Study on the expression and prognostic relationship of MYL6B in liver cancer based on bioinformatics.

BACKGROUND: Primary liver cancer is a prevalent and deadly cancer type. Despite treatment advances, prognosis remains poor, with high recurrence rates. Early detection is crucial but challenging due to the disease's insidious nature. Myosin proteins play significant roles in cancer development, influencing cell migration, invasion, and tumor suppression. MYL6B, a myosin light chain, is involved in various cellular processes and has been associated with poor prognosis in colorectal adenocarcinoma and potential as a biomarker in breast cancer. AIM: To investigate the expression of MYL6B in liver hepatocellular carcinoma (LIHC) and its impact on prognosis and potential mechanisms of action using bioinformatics methods. METHODS: The expression of MYL6B in pan-cancer and normal tissues was analyzed using the gene expression profiling interactive analysis 2 and tumor immune estimation resource databases. The expression level of MYL6B in LIHC tissues and its relationship with prognosis were analyzed, immunohistochemical analysis of MYL6B and its effect on immune cell infiltration, and the protein network were further studied. RESULTS: MYL6B was highly expressed in diffuse large b-cell lymphoma, LIHC, pancreatic adenocarcinoma, skin cutaneous melanoma, thymoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, and lowly expressed in kidney chromophobe, acute myeloid leukemia, testicular germ cell tumors. The expression level of MYL6B was significantly different between cancer and normal tissues. It had a significant impact on both overall survival and disease-free survival. MYL6B is highly expressed in hepatocellular carcinoma and its expression level increases with cancer progression. High MYL6B expression is associated with poor prognosis in terms of overall survival and recurrence-free survival. The immunohistochemical level of MYL6B is high in hepatocellular carcinoma tissues, and MYL6B has a high level of immune infiltration inflammation. In protein network analysis, MYL6B is correlated with MYL2, MYL6, MYL9, MYLK4, MYLK2, MYL12A, MYL12B, MYH11, MYH9 and MYH10. CONCLUSION: The expression level of MYL6B in LIHC was significantly higher than in normal liver tissues, and it was correlated with the degree of differentiation survival rate, and immune infiltration. MYL6B is a potential target for LIHC treatment.

Antibacterial Indole-diterpenoid Alkaloids from the Marine Fungus Penicillium sp. ZYX-Z-718.

Two new indole-diterpenoids, penpaxilloids F and G (1 and 2), along with 11 known analogues (3-13), were isolated from the marine fungus Penicillium sp. ZYX-Z-718. The structures of the new compounds were identified by extensive spectroscopic analyses including HR-ESI-MS, UV, and NMR, as well as theoretical NMR chemical shifts and ECD calculations. Compounds 6 and 10 showed antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and MRSA with MIC values ranging from 16.0 to 32.0 µg/mL.

Persteroid, a new steroid from the marine-derived fungus Penicillium sp. ZYX-Z-143.

A new steroid named persteroid (1) and seven known compounds (2-8) were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. The structure of 1 was determined by HRESIMS, NMR, and ECD calculations. Compound 1 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 46.31 ± 0.52 µM. Moreover, compound 1 potently suppressed nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The cytotoxicity and antibacterial activity of all isolates were tested.

Impact of ginsenoside Rb1 on gut microbiome and associated changes in pharmacokinetics in rats.

Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

A novel prognostic scoring system for AML patients undergoing allogeneic hematopoietic stem cell transplantation with real world validation.

OBJECTIVES: This study aims to develop a robust predictive model for survival in AML patients undergoing allo-HSCT. METHODS: It was performed a retrospective analysis of 336 AML patients who underwent allo-HSCT at Peking University First Hospital between September 2003 and March 2023. Univariable and multivariable Cox regression analyses were conducted to determine hazard ratios (HR) for overall survival. A predictive model was developed based on multivariable analysis results. Internal validation was carried out through bootstrap resampling, and the model's performance was assessed using the Concordance Index (C-index), Receiver Operating Characteristics (ROC) curve, calibration plots, and Decision Curve Analysis (DCA). RESULTS: Our prognostic model, which includes age, disease stage, donor/recipient gender, mononuclear cell counts, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), effectively stratified patients into low-risk and high-risk groups. The two groups showed significant differences in overall survival (P<0.0001), disease-free survival (P<0.0001), non-relapse mortality (NRM) (P<0.0001), and relapse rates (P=0.08). The model achieved a C-index of 0.71. Calibration plots and DCA confirmed strong alignment between predicted and observed outcomes. Subgroup analysis revealed that overall survival was significantly lower in the high-risk group compared to the low-risk group in both measurable residual disease (MRD) negative and MRD positive subgroups (P=0.015 for both). CONCLUSION: The developed prognostic model, which integrates comprehensive disease and patient characteristics, enhances risk stratification for AML patients undergoing allo-HSCT. This model effectively stratifies risk in both MRD-negative and MRD-positive subgroups and may facilitate more informed MRD-based treatment decisions.

MIGP: Metapath Integrated Graph Prompt Neural Network.

Graph neural networks (GNNs) leveraging metapaths have garnered extensive utilization. Nevertheless, the escalating parameters and data corpus within graph pre-training models incur mounting training costs. Consequently, GNN models encounter hurdles including diminished generalization capacity and compromised performance amidst small sample datasets. Drawing inspiration from the efficacy demonstrated by self-supervised learning methodologies in natural language processing, we embark on an exploration. We endeavor to imbue graph data with augmentable, learnable prompt vectors targeting node representation enhancement to foster superior adaptability to downstream tasks. This paper proposes a novel approach, the Metapath Integrated Graph Prompt Neural Network (MIGP), which leverages learnable prompt vectors to enhance node representations within a pretrained model framework. By leveraging learnable prompt vectors, MIGP aims to address the limitations posed by mall sample datasets and improve GNNs' model generalization. In the pretraining stage, we split symmetric metapaths in heterogeneous graphs into short metapaths and explicitly propagate information along the metapaths to update node representations. In the prompt-tuning stage, the parameters of the pretrained model are fixed, a set of independent basis vectors is introduced, and an attention mechanism is employed to generate task-specific learnable prompt vectors for each node. Another notable contribution of our work is the introduction of three patent datasets, which is a pioneering application in related fields. We will make these three patent datasets publicly available to facilitate further research on large-scale patent data analysis. Through comprehensive experiments conducted on three patent datasets and three other public datasets, i.e., ACM, IMDB, and DBLP, we demonstrate the superior performance of the MIGP model in enhancing model applicability and performance across a variety of downstream datasets. The source code and datasets are available in the website.1.

An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.

Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

Progression of Uterine Artery Pseudoaneurysm Documented by Ultrasonography: A Case Report.

Introduction: Uterine artery pseudoaneurysm (UAP) is a rare cause of late postpartum hemorrhage. Insufficient understanding of this condition among clinicians may result in delayed diagnosis and treatment, potentially leading to incorrect interventions and poor prognosis, including fatal hemorrhage and even necessitating hysterectomy in severe cases. Case Report: The patient, a 41-year-old woman with a history of three pregnancies and two deliveries, underwent cesarean section and subsequently experienced persistent small amounts of vaginal bleeding for a duration of two months. Transvaginal ultrasonography revealed a hypoechoic mass in the cervix that was initially misdiagnosed as a cervical fibroid. Approximately 12 h prior to admission, she experienced an episode of acute vaginal bleeding of significant intensity. Emergency transvaginal ultrasound demonstrated an intrauterine mass located in the posterior wall of the cervix with swirling blood flow, exhibiting a to-and-fro pattern. The mass was connected to the left uterine artery adjacent to the cervix through a tear measuring approximately 0.5 cm in diameter. Emergency bilateral uterine artery embolization was performed. After a follow-up period of ten months, there was no recurrence of abnormal vaginal bleeding, and subsequent ultrasound examination confirmed the complete resolution of the cervical lesions. Conclusion: The findings of this case suggest that the UAP undergoes a dynamic process. In the early stages, the lesion may manifest as a small hypoechoic or anechoic area within the myometrium. Color Doppler imaging might not reveal blood flow signals within the lesion, potentially leading to misdiagnosis as other common uterine lesions such as fibroids or cysts. However, considering the close association between UAP and the uterine artery, meticulous observation of the relationship between the uterine artery and its branches is crucial for identifying myometrial lesions to facilitate early detection of UAP and minimize misdiagnosis.

Gastric metastasis of small cell lung carcinoma: Three case reports and review of literature.

BACKGROUND: Small cell lung carcinoma (SCLC) is highly susceptible to metastasis in the early stages of the disease. However, the stomach is an uncommon site of metastasis in SCLC, and only a few cases of this type of metastasis have been reported. Therefore, SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed. CASE SUMMARY: We report three cases of gastric metastasis from SCLC in this article. The first patient presented primarily with cough, hemoptysis, and epigastric fullness. The other two patients presented primarily with abdominal discomfort, epigastric distension, and pain. All patients underwent gastroscopy and imaging examinations. Meanwhile, the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma. Finally, the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis. The three patients did not receive appropriate treatment and died within a short time. CONCLUSION: Here, we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians' understanding of this disease.

[Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35, TGF-ß and IL-10 in Hemophilia A Patients with Fâ § Inhibitor].

OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model.

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG-E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1ß, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Global Trends of Antibiotic Resistance Genes in Staphylococcus aureus: A Comprehensive Genomic Analysis.

Staphylococcus aureus (S. aureus) is a pathogen capable of causing severe diseases and exhibiting resistance to multiple antibiotics. However, there is a significant lack of comprehensive research on the global prevalence of its antibiotic resistance genes (ARGs). This study provided a comprehensive analysis of ARGs in S. aureus, using 113,842 S. aureus genome sequences from the National Center for Biotechnology Information database. The results revealed that a significant majority (84%) of these genomes harbored at least one ARG, with a total of 389,464 ARG sequences identified across 19 major types and 103 subtypes. These ARGs exhibited varied abundances and diversities, linked primarily to clinical cases worldwide. ARGs for fluoroquinolones, multidrug resistance, bacitracin, tetracyclines, beta-lactams, and aminoglycosides were notably abundant, ranging from 3.16 × 10-5 to 1.49 copies of ARG per million bp. Variations in the abundance and diversity of ARGs were observed between countries, with middle- and low-income countries showing higher gene abundance but lower diversity compared with high-income countries. Temporal analysis over 30 years showed a fluctuating decline in ARG abundance alongside an increase in diversity, suggesting evolving resistance mechanisms. The study also explored the role of mobile genetic elements in ARG dissemination, finding a substantial proportion of ARG subtypes associated with plasmids and insertion sequence elements, indicating their potential for spread across borders. The global distribution of mobile ARGs was further analyzed, revealing the extensive reach of certain ARGs across countries. This research provides valuable insights into the prevalence and dissemination of antibiotic resistance in S. aureus on a global scale, aiding in the development of effective monitoring and control strategies to combat ARGs in S. aureus and other pathogens.

Electro-Osmotic Flow and Mass Transfer through a Rough Microchannel with a Modulated Charged Surface.

In this paper, we investigate the electro-osmotic flow (EOF) and mass transfer of a Newtonian fluid propelled by a pressure gradient and alternating current (AC) electric field in a parallel microchannel with sinusoidal roughness and modulated charged surfaces. The two-wall roughness is described by in-phase or out-of-phase sine functions with a small amplitude δ. By employing the method of perturbation expansion, the semi-analytical solutions of the Poisson-Boltzmann (P-B) equation based on the Debye-Hückel approximation and the modified Navier-Stokes (N-S) equation are obtained. The numerical solution of the concentration equation is obtained by the finite difference method. The effects of sinusoidal roughness, modulated charged surface, and the AC electric field on the potential field, velocity field, and concentration field are discussed. Under the influence of the modulated charged surface and sinusoidal roughness, vortices are generated. The velocity oscillates due to the effect of the AC electric field. The results indicate that solute diffusion becomes enhanced when the oscillation Reynolds number is below a specific critical value, and it slows down when the oscillation Reynolds number exceeds this critical value.

Distribution and spread of tigecycline resistance gene tet(X4) in Escherichia coli from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.

Substrate Characterization for Hydrolysis of Multiple Types of Aromatic Esters by Promiscuous Aminopeptidases.

Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.

Caregivers' experiences in helping individuals with severe and enduring mental health challenges integrate into the community: A qualitative descriptive study in Singapore.

WHAT IS KNOWN ABOUT THE SUBJECT: Individuals with severe and enduring mental health challenges continued to consume mental health services for an average of 13 years as they needed multiple acute psychiatric admissions due to the challenges they experienced in their everyday activities. As caregivers of individuals with severe and enduring mental health challenges, they often bear the brunt of caregiving through their assistance with activities of daily living (ADL), providing emotional support and ensuring medication compliance for their loved ones. When caring for their loved ones, caregivers often reported psychological stress, social isolation and emotional exhaustion due to stressors such as uncertainty of the future, the lack of support from professional services and the isolation from their own social network and support mechanism. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Insights from this study revealed that caregivers for individuals with severe and enduring mental health challenges went through a lonely and exhausting journey fraught with psychological, physical, social and financial challenges, echoing the caregiving needs and the prevalence of the caregiver burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Insights shared by the caregivers demonstrated the need for a centralised point of contact to navigate Singapore's fragmented mental healthcare sector. Peer-support groups should be further promoted because they offer the benefits of information exchange, mutual support and a sense of empowerment and hopefulness, which may help ease the caregiver burden. Life skills training, such as teaching how to communicate empathetically with family members, resolve conflicts using open communication, maintain a structured daily routine and solve pragmatic problems in daily life, is more critical for individuals with severe and enduring mental health challenges. This will help them learn how to manage their well-being, live independently, and stabilise their conditions. Lastly, public awareness campaigns should honour caregivers by highlighting their strength, resilience, and dedication. The state can provide financial assistance in the form of tax relief for their income per annum or caregiver allowance to alleviate the financial stress that caregivers are facing. ABSTRACT: Introduction The progressive deinstitutionalisation of mental healthcare has increasingly shifted care responsibilities from healthcare professionals to family caregivers for individuals with severe mental illness. Caregivers must balance many obligations, which often compromise their overall health and well-being, while helping their loved ones integrate into the community. Aim To identify and understand caregivers' needs and challenges as they help individuals with severe and enduring mental health challenges integrate into the community. Methods This study used a descriptive qualitative approach to explore the experiences and challenges of caregivers for individuals with severe and enduring mental health challenges when integrating back into the community. A semi-structured guide was used during the video-conferencing interviews conducted between December 2021 and November 2022. This study was reported according to the 32-item Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Findings Fourteen caregivers were individually interviewed by the primary author. Most caregivers were female, with an average of 15 years of experience caring for their loved ones. Using Braun and Clark's six-phase thematic framework, we inductively generate the themes and subthemes from the data. The two themes were (i) challenges (whose subthemes included personal challenges in caregiving, the lack of awareness, and stigma and employment) and (ii) support (whose subthemes included the importance of socialisation for individuals with mental health conditions, existing avenues of support and potential areas for support). Discussion Our findings informed the contemporary needs of caregivers caring for individuals with severe and enduring mental health challenges integrating into the community. Like the global challenges for people with mental health issues, psychosocial support and other supplementary support are still common themes in mental health settings. The findings further specifically highlighted the importance of accessible points of contact as resources and employment-enabling and sustaining initiatives to help manage caregivers' emotional and system challenges, which addresses the gaps identified in the findings. Caregivers' peer-support groups, life skills training and public mental health awareness are also necessitated by the caregivers' voices. Implications for Practice Priority areas include having a centralised point of contact within the community for caregivers. Government or not-for-profit organisations can take the lead by initiating employment-enabling initiatives for individuals with severe and enduring mental health challenges and their caregivers.

Rapid solar-driven atmospheric water-harvesting with MAF-4-derived nitrogen-doped nanoporous carbon.

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.