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Tuberculosis (TB) remains a persistent global health threat, with Mycobacterium tuberculosis (Mtb) continuing to be a leading cause of mortality worldwide. Despite efforts to control the disease, the emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) TB strains presents a significant challenge to conventional treatment approaches. Addressing this challenge requires the development of novel anti-TB drug molecules. This study employed de novo drug design approaches to explore new EthR ligands and ethionamide boosters targeting the crucial enzyme InhA involved in mycolic acid synthesis in Mtb. Leveraging REINVENT4, a modern open-source generative AI framework, the study utilized various optimization algorithms such as transfer learning, reinforcement learning, and curriculum learning to design small molecules with desired properties. Specifically, focus was placed on molecule optimization using the Mol2Mol option, which offers multinomial sampling with beam search. The study's findings highlight the identification of six promising compounds exhibiting enhanced activity and improved physicochemical properties through structure-based drug design and optimization efforts. These compounds offer potential candidates for further preclinical and clinical development as novel therapeutics for TB treatment, providing new avenues for combating drug-resistant TB strains and improving patient outcomes.

Intracerebral hemorrhage (ICH) is a significant global public health issue that is characterized by a rapid start, severe symptoms, and a poor prognosis. It is the most common type of hemorrhagic stroke. We analyzed global intracranial hemorrhage incidence, mortality, disability-adjusted life years (DALYs), and corresponding age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) by using GBD 2021 data. The data were further stratified by age, sex, and region to assess the global burden of ICH from 1990 to 2021, providing the most up-to-date epidemiologic reference data for public health prevention and treatment strategies. In 2021, there were 3,444,300 (95 % UI, 305.30 to 381.20) new cases, 3,308,400 (302.11-359.47) deaths and 79,457,400 (7230.45-8548.02) DALYs. The burden of intracranial hemorrhage was higher in Oceania and Southeast Asia (Age-standardized DALY rates of 2582.46 per 100,000 and 1976.78 per 100,000), but lower in Australasia (126.59), high-income North America (221.19), and Western Europe (161.23). Of the 204 countries and territories globally, the burden of intracranial hemorrhage is higher in countries such as Nauru, Solomon Islands and Marshall Islands. From 1990 to 2021, global age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) declined, corresponding to EAPCs of -1.52, -1.63 and -1.75, with females declining more than males. In 2021, the most significant risk factor for ICH was high systolic blood pressure, accounting for 56.4 % of total DALYs for intracranial hemorrhage. Other major risk factors include: ambient particulate matter pollution, smoking, solid fuel pollution of household air, high sodium diet, and renal dysfunction. We need to target interventions at relevant risk factors, such as hypertension management, environmental particulate management, smoking cessation campaigns, focusing on high-risk groups and high-burden areas, and continue to deepen the implementation of the universal primary prevention strategy.

Green synthesis, an approach that has gained widespread recognition in recent years due to environmental and health concerns, was employed to synthesize green zinc oxide nanoparticles (G-ZnO NPs) using a hydro-alcoholic extract derived from dried damask rose petals. The synthesized nanoparticles were confirmed using an X-ray diffractometer, UV-visible, and Fourier transform infrared spectrometry. A morphological examination with a field emission scanning electron microscope revealed that the G-ZnO NPs had a diameter ranging from 44.66 to 83.74 nm and a purity of 93.2 %. Furthermore, the antioxidant, photocatalytic, antimicrobial, and anti-diabetic properties of G-ZnO NPs were investigated and compared with two commercial ZnO NPs of different sizes (C-ZnO NPs1 (10-30 nm) and C-ZnO NPs2 (50-60 nm)). The G-ZnO NPs demonstrated the highest antioxidant activity (46.49 %). In terms of photocatalytic activity against methylene blue, G-ZnO NPs exhibited a higher degradation rate (61 %) than C-ZnO NPs1 and C-ZnO NPs2 (53.65 and 25.63 %). The ability of nanoparticles to inhibit the growth of two bacteria Escherichia coli and Staphylococcus aureus showed that G-ZnO NPs displayed the highest inhibition rate against bacterial growth for both strains. Finally, the inhibitory effect of ZnO NPs on α-glucosidase and acetylcholinesterase enzymes was examined, revealing significant inhibition. G-ZnO NPs (600 μg/ml) exhibited stronger inhibitory effects compared to C-ZnO NPs1 and C-ZnO NPs2 for both enzymes.

Hummus provides an ideal environment for microbial growth. The objectives of this study were to evaluate the effect of high-pressure processing (HPP) on i) microbial safety/quality, ii) physical/chemical properties, and iii) sensory characteristics of hummus. Uninoculated and hummus inoculated with Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes were subjected to HPP at 350 MPa for 1-5 min. After treatment, the D-value of the pathogens was calculated and uninoculated samples were stored for up to 28 d at 4 and 10 °C and total microbial counts (TMC) were enumerated. Thiobarbituric acid reactive substances (TBARS), colour, textural and rheological properties and sensory characteristics of hummus were also analysed. The D₁₀-value for Salmonella spp., E. coli O157:H7 spp. and L. monocytogenes were 2.10 ± 0.13, 1.48 ± 0.08, and 3.77 ± 0.36 min, respectively. As compared to the control, HPP for 1, 2, 3, 4, and 5 min instantly decreased TMC on average by 0.7, 1.2, 1.6, 1.4 and 1.8 log cfu/g, respectively. The shelf life of hummus in this study after an HPP treatment of 350 MPa for 2-5 min was 28 d at 4^oC and one week at 10 °C, while it was 14 d and 7 d in the control samples, respectively. HPP decreased TBARS but did not significantly change hummus lightness, greenness, and yellowness. HPP enhanced the gel strength and viscoelastic properties of hummus without compromising its sensory qualities. Thereby, HPP at 350 MPa for 1-5 min can be effective and adopted by producers.

RNA-sequencing (RNA-seq) is an important tool to explore molecular mechanisms of disease. Technological advances mean this can be performed at the single-cell level, but the large sample sizes needed in clinical studies are currently prohibitively expensive and complex. Deconvolution of bulk RNA-seq offers an opportunity to bridge this gap by defining the cell lineage composition of samples. This approach is widely used in immunology studies, but currently there are no validated pipelines for researchers analysing human myocardium or skeletal muscle. Here, we describe the application and in silico validation of two pipelines to deconvolute human right atrium, left ventricle and skeletal muscle bulk RNA-seq data. Specifically, we have defined the major cell lineages of these tissues using single cell/nucleus RNA-seq data from the Heart Cell Atlas, which are then applied during deconvolution using the CIBERSORTx or BayesPrism deconvolution packages. Both pipelines gave robust estimates of the proportion of all major cell lineages in these tissues. We demonstrate their value in defining age- and sex-differences in tissue composition using bulk RNA-seq data from the GTEx consortium. Our validated pipelines can be rapidly applied by researchers working with existing or novel bulk RNA-seq of myocardium or skeletal muscle to gain novel insights.

Early recognition and management of risk factors that reduce kidney function are essential. This study aims to analyze the relationship between the components of metabolic syndrome and estimated glomerular filtration rate (eGFR), and to provide basic data that can help develop educational materials for the prevention of kidney diseases. Data from the second round of the KNHNES(korea national health and nutrition examination survey, 8th) which was conducted by the Korea Disease Control and Prevention Agency (2020), were downloaded and analyzed for the current research. Binary logistic analysis was used to identify factors that were risk predictors for metabolic syndrome. Identified factors were categories of metabolic syndrome, including waist circumference, blood pressure, triglycerides, blood glucose, HDL-cholesterol, triglycerides, and eGFR. eGFR was 0.03 % lower in males with metabolic syndrome (OR:0.973) and 0.03 % lower in females (OR:0.974). The eGFR was significantly lower for those with metabolic syndrome. According to this study, there was a significant correlation between reduced GFR and metabolic syndrome. Therefore, the meaningful baseline data for decreasing the prevalence of kidney disease and preventing metabolic syndrome provided by this study's results are significant.

Objective: To investigate the diagnosis and treatment of T lymphoblastic lymphoma (T-LBL) progressing into acute monocytic leukemia (AML-M5b) and explore possible pathogenic mechanisms.

Methods: Comprehensive diagnosis and evaluation of the patient's disease status were conducted through lymph node biopsy, bone marrow aspiration and biopsy, PET/CT, immunohistochemistry, flow cytometry, fusion gene detection, and whole-exome sequencing (WES) based on the clinical manifestations at different stages.

Results: The lymph node biopsy revealed Ki67 positivity at 80 % and expression of TDT, CD4, CD8, CD3, and CD5. The PET/CT scan showed increased FDG metabolism at multiple sites. Based on relevant tests and examination results, the patient was diagnosed with T-LBL (stage IV; IPI score, 3). After three cycles of chemotherapy, abnormal immature monocytes were detected using bone marrow flow cytometry, suggesting an acute progression from T-LBL to AML-M5b. Chromosomal karyotype analysis revealed t(9; 11)(p22; q23) and the MLL-AF9 fusion gene. WES analysis identified mutations in several genes, among which mutations in SET domain-containing protein 2 and CBL may be associated with the occurrence of acute myeloid leukemia. The patient died 1 month after AML-M5b diagnosis.

Conclusion: Patients with T-LBL progression to AML have a poor prognosis and shorter overall survival. Hence, exploring the pathogenic mechanisms and reasons for disease progression has significant implications for finding effective treatment modalities and prolonging patient survival.

Background: Radiotherapy is a vital postoperative adjuvant treatment for gliomas. However, radioresistance seriously affect the treatment efficacy. Excavating the feature of radioresisrtance in gliomas comprehensively are necessary.

Methods: In the training set, 191 patients from the Chinese Glioma Genome Atlas (CGGA) were included, of which all patients had received postoperative radiotherapy. The epidemiological data and RNA sequencing data of 430 patients with whole grade glioma were obtained from the Cancer Genome Atlas (TCGA), which was used for validation.

Results: Based on the Lasso regression analysis, five-gene signature was established which was associated with VAT1-related radioresistance in gliomas. High-risk patients showed higher proportion of elders, high-grade glioma, oligodendroglial histology and IDH wild type. The risk score was identified as an independent prognostic factor in the CGGA dataset, and the high-risk score impaired the overall survival time. The biological processes of positively expressed genes of risk score were functionally involved in inflammatory and immune response. And the activation of signaling pathways in high-risk score group also showed close correlation with tumor occurrence, progression and immune microenvironment. What's more, the immune cell infiltration analysis showed that high-risk score indicated decreased CD8⁺ T cell and the upregulation of the immune checkpoints, which probably promoted the immunosuppressive microenvironment.

Conclusion: The five-gene signature can predict the survival of patients with glioma received postoperative radiotherapy efficiently. The immunosuppressive microenvironment, as a feature of glioma, potentially devote to the radioresistance.

Agricultural information is essential for the development of agriculture and the improvement of farmers' living standards. This study evaluated the utilization of agricultural information and its intensity among smallholder farmers in the East Gojjam Zone of the Amhara Regional State in Ethiopia. Data was collected through structured interviews, focus group discussions, and key informant interviews; it was analyzed using frequency counts, percentages, and an ordered probit model in Stata. The results reveal that family members, extension workers, and neighboring farmers are the primary sources of agricultural knowledge for smallholder farmers in the study area. The ordered probit regression analysis identified several significant predictors of agricultural information utilization, including marital status, farm experience, exposure to electronic and printed media, access to extension services, availability of farm inputs, training opportunities, market distance, proximity to development agent centers, and attendance in Farmer Training Center (FTC) events. Major constraints to information utilization were found to include limited cultivated land (92.56 %), uncertainties (92.31 %), weak economic conditions (91.32 %), lack of credit for technological inputs (86.10 %), insufficient facilities and professionals (78.75 %), and labor shortages (76.92 %). The study recommends that policymakers and local governments enhance extension services, invest in training centers, improve credit accessibility, leverage media and ICT, strengthen infrastructure, and implement targeted training programs to optimize agricultural information dissemination and utilization. These measures are crucial for boosting productivity and improving farmers' livelihoods in the study area.

Background: Volvariella volvacea is a highly nutritious edible mushroom grown mainly in Southeast Asian countries. However, the low yield of V. volvacea has discouraged farmers from engaging in its production.

Objective: The study was conducted to observe the improvement of V. volvacea yield depending on various physiochemical parameters of V. volvacea growth.

Methods: The parameters tested in this study include the weight of the substrate, i.e., 2 kg (W1) and 6 kg (W2); the surface area of the substrate: A1 (1218 cm²), A2 (1530 cm²) and A3 (2000 cm²); and four different substrate formulations (F1, F2, F3 and F4).

Results: Substrate weight and surface area were found to be important, but not critical, factors in determining fruiting bodies formation, total fungal mass, and BE rate. However, the formulation media showed a significant contribution that could help in the induction of fruiting bodies. According to the results, the culture medium with a mixture of EFB substrate and black soil showed the highest BE percentage of 17.75 % (at optimised substrate weights = 2 kg).

Conclusion: The results of this study can be used as a reference for further studies to improve the cultivation of V. volvacea, especially when EFB fibres are used as the main substrate. Future studies to identify genes involved in the formation of fruiting bodies are strongly recommended.