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BACKGROUND: Bibliometric analysis of liver cancer research, particularly in immunotherapy, reveals crucial insights. The US leads in liver cancer mortality but ranks fifth globally. OBJECTIVE: Scopus database analysis identified 2,349 papers, with the top 100 ranging from 127 to 4,959 citations. Notably, "Microenvironmental Regulation of Tumours Progression and Metastasis" in the Journal of Nature Medicine garnered the highest citations. METHODS: Journals like the Journal of Hepatology, Hepatology, and Nature Reports Clinical Oncology contributed significantly. Understanding molecular mechanisms and prognostic indicators is paramount for advancing combination therapies. RESULTS: For better patient outcomes, research trends in liver cancer immunotherapy point to improved treatment protocols, knowledge of the tumor microenvironment, combining therapies, predicting disease course, international cooperation, sophisticated surgical techniques, early detection, oncolytic virotherapy, and patient-centered care. CONCLUSIONS: This research underscores immunotherapy's pivotal role and encourages further exploration, offering valuable insights into liver cancer treatment trends.
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Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.
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Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Osteoporose/metabolismo , Osteoporose/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Massa Corporal , Idoso , Circunferência da Cintura , Obesidade/complicações , Obesidade/metabolismo , Relação Cintura-QuadrilRESUMO
OBJECTIVE: This study compared the outcomes of radiofrequency ablation (RFA) and microwave ablation (EMA) for treating lower limb varicose veins. METHODS: Patients who underwent RFA (n = 240) or EMA (n = 209) at our institute from December 2020 to August 2022 were included in this retrospective investigation. Follow-up outcomes included active vein occlusion rate, Venous Clinical Severity Score (VCSS), the Aberdeen Varicose Vein Questionnaire (AVVQ), and Chronic Insufficiency Venous Quality of Life questionnaire-14 (CIVIQ-14)score. RESULTS: There was no significant difference in the active vein occlusion rate between the two groups after the operation (p > .05). Compared to pre-surgery scores, both groups showed substantial improvement in VCSS, AVVQ, and CIVIQ-14 scores(p < .05), there was no significant difference in these scores in either group (p > .05). CONCLUSION: Intravenous radiofrequency and microwave ablation effectively improve the quality of life for patients with lower limb varicose veins, with low post-operative complication and recurrence rates.
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Background: Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Methodology: Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. Results: RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. Conclusion: The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.
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OBJECTIVE: The specific anatomic characteristics of the right internal spermatic vein (ISV) are pivotal factors in embolism failure. However, the inherent angles and configurations of the right ISV remain incompletely explored. This study aimed to address this gap by conducting a thorough investigation into the specific anatomic characteristics of the right ISV using imaging analysis in southwest China. METHODS: This retrospective study analyzed the imaging data of 1000 male patients who underwent multidetector spiral computed tomography (MCT). Anatomic characteristics of the right ISV, including position, type, distance, and angle, were also evaluated. RESULTS: The most common anatomic type (87.8%) of the right ISV was direct drainage into the inferior vena cava, with 90% of the angles below 25.7°. There were 22 cases (2.2%) with parallel right spermatic veins. In the axial plane, the right ISV (86.4%) was located in the third and fourth quadrants. The diameter at the entrance of the right ISV ranged from 2.7-3.8 mm. When the right ISV drained into the inferior vena cava, 83% of cases were located within 40 mm distance below the ostium of the right renal vein, while during draining into the right renal vein, the average distance from the main vein was 6.3 mm. CONCLUSION: This study concluded that MCT can be used to evaluate the anatomical characteristics of the right ISV. The optimal interventional approach was through the jugular vein route to locate the ISV opening and improve the success rate of the embolization.
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Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.
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Catequina , Etanol , Fator 2 Relacionado a NF-E2 , NF-kappa B , Transdução de Sinais , Etanol/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , NF-kappa B/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
BACKGROUND: Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach. METHODS: This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran's Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes. RESULTS: This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran's Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods. CONCLUSIONS: This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Doenças da Glândula Tireoide , Trombose Venosa , Humanos , Trombose Venosa/genética , Trombose Venosa/epidemiologia , Análise da Randomização Mendeliana/métodos , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/complicações , Predisposição Genética para Doença , Hipertireoidismo/genética , Hipertireoidismo/complicaçõesRESUMO
A general strategy for confining Pd, Ti-bimetallic sites in the MFI zeolite by crystal epitaxy was developed. The tailored spatial intimacy of the bimetallic sites demonstrated distinct catalytic performance for the oxidation of benzylalcohol. The related mechanism was clarified and afforded a valuable pathway for rational catalyst design.
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The influence of organic carbon on the proliferation of antibiotic resistance genes (ARGs) in the soil has been widely documented. However, it is unclear how soil organic carbon (SOC) interacts with the evolution of antibiotic resistance in bacteria. Here, we examined the variations in ARGs abundance during SOC mineralization and explored the microbiological mechanisms and key metabolic pathways involved in their coevolution. The results showed that the SOC mineralization rate was closely correlated with ARGs abundance (p < 0.05). High organic carbon (OC) mineralization was conducive to the occurrence of multidrug resistance genes. For example, multidrug_transporter and mexB increased 2.26 and 7.83 times from the initial level. The competitor (stress) evolutionary strategy model revealed that higher OC inputs drive environmental microorganisms to evolve from stress tolerant to high resistance and strong adaptation. Meta-genomic and transcriptomic analyses revealed that the conversion process of pyruvate to acetyl-CoA to acetate was the critical metabolic pathway for the co-regulation of antibiotic resistance. Gene deletion validation trials have demonstrated that the key functional genes (ackA and pta) involved in this process can modulate the development of vancomycin and multidrug resistance. This outcome provides a preliminary framework for microbial mechanisms that target the co-regulation of microbial OC conversion and the evolution of antibiotic resistance.
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Carbono , Microbiologia do Solo , Solo , Carbono/metabolismo , Carbono/química , Solo/química , Bactérias/metabolismo , Bactérias/genética , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes BacterianosRESUMO
Purpose: To establish, validate, and clinically evaluate a nomogram for predicting the risk of sarcopenia in patients with peripheral arterial disease (PAD) based on clinical and lower extremity computed tomography angiography (LE-CTA) imaging characteristics. Methods: Clinical data and CTA imaging features from 281 PAD patients treated between January 1, 2019, and May 1, 2023, at two hospitals were retrospectively analyzed using binary logistic regression to identify the independent risk factors for sarcopenia. These identified risk factors were used to develop a predictive nomogram. The nomogram's effectiveness was assessed through various metrics, including the receiver operating characteristic (ROC) curve, area under the curve (AUC), concordance index (C-index), Hosmer-Lemeshow (HL) test, and calibration curve. Its clinical utility was demonstrated using decision curve analysis (DCA). Results: Several key independent risk factors for sarcopenia in PAD patients were identified, namely age, body mass index (BMI), history of coronary heart disease (CHD), and white blood cell (WBC) count, as well as the severity of luminal stenosis (P < 0.05). The discriminative ability of the nomogram was supported by the C-index and an AUC of 0.810 (95% confidence interval: 0.757-0.862). A robust concordance between predicted and observed outcomes was reflected by the calibration curve. The HL test further affirmed the model's calibration with a P-value of 0.40. The DCA curve validated the nomogram's favorable clinical utility. Lastly, the model underwent internal validation. Conclusions: A simple nomogram based on five independent factors, namely age, BMI, history of CHD, WBC count, and the severity of luminal stenosis, was developed to assist clinicians in estimating sarcopenia risk among PAD patients. This tool boasts impressive predictive capabilities and broad utility, significantly aiding clinicians in identifying high-risk individuals and enhancing the prognosis of PAD patients.
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BACKGROUND: Fibronectin type III domain containing 3B (FNDC3B), a member of the fibronectin type III domain-containing protein family, has been indicated in various malignancies. However, the precise role of FNDC3B in the progression of pancreatic cancer (PC) still remains to be elucidated. METHODS: In this study, we integrated data from the National Center for Biotechnology Information, the Cancer Genome Atlas, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets to analyze FNDC3B expression and its association with various clinicopathological parameters. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, along with Gene Set Enrichment Analysis (GSEA), single sample Gene Set Enrichment Analysis (ssGSEA) and estimate analysis were recruited to delve into the biological function and immune infiltration based on FNDC3B expression. Additionally, the prognostic estimation was conducted using Cox analysis and Kaplan-Meier analysis. Subsequently, a nomogram was constructed according to the result of Cox analysis to enhance the prognostic ability of FNDC3B. Finally, the preliminary biological function of FNDC3B in PC cells was explored. RESULTS: The study demonstrated a significantly higher expression of FNDC3B in tumor tissues compared to normal pancreatic tissues, and this expression was significantly associated with various clinicopathological parameters. GSEA revealed the involvement of FNDC3B in biological processes and signaling pathways related to integrin signaling pathway and cell adhesion. Additionally, ssGSEA analysis indicated a positive correlation between FNDC3B expression and infiltration of Th2 cells and neutrophils, while showing a negative correlation with plasmacytoid dendritic cells and Th17 cells infiltration. Kaplan-Meier analysis further supported that high FNDC3B expression in PC patients was linked to shorter overall survival, disease-specific survival, and progression-free interval. However, although univariate analysis demonstrated a significant correlation between FNDC3B expression and prognosis in PC patients, this association did not hold true in multivariate analysis. Finally, our findings highlight the crucial role of FNDC3B expression in regulating proliferation, migration, and invasion abilities of PC cells. CONCLUSION: Despite limitations, the findings of this study underscored the potential of FNDC3B as a prognostic biomarker and its pivotal role in driving the progression of PC, particularly in orchestrating immune responses.
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Domínio de Fibronectina Tipo III , Neoplasias Pancreáticas , Humanos , Células Dendríticas , Nomogramas , Neoplasias Pancreáticas/genética , PrognósticoRESUMO
BACKGROUND: The rarity yet high malignancy of gallbladder adenocarcinoma (GBA) endows it with a distinctive nature. Radical resection remains the foremost therapeutic approach for GBA, while the impact of early recurrence and metastasis on patient prognosis necessitates the utilization of adjuvant chemotherapy (AC). Despite numerous previous studies on this topic, a consensus regarding the authentic efficacy of AC has yet to be reached. METHODS: We conducted an updated retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2020 to explore the association between AC and survival outcomes in patients with resected GBA. RESULTS: Our study included 2782 patients from the SEER database, with further evaluation of 843 patients in each cohort following meticulous execution of a 1:1 propensity score matching. Remarkably, the AC cohort exhibited a significant survival advantage when juxtaposed against the non-AC cohort. Multivariable Cox regression analysis identified age at diagnosis, year at diagnosis, grade, AJCC T stage, AJCC N stage as well as AC as independent prognostic factors. Furthermore, our findings unveiled that poor/undifferentiated tumor histology, pathological T2 or higher category and pathological N1 category were significantly associated with improved survival when treated with AC while simultaneously observing improved survival across all age categories. CONCLUSION: These results provide additional evidence supporting the survival benefits of AC and offer guidance for personalized therapy in patients with resected GBA.
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Adenocarcinoma , Neoplasias da Vesícula Biliar , Humanos , Estudos Retrospectivos , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Estadiamento de NeoplasiasRESUMO
PURPOSE: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes. However, its specific role and molecular mechanism in lung cancer radioresistance remain to be clarified. METHODS AND MATERIALS: The expression levels of OTUB1 in paired lung cancer tissues were determined by immunohistochemistry. In vitro and in vivo experiments were conducted to investigate the impact of OTUB1 on the growth and proliferation of lung cancer. Coimmunoprecipitation and Western blotting techniques were performed to examine the interaction between OTUB1 and CHK1. The DNA damage response was measured by comet tailing and immunofluorescence staining. KEGG pathways and Gene Ontology terms were analyzed based on RNA sequencing. RESULTS: Our findings reveal a high frequency of OTUB1 overexpression, which is associated with an unfavorable prognosis in patients with lung cancer. Through comprehensive investigations, we demonstrate that OTUB1 depletion impairs the process of DNA damage repair and overcomes radioresistance. In terms of the underlying mechanism, our study uncovers that OTUB1 deubiquitinates and stabilizes CHK1, which enhances CHK1 stability, thereby regulating DNA damage and repair. Additionally, we identify CHK1 as the primary downstream effector responsible for mediating the functional effects exerted by OTUB1 specifically in lung cancer. Importantly, OTUB1 has the potential to be a valuable marker for improving the efficacy of radiation therapy for lung adenocarcinoma. CONCLUSIONS: These findings unveil a novel role for OTUB1 in enhancing radioresistance by deubiquitination and stabilization of the expression of CHK1 in lung cancer and indicate that targeting OTUB1 holds great potential as an effective therapeutic approach for enhancing the efficacy of radiation therapy in lung cancer.
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Quinase 1 do Ponto de Checagem , Progressão da Doença , Neoplasias Pulmonares , Tolerância a Radiação , Ubiquitinação , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Quinase 1 do Ponto de Checagem/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Proliferação de Células , Reparo do DNA , Cisteína Endopeptidases/metabolismo , Dano ao DNA , Proteases Específicas de Ubiquitina/metabolismo , Feminino , Camundongos Nus , Enzimas Desubiquitinantes/metabolismo , Estabilidade ProteicaRESUMO
BACKGROUND: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases. The present study aimed to further investigate the roles of ADAMTS family members in aortic valve development and BAV formation. METHODS: Morpholino-based ADAMTS family gene-targeted screening for zebrafish heart outflow tract phenotypes combined with DNA sequencing in a 304 cohort BAV patient registry study was initially carried out to identify potentially related genes. Both ADAMTS gene-specific fluorescence in situ hybridization assay and genetic tracing experiments were performed to evaluate the expression pattern in the aortic valve. Accordingly, related genetic mouse models (both knockout and knockin) were generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) method to further study the roles of ADAMTS family genes. The lineage-tracing technique was used again to evaluate how the cellular activity of specific progenitor cells was regulated by ADAMTS genes. Bulk RNA sequencing was used to investigate the signaling pathways involved. Inducible pluripotent stem cells derived from both BAV patients and genetic mouse tissue were used to study the molecular mechanism of ADAMTS. Immunohistochemistry was performed to examine the phenotype of cardiac valve anomalies, especially in the extracellular matrix components. RESULTS: ADAMTS genes targeting and phenotype screening in zebrafish and targeted DNA sequencing on a cohort of patients with BAV identified ADAMTS16 (a disintegrin and metalloproteinase with thrombospondin motifs 16) as a BAV-causing gene and found the ADAMTS16 p. H357Q variant in an inherited BAV family. Both in situ hybridization and genetic tracing studies described a unique spatiotemporal pattern of ADAMTS16 expression during aortic valve development. Adamts16+/- and Adamts16+/H355Q mouse models both exhibited a right coronary cusp-noncoronary cusp fusion-type BAV phenotype, with progressive aortic valve thickening associated with raphe formation (fusion of the commissure). Further, ADAMTS16 deficiency in Tie2 lineage cells recapitulated the BAV phenotype. This was confirmed in lineage-tracing mouse models in which Adamts16 deficiency affected endothelial and second heart field cells, not the neural crest cells. Accordingly, the changes were mainly detected in the noncoronary and right coronary leaflets. Bulk RNA sequencing using inducible pluripotent stem cells-derived endothelial cells and genetic mouse embryonic heart tissue unveiled enhanced FAK (focal adhesion kinase) signaling, which was accompanied by elevated fibronectin levels. Both in vitro inducible pluripotent stem cells-derived endothelial cells culture and ex vivo embryonic outflow tract explant studies validated the altered FAK signaling. CONCLUSIONS: Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.
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Doença da Válvula Aórtica Bicúspide , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Humanos , Animais , Camundongos , Peixe-Zebra/genética , Doenças das Valvas Cardíacas/metabolismo , Células Endoteliais/metabolismo , Desintegrinas/genética , Desintegrinas/metabolismo , Hibridização in Situ Fluorescente , Valva Aórtica/metabolismo , Cardiopatias Congênitas/complicações , Matriz Extracelular/metabolismo , Trombospondinas/metabolismo , Metaloproteases/metabolismo , Proteínas ADAMTS/genética , Proteínas ADAMTS/metabolismoRESUMO
Background: The objective of this study was to explore the association between the sarcopenia index and abnormal liver function in adult individuals in the United States. Methodology: This study employed a rigorous cross-sectional analysis of data derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018. The primary objective was to investigate the correlation between the sarcopenia index and abnormal liver function. To achieve this, an advanced multivariate regression model was utilized, allowing for comprehensive analysis and meticulous adjustment of relevant variables. To ensure the robustness of the findings, a visually appealing smooth curve was constructed, and a two-stage regression model was applied for validation. Additionally, a detailed gender-stratified analysis was conducted to further explore the association between the sarcopenia index and abnormal liver function within distinct subgroups. Results: Through our rigorous participant selection process, a total of 1756 individuals were included in the study. The meticulously adjusted multivariate regression model revealed a significant negative association between the sarcopenia index and abnormal liver function, with an adjusted odds ratio (OR) of 0.73 and a 95% confidence interval (CI) ranging from 0.63 to 0.86. The robustness of this association was further supported by the visually appealing smooth curve plot. Moreover, in the gender-stratified subgroup analysis, after meticulous adjustment for confounding factors, notable differences in this association emerged (males: OR = 0.8, 95% CI: 0.66-0.98; females: OR = 0.61, 95% CI: 0.47-0.79). Conclusion: This cross-sectional study yields robust evidence indicating a negative correlation between the sarcopenia index and abnormal liver function, predominantly observed among females.
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Na+ plays a vital role in numerous physiological processes across humans and animals, necessitating a comprehensive understanding of Na+ transmembrane transport. Among the various Na+ pumps and channels, light-driven Na+-pumping rhodopsin (NaR) has emerged as a noteworthy model in this field. This review offers a concise overview of the structural and functional studies conducted on NaR, encompassing ground/intermediate-state structures and photocycle kinetics. The primary focus lies in addressing key inquiries: (1) unraveling the translocation pathway of Na+; (2) examining the role of structural changes within the photocycle, particularly in the O state, in facilitating Na+ transport; and (3) investigating the timing of Na+ uptake/release. By delving into these unresolved issues and existing debates, this review aims to shed light on the future direction of Na+ pump research.
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Rodopsina , Animais , Humanos , Rodopsina/química , Transporte BiológicoRESUMO
Microbial Na+ -pumping rhodopsin (NaR) is a promising optogenetic tool due to its unique ability to transport Na+ . Like most rhodopsin-based tools, NaR is limited to light-based control. In this study, our objective was to develop a novel mode of modulation for NaR beyond light control. By introducing a potential Cl- binding site near the putative Na+ release cavity, we engineered Nonlabens dokdonensis rhodopsin 2 (NdR2) to be modulated by Cl- , an essential chemical in organisms. The engineered NdR2 demonstrated an approximately two-fold increase in Na+ pump activity in the presence of 100â mM Cl- compared to Cl- -free solution. Increasing Cl- concentration decreased the lifetimes of the M and O intermediates accordingly. The analysis of competitive ion uptake suggested the bound Cl- may increase the Na+ affinity and selectivity. This chemical modulation allows for more diverse and precise control over cellular processes, advancing the development of next-generation optogenetic tools. Notably, our Cl- -modulated NdR2 establishes an innovative mechanism for linking Cl- to Na+ -related processes, with potential applications in optogenetic therapies for related diseases.
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Flavobacteriaceae , Rodopsina , Rodopsina/química , Rodopsina/metabolismo , Luz , Flavobacteriaceae/química , Flavobacteriaceae/metabolismo , Transporte de Íons , Sódio/metabolismoRESUMO
Engineering light-controlled K+ pumps from Na+-pumping rhodopsins (NaR) greatly expands the scope of optogenetic applications. However, the limited knowledge regarding the kinetic and selective mechanism of K+ uptake has significantly impeded the modification and design of light-controlled K+ pumps, as well as their practical applications in various fields, including neuroscience. In this study, we presented K+-dependent photocycle kinetics and photocurrent of a light-driven Na+ pump called Nonlabens dokdonensis rhodopsin 2 (NdR2). As the concentration of K+ increased, we observed the accelerated decay of M intermediate in the wild type (WT) through flash photolysis. In 100 mM KCl, the lifetime of the M decay was approximately 1.0 s, which shortened to around 0.6 s in 1 M KCl. Additionally, the K+-dependent M decay kinetics were also observed in the G263W/N61P mutant, which transports K+. In 100 mM KCl, the lifetime of the M decay was approximately 2.5 s, which shortened to around 0.2 s in 1 M KCl. According to the competitive model, in high KCl, K+ may be taken up from the cytoplasmic surface, competing with Na+ or H+ during M decay. This was further confirmed by the K+-dependent photocurrent of WT liposome. As the concentration of K+ increased to 500 mM, the amplitude of peak current significantly dropped to approximately ~60%. Titration experiments revealed that the ratio of the rate constant of H+ uptake (kH) to that of K+ uptake (kK) is >108. Compared to the WT, the G263W/N61P mutant exhibited a decrease of approximately 40-fold in kH/kK. Previous studies focused on transforming NaR into K+ pumps have primarily targeted the intracellular ion uptake region of Krokinobacter eikastus rhodopsin 2 (KR2) to enhance K+ uptake. However, our results demonstrate that the naturally occurring WT NdR2 is capable of intracellular K+ uptake without requiring structural modifications on the intracellular region. This discovery provides diverse options for future K+ pump designs. Furthermore, we propose a novel photocurrent-based approach to evaluate K+ uptake, which can serve as a reference for similar studies on other ion pumps. In conclusion, our research not only provides new insights into the mechanism of K+ uptake but also offers a valuable point of reference for the development of optogenetic tools and other applications in this field.
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Rodopsina , ATPase Trocadora de Sódio-Potássio , ATPase Trocadora de Sódio-Potássio/metabolismo , Rodopsina/metabolismo , Transporte de Íons , Transporte BiológicoRESUMO
The surface isotope radon measurement method (SIRMM) is widely used in fire source detection in abandoned mines. However, studies on the long-distance migration of radon during coal spontaneous combustion are lacking, which hinders the further popularization of this technology in coal fire prevention and control. For this reason, the migration law of radon in overlying strata in fire areas was studied through experiments and numerical simulation. The radon exhalation concentration of coal was found to increase at first and then decrease in the range of 30-350 °C through experiments. The radon concentration reaches the maximum value (557.1 Bq/m3) at 150 °C, which is 6.3 times higher than that at 30 °C. Based on the radon source term obtained by fitting the experimental data, the radon migration model of coal spontaneous combustion in abandoned goaf was constructed, and the dynamic distribution characteristics of the airflow, temperature, and radon concentration fields in the overlying strata area were analyzed. The internal relationship between surface radon and underground fire source was discussed. The simulation results revealed the sharp change in the porosity of the overlying rock causes radon concentration at the interface between the caving and fissure zones to increase continually with the process of spontaneous combustion, providing material and energy support for the long-distance radon migration. When the maximum temperature of the coal pile reaches 70 °C, the concentration of radon released from the coal pile increases rapidly to 13696 Bq/m3, and the radon from the underground space appears on the surface at this temperature. In the range of 70-150 °C, with rapid increase in radon released from coal piles, the surface concentration of radon also increased rapidly to 225 Bq/m3. At the high-temperature stage exceeding 150 °C, the concentration of radon released from coal piles exhibited a downward trend, resulting in a decrease in the rate of increase of radon concentration on the surface. A close relationship between the surface radon concentration and underground fire source temperature in the process of coal spontaneous combustion was observed. In the spatial position, the peak position of radon on the surface was highly consistent with that of the fire source longitudinally, which ensures the accuracy of the SIRMM to determine the location of the hidden fire source. This suggests that the SIRMM can accurately evaluate the fire source's temperature and fire area's development trend.
Assuntos
Minas de Carvão , Incêndios , Monitoramento de Radiação , Radônio , Radônio/análise , Combustão Espontânea , Carvão Mineral/análise , Monitoramento de Radiação/métodos , Incêndios/prevenção & controleRESUMO
Background: Acute cholangitis is a severe inflammatory disease associated with an infection of the biliary system, which can lead to complications and adverse outcomes. The existing nomogram-based risk assessment methods largely rely on a limited set of clinical features and laboratory indicators, and are mostly constructed using univariable models, which have limitations in predicting the severity. This study aims to develop a nomogram-based model that integrates multiple variables to improve risk prediction for acute cholangitis. Methods: Data were retrospectively collected from 152 patients with acute cholangitis who attended the People's Hospital of Jiangsu University between January 2019 and March 2022, and were graded as having mild to moderate versus severe cholangitis according to the 2018 Tokyo guidelines. Univariate and multivariate analyses were employed to discern independent risk factors associated with severe acute cholangitis, which were subsequently integrated into a nomogram model. The efficacy of the model was appraised by leveraging Receiver Operating Characteristic (ROC) curves, calibration curves, and Decision Curve Analysis (DCA). Results: Aspartate to alanine transaminase ratio (Transaminase ratio or TR), Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and D-dimer (DD) levels were independent risk factors for severe acute cholangitis. A nomogram model was constructed based on these 4 risk factors. ROC and calibration curves were well differentiated and calibrated. DCA had a high net gain in the range of 7% to 83%. The above model was tested internally. According to the nomogram model when patients using characteristic curve critical values were divided into a low-risk group and a high-risk group, the incidence in the high-risk group was significantly higher than in the low-risk group. Conclusion: This nomogram model may provide clinicians with an effective tool to predict the potential risk of severe acute cholangitis in patients and guide informed intervention measures and treatment decisions.