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Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.
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Elementos Nucleotídeos Longos e Dispersos , Proteínas de Ligação à Região de Interação com a Matriz , RNA Polimerase II , Receptores de Estrogênio , Transcrição Gênica , Humanos , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas Associadas à Matriz Nuclear/genética , Regulação da Expressão Gênica , Ligação Proteica , Células HEK293 , Genoma HumanoRESUMO
In situ characterizations of charge injection dynamics, equilibrated concentration, and electric field distributions shed light on the critical mechanisms of quantum dot light-emitting diodes (QD-LEDs). In this work, we developed electrically excited transient absorption spectroscopy, which can provide the above key information, to investigate the efficiency roll-off of QD-LEDs. We found that the average electron populations per QD are low when QD-LEDs exhibit efficiency roll-off, excluding Auger recombination as the main cause. We also revealed that the weak electrical field inside the QD layer under forward biases has a negligible impact on the efficiency. Interestingly, we found that as the voltage increases the electron concentration in the QD layer saturates at very low levels. When combined with the concomitant efficiency roll-off, we propose electron leakage is the main loss at elevated driving voltages. We further demonstrate that increasing the electron confinement potential with the ZnS shell enables us to efficiently mitigate the efficiency roll-off.
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O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and OGlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.
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Acetilglucosamina , N-Acetilglucosaminiltransferases , Humanos , Animais , N-Acetilglucosaminiltransferases/metabolismo , Acetilglucosamina/metabolismo , Osso e Ossos/metabolismo , Processamento de Proteína Pós-Traducional , Doenças Ósseas/metabolismoRESUMO
BACKGROUND: Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection. CASE PRESENTATION: A 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months. CONCLUSIONS: This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.
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Linfoma Anaplásico de Células Grandes , Neoplasias Cutâneas , Humanos , Feminino , Idoso , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Recidiva Local de NeoplasiaRESUMO
BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5âcm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (>â3.0âcm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.
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Ressecção Endoscópica de Mucosa , Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Ressecção Endoscópica de Mucosa/métodos , Gastroscopia/métodosRESUMO
BACKGROUND: Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. METHODS: Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan-Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. RESULTS: LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells ( P < 0.01), elevated SW480 cells sensitivity to 5-FU ( P < 0.01), reduced LC3 punctate aggregates ( P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 ( P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. CONCLUSION: LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Autofagia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
INTRODUCTION: Atrial fibrillation (AF) adversely impacts right ventricular (RV) and right atrial (RA) structure and function. There are limited data on these changes after electrical cardioversion (ECV) and the relative contribution of heart rate to evaluate the immediate (1-2 h) and short-term (4-6 weeks) changes in right cardiac chamber dimensions and RV function after ECV in patients with persistent AF. METHODS: Right cardiac chamber dimensions and RV function were measured in 64 patients using transthoracic echocardiography 1-2 h before, immediately after, and 4-6 weeks after ECV. Associations between changes in right-heart measures and rhythm status at follow-up were assessed using linear regression models. RESULTS: For patients who remained in sinus rhythm 4-6 weeks after ECV (n = 48), median fractional area change (FAC) at baseline, immediately after ECV, and 4-6 weeks after ECV were 39 (Q1:35, Q3:42) %, 42 (Q1:39, Q3:46) %, 46 (Q1:43, Q3:49) % (p < 0.01); median tricuspid annular plane systolic excursion (TAPSE) values at the same time points were 18 (Q1:17, Q3:20) mm, 20 (Q1:18, Q3:23) mm, and 24 (Q1:22, Q3:26) mm (p < 0.01), respectively. There was no significant difference in RV end systolic area and RA volume index before and after ECV. However, RV end systolic area and RA volume index decreased significantly after 4-6 weeks from a median of 10 (Q1:8, Q3:13) cm2 to 8 (Q1:7, Q3:10) cm2 (p < 0.01), and from a median of 30 (Q1:24, Q3:36) mL/m2 to 24 (Q1:20, Q3:27) mL/m2 (p < 0.01). Changes in TAPSE were significantly associated with sinus rhythm at follow-up (p = 0.027), changes in FAC showed a strong trend to association with sinus rhythm (p = 0.053), and this was not true for RA measures (p = 0.64). CONCLUSIONS: Among AF patients who remained in sinus rhythm after ECV, RV function improved immediately after ECV with further improvement at 4-6 weeks following sinus rhythm restoration.
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Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Cardioversão Elétrica , Átrios do Coração/diagnóstico por imagem , Frequência Cardíaca/fisiologia , Ecocardiografia , Função Ventricular DireitaRESUMO
There is an interactive effect between ammonium perchlorate (AP) and aluminum (Al) powder during the combustion process of composite solid propellants, but the mechanism of this effect is still lacking. Using quantum chemical methods, we investigated this mechanism from a molecular perspective. The interaction process between Al and AP was analyzed by comparing the chemical bond changes between the atoms during the reaction process of the Al/AP system and the AP unimolecular thermal decomposition system. The results show that Al atoms alter the reaction mechanism of AP thermal decomposition, significantly decreasing the activation energy of AP decomposition at high temperature but increasing that at low temperature. Meanwhile, the temperature-dependent rate constant of each basic reaction was calculated by transition state theory. The rate constants increase with temperature. Under high temperature and pressure, Al can increase the high-temperature decomposition rate of AP by up to 1-3 orders of magnitude.
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BACKGROUND: There has always been a debate on the optimal timing of endoscopy in patients with acute variceal bleeding (AVB). OBJECTIVE: This study aimed to examine the relation between the timing of endoscopy and the short-term outcomes of patients with AVB. METHODS: Patients with AVB who underwent endoscopy within 24 h after admission at our tertiary care center from 2014 to 2022 were evaluated retrospectively. The primary outcomes were the 6-week mortality and re-bleeding. The secondary outcomes included the total number of blood units transfused, the length of hospital stay, and the need for salvage therapy. We used Cox proportional hazards model to analyze the predictors of 6-week mortality in all patients as well as in those who were at high risk of further bleeding or death. RESULTS: A total of 312 patients were enrolled. Among them, 170 patients (54.49%) underwent urgent endoscopy (< 6 h), and 142 patients (45.51%) underwent early endoscopy (6-24 h). There were no significant differences between the urgent-endoscopy group and the early-endoscopy group, regarding the 6-week mortality (16.47% vs. 10.56%; P value = 0.132) and 6-week re-bleeding rate (11.2% vs. 16.2%; P value = 0.196). In multivariate analysis, time to endoscopy was independent of 6-week mortality (P value = 0.170), but the time between the beginning of bleeding and endoscopy (within 12 h) was significantly associated with low 6-week mortality (OR: 0.16; 95% CI: 0.06-0.46; P value = 0.001). Time to endoscopy was still not associated with 6-week mortality in patients at high risk for further bleeding or death (Glasgow-Blatchford score ≥ 12, n = 138, P value = 0.902). CONCLUSIONS: Endoscopy performed within 6 h of admission, rather than within 6 to 24 h, did not improve six-week clinical outcomes in patients in stable condition with AVB and even those who were at high risk of further bleeding and death.
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Varizes Esofágicas e Gástricas , Humanos , Estudos de Coortes , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Estudos RetrospectivosRESUMO
AIM: To explore the endoscopic features and risk factors of early gastric cancer (EGC) after eradication of Helicobacter pylori (H. pylori). METHODS: A total of 1961 patients who underwent esophago-gastro-duodenoscopy (EGD) with a history of successful H. pylori eradication were enrolled in this multicenter research. Among them, 162 EGC lesions of 132 patients were detected. The endoscopic features and risk factors of post-eradication EGC were explored. RESULTS: Severe atrophy (75.3% vs. 16.7%, p value <.01), intestinal metaplasia (96.3% vs. 77.1%, p value <.01), map-like redness (89.5% vs. 65.4%, p value <.01), distinct intermediate zone (IZ) (68.5% vs. 23.4%, p value <.01) and xanthoma (58.0% vs. 17.9%, p value <.01) were significantly more frequent in the CA group (patients with newly detected EGC after eradication of H. pylori) than in the NC group (patients without gastric cancer after eradication of H. pylori). In multivariate analysis, severe atrophy (odds ratio (OR) = 8.08; 95% confidence interval (CI), 3.43-20.0; p value<.01), map-like redness (OR = 1.75; 95% CI, 0.11-5.25; p value = .04), distinct IZ (OR = 2.87; 95% CI, 1.20-6.93; p value = .02) and xanthoma (OR = 2.84; 95% CI, 1.20-7.03; p value=.02) were proved to be risk factors for detection of EGC after eradication of H. pylori. CONCLUSIONS: Severe atrophy and map-like redness and distinct IZ and xanthoma are risk factors of EGC after eradication of H. pylori.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Mucosa Gástrica , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Humanos , Fatores de Risco , Neoplasias Gástricas/etiologiaRESUMO
OBJECTIVES: To assess the geographic variation of sudden unexpected infant death (SUID) and test if variation in geographic factors, such as state, latitude, and longitude, play a role in SUID risk across the US. STUDY DESIGN: We analyzed the Centers for Disease Control and Prevention's Cohort Linked Birth/Infant Death dataset (2005-2010; 22â882 SUID cases, 25â305â837 live births, rate 0.90/1000). SUID was defined as infant deaths (ages 7-364 days) that included sudden infant death syndrome, ill-defined and unknown cause of mortality, and accidental suffocation and strangulation in bed. SUID geographic variation was analyzed using 2 statistical models, logistic regression and generalized additive model (GAM). RESULTS: Both models produced similar results. Without adjustment, there was marked geographic variation in SUID rates, but the variation decreased after adjusting for covariates including known risk factors for SUID. After adjustment, nine states demonstrated significantly higher or lower SUID mortality than the national average. Geographic contribution to SUID risk in terms of latitude and longitude were also attenuated after adjustment for covariates. CONCLUSION: Understanding why some states have lower SUID rates may enhance SUID prevention strategies.
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Morte Súbita do Lactente/epidemiologia , Centers for Disease Control and Prevention, U.S. , Conjuntos de Dados como Assunto , Geografia Médica , Humanos , Lactente , Recém-Nascido , Modelos Estatísticos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: With a shift in the healthcare paradigm towards a more patient-centered approach, data on inflammatory bowel disease (IBD) needs to be further explored. This study aimed to determine patient perspectives on the effect of IBD and features of patients with lower satisfaction level and compare patient and physician perception of IBD-related Quality of Care (QoC). METHODS: A previously developed pre-standardised set of questions regarding patient-centered outcome (PRO) measures for IBD, comprising 36 items, was administered in five centers, and a concomitant questionnaire for specialised physicians was adapted and administered. RESULTS: Overall, 1005 patients with IBD met the inclusion criteria. Sixty-five questionnaires were administered to specialised physicians. Both patients and physicians perceived the IBD-related QoC as being satisfactory. Furthermore, this study revealed areas of shortcomings where it comes to patient perceptions. Female sex and the presence of negatively impacting disease characteristics (presence of significant pain or discomfort, lack of energy, feeling fatigued most of the time, experiencing anxiety or depression in the last 2 weeks) were associated with lower satisfaction levels. CONCLUSIONS: Our findings can be used in establishing strategies aimed at improving patient QoC and defining strategic priorities. These data can aid in improving the communication of the pressing needs of IBD patients, to both the public payers and health authorities.
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Doenças Inflamatórias Intestinais/psicologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Adulto , Idoso , Consenso , Estudos Transversais , Feminino , Humanos , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/normas , Qualidade da Assistência à Saúde/normas , Qualidade de Vida , Adulto JovemRESUMO
Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8's role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients' data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3ß from the Wnt/ß-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven ß-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3ß, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.
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Colite , Canais de Cátion TRPM , Humanos , Camundongos , Animais , Substância P/efeitos adversos , Substância P/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Mentol/farmacologia , Colite/genética , Células Receptoras Sensoriais/metabolismo , Epitélio/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Gânglios Espinais/metabolismo , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: Macrophages exhibit different phenotypes in inflammatory bowel disease (IBD) and promote inflammation or tissue repair depending on their polarization state. Alcohol is a widely used solvent in pharmaceutical formulations, and its consumption is associated with an increased risk of colitis; however, its effects on macrophages in IBD remain poorly understood. PURPOSE: This study aimed to investigate the effect of alcohol on macrophages in dextran sodium sulfate (DSS)-induced colitis and understand the underlying mechanisms. METHODS: DSS-treated C57BL/6 mice were exposed to varying concentrations of alcohol, transient receptor potential vanilloid 1 (TRPV1) antagonist, and 5-aminosalicylic acid. The distal colon was resected, fixed, stained, and histologically analyzed, through hematoxylin and eosin (H&E) staining and immunofluorescence staining. Ratio [Ca2+]i measurements, western blotting, quantitative polymerase chain reaction, cytokine measurements, and RNA sequencing analyses were also performed. Peritoneal macrophages and RAW264.7 cells were used for in vitro experiments, and various assays were performed to evaluate cellular responses, gene expression, and signaling pathways. RESULTS: Alcohol exacerbated DSS-treated mice colitis and promoted the secretion of various inflammatory cytokines from colonic macrophages. Alcohol enhances the calcium ion influx induced by lipopolysaccharide (LPS) in peritoneal macrophages, while the TRPV1 antagonist capsazepine (CPZ) inhibits LPS- and/or alcohol- induced calcium influx in macrophages. Alcohol and LPS activate the MAPK/P38, MAPK/ERK, and NF-κB signaling pathways and induce the macrophage M2b polarization, resulting in the increased expression level of inflammatory cytokines such as Tnf, Il1b, and Il10. Additionally, CPZ can inhibit the facilitatory effects of alcohol or LPS on the abovementioned pathways and inflammatory factors, reversing macrophage M2b polarization and promoting alcohol-induced colitis. The inhibition of nucleotide binding oligomerization domain containing 2 (NOD2) partially suppressed the alcohol and LPS effects on macrophages. CONCLUSION: Alcohol exacerbates experimental colitis and induces M2b polarization of macrophage via TRPV1-MAPK/NF-κB. Our study provides new insights into the potential therapeutic targets for IBD treatment by elucidating the role of TRPV1 in alcohol-exacerbated colitis, using CPZ as a potential therapeutic option. The identification of transient receptor potential ankyrin subtype 1 (TRPA1) as a therapeutic target expands the scope of future research.
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Colite , Sulfato de Dextrana , Etanol , Macrófagos , NF-kappa B , Canais de Cátion TRPV , Animais , Masculino , Camundongos , Capsaicina/análogos & derivados , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismoRESUMO
Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR-Cas9 screening using a reporter driven by the L1 5' UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
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Sistemas CRISPR-Cas , Elementos Nucleotídeos Longos e Dispersos , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Animais , Camundongos , Ativação Transcricional , Zigoto/metabolismo , Transcrição Gênica , Regulação da Expressão Gênica , Regiões 5' não TraduzidasRESUMO
Using fixed, mediating, and moderating effect models, we explored the impact of the digital economy on carbon emission intensity and its mechanisms based on panel data of 100 cities in 6 Chinese urban agglomerations from 2011 to 2019. The results show that (1) the digital economy development in the urban agglomerations can significantly reduce carbon emission intensity. (2) The digital economy in the urban agglomerations can indirectly reduce carbon emission intensity through the channels of green technology innovation and the information communications technology (ICT) industry. Furthermore, a higher degree of marketization in the urban agglomerations leads to a more pronounced effect of the digital economy on reducing carbon emission intensity. (3) The impact of the digital economy on the carbon emission intensity in the urban agglomerations is regionally heterogeneous. When the carbon emission intensity is at different quantiles, the effects of the digital economy on reducing carbon emission intensity are different. (4) The digital economy development has different impacts on carbon emission intensity when different urban agglomerations are approved. The digital economy development in the urban agglomerations can better reduce carbon emission intensity than that in other cities. Currently, China is in a significant period of rapid digital economy development and energy conservation and emission reduction. We revealed some new features of the digital economy and carbon emission intensity in urban agglomerations, providing a reference for promoting the construction of urban agglomerations, developing the digital economy, and reducing carbon emission intensity.
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Poluentes Atmosféricos , Desenvolvimento Econômico , Carbono , China , Cidades , Poluentes Atmosféricos/análiseRESUMO
Accurately assessing the impact of low-carbon urban construction on green economic development has great significance for achieving economic development with environmental protection, and for building an ecological civilization and a beautiful China. Based on panel data for 271 cities in China from 2004 to 2019, multi-period and spatial difference-in-difference econometric models were used to comprehensively investigate the impact of three batches of low-carbon city pilot policies on green economic development, finding the following: The contribution of low-carbon urban construction on urban green economic development is significant and positive, and still holds under a series of robustness tests. Parallel trend tests also show a lag in the policy effect, and the effect is strengthened over policy implementation time. Green orientation of technological progress, green transformation of industry, and green upgrade of consumption are important channels for the effect of the policies. The promotion effect of low-carbon city construction is stronger in the central and northern cities, and in cities with high green economic development, than in western and southern cities, and those with low green economic development. Construction of low-carbon pilot cities not only promotes their own green economic development, but also that in neighboring cities, exerting a demonstration effect. This effect is greater in urban areas. This study provides empirical support for policy planning to promote low-carbon urban construction across the country.
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Carbono , Desenvolvimento Econômico , Cidades , China , PolíticasRESUMO
This research investigated the potential use of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) as a biocide in aircraft fuel systems, which is rarely studied due to the unique properties of such systems. The study assessed the effectiveness of CMIT against three microbial isolates using minimum inhibitory concentrations and bacteriostatic tests, and showed that CMIT had good activity against them. Electrochemical studies were conducted to determine the impact of CMIT on the 7B04 aluminum alloy, which demonstrated that CMIT acted as a cathodic inhibitor and exhibited certain levels of short-term and long-term corrosion inhibition effects at concentrations of 100 mg L-1 and 60 mg L-1, respectively. Additionally, the research provided insights into the mechanisms governing microbial problems by studying the reaction of CMIT with glutathione and sulfate. Overall, the study suggested that CMIT may be a useful biocide in aircraft fuel systems and provided important information on its efficacy and mechanism of action.
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This study aimed to investigate the association between air pollution and gestational diabetes mellitus (GDM) in small- and medium-sized cities, identify sensitive periods and major pollutants, and explore the effects of air pollution on different populations. A total of 9820 women who delivered in Handan Maternal and Child Health Hospital in the Hebei Province from February 2018 to July 2020 were included in the study. Logistic regression and principal component logistic regression models were used to assess the effects of air pollution exposure during preconception and pregnancy on GDM risk and the differences in the effects across populations. The results suggested that each 20 µg/m3 increase in PM2.5 and PM10 exposure during preconception and pregnancy significantly increased the risk of GDM, and a 10 µg/m3 increase in NO2 exposure during pregnancy was also associated with the risk of GDM. In a subgroup analysis, pregnant women aged 30-35 years, nulliparous women, and those with less than a bachelor's education were the most sensitive groups. This study provides evidence for an association between air pollution and the prevalence of GDM, with PM2.5, PM10, and NO2 as risk factors for GDM.
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Background: N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD. Methods: The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry. Results: In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells. Conclusion: A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.