Modeling the efficacy of a novel antidepressant zuranolone for major depressive disorder.

This research aimed to quantify the treatment potential of zuranolone-a novel positive allosteric GABA receptor modulator-in adults with major depressive disorder (MDD). Publicly available databases were systematically searched to identify randomized, placebo-controlled trials. We used changes in rating scale scores from baseline to perform a model-based meta-analysis, characterizing the progression of drug efficacy and placebo response over time and comparing zuranolone's efficacy and safety profiles with those of established antidepressants (escitalopram and amitriptyline).

SparseTSF: Lightweight and Robust Time Series Forecasting via Sparse Modeling.

This paper introduces SparseTSF, a novel and extremely lightweight method for Long-term Time Series Forecasting (LTSF), designed to address the challenges of modeling complex temporal dependencies over extended horizons with minimal computational resources. At the heart of SparseTSF lies the Cross-Period Sparse Forecasting technique, which simplifies the forecasting task by downsampling the original sequences to focus on cross-period trend prediction. This technique not only significantly reduces model complexity and the number of parameters but also serves as an implicit regularization mechanism that enhances the model's robustness, achieving an optimal balance between performance and efficiency.

The association between serum 25-hydroxyvitamin D levels and clinical outcomes in Chinese adult inpatients: a retrospective cohort study.

Objectives: Previous studies reported the controvertible association between serum 25-hydroxyvitamin D [25(OH)D] level and clinical outcomes, however, whether serum 25(OH)D level were associated with length of hospital stay (LOS) and mortality remained uncertain.

Methods: Participants were recruited from three teaching hospitals between January 1, 2018 and October 31, 2022 in Shanghai and Beijing, China. Serum concentration of 25(OH)D and other clinical information was collected from medical records.

Changes in enzyme activity and microbial community of rhizosphere soil under continuously monocultured Passiflora edulis treatment.

In response to the severe continuous cropping obstacles encountered during the cultivation of passion fruit, which leads to significant declines in yield and quality, as well as rampant pests and diseases, it is particularly important to explore strategies for mitigating these obstacles. The present study used the rhizosphere soil samples from one-year-old (FY, first-year cropping) and two-year-old (SY, second-year cropping) "Golden Passion Fruit" plants, along with soil from uncropped land (CK) as a control and the techniques such as high-throughput sequencing, qRT-PCR, and HPLC-MS to analyze the main physicochemical properties, phenolic acid content, and microbial community changes in the rhizosphere soil of passion fruit under different continuous cropping durations, the results indicated that the contents of total nitrogen, total phosphorus, available nitrogen, available phosphorus, available potassium, and organic matter in FY soil were significantly higher than those in SY soil, and the pH value of the FY soil was also significantly higher than that of SY soil. Additionally, compared with FY soil, the activities of polyphenol oxidase, peroxidase, urease, and invertase in SY soil were significantly reduced by 18.

Multi-source positioning information fusion method based on improved robust Kalman filter.

Enhancing positioning accuracy in rolling machinery is vital for quality and construction efficiency. To mitigate random noise interference in deep and narrow valleys, a multi-source positioning information fusion method utilizing an improved robust Kalman filter is proposed. This method adaptively selects optimal observations from GNSS, Robotic Total Station (RTS) and Ultra Wide Band (UWB) data, compensates for location deviation and data loss from noise interference, thus improving data robustness.

Physiologically based pharmacokinetic model of IgG to predict mother-to-fetus transfer of ustekinumab in pregnant patients with inflammatory bowel disease.

The placenta serves as a critical interface for maternal-fetal substance exchange, including the active transport of immunoglobulin G (IgG), which is essential for neonatal immune protection. While mechanisms of IgG transfer are well-studied, the impact of therapeutic monoclonal antibodies (mAbs) on placental IgG dynamics during pregnancy remains unclear. This study aimed to predict maternal and fetal drug concentrations of ustekinumab (UST), an IgG1 monoclonal antibody used for treating inflammatory bowel disease (IBD), using a physiologically based pharmacokinetic (PBPK) model.

Progressive Remodeling of Global Protein Interaction Networks in a Mouse Model of Tauopathy.

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present the first temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas identifies functionally validated assemblies-including MAPT-Dpysl2 and Cyfip1-actin complexes-that modulate early disease phenotypes in vivo.

Effects of Curcumin on miR-21/Tregs and IL-6 in PBMCs From Patients With Myocardial Infarction.

The present study aimed to evaluate the effects of curcumin on the percentage of Tregs as well as miR-21 gene expression and IL-6 levels in peripheral blood mononuclear cells (PBMCs) in patients experiencing myocardial infarction (MI) compared to the controls. Isolation of PBMCs was performed from the peripheral blood of the subjects of the studied groups (50 patients with MI as a case group, and 50 controls). The effects of the low doses of curcumin (0.

Precision dosing of perampanel in pediatric patients receiving oxcarbazepine combination therapy: physiologically based pharmacokinetic modeling and simulation.

Background: The combination of oxcarbazepine (OXC) with perampanel (PER) considerably reduces the blood concentration of PER in children, decreasing the antiepileptic effect of PER. This study aimed to predict PER exposure and provide recommendations for dose adjustment in pediatric patients.

Research Design And Methods: Physiologically based pharmacokinetic (PBPK) models of PER and OXC for adults and pediatrics were developed and verified, followed by drug - drug interaction (DDI) modeling and validation of the models against available pharmacokinetic data.

Children's Lung Function Was Lower in 2017-2018 than in 1995-1996: The Roles of Air Quality Change and Individual-Level Risk Factors.

Air quality has improved while the lifestyle of children has changed substantially over the past 2 decades in four Chinese cities. It is unknown how these changes affected the lung function of children. We analyzed data collected in 1995-1996 and 2017-2018.

AdaptiveFL: Communication-Adaptive Federated Learning Under Dynamic Bandwidth.

Federated learning (FL) is a distributed machine learning paradigm that enables heterogeneous devices to train a model collaboratively. Recognizing communication as a bottleneck in FL, existing communication-efficient solutions, e.g.

First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report.

Background: Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used as an effective therapy against relapsed/refractory multiple myeloma (MM). However, the relapse rates in these patients are still high, which may be related to the poor quality of T cells after multiple chemotherapies. The case reported here demonstrated the effectiveness and safety of first-line anti-BCMA CAR-T cell therapy for high-risk MM patients, even in frailty with multiple comorbidities.

Protocol for dual metabolomics and proteomics using nanoflow liquid chromatography-tandem mass spectrometry.

Nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS) benefits untargeted metabolomics by enhancing sensitivity and integrating proteomics for the same sample. Here, we present a protocol to enable nLC-MS for dual metabolomics and proteomics. We describe steps for solid-phase micro-extraction (SPME)-assisted metabolite cleaning and enrichment, which avoids capillary column blockage.

The involvement of auxin response factor OsARF7 in positively regulating root development by mediating the expression of OsCRL1 in rice (Oryza sativa L.).

The root is one of the most important organs that determines the final grain yield in rice. Auxin is essential for root development in plants. Rice auxin response factor7 (OsARF7), belonging to the ARF family, is a key regulator of root development.

Toward Precision Dosing of Lamotrigine During Pregnancy: Physiologically Based Pharmacokinetic Modeling and Simulation.

Lamotrigine is a commonly used anti-seizure medication in pregnant women. However, its pharmacokinetics (PK) during pregnancy markedly change, increasing the frequency of seizures and endangering the safety of the mother and fetus. Meanwhile, insufficient PK data on lamotrigine during pregnancy hinders its dose adjustment.

Physiologically based pharmacokinetic model for oxcarbazepine active metabolite to predict pharmacokinetics in paediatric patients with renal impairment and adjust dosages.

Aims: Oxcarbazepine (OXC) has been approved as monotherapy or adjunctive therapy for paediatric partial seizures. There are few reports on the pharmacokinetics (PK) of OXC in paediatric patients with renal impairment (RI), especially dosage studies of RI, which are rarely conducted on paediatric patients. This study aimed to predict the PK of OXC in children with RI and to provide recommendations for dose adjustment in this population.

Impacts of changes in PM concentrations and their major components on blood pressure during pregnancy.

Sulfate, nitrate, ammonium, organic matter, and black carbon account for more than two-thirds of the total mass of PM and have stronger cardiovascular toxicity than other components. However, evidence regarding the gestational cardiovascular toxicity of these PM components is lacking. A prospective cohort study was conducted among 1913 pregnant women in Guangzhou, Pearl River Delta, China, from 2017 to 2020.

High-Density Donor-Acceptor Pair Mediated Carrier Transport Dynamics for Hydrogen Production Performance Promotion Based on Nonstoichiometric Quantum Dots.

Ternary I-III-VI semiconductors are useful light-capture materials, but the presence of a special donor-acceptor pair complicates the dynamics of carriers in the photocatalytic process, and the combined effect of multiple types of defects makes it difficult to study the single type of defect on carrier dynamics. Here, excess inorganic S ligand is used to passivate the surface defects of the nonstoichiometric ratio Ag-In-Zn-S quantum dots (QDs), which enables the systematic investigation of the effects of high-density donor-acceptor pairs on the carrier separation and transfer path during photocatalysis. The results show that the donor-acceptor pair defects in quantum dots can effectively separate the carriers because the defects generated by the donor or acceptor can effectively "store" the carriers at the fixed energy level and provide an additional path for the transfer of the carriers.

Multiomics identify the gene expression signature of the spinal cord during aging process.

Age-related long-term disability is attracting increasing attention due to the growing ageing population worldwide. However, the current understanding of the senescent spinal cord remains insufficient. Bulk RNA sequencing reveals that 526 genes are upregulated and 300 genes are downregulated in senescent spinal cords.

Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.

Repeated antigen exposure leads to T-cell exhaustion, a transcriptionally and epigenetically distinct cellular state marked by loss of effector functions (e.g., cytotoxicity, cytokine production/release), up-regulation of inhibitory receptors (e.

CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells.

Glioblastoma (GBM) stem cells (GSCs) contribute to poor prognosis in patients with GBM. Identifying molecular markers is crucial for developing targeted therapies. Here, we identify cluster of differentiation 97 (CD97) as an optimal GSC surface antigen for potential targeting by chimeric antigen receptor (CAR) T cell therapy through in vitro antibody screening.

PhyloForge: Unifying Micro- and Macroevolution With Comprehensive Genomic Signals.

The dimensions of phylogenetic research have expanded to encompass the study of large-scale populations at the microevolutionary level and comparisons between different species or taxonomic units at the macroevolutionary level. Traditional phylogenetic tools often struggle to handle the diverse and complex data required for these different evolutionary scales. In response to this challenge, we introduce PhyloForge, a robust tool designed to seamlessly integrate the demands of both micro- and macroevolution, comprehensively utilising diverse phylogenomic signals, such as genes, SNPs, and structural variations, as well as mitochondrial and chloroplast genomes.

P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker.

Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway.