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The access of new energy improves the flexibility of distribution network operation, but also leads to more complex mechanism of line loss. Therefore, starting from the nonlinear, fluctuating and multi-scale characteristics of line loss data, and based on the idea of decomposition prediction, this paper proposes a new method of line loss frequency division prediction based on wavelet transform and BIGRU-LSTM (Bidirectional Gated Recurrent Unit-Long Short Term Memory Network).Firstly, the grey relation analysis and the improved NARMA (Nonlinear Autoregressive Moving Average) correlation analysis method are used to extract the non-temporal and temporal influencing factors of line loss, and the corresponding feature data set is constructed. Then, the historical line loss data is decomposed into physical signals of different frequency bands by using wavelet transform, and the multi-dimensional input data of the prediction network is formed with the above characteristic data set. Finally, the BIGRU-LSTM prediction network is built to realize the probabilistic prediction of high-frequency and low-frequency components of line loss. The effectiveness and applicability of the method proposed in this paper were verified through numerical simulation. By dividing the line loss data into different frequency bands for frequency prediction, the mapping relationship between different line loss components and influencing factors was accurately matched, thereby improving the prediction accuracy.
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Redes Neurais de Computação , Análise de Ondaletas , AlgoritmosRESUMO
OBJECTIVE: To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC). METHODS: Transcriptome sequencing was used to analyze the distribution and composition of miRNA in Lycium barbarum fruit. Lb-miR166a was introduced into TNBC MB-231 cells by lentiviral transfection to study its effects on cell proliferation, apoptosis, invasion, and metastasis both in vivo and in vitro. Bioinformatic and dual-luciferase assays identified the target gene of Lb-miR166a. The role of STK39 in TNBC progression was elucidated through clinical data analysis combined with cellular studies. The influence of Lb-miR166a on the STK39/MAPK14 pathway was confirmed using a target-specific knockout MB-231 cell line. RESULTS: Lb-miR166a was found to be highly expressed in Lycium barbarum. It inhibited MB-231 cell proliferation, invasion, and metastasis, and promoted apoptosis. STK39 was overexpressed in TNBC and was associated with increased invasiveness and poorer patient prognosis. Gene enrichment analysis and dual-luciferase assays demonstrated that Lb-miR166a regulates STK39 expression cross-border and inhibits MAPK14 phosphorylation, impacting the phosphorylation of downstream target genes. CONCLUSION: The downregulation of STK39 and subsequent inhibition of MAPK14 phosphorylation by Lb-miR166a leads to reduced proliferation, migration, and invasion of TNBC cells. These findings suggest a novel therapeutic strategy for TNBC treatment, highlighting possible clinical applications of Lb-miR166a in managing this aggressive cancer type.
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BACKGROUND: Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. METHODS: In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. RESULTS: Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. CONCLUSIONS: Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.
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Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Fatores de Transcrição da Família Snail , Fator de Transcrição AP-2 , Neoplasias de Mama Triplo Negativas , Fator de Transcrição AP-2/metabolismo , Fator de Transcrição AP-2/genética , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , MicroRNAs/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação para Baixo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means. Case Description: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months. Conclusions: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.
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The aim of this study is to conduct a systematic analysis of the SARS-CoV-2 levels in urban sewage and evaluate the associated positivity rates, thereby developing comprehensive insights into the epidemic situation and providing valuable inputs for the development of effective disease prevention and control strategies. The PubMed, Scopus, Embase, China National Knowledge Infrastructure, Wanfang Database, and VIP databases were systematically searched based on the predefined retrieval strategy. The literature published up to February 2023 was meticulously screened according to the predetermined inclusion and exclusion criteria, and the relevant data were extracted for subsequent integration. The quality assessment of the included studies adhered to the rigorous Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines. The meta-analysis was conducted using Stata 17.0 software. The meta-analysis included a total of 34 studies, encompassing 8429 municipal wastewater samples. A random effects model was employed for the analysis, revealing an overall SARS-CoV-2 positivity rate of 53.7% in the municipal wastewater samples. The subgroup analyses demonstrated significant regional variations in the SARS-CoV-2 positivity rate in municipal wastewater, with Africa exhibiting the highest rate at 62.5% (95% confidence interval [CI] 47.4 ~ 76.0%) and Oceania displaying the lowest at 33.3% (95% CI 22.0 ~ 46.3%). However, the subgroup analyses based on the sampling site, strain prevalence period, and laboratory testing method did not yield any statistically significant differences. The SARS-CoV-2 positivity rate in wastewater is relatively high globally, although it exhibits regional disparities. Regions with larger populations and lower economic levels demonstrate higher viral detection rates in sewage. Different types of wastewater sampling sites can be employed to monitor distinct aspects of the COVID-19 pandemic. Continuous surveillance of SARS-CoV-2 in wastewater plays a pivotal role in complementing clinical data, helping to track outbreak progression across diverse regions.
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COVID-19 , SARS-CoV-2 , Águas Residuárias , Águas Residuárias/virologia , COVID-19/epidemiologia , Humanos , Cidades/epidemiologia , Esgotos/virologiaRESUMO
This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers - namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 - was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (ORâ =â 0.86, 95% CIâ =â 0.74-0.99, Pâ =â .03), whereas fatty acid-binding protein 4 was found to elevate the risk (ORâ =â 1.21, 95% CIâ =â 1.05-1.39, Pâ =â .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Reprodutibilidade dos Testes , Biomarcadores , Proteínas de Ligação a Ácido Graxo , Receptores de Interleucina-6RESUMO
Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.
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Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/diagnóstico , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Genômica , Proteínas de Ligação a RNA/genéticaRESUMO
Understanding oncogenic processes and underlying mechanisms to advance research into human tumors is critical for effective treatment. Studies have shown that Metal regulatory transcription factor 2ï¼MTF2) drives malignant progression in liver cancer and glioma. However, no systematic pan-cancer analysis of MTF2 has been performed. Here, we use University of California Santa Cruz, Cancer Genome Atlas , Genotype-Tissue Expression data, Tumor Immune Estimation Resource, and Clinical Proteomic Tumor Analysis Consortium bioinformatics tools to explore differential expression of MTF2 across different tumor types. MTF2 was found to be highly expressed in the cancer lines that were available through the respective databases included in the study, and overexpression of MTF2 may lead to a poor prognosis in tumor patients such as glioblastoma multiforme, brain lower grade glioma, KIPAN, LIHC, adrenocortical carcinoma, etc. We also validated MTF2 mutations in cancer, compared MTF2 methylation levels in normal and primary tumor tissues, analyzed the association of MTF2 with the immune microenvironment, and validated the functional role of MTF2 in glioma U87 and U251 and breast cancer MDA-MB-231 cell lines by cytometry. This also indicates that MTF2 has a promising application prospect in cancer treatment.
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Neoplasias da Mama , Glioblastoma , Glioma , Neoplasias Hepáticas , Humanos , Feminino , Proteômica , Glioblastoma/genética , Microambiente Tumoral/genéticaRESUMO
Evidence of an association between acute air pollution exposure and lung function in the elderly is limited. This study is cross-sectional. We quantified the effects of air pollution exposure on lung function among 256 elderly by using a linear mixed model. The results revealed that air pollutants had lag effects on lung function after adjusting for confounders. PM2.5 (Lag03, Lag 03 was defined three-day moving average, and so forth), PM10, NO2 (Lag04-Lag05) were significantly associated with reduced FEV1. PM2.5 (Lag01-Lag02), PM10 (Lag0-Lag07), NO2 (Lag0, Lag04), and SO2 (Lag0) were significantly associated with reduced Forced vital capacity (FVC). PM2.5 (Lag04-Lag07) and NO2 (Lag01-Lag07) were significantly associated with reduced FEF25%-75%. The results showed the adverse change was stronger after adjusting for other pollutants in the PM models, and women were more susceptible to air pollutants. Therefore, we should pay attention to the problem of air pollution in the elderly, especially in women.
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Poluentes Atmosféricos , Poluição do Ar , Humanos , Feminino , Idoso , Dióxido de Nitrogênio/toxicidade , Dióxido de Nitrogênio/análise , Estudos Transversais , Material Particulado/toxicidade , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , China , Pulmão , Exposição Ambiental/efeitos adversosRESUMO
OBJECTIVE: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case-control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. METHODS: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. RESULTS: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. CONCLUSION: The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.
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Benzylic azides, an important class of active organic synthons, were synthesized in high yields from the easily accessible N-triftosylhydrazones with stable TMSN3 under mild conditions. The reaction features high efficiency and excellent functional group tolerance, as illustrated by gram-scale synthesis and the synthesis of drug-like molecules. Mechanistic studies reveal that azidation occurs at the electron-deficient diazo-carbon via the elimination of N2 by an azide ion.
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Azidas , Elementos de Transição , CarbonoRESUMO
As a member of the nuclear receptor (NR) superfamily, pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. The tissue distribution of PXR is parallel to its function with high expression in the liver and small intestine and moderate expression in the kidney, stomach, skin, and blood-brain barrier, which are organs and tissues in frequent contact with xenobiotics. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. In this review, we summarized the functions of PXR in metabolism of different substances such as glucose, lipid, bile acid, vitamin, minerals, and endocrines, and also included insights of the application of PXR ligands (drugs) in specific diseases.
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Receptor de Pregnano X , Receptores de Esteroides , Xenobióticos , Animais , Ácidos e Sais Biliares , Glucose , Ligantes , Lipídeos , Mamíferos/metabolismo , Receptor de Pregnano X/metabolismo , Receptores Citoplasmáticos e Nucleares , Receptores de Esteroides/fisiologia , Vitaminas , Xenobióticos/metabolismoRESUMO
High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019 (COVID-19) pandemic and ensure people's health and safety. Chloroquine (CQ) and hydroxychloroquine (HCQ) have received much attention. This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards, improving review efficiency, ensuring the rights and interests of subjects and that ethics committees conduct independent reviews, and achieving full ethics supervision of research conducted during an emergency. Research must be both rigorous and prudent to ensure the best outcome, with the maximization of benefits as the core principle. Standardization of the application, implementation and ethical review processes are needed to prevent unnecessary risk.
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Schizophrenia stands out as one of the most devastating psychiatric disorders. Previous findings have shown that schizophrenia is a polygenic genetic disorder. Thus, abnormal neurodevelopment and neurogenesis may be associated with the etiology of schizophrenia, so genes which affect these processes may be potential candidate genes of schizophrenia. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) gene is a member of the mitogen-activated protein kinase family. Taking into account previous findings, MAP3K4 plays a crucial role in the fundamental pathology of various nervous system diseases. In the present study, we aim to explore the association of MAP3K4 and schizophrenia in an independent case-control sample including 627 schizophrenic patients and 1175 healthy controls from a Northeast Chinese Han population. Both the allelic and genotypic association analyses showed that 6 SNPs in MAP3K4 were significantly associated with schizophrenia (rs590988, rs625977, rs9295134, rs12110787, rs1001808 and rs9355870). After rigorous Bonferroni correction, 4 SNPs (rs9295134, rs12110787, rs1001808 and rs9355870) were still significantly associated with the disease. The haplotype composed of these four SNPs also showed significantly global and individual association with schizophrenia. These results suggest that MAP3K4 is a susceptibility gene for schizophrenia in the Northeast Chinese Han population.
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MAP Quinase Quinase Quinase 4/genética , Esquizofrenia , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genéticaRESUMO
The initial mechanical damage of a spinal cord injury (SCI) triggers a progressive secondary injury cascade, which is a complicated process integrating multiple systems and cells. It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development. The differences between the rostral and caudal regions around an SCI lesion have received little attention. Here, we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI. We identified a set of differentially expressed genes, including Col3a1, Col1a1, Dcn, Fn1, Kcnk3, and Nrg1, between rostral and caudal regions at different time points following SCI. Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus, blood vessel development, and brain development. We then chose Col3a1, Col1a1, Dcn, Fn1, Kcnk3, and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation. Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas, providing new insights into the pathology of SCI.
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Monolayer Cr2Ge2Te6 (ML-CGT) has attracted broad interest due to its novel electronic and magnetic properties. However, there are still controversies on the origin of its intrinsic magnetism. Here, by exploring the electronic and magnetic properties of ML-CGT, we find that the magnetic shape anisotropy (MSA) is vital for establishing the long-range ferromagnetism, except for the contribution from magnetocrystalline anisotropy energy (MCA). Electronic band analysis, combined with atomic- and orbital-resolved magnetic anisotropy from a second-order perturbation theory, further reveals that the MCA of ML-CGT is mainly originated from hybridized Te-py and -pz orbitals. The MSA from magnetic Cr atoms in ML-CGT is larger than MCA, resulting in an in-plane magnetic anisotropy. Noticeably, by constructing a heterostructure (HTS) with ferroelectric Sc2CO2, CGT undergoes an in-plane to out-of-plane spin reorientation via ferroelectric polarization switching, accompanied with an electronic property transition from semiconductor to half-metal. The Curie temperature of CGT/Sc2CO2 HTS can be enhanced to 92.4 K under the ferroelectric polarization, which is much higher than that of pristine ML-CGT (34.7 K). These results not only clarify the contradiction of magnetic mechanism of ML-CGT in previous experimental and theoretical works, but also open the door for realizing nonvolatile magnetic memory devices based on a multifunctional ferromagnetic/ferroelectric HTS.
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BACKGROUND: Longstanding intestinal inflammation increases the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD). Accurately predicting the risk of colorectal neoplasia in the early stage is still challenging. Therefore, identifying visible warning markers of colorectal neoplasia in IBD patients is the focus of the current research. Post-inflammatory polyps (PIPs) are visible markers of severe inflammation under endoscopy. To date, there is controversy regarding the necessity of strengthened surveillance strategies for IBD patients with PIPs. AIM: To determine whether IBD patients with PIPs carryan increased risk of colorectal neoplasia. METHODS: Researchers searched the following databases up to July 31, 2021: MEDLINE (PubMed), MEDLINE (Ovid), EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wan-Fang Data, China Science and Technology Journal Database and Chinese BioMedical Literature Database. Cohort and case-control studies that compared the risk of colorectal neoplasia between IBD patients with or without PIPs and published in English or Chinese were included. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions assessment tool. The outcomes of interest were the rates of various grades of colorectal neoplasia. The pooled risk ratio (RR) and 95% confidence interval (95%CI) were calculated using the random-effects model. Begg's test and Egger's test were used to calculate the publication bias. Sensitivity and subgroup analyses were performed to verify the robustness of the results. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess the overall quality of evidence supporting the outcomes of interest. RESULTS: Nine studies involving 5424 IBD patients (1944 with PIPs vs 3480 without PIPs) were included. The overall bias in each included study ranged from moderate to serious. Compared with nonconcurrent PIPs, patients with PIPs had a higher risk of colorectal neoplasia (RR = 1.74, 95%CI: 1.35-2.24, P < 0.001, I2 = 81.4%; aHR = 1.31, 95%CI: 1.01-1.70, P = 0.04, I 2 = 26.2%; aOR = 2.62, 95%CI: 1.77-3.88, P < 0.001, I 2 = 0%), advanced colorectal neoplasia (RR = 2.07, 95%CI: 1.49-2.87, P < 0.001, I 2 = 77.4%; aHR = 1.63, 95%CI: 1.05-2.53, P = 0.03, I 2 = 10.1%) and colorectal cancer (RR = 1.93, 95%CI: 1.32-2.82, P = 0.001, I 2 = 83.0%). Publication bias was not observed in Begg's test or Egger's test. Sensitivity and subgroup analyses showed that the results are robust. The overall quality of evidence was assessed as moderate to low. CONCLUSION: IBD patients with PIPs may have an increased incidence of colorectal neoplasia.
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BACKGROUND: Despite the clinical success of androgen receptor (AR)-targeted therapies, prostate cancer (PCa) inevitably progresses to castration-resistant prostate cancer (CRPC). Transcription factor 6 α (ATF6α), an effector of the unfolded protein response (UPR) that modulates the cellular response to endoplasmic reticulum (ER) stress, has been linked to tumor development, metastasis, and relapse. However, the role of ATF6α in CRPC remains unclear. METHODS: The effect of ATF6α on the CRPC-like phenotype in PCa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carb-Oxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), 5-Bromo-2-deoxyUridine (BrdU) incorporation analysis, and cell death assay. Mechanistically, bioinformatic analysis was utilized to evaluate the potential of PLA2G4A as the target of ATF6α. Moreover, Western blot analysis, real-time polymerase chain reaction, chromatin immunoprecipitation, arachidonic acid (AA), and prostaglandin E2 (PGE2) assays were performed to identify the regulatory effect of ATF6α on PLA2G4A. RESULTS: In this study, we found that the increase of ATF6α expression in response to androgen deprivation generates PCa cells with a CRPC-like phenotype. PCa cells with high levels of ATF6α expression are resistant to ferroptosis, and genetic and pharmacological inhibition of ATF6α could, therefore, promote the ferroptotic death of tumor cells and delay PCa progression. Molecular analyses linked ATF6α regulation of ferroptosis to the PLA2G4A-mediated release of AA and the resulting increase in PGE2 production, the latter of which acts as an antiferroptotic factor. CONCLUSIONS: This study defines ATF6α as a novel antiferroptotic regulator that exacerbates PCa progression. In addition, our data establish ATF6α-PLA2G4A signaling as an important pathological pathway in PCa, and targeting this pathway may be a novel treatment strategy.