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MOTIVATION: High-throughput technologies yield a broad spectrum of multi-omics datasets, which offer unparalleled insights into complex biological systems. However, effectively analyzing this diverse array of data presents challenges, considering factors such as species diversity, data types, costs, and limitations of the available tools. RESULTS: Herein, we present ExpOmics, a comprehensive web platform featuring seven applications and four toolkits, with 28 customizable analysis functions spanning various analyses of differential expression, co-expression, Weighted Gene Co-expression Network Analysis (WGCNA), feature selection, and functional enrichment. ExpOmics allows users to upload and explore multi-omics data without organism restrictions, supporting various expression data, including genes, mRNAs, lncRNAs, miRNAs, circRNAs, piRNAs, and proteins and is compatible with diverse gene nomenclatures and expression values. Moreover, ExpOmics enables users to analyze 22,427 transcriptomic datasets of 196 cancer subtypes sourced from 63 projects of The Cancer Genome Atlas Program (TCGA) to identify cancer biomarkers. The analysis results from ExpOmics are presented in high-quality graphical formats suitable for publication and are available for free download. A case study using ExpOmics identified two potential oncogenes, SERPINE1 and SLC43A1, that may regulate colorectal cancer through distinct biological processes. In summary, ExpOmics can serves as a robust platform for global researchers to explore multi-omics data, gain biological insights, and formulate testable hypotheses. AVAILABILITY AND IMPLEMENTATION: ExpOmics is available at http://www.biomedical-web.com/expomics. CONTACT: zhangwl25@mail3.sysu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Winter jasmine (Jasminum nudiflorum Lindl.) is a medium-sized, deciduous shrub native to China that has become a popular choice among gardeners and landscapers. In 2020 to 2021, symptoms of anthracnose including brown necrotic spots, enlarged irregular lesions and leaf blight were observed on leaves of 20 winter jasmine shrubs in a public garden (22°34'58'' N; 113°56'23'' E) in Shenzhen, China, and with an estimated disease incidence of 65%. Tissues samples (6 × 6 mm2) surrounding the necrotic spots were surface sterilized with 75% ethanol for 30 s, followed by 2% NaClO for 1 min, then rinsed with sterile water for three times and dried with sterile filter paper. Tissues were placed on potato dextrose agar (PDA) medium and incubated at 25â. After 3 to 7 d, pure cultures were obtained by transferring hyphal tips to new plates and 32 isolates producing Colletotrichum-like colonies were obtained from 40 tissues (isolation frequency=32/(4×10)=80%). Three representative isolates YCH09, YCH23 and YCH32 were selected for further study. Three selected isolates were identical in morphological characteristics. Colonies on PDA after 5 d at 25â were white to gray with cottony mycelia and grayish-white on the underside of the culture. Conidia (n = 60) measured 15.4 ± 1.1 µm (13.0 to 17.1 µm) in length and 5.4 ± 0.3 µm (4.9 to 6.0 µm) in width and were hyaline, single-celled, cylindrical with rounded ends. Appressoria (n = 15) measured 7.1 ± 0.1 µm (5.3 to 8.9 µm) in length and 5.2 ± 0.2 µm (4.1 to 6.2 µm) in width and were brown to dark brown, ovoid. These morphological features were aligned with those of Colletotrichum spp. (Weir et al. 2012). Sequences of five genetic markers of representative isolates YCH09, YCH23 and YCH32 including the rDNA internal transcribed spacer region, chitin synthase, partial actin, ß-tubulin 2 and Apn2-Mat1-2 intergenic spacer and partial mating type (Mat1-2) region were 99.3 to 100% identical to the ex-type isolate of C. fructicola strain ICMP 18581 (Zhang et al., 2020). From the maximum likelihood phylogenetic tree which was constructed based on concatenated sequences, three representative isolates (YCH09, YCH23 and YCH32) were clustered with other isolates of C. fructicola. The above morphological and molecular characteristics suggest that causal agent was C. fructicola. Pathogenicity was tested using a whole-plant assay. Five healthy plants were inoculated by spraying a conidial suspension (1.5×104 conidia/ml; 20 ml per plant) of the isolate YCH23 onto the foliage (Marshall et al., 2023). Three noninoculated control plants were sprayed with sterile water. All plants were placed in a greenhouse at 25±2â with approximately 75% relative humidity. Yellow lesions appeared on leaves of inoculated plants as early as 4 days after inoculation (DAI), and irregularly shaped brown spots similar to those observed in the field were formed on 10 DAI. Noninoculated plants remained asymptomatic. Colletotrichum isolates resembling morphological characters of YCH23 were reisolated from all inoculated plants, then identified as C. fructicola by DNA sequence analysis. C. fructicola is a well-known fungus causing anthracnose on more than 63 plant species including agricultural and horticultural plants worldwide (Talhinhas and Baroncelli, 2021). To our knowledge, this is the first report of C. fructicola infecting J. nudiflorum plants in China. Since its potential risk to other horticultural plant species, precautions may be necessary to minimize the spread of this fungi.
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Electrosynthesis of hydrogen peroxide (H2O2) based on proton exchange membrane (PEM) reactor represents a promising approach to industrial-level H2O2 production, while it is hampered by the lack of high-efficiency electrocatalysts in acidic medium. Herein, we present a strategy for the specific oxygen functional group (OFG) regulation to promote the H2O2 selectivity up to 92 % in acid on cobalt-porphyrin molecular assembled with reduced graphene oxide. In situ X-ray adsorption spectroscopy, in situ Raman spectroscopy and Kelvin probe force microscopy combined with theoretical calculation unravel that different OFGs exert distinctive regulation effects on the electronic structure of Co center through either remote (carboxyl and epoxy) or vicinal (hydroxyl) interaction manners, thus leading to the opposite influences on the promotion in 2e- ORR selectivity. As a consequence, the PEM electrolyzer integrated with the optimized catalyst can continuously and stably produce the high-concentration of ca. 7â wt % pure H2O2 aqueous solution at 400â mA cm-2 over 200â h with a cell voltage as low as ca. 2.1â V, suggesting the application potential in industrial-scale H2O2 electrosynthesis.
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The field of P-band (0.3-1 GHz) absorption has witnessed rapid development in metamaterial absorbers due to their exceptional designability and the absence of restrictions imposed by the one-fourth wavelength rule. In this study, we combined carbonyl iron powder (CIP) composites with a periodic structure composed of metal capacitive patterns and employed a genetic algorithm (GA) to optimize the electromagnetic parameters of the CIP substrate. By selecting the appropriate shape and material for the units of pattern based on transmission line theory, as well as regulating relevant structural parameters, we successfully designed an ultra-thin broadband metamaterial absorber for the P-band. Experimental results demonstrate that within the range of 0.3-0.85 GHz, the reflection loss of our absorber remains below -5 dB, with a maximum value of -9.54 dB occurring at 0.45 GHz. Remarkably, this absorber possesses a thickness equivalent to only 1/293 of its working wavelength. Then, we conducted analyses on electric field distribution, magnetic field distribution, and energy loss density. Our findings suggest that high-performance absorption in metamaterials can be attributed to λ/4 resonant or coupling effects between structural units or diffraction phenomena. This absorber offers several advantages, including broad low-frequency absorption capability, ultra-thin profile, and convenient fabrication process, thus providing valuable theoretical insights for designing metamaterial structures.
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OBJECTIVES: SARS-CoV-2 pneumonia poses significant challenges to health systems worldwide, particularly, in severe and critical cases. Immunosuppressed renal transplant recipients appear to be at a particularly high risk for severe or critical COVID-19 illness. However, few studies elucidated the risk factors of SARS-CoV-2 pneumonia in renal transplant recipients with COVID-19. METHODS: A postinfection cross-sectional survey was conducted in 312 renal transplant recipients and 503 age- and sex-matched controls to explore risk factors for SARS-CoV-2 pneumonia in immunosuppressed renal transplant recipients. RESULTS: The results showed that renal transplant recipients had a much higher incidence of SARS-CoV-2 pneumonia (48.1%) after infection with the SARS-CoV-2 Omicron variant than controls (5.6%). The multivariate binary logistic regression analysis identified older age, lower creatinine clearance before infection, and higher dose of prednisone before infection as risk factors for SARS-CoV-2 pneumonia in renal transplant recipients. Preexisting renal dysfunction was a major risk factor for SARS-CoV-2 pneumonia, with an odds ratio of 3.27 (1.01-10.61). CONCLUSIONS: Preexisting renal graft dysfunction was a major risk factor for SARS-CoV-2 Omicron variant pneumonia. It is suggested that high-risk renal transplant recipients should undergo computed tomography scanning within 14 days after infection with SARS-CoV-2.
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COVID-19 , Transplante de Rim , Pneumonia , Humanos , Transplante de Rim/efeitos adversos , SARS-CoV-2 , Estudos Transversais , COVID-19/complicações , COVID-19/epidemiologia , Fatores de Risco , TransplantadosRESUMO
Background: There may be a higher risk of sexual dysfunction in the schizophrenia population. China has made significant contributions to the global community of patients with schizophrenia. Currently, there is no estimation of the prevalence of sexual dysfunction in Chinese patients with schizophrenia. Aim: We conducted a meta-analysis to pool the evaluated prevalence of sexual dysfunction in Chinese patients with schizophrenia. Methods: We systematically searched PubMed, Web of Science, Embase, PsycINFO, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Medical Network, and Huayi Academic Literature Database from inception to September 2023. Meta-analysis was conducted with R version 4.3.1. Outcomes: To examine the pooled prevalence of sexual dysfunctions among Chinese patients with schizophrenia. Results: In our meta-analysis, we included 16 studies with 5417 participants, among whom 1727 experienced sexual dysfunction. The results of the meta-analysis reveal that the prevalence of sexual dysfunction in Chinese patients with schizophrenia is 50.43% (95% CI, 37.86%-62.95%). Subgroup analysis results indicate that various factors-including the specific type of dysfunction, duration of illness, assessment tools, mean ages, study region, gender, research setting, marital status, publication years, and type of antipsychotics-all have a particular impact on the occurrence rate of sexual dysfunction in Chinese patients with schizophrenia. Female patients had a slightly higher prevalence of sexual dysfunction than male patients (65.22% vs 54.84%). Clinical Implications: The findings of this study can be used in high-quality nursing care for the schizophrenia population, particularly for the care of specific sexual dysfunction nursing. Strengths and Limitations: This meta-analysis is the first to evaluate the prevalence of sexual dysfunction in China among patients with schizophrenia. The limited number of studies is the most important limitation. Conclusions: The pooled prevalence of sexual dysfunction in Chinese patients with schizophrenia is relatively high, and the prevention and intervention of individual sexual dysfunctions in schizophrenia are advised.
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Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy.
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PURPOSE: Numerous barriers hinder individuals with mental illness from seeking medical assistance in rural regions, yet a comprehensive understanding of these challenges remains elusive. This meta-synthesis aims to understand the barriers and facilitators in medical help-seeking among rural individuals with mental illness. METHODS: We systematically searched seven databases [PubMed, CINAHL, Medline (OVID), PsycINFO (OVID), Cochrane, Embase, and ProQuest] in May 2023 and included the studies if they reported the barriers or/and facilitators to seek healthcare in rural patients with mental illness. We conducted hand search and citation search on Google Scholar for literature supplements. Thematic analysis was employed. RESULTS: The study included 27 articles reporting on the barriers and facilitators to seeking medical help in this population from 2007 to 2023. We ultimately identified themes at three levels: navigating the terrain of vulnerability and empowerment (the individual with mental illness), navigating the terrain of external environment (the external environment) and connectivity within the healthcare ecosystem for mental health (the health service system). CONCLUSIONS: We must design more effective strategies to improve mental healthcare access for rural patients, considering cultural nuances and health service utilization patterns. This requires a multi-level approach, tailored to the unique needs of diverse populations.
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Acessibilidade aos Serviços de Saúde , Transtornos Mentais , Aceitação pelo Paciente de Cuidados de Saúde , População Rural , Humanos , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pesquisa Qualitativa , Comportamento de Busca de Ajuda , Serviços de Saúde MentalRESUMO
OBJECTIVES: This study explores the combinations of conditional variables contributing to depressive symptoms in rural children. METHODS: We analyzed data from 715 children from a rural mental health database, conducting detailed follow-up investigations on 129 children in Zhejiang and Henan provinces. We used fuzzy set Qualitative Comparative Analysis (fsQCA) and regression analysis to identify causal pathways leading to depression. RESULTS: The results indicate that depression in rural children does not stem from a single, necessary condition but arises from multiple factors. Our findings highlight significant contributions from both maternal and paternal involvement. Specifically, maternal involvement, combined synergistically with peer support and problematic behaviors, as well as paternal involvement, together with peer support and anxiety, significantly affects depressive outcomes. Additionally, anxiety and strong peer relationships independently have a substantial impact on these outcomes. Effective mitigation strategies involve active parental engagement and robust peer support, reducing the influence of risk factors such as problematic behaviors and anxiety. LIMITATIONS: The generalizability of the results is limited by cultural and geographical variations. The study also does not account for all potential factors influencing depression in rural children. CONCLUSION: Depression in rural children results from multiple interacting factors. Tailored interventions addressing these specific combinations are recommended.
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Decoupled electrolysis for hydrogen production with the aid of a redox mediator enables two half-reactions operating at different rates, time, and spaces, which offers great flexibility in operation. Herein, a pre-protonated vanadium hexacyanoferrate (p-VHCF) redox mediator is synthesized. It offers a high reversible specific capacity up to 128 mAh g-1 and long cycling performance of 6000 cycles with capacity retention about 100% at a current density of 10 A g-1 due to the enhanced hydrogen bonding network. By using this mediator, a membrane-free water electrolytic cell is built to achieve decoupled hydrogen and oxygen production. More importantly, a decoupled electrolysis system for hydrogen production and hydrazine oxidation is constructed, which realizes not only separate hydrogen generation but electricity generation through the p-VHCF-N2H4 liquid battery. Therefore, this work enables the flexible energy conversion and storage with hydrogen production driven by solar cell at day-time and electricity output at night-time.
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INTRODUCTION: Health care workers represent a substantial demographic whose welfare and work efficiency are crucial to public health and societal well-being. However, the prevalence of sexual dysfunction within this group is often overlooked, despite its significant occurrence. OBJECTIVE: To evaluate the worldwide prevalence of sexual dysfunction among health care workers. METHODS: A comprehensive systematic review and meta-analysis of observational studies ranging from 2003 to 2023 were performed to compile prevalence estimates of sexual dysfunction among health care workers. A random effects model was implemented to amalgamate the prevalence analysis. Study heterogeneity was discerned by I2 and χ2 statistics. To assess potential publication bias, an Egger's test and a funnel plot were employed. RESULTS: This meta-analysis incorporated 39 studies from 16 countries, encompassing 44 017 health care workers. The pooled prevalence of sexual dysfunction among health care workers was 46.79% (95% CI, 38.09%-55.68%), with a slightly higher prevalence of 49.57% (95% CI, 38.18%-61.01%) among clinical health care workers. The most prevalent forms of sexual dysfunction identified were loss of libido (51.26%), erectile dysfunction (36.99%), sexual dissatisfaction (36.90%), pain during intercourse (28.23%), orgasmic disorders (25.13%), low sexual arousal (23.54%), and lubrication disorders (22.62%). Among various health care professions, nurses exhibited the highest prevalence of sexual dysfunction (56.29%), followed by doctors (37.63%) and other health care workers (24.96%). Additionally, female health care workers experienced a higher prevalence of sexual dysfunction (47.61%) as compared with their male counterparts (32.01%). CONCLUSION: This study indicates that nearly half of health care professionals report experiencing sexual dysfunction, with loss of libido being the most common manifestation. Addressing this issue requires a multistakeholder approach.
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Reports regarding the composition and functions of microorganisms in activated sludge from wastewater treatment plants for treating tuna processing wastewater remains scarce, with prevailing studies focusing on municipal and industrial wastewater. This study delves into the efficiency and biological dynamics of activated sludge from tuna processing wastewater, particularly under conditions of high lipid content, for pollutant removal. Through metagenomic analysis, we dissected the structure of microbial community, and its relevant biological functions as well as pathways of nitrogen and lipid metabolism in activated sludge. The findings revealed the presence of 19 phyla, 1,880 genera, and 7,974 species, with Proteobacteria emerging as the predominant phylum. The study assessed the relative abundance of the core microorganisms involved in nitrogen removal, including Thauera sp. MZ1T and Alicycliphilus denitrificans K601, among others. Moreover, the results also suggested that a diverse array of fatty acid-degrading microbes, such as Thauera aminoaromatica and Cupriavidus necator H16, could thrive under lipid-rich conditions. This research can provide some referable information for insights into optimizing the operations of wastewater treatment and identify some potential microbial agents for nitrogen and fatty acid degradation.
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BACKGROUND: The incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes. METHODS: We conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis. RESULTS: One hundred twenty-one of 172 patients died during follow-up, with a median follow-up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride-glucose index (TyG), triglyceride-glucose index-body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c). The ROC curve indicated that TyG, TyG-BMI, and TG/HDL-c had prognostic efficacy for PC with diabetes. We next optimized TyG-BMI and obtained a new parameter, namely glucose-lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG-BMI, TyG/HDL-c, BMI, TG, total cholesterol (TC), TC/HDL-c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG-BMI. CONCLUSIONS: IR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Neoplasias Pancreáticas , Humanos , Glucose , Prognóstico , Glicemia/metabolismo , Estudos Retrospectivos , Biomarcadores , Triglicerídeos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , ColesterolRESUMO
Pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies that enhance or recruit antitumor immune cells into the tumor microenvironment (TME) remain promising strategies for PC treatment. Consequently, a deeper understanding of the molecular mechanisms involved in PC immune suppression is critical for developing immune-based therapies to improve survival rates. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify Filamin B (FLNB) correlated with the infiltration of CD8+ T cells and tumor-associated macrophages (TAMs). The clinical significance and potential biological function of FLNB were evaluated using bioinformatic analysis. The oncogenic role of FLNB in PC was determined using in vitro and in vivo studies. We further analyzed possible associations between FLNB expression and tumor immunity using CIBERSORT, single sample gene set enrichment analysis, and ESTIMATE algorithms. We found FLNB was overexpressed in PC tissues and was correlated with poorer overall survival, tumor recurrence, larger tumor size, and higher histologic grade. Moreover, FLNB overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. Functional enrichment analysis identified the role of FLNB in the regulation of cell cycle, focal adhesion, vascular formation, and immune regulation. Knockdown of FLNB expression inhibited cancer cell proliferation and migration in-vitro and suppressed tumor growth in-vivo. Furthermore, FLNB overexpression caused high infiltration of Treg cells, Th2 cells, and TAMs, but reduced infiltration of CD8+ T cells and Th1/Th2. Collectively, our findings suggest FLNB promotes PC progression and may be a novel biomarker for PC.
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Ninjurin-1 (NINJ1), initially identified as a stress-induced protein in neurons, recently emerged as a key mediator of plasma membrane rupture during apoptosis, necrosis, and pyroptosis. However, its involvement in ferroptosis remains unknown. Here, we demonstrate that NINJ1 also plays a crucial role in ferroptosis, but through a distinct mechanism. NINJ1 knockdown significantly protected cancer cells against ferroptosis induced by xCT inhibitors but no other classes of ferroptosis-inducing compounds (FINs). Glycine, known to inhibit canonical NINJ1-mediated membrane rupture in other cell deaths, had no impact on ferroptosis. A compound screen revealed that NINJ1-mediated ferroptosis protection can be abolished by pantothenate kinase inhibitor (PANKi), buthionine sulfoximine (BSO), and diethylmaleate (DEM). These results suggest that this ferroptosis protection is mediated via Coenzyme A (CoA) and glutathione (GSH), both of which were found to be elevated upon NINJ1 knockdown. Furthermore, we discovered that NINJ1 interacts with the xCT antiporter, which is responsible for cystine uptake for the biosynthesis of CoA and GSH. The removal of NINJ1 increased xCT levels and stability, enhanced cystine uptake, and contributed to elevated CoA and GSH levels, collectively contributing to ferroptosis protection. These findings reveal that NINJ1 regulates ferroptosis via a non-canonical mechanism, distinct from other regulated cell deaths.
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Recent advances in nanoparticle materials can facilitate the electro-reduction of carbon dioxide (CO2) to form valuable products with high selectivity. Copper (Cu)-based electrodes are promising candidates to drive efficient and selective CO2 reduction. However, the application of Cu-based chalcopyrite semiconductors in the electrocatalytic reduction of CO2 is still limited. This study demonstrated that novel zinc oxide (ZnO)/copper indium gallium sulfide (CIGS)/indium sulfide (InS) heterojunction electrodes could be used in effective CO2 reduction for formic acid production. It has been determined that Faradaic efficiencies for formic acid production using ZnO nanowire (NW) and nanoflower (NF) structures vary due to structural and morphological differences. A ZnO NW/CIGS/InS heterojunction electrode resulted in the highest efficiency of 77.2% and 0.35 mA cm-2 of current density at a -0.24 V (vs. reversible hydrogen electrode) bias potential. Adding a ZTO intermediate layer by the spray pyrolysis method decreased the yield of formic acid and increased the yield of H2. Our work offers a new heterojunction electrode for efficient formic acid production via cost-effective and scalable CO2 reduction.
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Background: Accurate detection of the histological grade of pancreatic neuroendocrine tumors (PNETs) is important for patients' prognoses and treatment. Here, we investigated the performance of radiological image-based artificial intelligence (AI) models in predicting histological grades using meta-analysis. Method: A systematic literature search was performed for studies published before September 2023. Study characteristics and diagnostic measures were extracted. Estimates were pooled using random-effects meta-analysis. Evaluation of risk of bias was performed by the QUADAS-2 tool. Results: A total of 26 studies were included, 20 of which met the meta-analysis criteria. We found that the AI-based models had high area under the curve (AUC) values and showed moderate predictive value. The pooled distinguishing abilities between different grades of PNETs were 0.89 [0.84-0.90]. By performing subgroup analysis, we found that the radiomics feature-only models had a predictive value of 0.90 [0.87-0.92] with I2 = 89.91%, while the pooled AUC value of the combined group was 0.81 [0.77-0.84] with I2 = 41.54%. The validation group had a pooled AUC of 0.84 [0.81-0.87] without heterogenicity, whereas the validation-free group had high heterogenicity (I2 = 91.65%, P=0.000). The machine learning group had a pooled AUC of 0.83 [0.80-0.86] with I2 = 82.28%. Conclusion: AI can be considered as a potential tool to detect histological PNETs grades. Sample diversity, lack of external validation, imaging modalities, inconsistent radiomics feature extraction across platforms, different modeling algorithms and software choices were sources of heterogeneity. Standardized imaging, transparent statistical methodologies for feature selection and model development are still needed in the future to achieve the transformation of radiomics results into clinical applications. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022341852.
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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with an extremely poor prognosis. Cancer stem cells (CSCs) are considered to be responsible for the poor survival, recurrence and therapy resistance of PDAC. Ferroptosis plays a crucial role in the sustain and survival of CSCs. Here, we employed a rigorous evaluation of multiple datasets to identify a novel stemness-based and ferroptosis-related genes (SFRGs) signature to access the potential prognostic application. This work we retrieved RNA-sequencing and clinical annotation data from the TCGA, ICGC, GTEx and GEO database, and acquired 26 stem cell gene sets and 259 ferroptosis genes from StemChecker database and FerrDb database, respectively. Based on consensus clustering and ssGSEA analysis, we identified two expression patterns of CSCs traits (C1 and C2). Then, WGCNA analysis was implemented to screen out hub module genes correlated with stemness. Furthermore, differential expression analysis, Pearson correlation analysis, and the Least absolute shrinkage and selection operator (LASSO) and Cox regression were performed to identify the SFRGs and to construct model. In addition, the differences in prognosis, tumor microenvironment (TME) components and therapy responses were evaluated between two risk groups. Finally, we verified the most influential marker ARNTL2 experimentally by western blot, qRT-PCR, sphere formation assay, mitoscreen assay, intracellular iron concentration determination and MDA determination assays. In conclusion, we developed a stemness-based and ferroptosis-related prognostic model, which could help predict overall survival for PDAC patients. Targeting ferroptosis may be a promising therapeutic strategy to inhibit PDAC progression by suppressing CSCs.
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Background and Aims: Organic anion-transporting polypeptides (OATPs) play a crucial role in the transport of bile acids and bilirubin. In our previous study, interleukin 6 (IL-6) reduced OATP1B3 levels in cholestatic disease. However, it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases. This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms. Methods: The effect of stimulator of interferon genes (STING) signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay. To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma, we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α, IL-1ß, and IL-6. To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression, we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot. The interaction mechanism between ß-catenin/TCF4 and OATP1B1 was investigated by knocking down ß-catenin/TCF4 through siRNA transfection. Results: The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model, with IL-6 exhibiting the most potent inhibitory effect on OATP1B1. IL-6 downregulated ß-catenin/TCF4, leading to decreased OATP1B1 expression. Knocking-down ß-catenin/TCF4 counteracted the ß-catenin/TCF4-mediated repression of OATP1B1. Conclusions: STING-mediated IL-6 up-regulation may inhibit OATP1B1, leading to reduced transport of bile acids and bilirubin by OATP1B1. This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.
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BACKGROUND: Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. METHODS: The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People's Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. RESULTS: LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. CONCLUSION: We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer.