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We present here a novel paired electrocatalysis-enabled convenient synthesis of the (E)-vinyl sulfoximines through the cross-coupling reaction of sulfinamides and olefins. This protocol showed a broad substrate scope and excellent E selectivity of products under metal- and oxidant-free conditions. A preliminary mechanistic study suggested that fluorinated sulfoximine generated from anodic oxidation of sulfinamide was the key intermediate that was then converted into the sulfonimidoyl radical at the cathode with the help of DBU in this reaction.

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BACKGROUND: The KT/HAK/KUP is the largest K+ transporter family in plants, playing crucial roles in K+ absorption, transport, and defense against environmental stress. Sweet watermelon is an economically significant horticultural crop belonging to the genus Citrullus, with a high demand for K+ during its growth process. However, a comprehensive analysis of the KT/HAK/KUP gene family in watermelon has not been reported. RESULTS: 14 KT/HAK/KUP genes were identified in the genomes of each of seven Citrullus species. These KT/HAK/KUPs in watermelon were unevenly distributed across seven chromosomes. Segmental duplication is the primary driving force behind the expansion of the KT/HAK/KUP family, subjected to purifying selection during domestication (Ka/Ks < 1), and all KT/HAK/KUPs exhibit conserved motifs and could be phylogenetically classified into four groups. The promoters of KT/HAK/KUPs contain numerous cis-regulatory elements related to plant growth and development, phytohormone response, and stress response. Under K+ deficiency, the growth of watermelon seedlings was significantly inhibited, with cultivated watermelon experiencing greater impacts (canopy width, redox enzyme activity) compared to the wild type. All KT/HAK/KUPs in C. lanatus and C. amarus exhibit specific expression responses to K+-deficiency and drought stress by qRT-PCR. Notably, ClG42_07g0120700/CaPI482276_07g014010 were predominantly expressed in roots and were further induced by K+-deficiency and drought stress. Additionally, the K+ transport capacity of ClG42_07g0120700 under low K+ stress was confirmed by yeast functional complementation assay. CONCLUSIONS: KT/HAK/KUP genes in watermelon were systematically identified and analyzed at the pangenome level and provide a foundation for understanding the classification and functions of the KT/HAK/KUPs in watermelon plants.

Assuntos

Citrullus , Secas , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Citrullus/genética , Citrullus/metabolismo , Citrullus/crescimento & desenvolvimento , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Potássio/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Deficiência de Potássio/genética , Deficiência de Potássio/metabolismo , Regiões Promotoras Genéticas

RESUMO

In photoelectrochemical (PEC) sensors, traditional detection modes such as "signal-on", "signal-off", and "polarity-switchable" limit target signals to a single polarity range, necessitating novel design strategies to enhance the operational scope. To overcome this limitation, we propose, for the first time, a "polarity-transcendent" design concept that enables a continuous response across the polarity spectrum, significantly broadening the sensor's concentration detection range. This concept is exemplified in our new "background-enhanced signal-off polarity-switchable" (BESOPS) mode, where the model analyte let-7a activates a cascade shearing reaction of a DNAzyme walker in conjunction with CRISPR/Cas12a, quantitatively peeling off Cu2O-H2 strands at the Cu2O/TiO2 electrode interface to expose the TiO2 surface. This exposure generates an anodic photocurrent at the expense of the cathodic photocurrent from Cu2O/TiO2, facilitating a seamless transition of the target signal from cathodic to anodic. Through systematic experiments and comparative analyses, the BESOPS sensor demonstrates highly sensitive and precise quantification of let-7a, with a detection limit of 2.5 aM and a broad operating range of 10 aM to 10 nM. Its performance exceeds most reported sensor platforms, highlighting the significant potential of our polarity-transcendent design in expanding the operational range of PEC sensors. This innovative approach paves the way for developing next-generation PEC sensors with enhanced applicability and heightened sensitivity in various critical fields.

Assuntos

Técnicas Biossensoriais , Cobre , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Cobre/química , Titânio/química , MicroRNAs/análise , Humanos , Desenho de Equipamento , Sistemas CRISPR-Cas , Eletrodos

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BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Assuntos

Antituberculosos , Clofazimina , Ciclosserina , Diarilquinolinas , Levofloxacino , Linezolida , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Masculino , Feminino , Adulto , Clofazimina/uso terapêutico , Clofazimina/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Linezolida/uso terapêutico , Linezolida/administração & dosagem , Diarilquinolinas/uso terapêutico , Diarilquinolinas/administração & dosagem , Pessoa de Meia-Idade , China/epidemiologia , Ciclosserina/uso terapêutico , Ciclosserina/administração & dosagem , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Rifampina/uso terapêutico , Rifampina/administração & dosagem , Estudos Prospectivos , Quimioterapia Combinada , Resultado do Tratamento , Adulto Jovem , Idoso

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BACKGROUND: Pneumonia, a leading cause of morbidity and mortality worldwide, often necessitates Intensive Care Unit (ICU) admission. Accurate prediction of pneumonia mortality is crucial for tailored prevention and treatment plans. However, existing mortality prediction models face limited adoption in clinical practice due to their lack of interpretability. OBJECTIVE: This study aimed to develop an interpretable model for predicting pneumonia mortality in ICUs. Leveraging the Shapley Additive Explanation (SHAP) method, we sought to elucidate the Extreme Gradient Boosting (XGBoost) model and identify prognostic factors for pneumonia. METHODS: Conducted as a retrospective cohort study, we utilized electronic health records from the eICU-CRD (2014-2015) for all adult pneumonia patients. The first 24 h of each ICU admission records were considered, with 70% of the dataset allocated for model training and 30% for validation. The XGBoost model was employed, and performance was assessed using the area under the receiver operating characteristic curve (AUC). The SHAP method provided insights into the XGBoost model. RESULTS: Among 10,962 pneumonia patients, in-hospital mortality was 16.33%. The XGBoost model demonstrated superior predictive performance (AUC: 0.778 ± 0.016)) compared to traditional scoring systems and other machine learning method, which achieved an improvement of 10% points. SHAP analysis identified Aspartate Aminotransferase (AST) as the most crucial predictor. CONCLUSIONS: Interpretable predictive models enhance mortality risk assessment for pneumonia patients in the ICU, fostering transparency. AST emerged as the foremost predictor, followed by patient age, albumin, BMI et al. These insights, rooted in strong correlations with mortality, facilitate improved clinical decision-making and resource allocation.

Assuntos

Mortalidade Hospitalar , Unidades de Terapia Intensiva , Pneumonia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Medição de Risco/métodos , Aprendizado de Máquina , Idoso de 80 Anos ou mais , Fatores de Risco , Adulto

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Underwater imaging technology plays a pivotal role in marine exploration and reconnaissance, necessitating photodetectors (PDs) with high responsivity, fast response speed, and low preparation costs. This study presents the synergistic optimization of responsivity and response speed in self-powered photoelectrochemical (PEC)-type photodetector arrays based on oxygen-vacancy-tuned amorphous gallium oxide (a-Ga2O3) thin films, specifically designed for solar-blind underwater detection. Utilizing a low-cost one-step sputtering process with controlled oxygen flow, a-Ga2O3 thin films with varying oxygen vacancy (VO) concentrations are fabricated. By balancing the trade-offs among electrocatalytic reactions, charge transfer, carrier recombination, and trapping, both the responsivity and response speed of a-Ga2O3-based self-powered PEC-PDs are simultaneously improved. Consequently, the optimized PEC-PDs demonstrated exceptional performance, achieving a responsivity of 33.75 mA W-1 and response times of 12.8 ms (rise) and 31.3 ms (decay), outperforming the vast majority of similar devices. Furthermore, a pronounced positive correlation between anomalous transient photocurrent spikes and the concentration of VO defects is observed, offering compelling evidence for VO-mediated indirect recombination. Finally, the proof-of-concept solar-blind underwater imaging system, utilizing an array of self-powered PEC-PDs, demonstrated clear imaging capabilities in seawater. This work provides valuable insight into the potential for developing cost-effective, high-performance a-Ga2O3 thin-film-based PEC-PDs for advanced underwater imaging technology.

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The European sweet cherry Prunus avium (L.), a member of the Rosaceae family, is one of the most popular and economically valuable fruits. However, the rapid spread of gummosis and poor management practices have become the major obstacles to their production. To identify pathogenic microorganisms responsible for gummosis disease, we conducted observations comparing the garden of Bailuyuan, which heavily suffered from gummosis disease and horn beetle damage, with the orchard of Mayuhe, which only suffered from gummosis disease, both from Xi'an, Shaanxi, China. Samples were obtained from the healthy tissues and gummosis disease tissues that used the Illumina sequence of 16S rRNA and the internal transcribed spacer region (ITS) to identify bacterial and fungal communities in these samples. An alpha diversity analysis revealed a significantly higher fungal diversity of disease than in healthy tissue in the gummosis period. The results suggested that an imbalance in the fungal genera may be associated with gummosis disease. Species relative analyses showed some bacterial genera (Pelagibacterium, Halomonas, Azospirillum, Aquabacterium and Alistipes) and fungal genera (Penicillium, Alternaria and Rhodotorula) in the diseased tissues of gummosis. Among these, the increased relative abundance of the bacteria genes Halomonas, Pelagibacterium, Chelativorans, Pantoea, Aquabacterium, Alternaria and fungi genes Penicillium, Cystobasidium, Rhodotorula may be associated with gummosis of P. avium. The bacterial genera Methylobacterium, Psychroglaciecola, Aeromonas, Conexibacter and fungal genera Didymella, Aureobasidium, Mycosphaerella, Meyerozyma are probably antagonists of the pathogen of gummosis. These findings are an initial step in the identification of potential candidates for the biological control of the disease.

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In patients with diabetes, chronic hyperglycemia impairs immune function at wound sites, increasing susceptibility to infections, prolonging inflammation, and delaying healing. This study aimed to develop wound dressings that control bacterial infections and accelerate healing. Phloretin (PHL), which has antibacterial and anti-inflammatory properties, was encapsulated with γ-cyclodextrin (γ-CD) to form a PHL@CD complex with enhanced bioavailability. This complex was incorporated into nanofiber wound dressings composed of polycaprolactone and natural silk protein. The resulting dressings exhibited favorable physical and chemical properties, including nutrient transport and gas exchange, which are essential for wound healing. The nanofiber membranes exhibited antibacterial activity against Staphylococcus aureus (90.31 ± 4.41 % inhibition), with high antioxidant capacity (91.48 ± 0.33 % ABTS scavenging) and blood compatibility. The membranes also promoted cell viability. Importantly, the nanofiber dressings accelerated wound healing in a diabetic mouse model by reducing the duration of inflammation. The novel nanofiber wound dressing can significantly improve the treatment of diabetic wounds.

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Purpose: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. Patients and Methods: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs. Results: After false discovery rate correction, patients with MDD exhibited higher CD81 levels (P FDR = 0.040) and lower BDNF levels (P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (P FDR = 0.002) and Alix (P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (P FDR = 0.046), while BDNF levels normalized to CD81 increased (P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334). Conclusion: This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.

Assuntos

Astrócitos , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo , Transtorno Depressivo Maior , Vesículas Extracelulares , Plasticidade Neuronal , Humanos , Fator Neurotrófico Derivado do Encéfalo/sangue , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Masculino , Feminino , Plasticidade Neuronal/fisiologia , Adulto , Pessoa de Meia-Idade , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Biomarcadores/sangue , Astrócitos/metabolismo , Tetraspanina 28/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Estudos de Casos e Controles , Proteínas de Ligação ao Cálcio , Proteínas de Ciclo Celular , Complexos Endossomais de Distribuição Requeridos para Transporte

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Virus-like particles (VLPs) are used as nanocontainers for targeted drug, protein, and vaccine delivery. The phage P22 VLP is an ideal macromolecule delivery vehicle, as it has a large exterior surface area, which facilitates multivalent genetic and chemical modifications for cell recognition and penetration. Arginine-rich cell-penetrating peptides (CPPs) can increase cargo transport efficiency in vivo. However, studies on the tissue distribution and retention of P22 VLPs mediated by TAT and 8R are lacking. This study aimed to analyze the TAT and 8R effects on the P22 VLPs transport efficiency and tissue distribution both in vitro and in vivo. We used a prokaryotic system to prepare P22 VLP self-assembled particles and expressed TAT-or 8R-conjugated mCherry on the VLP capsid protein as model cargoes and revealed that the level of P22 VLP-mCherry penetrating the cell membrane was low. However, both TAT and 8R significantly promoted the cellular uptake efficiency of P22 VLPs in vitro, as well as enhanced the tissue accumulation and retention of P22 VLPs in vivo. At 24 h postinjection, TAT enhanced the tissue distribution and retention in the lung, whereas 8R could be better accumulation in brain. Thus, TAT was superior in terms of cellular uptake and tissue accumulation in the P22 VLPs delivery system. Understanding CPP biocompatibility and tissue retention will expand their potential applications in macromolecular cargo delivery.

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BACKGROUND: Globally, breast cancer is the most common type of malignant tumor. It has been demonstrated that TMEM41A is abnormally expressed in a number of cancers and is linked to a dismal prognosis. TMEM41A's involvement in breast cancer remains unknown, though. METHODS: Data from databases such as TCGA were used in this study. Expression differences were compared using non-parametric tests. Cox regression analysis was employed, and analyses such as Nomogram were used to assess the significance of TMEM41A in predicting the prognosis of breast cancer. Lastly, it was looked into how immune cell infiltration in breast cancer is related to TMEM41A expression levels. RESULTS: The results suggest that TMEM41A is overexpressed in breast cancer and correlates with poor prognosis (P = 0.01), particularly in early-stage and ductal A breast cancer (P < 0.01). Breast cancer patients' expression of TMEM41A was found to be an independent risk factor (HR = 1.132, 95% CI 1.036-1.237) by multifactorial Cox regression analysis. The Nomogram prediction model's c-index was 0.736 (95% CI 0.684-0.787). The results of GSEA biofunctional enrichment analysis included the B cell receptor signaling pathway (P < 0.05). Ultimately, there was a significant correlation (P < 0.05) between TMEM41A expression in breast cancer and an infiltration of twenty immune cells. CONCLUSIONS: Breast cancer tissues overexpress TMEM41A, which is linked to immune cell infiltration and prognosis (particularly in early stage and luminal A breast cancer). Overexpression of TMEM41A is anticipated to serve as a novel prognostic indicator and therapeutic target for breast cancer.

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Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages.

Assuntos

Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neovascularização Patológica , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Microambiente Tumoral/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/metabolismo , Animais , Neovascularização Patológica/metabolismo , Neovascularização Patológica/virologia , Camundongos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Quimiocina CCL5/metabolismo , Inibidores da Angiogênese/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Feminino

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) is a candidate mediator of blood-brain barrier (BBB) disruption in depression. However, previous studies have mainly focused on peripheral blood VEGF levels, and the results are heterogeneous. Here we use astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma to explore the in vivo changes of VEGF levels in patients with major depressive disorder (MDD). METHODS: Thirty-five unmedicated patients with MDD and 35 healthy controls (HCs) were enrolled, and plasma ADEVs were isolated from each participant. VEGF levels in ADEVs and glial fibrillary acidic protein (GFAP) in plasma were measured. Additionally, Alix and CD81, two established extracellular vesicle markers, were quantified in ADEVs. RESULTS: At baseline, MDD patients exhibited significantly increased levels of VEGF in ADEVs and GFAP in plasma. Following four weeks of selective serotonin reuptake inhibitor treatment, these target protein levels did not significantly change. ROC curve analysis revealed an AUC of 0.711 for VEGF in ADEVs. In exploratory analysis, VEGF levels in ADEVs were positively correlated with Alix and CD81. LIMITATIONS: Multiple factors regulate BBB permeability. This study focused solely on VEGF and the sample size for longitudinal analysis was relatively small. CONCLUSION: Our study is the first to confirm increased ADEV-derived VEGF levels in patients with MDD, thereby providing preliminary evidence supporting the hypothesis that the BBB is disrupted in depression.

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Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system.

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BACKGROUND: The emergence and integration of mobile healthcare technology have fundamentally transformed the healthcare industry, providing unprecedented opportunities to improve healthcare services and professional practice. Despite its immense potential, the adoption of mobile healthcare technology among healthcare professionals remains uneven, particularly in developing regions. OBJECTIVE: This study aims to explore the usage and influencing factors of mobile healthcare among healthcare professionals in the Sichuan-Chongqing region of China and make recommendations. METHODS: Convenience sampling was used in a cross-sectional study conducted from November 8th to November 14th, 2023, to survey frontline clinical healthcare professionals at five district-level secondary public hospitals in the Sichuan-Chongqing region. An online questionnaire was used to investigate the usage of mobile healthcare and its influencing factors among the participants. Descriptive analysis and logistic regression analysis were employed in the study. RESULTS: A total of 550 valid questionnaires were completed. Among the surveyed healthcare professionals, only 18.7% used mobile healthcare, with a satisfaction rate of only 50.5%. 81.3% did not use any form of mobile healthcare. The age group of 30-39 was found to be a significant factor influencing the use of mobile healthcare by healthcare professionals (P =.03). The main reasons for not using mobile healthcare among healthcare professionals were: lack of appropriate technical training and support (59.5%), lack of suitable management-specific apps (45.6%), and concerns about increased workload (40.3%). There were significant differences in the single-factor analysis of the reasons for non-use of mobile healthcare among healthcare professionals from different specialties (P=.04). Logistic regression analysis indicated that age was the only significant factor influencing the use of mobile healthcare by healthcare professionals (P =.04). CONCLUSIONS: The utilization rate of mobile healthcare among healthcare professionals in the Sichuan-Chongqing region is low. Age is a significant factor that influences whether healthcare professionals use mobile healthcare. Providing appropriate technical training and support may help improve the enthusiasm of healthcare professionals in using mobile healthcare.

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Purpose: To assess the crescentic status of IgA nephropathy (IgAN) non-invasively using a superb microvascular imaging (SMI)-based radiomics machine learning (ML) model. Patients and Methods: IgAN patients who underwent renal biopsy from June 2022 to October 2023, with two-dimensional ultrasound (US) and SMI examinations conducted one day prior to the renal biopsy. The patients selected were divided randomly into a training group and a test group in a 7:3 ratio. Radiomic features were extracted from US and SMI images, then radiomic features were constructed and ML models were further established using logistic regression (LR) and extreme gradient boosting (XGBoost)XGBoost to determine the crescentic status. The utility of the proposed model was evaluated using receiver operating characteristics, calibration, and decision curve analysis. The SHapley Additive exPlanations (SHAP) was utilized to explain the best-performing ML model. Results: A total of 147 IgAN patients were included in the study, with 103 in the training group and 44 in the test group .Among them, the US-SMI based XGBoost model achieved the best results, with an the area under the curve (AUC) of 0.839 (95% CI,0.756-0.910) and an accuracy of 78.6% in the training group.In the test group, the AUC was 0.859 (95% CI,0.721-0.964), and the accuracy was 81.8%, significantly surpassing the ML model of a single modality and the clinical model established based on occult blood. Additionally, the decision curve analysis (DCA) demonstrated that the XGBoost model provided a higher overall net benefit in the both groups. Conclusion: The SMI radiomics ML model has the capability to accurately predict the crescentic status of IgAN patients, providing effective assistance for clinical treatment decisions.

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The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2. In addition, the review emphasizes the immune evasion strategies of the SARS-CoV-2, including inhibition of interferon production and induction of cytokine storms, along with the resulting clinical outcomes. Finally, we assess the efficacy of current treatment strategies, including antiviral drugs, monoclonal antibodies, and anti-inflammatory treatments, and discuss their role in providing immunity and preventing severe disease.

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The healing of diabetic wounds has long been a significant challenge in the field of medicine. The elevated sugar levels surrounding diabetic wounds create a conducive environment for harmful bacterial growth, resulting in purulent infections that impede the healing process. Thus, the development of a biomaterial that can enhance the healing of diabetic wounds holds great importance. This study developed electrospun dressings for wound healing by combining traditional Chinese medicine and clay. The study utilized electrospinning technology to prepare polyvinyl alcohol (PVA) nanofiber membranes containing ASB and HNTs. These ASB@HNTs-PVA nanofiber membranes demonstrated rapid hemostasis, along with antibacterial and anti-inflammatory properties, facilitating the recovery of type 2 diabetic (T2D) wounds. Various analyses were conducted to assess the performance of the composite nanofiber membrane, including investigations into its biocompatibility and hemostatic abilities through antibacterial experiments, cell experiments, and mouse liver tail bleeding experiments. Western blot analysis confirmed that the composite nanofiber membrane could decrease the levels of inflammatory factors IL-1ß and TNF-α. A type 2 diabetic mouse model was utilized, with wounds artificially induced on the backs of mice. Application of the nanofiber membrane to the wounds further confirmed its anti-inflammatory effects and ability to enhance wound healing in vivo.

Assuntos

Anti-Inflamatórios , Diabetes Mellitus Tipo 2 , Hemostáticos , Nanofibras , Álcool de Polivinil , Cicatrização , Animais , Nanofibras/química , Cicatrização/efeitos dos fármacos , Álcool de Polivinil/química , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemostáticos/farmacologia , Hemostáticos/química , Masculino , Humanos , Pele/patologia , Pele/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Diabetes Mellitus Experimental , Bandagens , Células RAW 264.7

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OBJECTIVE: The benefits of rhythm control in early atrial fibrillation (AF) are increasingly recognized. This study aimed to investigate whether early AF ablation contributes to long-term sinus rhythm maintenance and to identify a suitable predictive score. METHODS: According to diagnosis-to-ablation time, this study prospectively enrolled 245 patients with very early AF, 262 with early AF, and 588 with late AF for radiofrequency ablation from June 2017 to December 2022. Clinical data, risk scores, and follow-up results were collected and analyzed. RESULTS: Baseline characteristics were similar among the three cohorts. During a median follow-up period of 26 months, AF recurrence was observed in 61 (24.9%), 66 (25.2%), and 216 (36.7%) patients in the very early, early, and late AF cohorts, respectively. In the multivariable-adjusted model, very early and early AF were associated with a reduced risk of AF recurrence, with hazard ratios of 0.72 (95% confidence interval [CI] 0.52-0.99) and 0.57 (95% CI 0.41-0.78), respectively. The APPLE score demonstrated the highest predictive power for very early AF, with an area under the curve (AUC) of 0.74. However, its predictive power decreased with time from diagnosis, showing low predictive power for late AF (AUC = 0.58). In addition, the time-dependent concordance index showed consistent results. For very early AF, the Akaike information criterion and decision curve analysis showed that APPLE had the highest predictive value. CONCLUSION: Very early AF ablation was associated with a lower recurrence rate, and the APPLE score provided a higher predictive value for these patients. (URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR-OIN-17013021).

RESUMO

Cytochromes P450 (P450s or CYPs) are the most important phase I metabolic enzymes in the human body and are responsible for metabolizing ∼75% of the clinically used drugs. P450-mediated metabolism is also closely associated with the formation of toxic metabolites and drug-drug interactions. Therefore, it is of high importance to predict if a compound is the substrate of a given P450 in the early stage of drug development. In this study, we built the multitask learning models to simultaneously predict the substrates of five major drug-metabolizing P450 enzymes, namely, CYP3A4, 2C9, 2C19, 2D6, and 1A2, based on the collected substrate data sets. Compared to the single-task model and conventional machine learning models, the multitask fingerprints and graph neural networks model achieved superior performance with the average AUC values of 90.8% on the test set. Notably, the multitask model demonstrated its good performance on the small amount of substrate data sets such as CYP1A2, 2C9, and 2C19. In addition, the Shapley additive explanation and the attention mechanism were used to reveal specific substructures associated with P450 substrates, which were further confirmed and complemented by the substructure mining tool and the literature.

Assuntos

Sistema Enzimático do Citocromo P-450 , Aprendizado Profundo , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Especificidade por Substrato