Characterisation of tonoplast intrinsic proteins in birch: BpTIP1;3 confers drought tolerance by regulating the scavenging of reactive oxygen species.

Aquaporins (AQPs) are essential membrane channel proteins in plants, with tonoplast intrinsic proteins (TIPs) representing a subfamily of AQPs that play a crucial role in responses to abiotic stress. Here, we identified 10 BpTIP genes in birch (Betula platyphylla), distributed across seven chromosomes, all of which contain conserved major intrinsic protein domains. Polyethylene glycol-induced drought simulation induced the expression of all BpTIP genes except BpTIP5; 1.

The bidirectional relationship between knee osteoarthritis and frailty in China: A longitudinal study.

Background: Knee osteoarthritis is a common disease that causes disability and loss of independence in middle-aged and older adults, and may interact with frailty through shared pathways. Understanding their bidirectional relationship is clinically meaningful for early intervention. This study aimed to investigate the associations between knee osteoarthritis and frailty among middle-aged and older adults in China.

A versatile enzymatic pathway for modification of peptide C-termini.

Advances in bioinformatics have enabled the discovery of unique enzymatic reactions, particularly for ribosomally synthesized and post-translationally modified peptides (RiPPs). The recently discovered daptides, peptides with their C-terminus replaced by an amine, represent one such case, but the diversity, requirements, and engineering potential of daptide biosynthesis remain to be established. Using the daptide biosynthetic gene clusters from and , we reconstituted daptide biosynthesis , revealing the enzymatic requirements for successive oxidative decarboxylation, transamination, and -dimethylation.

Synthesis and biological activity study of tanshinone I-pyridinium salt derivatives.

Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4, bearing a 4-bromobenzoylmethyl substituent at the N-1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC values of 1.

AccFG: Accurate Functional Group Extraction and Molecular Structure Comparison.

Functional groups are specific molecular patterns that influence a molecule's chemical and physical properties. Identifying them is crucial for understanding the structure-activity relationships. Currently, accurately extracting functional groups from complex molecular structures remains a challenge.

Design and synthesis of novel saponin-triazole derivatives in the regulation of adipogenesis.

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy.

Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis.

Microbial production of chemicals may suffer from inadequate cofactor provision, a challenge further exacerbated in yeasts due to compartmentalized cofactor metabolism. Here, we perform cofactor engineering through the decompartmentalization of mitochondrial metabolism to improve succinic acid (SA) production in Issatchenkia orientalis. We localize the reducing equivalents of mitochondrial NADH to the cytosol through cytosolic expression of its pyruvate dehydrogenase (PDH) complex and couple a reductive tricarboxylic acid pathway with a glyoxylate shunt, partially bypassing an NADH-dependent malate dehydrogenase to conserve NADH.

Discovery and Characterization of Oxazolismycin, an Oxazole-Containing Natural Product with an Atypical Loading Mechanism.

Natural products (NPs) remain a vital source of bioactive molecules, with pyridine-containing compounds displaying diverse biological activities. This study presents the discovery of oxazolismycin, a novel pyridine-containing NP characterized by an oxazole-pyridine scaffold. Genome mining of ATCC 14511 revealed a biosynthetic gene cluster encoding an NRPS-PKS assembly line homologous to those responsible for caerulomycin and collismycin biosynthesis.

Translational Model-Informed Dose Selection for Iruplinalkib, a Selective Oral ALK/ROS1 Tyrosine Kinase Inhibitor.

We utilized an integrated approach for model-informed dose selection to predict the recommended phase 2 dose (RP2D) of iruplinalkib, a selective oral ALK and ROS1 tyrosine kinase inhibitor. The efficacy and pharmacokinetics data obtained from ROS1 or ALK-overexpressing cell-derived xenograft models were used for pharmacokinetics pharmacodynamics (PKPD) modeling and calculating human iruplinalkib tumor static concentration (TSC). The plasma concentration-time profile based on pooled clinical data was included in population PK (PopPK) analysis.

A generalized platform for artificial intelligence-powered autonomous enzyme engineering.

Proteins are the molecular machines of life with numerous applications in energy, health, and sustainability. However, engineering proteins with desired functions for practical applications remains slow, expensive, and specialist-dependent. Here we report a generally applicable platform for autonomous enzyme engineering that integrates machine learning and large language models with biofoundry automation to eliminate the need for human intervention, judgement, and domain expertise.

Reprogramming yeast metabolism to Alter fatty acid profiles from even-chain to odd-chain Configuration.

Odd-chain fatty acids have significant applications in biofuels and pharmaceutical industries. In this study, a yeast cell factory was engineered to produce odd-chain fatty acids and their derivatives. The threonine biosynthesis pathway was initially engineered to enable the de novo synthesis of odd-chain fatty acids, resulting in odd-chain fatty acids accounting for 24.

Early Th1-Th2 cytokine imbalance as a predictor for post-stroke depression at 3 months.

Background: The relationship between the imbalance of TH1-TH2 cytokine levels in the early stages of acute ischemic stroke (AIS) and the subsequent development of post-stroke depression (PSD) remains unclear. Early detection of PSD and understanding its progression hold critical clinical significance.

Methods: A prospective cohort study was conducted involving 119 patients with AIS admitted to Suzhou Municipal Hospital.

Induction therapy with dabrafenib, trametinib, and PD-1 inhibitor and surgical conversion in unresectable stage III non-small cell lung cancers with BRAF V600E mutation: 2 cases.

Chemoradiotherapy followed by consolidative immunotherapy is the standard-of-care for unresectable stage III non-small cell lung cancers (NSCLC), yet confers limited benefit in those with driver mutations, BRAF-V600x included. Here, we report two cases of unresectable stage III NSCLC harboring BRAF V600E mutation treated with induction dabrafenib, trametinib, and a PD-1 inhibitor. Both patients exhibited significant tumor regression, enabling surgical conversion and achieving pathological complete or major response, without significant adverse events.

Research on early warning model of coal spontaneous combustion based on interpretability.

Predicting the temperature of the coal spontaneous combustion (CSC) is essential for preventing and managing coal mine fires. In this paper, a Rough Set-Stacking-SHapley Additive Explanations (RS-Stacking-SHAP) prediction model of CSC based on grid search optimized is proposed. Compared with the traditional machine learning model, the model has better prediction accuracy and generalization ability.

Risk Assessment of Hydrogen-Powered Aircraft: An Integrated HAZOP and Fuzzy Dynamic Bayesian Network Framework.

To advance the hydrogen energy-driven low-altitude aviation sector, it is imperative to establish sophisticated risk assessment frameworks tailored for hydrogen-powered aircraft. Such methodologies will deliver fundamental guidelines for the preliminary design phase of onboard hydrogen systems by leveraging rigorous risk quantification and scenario-based analytical models to ensure operational safety and regulatory compliance. In this context, this study proposes a comprehensive hazard and operability analysis-fuzzy dynamic Bayesian network (HAZOP-FDBN) framework, which quantifies risk without relying on historical data.

A sludge volume index model based on components of extracellular polymeric substances during temperature decline.

Sludge bulking remains a persistent challenge in wastewater treatment plants due to the hardness of its prediction. In this research, sludge bulking was simulated in a sequencing batch reactor (SBR) under stepwise cooling conditions to simulate the temperature fluctuations typically happening in the early winter period. The variations in the formulation and concentrations of extracellular polymeric substances (EPS) and the Sludge Volume Index (SVI) during progressive temperature decline were systematically recorded and analysed.

A "Turn-on" fluorescence sensing strategy based on DNA-templated silver nanoclusters for the detection of antibiotic resistance genes.

Background: Antibiotic resistance genes (ARGs) are emerging environmental contaminants that pose serious threats to human health and ecological security due to their rapid migration and transformation in the environment. Thus, developing a sensitive and rapid method to detect ARGs is significant.

Results: In this study, the neighborhood-dependent fluorescent sensor was established with DNA templated silver nanoclusters (AgNCs) and multi-branched linear structure to detect the typical macrolide resistance gene ermB.

γ-cyclodextrin metal-organic framework-activated gold nanoclusters with water solubility as multi-enzyme mimics for simultaneous detection of pesticide and cholinesterase activity.

Cyclodextrin metal-organic framework (CD-MOF) with environmentally friendly components has attracted enormous attention in the past few decades. However, the fragile aqueous stability has limited its application in aqueous catalysis. In this work, we have devised a novel strategy to cope with the problems by introducing the well-defined gold nanoclusters (AuNCs) onto the cyclodextrin ligand through host-guest chemistry.

Genomic epidemiology of a novel group caused severe bloodstream infection in Hainan, China, 2021-2024.

Introduction: Rarely does occur in bloodstream infections (BSI), although it's typically found in cystic fibrosis. This study aims to decipher the genetic map and obtain insights of clinical symptoms into Pandoraea from BSI patients.

Methods: 30 suspected BSI patients' diagnostic records and medical histories were recorded.

Engineering oleaginous yeast Rhodotorula toruloides for production of alkanes and alkenes.

Due to limited reserves and excessive carbon emission of fossil fuels, there has been an increasing interest in developing advanced biofuels with high energy density such as alkanes and alkenes. Here we report the design and construction of three heterologous biosynthetic pathways of alkanes and alkenes in oleaginous yeast Rhodotorula toruloides, including the AAR/ADO, UndA/UndB and FAP pathways. The performance of various enzymes from different organisms was evaluated within R.

Design of diverse, functional mitochondrial targeting sequences across eukaryotic organisms using variational autoencoder.

Mitochondria play a key role in energy production and metabolism, making them a promising target for metabolic engineering and disease treatment. However, despite the known influence of passenger proteins on localization efficiency, only a few protein-localization tags have been characterized for mitochondrial targeting. To address this limitation, we leverage a Variational Autoencoder to design novel mitochondrial targeting sequences.

BACH1 deficiency improves placental angiogenesis via SLC25A51-mediated mitochondrial NAD transport in intrahepatic cholestasis of pregnancy.

Background: Placental angiogenesis is particularly important in the treatment of intrahepatic cholestasis of pregnancy (ICP). Although BACH1 has been implicated in angiogenesis associated with cardiovascular diseases, its specific role and underlying mechanisms in ICP remain unclear. This study aims to investigate the role of BACH1 in ICP.

Late neurological improvement during hospitalization is a predicative factor for acute ischemic stroke.

Purpose: This study aimed to investigate whether late neurological improvement (LNI) during hospitalization serves as a favorable prognostic indicator in patients with acute ischemic stroke (AIS) and to identify the predictors of LNI.

Methods: We retrospectively analyzed data from the Safe Implementation of Treatments in Stroke (SITS) registry at two stroke centers in Egypt. LNI was defined as the lack of early neurological improvement (ENI) within 24 h after admission, accompanied by neurological improvement within 7 days of hospitalization.

Extramural venous invasion in gastric cancer: 9.4T magnetic resonance imaging assessment and circular RNA functional analysis.

Background: Extramural venous invasion (EMVI) is a critical prognostic factor in gastric cancer (GC); however, its detection and underlying molecular mechanisms remain underexplored.

Aim: To investigate the relationship between EMVI and expression of the circular RNA hsa_circ_0097977 in orthotopic GC mouse models.

Methods: A retrospective analysis was conducted in addition to a preclinical animal study, involving 13 GC patients and 24 orthotopic GC mouse models, respectively.

Brain age prediction based on brain region volume modeling under broad network field of view.

Background And Objective: Brain region volume from Structural Magnetic Resonance Imaging (sMRI) can directly reflect abnormal states in brain aging. While promising for clinical brain health assessment, existing volume-based brain age prediction methods fail to explore both linear and nonlinear relationships, resulting in weak representation and suboptimal estimates.

Methods: This paper proposes a brain age prediction method, RFBLSO, based on Random Forest (RF), Broad Learning System (BLS), and Leave-One-Out Cross Validation (LOO).