to a reference MED-S strain, the field-developed resistant Haidian (HD) population showed 36.5-fold resistance to afidopyropen. Significant reversion of resistance to afidopyropen was found in the HD population when it was kept with no selective pressure of the insecticide. The HD-Afi strain, developed from the HD population with afidopyropen pressure, developed 104.3-fold resistance to afidopyropen and significant cross-resistance to sulfoxaflor. Piperonyl butoxide (PBO) largely inhibited afidopyropen resistance in the HD-Afi strain, which indicates that P450 monooxygenase could be involved in the resistance. Significant fitness costs associated with afidopyropen resistance were observed in HD-Afi. This study indicates that a rotation of afidopyropen with other chemical control agents could be useful for impeding afidopyropen resistance in . In addition, we expanded upon the understanding of resistance to afidopyropen, offering evidence suggesting the importance of devising better strategies for the management of whiteflies.
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http://dx.doi.org/10.3390/toxins14070453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320511PMC
July 2022

Pyroptosis-Related lncRNA Prognostic Model for Renal Cancer Contributes to Immunodiagnosis and Immunotherapy.

Front Oncol 2022 4;12:837155. Epub 2022 Jul 4.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Renal clear cell cancer (ccRCC) is one of the most common cancers in humans. Thus, we aimed to construct a risk model to predict the prognosis of ccRCC effectively.

Methods: We downloaded RNA sequencing (RNA-seq) data and clinical information of 539 kidney renal clear cell carcinoma (KIRC) patients and 72 normal humans from The Cancer Genome Atlas (TCGA) database and divided the data into training and testing groups randomly. Pyroptosis-related lncRNAs (PRLs) were obtained through Pearson correlation between pyroptosis genes and all lncRNAs ( < 0.05, coeff > 0.3). Univariate and multivariate Cox regression analyses were then performed to select suitable lncRNAs. Next, a novel signature was constructed and evaluated by survival analysis and ROC analysis. The same observation applies to the testing group to validate the value of the signature. By gene set enrichment analysis (GSEA), we predicted the underlying signaling pathway. Furthermore, we calculated immune cell infiltration, immune checkpoint, the T-cell receptor/B-cell receptor (TCR/BCR), SNV, and Tumor Immune Dysfunction and Exclusion (TIDE) scores in TCGA database. We also validated our model with an immunotherapy cohort. Finally, the expression of PRLs was validated by quantitative PCR (qPCR).

Results: We constructed a prognostic signature composed of six key lncRNAs (U62317.1, MIR193BHG, LINC02027, AC121338.2, AC005785.1, AC156455.1), which significantly predict different overall survival (OS) rates. The efficiency was demonstrated using the receiver operating characteristic (ROC) curve. The signature was observed to be an independent prognostic factor in cohorts. In addition, we found the PRLs promote the tumor progression immune-related pathways revealed in GSEA. Furthermore, the TCR, BCR, and SNV data were retrieved to screen immune features, and immune cell scores were calculated to measure the effect of the immune microenvironment on the risk model, indicating that high- and low-risk scores have different immune statuses. The TIDE algorithm was then used to predict the immune checkpoint blockade (ICB) response of our model, and subclass mapping was used to verify our model in another immunotherapy cohort data. Finally, qPCR validates the PRLs in cell lines.

Conclusion: This study provided a new risk model to evaluate ccRCC and may be pyroptosis-related therapeutic targets in the clinic.
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http://dx.doi.org/10.3389/fonc.2022.837155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291251PMC
July 2022

Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer.

N Engl J Med 2022 07;387(3):217-226

From the International Breast Cancer Center, Pangaea Oncology, Quirónsalud Group, Barcelona (J.C., J.P.-G.), and the Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid (J.C.) - both in Spain; the Department of Medicine, University of California San Francisco Comprehensive Cancer Center, San Francisco (H.S.R.); Princess Margaret Cancer Centre, Toronto (D.W.C.); Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul (S.-A.I.); Cancer Center at Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia (M.M.Y.); the Oncology Institute, Arturo Lopez Perez Foundation, Santiago, Chile (C.G.); the Department of Oncology, Republican Clinical Oncology Dispensary, Ufa, Russia (O.L.); the Oncology Research Unit, Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil (C.H.B.); the Department of Breast Oncology, Aichi Cancer Center Hospital (H.I.), and the Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine (N.M.) - both in Nagoya, Japan; the Department of Hematology and Oncology, Oncomedica, Montería, Colombia (M.T.O.); Ege University Medical Faculty, Izmir, Turkey (E.G.); the Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville - both in Australia (S.L.); Merck, Rahway, NJ (Z.G., X.Z., V.K., W.P.); and the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London (P.S.).

Background: In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported.

Methods: We randomly assigned patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer in a 2:1 ratio to receive pembrolizumab (200 mg) every 3 weeks plus the investigator's choice of chemotherapy (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin) or placebo plus chemotherapy. The primary end points were progression-free survival (reported previously) and overall survival among patients whose tumors expressed PD-L1 with a CPS of 10 or more (the CPS-10 subgroup), among patients whose tumors expressed PD-L1 with a CPS of 1 or more (the CPS-1 subgroup), and in the intention-to-treat population. Safety was also assessed.

Results: A total of 847 patients underwent randomization: 566 were assigned to the pembrolizumab-chemotherapy group, and 281 to the placebo-chemotherapy group. The median follow-up was 44.1 months. In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met]); in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively (hazard ratio, 0.86; 95% CI, 0.72 to 1.04; two-sided P = 0.1125 [not significant]); and in the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (hazard ratio, 0.89; 95% CI, 0.76 to 1.05 [significance not tested]). Adverse events of grade 3, 4, or 5 that were related to the trial regimen occurred in 68.1% of the patients in the pembrolizumab-chemotherapy group and in 66.9% in the placebo-chemotherapy group, including death in 0.4% of the patients in the pembrolizumab-chemotherapy group and in no patients in the placebo-chemotherapy group.

Conclusions: Among patients with advanced triple-negative breast cancer whose tumors expressed PD-L1 with a CPS of 10 or more, the addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone. (Funded by Merck Sharp and Dohme; KEYNOTE-355 ClinicalTrials.gov number, NCT02819518.).
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http://dx.doi.org/10.1056/NEJMoa2202809DOI Listing
July 2022

Ribosomal S6 protein kinase 2 aggravates process of systemic scleroderma.

J Invest Dermatol 2022 Jul 16. Epub 2022 Jul 16.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, P.R. China. Electronic address:

Systemic sclerosis (SSc) is a complex process of pathogenesis, and the contributions of inherited genes, infections, and chemicals remain largely unknown. Here, we demonstrated that p90 ribosomal S6 protein kinase 2 (RSK2) was selectively upregulated in fibrotic skin and fibroblasts treated with the profibrotic cytokine transforming growth factor β (TGF-β). Moreover, knockout of RSK2 specifically in skin fibroblasts or pharmacological inhibition of RSK2 attenuated skin fibrosis in mouse model. Mechanistically, RSK2 directly interacted with glycogen synthase kinase 3β (GSK3β) in vivo and in vitro, and thereby induced phosphorylation of GSK3β at Ser9 to inhibit ubiquitination and degradation of Gli1, which promoted fibroblast differentiation and skin fibrosis. Consequently, RSK2 plays an important role in the dermal skin of SSc. These findings provided a potential therapeutic target for SSc.
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http://dx.doi.org/10.1016/j.jid.2022.06.020DOI Listing
July 2022

An Autophagy-Related Gene Signature can Better Predict Prognosis and Resistance in Diffuse Large B-Cell Lymphoma.

Front Genet 2022 30;13:862179. Epub 2022 Jun 30.

Department of Hematology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease, and about 30%-40% of patients will develop relapsed/refractory DLBCL. In this study, we aimed to develop a gene signature to predict survival outcomes of DLBCL patients based on the autophagy-related genes (ARGs). We sequentially used the univariate, least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses to build a gene signature. The Kaplan-Meier curve and the area under the receiver operating characteristic curve (AUC) were performed to estimate the prognostic capability of the gene signature. GSEA analysis, ESTIMATE and ssGSEA algorithms, and one-class logistic regression were performed to analyze differences in pathways, immune response, and tumor stemness between the high- and low-risk groups. Both in the training cohort and validation cohorts, high-risk patients had inferior overall survival compared with low-risk patients. The nomogram consisted of the autophagy-related gene signature, and clinical factors had better discrimination of survival outcomes, and it also had a favorable consistency between the predicted and actual survival. GSEA analysis found that patients in the high-risk group were associated with the activation of doxorubicin resistance, NF-κB, cell cycle, and DNA replication pathways. The results of ESTIMATE, ssGSEA, and mRNAsi showed that the high-risk group exhibited lower immune cell infiltration and immune activation responses and had higher similarity to cancer stem cells. We proposed a novel and reliable autophagy-related gene signature that was capable of predicting the survival and resistance of patients with DLBCL and could guide individualized treatment in future.
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http://dx.doi.org/10.3389/fgene.2022.862179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280409PMC
June 2022

Internal and external validation of machine learning-assisted prediction models for mechanical ventilation-associated severe acute kidney injury.

Aust Crit Care 2022 Jul 13. Epub 2022 Jul 13.

Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, General Hospital of People's Liberation Army, Beijing, 100853, China; National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address:

Background: Currently, very few preventive or therapeutic strategies are used for mechanical ventilation (MV)-associated severe acute kidney injury (AKI).

Objectives: We developed clinical prediction models to detect the onset of severe AKI in the first week of intensive care unit (ICU) stay during the initiation of MV.

Methods: A large ICU database Medical Information Mart for Intensive Care IV (MIMIC-IV) was analysed retrospectively. Data were collected from the clinical information recorded at the time of ICU admission and during the initial 12 h of MV. Using univariate and multivariate analyses, the predictors were selected successively. For model development, two machine learning algorithms were compared. The primary goal was to predict the development of AKI stage 2 or 3 (AKI-23) and AKI stage 3 (AKI-3) in the first week of patients' ICU stay after initial 12 h of MV. The developed models were externally validated using another multicentre ICU database (eICU Collaborative Research Database, eICU) and evaluated in various patient subpopulations.

Results: Models were developed using data from the development cohort (MIMIC-IV: 2008-2016; n = 3986); the random forest algorithm outperformed the logistic regression algorithm. In the internal (MIMIC-IV: 2017-2019; n = 1210) and external (eICU; n = 1494) validation cohorts, the incidences of AKI-23 were 154 (12.7%) and 119 (8.0%), respectively, with areas under the receiver operator characteristic curve of 0.78 (95% confidence interval [CI]: 0.74-0.82) and 0.80 (95% CI: 0.76-0.84); the incidences of AKI-3 were 81 (6.7%) and 67 (4.5%), with areas under the receiver operator characteristic curve of 0.81 (95% CI: 0.76-0.87) and 0.80 (95% CI: 0.73-0.86), respectively.

Conclusions: Models driven by machine learning and based on routine clinical data may facilitate the early prediction of MV-associated severe AKI. The validated models can be found at: https://apoet.shinyapps.io/mv_aki_2021_v2/.
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http://dx.doi.org/10.1016/j.aucc.2022.06.001DOI Listing
July 2022

Programmable dual-electric-field immunosensor using MXene-Au-based competitive signal probe for natural parathion-methyl detection.

Biosens Bioelectron 2022 Oct 7;214:114546. Epub 2022 Jul 7.

Food & Biological Engineering, Jiangsu University, China. Electronic address:

Immunosensor is a promising tool for natural parathion-methyl (PTM) detection, and its analytical advantages can be magnified by introducing flexibly-fabricating technique. Herein, we present a dual-electric-field PTM immunosensor on highly-compatible screen-printed electrode (SPE). MXene-Au, the product of in-situ gold nanoparticle growth on MXene, provides considerable binding sites for PTM antigen (ATG) and methylene blue (MB). During sensing, the MXene-Au-MB-ATG probe competitively binds antibody against PTM, composing a ratiometric immune-system. With DC-biased sine excitations from complementary waveforms, on-chip electric field couple improves immunoreactions among PTM, probe, and antibody. Electric field distribution is programmed by trimming bypass resistors to pursue optimal performance. Probe synthesis is solidly proven with morphological examinations, and competition mechanism between the probe and target PTM is clarified in electrochemical analyses. Remarkably, this method brings less consumption of immune time than electric-field-free or solo-electric-field setup (50 s vs. 900 or 70 s), and simultaneously provides more powerful ratiometric signal than the rivals. Log-linear relationship, between PTM level and sensor readout, is established in 0.02-38 ng/mL, and limit of detection is found as 0.01 ng/mL. This method is applied in laboratorial and natural PTM analyses, and the readouts are consistent with high performance liquid chromatography and recovery test.
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http://dx.doi.org/10.1016/j.bios.2022.114546DOI Listing
October 2022

Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

J Agric Food Chem 2022 Jul 11;70(28):8619-8630. Epub 2022 Jul 11.

College of Food Science, Northeast Agricultural University, Harbin, 150030, China.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. () 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the -GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.
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http://dx.doi.org/10.1021/acs.jafc.2c01950DOI Listing
July 2022

Parenting sense of competence and its predictors among primiparous women: a longitudinal study in China.

BMC Pregnancy Childbirth 2022 Jul 7;22(1):548. Epub 2022 Jul 7.

Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.

Background: Parenting sense of competence significantly affects the quality of parenting behaviours and healthy infant development. However, primiparous women without parenting experience may lack confidence and feel stress. This study aimed to explore the status of parenting sense of competence and identify its predictors among primiparous women.

Methods: A longitudinal study design was used. Primiparous women were recruited by using a convenience sample from two women's and children's hospitals in two cities in China. All primiparous women completed questionnaires on demographic characteristics, infant characteristics, family function, and parenting sense of competence at 1 month postpartum. At 3 months postpartum, each women's parenting sense of competence was re-assessed. Generalised linear regression was applied to identify the predictors of parenting sense of competence at 3 months postpartum.

Results: A total of 743 Chinese primiparous women were included in the analysis. The average parenting sense of competence score of the participants at 3 months postpartum was 70.18 (SD = 12.33). According to the generalised linear regression analysis, higher levels of parenting sense of competence at 3 months postpartum were significantly associated with older age (β = 0.13, P = 0.005), better family function (β = 0.37, P <  0.001), and higher levels of parenting sense of competence (β = 0.35, P <  0.001) at 1 month postpartum. In contrast, lower levels of parenting sense of competence at 3 months postpartum were associated with poorer self-rated economic status (β = - 0.16, P = 0.027), poorer infant health (β = - 0.26, P = 0.007), and mixed or formula feeding (β = - 0.11, P = 0.018) at 1 month postpartum.

Conclusions: Chinese primiparous women have a relatively good parenting sense of competence, but there is still room for improvement. Maternal age, economic status, family function, infant health, and feeding patterns were significant predictors. To improve their parenting sense of competence, more attention should be paid to primiparous women who are young, with poor economic status, having an unhealthy infant, and mixed or formula feeding. In addition, measures should also be taken during the early postpartum period to improve family function.
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http://dx.doi.org/10.1186/s12884-022-04881-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260977PMC
July 2022

Catalyst-dependent chemoselective insertion of diazoalkanes into the N-H/C-H/O-H/C-O bonds of 2-hydroxybenzothiazoles.

Org Biomol Chem 2022 Jul 6. Epub 2022 Jul 6.

Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.

The control of chemoselective insertions of diazoalkanes into 2-hydroxybenzothiazoles is challenging. Herein, the chemoselective N-H, O-H, C-O or C-H bond insertions of diazoalkanes into 2-hydroxybenzothiazoles are achieved using B(CF), Rh(OAc) or TfOH as the catalyst. This affords routes to 54 benzothiazole derivatives. These protocols are scalable and demonstrate the complementary nature of Lewis acid, transition metal and Brønsted acid catalyses.
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http://dx.doi.org/10.1039/d2ob01048hDOI Listing
July 2022

The Relationship Between Occupational Stress and Turnover Intention Among Emergency Physicians: A Mediation Analysis.

Front Public Health 2022 16;10:901251. Epub 2022 Jun 16.

Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: There is evidence that occupational stress is a risk factor for turnover intentions. However, the structural relationship between occupational stress and turnover intention among emergency physicians has rarely been studied. This study aimed to examine the pathways of occupational stress on turnover intention through job satisfaction and depressive symptoms among emergency physicians in China.

Methods: A cross-sectional study was conducted in China from July 2018 to August 2018. Data were collected using a structured questionnaire that included demographic characteristics, occupational stress, job satisfaction, depressive symptoms, and turnover intention. Hierarchical linear regression was performed to explore the related factors of turnover intention. Structural equation modeling was used to examine the pathways from occupational stress to turnover intention.

Results: A total of 10,457 emergency physicians completed the questionnaire. The score of turnover intention was 11.34 (SD = 3.25), and the average item score of turnover intention was 2.84 (SD = 0.81). In structural equation modeling, the occupational stress not only had a direct effect on turnover intention (standardized direct effect = 0.311, bias-corrected 95% confidence interval [0.261, 0.361], < 0.001), but also had an indirect effect through job satisfaction and depressive symptoms (standardized indirect effect = 0.448, bias-corrected 95% confidence interval [0.412, 0.484], < 0.001). However, the effect of depressive symptoms on turnover intention was weak (standardized coefficient [β] = 0.08, < 0.001).

Conclusions: Job satisfaction partially mediated the relationship between occupational stress and turnover intention. However, due to the weak effect of depressive symptoms on turnover intention, the mediating role of depressive symptoms between occupational and turnover intention had little practical value. It is recommended that hospital administrators prioritize increasing job satisfaction of emergency physicians to reduce the impact of occupational stress on their turnover intention.
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http://dx.doi.org/10.3389/fpubh.2022.901251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245016PMC
June 2022

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease: Mendelian Randomization and Polygenic Risk Score Analysis.

Front Genet 2022 13;13:814457. Epub 2022 Jun 13.

Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Growth differentiation factor 15 (GDF-15) levels have been revealed as a robust biomarker for metformin use. We conducted Mendelian randomization (MR) analysis to explore the association between GDF-15 and gallstone disease to inform potential therapeutic effects targeting GDF-15. Four genetic variants associated with GDF-15 levels at < 5 × 10 were selected as instrumental variables from a genome-wide association meta-analysis including 21,758 individuals. Two-sample MR analysis was conducted using summary-level data from UK Biobank (10,520 gallstone cases and 350,674 controls) and FinnGen consortium (19,023 gallstone cases and 195,144 controls). Polygenic risk score analysis using individual-level data in UK biobank was performed to complement the MR findings by examining the non-linearity of the association. Diabetic complications were taken as positive controls to validate the therapeutic effect of targeting GDF-15. Linear and nonlinear associations between genetically predicted GDF-15 levels and gallstones were estimated with stratification by the diabetic status. In the two-sample MR analysis, the odds ratio (OR) of gallstones was 1.09 (95% confidence interval (CI), 1.03-1.15; = 0.001) for one standard deviation increase in genetically predicted GDF-15 levels in the meta-analysis of two datasets. Polygenic risk score analysis found this association to be U-shaped ( = 0.037). The observed association was predominantly seen in nondiabetic population (OR = 1.11, 95% CI: 1.01-1.21; = 0.003). An inverse association between genetically predicted GDF-15 levels and diabetic complications (OR = 0.77, 95% CI: 0.62-0.96; = 0.023) was observed, validating the potential therapeutic effects of targeting GDF-15 levels. This MR study indicates that the increased risk of gallstone disease should be taken into account when considering GDF-15 as a therapeutic target for diabetic complications.
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http://dx.doi.org/10.3389/fgene.2022.814457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234303PMC
June 2022

Deep learning to diagnose Hashimoto's thyroiditis from sonographic images.

Nat Commun 2022 06 29;13(1):3759. Epub 2022 Jun 29.

Tianjin Cancer Institute, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

Hashimoto's thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836-0.939) and 0.895 (0.862-0.927). HTNet exceeds radiologists' performance on accuracy (83.2% versus 79.8%; binomial test, p < 0.001) and sensitivity (82.6% versus 68.1%; p < 0.001). By integrating serologic markers with imaging data, the performance of HTNet was significantly and marginally improved on the video (AUC, 0.949 versus 0.888; DeLong's test, p = 0.004) and static-image (AUC, 0.914 versus 0.901; p = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.
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http://dx.doi.org/10.1038/s41467-022-31449-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243092PMC
June 2022

The effect of self-management programs on post-stroke social participation: A systematic review and meta-analysis.

Clin Rehabil 2022 Sep 28;36(9):1141-1152. Epub 2022 Jun 28.

Department of nursing, 92323Zhongshan Hospital Fudan University, Shanghai, 200032, China.

Objective: The aim of this study was to identify the effectiveness of self-management programs on the improvement of social participation among stroke survivors. Data Sources: Cochrane Library, PubMed, Web of Science database, EMBASE, Medline, CINAHL plus, and APA PsycArticles were searched from their inception to December 20, 2021.

Methods: We considered randomized controlled trials and non-randomized controlled trials without language limits. Two reviewers independently screened the literature, evaluated risk of bias using the Cochrane's risk of bias tool, scored the methodological quality using criteria of the Australian Evidence-based Health Care Center, and extracted the data. The outcome was social participation. RevMan 5.3 was used, and intergroup differences were determined by calculating standardized mean difference (SMD) and 95% confidence intervals (CIs).

Results: Of 1894 initial studies, totally 15 studies met the eligible criteria, consisting of six randomized controlled trials and nine non-randomized controlled trials. Four randomized controlled trials showed high methodological quality and two demonstrated medium quality. The randomized controlled trials involved a total of 430 stroke survivors and were published between 2007 and 2020. The meta-analysis from five randomized controlled trials demonstrates that the overall effect of self-management programs on social participation was not statistically significant (95% CI, -0.23 to 0.40; p = 0.61). Most of the non-randomized controlled trials were pre-/post-test design with an average sample size of 15.4. The effect of self-management program on social participation in most non-randomized controlled trials was insignificant as well.

Conclusion: The self-management programs seem not to be superior to usual care for the improvement on social participation in stroke survivors based on current evidence. Further well-designed investigation considering social participation as the primary outcome is still warranted.
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http://dx.doi.org/10.1177/02692155221095477DOI Listing
September 2022

Organophosphate flame retardant TDCPP: A risk factor for renal cancer?

Chemosphere 2022 Oct 25;305:135485. Epub 2022 Jun 25.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; Department of Urology, The Affiliated Kizilsu Kirghiz Autonomous Prefecture People's Hospital of Nanjing Medical University, Artux, 845350, China. Electronic address:

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a chlorinated organophosphate flame retardants(OPFRs), is widely used in a range of plastic foams, resins, and latexes. It can be detected in human tissues, including urine, and milk. Recent research has suggested that TDCPP has neurotoxic, reproductive, and potentially carcinogenic. In our study, we proposed a novel method for predicting the gene associated with tumor-compound interactions. We firstly used The Comparative Toxicogenomics Database (CTD) and downloaded potentially interactive genes about TDCPP in renal carcinoma. Gene expression data and the corresponding clinical information of the Kidney renal clear cell cancer (KIRC) patients were obtained from The Cancer Genome Atlas database (TCGA). Data from normal people in The Genotype-Tissue Expression (GTEx) databases was used to supplement the calculations. After being predicted by PharmMapper database, and validated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, 25 genes were selected to construct protein-protein interaction network analysis. The prognostic value of these genes was evaluated with Kaplan-Meier analysis, and four interactive genes were selected. Gene set variation analysis and drug-target binding prediction proved the hub gene has a potential relationship with renal clear cell carcinoma. We then used the ChEA3 (Chip-X Enrichment Analysis, Version 3) database to predict the upstream of these interactive genes. Molecular docking was used to predict the binding of these transcription factors to TDCPP and interactive genes to TDCPP. Moreover, in cell lines and in vivo experiments demonstrated the cancer-promoting effect of TDCPP. The expression of the interactive genes was verified by qPCR and Western blot. Combining binding energy and qPCR results, we choose EPAS1 to verify its function in renal carcinoma cell lines. Our study provides a novel method to predict the potential interactive genes between TDCPP and renal cancer, which may reveal potential targets for the treatment and prevention of diseases.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135485DOI Listing
October 2022

The tetratricopeptide repeat protein OsTPR075 promotes heading by regulating florigen transport in rice.

Plant Cell 2022 Jun 28. Epub 2022 Jun 28.

State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou, 311400, China.

Rice (Oryza sativa) is one of the most important crops worldwide. Heading date is a vital agronomic trait that influences rice yield and adaption to local conditions. Hd3a, a proposed florigen that primarily functions under short-day conditions (SDs), is a mobile flowering signal that promotes the floral transition in rice. Nonetheless, how Hd3a is transported from leaves to the shoot apical meristem (SAM) under SDs remains elusive. Here, we report that FT-INTERACTING PROTEIN9 (OsFTIP9) specifically regulates rice flowering time under SDs by facilitating Hd3a transport from companion cells to sieve elements. Furthermore, we show that the tetratricopeptide repeat (TPR) protein OsTPR075 interacts with both OsFTIP9 and OsFTIP1 and strengthens their respective interactions with Hd3a and the florigen RFT1. This in turn affects the trafficking of Hd3a and RFT1 to the SAM, thus regulating flowering time under SDs and long-day conditions, respectively. Our findings suggest that florigen transport in rice is mediated by different OsFTIPs under different photoperiods and that interactions between OsTPR075 and OsFTIPs are essential for mediating florigen movement from leaves to the SAM.
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http://dx.doi.org/10.1093/plcell/koac190DOI Listing
June 2022

The Organ Size and Morphological Change During the Domestication Process of Soybean.

Front Plant Sci 2022 9;13:913238. Epub 2022 Jun 9.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, CAS Center for Excellence in Molecular Plant Sciences, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, China.

Soybean is one of the most important legume crops that can provide the rich source of protein and oil for human beings and livestock. In the twenty-one century, the total production of soybean is seriously behind the needs of a growing world population. Cultivated soybean [ (L.) Merr.] was domesticated from wild soybean ( Sieb. and Zucc.) with the significant morphology and organ size changes in China around 5,000 years ago, including twisted stems to erect stems, small seeds to large seeds. Then it was spread worldwide to become one of the most popular and important crops. The release of the reference soybean genome and omics data provides powerful tools for researchers and breeders to dissect the functional genes and apply the germplasm in their work. Here, we summarized the function genes related to yield traits and organ size in soybean, including stem growth habit, leaf size and shape, seed size and weight. In addition, we also summarized the selection of organ traits during soybean domestication. In the end, we also discussed the application of new technology including the gene editing on the basic research and breeding of soybean, and the challenges and research hotspots in the future.
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http://dx.doi.org/10.3389/fpls.2022.913238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221068PMC
June 2022

Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.

Nat Commun 2022 06 25;13(1):3646. Epub 2022 Jun 25.

Department of Research Laboratories and Director of Center for Stem Cell and Cell Therapy, Instituto G. Gaslini Children Hospital Scientific Institute, 16147, Genova, Italy.

The diverse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Loss of WASP binding to splicing factor gene promoters frequently leads to aberrant epigenetic activation. WASP interacts with dozens of nuclear speckle constituents and constrains SRSF2 mobility. Using an optogenetic system, we showed that WASP forms phase-separated condensates that encompasses SRSF2, nascent RNA and active Pol II. The role of WASP in gene body condensates is corroborated by ChIPseq and RIPseq. Together our data reveal that WASP is a nexus regulator of RNA splicing that controls the transcription of splicing factors epigenetically and the dynamics of the splicing machinery through liquid-liquid phase separation.
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http://dx.doi.org/10.1038/s41467-022-31220-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233711PMC
June 2022

A review on pathology, mechanism, and therapy for cerebellum and tremor in Parkinson's disease.

NPJ Parkinsons Dis 2022 Jun 24;8(1):82. Epub 2022 Jun 24.

Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Tremor is one of the core symptoms of Parkinson's disease (PD), but its mechanism is poorly understood. The cerebellum is a growing focus in PD-related researches and is reported to play an important role in tremor in PD. The cerebellum may participate in the modulation of tremor amplitude via cerebello-thalamo-cortical circuits. The cerebellar excitatory projections to the ventral intermediate nucleus of the thalamus may be enhanced due to PD-related changes, including dopaminergic/non-dopaminergic system abnormality, white matter damage, and deep nuclei impairment, which may contribute to dysregulation and resistance to levodopa of tremor. This review summarized the pathological, structural, and functional changes of the cerebellum in PD and discussed the role of the cerebellum in PD-related tremor, aiming to provide an overview of the cerebellum-related mechanism of tremor in PD.
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http://dx.doi.org/10.1038/s41531-022-00347-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232614PMC
June 2022

Microbial biodiversity contributes to soil carbon release: a case study on fire disturbed boreal forests.

FEMS Microbiol Ecol 2022 Jul;98(8)

Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu campus, 80101 Joensuu, Finland.

Microbial communities often possess enormous diversity, raising questions about whether this diversity drives ecosystem functioning, especially the influence of diversity on soil decomposition and respiration. Although functional redundancy is widely observed in soil microorganisms, evidence that species occupy distinct metabolic niches has also emerged. In this paper, we found that apart from the environmental variables, increases in microbial diversity, notably bacterial diversity, lead to an increase in soil C emissions. This was demonstrated using structural equation modelling (SEM), linking soil respiration with naturally differing levels of soil physio-chemical properties, vegetation coverage, and microbial diversity after fire disturbance. Our SEMs also revealed that models including bacterial diversity explained more variation of soil CO2 emissions (about 45%) than fungal diversity (about 38%). A possible explanation of this discrepancy is that fungi are more multifunctional than bacteria and, therefore, an increase in fungal diversity does not necessarily change soil respiration. Further analysis on functional gene structure suggested that bacterial and fungal diversities mainly explain the potential decomposition of recalcitrant C compare with that of labile C. Overall, by incorporating microbial diversity and the environmental variables, the predictive power of models on soil C emission was significantly improved, indicating microbial diversity is crucial for predicting ecosystem functions.
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http://dx.doi.org/10.1093/femsec/fiac074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303362PMC
July 2022

Effect of hypertensive disorders of pregnancy on pubertal development in daughters and sons: a systematic review and meta-analysis.

J Hum Hypertens 2022 Jun 23. Epub 2022 Jun 23.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal and offspring morbidity and mortality worldwide. Several studies in recent years have focused on the link between HDP and pubertal development in offspring. The goal of this study was to synthesize the published literature on the effect of HDP on pubertal development in offspring by a systematic review and meta-analysis (PROSPERO 2021: CRD42020148736). A systematic literature search of several databases was conducted through December 2021, focusing on studies reporting pubertal development in offspring of women with and without HDP exposure. Primary outcomes of interest included offspring body mass index (BMI), height, waist and hip circumference, fat mass, pubarche, thelarche, and age at menarche. A total of 21 studies were finally included. Significantly higher values of BMI (SMD: 0.16 [0.11, 0.22]; p < 0.01) and waist circumference (SMD: 0.21 [0.14, 0.29]; p < 0.01) were found in offspring exposed to maternal HDP. In addition, a tendency of the early development of secondary sexual characteristics only in daughters was presented in offspring whose mothers were diagnosed with HDP. The findings imply a possible effect of HDP on pubertal development in offspring, especially for their BMI and waist circumference, which highlights the importance of focusing on adolescent developmental abnormalities in offspring exposed to HDP.
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http://dx.doi.org/10.1038/s41371-022-00715-8DOI Listing
June 2022

Overweight/Obesity in Childhood and the Risk of Early Puberty: A Systematic Review and Meta-Analysis.

Front Pediatr 2022 3;10:795596. Epub 2022 Jun 3.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.

Purpose: To determine the relationship between childhood overweight/obesity and early puberty in both boys and girls. Specifically, this is the first time to conduct a meta-analysis of the relationship between childhood overweight/obesity and early puberty in boys.

Methods: Relevant studies were identified from PubMed, Web of Science, and EMBASE searches. The exposure of interest was overweight/obesity in childhood. Childhood was defined internationally as the age range of 0-18 years. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were performed to explore possible sources of heterogeneity and to assess the robustness of the results.

Results: A total of 10 studies involving 13,338 girls and 12,796 boys were included. Results showed that childhood overweight/obesity were associated with a significantly higher risk of early puberty in girls [odds ratio (OR): 2.22, 95% CI: 1.65-2.99]. Although without statistical significance, a higher risk of early puberty was also found in boys who were overweight/obese in childhood (OR: 1.29, 95% CI: 0.98-1.70). Heterogeneity in the risk estimates of early puberty was partially explained by study design, sample size, follow-up duration, definitions of early puberty and confounders controlled. Sensitivity analyses validated the robustness of the findings.

Conclusions: Our findings showed that for girls the associate between overweight/obesity and early puberty is definite or strong whereas for males, such an association is possible, prompting that future studies need to further explore the possible relationship between overweight/obesity and early puberty in boys.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021264649, PROSPERO CRD42021264649.
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http://dx.doi.org/10.3389/fped.2022.795596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203728PMC
June 2022

Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.

Eur J Epidemiol 2022 Jul 16;37(7):701-712. Epub 2022 Jun 16.

Department of Big Data in Health Science School of Public Health, and Centre of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption ("drinks per week") and pathological drinking behaviours ("alcohol use disorder" and "problematic alcohol use"), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose-response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption ("drinks per week") was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.
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http://dx.doi.org/10.1007/s10654-022-00886-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329409PMC
July 2022

Erectile dysfunction in hypospadiac male adult rats induced by maternal exposure to di-n-butyl phthalate.

Toxicology 2022 06 8;475:153227. Epub 2022 Jun 8.

Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, China; The Affiliated Kezhou People's Hospital of Nanjing Medical University, Kezhou, Xinjiang 845350, China. Electronic address:

For the treatment of hypospadias, a significant number of studies focus on penile reconstruction. However, scant attention is given to sexual behavior of hypospadiac patients and underlying mechanisms. A rat model of hypospadias was constructed by maternal di-n-butyl phthalate (DBP) exposure (800 mg/kg/day by gavage during gestational days 14-18). Ten-week-old male rats with hypospadias undertook significantly decreased penis/body weight ratio, reduced testis/body weight ratio, lower serum testosterone level and thinner myelin sheath thickness of cavernosum nerves. Meanwhile, erectile dysfunction (ED) was found in hypospadiac rats, which showed significant increases in transforming growth factor-β1 (TGF-β1) protein expression and decreases in the expression of alpha smooth muscle actin (α-SMA) protein, neuronal and endothelial nitric oxide synthase protein (nNOS and eNOS). In addition, phosphorylated protein kinase B/protein kinase B (pAkt/Akt) ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratios, caspase-3 protein expression, nuclear factor erythroid 2-related factor 2/ Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) ratios, NAD(P)H dehydrogenase quinone 1(NQO1) protein expression and heme oxygenase-1 (HO-1) protein expression were higher in the hypospadias groups than the control group. Notably, ED is comorbid with hypospadias in cases. Penile fibrosis, testosterone deficiency, and endothelial dysfunction lead to ED in hypospadias induced by DBP eventually, which might be explained by activating Akt/Bad/Bax/caspase-3 pathway, Nrf2/Keap-1 pathway and suppressing NOS/cGMP pathway in penis.
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http://dx.doi.org/10.1016/j.tox.2022.153227DOI Listing
June 2022
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