RESUMO

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

Assuntos

Embalagem de Alimentos , Gelatina , Juglans , Óleos de Plantas , Embalagem de Alimentos/instrumentação , Gelatina/química , Juglans/química , Óleos de Plantas/química , Óleos Voláteis/química , Resistência à Tração , Malus/química , Solubilidade

RESUMO

With the increasing severity of arsenic (As) pollution, quantifying the environmental behavior of pollutant based on numerical model has become an important approach to determine the potential impacts and finalize the precise control strategies. Taking the industrial-intensive Jinsha River Basin as typical area, a two-dimensional hydrodynamic water quality model coupled with Soil and Water Assessment Tool (SWAT) model was developed to accurately simulate the watershed-scale distribution and transport of As in the terrestrial and aquatic environment at high spatial and temporal resolution. The effects of hydro-climate change, hydropower station construction and non-point source emissions on As were quantified based on the coupled model. The result indicated that higher As concentration areas mainly centralized in urban districts and concentration slowly decreased from upstream to downstream. Due to the enhanced rainfall, the As concentration was significantly higher during the rainy season than the dry season. Hydro-climate change and the construction of hydropower station not only affected the dissolved As concentration, but also affected the adsorption and desorption of As in sediment. Furthermore, As concentration increased with the input of non-point source pollution, with the maximum increase about 30%, resulting that non-point sources contributed important pollutant impacts to waterways. The coupled model used in pollutant behavior analysis is general with high potential application to predict and mitigate water pollution.

Assuntos

Arsênio , Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Arsênio/análise , China , Poluentes Químicos da Água/análise , Rios/química , Monitoramento Ambiental/métodos , Modelos Químicos , Modelos Teóricos

RESUMO

Emission characteristics of biogenic volatile organic compounds (BVOCs) from dominant tree species in the subtropical pristine forests of China are extremely limited. Here we conducted in situ field measurements of BVOCs emissions from representative mature evergreen trees by using dynamic branch enclosures at four altitude gradients (600-1690 m a.s.l.) in the Nanling Mountains of southern China. Composition characteristics as well as seasonal and altitudinal variations were analyzed. Standardized emission rates and canopy-scale emission factors were then calculated. Results showed that BVOCs emission intensities in the wet season were generally higher than those in the dry season. Monoterpenes were the dominant BVOCs emitted from most broad-leaved trees, accounting for over 70% of the total. Schima superba, Yushania basihirsuta and Altingia chinensis had relatively high emission intensities and secondary pollutant formation potentials. The localized emission factors of isoprene were comparable to the defaults in the Model of Emissions of Gases and Aerosols from Nature (MEGAN), while emission factors of monoterpenes and sesquiterpenes were 2 to 58 times of those in the model. Our results can be used to update the current BVOCs emission inventory in MEGAN, thereby reducing the uncertainties of BVOCs emission estimations in forested regions of southern China.

Assuntos

Poluentes Atmosféricos , Monitoramento Ambiental , Florestas , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , China , Poluentes Atmosféricos/análise , Árvores , Estações do Ano

RESUMO

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

Assuntos

Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia Mieloide Aguda , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Idoso , Masculino , Leucemia Mieloide Aguda/terapia , Imunoterapia Adotiva/métodos , Terapia Combinada , Resultado do Tratamento , Indução de Remissão

RESUMO

Thermokarst landslide (TL) activity in the Qinghai-Tibet Plateau (QTP) is intensifying due to climate warming-induced permafrost degradation. However, the mechanisms driving landslide formation and evolution remain poorly understood. This study investigates the spatial distribution, annual frequency, and monthly dynamics of TLs along the Qinghai-Tibet engineering corridor (QTEC), in conjunction with in-situ temperature and rainfall observations, to elucidate the interplay between warming, permafrost degradation, and landslide activity. Through the analysis of high-resolution satellite imagery and field surveys, we identified 1298 landslides along the QTEC between 2016 and 2022, with an additional 386 landslides recorded in a typical landslide-prone sub-area. In 2016, 621 new active-layer detachments (ALDs) were identified, 1.3 times the total historical record. This surge aligned with unprecedented mean annual and August temperatures. The ALDs emerged primarily between late August and early September, coinciding with maximum thaw depth. From 2016 to 2022, 97.8 % of these ALDs evolved into retrogressive thaw slumps (RTSs), identified as active landslides. Landslides typically occur in alpine meadows at moderate altitudes and on gentle northward slopes. The thick ice layer near the permafrost table serves as the material basis for ALD occurrence. Abnormally high temperature significantly increased the active layer thickness (ALT), resulting in melting of the ice layer and formation of a thawed interlayer, which was the direct causing factor for ALD. By altering the local material, micro-topography, and thermal conditions, ALD activity significantly increases RTS susceptibility. Understanding the mechanisms of ALD formation and evolution into RTS provides a theoretical foundation for infrastructure development and disaster mitigation in extreme environments.

RESUMO

Since the inception of the concept of nanozymes, there has been a growing interest in the rational design and controllable synthesis of nanozymes with adjustable activities. In this study, onion-liked carbon (OLC) with remarkable peroxidase-like (POD) activity are developed through delicately controlling the sp2/sp3 configuration. The investigation reveals that enzymatic activity of OLC increases first and then decreases with the increased graphitic degree, with the highest activity observed at a moderate sp2/sp3 ratio of 17.17%. A series of experiments and theoretical calculations are conducted to elucidate the catalytic mechanism, and the structure-dependent activity is attributed to a synergistic effect of surface adsorption and electron transfer processes. The POD activity enables the OLC to catalyze the decomposition of H2O2, producing reactive oxygen species for eradicating Gram-positive and Gram-negative bacteria. Additionally, toxicity tests based on nematode and mouse models confirmed the excellent biocompatibility of OLC. Furthermore, the OLC exhibited antibacterial ability and promoted bacterial-infected wound healing in a mouse model. This work not only gives a deeper understanding of the structure-activity relationship and catalytic mechanism of carbon-based nanozymes, but also unveils a novel avenue for antibacterial therapy and wound healing applications.

RESUMO

Silk sutures are common in surgeries, and silk-based textiles are widely used in clinical medicine on account of their great mechanical properties and biodegradability. However, due to the lack of biocatalytic activity, silk sutures show unsatisfactory anti-inflammatory properties and healing speed. To address this constraint, we construct clinical grade bioactive gold cluster-sutures through a heterojunction. The antioxidant activity of bioactive gold cluster-sutures is ∼160 times more than that of clinical sutures. Meanwhile, the suture displays superb reactive oxygen species (ROS) scavenging, superoxide dismutase-like (SOD-like, 5 times more than the silk suture), and catalase-like (CAT-like) activities. The clusters assemble on the surface of silk through hydrogen bonding, leading to a durable catalytic and structural stability for 15 months without decay. Subsequently, the suture significantly accelerates wound healing by exerting excellent anti-inflammatory effects, improving neovascularization and collagen deposition. Clinical grade bioactive gold clusters with high bioactivity, stability, and biocompatibility hold promise for clinical translation and pave the way for other implanted biomaterials from wound healing to intelligent textiles.

RESUMO

Objective: Skin wound exposed to complex external environment for a long time is highly susceptible to bacterial infection. Impact Statement: This work designs a Janus adhesive dual-layer hydrogel containing in situ silver nanoparticles (named PSAP/DXP@AgNPs) with integrated attack and defense to simultaneously kill the existing bacteria and prevent foreign bacterial contamination. Introduction: The current gauze dressing fixed by tape fails to well fit at skin wound and lacks intrinsic antibacterial property, making it highly prone to causing secondary infection. Moreover, foreign bacteria may contaminate the wound dressing during use, further increasing the risk of secondary infection. Methods: In this work, a Janus adhesive dual-layer PSAP/DXP@AgNPs hydrogel is prepared by sequentially building the PSAP gel layer containing zwitterionic poly(sulfobetaine methacrylamide) (PSBMA) on the DXP@AgNPs gel layer containing in situ catechol-reduced AgNPs. Results: The flexible PSAP/DXP@AgNPs can adapt shape change of skin and adhere to skin tissue with interfacial toughness of 153.38 J m-2 relying on its DXP@AgNPs layer, which is beneficial to build favorable fit. The in situ reduced AgNPs released from the DXP@AgNPs layer of PSAP/DXP@AgNPs exhibit obvious antibacterial effects against Escherichia coli and Staphylococcus aureus, with antibacterial rates of 99% and 88%, respectively. Meanwhile, the hydrated PSAP layer of PSAP/DXP@AgNPs containing PSBMA is able to prevent the bacterial contamination, decreasing the risk of secondary infection. Besides, cell experiments demonstrate that PSAP/DXP@AgNPs is biocompatible. Conclusion: The PSAP/DXP@AgNPs hydrogel with integrated attack and defense simultaneously possessing bacteria-killing and bacteria-antifouling properties is a potential alternative in treating infected skin wound.

RESUMO

BACKGROUND: The use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database. METHODS: In the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics. RESULTS: In the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p < 0.001). CONCLUSIONS: Among patients undergoing laparoscopic radical resection of colorectal cancer with general anesthesia, all four FAW systems effectively prevented perioperative hypothermia. However, the system in Group A minimized heat loss more effectively than the others, providing superior thermal protection. TRIAL REGISTRATION: ChiCTR2200065394, 03/11/2022.

Assuntos

Anestesia Geral , Temperatura Corporal , Hipotermia , Manequins , Humanos , Masculino , Feminino , Hipotermia/prevenção & controle , Pessoa de Meia-Idade , Temperatura Corporal/fisiologia , Anestesia Geral/métodos , Adulto , Roupas de Cama, Mesa e Banho , Idoso , Estremecimento/fisiologia

RESUMO

Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression1-3. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal4,5. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells5 is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. TET2 depletion thereby leads to globally decreased H2AK119ub, more open chromatin and increased transcription in stem cells. TET2-mutant human leukaemia becomes dependent on this gene activation pathway, with MBD6 depletion selectively blocking proliferation of TET2-mutant leukaemic cells and largely reversing the haematopoiesis defects caused by Tet2 loss in mouse models. Together, our findings reveal a chromatin regulation pathway by TET2 through retrotransposon RNA m5C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against TET2 mutant malignancies.

RESUMO

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

Assuntos

Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Colangiocarcinoma , Compostos de Fenilureia , Quinolinas , Humanos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidade , Masculino , Feminino , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Idoso , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/genética , Adulto , Prognóstico , Idoso de 80 Anos ou mais

RESUMO

BACKGROUNDS: Acute transplant rejection is a major component of poor prognoses for organ transplantation. Owing to the multiple complex mechanisms involved, new treatments are still under exploration. Endometrial regenerative cells (ERCs) have been widely used in various refractory immune-related diseases, but the role of ERC-derived exosomes (ERC-Exos) in alleviating transplant rejection has not been extensively studied. Signaling lymphocyte activation molecule family 6 (SLAMF6) plays an important role in regulating immune responses. In this study, we explored the main mechanism by which ERC-Exos loaded with siSLAMF6 can alleviate allogeneic transplant rejection. METHODS: C57BL/6 mouse recipients of BALB/c mouse kidney transplants were randomly divided into four groups and treated with exosomes. The graft pathology was evaluated by H&E staining. Splenic and transplanted heart immune cell populations were analyzed by flow cytometry. Recipient serum cytokine profiles were determined by enzyme-linked immunosorbent assay (ELISA). The proliferation and differentiation capacity of CD4+ T cell populations were evaluated in vitro. The α-2,6-sialylation levels in the CD4+ T cells were determined by SNA blotting. RESULTS: In vivo, mice treated with ERC-siSLAMF6 Exo achieved significantly prolonged allograft survival. The serum cytokine profiles of the recipients were significantly altered in the ERC-siSLAMF6 Exo-treated recipients. In vitro, we found that ERC-siSLAMF6-Exo considerably downregulated α-2,6-sialyltransferase (ST6GAL1) expression in CD4+ T cells, and significantly reduced α-2,6-sialylation levels. Through desialylation, ERC-siSLAMF6 Exo therapy significantly decreased CD4+ T cell proliferation and inhibited CD4+ T cell differentiation into Th1 and Th17 cells while promoting regulatory T cell (Treg) differentiation. CONCLUSIONS: Our study indicated that ERC-Exos loaded with siSLAMF6 reduce the amount of sialic acid connected to α-2,6 at the end of the N-glycan chain on the CD4+ T cell surface, increase the number of therapeutic exosomes endocytosed into CD4+ T cells, and inhibit the activation of T cell receptor signaling pathways, which prolongs allograft survival. This study confirms the feasibility of using ERC-Exos as natural carriers combined with gene therapy, which could be used as a potential therapeutic strategy to alleviate allograft rejection.

Assuntos

Endométrio , Exossomos , Rejeição de Enxerto , Transplante de Coração , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Exossomos/metabolismo , Rejeição de Enxerto/imunologia , Feminino , Camundongos , Endométrio/metabolismo , Aloenxertos , Citocinas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células , Sobrevivência de Enxerto

RESUMO

AIM: To explore, using network pharmacology and RNA-seq technologies, potential active targets and mechanisms underpinning Radix Bupleuri's effectiveness during sepsis treatment. METHODS: Following the Sepsis-3.0 criteria, the research cohort, comprising 23 sepsis patients and 10 healthy participants, was obtained from public databases. Peripheral blood samples were collected and subjected to RNA-seq analysis. Active ingredients and potential targets of Radix Bupleuri were identified using the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine 2.0 (BATMAN-TCM 2.0) database and TCMSP database. Subsequently, protein-protein interaction (PPI) network construction, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to explore cross-targets between disease and drugs. Survival analysis of key targets was performed using the GSE65682 dataset, and single-cell RNA-seq was employed for cellular localization analysis of key genes. Finally, molecular docking and Molecular dynamics simulation of the core target was conducted. RESULTS: Differential expression analysis revealed 4253 genes associated with sepsis. Seventy-six active components and 1030 potential targets of Radix Bupleuri were identified. PPI, GO, and pathway enrichment analyses indicated involvement in the regulation of transmembrane transport, monatomic ion transport, and MAPK signaling. Survival curve analysis identified PIK3CD, ARRB2, SUCLG1, and SPI1 as key targets associated with lower mortality in the high expression group, while higher mortality was observed in the high PNP and FURIN expression groups. Single-cell RNA sequencing unveiled the cellular localization of PIK3CD, PNP, SPI1, and FURIN within macrophages, while ARRB2 and SUCLG1 exhibited localization in both macrophages and T-cells. Subsequent molecular docking and Molecular dynamics simulation indicated a potential binding interaction for Carvone-PIK3CD, Encecalin-ARRB2, Lauric Acid-SUCLG1, Pulegone-FURIN, Nootkatone-SPI1, and Saikogenin F-PNP. CONCLUSION: Radix Bupleuri could modulate immune function by affecting PIK3CD, ARRB2, SUCLG1, FURIN, SPI1, and PNP, thereby potentially improving the prognosis of sepsis.

Assuntos

Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Sepse , Humanos , Sepse/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Bupleurum/química , Masculino , Mapas de Interação de Proteínas , Pessoa de Meia-Idade , Feminino

RESUMO

Amphibians face the threat of decline and extinction, and their health is crucially affected by the microbiota. Their health and ecological adaptability essentially depend on the diverse microbial communities that are shaped by unique host traits and environmental factors. However, there is still limited research on this topic. In this study, cutaneous (C) and gut (G) microbiota in Rana amurensis (A) and R. dybowskii (D) was analyzed through 16S amplicon sequencing. Groups AC and DC significantly differed in alpha diversity, while the gut groups (AG and DG) showed no such differences. Analyses of Bray-Curtis dissimilarity matrix and unweighted UniFrac distances showed significant differences in cutaneous microbiota between groups AC and DC, but not between groups AG and DG. Stochastic processes significantly influenced the assembly of cutaneous and gut microbiota in amphibians, with a notably higher species dispersal rate in the gut. The predominant phyla in the skin of R. amurensis and R. dybowskii were Bacteroidetes and Proteobacteria, respectively, with significant variations in Bacteroidota. Contrarily, the gut microbiota of both species was dominated by Firmicutes, Proteobacteria, and Bacteroidetes, without significant phylum-level differences. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial enrichment in each group. Predictive analysis using phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) revealed the significant functional pathways associated with the microbiota, which indicates their potential roles in immune system function, development, regeneration, and response to infectious diseases. This research underscores the critical impact of both host and environmental factors in shaping amphibian microbial ecosystems and emphasizes the need for further studies to explore these complex interactions for conservation efforts.

Assuntos

Bactérias , Microbioma Gastrointestinal , Filogenia , RNA Ribossômico 16S , Ranidae , Pele , Animais , Pele/microbiologia , Ranidae/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Microbiota , Biodiversidade

RESUMO

OBJECTIVE: Apolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship. METHODS: A total of 1713 patients with hypertension who were admitted to Meizhou People's Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed. RESULTS: There were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4 genotype, respectively. The frequency of APOE ɛ3/ɛ4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (24.0 kg/m2 vs. 18.5-23.9 kg/m2, odds ratio (OR): 1.361, 95% confidence interval (CI): 1.112-1.666, p = 0.003), advanced age (≥ 65/<65, OR:1.303, 95% CI: 1.060-1.602, p = 0.012), history of smoking (OR: 1.830, 95% CI: 1.379-2.428, p < 0.001), diabetes mellitus (OR: 1.380, 95% CI: 1.119-1.702, p = 0.003), hyperlipidemia (OR: 1.773, 95% CI: 1.392-2.258, p < 0.001), and APOE ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 1.514, 95% CI: 1.133-2.024, p = 0.005) were associated with coronary atherosclerosis in hypertensive patients. CONCLUSIONS: Overweight (BMI ≥ 24.0 kg/m2), advanced age, history of smoking, diabetes mellitus, and APOE ɛ3/ɛ4 genotype were independent risk factors for coronary atherosclerosis in hypertensive patients.

Assuntos

Apolipoproteína E3 , Apolipoproteína E4 , Doença da Artéria Coronariana , Predisposição Genética para Doença , Hipertensão , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/genética , Pessoa de Meia-Idade , Hipertensão/genética , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Estudos Retrospectivos , Medição de Risco , Idoso , Fatores de Risco , Apolipoproteína E3/genética , Apolipoproteína E4/genética , China/epidemiologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos de Associação Genética , Apolipoproteínas E

RESUMO

Objective: Non-Hispanic Black (NHB) and Hispanic/Latino (Hispanic) patients wait longer in the emergency department (ED) to see practitioners when compared with non-Hispanic White (NHW) patients. We investigate factors contributing to longer wait times for NHB and Hispanic patients using a linear decomposition approach. Methods: This retrospective observational study included patients presenting to one tertiary hospital ED from 2019 to 2021. Median wait times among NHW, NHB, and Hispanic were calculated with multivariable linear regressions. The extent to which demographic, clinical, and hospital factors explained the differences in average wait time among the three groups were analyzed with Blinder‒Oaxaca post-linear decomposition model. Results: There were 310,253 total patients including 34.7% of NHW, 34.7% of NHB, and 30.6% of Hispanic patients. The median wait time in NHW was 9 min (interquartile range [IQR] 4‒47 min), in NHB was 13 min (IQR 4‒59 min), and in Hispanic was 19 min (IQR 5‒78 min, p < 0.001). The top two contributors of average wait time difference were mode of arrival and triage acuity level. Post-linear decomposition analysis showed that 72.96% of the NHB‒NHW and 87.77% of the Hispanic‒NHW average wait time difference were explained by variables analyzed. Conclusion: Compared to NHW patients, NHB and Hispanic patients typically experience longer ED wait times, primarily influenced by their mode of arrival and triaged acuity levels. Despite these recognized factors, there remains 12%‒27% unexplained factors at work, such as social determinants of health (including implicit bias and systemic racism) and many other unmeasured confounders, yet to be discovered.

RESUMO

This study explores the nuances of information sharing in the context of infodemics, with a concentrated examination of the effects of opinion leaders and information attention on users' disposition towards sharing information during public health emergencies. The research adopts a quantitative methodology, employing Structural Equation Modeling (SEM) to empirically test the proposed hypotheses. By employing a rigorous analytical framework, the research also scrutinizes the mediating role of risk perception in shaping users' intentions to disseminate information related to public health emergencies. Additionally, it investigates the moderating effect of perceived usefulness, shedding light on how it influences the strength of the relationship between information attention and risk perception. The findings underscore the significance for public health communication strategies, emphasizing targeted messaging utilizing trusted opinion leaders and emphasizing information utility to foster responsible sharing. This research contributes to the academic conversation on infodemic management, providing empirical insights to guide policies and practices in mitigating misinformation during public health emergencies.

Assuntos

Emergências , Disseminação de Informação , Saúde Pública , Humanos , Saúde Pública/métodos , Disseminação de Informação/métodos , Meios de Comunicação de Massa , Comunicação , Masculino , Feminino

RESUMO

As a new therapeutic method, extracorporeal shock wave (ESW) has shown remarkable efficacy in the treatment of temporomandibular joint disorder syndrome. Numerous studies have shown that it has the advantages of noninvasiveness, short treatment time, etc. It can effectively relieve pain and improve symptoms such as joint mobility and opening degree. In clinical practice, through accurate diagnosis and positioning of different patients, appropriate treatment parameters such as therapeutic transducer, frequency and pressure can be selected to significantly improve the efficacy. At the same time, follow-up evaluation after treatment, including temporomandibular joint disorder index and visual analogue score, is also helpful to fully understand the rehabilitation of patients. Extracorporeal shock wave therapy (ESWT) brings new hope to patients with temporomandibular joint disorder syndrome and has a broad application prospect.

RESUMO

Background: Currently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomization (MR) methodology to investigate the causal relationship between the two. Methods: This study selected 110 single-nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome-wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalog and FINNGEN database, primarily analyzed using inverse variance weighting (IVW) and sensitivity analysis. Results: Through MR analysis, we identified 9 primary immunodeficiency-related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections. Conclusions: This study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations are warranted to explore the specific mechanisms underlying these connections.

Assuntos

Estudo de Associação Genômica Ampla , Herpesvirus Humano 3 , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Herpesvirus Humano 3/imunologia , Herpes Zoster/genética , Herpes Zoster/imunologia , Herpes Zoster/virologia , Ativação Viral , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/imunologia , Predisposição Genética para Doença , Infecção pelo Vírus da Varicela-Zoster/genética , Infecção pelo Vírus da Varicela-Zoster/imunologia , Síndromes de Imunodeficiência/genética

RESUMO

Transdermal microneedle-mediated glucose-responsive insulin delivery systems can modulate insulin release based on fluctuations in blood glucose levels, thus maintaining normoglycemia effectively in a continuous, convenient, and minimally invasive manner. However, conventional microneedles are limited by the low drug loading capacity, making it challenging to be applied on human skin at a reasonable size for a lasting glucose-controlling effect, thus hindering their clinical translation. Here, we design a microneedle patch with a solid insulin powder core to achieve a high loading capacity of insulin (>70 wt %) as well as a glucose-sensitive polymeric shell to realize glucose-responsive insulin release. Once exposed to hyperglycemia, the formation of negatively charged glucose-boronate complexes increases the charge density of the shell matrix, leading to swelling of the shell and accelerating insulin release from the core. We have demonstrated that this glucose-responsive microneedle patch could achieve long-term regulation of blood glucose levels in both type 1 diabetic mice and minipigs (up to 48 h with patches of ∼3.5 cm2 for minipigs >25 kg).