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The Hunga Tonga-Hunga Ha'apai (HT-HH) volcanic eruptions on January 13 and 15, 2022, produced a plume with the highest signal in stratospheric aerosol optical depth observed since the eruption of Mt. Pinatubo in 1991. Suites of balloon-borne instruments on a series of launches from Réunion Island intercepted the HT-HH plume between 7 and 10 d of the eruptions, yielding observations of the aerosol number and size distribution and sulfur dioxide (SO2) and water vapor (H2O) concentrations. The measurements reveal an unexpected abundance of large particles in the plume, constrain the total sulfur injected to approximately 0.2 Tg, provide information on the altitude of the injection, and indicate that the formation of sulfuric acid aerosol was complete within 3 wk. Large H2O enhancements contributed as much as ~30% to ambient aerosol surface area and likely accelerated SO2 oxidation and aerosol formation rates in the plume to approximately three times faster than under normal stratospheric conditions.
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Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote the production of IL-22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2-Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)-induced colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.
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Colite , Neoplasias Colorretais , Humanos , Camundongos , Animais , Imunidade Inata , Linfócitos , Carcinogênese , Transformação Celular Neoplásica , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais de Doenças , Butirofilinas , Interleucina 22RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus, which mainly causes respiratory and enteric diseases and is responsible for the outbreak of coronavirus disease 19 (COVID-19). Numerous studies have demonstrated that SARS-CoV-2 infection will lead to a significant dysregulation of protein post-translational modification profile in human cells. The accurate recognition of phosphorylation sites in host cells will contribute to a deep understanding of the pathogenic mechanisms of SARS-CoV-2 and also help to screen drugs and compounds with antiviral potential. Therefore, there is a need to develop cost-effective and high-precision computational strategies for specifically identifying SARS-CoV-2-infected phosphorylation sites. In this work, we first implemented a custom neural network model (named PhosBERT) on the basis of a pre-trained protein language model of ProtBert, which was a self-supervised learning approach developed on the Bidirectional Encoder Representation from Transformers (BERT) architecture. PhosBERT was then trained and validated on serine (S) and threonine (T) phosphorylation dataset and tyrosine (Y) phosphorylation dataset with 5-fold cross-validation, respectively. Independent validation results showed that PhosBERT could identify S/T phosphorylation sites with high accuracy and AUC (area under the receiver operating characteristic) value of 81.9% and 0.896. The prediction accuracy and AUC value of Y phosphorylation sites reached up to 87.1% and 0.902. It indicated that the proposed model was of good prediction ability and stability and would provide a new approach for studying SARS-CoV-2 phosphorylation sites.
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The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.
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Neoplasias Colorretais , Receptor EphA1 , Animais , Humanos , Camundongos , Carcinogênese , Neoplasias Colorretais/genética , Citocinas , Células Epiteliais/metabolismo , Receptor EphA1/metabolismo , Transdução de Sinais , Tirosina , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Receptor EphB2RESUMO
Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9 Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow-derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.
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Candida albicans/fisiologia , Candidíase/imunologia , Imunidade Inata/imunologia , Leucócitos Mononucleares/imunologia , Microtúbulos/imunologia , Miosina Tipo I/metabolismo , Miosina Tipo I/fisiologia , Acetilação , Animais , Antifúngicos/farmacologia , Candidíase/tratamento farmacológico , Candidíase/metabolismo , Candidíase/microbiologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Microtúbulos/microbiologia , Miosina Tipo I/genética , Transdução de SinaisRESUMO
Natural aerosols in pristine regions form the baseline used to evaluate the impact of anthropogenic aerosols on climate. Sea spray aerosol (SSA) is a major component of natural aerosols. Despite its importance, the abundance of SSA is poorly constrained. It is generally accepted that wind-driven wave breaking is the principle governing SSA production. This mechanism alone, however, is insufficient to explain the variability of SSA concentration at given wind speed. The role of other parameters, such as sea surface temperature (SST), remains controversial. Here, we show that higher SST promotes SSA mass generation at a wide range of wind speed levels over the remote Pacific and Atlantic Oceans, in addition to demonstrating the wind-driven SSA production mechanism. The results are from a global scale dataset of airborne SSA measurements at 150 to 200 m above the ocean surface during the NASA Atmospheric Tomography Mission. Statistical analysis suggests that accounting for SST greatly enhances the predictability of the observed SSA concentration compared to using wind speed alone. Our results support implementing SST into SSA source functions in global models to better understand the atmospheric burdens of SSA.
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Objectives: To evaluate the efficacy of miniprobe endoscopic ultrasonography for the diagnosis and adjuvant treatment of patients with colorectal submucosal lesions. METHODS: The retrospective study was conducted at the Beijing Chao-Yang Hospital, Capital Medical University, China, and comprised data from January 1, 2016, to July 31, 2021, related to patients of either gender with colorectal submucosal lesions who underwent miniprobe endoscopic ultrasonography. The findings were compared with biopsy specimens and clinical diagnoses. Diagnostic features of miniprobe endoscopic ultrasonography were assessed along with its accuracy. Data was analysed using R 4.1.2. RESULTS: Of the 237 patients, 121(51.1%) were female and 116(48.9%) were male. The overall mean age was 55.6±12.9 years. Miniprobe endoscopic ultrasonography successfully imaged all 237(100%) colorectal submucosal lesions, and 188(79.3%) had consistent results compared to histopathological findings. The majority of lesions were <10mm 102(43.4%) or 10-19mm 84(35.7%) in size. Those detected with high echogenicity were 126(53.2%) and those with low/low-medium echogenicity were 83(35.0%). Tumour size 10-19mm and uneven echo quality significantly increased the accuracy of miniprobe endoscopic ultrasonography (p<0.05). CONCLUSIONS: Miniprobe endoscopic ultrasonography was able to provide precise information about the size, layer of origin, echogenicity and border of colorectal submucosal lesions, and had a high accuracy in the differential diagnosis of such lesions.
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Neoplasias Colorretais , Endossonografia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Endossonografia/métodos , Estudos Retrospectivos , China , Diagnóstico Diferencial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
Hydrogen sulfide (H2S) promotes microangiogenesis and revascularization after ischemia. Neovascularization starts with the destruction of intercellular junctions and is accompanied by various endothelial cell angiogenic behaviors. Follistatin-like 1 (FSTL1) is a cardiovascular-protective myokine that works against ischemic injury. The present study examined whether FSTL1 was involved in H2S-induced angiogenesis and explored the underlying molecular mechanism. We observed that H2S accelerated blood perfusion after ischemia in the mouse hindlimb ischemia model. Western blot analysis showed that H2S stabilized FSTL1 transcript and increased FSTL1 and Human antigen R (HuR) levels in skeletal muscle. RNA-interference HuR significantly inhibited the H2S-promoted increase in FSTL1 levels. Exogenous FSTL1 promoted the wound-healing migration of human umbilical vein endothelial cells (HUVECs) and increased monolayer endothelial barrier permeability. Immunostaining showed that FSTL1 increased interendothelial gap formation and decreased VE-Cadherin, Occludin, Connexin-43, and Claudin-5 expression. In addition, FSTL1 significantly increased the phosphorylation of Src and VEGFR2. However, the Src inhibitor, not the VEGFR2 inhibitor, could block FSTL1-induced effects in angiogenesis. In conclusion, we demonstrated that H2S could upregulate the expression of FSTL1 by increasing the HuR levels in skeletal muscle, and paracrine FSTL1 could initiate angiogenesis by opening intercellular junctions via the Src signaling pathway.NEW & NOTEWORTHY The myocyte-derived paracrine protein FSTL1 acts on vascular endothelial cells and initiates the process of angiogenesis by opening the intercellular junction via activating Src kinase. H2S can significantly upregulate FSTL1 protein levels in skeletal muscles by increasing HuR expression.
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BACKGROUND: The immune system plays a crucial role in initiating, progressing, and disseminating HNSCC. This study aims to investigate the differences in immune microenvironments between 2D-4-culture and 3D-4-culture models of head and neck squamous cell carcinoma (HNSCC) cells (FaDu), human fibroblasts (HF), human monocytes (THP-1), and human endothelial cells (HUVEC). METHODS: For the 3D-4-culture model, FaDu:HF:THP-1 (2:1:1) were inoculated in an ultra-low attachment culture plate, while HUVECs were placed in a transwell chamber. The ordinary culture plate was used for the 2D-4-culture model. Tumor-associated macrophage markers (CD163), tumor-associated fibroblast markers (FAP), and epithelial-mesenchymal transition (EMT) were detected by western blot. Inflammatory cytokines (IL-4, IL-2, CXCL 10, IL-1 ß, TNF-α, CCL 2, IL-17 A, IL-6, IL-10, IFN-γ, IL-12 p 70, CXCL 8, TGFß1) in the supernatant were measured by flow cytometry. HUVEC migration was observed under a microscope. The 3D spheres were stained and observed with a confocal microscope. CCK8 assay was used to detect the resistance of mixed cells to cisplatin in both 2D-4-culture and 3D-4-culture. RESULTS: After three days of co-culture, the 3D-4-culture model showed increased expression levels of CD163 and FAP proteins (both P < 0.001), increased expression of E-cadherin protein and N-cadherin protein expression (P < 0.001), decreased expression of vimentin (P < 0.01) and Twist protein (P < 0.001). HUVEC migration significantly increased (P < 0.001), as did the concentrations of IP-10, MCP-1, IL-6, and IL-8 (all P < 0.001). Confocal microscopy showed that 3D-4-culture formed loose cell clusters on day 1, which gradually became a dense sphere surrounded by FaDu cells invading the inside. After co-culturing for 24 h, 48 h, and 72 h, the resistance of mix cells to cisplatin in 3D-4-culture was significantly higher than in 2D-4-culture (P < 0.01 for all). CONCLUSION: Compared to 2D-4-culture, 3D-4-culture better simulates the in vivo immune microenvironment of HNSCC by promoting fibroblast transformation into tumor-associated fibroblasts, monocyte transformation into tumor-associated macrophages, enhancing endothelial cell migration ability, partial EMT formation in HNSCC cells, and is more suitable for studying the immunosuppressive microenvironment of HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Cisplatino , Células Endoteliais/metabolismo , Interleucina-6 , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Fatores de Transcrição , Microambiente TumoralRESUMO
IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Fator Regulador 1 de Interferon/metabolismo , Interleucina-17/metabolismo , Psoríase/metabolismo , RNA Longo não Codificante/metabolismo , RNA/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Transdução de Sinais/genética , Animais , Proteínas de Ciclo Celular/genética , Técnicas de Inativação de Genes , Células HaCaT , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , RNA/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Fatores de Processamento de Serina-Arginina/genética , TransfecçãoRESUMO
Small uncrewed aerial systems (sUASs) have the potential to serve as ideal platforms for high spatial and temporal resolution wildfire measurements to complement aircraft and satellite observations, but typically have very limited payload capacity. Recognizing the need for improved data from wildfire management and smoke forecasting communities and the potential advantages of sUAS platforms, the Nighttime Fire Observations eXperiment (NightFOX) project was funded by the US National Oceanic and Atmospheric Administration (NOAA) to develop a suite of miniaturized, relatively low-cost scientific instruments for wildfire-related measurements that would satisfy the size, weight and power constraints of a sUAS payload. Here we report on a remote sensing system developed under the NightFOX project that consists of three optical instruments with five individual sensors for wildfire mapping and fire radiative power measurement and a GPS-aided inertial navigation system module for aircraft position and attitude determination. The first instrument consists of two scanning telescopes with infrared (IR) channels using narrow wavelength bands near 1.6 and 4 µm to make fire radiative power measurements with a blackbody equivalent temperature range of 320-1500 °C. The second instrument is a broadband shortwave (0.95-1.7 µm) IR imager for high spatial resolution fire mapping. Both instruments are custom built. The third instrument is a commercial off-the-shelf visible/thermal IR dual camera. The entire system weighs about 1500 g and consumes approximately 15 W of power. The system has been successfully operated for fire observations using a Black Swift Technologies S2 small, fixed-wing UAS for flights over a prescribed grassland burn in Colorado and onboard an NOAA Twin Otter crewed aircraft over several western US wildfires during the 2019 Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) field mission.
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Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.
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Testes Genéticos/métodos , Perda Auditiva/diagnóstico , Pequim , Teste em Amostras de Sangue Seco , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Tumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role of TNFAIP2 in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role of TNFAIP2 in leukemogenesis. METHODS: TNFAIP2 mRNA level, prognostic value, co-expressed genes, differentially expressed genes, DNA methylation, and functional enrichment analysis in AML patients were explored via multiple public databases, including UALCAN, GTEx portal, Timer 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and String databases. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Beat AML database were used to determine the associations between TNFAIP2 expression and various clinical or genetic parameters of AML patients. Moreover, the biological functions of TNFAIP2 in AML were investigated through in vitro experiments. RESULTS: By large-scale data mining, our study indicated that TNFAIP2 was differentially expressed across different normal and tumor tissues. TNFAIP2 expression was significantly increased in AML, particularly in French-American-British (FAB) classification M4/M5 patients, compared with corresponding control tissues. Overexpression of TNFAIP2 was an independent poor prognostic factor of overall survival (OS) and was associated with unfavorable cytogenetic risk and gene mutations in AML patients. DNA hypermethylation of TNFAIP2 at gene body linked to upregulation of TNFAIP2 and inferior OS in AML. Functional enrichment analysis indicated immunomodulation function and inflammation response of TNFAIP2 in leukemogenesis. Finally, the suppression of TNFAIP resulted in inhibition of proliferation by altering cell-cycle progression and increase of cell death by promoting early and late apoptosis in THP-1 and U937AML cells. CONCLUSION: Collectively, the oncogenic TNFAIP2 can function as a novel biomarker and prognostic factor in AML patients. The immunoregulation function of TNFAIP2 warrants further validation in AML.
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Leucemia Mieloide Aguda , Fator de Necrose Tumoral alfa , Biomarcadores Tumorais/genética , Carcinogênese , Citocinas , DNA , Humanos , Inflamação , Leucemia Mieloide Aguda/patologia , Prognóstico , RNA Mensageiro/genéticaRESUMO
BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
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COVID-19 , Humanos , Feminino , Saúde Mental , SARS-CoV-2 , Depressão/epidemiologia , Ansiedade/psicologia , Surtos de Doenças , Inquéritos e Questionários , China/epidemiologiaRESUMO
PURPOSE: This study aimed to explore the prevalence and distribution of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China. METHODS: A multi-stage, group-matching random sampling method was adopted with 2579 elderly participants (≥ 60 years old) who were interviewed from January to May 2019. Preliminary screening was conducted using the scale by trained psychiatric nurses, followed by a diagnostic interview during the second stage using Chinese Version of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorder by trained psychiatrists. RESULTS: A total of 2561 participants were included in this study with complete data. The weighted lifetime prevalence of all mental disorders in the elderly was 16.2% (95% CI 15.3-17.1), and the weighted 12-month prevalence was 15.2% (95% CI 13.4-17.0). Depressive disorders, anxiety disorders, substance-related and addictive disorders were the most common mental disorders. The 12-month prevalence of all mental disorders were significantly higher in the elderly living alone, with chronic somatic disease, and being poor (P < 0.05). The 12-month prevalence of posttraumatic stress disorder (PTSD) was significantly higher in the elderly in extremely severely earthquake-affected areas (P < 0.001). CONCLUSION: The results of this study show that mental health status of the elderly in Ya'an area differ by socio-economic development, geographical location, and natural disasters. The social and economic development characteristics, the impact of major natural disasters (e.g., earthquakes), and population characteristics should be combined to formulate strategies and interventions to promote the mental health of the elderly.
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Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , Idoso , Humanos , Pessoa de Meia-Idade , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , China/epidemiologia , Fatores de Risco , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologiaRESUMO
Long non-coding RNAs (lncRNAs), which belong to the non-protein-coding RNAs, are greater than 200 nt in length. Although they have been found to play crucial roles in the regulation of cell growth and development, cell metabolism and the development of diseases, they are rarely reported in decidualization. The objective of our study is to explore the expression of lincRNA AC027700.1 in the endometrium of early pregnant mice and its role in decidualization. The expression of AC027700.1 in uterine tissues at implantation sites and inter implantation sites on the 6th day of pregnancy were detected by qRT-PCR. The relative expression of AC027700.1 in an in vivo model of induced decidualization in pseudopregnant mice and in in vitro model of induced decidualization in primary stromal cells and nucleus/cytoplasmic fractions were detected by qRT-PCR. GO and KEGG analysis of downstream target genes were performed by GOseq and KOBAS, respectively. The results show that AC027700.1 expression is significantly increased in tissues at implantation sites on the 6th day of pregnancy and in decidualized endometrial tissues and stromal cells. Furthermore, AC027700.1 localizes in the nuclear fraction and the downstream targeted genes are mainly involved in autophagy, cell cycle and RNA transport pathways. This study revealed that lincRNA AC027700.1 may be involved in decidualization of endometrium in early pregnancy, but the specific role and regulatory mechanism remain to be further studied.
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Decídua , RNA Longo não Codificante , Animais , Autofagia , Decídua/metabolismo , Implantação do Embrião , Endométrio/metabolismo , Feminino , Camundongos , Gravidez , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células Estromais/metabolismoRESUMO
Aim: To investigate the role of LINC01160 in nasopharyngeal carcinoma (NPC). Materials & methods: Using NPC cells CNE-2 and HNE-2 in vitro, we performed quantitative PCR to determine mRNA expression and western blotting to determine protein expression. CCK-8, transwell, flow cytometry and wound healing assays were done to examine the function of LINC01160 and STAT1. Chromatin immunoprecipitation PCR (ChIP-PCR) confirmed that STAT1 combines with the LINC01160 promoter region. Xenograft experiments were used to verify the role of STAT1 and LINC01160 in vivo. Results: LINC01160 is upregulated in NPC and can promote a malignant cell phenotype. STAT1 is a transcription factor of LINC01160 and can promote a malignant cell phenotype through upregulating LINC01160 expression. Conclusion: STAT1 can promote a malignant cell phenotype by upregulating LINC01160.
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Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT1/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Feminino , Humanos , Camundongos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética , Regiões Promotoras Genéticas/genética , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.
Assuntos
Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicólise , Proteínas Nucleares/genética , Neoplasias Pancreáticas/metabolismo , Proteína 1 Relacionada a Twist/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Ligação a Hormônio da TireoideRESUMO
PURPOSE: This study aimed to (1) explore the prevalence and relevant influencing factors of different mental disorders 5 years after the Lushan earthquake in Ya'an, China. METHODS: An epidemiological mental health survey was conducted to identify the prevalence of mental disorders in general population in Ya'an. A multi-stage, group-matching random sampling method was adopted. Face-to-face interviews were done with a two-stage design by trained interviewers and psychiatrists. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was used for the diagnosis. RESULTS: There were 8876 participants who were interviewed in this study. The total 12-month and lifetime prevalence of all mental disorders were 12.5% and 14.7%, respectively. There was a significant difference between males and females in the prevalence patterns of several mental disorders. Han ethnic group had higher prevalence of anxiety disorders (2.7%), and the Tibetan group had higher prevalence of alcohol-related disorders (5.0%). Logistic regression analysis showed that the areas severely affected by the earthquake had significantly higher prevalence of depressive disorders, and the extremely severe affected areas had significantly higher prevalence of trauma- and stressor-related disorders. CONCLUSION: Our findings show that the prevalence of a range of mental disorders 5 years after the earthquake in Ya'an are high, and the prevalence of depressive and trauma- and stressor-related disorders may be influenced differently by the various severity of earthquake impact. This study may be crucial for the health policy-making, cultural-specific mental health services and long-term mental recovery after the earthquake.
Assuntos
Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Depressão , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Prevalência , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , SobreviventesRESUMO
Staphylococcal nuclease domain-containing protein 1 (SND1) has been reported as an oncoprotein in a variety of cancers involving multiple processes, including proliferation, angiogenesis, and metastasis. However, the mechanisms underlying metastasis remain largely unknown. Herein, by using the ovarian cancer cell line SKOV3, which has high metastasis ability, we showed that loss-of-function of SND1 dramatically suppressed the invasion and migration of SKOV3 cells. We then performed gene expression profiles and further verified (by use of quantitative PCR and Western blot analysis) that loss-of-function of SND1 resulted in up-regulation of epithelial markers, such as epithelial cadherin and claudin 1, and down-regulation of mesenchymal markers, including neural cadherin and vimentin. Moreover, we illustrated that SLUG, a key transcription factor implicated in epithelial-mesenchymal transition and metastasis, acts as an essential effector of the SND1-promoted epithelial-mesenchymal transition process via regulating N-CAD and VIM expression (or E-CAD and CLDN1). The underlying molecular mechanisms illustrated that SND1 regulates the gene transcriptional activation of SLUG by increasing chromatin accessibility through the recruitment of the acetyltransferases GCN5 and CBP/p300 to the SLUG promoter proximal region. Overall, SND1 was identified as a novel upstream regulator of SLUG, which plays important roles in regulating the E-CAD/N-CAD expression switch.-Xin, L., Zhao, R., Lei, J., Song, J., Yu, L., Gao, R., Ha, C., Ren, Y., Liu, X., Liu, Y., Yao, Z., Yang, J. SND1 acts upstream of SLUG to regulate the epithelial-mesenchymal transition (EMT) in SKOV3 cells.