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The development of bacterial resistance significantly contributes to the persistence of infections. Although previous studies have highlighted the benefits of metal-doped positive carbon nanodots in managing bacterial wound infections, their mechanism of action is relatively simple and they may pose potential hazards to human cells. Therefore, it is essential to develop a one-stop carbon dot nanoplatform that offers high biocompatibility, antibacterial properties, and anti-inflammatory activities for wound infection management. This study explores the antibacterial efficacy, without detectable resistance, and wound-healing potential of nitrogen-doped (N-doped) negatively charged carbon dots (TPP-CDs). These carbon dots are synthesized using tannic acid (TA), polyethylene polyamine, and polyethylene glycol (PEG) as precursors, with a focus on their biocompatibility. Numerous systematic studies have shown that TPP-CDs can effectively destroy bacterial biofilms and deoxyribonucleic acid (DNA), while also inducing oxidative stress, leading to a potent antimicrobial effect. TPP-CDs also demonstrate the ability to scavenge excess free radicals, promote cellular proliferation, and inhibit inflammatory factors, all of which contribute to improved wound healing. TPP-CDs also demonstrate favorable cell imaging capabilities. These findings suggest that N-doped negatively charged TPP-CDs hold significant potential for treating bacterial infections and offer practical insights for their application in the medical field.
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Antibacterianos , Antiinflamatorios , Materiales Biocompatibles , Carbono , Pruebas de Sensibilidad Microbiana , Nitrógeno , Puntos Cuánticos , Antibacterianos/farmacología , Antibacterianos/química , Carbono/química , Carbono/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos , Puntos Cuánticos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nitrógeno/química , Staphylococcus aureus/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Tamaño de la Partícula , Animales , Propiedades de Superficie , Biopelículas/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Ratones , Escherichia coli/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
This study aimed to create Pickering emulsions with varying oil fractions and assess the impact of ultrasonic treatment on the properties of Whey Protein Isolates (WPIs). At 640 W for 30 min, ultrasound reduced WPI aggregate size, raised zeta potential, and improved foaming, emulsifying, and water-holding capacities. FTIR analysis showed structural changes, while fluorescence and hydrophobicity increased, indicating tertiary structure alterations. This suggests that sonication efficiently modifies WPI functionality. Under ideal conditions, φ = 80 emulsions were most stable, with no foaming or phase separation. Laser scanning revealed well-organized emulsions at φ = 80. This study provides a reference for modifying and utilizing WPI.
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INTRODUCTION: Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. METHODS: We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. RESULTS: The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. CONCLUSION: Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.
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OBJECTIVE: This study aims to evaluate the efficacy of a novel simple suture method in establishing an optimal animal model for preclinical research in pancreatic cancer. METHODS: To establish a novel simple suture method, the tumor fragment was placed on the tail of the pancreas and securely wrapped into the pancreas, and compared with two conventional methods: the cell injection method and the tumor fragment embedding method. Subsequently, emission tomography/computed tomography scanning, gross anatomy observation, hematoxylin and eosin staining, and immunohistochemistry staining were performed to assess the effectiveness of these methods. RESULTS: The emission tomography/computed tomography scanning and anatomical examinations confirmed the successful construction of orthotopic pancreatic cancer models using all three methods. Histopathological analysis of the orthotopic masses and metastatic lesions revealed malignant transformation with tumor infiltration into normal tissue. Comparative analysis demonstrated that the cell injection method was easy to perform but resulted in poor uniformity of tumor size and had high costs. The tumor fragment embedding method exhibited excellent uniformity of tumor size, with the highest tumor growth rates and a greater pancreatic impairment. In contrast, the novel simple suture method featured a relatively simple surgical procedure, slower growth rates, good uniformity of tumor size, and minimal pancreatic impairment. CONCLUSION: The novel simple suture method is the optimal protocol for establishing an orthotopic pancreatic cancer mouse model, providing a robust foundation for preclinical studies on pancreatic cancer.
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Context: In normal physiological conditions, calcium ions (Ca2+) have an important effect in terms of the regulation of hair cell (HC) functions, and T-type calcium antagonists may be protective against hearing loss. However, no studies have occurred related to a T-type calcium-channel antagonist with regard to otoprotection in a Cdh23 mouse model. Objective: The study intended to examine the protective efficacy of ethosuximide-a T-type calcium-channel antagonist-against age-related hearing loss in a Cadherin 23 (Cdh23) erl/erl mouse model, to potentially offer an insight and foundation for therapy in the near future for patients in clinical practice who suffer from age-related hearing loss. Design: The research team conducted an animal study. Animals: The animals were 12 male and 12 female, Cdh23 erl/erl mice. Intervention: The research team randomly divided the mice into two groups, with 12 mice in each group: (1) the control group, the saline group, which received saline at 10 mL/kg of body weight, and (2) the intervention group, the ethosuximide group, which received ethosuximide at 10 mL/kg of body weight. Both groups received the treatments intraperitoneally every other day, beginning postnatally at 7 days until the mice were 8 weeks old. Outcome Measures: For both groups, the research team: (1) measured auditory brainstem response (ABR); (2) measured distortion product otoacoustic emission (DPOAE) at 4, 6, and 8 weeks of age; (3) separated the basilar membrane from the modiolus and lateral tissues and determined the percentage of inner-and-outer hair-cell (IHC and OHC) loss; (4) investigated relative levels of apoptosis-related gene mRNA using reverse transcription polymerase chain reaction (PCR); and (5) examined relative levels of apoptosis-related protein, using immunofluorescent (IF) staining. Results: Compared to the saline group, the ethosuximide group: (1) had significantly lower ABR thresholds for click at 8 weeks, for 8 KHz at 6 and 8 weeks, and for 16 KHz and 32 KHz (all P < .01); (2) had significantly higher DPOAE amplitudes at 4 weeks at 15.4 KHz and 17.7 KHz (both P < .01); at 6 weeks at 8.8 KHz (P < .05), 10.1 KHz (P < .01), 11.7 KHz (P < .01), 13.4 KHz (P < .01), 15.4 KHz (P < .01), and 17.7 KHz (P < .01); and at 8 weeks at 6.7 KHz (P < .05), 7.7 KHz (P < .05), 10.1 KHz (P < .01), 11.7 KHz (P < .01), 13.4 KHz (P < .01), 15.4 KHz (P < .01), and 17.7 KHz (P < .01); (3) had significantly lower OHC loss in the middle and basal turns of the cochlea's surface (both P < .05); (4) at the age of 2 months, had significantly lower mRNA relative levels of apoptosis-related genes, including caspase-3, caspase-9, caspase-12, m-calpain and u-calpain, as found using a polymerase chain reaction (PCR); and (5) had weaker protein levels of caspase-3 and caspase-9 in the inner ears, as found using immunofluorescent (IF) staining. Conclusions: T-type calcium-channel antagonists can exert protective efficacy in terms of the hearing function among cdh23 erl/erl mouse.
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Bioflocculants are eco-friendly water treatment agents produced by bioflocculant-producing strains that are valuable in drinking water turbidity removal. The major challenges in the application of bioflocculants include low flocculation efficiency, high production costs, and unclear flocculation-related genes. In this study, Pseudomonas sp. ZC-41 a highly efficient bioflocculant-producing strain, was isolated from activated sludge to produce polysaccharide-based bioflocculant MBF-ZC with 94.12% flocculation efficiency under more economical culture conditions, which can solve the problem of low flocculation efficiency. Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed MBF-ZC contained hydroxyl, carboxyl, and amine groups, crucial for flocculation via adsorption bridging effects as the main flocculation mechanism. The 2393 differentially expressed genes (DEGs) in the transcriptome of strain ZC-41 were classified into five co-expression modules, and the turquoise module was associated with flocculation efficiency and bioflocculant yield. Nineteen flocculation-related genes were identified by combining functional pathways related to sugars. In addition, response surface methodology was optimized to achieve the efficiency of 93.57% for turbidity removal from high-turbidity water by bioflocculant. The results not only provide a solid theoretical foundation to solve the challenges of bioflocculants, but also enrich strategies for high-turbidity drinking water treatment.
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Agua Potable , Floculación , Purificación del Agua , Agua Potable/química , Purificación del Agua/métodos , Pseudomonas/genética , Pseudomonas/metabolismo , Aguas del AlcantarilladoRESUMEN
The rapid advancement of Industry 4.0 necessitates close collaboration among material research institutions to accelerate the development of novel materials. However, multi-institutional cooperation faces significant challenges in protecting sensitive data, leading to data silos. Additionally, the heterogeneous and non-independent and identically distributed (non-i.i.d.) nature of material data hinders model accuracy and generalization in collaborative computing. In this paper, we introduce the MatSwarm framework, built on swarm learning, which integrates federated learning with blockchain technology. MatSwarm features two key innovations: a swarm transfer learning method with a regularization term to enhance the alignment of local model parameters, and the use of Trusted Execution Environments (TEE) with Intel SGX for heightened security. These advancements significantly enhance accuracy, generalization, and ensure data confidentiality throughout the model training and aggregation processes. Implemented within the National Material Data Management and Services (NMDMS) platform, MatSwarm has successfully aggregated over 14 million material data entries from more than thirty research institutions across China. The framework has demonstrated superior accuracy and generalization compared to models trained independently by individual institutions.
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Sepsis, characterized by a widespread and dysregulated immune response to infection leading to organ dysfunction, presents significant challenges in diagnosis and treatment. In this study, we investigated 203 coagulation-related genes in sepsis patients to explore their roles in the disease. Through differential gene expression analysis, we identified 20 genes with altered expression patterns. Subsequent correlation analysis, visualized through circos plots and heatmaps, revealed significant relationships among these genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these genes are involved in immune response activation, coagulation, and immune receptor activity. Disease Ontology (DO) enrichment analysis further linked these genes to autoimmune hemolytic anemia and tumor-related signaling pathways. Additionally, the CIBERSORT analysis highlighted differences in immune cell composition in sepsis patients, revealing an increase in neutrophils and monocytes and a decrease in inactive NK cells, CD8 T cells, and B cells. We employed machine learning techniques, including random forest and SVM, to construct a diagnostic model, identifying FCER1G and FYN as key biomarkers. These biomarkers were validated through their expression levels and ROC curve analysis in an independent validation cohort, demonstrating strong diagnostic potential. Single-cell analysis from the GSE167363 dataset further confirmed the distinct expression profiles of these genes across various cell types, with FCER1G predominantly expressed in monocytes, NK cells, and platelets, and FYN in CD4+ T cells and NK cells. Enrichment analysis via GSEA and ssGSEA revealed that these genes are involved in critical pathways, including intestinal immune networks, fatty acid synthesis, and antigen processing. In conclusion, our comprehensive analysis identifies FCER1G and FYN as promising biomarkers for sepsis, providing valuable insights into the molecular mechanisms of this complex condition. These findings offer new avenues for the development of targeted diagnostic and therapeutic strategies in sepsis management.
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Biomarcadores , Coagulación Sanguínea , Sepsis , Humanos , Sepsis/inmunología , Sepsis/genética , Sepsis/diagnóstico , Perfilación de la Expresión Génica , Transducción de Señal , Ontología de Genes , Transcriptoma , Aprendizaje Automático , Regulación de la Expresión Génica , Biología Computacional/métodosRESUMEN
Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.
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This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome's functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function. IMPORTANCE: Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.
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This study describes the synthesis and characterization of a novel near-infrared (NIR) fluorescent probe RBNE based on a hybrid rhodamine dye, which shows excellent optical capability for detecting and imaging ONOO- in necrotizing enterocolitis (NEC) mouse model. The probe RBNE undergoes hydrazine redox-process, and subsequently the spirocyclic structure's opening, resulting in a turn-on fluorescence emission with the presence of ONOO-, which exhibits several excellent features, including a significant Stokes shift of 108 nm, near-infrared emission at 668 nm, a lower detection limit of 56 nM, low cytotoxicity, and excellent imaging ability for ONOO- both in vitro and in vivo. The presented study introduces a novel optical tool that has the potential to significantly advance our understanding of peroxynitrite (ONOO-) behaviors in necrotizing enterocolitis (NEC).
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Enterocolitis Necrotizante , Colorantes Fluorescentes , Hidrazinas , Ácido Peroxinitroso , Rodaminas , Ácido Peroxinitroso/análisis , Ácido Peroxinitroso/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Enterocolitis Necrotizante/diagnóstico por imagen , Rodaminas/química , Rodaminas/síntesis química , Animales , Ratones , Hidrazinas/química , Hidrazinas/síntesis química , Estructura Molecular , Modelos Animales de Enfermedad , Humanos , Imagen ÓpticaRESUMEN
Hydrogen sulfide (H2S), methanethiol (MeSH) and dimethylsulfide (DMS) are abundant sulfur gases with roles in biogeochemical cycling, chemotaxis and/or climate regulation. Catabolism of the marine osmolyte dimethylsulfoniopropionate (DMSP) is a major source of DMS and MeSH, but both also result from S-methylation of H2S via MddA, an H2S and MeSH S-methyltransferase whose gene is abundant in soil but scarce in marine environments. Here we identify the S-adenosine methionine (SAM)-dependent MeSH and H2S S-methyltransferase 'MddH', which is widespread in diverse marine bacteria and some freshwater and soil bacteria. mddH is predicted in up to ~5% and ~15% of seawater and coastal sediment bacteria, respectively, which is considerably higher than mddA. Furthermore, marine mddH transcript levels are similar to those for the most abundant DMSP lyase gene dddP. This study implies that the importance of H2S and MeSH S-methylation pathways in marine environments is significantly underestimated.
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Bacterias , Sulfuro de Hidrógeno , Metiltransferasas , Agua de Mar , Sulfuros , Compuestos de Sulfonio , Bacterias/genética , Bacterias/metabolismo , Bacterias/enzimología , Bacterias/clasificación , Sulfuros/metabolismo , Agua de Mar/microbiología , Metiltransferasas/metabolismo , Metiltransferasas/genética , Compuestos de Sulfonio/metabolismo , Sulfuro de Hidrógeno/metabolismo , Filogenia , Metilación , Compuestos de Sulfhidrilo/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Sedimentos Geológicos/microbiologíaRESUMEN
Diarylethenes (DAEs) are an exciting class of stimulus-responsive organic molecules that exhibit electrocyclization reactions upon exposure to light, heat, or other stimuli. The rational design of DAE-based crystalline materials is, however, complicated by the presence of DAE atropisomers, only one of which is photoactive. Data mining of the CSD produced 1349 unique molecular DAE structures that were subsequently analyzed according to selected chemical and geometric attributes. Additional analyses were performed on 1078 dithienylethene (DTE) structures-the largest subgroup within the ensemble. The crystal structure landscape, based upon D-D parameterization and analysis, revealed a vast array of molecular geometries, many of which may not correspond to energetic minima. The analyses link various chemical and geometric parameters to isomers observed in the lattice and their reactivity; however, potential biases intrinsic to this ensemble of structures complicate the determination of causal relationships. We believe that this retrospective comprehensive analysis of DAE structures represents an important step for understanding more broadly the crystal landscape of this class of materials.
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OBJECTIVES: This study aimed to investigate the impact of calcific (Ca) on the efficacy of coronary computed coronary angiography (CTA) in evaluating plaque burden (PB) and composition with near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) serving as the reference standard. MATERIALS AND METHODS: Sixty-four patients (186 vessels) were recruited and underwent CTA and 3-vessel NIRS-IVUS imaging (NCT03556644). Expert analysts matched and annotated NIRS-IVUS and CTA frames, identifying lumen and vessel wall borders. Tissue distribution was estimated using NIRS chemograms and the arc of Ca on IVUS, while in CTA Hounsfield unit cut-offs were utilized to establish plaque composition. Plaque distribution plots were compared at segment-, lesion-, and cross-sectional-levels. RESULTS: Segment- and lesion-level analysis showed no effect of Ca on the correlation of NIRS-IVUS and CTA estimations. However, at the cross-sectional level, Ca influenced the agreement between NIRS-IVUS and CTA for the lipid and Ca components (p-heterogeneity < 0.001). Proportional odds model analysis revealed that Ca had an impact on the per cent atheroma volume quantification on CTA compared to NIRS-IVUS at the segment level (p-interaction < 0.001). At lesion level, Ca affected differences between the modalities for maximum PB, remodelling index, and Ca burden (p-interaction < 0.001, 0.029, and 0.002, respectively). Cross-sectional-level modelling demonstrated Ca's effect on differences between modalities for all studied variables (p-interaction ≤ 0.002). CONCLUSION: Ca burden influences agreement between NIRS-IVUS and CTA at the cross-sectional level and causes discrepancies between the predictions for per cent atheroma volume at the segment level and maximum PB, remodelling index, and Ca burden at lesion-level analysis. CLINICAL RELEVANCE STATEMENT: Coronary calcification affects the quantification of lumen and plaque dimensions and the characterization of plaque composition coronary CTA. This should be considered in the analysis and interpretation of CTAs performed in patients with extensive Ca burden. KEY POINTS: Coronary CT Angiography is limited in assessing coronary plaques by resolution and blooming artefacts. Agreement between dual-source CT angiography and NIRS-IVUS is affected by a Ca burden for the per cent atheroma volume. Advanced CT imaging systems that eliminate blooming artefacts enable more accurate quantification of coronary artery disease and characterisation of plaque morphology.
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Many neuropsychiatric disorders are considered to be associated with abnormalities in the functional connectivity networks of the brain. The research on the classification of functional connectivity can therefore provide new perspectives for understanding the pathology of disorders and contribute to early diagnosis and treatment. Functional connectivity exhibits a nature of dynamically changing over time, however, the majority of existing methods are unable to collectively reveal the spatial topology and time-varying characteristics. Furthermore, despite the efforts of limited spatial-temporal studies to capture rich information across different spatial scales, they have not delved into the temporal characteristics among different scales. To address above issues, we propose a novel Multi-Scale Spatial-Temporal Attention Networks (MSSTAN) to exploit the multi-scale spatial-temporal information provided by functional connectome for classification. To fully extract spatial features of brain regions, we propose a Topology Enhanced Graph Transformer module to guide the attention calculations in the learning of spatial features by incorporating topology priors. A Multi-Scale Pooling Strategy is introduced to obtain representations of brain connectome at various scales. Considering the temporal dynamic characteristics between dynamic functional connectome, we employ Locality Sensitive Hashing attention to further capture long-term dependencies in time dynamics across multiple scales and reduce the computational complexity of the original attention mechanism. Experiments on three brain fMRI datasets of MDD and ASD demonstrate the superiority of our proposed approach. In addition, benefiting from the attention mechanism in Transformer, our results are interpretable, which can contribute to the discovery of biomarkers. The code is available at https://github.com/LIST-KONG/MSSTAN.
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Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC. Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment. Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49). Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC.
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Currently, multifunction has become an essential direction of personal protective equipment (PPE), but achieving the protective effect, flexibility, physiological comfort, and intelligent application of PPE simultaneously is still a challenge. Herein, inspired by the meso-structure of rhinoceros skin, a novel strategy is proposed by compounding an ammonium sulfate ((NH4)2SO4) solution soaked gelatin hydrogel with the high weight fraction and vertically interwoven Kevlar fibers to manufacture a flexible and wearable composite with enhanced puncture resistance and strain-sensing properties. After (NH4)2SO4 solution immersion, the hydrogel's tensile strength, toughness, and fracture strain were up to 3.77 MPa, 4.26 MJ/m3, and 305.19%, respectively, indicating superior mechanical properties. The Kevlar/hydrogel composites revealed excellent puncture resistance (quasi-static of 132.06 N and dynamic of 295.05 N), flexibility (138.13 mN/cm), and air and moisture permeability (17.83 mm/s and 2092.73 g m-2 day-1), demonstrating a favorable balance between the protective effect and wearing comfort even after 7 days of environmental exposure. Meanwhile, salt solution immersion endowed the composite with excellent strain-sensing properties at various bending angles (30-90°) and frequencies (0.25-1 Hz) and allowed it to monitor different human motions directly in real-time. The rhinoceros-skin-inspired Kevlar/hydrogel composites provide a simple and economical solution for antipuncture materials that combine high protective effects, a comfortable wearing experience, and good strain-sensing properties, promising multifunctional PPE in the future.
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Hidrogeles , Dispositivos Electrónicos Vestibles , Hidrogeles/química , Humanos , Equipo de Protección Personal , Resistencia a la Tracción , Animales , Gelatina/química , Materiales Biomiméticos/químicaRESUMEN
Background: Patients with coronavirus disease 2019 (COVID-19) often experience persistent symptoms, known as postacute sequelae of COVID-19 or long COVID, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Chronic lung disease (CLD) has been identified in small-scale studies as a potential risk factor for long COVID. Methods: This large-scale retrospective cohort study using the National COVID Cohort Collaborative data evaluated the link between CLD and long COVID over 6 months after acute SARS-CoV-2 infection. We included adults (aged ≥18 years) who tested positive for SARS-CoV-2 during any of 3 SARS-CoV-2 variant periods and used logistic regression to determine the association, considering a comprehensive list of potential confounding factors, including demographics, comorbidities, socioeconomic conditions, geographical influences, and medication. Results: Of 1 206 021 patients, 1.2% were diagnosed with long COVID. A significant association was found between preexisting CLD and long COVID (adjusted odds ratio [aOR], 1.36). Preexisting obesity and depression were also associated with increased long COVID risk (aOR, 1.32 for obesity and 1.29 for depression) as well as demographic factors including female sex (aOR, 1.09) and older age (aOR, 1.79 for age group 40-65 [vs 18-39] years and 1.56 for >65 [vs 18-39] years). Conclusions: CLD is associated with higher odds of developing long COVID within 6 months after acute SARS-CoV-2 infection. These data have implications for identifying high-risk patients and developing interventions for long COVID in patients with CLD.
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Pseudorabies virus (PRV), an α-herpesvirus, induces immunosuppression and can lead to severe neurological diseases. N-methyl-D-aspartate receptor (NMDAR), an important excitatory nerve receptor in the central nervous system, is linked to various nervous system pathologies. The link between NMDAR and PRV-induced neurological diseases has not been studied. In vivo studies revealed that PRV infection triggers a reduction in hippocampal NMDAR expression, mediated by inflammatory processes. Extensive hippocampal neuronal degeneration was found in mice on the 6th day by hematoxylin-eosin staining, which was strongly correlated with increased NMDAR protein expression. In vitro studies utilizing the CCK-8 assay demonstrated that treatment with an NMDAR antagonist significantly heightened the cytotoxic effects of PRV on T lymphocytes. Notably, NMDAR inhibition did not affect the replication ability of PRV. However, it facilitated the accumulation of pro-inflammatory cytokines in PRV-infected T cells and enhanced the transcription of the CD25 gene through the secretion of interleukin-2 (IL-2), consequently exacerbating immunosuppression. In this study, we found that NMDAR has functional activity in T lymphocytes and is crucial for the inflammatory and immune responses triggered by PRV infection. These discoveries highlight the significant role of NMDAR in PRV-induced neurological disease pathogenesis.
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Herpesvirus Suido 1 , Seudorrabia , Receptores de N-Metil-D-Aspartato , Animales , Ratones , Herpesvirus Suido 1/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/metabolismo , Seudorrabia/virología , Seudorrabia/inmunología , Linfocitos T/inmunología , Linfocitos T/virología , Hipocampo/virología , Hipocampo/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Citocinas/genética , Terapia de Inmunosupresión , Tolerancia Inmunológica , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Interleucina-2/inmunología , Interleucina-2/genéticaRESUMEN
OBJECTIVE: To understand the status and problems of microbial pollution in shopping malls and supermarkets in China. METHODS: Microbial pollution in shopping malls and supermarkets was assessed by literature search, key information extraction and analysis. The strengths, weaknesses, opportunities and threats(SWOT) of risk control of pathogenic microorganisms in shopping malls and supermarkets were analyzed by SWOT analysis. RESULTS: Common bacteria in the indoor air of shopping malls and supermarkets included staphylococcus and Bacillus, and common fungi include Aspergillus and Penicillium. The bacteria detected in dust samples, escalator surfaces and floor surfaces were mainly Proteobacteria and Actinomyces. The complete public places laws and regulations, standards and health supervision system were the advantages of the risk prevention and control countermeasures of microbial contamination in shopping malls and supermarkets. At the same time, it also had the disadvantages of incomplete microbial-related indexes in the premises, and insufficiently detailed countermeasures for prevention and control in the premises. There were opportunities for multi-sectoral participation and post-licensing risk prevention, and it was also facing challenges brought by many factors affecting the health microenviroment and over-disinfection. CONCLUSION: The main sites for microbial risk prevention and control in superstore-type public places included high-frequency contact areas, key public supplies and utensils, indoor air, etc. , which could be prevented and controlled through a variety of measures such as controlling the release of the source, dilution and reduction, disinfection and denaturation, etc. , and exploring a comprehensive prevention and control system that involves the autonomy of the organization, industry self-regulation, collaboration of multi-government departments, and participation of the whole society.