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Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.
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PURPOSE: Bufalin (BU) is a bioactive ingredient extracted from the skin and parotid venom glands of Bufo raddei, which can effectively inhibit angiogenesis. The aim of this study was to investigate whether BU could affect corneal neovascularization (CoNV). METHODS: A rat CoNV model (right eye) was constructed by administration of NaOH, and the left eye served as a control. Corneal damage scores of rats were detected. Hematoxylin & eosin, TUNEL, and Masson staining examined pathological changes, apoptosis, and fibrosis of corneal tissues. Immunohistochemistry and western blotting assessed the expression of proteins. RESULTS: BU intervention resulted in a significant reduction in corneal inflammatory cells, repair of corneal epithelial hyperplasia, significant reduction in stromal edema, and reduction in vascular proliferation. BU can inhibit corneal neovascularization. CONCLUSION: This study demonstrated that BU inhibits CoNV, fibrosis, and inflammation by modulating the STAT3 signaling pathway, elucidating the intrinsic mechanism of its protective effect. BU has great potential in the treatment of CoNV caused by corneal alkali burns.
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BACKGROUND: Deficits in speech and emotion perception are intertwined with psychiatric symptoms. How the happy prosody embedded in speech affects target speech-in-noise recognition (TSR) and relates to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study examined spontaneous brain activity underlying happy TSR and its association with psychiatric symptom dimensions in SCHs. METHODS: Fifty-four SCHs and 59 healthy control participants (HCs) underwent the TSR task, Positive and Negative Syndrome Scale (PANSS) assessment, and magnetic resonance imaging scanning. Multivariate analyses of partial least squares (PLS) regression were used to explore the associations between whole-brain fractional amplitude of low-frequency fluctuations (fALFF), happy-neutral TSR (target pseudo-sentences were uttered in happy and neutral prosodies), and five PANSS factor scores (excitement/hostility, depression/anxiety, cognition, positive, and negative). RESULTS: The happy prosody did not alter TSR or TSR changing rates in either SCHs or HCs. SCHs exhibited lower happy and neutral TSR than HCs. A fALFF PLS component (including precentral/postcentral gyrus, Subcallosal Cortex, several temporal regions, and cerebellum) was associated with happy and neutral TSR. SCHs demonstrated higher PLS fALFF scores and PLS TSR scores than HCs. In SCHs, PLS fALFF scores were correlated with the PANSS positive factor score, and PLS TSR scores were correlated with the PANSS cognition factor score. CONCLUSIONS: The positive-psychiatric-symptoms-related spontaneous activity profile was associated with happy and neutral TSR, contributing to the cognition psychiatric symptoms dimension. The findings suggest the potential to improve positive and cognitive symptoms by enhancing happy and neutral TSR in schizophrenia based on neuroplasticity.
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Objective: This cross-sectional study examined the influence of sedentary behavior (SB) time substitution with physical activity (PA) on depressive symptoms among adults with overweight/obesity. SB time was replaced with equal amount of walking/bicycling or leisure-time moderate-to-vigorous PA (MVPA). Methods: Data of the 18344 adults, who were overweight and obesity was obtained from the National Health and Nutrition Examination Survey 2006-2018. PA of participants was measured by the Global Physical Activity Questionnaire. Depressive symptoms, including overall, somatic, and cognitive depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Isotemporal substitution model based on weighted multiple linear regression was used to assess the association of SB time substitution with PA on depressive symptoms. Results: Independent model analysis showed that 30 min/day SB time was significantly associated with higher PHQ-9 depressive symptoms, while engage in walking/bicycling or leisure-time MVPA for 30 min/day was associated with lower depressive symptoms. Isotemporal substitution analyses revealed that replacing 30 min/day SB time with equal amount of walking/bicycling or leisure-time MVPA was associated with significant lower PHQ-9 total scores (walking/bicycling: ß = -0.088, 95%CI = -0.129, -0.047, P < 0.01; MVPA: ß = -0.160, 95%CI = -0.185, -0.134, P < 0.01). Moreover, cognitive depressive symptoms (walking/bicycling: ß = -0.035, 95%CI = -0.058, -0.013, P < 0.01; MVPA: ß = -0.074, 95%CI = -0.088, -0.060, P < 0.01), and somatic depressive symptoms (walking/bicycling: ß = -0.053, 95%CI = -0.075, -0.030, P < 0.01; MVPA: ß = -0.085, 95%CI = -0.100, -0.071, P < 0.01) were also significantly lower after replacing SB time with either walking/bicycling or MVPA. However, replacing 30 min/day PA with SB time represented with higher depressive symptoms. Conclusions: Replacing SB time with walking/bicycling or MVPA is beneficial in lowering the depressive symptoms among overweight/obese adults. Owing to the benefits of PA on depression, strategies promoting PA participation, are necessary for better social/mental well-being and healthy society.
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Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene complex [Ru(η6-p-cym)(BTBpy)Cl] (RuBTB) is developed for ferroptosis-enhanced antitumor immunity and drug resistance reversal via glutathione (GSH) metabolism imbalance. RuBTB shows significantly enhanced antiproliferation activity against cisplatin (CDDP)-resistant lung cancer cells (A549R), with 26.35-fold better anticancer effects than CDDP. Immunogenic ferroptosis is induced by GSH depletion/glutathione peroxidase 4 (GPX4) inactivation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in RuBTB-treated cells. Mechanism studies indicate that RuBTB regulates ferroptosis and immune-related pathways, coordinating with GSH metabolism-mediated glutathione S-transferase (GST) inhibition to reverse drug resistance in platinum-combined therapy. Tumor vaccination experiments demonstrate the intensified antitumor effects endowed by highly immunogenic ferroptosis in vivo. This study provides the first example of a metal-arene complex for achieving satisfactory ferroptosis therapeutic effects with efficient immunogenicity to overcome drug resistance in metal-based immunochemotherapy.
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Source monitoring (SM) refers to attributing sources of information. There are various methods for measuring SM in children. We searched the PubMed, PsycINFO, Embase, Web of Science and Cochrane Library databases from their inception to February 24, 2023, to summarize the methods and measures of SM in children, identifying 141 studies. The procedure for the SM tasks encompassed encoding, interval and testing. The encoding tasks were classified into ground-based activities (n = 67), computer-based experiments (n = 42) and mixed methods (n = 34). The testing approaches were categorized into old/new recognition and source discrimination, n-alternative forced-choice, yes/no questions and recall/direct questions. Among 10 commonly used indicators, source-correct, source-incorrect, discrimination score and source accuracy were recommended to present the SM function. We also discussed the advantages and disadvantages of different SM methods in children, providing a reference for researchers to design and select SM measurements that meet their research objectives.
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AIM: To construct learning objectives and educational content for emergency triage nurses based on core competencies. BACKGROUND: The core competencies of emergency triage nurses has an impact on the quality of medical services and patient treatment outcomes. However, research on learning objectives and educational content aimed at cultivating the core competencies of emergency triage nurses is limited. DESIGN: A Delphi study. METHODS: To develop a draft of the teaching objectives and content for emergency triage nurses based on core competencies, a literature review, semistructured interviews and expert group meetings were conducted. Then, 24 experts were invited to provide feedback on the draft and suggest revisions through two rounds of Delphi consultation. RESULTS: Consensus was reached on six core competencies, 30 learning objectives and 43 educational contents. The response rate for the two rounds of expert questionnaires was 100â¯%, with 79.2â¯% and 54.2â¯% of the experts providing feedback in the first and second rounds, respectively. The judgement coefficient (Ca) was 0.910, the familiarity coefficient (Cs) was 0.917 and the authority coefficient (Cr) was 0.914. The Kendall's W coefficients for the two rounds of expert inquiry were 0.321 and 0.334, indicating a statistically significant difference (P<0.05). CONCLUSIONS: Constructing learning objectives and educational content for emergency triage nurses based on core competencies is scientific and reliable and can provide a reference for the training and management of emergency triage nurses.
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Conventional dielectric solid materials, both natural and artificial, lack electromagnetic self-duality and thus require additional coatings to achieve impedance matching with free space. Here, we present a class of dielectric metamaterials that are effectively self-dual and vacuum-like, thereby exhibiting full-polarization omnidirectional impedance matching as an unusual Brewster effect extended across all incident angles and polarizations. With both birefringence and reflection eliminated regardless of wavefront and polarization, such anisotropic metamaterials could establish the electromagnetic equivalence with "stretched free space" in transformation optics, as substantiated through full-wave simulations and microwave experiments. Our findings open a practical pathway for realizing unprecedented polarization-independence and omnidirectional impedance-matching characteristics in pure dielectric solids.
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Nucleic acid strand displacement is a pivotal concept in dynamic nucleic acid nanotechnologies, which has been extensively investigated and applied across various fields. Compared with DNA systems, the genetically expressed RNA strand displacement technology offers unique advantages for construction of genetic circuits in living cells, where RNA expression and modulation may be seamlessly integrated into the genomic network for long-term and stable regulations of diversified biological functionalities. This Concept paper provides an overview of previous efforts on developments of synthetic gene circuits through utilization of RNA strand displacement, including our endeavors in this field. Moreover, future prospects, potential applications and challenges of the genetically expressed RNA strand displacement technology are also discussed.
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Transposon mutagenesis screening of Bacillus subtilis YB-1471, a novel rhizosphere biocontrol agent of Fusarium crown rot (FCR) of wheat, resulted in the identification of orf04391, linked to reduced biofilm formation. The gene encodes a protein possessing a putative tertiary structure of a "double-wing" DNA-binding domain. Expression of orf04391 increased during biofilm development in stationary cultures and during rapid growth in shaking cultures. An orf04391 deletion strain showed reduced biofilm production related to lower levels of the extracellular matrix, and the mutant also had reduced sporulation, adhesion, root colonization, and FCR biocontrol efficiency. Transcriptome analysis of YB-1471 and Δorf04391 in stationary culture showed that the loss of orf04391 resulted in altered expression of numerous genes, including sinI, an initiator of biofilm formation. DNA binding was shown with his-tagged Orf04391 binding to the sinIR operon in vivo and in vitro. Orf04391 appears to be a transcriptional regulator of biofilm formation in B. subtilis through the Spo0A-SinI/SinR pathway.
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Bacillus subtilis , Proteínas de Bactérias , Fusarium , Doenças das Plantas , Triticum , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Biofilmes/crescimento & desenvolvimento , Fusarium/genética , Fusarium/metabolismo , Fusarium/fisiologia , Regulação Bacteriana da Expressão Gênica , Doenças das Plantas/microbiologia , Triticum/microbiologiaRESUMO
Allosteric drugs offer a new avenue for modern drug design. However, the identification of cryptic allosteric sites presents a formidable challenge. Following the allostery nature of residue-driven conformation transition, we propose a state-of-the-art computational pipeline by developing a residue-intuitive hybrid machine learning (RHML) model coupled with molecular dynamics (MD) simulation, through which we can efficiently identify the allosteric site and allosteric modulator as well as reveal their regulation mechanism. For the clinical target ß2-adrenoceptor (ß2AR), we discover an additional allosteric site located around residues D792.50, F2826.44, N3187.45 and S3197.46 and one putative allosteric modulator ZINC5042. Using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and protein structure network (PSN), the allosteric potency and regulation mechanism are probed to further improve identification accuracy. Benefiting from sufficient computational evidence, the experimental assays then validate our predicted allosteric site, negative allosteric potency and regulation pathway, showcasing the effectiveness of the identification pipeline in practice. We expect that it will be applicable to other target proteins.
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Sítio Alostérico , Aprendizado de Máquina , Receptores Adrenérgicos beta 2 , Humanos , Regulação Alostérica , Desenho de Fármacos , Simulação de Dinâmica Molecular , Conformação Proteica , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/metabolismoRESUMO
BACKGROUND: Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. METHODS: A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). RESULTS: In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334-5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836-21.328, P < 0.001). CONCLUSIONS: Compared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.
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Alanina , Antivirais , Hepatite B Crônica , Lipídeos , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Antivirais/uso terapêutico , Alanina/uso terapêutico , Lipídeos/sangue , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/induzido quimicamente , Adenina/análogos & derivados , Adenina/uso terapêutico , Triglicerídeos/sangue , Colesterol/sangueRESUMO
Carbon dioxide (CO2) serves as a crucial greenhouse gas that traps heat and regulates the Earth's temperature. High spatiotemporal resolution CO2 estimation can provide valuable information to understand the characteristics of fine-scale climate change trends and to formulate more effective emission reduction strategies. This study presents a spatiotemporal ResNet model (ST-ResNet) specifically developed to estimate the highest resolution (1 km × 1 km) daily column-averaged dry-air mole fraction of CO2 (XCO2) in China from 2015 to 2020. The ST-ResNet model excels in estimating XCO2 by comprehensively considering the complex relationships between XCO2 and its various influencing factors, while efficiently capturing both temporal and spatial correlations, thereby demonstrating remarkable generalization capability. The results show that the ST-ResNet generates a highly accurate XCO2 dataset, outperforming the traditional ResNet. Ground-based validation results further confirm the high accuracy and spatiotemporal resolution of our estimated data product. Using this dataset, the spatial and temporal characteristics of XCO2 across the entire China and several urban agglomerations have been analyzed. The high spatiotemporal resolution estimated XCO2 dataset for China is made publicly available at [https://doi.org/10.6084/m9.figshare.25272868], offering substantial potential for fine-scale carbon research.
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Background: The clinical significance of gastrointestinal (GI) symptoms in patients with severe fever and thrombocytopenia syndrome (SFTS) is poorly characterized. This study aimed to determine the prevalence and effect of GI symptoms on the prognosis of patients with SFTS. Methods: This was a retrospective multi-center cohort study that included hospitalized patients with SFTS from three institutions between October 2010 and August 2022. The risk factors for mortality and intensive care unit (ICU) admission were identified by Cox and logistic regression analyses, respectively. Kaplan-Meier curves were used to analyze the cumulative mortality risk. Results: Among 304 patients, the median age was 62.0 years and 51.0 % of the patients were male. A total of 202 patients (66.4 %) had at least one GI symptom on admission. Diarrhea (69.8 %) and nausea (57.4 %) were the most common symptoms. Patients with GI symptoms had lower male proportion (46.0 % vs. 60.8 %, P = 0.015), higher aspartate aminotransferase (177.5 U/L vs. 118.0 U/L, P = 0.010) and lactic dehydrogenase (771.0 U/L vs. 666.5 U/L, P = 0.017) levels than that of patients without GI symptoms. However, there was no significant difference in mortality rates (23.8 % vs. 21.6 %, P = 0.668) and ICU admission (14.4 % vs. 12.7 %, P = 0.701) between SFTS patients with and without GI symptoms. Multivariate analysis suggested that GI symptoms at admission were not associated with mortality and ICU admission. Conclusions: GI symptoms are common in patients with SFTS. However, the presence of GI symptoms was not an independent risk factor for poor prognosis.
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Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.
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Antivirais , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Hepatite B Crônica , Interferon-alfa , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Anticorpos Anti-Hepatite B/sangue , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Antígenos E da Hepatite B/sangue , Interferon-alfa/uso terapêutico , Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Resultado do Tratamento , Quimioterapia Combinada , Soroconversão , Adulto Jovem , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/imunologiaRESUMO
BACKGROUND: Ferroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects. AIM OF THE STUDY: We aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action. MATERIALS AND METHODS: We used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin. RESULTS: In this study, we found that ferroptosis's inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased. CONCLUSIONS: This study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.
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Carcinoma Hepatocelular , Proliferação de Células , Coenzima A Ligases , Curcumina , Ferroptose , Neoplasias Hepáticas , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Ferroptose/efeitos dos fármacos , Curcumina/farmacologia , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Animais , Camundongos , Coenzima A Ligases/metabolismo , Regulação para Cima/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Camundongos Nus , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Células Hep G2 , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells' vulnerabilities, potentially marking a significant advancement in managing this deadly disease.
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Adenoviridae , Neoplasias Pulmonares , Terapia Viral Oncolítica , Vírus Oncolíticos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-met , Sirolimo , Humanos , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Regiões Promotoras Genéticas/genética , Adenoviridae/genética , Linhagem Celular Tumoral , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologiaRESUMO
With the rapid advancement of intelligent manufacturing technologies, the operating environments of modern robotic arms are becoming increasingly complex. In addition to the diversity of objects, there is often a high degree of similarity between the foreground and the background. Although traditional RGB-based object-detection models have achieved remarkable success in many fields, they still face the challenge of effectively detecting targets with textures similar to the background. To address this issue, we introduce the WoodenCube dataset, which contains over 5000 images of 10 different types of blocks. All images are densely annotated with object-level categories, bounding boxes, and rotation angles. Additionally, a new evaluation metric, Cube-mAP, is proposed to more accurately assess the detection performance of cube-like objects. In addition, we have developed a simple, yet effective, framework for WoodenCube, termed CS-SKNet, which captures strong texture features in the scene by enlarging the network's receptive field. The experimental results indicate that our CS-SKNet achieves the best performance on the WoodenCube dataset, as evaluated by the Cube-mAP metric. We further evaluate the CS-SKNet on the challenging DOTAv1.0 dataset, with the consistent enhancement demonstrating its strong generalization capability.
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This cross-sectional study compares rates of hepatitis B treatment eligibility among treatment-naive patients according to the World Health Organization (WHO) 2024 guidelines with eligibility rates across other international guidelines.
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Guias de Prática Clínica como Assunto , Organização Mundial da Saúde , Humanos , Hepatite B/tratamento farmacológico , Masculino , Feminino , Adulto , Antivirais/uso terapêutico , Pessoa de Meia-IdadeRESUMO
BACKGROUND: During wound healing, fibroblast to myofibroblast transition is required for wound contraction and remodeling. While hypoxia is an important biophysical factor in wound microenvironment, the exact regulatory mechanism underlying hypoxia and fibroblast-to-myofibroblast transition remains unclear. We previously found that tetraspanin CD9 plays an important role in oxygen sensing and wound healing. Herein, we investigated the effects of physiological hypoxia on fibroblast-to-myofibroblast transition and the biological function and mechanism of CD9 in it. METHODS: Human skin fibroblasts (HSF) and mouse dermis wounds model were established under physiological hypoxia (2% O2). The cell viability and contractility of HSF under hypoxia were evaluated by CCK8 and collagen gel retraction, respectively. The expression and distribution of fibroblast-to-myofibroblast transition markers and CD9 in HSF were detected by Western blotting and immunofluorescence. CD9 slicing and overexpressing HSFs were constructed to determine the role of CD9 by small interfering RNA and recombinant adenovirus vector. The association of TßR2 and TßR1 was measured by immunoprecipitation to explore the regulatory mechanism. Additionally, further validation was conducted on mouse dermis wounds model through histological analysis. RESULTS: Enhanced fibroblast-to-myofibroblast transition and upregulated CD9 expression was observed under hypoxia in vitro and in vivo. Besides, reversal of fibroblast-to-myofibroblast transition under hypoxia was observed when silencing CD9, suggesting that CD9 played a key role in this hypoxia-induced transition. Moreover, hypoxia increased fibroblast-to-myofibroblast transition by activating TGF-ß1/Smad2/3 signaling, especially increased interaction of TßR2 and TßR1. Ultimately, CD9 was determined to directly affect TßR1-TßR2 association in hypoxic fibroblast. CONCLUSION: Collectively, these findings suggest that CD9 promotes TßR2-TßR1 association, thus driving the transition of human dermal fibroblasts to myofibroblast under hypoxia.