Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This study investigates the effects of Arctiin, known for its diverse biological properties, on experimental autoimmune uveitis (EAU) through its action on Th17 cells and the JAK/STAT signaling pathway. Our findings reveal that Arctiin significantly alleviates EAU by reducing clinical scores, inflammatory cell infiltration, and levels of inflammatory cytokines like IL-17 and TNF-α in the eye.
View Article and Find Full Text PDFMolybdenum (Mo) is widely used as a micronutrient fertilizer to improve plant growth and soil quality. However, the interactions between cell wall biosynthesis and molybdenum have not been explored sufficiently. This study thoroughly investigated the regulatory effects of different concentrations of Mo on tobacco cell wall biosynthesis from physiological and metabolomic aspects.
View Article and Find Full Text PDF: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. : Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis.
View Article and Find Full Text PDFBackground: Pancreatic cancer remains one of the deadliest malignancies, largely due to its late diagnosis and lack of effective therapeutic targets.
Materials And Methods: Using traditional machine learning methods, including random-effects meta-analysis and forward-search optimization, we developed a robust signature validated across 14 publicly available datasets, achieving a summary AUC of 0.99 in training datasets and 0.
Nat Med
January 2025
Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.
View Article and Find Full Text PDFSelenopeptides can be ideal dietary selenium (Se) supplements for humans. Currently, rice is not used much as a source of selenopeptides. Here, we executed the selenopeptidomics analysis of selenium-enriched rice protein hydrolysates using the full MS-dd-MS2 acquisition method and identified selenopeptides, including L{Se-Met}AK and other selenopeptides.
View Article and Find Full Text PDFGrating under auto-collimation configuration with polarization-independent high diffraction efficiency plays an important role in the displacement measurement system, spectral beam combining system and so on. In this paper, we proposed, for the first time, a reflective two-dimensional metal-dielectric grating of which the (-1, -1) order beam is diffracted back along the input light direction, when the incident azimuth angle is 45°. With optimized structure, the (-1, -1) order diffraction efficiencies of transverse electric polarization (TE) and transverse magnetic polarization (TM) are 95.
View Article and Find Full Text PDFMyeloid malignancies include various types of cancers that arise from abnormal development or proliferation of myeloid cells within the bone marrow. Chimeric antigen receptor (CAR) T cell treatments, which show great potential for B cell and plasma cell cancers, face major challenges when used for myeloid malignancies. CAR natural killer (NK) cell-based immunotherapy encounters several challenges in treating myeloid cancers, including: (1) poor gene transfer efficiency and expansion platforms in vitro, (2) limited proliferation and persistence in vivo, (3) antigenic heterogeneity, and (4) an immunosuppressive tumor microenvironment.
View Article and Find Full Text PDFObjectives: This study seeks to delineate the sleep architecture characteristics in older adults with short-term insomnia and mild cognitive impairment (MCI) and to explore their association with cognitive performance.
Methods: Ninety elderly individuals with short-term insomnia were enrolled and stratified into two cohorts based on their Montreal Cognitive Assessment (MoCA) scores: the Short-Term Insomnia Group (STID) comprising 35 participants and the Short-Term Insomnia with Cognitive Impairment Group (STID-MCI) with 55 participants. Demographic data, Pittsburgh Sleep Quality Index (PSQI), MoCA, Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and polysomnography (PSG) parameters were compared between groups.
Microcystin LR (MC-LR) pollution is a serious threat to aquatic ecosystems and public health in China and is an environmental problem that urgently needs to be solved. However, few studies have investigated the anaerobic degradation pathway and related molecular biological mechanisms of MC-LR. In this study, a bacterium capable of degrading MC-LR with a degradation efficiency of 0.
View Article and Find Full Text PDFCellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro.
View Article and Find Full Text PDFDendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74).
View Article and Find Full Text PDFBackground: Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from Schisandra chinensis (Turcz.
View Article and Find Full Text PDFApproaches of promoting a neural milieu permissive for plasticity and resilience against neuronal injury are important strategies for the treatment of a range of neurological disorders. Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective against various mental diseases. However, the underlying molecular mechanisms remain elusive.
View Article and Find Full Text PDFTo improve the effectiveness of government environmental attention on resource allocation, this study proposes a measurement framework using text analysis and an unsupervised Word2vec model to quantify local government environmental attention of 288 Chinese cities. We further examine its impact on total factor productivity (TFP) of China's listed firms from 2010 to 2021 using the high-dimensional fixed-effects and panel quantile regression models. The findings show that: (1) Local government environmental attention contributes positively to TFP, with each unit increase raising TFP by approximately 1.
View Article and Find Full Text PDFMulberry ( spp.) is an economically significant plant in the production of silk through feeding leaves to silkworm larvae. Traditional silkworm rearing is heavily labor-intensive, particularly in leaf collection, which leads to low efficiency and impedes the development of sericulture.
View Article and Find Full Text PDFBud dormancy is a critical adaptive trait in woody plants, essential for enduring harsh winter conditions. The relationship between bud break timing and cold resistance is complex and has been a subject of debate. This study utilizes a Genome-Wide Association Study (GWAS) on 201 natural mulberry populations to identify the gene, which shows the strongest association with bud break timing.
View Article and Find Full Text PDFBackground: Type 2 diabetes mellitus (T2DM) development is closely linked to microbiota, influenced by geography, ethnicity, gender, and age. While the relationship between oral microbiota and T2DM has been explored, specific microbiota associated with T2DM in the Dai and Han populations remains unclear. This study aims to compare oral microbiota differences and identify keystone species between these populations, both with and without T2DM.
View Article and Find Full Text PDFBackground: This study aims to explore the value of habitat-based magnetic resonance imaging (MRI) radiomics for predicting the origin of brain metastasis (BM).
Purpose: To investigate whether habitat-based radiomics can identify the metastatic tumor type of BM and whether an imaging-based model that integrates the volume of peritumoral edema (VPE) can enhance predictive performance.
Methods: A primary cohort was developed with 384 patients from two centers, which comprises 734 BM lesions.
The global prevalence of ST11 hypervirulent carbapenem-resistant (hv-CRKP) isolates has been increasingly documented, yet genomic characterization of this clone remains insufficiently explored. Here, we report a clinical ST11-KL25 hv-CRKP strain (KP156) that exhibited resistance to multiple antibiotics and demonstrated hypervirulence in a mouse infection model. Whole-genome sequencing revealed that KP156 harbored one virulence plasmid (pKP156-Vir) and two resistance plasmids (pKP156-KPC and pKP156-tetA).
View Article and Find Full Text PDFNeuroblastoma is the most prevalent extracranial solid tumor among children and exhibits remarkable heterogeneity. The methylation of cytosine to form 5-methylcytosine (m5C) is the primary type of modification found in DNA and RNA. The NOL1/NOP2/sun (NSUN) family, specifically NSUN1, is responsible for the methylation process and has been shown to play a key role in cell differentiation and cancer development.
View Article and Find Full Text PDFBackground: Patients with Gram-negative bloodstream infections are at risk of serious adverse outcomes without active treatment, but identifying who has antimicrobial resistance (AMR) to target empirical treatment is challenging.
Methods: We used XGBoost machine learning models to predict antimicrobial resistance to seven antibiotics in patients with Enterobacterales bloodstream infection. Models were trained using hospital and community data from Oxfordshire, UK, for patients with positive blood cultures between 01-January-2017 and 31-December-2021.
CAR-T cell therapy, a cutting-edge cellular immunotherapy with demonstrated efficacy in treating hematologic malignancies, also exhibits significant promise for addressing autoimmune diseases. This innovative therapeutic approach holds promise for achieving long-term remission in autoimmune diseases, potentially offering significant benefits to affected patients. Current targets under investigation for the treatment of these conditions include CD19, CD20, and BCMA, among others.
View Article and Find Full Text PDFThis study isolated a myosmine-degrading bacterial strain J-6 from tobacco-growing soil. The identification of this strain revealed it to be a new species within the genus Sphingopyxis. Analysis of the myosmine degradation products by HPLC, preparative HPLC, and UHPLC-MS/MS identified 8 metabolites, among which 3-pyridylacetic acid (3-PAA), 5-(3-pyridyl)tetrahydrofuranone-2 (PTHF), and 4-hydroxy-4-(3-pyridyl)butanoic acid (HPBA) were three novel metabolites that were not previously found in microbial degradation of tobacco alkaloids.
View Article and Find Full Text PDFBackground: Current guidelines recommend combining a macrolide with a β-lactam antibiotic for the empirical treatment of moderate-to-high severity community-acquired pneumonia (CAP); however macrolide use is associated with potential adverse events and antimicrobial resistance.
Methods: We analysed electronic health data from 8,872 adults in Oxfordshire, UK, hospitalised with CAP between 01-January-2016 and 19-March-2024, who received either amoxicillin or co-amoxiclav as initial treatment. We examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score, using inverse probability treatment weighting to address confounding by baseline severity.