ABSTRACT
Purpose: The aim of the present study was to assess the clinical outcomes and prognostic factors of lung adenocarcinoma patients with brain metastases (BMs) after intracranial local therapy. Patients and Methods: A total of 83 lung adenocarcinoma patients with BMs who underwent craniotomy combined with radiotherapy or intracranial radiotherapy alone were retrospectively analyzed. The intracranial tumor response was determined according to the Response Assessment in Neuro-Oncology of Brain Metastases (RANO-BM) criteria. The median overall survival (OS), intracranial progression-free survival (iPFS), and related prognostic factors were analyzed with the KaplanâMeier estimator method and Cox proportional hazards regression model. Results: Among 83 patients, 20 patients received craniotomy combined with radiotherapy, and 63 patients received intracranial radiotherapy alone. Following intracranial local therapy, 11 patients (13.3%) achieved complete response (CR); among them, 8 patients underwent neurosurgical resection. In addition, 32 patients (38.55%) achieved partial response (PR), 32 patients (38.55%) experienced stable disease (SD), and 8 (9.6%) experienced progressive disease (PD). The median follow-up period was 25.4 months (range 0.8-49.6 months). The median follow-up time for the iPFS was 16.2 months (range 0.6-41.2 months). The median OS, iPFS were 28.2 months and 24.7 months. Epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) mutations (HR 3.216, 95% confidence interval (CI) 1.269-8.150, p = 0.014) and iPFS (HR 0.881, 95% CI 0.836-0.929, p < 0.001) were found to be beneficial factors for OS. An intracranial-tumor CR was associated with a longer iPFS (PR: HR 0.052, 95% CI 0.009-0.297, p = 0.001; SD: HR 0.081, 95% CI 0.025-0.259, p < 0.001; PD: HR 0.216, 95% CI 0.077-0.606, p = 0.004). Conclusion: Prolonged iPFS was associated with better OS in lung adenocarcinoma patients with BMs following intracranial local therapy, and mutations of EGFR / ALK or an intracranial-tumor CR are independent prognostic factors for prolonged survival.
ABSTRACT
Microbial necromass carbon (MNC) is an important stable organic C component. However, the variation of MNC and its potential relationship with humus components in composting remains uncertain. During a 45-day chicken manure composting study with and without biochar, MNC ranged from 24.9 to 77.9 g/kg and increased significantly by 80.9 % to 133 %. MNC constituted 5.77 % to 21.3 % of total organic C, with bacterial/fungal necromass C ratio ranging from 0.82 to 1.78. The MNC/humus C ratio ranged from 0.15 to 0.55, and humic acid C showed significant positive associations with bacterial necromass C (R2 = 0.72) and fungal necromass C (R2 = 0.51). Biochar addition reduced electrical conductivity and moisture content, increased pH, and induced microbial phosphorus limitation, thereby enhancing MNC content by 29.2 % and promoting humification. Our study is the first to elucidate the relationship between microbial necromass and humus substances, providing fundamental data for advancing the microbial carbon pump theory in composting.
ABSTRACT
BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.
Subject(s)
Intraocular Pressure , Myopia, Degenerative , Humans , Prospective Studies , Adult , Disease Progression , Randomized Controlled Trials as Topic , Ophthalmic Solutions , Male , Female , Axial Length, Eye , Middle Aged , Visual FieldsABSTRACT
Oligomeric Aß42 is considered to play a harmful role in the pathophysiology of Alzheimer's disease (AD). Prolonged exposure to oligomeric Aß42 could induce neuronal damage including cellular senescence. Amelioration of Aß42-induced cellular senescence has been considered as a promising strategy for the treatment of AD. Chromofungin, a chromogranin A-derived peptide, has displayed various biological functions in different types of cells and tissues. However, the effects of Chromofungin on oligomeric Aß42-induced cellular senescence have not been previously reported. In the current study, we report a novel function of Chromofungin by showing that treatment with Chromofungin could ameliorate Aß42-induced neurotoxicity in M17 neuronal cells. The Cell Counting Kit-8 (CCK-8) assay and the lactate dehydrogenase (LDH) release experiments revealed that 0.5 and 1 mM are the optimal concentrations of Chromofungin for cell culture in M17 cells. Challenging with oligomeric Aß42 (5 µM) for 7 and 14 days led to a significant decrease in telomerase activity, which was rescued by Chromofungin dose-dependently. Additionally, the senescence-associated ß-galactosidase (SA-ß-gal) staining assay demonstrated that Chromofungin mitigated oligomeric Aß42-induced cellular senescence. Correspondingly, treatment with Chromofungin reversed the gene expression of human telomerase reverse transcriptase (hTERT), telomeric repeat-binding factor 2 (TERF2), and p21 against oligomeric Aß42 in M17 neurons. Interestingly, Chromofungin attenuated oligomeric Aß42-induced oxidative stress (OS) in M17 cells by reducing the production of intracellular reactive oxygen species (ROS) but increasing the levels of intracellular superoxide dismutase (SOD). Importantly, the presence of Chromofungin reduced the expression of cyclooxygenase2 (COX-2) as well as the generation of prostaglandin E2 (PGE2). Transduction with Ad-COX-2 impaired the effects of Chromofungin on telomerase activity and the profile of cellular senescence. Our findings suggest that Chromofungin might act as a potential agent for the treatment of AD.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Cellular Senescence , Neurons , Peptide Fragments , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Neurons/drug effects , Neurons/metabolism , Humans , Peptide Fragments/toxicity , Cellular Senescence/drug effects , Neuroprotective Agents/pharmacology , Reactive Oxygen Species/metabolism , Telomerase/metabolism , Oxidative Stress/drug effects , Chromogranin A/metabolism , Chromogranin A/pharmacologyABSTRACT
Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.
Subject(s)
Dendritic Cells , Hepatitis B , Membrane Transport Proteins , Humans , Autophagy/genetics , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/metabolism , Down-Regulation , Hepatitis B/metabolism , Hepatitis B Core Antigens/genetics , Hepatitis B virus , Hepatocytes/metabolism , Induced Pluripotent Stem Cells , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Phosphatidylinositol 3-Kinases/metabolism , RNA, Small Interfering/genetics , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Organoids/metabolism , Organoids/virologyABSTRACT
Phenomenon: The increase in clinical and teaching workload has brought enormous pressure to clinical teachers. Clinical teachers play an extremely important role in the quality of higher medical education and the cultivation of medical talents. However, few studies have examined the attitudes and practices of clinical teachers regarding the role of teachers in China. This study aimed to investigate clinical teachers' perceptions about their roles and current practices at affiliated hospitals of medical universities in China. Approach: Responses from 312 Chinese clinical teachers were included in the analyses. The data were collected using the questionnaires of perception and practice regarding the role of teachers which consisted of 12 items rated on a 5-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree), and scored by calculating the mean. The data were analyzed using the Statistical Package for Social Sciences, version 22.0 (IBM SPSS Corp). Findings: The mean score of perception of clinical teachers regarding the role of teachers was 4.51 (SD = 0.72), and the mean score of practice was 3.69 (SD = 1.17). Multivariable binary logistic regression model showed that undertaking very few/few clinical teaching workload, 'thinking it is my obligation to carry out teaching work seriously' and 'thinking it is my duty to train medical talents' were not only significant determinants of good perception but also good practice. Additionally, 'thinking hospital attached great importance to clinical teaching' was the significant determinant of good perception. Insights: Chinese clinical teachers demonstrate less positive perception and practice regarding the roles of teacher than clinical teachers in developed countries. Affiliated hospitals of medical universities should hold training sessions regularly and take targeted intervention measures to enhance clinical teachers' perception and practice regarding the roles of teacher.
Subject(s)
Education, Medical , Faculty , Humans , Universities , Surveys and Questionnaires , PerceptionABSTRACT
Redox condition is an important controlling factor for contaminant removal in constructed wetlands; however, the redox-sensitivity of antibiotic removal in wetland sediments under controlled conditions with specific electron acceptors remains unclear. Here, using a 14C radioactive tracer, we explored fate of sulfamethoxazole (SMX) in a wetland sediment slurry under oxic, nitrate-reducing, iron-reducing, and methanogenic conditions. In the sterile treatment, unlike the comparable SMX dissipation from the water phase under four redox conditions, non-extractable residues (NERs) of SMX was highest formed in the sediment under oxic condition, mainly in sequestered and ester/amide-linked forms. Microorganisms markedly promoted SMX transformation in the slurry. The dissipation rate of SMX and its transformation products (TPs) followed the order: oxic ≈ iron-reducing > methanogenic >> nitrate-reducing conditions, being consistent with the dynamics of microbial community in the sediment, where microbial diversity was greater and networks connectivity linking dominant bacteria to SMX transformation were more complex under oxic and iron-reducing conditions. Kinetic modeling indicated that the transformation trend of SMX and its TPs into the endpoint pool NERs depended on the redox conditions. Addition of wetland plant exudates and sediment dissolved organic matter at environmental concentrations affected neither the abiotic nor the biotic transformation of SMX. Overall, the iron-reducing condition was proven the most favorable and eco-friendly for SMX transformation, as it resulted in a high rate of SMX dissipation from water without an increase in toxicity and subsequent formation of significant stable NERs in sediment. Our study comprehensively revealed the abiotic and biotic transformation processes of SMX under controlled redox conditions and demonstrated iron-reducing condition allowing optimal removal of SMX in constructed wetlands.
Subject(s)
Sulfamethoxazole , Wetlands , Sulfamethoxazole/chemistry , Nitrates , Anti-Bacterial Agents , Oxidation-Reduction , Iron , Organic Chemicals , WaterABSTRACT
Efficient electrochemical CO2 reduction reaction (ECO2RR) to multi-electron reductive products remains a great challenge. Herein, molecular engineering of copper phthalocyanines (CuPc) was explored by modifying electron-withdrawing groups (EWGs) (cyano, sulfonate anion) and electron-donating groups (EDGs) (methoxy, amino) to CuPc, then supporting onto carbon paper or carbon cloth by means of droplet coating, loading with carbon nanotubes and coating in polypyrrole (PPy). The results showed that the PPy-coated CuPc effectively catalysed ECO2RR to CH4. Interestingly, experimental results and DFT calculations indicated EWGs markedly improved the selectivity of methane for the reason that the introduction of EWGs reduces electron density of catalytic active center, resulting in a positive move to initial reduction potential. Otherwise, the modification of EDGs significantly reduces the selectivity towards methane. This electronic effect and heterogenization of CuPc are facile and effective molecular engineering, benefitting the preparation of electrocatalysts for further reduction of CO2.
ABSTRACT
PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism. METHODS AND MATERIALS: A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor-ß1 (TGF-ß1) inhibitor to block TGF-ß1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-ß1 levels was performed to verify the roles of TGF-ß1 and Treg cells. RESULTS: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-ß1 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-ß1 inhibitor, by decreasing TGF-ß1. Furthermore, reinfusion of Treg cells upregulated TGF-ß1 levels and exacerbated RIPF in GA-treated RIPF mice. CONCLUSIONS: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-ß1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.
Subject(s)
Glycyrrhetinic Acid , Lung Injury , Pulmonary Fibrosis , Radiation Injuries , Animals , Mice , Epithelial-Mesenchymal Transition , Fibroblasts/radiation effects , Glycyrrhetinic Acid/pharmacology , Lung/radiation effects , Lung Injury/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/prevention & control , Radiation Injuries/pathology , T-Lymphocytes, Regulatory , Transforming Growth Factor beta1ABSTRACT
Inverse probability weighting (IPW) is frequently used to reduce or minimize the observed confounding in observational studies. IPW creates a pseudo-sample by weighting each individual by the inverse of the conditional probability of receiving the treatment level that he/she has actually received. In the pseudo-sample there is no variation among the multiple individuals generated by weighting the same individual in the original sample. This would reduce the variability of the data and therefore bias the variance estimate in the target population. Conventional variance estimation methods for IPW estimators generally ignore this underestimation and tend to produce biased estimates of variance. We here propose a more reasonable method that incorporates this source of variability by using parametric bootstrapping based on intra-stratum variability estimates. This approach firstly uses propensity score stratification and intra-stratum standard deviation to approximate the variability among multiple individuals generated based on a single individual whose propensity score falls within the corresponding stratum. The parametric bootstrapping is then used to incorporate the target variability by re-generating outcomes after adding a random error term to the original data. The performance of the proposed method is compared with three existing methods including the naïve model-based variance estimator, the nonparametric bootstrap variance estimator, and the robust variance estimator in the simulation section. An example of patients with sarcopenia is used to illustrate the implementation of the proposed approach. According to the results, the proposed approach has desirable statistical properties and can be easily implemented using the provided R code.
ABSTRACT
BACKGROUND: China is one of the countries with the fastest growing prevalence of diabetes mellitus (DM) in the world. This study intended to investigate the association of single nucleotide polymorphisms (SNPs) of FHL5 and LPA with DM risk in the Chinese population. METHODS: This case-control study involved 1,420 Chinese individuals (710 DM patients and 710 controls). Four candidate loci (rs2252816/rs9373985 in FHL5 and rs3124784/rs7765781 in LPA) were successfully screened. The association of SNPs with DM risk was assessed by logistic regression analysis. Differences in clinical characteristics among subjects with different genotypes were analyzed by one-way analysis of variance. RESULTS: Overall analysis indicated that rs3124784 was associated with an increased risk of DM. Stratification analysis showed that rs3124784 significantly increased DM risk in different subgroups (male, non-smoking, non-drinking, and BMI > 24), while rs7765781 increased DM risk only in participants with BMI ≤ 24. Rs2252816 was associated with the course of DM. We also found that rs2252816 GG genotype and rs9373985 GG genotype were linked to the increased cystatin c in DM patients. CONCLUSION: The genetic polymorphisms of LPA may be associated with DM risk in the Chinese population, which will provide useful information for the prevention and diagnosis of DM.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetes Mellitus , Humans , Male , Case-Control Studies , Polymorphism, Single Nucleotide , Genotype , China/epidemiology , Transcription Factors/genetics , LIM Domain Proteins/geneticsABSTRACT
Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.
Subject(s)
Gastrointestinal Microbiome , Nanostructures , Nanotubes, Carbon , Humans , Animals , Mice , Gastrointestinal Microbiome/physiology , Nanotubes, Carbon/adverse effects , Fermentation , Butyrates/metabolismABSTRACT
Hepatitis B virus (HBV) specific T cell immune response plays a vital role in viral clearance. Dendritic cell derived exosomes (Dexs) can activate T cell immunity effectively. Tapasin (TPN) is involved in antigen processing and specific immune recognition. In the present study, we elucidated that Dexs loading TPN (TPN-Dexs) could enhance CD8+ T cell immune response and inhibit virus replication in HBV transgenic mice. T cell immune response and the ability of inhibiting HBV replication were measured in HBV transgenic mice immunized with TPN-Dexs. Meanwhile, CD8+ T cell autophagy and specific T cell immune responses were measured in vitro and vivo, and the mechanisms probably involved in were explored. Purified TPN-Dexs could be taken up into the cytoplasm of DCs and upregulate CD8+ T cell autophagy to enhance specific T cell immune response. In addition, TPN-Dexs could increase the expression of AKT and decrease the expression of mTOR in CD8+ T cells. Further research confirmed that TPN-Dexs could inhibit virus replication and decrease the expression of HBsAg in the liver of HBV transgenic mice. Nevertheless, those also could elicit mice hepatocytes damage. In conclusion, TPN-Dexs could enhance specific CD8+ T cell immune responses via the AKT/mTOR pathway to regulate the autophagy and exert the antiviral effect in HBV transgenic mice.
Subject(s)
Exosomes , Hepatitis B virus , Mice , Animals , CD8-Positive T-Lymphocytes , Proto-Oncogene Proteins c-akt , Mice, Transgenic , TOR Serine-Threonine Kinases , Antigen Presentation , Autophagy , Mice, Inbred C57BLABSTRACT
PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiation therapy, but the underlying mechanisms are unknown. B10 cells, as negative B regulatory cells, play important roles in regulating inflammation and autoimmunity. However, the role of B10 cells in RIPF progression is unclear. The aim of this study was to determine the role of B10 cells in aggravating RIPF and the underlying mechanism. METHODS AND MATERIALS: The role of B10 cells in RIPF was studied by constructing mouse models of RIPF and depleting B10 cells with an anti-CD22 antibody. The mechanism of B10 cells in RIPF was further explored through cocultivation of B10 cells and MLE-12 or NIH3T3 cells and administration of an interleukin (IL)-10 antibody to block IL-10. RESULTS: B10 cell numbers increased significantly during the early stage in the RIPF mouse models compared with the controls. In addition, depleting B10 cells with the anti-CD22 antibody attenuated the development of lung fibrosis in mice. Subsequently, we confirmed that B10 cells induced epithelial-mesenchymal transition and the transformation of myofibroblasts via activation of STAT3 signaling in vitro. After blockade of IL-10, it was verified that IL-10 secreted by B10 cells mediates the epithelial-mesenchymal transition of myofibroblasts, thereby promoting RIPF. CONCLUSIONS: Our study uncovers a novel role for IL-10-secreting B10 cells that could be a new target of research for relieving RIPF.
Subject(s)
B-Lymphocytes, Regulatory , Pulmonary Fibrosis , Animals , Mice , Pulmonary Fibrosis/etiology , Interleukin-10 , NIH 3T3 Cells , Epithelial-Mesenchymal Transition , Disease Models, AnimalABSTRACT
Background: Hepatocellular carcinoma (HCC) is a malignant cancer with rapid progression, vascular invasion, a high recurrence rate and poor prognosis, so it is necessary to take early measures to halt this process. Accumulating evidence indicates that collagen XV (translated by Col15a1) is a basement membrane molecule related to tumour metastasis in several organs. However, the potential function of collagen XV in the liver associated with HCC remains to be further elucidated. Methods: Col15a1 was overexpressed in HepG2 and HCCLM3 cells. CCK8 and colony formation assays were used to assess the capacity of cell proliferation, and Transwell and wound healing assays were utilized to measure cell migration. Western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) quantified the protein and mRNA expression levels of genes related to the epithelial-mesenchymal transition (EMT). Then, the effect of collagen XV on tumour metastasis was confirmed in vivo. Finally, we inhibited discoidin domain receptor 1 (DDR1) via DDR1-IN-1 to explore whether the collagen XV interacted with DDR1 to regulate EMT. Results: Patients of HCC with higher expression of Col15a1 showed better survival than patients with low expression. Overexpression of collagen XV in HepG2 and HCCLM3 cells suppressed cell proliferation and migration in vitro and inhibited pulmonary and liver metastasis in vivo. In addition, collagen XV downregulated the DDR1 and transcription factor (Snail, Slug), regulated the EMT markers (Vimentin, E-cadherin, N-cadherin, and MMP9). Furthermore, inhibition of the DDR1 receptor by DDR1-IN-1 suppressed the gene promoting the EMT. Conclusions: Collagen XV functioned as a metastasis inhibitor in HCC by regulating the DDR1-Snail/Slug axis to regulate EMT.
ABSTRACT
Background: HIV-positive men who have sex with men (MSM) tend to have high syphilis incidence. Our objective is to evaluate the prevalence of syphilis and determine the risk factors of syphilis among HIV-positive MSM. Methods: A cross-sectional study with convenience sampling was performed among HIV-positive MSM in six cities of Guangdong Province from June 2020 to August 2021. Participants completed a survey including social-demographic characteristics, sexual behaviors and self-reported syphilis, chlamydia, gonorrhea, herpes, human papillomavirus statuses after HIV diagnosis. Multivariate logistic regression was used to determine the factors associated with syphilis and sexually transmitted diseases (STD). Results: Among 944 HIV-positive MSM, 141 (14.9, 95% CI: 12.7-17.2%) men had syphilis and 220 (23.3, 95% CI: 20.6-26.0%) men had STD. Multivariate analysis indicated that MSM who met male sexual partners mainly through traditional meeting places (spa or bath house, sauna, foot or body massage parlor) in the last 6 months [adjusted Odds Ratio (aOR) = 2.91, 95% CI: 1.09-7.79], and who were diagnosed with herps after the HIV diagnosis (aOR = 3.79, 95% CI: 1.16-12.39) were more likely to have syphilis. In addition, MSM who met male sexual partners mainly through traditional meeting places in the last 6 month (aOR = 2.55, 95% CI: 1.01-6.42), and who had more than one male sexual partner in the last 6 months (aOR = 1.88, 95% CI: 1.17-3.02) were more likely to have STD. Conclusions: The prevalence of syphilis and other STDs is relatively high among HIV-positive MSM in southern China. Routine syphilis screening as a part of HIV monitoring among HIV-positive MSM will have important epidemiological significance for the management of infected patients, and can help reduce the spread of syphilis.
Subject(s)
HIV Infections , Sexual and Gender Minorities , Sexually Transmitted Diseases , Syphilis , Humans , Male , Female , Syphilis/epidemiology , Homosexuality, Male , Prevalence , Cross-Sectional Studies , HIV Infections/epidemiology , Sexually Transmitted Diseases/epidemiology , Risk FactorsABSTRACT
Spinal infection is a rarely occurred pathology, whose diagnosis remains a major challenge due to the low sensitivity of culturing techniques. Metagenomic next-generation sequencing (mNGS) is a novel approach to identify the pathogenic organisms in infectious diseases. In this study, mNGS technology was adopted for pathogenic detection in spinal infection from the tissue and pus samples. Additionally, the diagnostic performance of mNGS for spinal infection was evaluated, by comparing it with that of the conventional microbial culture, with the histopathological results as the gold standard. Overall, 56 samples from 38 patients were enrolled for mNGS testing, and 69 samples were included for microbial culture. 30 patients (78.95%) were identified to be positive by the mNGS method, which was higher than that of microbial culture (17, 44.74%). The sensitivity and specificity of mNGS with pus samples were 84.2% and 100.0%, respectively, which outperformed those of microbial culture (42.1% and 100.0%). The pathogen identification results were applied to medication guidance, and all 38 patients experienced favorable outcomes at three months, followed-up post-treatment, without any adverse effects. These findings proved that mNGS was superior to microbial culture in pathogenic identification of the spinal infection, thereby showing great promise in guiding drug administration and improving clinical outcomes.
Subject(s)
Metagenome , Metagenomics , Humans , Metagenomics/methods , High-Throughput Nucleotide Sequencing/methods , Sensitivity and Specificity , SuppurationABSTRACT
Immobilizing cobalt phthalocyanine (CoPc) onto the electrode surface is a significant approach to performing efficient electrochemical CO2 reduction reaction (ECO2 RR). Herein, sulfylphenoxy decorated CoPc cross-linked polypyrrole is prepared by inâ situ polymerization on the surface of carbon cloth. The synthesized N-rich catalyst exhibits above 95 % Faradaic efficiency toward CO (FECO ) at -0.9â V versus reversible hydrogen electrode (RHE) at least for 10â h in aqueous solution and even enables direct electrolysis at low CO2 concentrations, being potential for coupling ECO2 RR with CO2 capture. This facile inâ situ polymerization strategy would pave the way for developing efficient and practical electrocatalysis for ECO2 RR.
Subject(s)
Polymers , Pyrroles , Carbon Dioxide , IndolesABSTRACT
The electrocatalytic CO2 reduction reaction (ECO2 RR) is one promising method for storing intermittent clean energy in chemical bonds and producing fuels. Among various kinds of catalysts for ECO2 RR, molecular metal complexes with well-defined structures are convenient for studies of their rational design, structure-reactivity relationships, and mechanisms. In this Review, we summarize the molecular engineering of several N-based metal complexes including Re/Mn bipyridine compounds and metal macrocycles, concluding with general modification strategies to devise novel molecular catalysts with high intrinsic activity. Through physical adsorption, covalent linking, and formation of a periodic backbone, these active molecules can be heterogenized into immobilized catalysts with more practical prospects. Finally, significant challenges and opportunities based on molecular catalysts are discussed.