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1.
Artigo em Inglês | MEDLINE | ID: mdl-36734529

RESUMO

OBJECTIVE: To evaluate the role of induced immunosuppressive T regulatory (iTr) 35 cells in systemic sclerosis (SSc)-related inflammation and fibrosis. METHODS: 68 SSc patients were enrolled in this study. Subsets of iTr35 and Tr1 were measured by flow cytometry. Interleukin (IL)-35 and IL-10 levels were measured using enzyme-linked immunosorbent assay (ELISA). Expressions of iTr35, Tr1, fibrosis-related genes, and proteins associated with signalling pathways were determined using immunofluorescence, western blot, and immunohistochemistry assays. RESULTS: In peripheral blood, the proportions of the iTr35 cells were higher and Tr1 cells were lower than the control group. Similarly, IL-35 expression was increased, while IL-10 levels were decreased. In fibroblasts from skin tissue, the expression levels of EBI3, IL-12Ap35, Foxp3, and IL-10 were decreased, but collagen I, TGF-ß, α-SMA, and fibronectin levels were increased. Phosphorylated STAT3/6 were increased, but iTr35 and Tr1 cell levels were significantly decreased. When CD4+ cells were incubated with both rhIL-35 and rhIL-10, the cell numbers of iTr35 and Tr1 were greater than the same type of cells treated with rhIL-35 or rhIL-10 alone. However, the viability of conventional CD4+ T cells was decreased by gradually increasing iTr35 cells. Moreover, iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway. CONCLUSION: Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.

2.
Environ Toxicol ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722453

RESUMO

Metastasis is a leading cause to treatment failure in hepatocellular carcinoma (HCC) patients. Exosomes act as pivotal mediators in communication between different cells and exert effects on recipient cells by delivering bioactive cargoes, such as microRNAs (miRNAs). MiRNAs function in multiple steps of HCC development, including metastasis. MiR-374c-5p was previously identified as a tumor suppressor in some malignancies, while the current knowledge of its role in HCC metastasis is still limited. Herein, miR-374c-5p was found to be downregulated in HCC cell lines and clinical samples, and positively related with favorable prognosis in HCC patients. MiR-374c-5p transferred by exosomes derived from bone marrow mesenchymal stem cell (BMSC) suppressed migration, invasion and proliferation of HCC cells. LIMK1 was verified as downstream target gene of miR-374c-5p. Knockdown of LIMK1 reduced invasion, migration and proliferation of HCC cells, whereas overexpression functioned oppositely. The miR-374c-5p/LIMK1 axis suppressed epithelial-mesenchymal transition (EMT) by inactivating Wnt/ß-catenin pathway. In addition, miR-374c-5p was downregulated and LIMK1 upregulated in TGF-ß1 induced EMT. This EMT model could be reversed by LIMK1 silencing or miR-374c-5p overexpression. These results suggest that exo-miR-374c-5p suppresses EMT via targeting LIMK1-Wnt/ß-catenin axis and the axis is involved in TGF-ß1 induced metastasis of HCC, thereby identifying miR-374c-5p as a potential target for HCC treatment.

3.
J Med Virol ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655740

RESUMO

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the COVID-19 pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south-central region of China, between 1 January 2018 and 31 December 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the pre-pandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the pre-pandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (ß= 0.07, SE = 0.02, P=1.35×10-3 ) and higher hospital costs (ß= 0.06, SE = 0.03, P=0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID-19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics. This article is protected by copyright. All rights reserved.

4.
J Transl Med ; 21(1): 48, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698208

RESUMO

BACKGROUND: Drug-target interaction (DTI) prediction has become a crucial prerequisite in drug design and drug discovery. However, the traditional biological experiment is time-consuming and expensive, as there are abundant complex interactions present in the large size of genomic and chemical spaces. For alleviating this phenomenon, plenty of computational methods are conducted to effectively complement biological experiments and narrow the search spaces into a preferred candidate domain. Whereas, most of the previous approaches cannot fully consider association behavior semantic information based on several schemas to represent complex the structure of heterogeneous biological networks. Additionally, the prediction of DTI based on single modalities cannot satisfy the demand for prediction accuracy. METHODS: We propose a multi-modal representation framework of 'DeepMPF' based on meta-path semantic analysis, which effectively utilizes heterogeneous information to predict DTI. Specifically, we first construct protein-drug-disease heterogeneous networks composed of three entities. Then the feature information is obtained under three views, containing sequence modality, heterogeneous structure modality and similarity modality. We proposed six representative schemas of meta-path to preserve the high-order nonlinear structure and catch hidden structural information of the heterogeneous network. Finally, DeepMPF generates highly representative comprehensive feature descriptors and calculates the probability of interaction through joint learning. RESULTS: To evaluate the predictive performance of DeepMPF, comparison experiments are conducted on four gold datasets. Our method can obtain competitive performance in all datasets. We also explore the influence of the different feature embedding dimensions, learning strategies and classification methods. Meaningfully, the drug repositioning experiments on COVID-19 and HIV demonstrate DeepMPF can be applied to solve problems in reality and help drug discovery. The further analysis of molecular docking experiments enhances the credibility of the drug candidates predicted by DeepMPF. CONCLUSIONS: All the results demonstrate the effectively predictive capability of DeepMPF for drug-target interactions. It can be utilized as a useful tool to prescreen the most potential drug candidates for the protein. The web server of the DeepMPF predictor is freely available at http://120.77.11.78/DeepMPF/ , which can help relevant researchers to further study.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , Simulação de Acoplamento Molecular , Semântica , Descoberta de Drogas/métodos , Proteínas
5.
Front Pharmacol ; 14: 1017475, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713833

RESUMO

Yeast ß-glucan is a polysaccharide purified from the Saccharomyces cerevisiae cell wall, and its multiple biological activities are essential for immune regulation. However, the effect of ß-glucan on the intestinal immune response during colitis-associated colorectal cancer (CAC) is unclear. Here, we explore the possible role of ß-glucan in the development of CAC. Wild type (WT) mice with CAC induced by azoxmethane (AOM) and dextran sodium sulfate (DSS) had fewer tumors than untreated mice after oral ß-glucan because of increased antitumor dendritic cells (DCs) in the tumor microenvironment, resulting in more CD8+ T cells and the production of related cytokines. ß-glucan also increased resistance to DSS-induced chronic colitis by reshaping the inflammatory microenvironment. These data suggest that ß-glucan improves experimental intestinal inflammation and delays the development of CAC. Therefore, ß-glucan is feasible for treating chronic colitis and CAC in clinical practice.

6.
SSM Popul Health ; 21: 101342, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36684397

RESUMO

Objective: China has undergone tremendous social changes in the last few decades. This study aimed to research the trends of the suicide rates from 2002 to 2019, and to differentiate effects attributable to age, period, and cohort by gender and residence in China. Methods: Suicide mortality data were obtained from China's Ministry of Health Vital Registration System. Joinpoint regression model was used to estimate the average annual percentage change (AAPC) of the suicide rates and ratios by gender and residence. The age-period-cohort framework was performed to analyze the underlying mechanisms for suicide mortality trends. Results: Over the observation period, the significant decrease in suicide mortality rates in China for the economic development and urbanization was observed but to different degrees across gender and regional subgroups. The male-to-female ratio of suicide rates increased year by year (AAPC: 1.9%, 95% CI: 0.2% to 3.7%) while the urban-rural ratio changed little (AAPC: 0.9%, 95% CI: -1.8% to 3.7%). The age-period-cohort analysis revealed a marked increased effect of age and overall decreased effect of both period and cohort on suicide mortality rates. However, the recent cohort has presented an inversely increasing effect. Conclusion: The suicide rate has fallen sharply in China which has undergone tremendous socioeconomic changes. The varied changes in the suicide rate of different residence-, gender-, and age-groups as well as the age, period, and cohort effect on suicide risk further indicate the relationship of development and the suicide rates may be neither static nor identical on different subgroups in a rapidly changing society.

7.
Chem Commun (Camb) ; 59(7): 900-903, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36594813

RESUMO

A hierarchically cleaved amphiphile, mPEG-pep-etcSS-CPT, was synthesized to pursue actively targeted cancer therapy through self-assembly. This micelle can respond to MMP-2 achieving dePEGylation and releasing RGD peptides to be internalized into targetable tumor cells. Inside the cell, free CPT could be released by reduction-response leading to cytotoxicity.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Metaloproteinase 2 da Matriz , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Micelas , Linhagem Celular Tumoral , Camptotecina/uso terapêutico
8.
ISME J ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639538

RESUMO

Methylmercury (MeHg) is a potent neurotoxin that bioaccumulates along food chains. The conversion of MeHg from mercury (Hg) is mediated by a variety of anaerobic microorganisms carrying hgcAB genes. Mangrove sediments are potential hotspots of microbial Hg methylation; however, the microorganisms responsible for Hg methylation are poorly understood. Here, we conducted metagenomic and metatranscriptomic analyses to investigate the diversity and distribution of putative microbial Hg-methylators in mangrove ecosystems. The highest hgcA abundance and expression occurred in surface sediments in Shenzhen, where the highest MeHg concentration was also observed. We reconstructed 157 metagenome-assembled genomes (MAGs) carrying hgcA and identified several putative novel Hg-methylators, including one Asgard archaea (Lokiarchaeota). Further analysis of MAGs revealed that Deltaproteobacteria, Euryarchaeota, Bacteroidetes, Chloroflexi, and Lokiarchaeota were the most abundant and active Hg-methylating groups, implying their crucial role in MeHg production. By screening publicly available MAGs, 104 additional Asgard MAGs carrying hgcA genes were identified from a wide range of coast, marine, permafrost, and lake sediments. Protein homology modelling predicts that Lokiarchaeota HgcAB proteins contained the highly conserved amino acid sequences and folding structures required for Hg methylation. Phylogenetic tree revealed that hgcA genes from Asgard clustered with fused hgcAB genes, indicating a transitional stage of Asgard hgcA genes. Our findings thus suggest that Asgard archaea are potential novel Hg-methylating microorganisms and play an important role in hgcA evolution.

9.
Int Arch Allergy Immunol ; : 1-9, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36634629

RESUMO

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by excessive inflammatory responses. This study explored the association between laboratory characteristics and outcomes in adult patients with HLH. METHODS: The adult patients diagnosed with HLH at the Second Hospital of Shanxi Medical University from September 2016 to September 2021 were retrospectively analyzed in this study. RESULTS: A total of 90 HLH patients were included. Among them, 60% were males, with a median age at diagnosis of 54 years. More than 85% of HLH patients presented with fever, splenomegaly, and cytopenias. IL-10 and IL-6 were elevated in 93.3% and 91.1% of patients, respectively. Elevated IL-10 levels were associated with lower platelet counts (r = -0.37, p < 0.001). Infections were seen in 46.7% (42/90) of cases. 29 patients with malignancy-associated HLH had T- or NK-cell (n = 16) or B-cell (n = 12) lymphoma. Autoimmune diseases accounted for 21.1% (19/90). Treatment was variable. In total, 36 patients survived (40%). The median overall survival (OS) was 1.5 months (95% confidence intervals [CI]: 0.2-2.8 months), with a 1-year OS of 40.9%. Patients with autoimmune diseases had markedly longer survival than those triggered by infection and malignancy (p < 0.001). Multivariate Cox regression analysis indicated that treatment delays (hazard ratios 0.36, 95% CI: 0.14-0.94, p = 0.036), platelet count (2.33, 1.30-4.18, p = 0.005), and IL-10 (2.07, 1.16-3.68, p = 0.014) were independent risk factors for poor outcome. CONCLUSION: Infection and lymphoma are the leading causes of HLH in adult patients with heterogeneous clinical manifestations. Survival of adult HLH is frustrating, especially those associated with malignancies. Besides, elevated IL-10 levels were associated with lower platelet counts, and these two markers were independent risk factors for poor prognosis. Earlier treatment led to better outcomes.

10.
Pharmacology ; : 1-9, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470213

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for about 85% of generally reported lung cancer patients. OBJECTIVES: This is a systematic review of the clinical efficacy and safety of osimertinib in treating epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC. METHODS: A network search was completed for clinical research literature (from inception of each database to May 30, 2020) on osimertinib for EGFR mutation-positive advanced NSCLC. Strict inclusion and exclusion criteria were formulated to screen the literature. After data extraction, RevMan 5.3 software was utilized for quality evaluation and meta-analysis. The primary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events of grades 3 and 4. RESULTS: Finally, 6 eligible articles and a total of 1,848 patients containing 1,123 in experimental groups and 725 in control groups were included. Meta-analysis indicated that ORR (odds ratio [OR] = 3.40, 95% CI 1.64∼7.01, p = 0.0009), DCR (OR = 4.36, 95% CI 3.09∼6.15, p < 0.00001), PFS (HR = 0.36, 95% CI 0.27∼0.47, p < 0.00001), and OS (OR = 0.58, 95% CI 0.46∼0.72, p < 0.00001) of the experimental group were prominently better than the control group. Adverse events of grades 3 and 4 mainly incorporated decreased nausea, rash, stomatitis, and vomiting, which were dramatically relieved compared with the control group. CONCLUSION: Osimertinib is currently an appreciably effective and well-tolerated therapeutic avenue for EGFR mutation-positive advanced NSCLC.

11.
J Ethnopharmacol ; : 115968, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36473617

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection (AD) is a traditional medical preparation that has a Chinese origin. It is extensively used particularly in combination with doxorubicin (DOX) for the management of hepatocellular carcinoma (HCC). However, the combination's synergistic mechanism has not yet been clarified. AIM OF THE STUDY: To investigate the anti-tumor impact of AD in combination with DOX and their synergistic mechanism in HCC. MATERIALS AND METHODS: An H22 mouse xenograft model was utilized to study the impact of AD, DOX, and their combination on HCC in vivo. Their effects on cell vitality, apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) production, caspase-3, and cleaved caspase-3 protein expression were also investigated in H22 cells in vitro. Subsequently, human umbilical vein endothelial cells (HUVECs) were utilized to investigate the impacts of AD, DOX, and their combination on cell viability, migration, invasion, tube formation, and vascular endothelial growth factor (VEGF) protein expression. RESULTS: The study established that the tumor inhibition rate of AD combined with DOX reached 79.51%, which was significantly higher than that of AD (25.14%) or DOX (49.48%) alone. Additionally, the Q-value characterizing the synergy between AD and DOX was 1.72, demonstrating a strong synergistic effect. Furthermore, compared to AD or DOX administration alone, the combined administration group significantly decreased the alpha-fetoprotein (AFP) level in the serum, increased the tumor necrosis area, increased the Bax/Bcl-2, Cyt-c, caspase-9, Fas, Fasl, caspase-8, and caspase-3 protein expression, and significantly increased the CD31 and Ki67 protein expression in tumor tissue. Compared to AD or DOX alone, AD combined with DOX treatment had a synergistic effect on H22 cells (combination index values < 0.9), which inhibited cell viability, reduced mitochondrial membrane potential (MMP), induced apoptosis, promoted MMP loss, and increased ROS generation, cleaved caspase-3/caspase-3 levels, and caspase-3 activity. Moreover, combined administration showed a more pronounced inhibition of cell viability, migration, invasion, tube formation, and VEGF protein expression in HUVECs. CONCLUSIONS: AD enhances the anti-tumor effect of DOX by promoting apoptosis and inhibiting angiogenesis and cell proliferation. The findings of this study lay experimental foundations for the clinical combination of AD and DOX.

12.
Cancer Med ; 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464853

RESUMO

BACKGROUND: In the phase 2 double-blind Study 211, a starting dose of lenvatinib 18 mg/day was compared with the approved starting dose of 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Predefined criteria for noninferiority for efficacy in the 18 mg arm were not met; safety was similar in both arms. Impact of lenvatinib treatment on health-related quality-of-life (HRQoL) was a secondary endpoint of Study 211. METHODS: Patients with RR-DTC were randomly assigned to a blinded starting dose of lenvatinib 18 mg/day or 24 mg/day. HRQoL was assessed at baseline, every 8 weeks until Week 24, then every 16 weeks, and at the off-treatment visit, using the EQ-5D-3L and FACT-G instruments. Completion and compliance rates, mean change from baseline, and times to first and definitive deterioration were evaluated. RESULTS: Baseline EQ-5D and FACT-G scores, and overall changes from baseline, were comparable between patients in the lenvatinib 18 mg/day (n = 77) and 24 mg/day arms (n = 75). For the 18 mg versus 24 mg arms, least squares mean differences were -0.42 (95% CI -4.88, 4.03) for EQ-5D-VAS and 0.47 (95% CI -3.45, 4.39) for FACT-G total. Time to first deterioration did not significantly favor either arm; EQ-5D-VAS HR [18 mg/24 mg] 0.93 (95% CI 0.61-1.40), EQ-5D-HUI HR [18 mg/24 mg] 0.68 (95% CI 0.44-1.05), FACT-G total HR [18 mg/24 mg] 0.73 (95% CI 0.48-1.12). Time to definitive deterioration did not significantly favor either arm, though EQ-5D-VAS showed a trend in favor of the 24 mg arm (HR [18 mg/24 mg] 1.72; 95% CI 0.99-3.01); EQ-5D-HUI HR [18 mg/24 mg] was 0.96 (95% CI 0.57-1.63), FACT-G total HR [18 mg/24 mg] was 0.72 (95% CI 0.43-1.21). CONCLUSIONS: In Study 211, HRQoL for patients in the lenvatinib 18 mg/day arm was not statistically different from that of patients in the 24 mg/day arm. These data further support the use of the approved lenvatinib starting dose of 24 mg/day in patients with RR-DTC. GOV NUMBER: NCT02702388.

13.
Front Neurosci ; 16: 1059320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466177

RESUMO

This longitudinal study explored the changed patterns of structural brain network after radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). Diffusion tensor imaging (DTI) data were gathered from 35 patients with NPC at four time points: before RT (baseline), 0∼3 (acute), 6 (early delayed), and 12 months (late-delayed) after RT. The graph theory was used to characterize the dynamic topological properties after RT and the significant changes were detected over time at the global, regional and modular levels. Significantly altered regional metrics (nodal efficiency and degree centrality) were distributed in the prefrontal, temporal, parietal, frontal, and subcortical regions. The module, that exhibited a significantly altered within-module connectivity, had a high overlap with the default mode network (DMN). In addition, the global, regional and modular metrics showed a tendency of progressive decrease at the acute and early delayed stages, and a partial/full recovery at the late-delayed stage. This changed pattern illustrated that the radiation-induced brain damage began at the acute reaction stage and were aggravated at the early-delayed stage, and then partially recovered at the late-delayed stage. Furthermore, the spearman's correlations between the abnormal nodal metrics and temporal dose were calculated and high correlations were found at the temporal (MTG.R and HES.L), subcortical (INS.R), prefrontal (ORBinf.L and ACG.L), and parietal (IPL.R) indicating that these regions were more sensitive to dose and should be mainly considered in radiotherapy treatment plan.

14.
EClinicalMedicine ; 53: 101704, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36467456

RESUMO

Background: Timely identification and regular surveillance of patients at high risk are crucial for early diagnosis of upper gastrointestinal cancer. However, traditional manual surveillance method is time-consuming, and current surveillance rate is below 50%. Here, we aimed to develop a surveillance system named ENDOANGEL-AS (automatic surveillance) for automatic identification and surveillance of high-risk patients. Methods: 7874 patients from Renmin Hospital of Wuhan University between May 1 and July 31, 2021 were used as the training set, 6762 patients between August 1 and October 31, 2021 as the internal test set, and 7570 patients from two other hospitals between August 1 and October 31, 2021 as the external test sets. We first extracted descriptions of abnormalities from endoscopic and pathological reports based on natural language processing techniques to identify individuals. Then patients were classified at nine risk levels according to endoscopic and pathological findings, and a deep learning model was trained to identify demarcation line (DL) in gastric low-grade intraepithelial neoplasia (LGIN) using 1561 white-light still images for risk stratification of gastric LGIN. Finally, patients undergoing upper endoscopy were classified and assigned one of ten surveillance intervals according to guidelines. The performance of ENDOANGEL-AS was evaluated and compared with physicians. Findings: Patient identification module achieved an accuracy of 100% and 99.91% in internal and external test sets, respectively. Risk level classification module achieved an accuracy of 100% and 99.85% in the internal and external test sets, respectively. DL identification module achieved an accuracy of 87.88%. ENDOANGEL-AS on surveillance interval assignment achieved an accuracy of 99.23% and 99.67% in internal and external test sets, respectively. ENDOANGEL-AS had significantly higher accuracy compared with physicians (99.00% vs 38.87%, p < 0.001). The accuracy (63.67%, p < 0.001) of endoscopists with the assistance of ENDOANGEL-AS was significantly improved. Interpretation: We established a surveillance system that can automatically identify patients and assign surveillance intervals with high accuracy and good transferability. Funding: This work was partly supported by a grant from the Hubei Province Major Science and Technology Innovation Project (2018-916-000-008) and the Fundamental Research Funds for the Central Universities (2042021kf0084).

15.
Front Nutr ; 9: 1007184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505248

RESUMO

Background: Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. Methods: This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). Results: In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Conclusion: Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

16.
Microbiol Spectr ; : e0411022, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36541777

RESUMO

Mangrove microorganisms are a major part of the coastal ecosystem and are directly associated with nutrient cycling. Despite their ecological significance, the collection of culturable mangrove microbes is limited due to difficulties in isolation and cultivation. Here, we report the isolation and genome sequence of strain FT118T, the first cultured representative of a previously uncultivated order UBA8317 within Alphaproteobacteria, based on the combined results of 16S rRNA gene similarity, phylogenomic, and average amino acid identity analyses. We propose Futianiales ord. nov. and Futianiaceae fam. nov. with Futiania as the type genus, and FT118T represents the type species with the name Futiania mangrovii gen. nov, sp. nov. The 16S rRNA gene sequence comparison reveals that this novel order is a rare member but has a ubiquitous distribution across various habitats worldwide, which is corroborated by the experimental confirmation that this isolate can physiologically adapt to a wide range of oxygen levels, temperatures, pH and salinity levels. Biochemical characterization, genomic annotation, and metatranscriptomic analysis of FT118T demonstrate that it is metabolically versatile and active in situ. Genomic analysis reveals adaptive features of Futianiales to fluctuating mangrove environments, including the presence of high- and low-affinity terminal oxidases, N-type ATPase, and the genomic capability of producing various compatible solutes and polyhydroxybutyrate, which possibly allow for the persistence of this novel order across various habitats. Collectively, these results expand the current culture collection of mangrove microorganisms, providing genomic insights of how this novel taxon adapts to fluctuating environments and the culture reference to unravel possible microbe-environment interactions. IMPORTANCE The rare biosphere constitutes an essential part of the microbial community and may drive nutrient cycling and other geochemical processes. However, the difficulty in microbial isolation and cultivation has hampered our understanding of the physiology and ecology of uncultured rare lineages. In this study, we successfully isolated a novel alphaproteobacterium, designated as FT118T, and performed a combination of phenotypic, phylogenetic, and phylogenomic analyses, confirming that this isolate represents the first cultured member of a previously uncultivated order UBA8317 within Alphaproteobacteria. It is a rare species with a ubiquitous distribution across different habitats. Genomic and metatranscriptomic analyses demonstrate that it is metabolically versatile and active in situ, suggesting its potential role in nutrient cycling despite being scarce. This work not only expands the current phylogeny of isolated Alphaproteobacteria but also provides genomic and culture reference to unravel microbial adaptation strategies in mangrove sediments and possible microbe-environment interactions.

17.
Microbiome ; 10(1): 224, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36510268

RESUMO

BACKGROUND: The metabolic interactions of microbes significantly affect the assembly of microbial communities that play important roles in biogeochemical processes. However, most interspecies interactions between microorganisms in natural communities remain unknown, leading to a poor understanding of community assembly mechanisms. RESULTS: Here, we used a genome-scale metabolic modeling-based approach to explore the potential interactions among bacteria and archaea in mangrove sediments. More than half of the assembled microbial species ([Formula: see text]) combined about 3000 pairwise metabolic interaction relationship with high potential. The examples of predicted interactions are consistent with the implications of studies based on microbial enrichment/culture, indicating the feasibility of our strategy for extracting diverse potential interactions from complex interspecies networks. Moreover, a substantial number of previously unknown microbial metabolic interactions were also predicted. We proposed a concept of microbial active functional module (mAFM), defined as a consortium constituted by a group of microbes possessing relatively high metabolic interactions via which they can actively realize certain dominant functions in element transformations. Based on the metabolic interactions and the transcript distribution of microorganisms, five mAFMs distributed in different layers of the sediments were identified. The whole group of mAFMs covered most of the principal pathways in the cycle of carbon, nitrogen, and sulfur, while each module possessed divergently dominant functions. According to thinctiis diston, we inferred that the mAFMs participated in the element cycles via their intra-cycle and the inter-exchange among them and the sediments. CONCLUSIONS: The results of this study greatly expanded interaction potential of microbes in mangrove sediments, which could provide supports for prospective mutualistic system construction and microbial enrichment culture. Furthermore, the mAFMs can help to extract valuable microbial metabolic interactions from the whole community and to profile the functioning of the microbial community that promote biogeochemical cycling in mangrove sediments. Video Abstract.


Assuntos
Sedimentos Geológicos , Microbiota , RNA Ribossômico 16S/genética , Sedimentos Geológicos/microbiologia , Estudos Prospectivos , Filogenia , Microbiota/genética
18.
Nat Commun ; 13(1): 7728, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36513677

RESUMO

The acquisition of germination and post-embryonic developmental ability during seed maturation is vital for seed vigor, an important trait for plant propagation and crop production. How seed vigor is established in seeds is still poorly understood. Here, we report the crucial function of Arabidopsis histone variant H3.3 in endowing seeds with post-embryonic developmental potentials. H3.3 is not essential for seed formation, but loss of H3.3 results in severely impaired germination and post-embryonic development. H3.3 exhibits a seed-specific 5' gene end distribution and facilitates chromatin opening at regulatory regions in seeds. During germination, H3.3 is essential for proper gene transcriptional regulation. Moreover, H3.3 is constantly loaded at the 3' gene end, correlating with gene body DNA methylation and the restriction of chromatin accessibility and cryptic transcription at this region. Our results suggest a fundamental role of H3.3 in initiating chromatin accessibility at regulatory regions in seed and licensing the embryonic to post-embryonic transition.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiologia , Histonas/genética , Histonas/metabolismo , Regulação da Expressão Gênica de Plantas , Sementes , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cromatina/genética , Germinação/genética
19.
Polymers (Basel) ; 14(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36559798

RESUMO

Superhydrophobic materials have recently attracted great interest from both academia and industry due to their promising applications in self-cleaning, oil-water separation, etc. Here, we developed a facile method to prepare hybrid PDMS/TiO2 fiber for superhydrophobic coatings. TiO2 could be uniformly distributed into PDMS, forming a hierarchical micro/nano structure on the surface of the substrate. The contact angle of the superhydrophobic coating could reach as high as 155°. The superhydrophobic coating possessed good self-cleaning performance, corrosion resistance, and durability. It was found that gravity-driven oil-water separation was achieved using stainless steel mesh coated with the PDMS/TiO2 coating. More importantly, the coated filter paper could not only separate oil and pure water but also corrosive solutions, including the salt, acid, and alkali solution.

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