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Vanillin is a commonly used synthetic flavoring agent in daily life. However, excessive intake of vanillin may pose risks to human health. Therefore, there is an urgent need for rapid and sensitive detection methods for vanillin. In this study, we developed a fluorescent sensor based on Cd-MOF for the sensitive and selective recognition of vanillin. The presence of vanillin leads to significant fluorescence quenching of Cd-MOF due to competitive absorption and photoinduced electron transfer (PET). The limit of detection was determined to be 39.6 nM, which is the lowest-among the reported fluorescent probes. The sensor was successfully applied for the detection of vanillin in real samples such as powdered milk and milk, with a recovery rate ranging from 96.88 % to 104.83 %. Furthermore, by immobilizing the Cd-MOF probe into a polyvinyl alcohol (PVA) film, we achieved a portable and visual detection composite materials for vanillin.

Asunto(s)

Benzaldehídos , Estructuras Metalorgánicas , Leche , Espectrometría de Fluorescencia , Benzaldehídos/análisis , Benzaldehídos/química , Leche/química , Animales , Espectrometría de Fluorescencia/métodos , Estructuras Metalorgánicas/química , Polvos , Colorantes Fluorescentes/química , Límite de Detección , Cadmio/análisis

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BACKGROUND: High internal phase emulsions (HIPE) are distinguished from ordinary emulsions by higher oil-phase percentage and better storage stability. Recently, HIPE stabilized with protein-based particles has received more attention. However, organic precipitation, chemical cross-linking and thermal denaturation are often needed to stabilize emulsions with natural proteins, and there is an urgent need to reduce the pollution of organic reagents. RESULTS: HIPE loaded with ß-carotene stabilized by phycocyanin was prepared under mild conditions. It demonstrated strong stability in terms of temperature and storage, as evidenced by its 94.17% retention rate and 81.06% bioavailability. This stability was ascribed to the efficient defense against heat and UV rays, which was probably associated with the oil-droplet environment and interfacial protection of phycocyanin. It is speculated that the possible main interaction site between phycocyanin and sorbitol exists near amino acids 110 to 120 of the B chain. The hydrogen bond and hydrophobic interaction between them make the phycocyanin fully adsorbed on the oil-water interface when sorbitol is stable, forming a strong oil-water structure, which increases the stability of the emulsion. CONCLUSION: The outstanding fluorescence characteristics provide a feasible alternative for fluorescent emulsions to distribute and trace active compounds in vitro. HIPE loaded with ß-carotene might have potential as a 3D printing material for edible functional foods. © 2024 Society of Chemical Industry.

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Coastal ecosystems are an important region for biogeochemical cycling, are a hotspot of anthropogenic disturbance and play a crucial role in global carbon cycling through the metabolic activities of bacterioplankton. Bacterioplankton can be broadly classified into two lifestyles: free-living (FL) and particle-attached (PA). However, how coastal bacterioplankton the community structure, co-occurrence networks and carbon metabolic functions with different lifestyles are differentiated is still largely unknown. Understanding these processes is necessary to better determine the contributions of coastal bacterioplankton to carbon cycling. Here, the characteristics of community structure and carbon metabolism function of bacterioplankton with two lifestyles in the coastal areas of Guangdong Province were investigated using amplicon sequencing, metagenomic, and metatranscriptomic techniques. The results show that the main bacterioplankton responsible for carbon metabolism were the Pseudomonadota, Bacteroidota, and Actinomycetota. The microbial community structure, carbon metabolic function, and environmental preferences differ between different lifestyles. FL and PA bacteria exhibited higher carbon fixation and degradation potentials, respectively. A range of environmental factors, such as dissolved oxygen, pH, and temperature, were associated with the community structure and carbon metabolic functions of the bacterioplankton. Human activities, such as nutrient discharge, may affect the distribution of functional genes and enhance the carbon degradation functions of bacterioplankton. In conclusion, this study increased the understanding of the role of microorganisms in regulating carbon export in coastal ecosystems with intense human activity. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00245-x.

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In recent years, there has been an increasing focus on microbial ecology and its possible impact on agricultural production, owing to its eco-friendly nature and sustainable use. The current study employs metabolomics technologies and bioinformatics approaches to identify changes in the exometabolome of Streptomyces albidoflavus B24. This research aims to shed light on the mechanisms and metabolites responsible for the antifungal and growth promotion strategies, with potential applications in sustainable agriculture. Metabolomic analysis was conducted using Q Exactive UPLC-MS/MS. Our findings indicate that a total of 3,840 metabolites were identified, with 137 metabolites exhibiting significant differences divided into 61 up and 75 downregulated metabolites based on VIP >1, |FC| >1, and p < 0.01. The interaction of S. albidoflavus B24 monoculture with the co-culture demonstrated a stronger correlation coefficient. The Principal Component Analysis (PCA) demonstrates that PCA1 accounted for 23.36%, while PCA2 accounted for 20.28% distinction. OPLS-DA score plots indicate significant separation among different groups representing (t1) 24% as the predicted component (to1) depicts 14% as the orthogonal component. According to the findings of this comprehensive study, crude extracts from S. albidoflavus demonstrated varying abilities to impede phytopathogen growth and enhance root and shoot length in tested plants. Through untargeted metabolomics, we discovered numerous potential molecules with antagonistic activity against fungal phytopathogens among the top 10 significant metabolites with the highest absolute log2FC values. These include Tetrangulol, 4-Hydroxybenzaldehyde, and Cyclohexane. Additionally, we identified plant growth-regulating metabolites such as N-Succinyl-L-glutamate, Nicotinic acid, L-Aspartate, and Indole-3-acetamide. The KEGG pathway analysis has highlighted these compounds as potential sources of antimicrobial properties. The inhibitory effect of S. albidoflavus crude extracts on pathogen growth is primarily attributed to the presence of specific gene clusters responsible for producing cyclic peptides such as ansamycins, porphyrin, alkaloid derivatives, and neomycin. Overall, it is apparent that crude extracts from S. albidoflavus exhibited varying abilities to inhibit the growth of three phytopathogens and enhancement in both root and shoot length of tested plants. This research enhances our understanding of how secondary metabolites contribute to growth promotion and biocontrol, supporting ecosystem sustainability and resilience while boosting productivity in sustainable agriculture.

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Importance: The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown. Objective: To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia. Design, Setting, and Participants: Randomized clinical trial conducted at 30 general respiratory non-intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV. Interventions: Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV. Main Outcomes and Measures: The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation. Results: The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, -9.0% [95% CI, -15.4% to -2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, -0.5% [95% CI, -4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]). Conclusions and Relevance: Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different. Trial Registration: ClinicalTrials.gov Identifier: NCT02985918.

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This study utilized high-throughput sequencing to investigate endophytic bacteria diversity in halophytic plants Anabasis truncate (AT) and Anabasis eriopoda (AE) from the Aral Sea region. Following sequence processing, 356 Amplicon Sequence Variants (ASVs) were discovered. The abundance and variety of endophytic bacteria were higher in AT. Bacillota, Pseudomonadota, Actinomycetota, and Bacteroidota constituted the dominant in AE, whereas Pseudomonadota, Actinomycetota, Bacteroidota, and Chloroflexota constituted the dominant in AT. Biomarkers were identified through LEFSe analysis, showing host-specific patterns. PCoA indicated distinct bacterial community structures. Phylogenetic analysis revealed diverse endophytic bacteria, including potential novel taxa. PICRUSt2 predicted diverse functions for endophytic bacteria in halophytes, indicating recruitment of beneficial bacterial taxa to adapt to extreme hypersaline conditions, including plant growth-promoting, biocontrol, and halophilic/tolerant bacteria. Moreover, the evolutionary relationship, metabolic capabilities, and plant beneficial potentials of the Bacillus swezeyi strains, previously isolated from the above two halophytes, were analyzed using comparative genomic and physiological analysis. The B. swezeyi strains displayed versatile environmental adaptability, as shown by their ability to use a wide range of carbon sources and their salt tolerances. B. swezeyi possessed a wide range of enzymatic capabilities, including but not limited to proteases, cellulases, and chitinases. Comparative genomic analysis revealed that despite some variations, they shared genetic similarities and metabolic capabilities among the B. swezeyi strains. B. swezeyi strains also displayed outstanding plant-growth-promoting and antagonistic potentials, offering potential solutions to the global food crisis. This study enhances our understanding of microbial diversity in halophytes on saline-alkali land in the West Aral Sea, shedding light on the halophyte microbiome and its collaboration with hosts in highly hypersaline environments. This study also provides a scientific basis for developing high-quality microbial fertilizers and implementing sustainable agricultural practices.

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Computer haptics (CH) is about integration of tactile sensation and rendering in Metaverse. However, unlike computer vision (CV) where both hardware infrastructure and software programs are well developed, a generic tactile data capturing device that serves the same role as what a camera does for CV, is missing. Bioinspired by electrophysiological processes in human tactile somatosensory nervous system, here we propose a tactile scanner along with a neuromorphically-engineered system, in which a closed-loop tactile acquisition and rendering (re-creation) are preliminarily achieved. Based on the architecture of afferent nerves and intelligent functions of mechano-gating and leaky integrate-and-fire models, such a tactile scanner is designed and developed by using piezoelectric transducers as axon neurons and thin film transistor (TFT)-based neuromorphic circuits to mimic synaptic behaviours and neural functions. As an example, the neuron-like tactile information of surface textures is captured and further used to render the texture friction of a virtual surface for "recreating" a "true" feeling of touch.

Asunto(s)

Tacto , Humanos , Tacto/fisiología , Percepción del Tacto/fisiología , Neuronas/fisiología , Axones/fisiología

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Opioid related aberrant behaviors (ORABs) present novel risk factors for opioid overdose. This paper introduces a novel biomedical natural language processing benchmark dataset named ODD, for ORAB Detection Dataset. ODD is an expert-annotated dataset designed to identify ORABs from patients' EHR notes and classify them into nine categories; 1) Confirmed Aberrant Behavior, 2) Suggested Aberrant Behavior, 3) Opioids, 4) Indication, 5) Diagnosed opioid dependency, 6) Benzodiazepines, 7) Medication Changes, 8) Central Nervous System-related, and 9) Social Determinants of Health. We explored two state-of-the-art natural language processing models (fine-tuning and prompt-tuning approaches) to identify ORAB. Experimental results show that the prompt-tuning models outperformed the fine-tuning models in most categories and the gains were especially higher among uncommon categories (Suggested Aberrant Behavior, Confirmed Aberrant Behaviors, Diagnosed Opioid Dependence, and Medication Change). Although the best model achieved the highest 88.17% on macro average area under precision recall curve, uncommon classes still have a large room for performance improvement. ODD is publicly available.

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Accurately predicting drug-target affinity is crucial in expediting the discovery and development of new drugs, which is a complex and risky process. Identifying these interactions not only aids in screening potential compounds but also guides further optimization. To address this, we propose a multi-perspective feature fusion model, MFF-DTA, which integrates chemical structure, biological sequence, and other data to comprehensively capture drug-target affinity features. The MFF-DTA model incorporates multiple feature learning components, each of which is capable of extracting drug molecular features and protein target information, respectively. These components are able to obtain key information from both global and local perspectives. Then, these features from different perspectives are efficiently combined using specific splicing strategies to create a comprehensive representation. Finally, the model uses the fused features to predict drug-target affinity. Comparative experiments show that MFF-DTA performs optimally on the Davis and KIBA data sets. Ablation experiments demonstrate that removing specific components results in the loss of unique information, thus confirming the effectiveness of the MFF-DTA design. Improvements in DTA prediction methods will decrease costs and time in drug development, enhancing industry efficiency and ultimately benefiting patients.

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The early diagnosis of liver cancer is crucial for the treatment and depends on the coordinated use of several test procedures. Early diagnosis is crucial for precision therapy in the treatment of the hepatocellular carcinoma (HCC). Therefore, in this study, the NK cell-related gene prediction model was used to provide the basis for precision therapy at the gene level and a novel basis for the treatment of patients with liver cancer. Natural killer (NK) cells have innate abilities to recognize and destroy tumor cells and thus play a crucial function as the "innate counterpart" of cytotoxic T cells. The natural killer (NK) cells is well recognized as a prospective approach for tumor immunotherapy in treating patients with HCC. In this research, we used publicly available databases to collect bioinformatics data of scRNA-seq and RNA-seq from HCC patients. To determine the NK cell-related genes (NKRGs)-based risk profile for HCC, we isolated T and natural killer (NK) cells and subjected them to analysis. Uniform Manifold Approximation and Projection plots were created to show the degree of expression of each marker gene and the distribution of distinct clusters. The connection between the immunotherapy response and the NKRGs-based signature was further analyzed, and the NKRGs-based signature was established. Eventually, a nomogram was developed using the model and clinical features to precisely predict the likelihood of survival. The prognosis of HCC can be accurately predicted using the NKRGs-based prognostic signature, and thorough characterization of the NKRGs signature of HCC may help to interpret the response of HCC to immunotherapy and propose a novel tumor treatment perspective.

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Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies1-4. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound5-7. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4+ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38-44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510 .

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A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, the color of the bacterial colony ranges from light yellow to yellow, designated YC-2023-2T, was isolated from sediment sample of Yuncheng salt lake. Growth occurred at 15-45℃ (optimum 37℃), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-8.0% NaCl (w/v, optimum 2.0%). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain YC-2023-2T belonged to the family Kordiimonadaceae. The closely related members were Gimibacter soli 6D33T (92.38%), Kordiimonas lipolytica M41T (91.88%), Eilatimonas milleporae DSM 25217T (91.88%) and Kordiimonas gwangyangensis JCM 12864T (91.84%). The genome of strain YC-2023-2T was 2957513 bp, and the genomic DNA G+C content was 63.91%. The main respiratory quinone was Q-10 and the major fatty acids (>10%) were iso-C15:0, C16:0, C19:0 cyclo ω8c, Summed Feature 8 (C18:1 ω6c or C18:1 ω7c) and Summed Feature 9 (iso-C17:1 ω9c or C16:0 10-methyl). The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid, unidentified lipid, and two unidentified aminolipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain YC-2023-2T is proposed to represent a novel species of a novel genus named Yunchengibacter salinarum gen. nov., sp. nov., within the family Kordiimonadaceae. The type strain is YC-2023-2T (= GDMCC 1.4502T = KCTC 8546T).

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Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Lagos , Filogenia , ARN Ribosómico 16S , Sedimentos Geológicos/microbiología , Lagos/microbiología , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , Técnicas de Tipificación Bacteriana , China , Análisis de Secuencia de ADN , Cloruro de Sodio/metabolismo

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In the current era of environmental disasters and the necessity of sustainable development, bacterial endophytes have gotten attention for their role in improving agricultural productivity and ecological sustainability. This review explores the multifaceted contributions of bacterial endophytes to plant health and ecosystem sustainability. Bacterial endophytes are invaluable sources of bioactive compounds, promising breakthroughs in medicine and biotechnology. They also serve as natural biocontrol agents, reducing the need for synthetic fertilizers and fostering environmentally friendly agricultural practices. It provides eco-friendly solutions that align with the necessity of sustainability since they can improve pest management, increase crop resilience, and facilitate agricultural production. This review also underscores bacterial endophytes' contribution to promoting sustainable and green industrial productions. It also presented how incorporating these microorganisms into diverse industrial sectors can harmonize humankind with ecological stability. The potential of bacterial endophytes has been largely untapped, presenting an opportunity for pioneering advancements in sustainable industrial applications. Their importance caught attention as they provided innovative solutions to the challenging problems of the new era. This review sheds light on the remarkable potential of bacterial endophytes in various industrial sectors. Further research is imperative to discover their multifaceted potential. It will be essential to delve deeper into their mechanisms, broaden their uses, and examine their long-term impacts.

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Agricultura , Endófitos , Ecosistema , Bacterias

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The instability of anthocyanins significantly reduces their bioavailability as food nutrients. This proof-of-concept study aimed to develop efficient carriers for anthocyanins to overcome this challenge. Characterization of the hydrogels via SEM (scanning electron microscope) and rheological analysis revealed the formation of typical gel structures. MTT (methyl thiazolyl tetrazolium) and hemolysis assays confirmed that their high biocompatibility. Encapsulation efficiency analysis and fluorescence microscopy images demonstrated successful and efficient encapsulation of anthocyanins by pH-responsive hydrogels. Stability studies further validated the effect of peptide hydrogels in helping anthocyanin molecules withstand factors such as gastric acid, high temperatures, and heavy metals. Subsequently, responsive studies in simulated gastric (intestinal) fluid demonstrated that the pH-responsive peptide hydrogels could protect anthocyanin molecules from gastric acid while achieving rapid and complete release in intestinal fluid environments. These results indicate that these peptide hydrogels could stabilize anthocyanins and facilitate their controlled release, potentially leading to personalized delivery systems.

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BACKGROUND: The opioid epidemic disproportionately affects individuals with co-occurring opioid use and mental health disorders (COD), who often have poor treatment engagement. Multicomponent treatment models are popular solutions to increase treatment access and engagement for those with COD. Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking (MISSION) is a hybrid multicomponent linkage and treatment approach that provides assertive community outreach combined with psychosocial treatment. This protocol paper describes a randomized controlled trial comparing MISSION and medication for opioid use disorder (MOUD), its multicomponent parts along with MOUD, and MOUD treatment as usual (TAU) to assess improvements in health and social outcomes. METHODS: This study will use a half fractional factorial design and randomize 1000 patients with COD to one of five treatment conditions: (1) the full MISSION intervention plus MOUD; (2-4) a combination of two out of three MISSION components plus MOUD; or (5) TAU. Secondary aims include examination of mechanisms of action, economic evaluation of the implementation of MISSION and/or its components plus MOUD versus TAU, and exploratory predictive modeling to match optimal MISSION parts with patient needs. DISCUSSION: This randomized controlled trial will help determine the effectiveness of MISSION (or its parts) and MOUD compared to TAU to improve engagement in treatment, substance use, and mental health symptoms. This trial is the first to compare MISSION and its parts with MOUD versus TAU in a real-world treatment scenario to determine which components are necessary and sufficient to drive treatment outcomes according to patient needs.

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Trastornos Mentales , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/terapia , Trastornos Relacionados con Opioides/psicología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/terapia , Trastornos Mentales/epidemiología , Intervención Psicosocial/métodos , Tratamiento de Sustitución de Opiáceos/métodos , Masculino , Femenino , Adulto , Analgésicos Opioides/uso terapéutico

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Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coli isolated from retail chicken meat. A total of 4 E. coli isolates co-harboring carbapenem resistance gene blaNDM (2 E. coli isolates with blaNDM-5 and 2 with blaNDM-9) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. coli strains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coli isolates belonged to a pathogenic E. coli lineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 blaNDM-harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for blaNDM. Comparative analysis exhibited that the mcr-1 or blaNDM-carrying plasmids of E. coli strains from chicken meat showed high identity with that from Enterobacteriaceae of human origin, which indicated the risk of mcr-1 or blaNDM dissemination from retail meat to human. The simultaneous occurrence of mcr-1 and blaNDM in E. coli emphasizes the significant of antimicrobial resistance surveillance in retail meat.

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BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Asunto(s)

Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Ratones Noqueados , Receptores Inmunológicos , Transducción de Señal , Animales , Ratones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/etiología , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/genética , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Ratones Endogámicos C57BL , Sinapsis/metabolismo , Sinapsis/patología , Sinapsis/efectos de los fármacos , Hormonas Peptídicas/metabolismo , Persona de Mediana Edad , Femenino

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The strain designated NCCP-602T was isolated from tannery effluent, and displayed aerobic, gram-positive, rod-shaped cells that were characterized by oxidase negative, catalase positive, and non-motile features. The most favourable growth conditions were observed at a temperature of 30°C, pH 7.0, and NaCl concentration of 1% (w/v). It tolerated heavy metals at high concentrations of chromium (3600 ppm), copper (3300 ppm), cadmium (3000 ppm), arsenic (1200 ppm) and lead (1500 ppm). The results of phylogenetic analysis, derived from sequences of the 16S rRNA gene, indicated the position of strain NCCP-602T within genus Brevibacterium and showed that it was closely related to Brevibacterium ammoniilyticum JCM 17537T. Strain NCCP-602 T formed a robust branch that was clearly separate from closely related taxa. A comparison of 16S rRNA gene sequence similarity and dDDH values between the closely related type strains and strain NCCP-602T provided additional evidence supporting the classification of strain NCCP-602T as a distinct novel genospecies. The polar lipid profile included diphosphatidylglycerol, glycolipid, phospholipids and amino lipids. MK-7 and MK-8 were found as the respiratory quinones, while anteiso-C15:0, iso-C15:0, iso-C16:0, iso-C17:0, and anteiso-C17:0 were identified as the predominant cellular fatty acids (> 10%). Considering the convergence of phylogenetic, phenotypic, chemotaxonomic, and genotypic traits, it is suggested that strain NCCP-602 T be classified as a distinct species Brevibacterium metallidurans sp. nov. within genus Brevibacterium with type strain NCCP-602T (JCM 18882T = CGMCC1.62055T).

Asunto(s)

Brevibacterium , Ácidos Grasos , Metales Pesados , Filogenia , ARN Ribosómico 16S , Brevibacterium/genética , Brevibacterium/clasificación , Brevibacterium/aislamiento & purificación , Brevibacterium/metabolismo , Brevibacterium/fisiología , ARN Ribosómico 16S/genética , Metales Pesados/metabolismo , Pakistán , Ácidos Grasos/análisis , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Composición de Base , Análisis de Secuencia de ADN , Fosfolípidos/análisis , Curtiembre , Genómica

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Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

Asunto(s)

Diferenciación Celular , Movimiento Celular , Epilepsia , Proteínas HSP90 de Choque Térmico , Accidente Cerebrovascular Isquémico , Células-Madre Neurales , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/genética , Animales , Células-Madre Neurales/metabolismo , Movimiento Celular/fisiología , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Diferenciación Celular/fisiología , Epilepsia/metabolismo , Epilepsia/genética , Ratones , Proto-Oncogenes Mas , Masculino , Humanos , Ratones Endogámicos C57BL , Progresión de la Enfermedad

RESUMEN

Bioinformatics is a rapidly growing field involving the application of computational methods to the analysis and interpretation of biological data. An important task in bioinformatics is the identification of novel drug-target interactions (DTIs), which is also an important part of the drug discovery process. Most computational methods for predicting DTI consider it as a binary classification task to predict whether drug target pairs interact with each other. With the increasing amount of drug-target binding affinity data in recent years, this binary classification task can be transformed into a regression task of drug-target affinity (DTA), which reflects the degree of drug-target binding and can provide more detailed and specific information than DTI, making it an important tool in drug discovery through virtual screening. Effectively predicting how compounds interact with targets can help speed up the drug discovery process. In this study, we propose a deep learning model called TC-DTA for the prediction of the DTA, which makes use of the convolutional neural networks (CNN) and encoder module of the transformer architecture. First, the raw drug SMILES strings and protein amino acid sequences are extracted from the dataset. These are then represented using different encoding methods. We then use CNN and the Transformer's encoder module to extract feature information from drug SMILES strings and protein amino acid sequences, respectively. Finally, the feature information obtained is concatenated and fed into a multi-layer perceptron for prediction of the binding affinity score. We evaluated our model on two benchmark DTA datasets, Davis and KIBA, against methods including KronRLS, SimBoost and DeepDTA. On evaluation metrics such as Mean Squared Error, Concordance Index and r2m index, TC-DTA outperforms these baseline methods. These results demonstrate the effectiveness of the Transformer's encoder and CNN in the extraction of meaningful representations from sequences, thereby improving the accuracy of DTA prediction. The deep learning model for DTA prediction can accelerate drug discovery by identifying drug candidates with high binding affinity to specific targets. Compared to traditional methods, the use of machine learning technology allows for a more effective and efficient drug discovery process.