Targeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 mA modification.

N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.

Managing root caries with silver diamine fluoride, sodium fluoride and direct restorations: A cost-effectiveness analysis.

Objective: To assess the cost-effectiveness of silver diamine fluoride (SDF) relative to sodium fluoride (NaF) and traditional resin-modified glass ionomer cements (RMGIC) restorations for the management of root caries in older adults aged 60 and above.

Methods: A Markov model design was chosen and two models were constructed: 1) Clinic-based model - with access to dental facility that allows for placement of traditional restorations, 2) Community-based model - without access to dental facility due to mobility, lack of executive function, or financial barriers. Modelling was done over a 10-year time horizon with a cycle length of one year.

Fabrication of doxycycline-loaded mesoporous polydopamine nanoparticles for pelvic infection nursing care via synergistic photodynamic therapy.

Pelvic infection has emerged as a significant health risk to women, making the accurate identification of possible pathogenic bacteria and pathogens crucial for its prevention and treatment. Photodynamic therapy (PDT) for antibacterial purposes has emerged as an alternative and promising therapeutic approach for pelvic infections. In this investigation, we developed new antibacterial nanomaterials (DCMP NPs) using doxycycline (DCL), chitosan (CH), and mesoporous polydopamine (MPD) nanoparticles.

A cohort of allogeneic hematopoietic stem cell transplantation for pediatric rare diseases (allo-HSCT-PRD): design and preliminary results.

Rare diseases in children have attracted widespread attention worldwide due to their rarity and difficulty in diagnosis and treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is emerging as a promising and curable therapy for multiple rare diseases. However, rare disease research in China is relatively backward, prompting us to construct the first cohort of allo-HSCT for pediatric rare diseases (allo-HSCT-PRD) involving those who underwent allo-HSCT at the Children's Hospital of Fudan University from 1 January 2014 to 31 October 2024.

Amorphous Silica Induced Loose CeO Clusters with Isolated Pt Atoms for Efficient Reverse-Water Gas Shift Reaction.

Pt-based catalysts exhibit extraordinary potential in reverse-water gas shift (RWGS) reactions, but often fail to possess a high reaction rate and high durability at the same time under high temperature. Herein, we designed a SiO-induced loose CeO as an effective capture for Pt atoms. The abundant surface O vacancies in the loose CeO can trigger significant electron transfer from Pt to CeO and play a crucial role in stabilizing Pt atoms, therefore, largely improving its thermal stability.

Fucoidan-driven Bacteroides xylanisolvens HS-1 alleviates hyperuricemia by promoting intestinal uric acid excretion via the PPARγ/ABCG2 signaling pathway.

The rising prevalence of hyperuricemia and associated complications present a substantial global health challenge. Fucoidan, a natural sulfate-rich polysaccharide degraded by gut microbiota, is under investigation as a potential therapeutic agent for reducing uric acid levels. However, the precise mechanism underlying its effects remains unclear.

Pasteurized Akkermansia muciniphila ameliorates insulin resistance by reducing placental inflammation in GDM mouse model.

Gestational diabetes mellitus (GDM) is a common and serious complication during pregnancy. Depleted next-generation probiotic, Akkermansia muciniphila (AKK) in GDM women indicates its potential on GDM prevention. However, the functions and mechanisms of AKK on GDM remain unclear.

Phosphorylation-dependent activation of MAP4K1/2 by OST1 mediates ABA-induced stomatal closure in Arabidopsis.

In higher plants, stomatal movements represent a critical physiological process that matains cellular water homestasis while enabling photosynthetic gas exchange. Open stomata 1 (OST1), a key protein kinase in the abscisic acid (ABA) signaling cascade, has been established as a central regulator of stomatal dynamics. This study reveals that two highly conserved mitogen-activated protein kinase 1 (MAP4K1) and MAP4K2 are positive regulators in ABA promoted stomatal closure, and ABA-activated OST1 potentiates MAP4K1/2 through phosphorylation at conserved serine and threonine residues (S166, T170, and S479/S488).

Epoxidation Selectivity of Cyclohexene Catalyzed by Electric Field at the Interface of Microdroplets without Catalyst.

The interface of aqueous microdroplets has been proven to have a large number of unique properties, which can initiate reactions that cannot occur in bulk solution. In this work, we found that cyclohexene spontaneously oxidized at the gas-liquid interface of the microdroplets under mild conditions. Notably, tetrabutylammonium bromide as an electrolyte added to the reaction system can promote the directional epoxidation of cyclohexene.

Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations.

Somatically acquired mitochondrial DNA mutations accumulate with age, but the mechanisms and consequences are poorly understood. Here we show that transient injuries induce a burst of persistent mtDNA mutations that impair resilience to future injuries. mtDNA mutations suppressed energy-intensive nucleotide metabolism.

Gut Microbiota Dysbiosis Remodels the Lysine Acetylome of the Mouse Cecum in Early Life.

The interaction between epigenetic mechanisms and the gut microbiome is potentially crucial for the development and maintenance of intestinal health. Lysine acetylation, an important post-translational modification, plays a complex and critical role in the epigenetic regulation of the host by the gut microbiota. However, there are currently no reports on how gut microbiota dysbiosis affects host physiology in early life through global lysine acetylation.

Effect of radical radiotherapy dose on the prognosis of limited-stage thoracic small cell carcinoma of the esophagus: A multicenter retrospective trial from China (CHiSCEC).

Background: The optimal radiation dose for the treatment of small cell carcinoma of the esophagus (SCEC) has not been established. This study aimed to investigate the treatment outcomes and toxicities in patients with limited-stage SCEC (LS-SCEC) treated by radiotherapy.

Methods: Patients with LS-SCEC from 14 institutions were retrospectively identified between December 2000 and October 2021.

Safety of fruquintinib in Chinese patients with colorectal cancer: an age subgroup analysis from a phase IV real-world clinical practice study.

Background: Colorectal cancer (CRC) is increasingly prevalent among young adults (<50 years) in China, a demographic that has been historically underrepresented in clinical studies. While most patients with CRC are aged ⩾65 years, this age group is also underrepresented in trials, highlighting the need for a better understanding of treatment outcomes in both younger and older populations. A recent phase IV trial evaluating the safety of fruquintinib in Chinese patients with metastatic CRC (mCRC) showed a manageable profile.

Ethylene Electrosynthesis from Acetylene at Ampere-Level Current Density via Promoting Interparticle Mass Transport.

The electrocatalytic acetylene semi-hydrogenation (EASH) driven by renewable energy offers an important non-petroleum route for ethylene production, yet suffers from insufficient reaction rate, ethylene selectivity, and energy efficiency. While tailoring catalytically active structures is effective for improving the EASH performance, the effects of mass transport at the mesoscale are poorly understood. Here, we show quantitatively the crucial role of interparticle mass transport within the catalyst layer of a gas diffusion electrode.

[Advances and future directions in discovery of active substances and target identification in traditional Chinese medicine: toward precision, efficiency, and intelligence].

The study of active substances in traditional Chinese medicine(TCM) is the foundation of TCM pharmacology, TCM quality control, and new drug development, and it is also one of the most popular directions in TCM modernization research in recent years. Due to their diverse chemical compositions and complex component-effect relationships, Chinese medicines often require the comprehensive use of multidisciplinary technologies such as chemistry, biology, and information science to reveal their active substances and targets. In this paper, we review the innovative breakthroughs made in the past 30 years in the discovery strategies and technological means for the research of active substances in traditional Chinese medicine from the perspective of technological changes, and focus on the new direction of the research of active substances in traditional Chinese medicine under the paradigm shift of scientific research brought about by artificial intelligence, with the aim of promoting research in related fields to move in the direction of more accurate, efficient, and intelligent, and providing innovative ideas for the research of active substances in traditional Chinese medicine under the new situation.

Effect of introducing electron-donating and electron-withdrawing substituents on the ESIPT process and fluorescence properties of 2-hydroxy-3-phenyliminomethyl-10-butyl phenothiazine derivatives: A DFT/TD-DFT study.

In this study, the influence of various substituents on the fluorescence properties and excited-state intramolecular proton transfer (ESIPT) process of 2-hydroxy-3-phenyliminomethyl-10-butyl phenothiazine (Ph) were systematically investigated using density-functional theory (DFT) and time-dependent density-functional theory (TD-DFT). Five Ph derivatives were strategically designed by incorporating two electron-donating groups (NH, MeO) and three electron-withdrawing groups (CN, CHO, NO). Analysis the structural parameters and IR spectra revealed that the intramolecular hydrogen bonding in Ph and its derivatives was enhanced in the S state.

Oxidative stress-related biomarkers in thyroid eye disease: evidence from bioinformatics analysis and experimental validation.

Background: Oxidative stress is a key contributor to the pathogenesis of the autoimmune condition thyroid eye disease (TED). However, its precise molecular mechanisms and reliable biomarkers remain unclear. Bioinformatics enables the identification of differentially expressed genes through transcriptomic analysis.

Microfluidic detection based on size-encoded microbeads and rolling circle amplification for multiplex respiratory virus nucleic acid detection.

Acute respiratory tract diseases (ARDs) are predominantly caused by viral infections, with one of their hallmark characteristics being multiple viral co-infections. Such multiple viral infections not only complicate therapeutic interventions but also lead to an increase in mortality rates. Most traditional bioassays, however, are limited to identifying a single type of virus, leading to missed diagnoses in samples with multiple respiratory pathogens.

Genetic and transcriptional insights reveal hepatitis C virus as a driver of kidney cancer.

Objectives: Observational studies suggest a potential link between Hepatitis C virus (HCV) infection and extrahepatic cancers, but the causal relationship remains unclear.

Methods: We applied a two-sample Mendelian randomization (MR) approach to evaluate the causal relationships between HCV infection and various extrahepatic cancers. A two-step MR was used to identify potential mediators, followed by colocalization analysis to identify HCV-associated susceptibility genes (HSGs).

Dose-optimised recombinant human thrombopoietin eltrombopag in patients with immune thrombocytopenia: a multicenter, randomised controlled trial (The TE-ITP Study).

Background: Recombinant human thrombopoietin (rhTPO) at a fixed dose of 300 U/kg/day for 2 weeks has demonstrated good efficacy and safety in adults with immune thrombocytopenia (ITP). This trial aimed to develop a flexible and personalized rhTPO regimen that ensures efficacy and safety beyond previous fixed dose, with eltrombopag as an active comparator.

Methods: The TE-ITP trial was conducted in 12 centers across China.

Clinical and hemodynamic outcomes of side-to-side anastomosis in superficial temporal artery-middle cerebral artery bypass for adult patients with moyamoya disease: a prospective cohort study.

Objective: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass, characterized by side-to-side (S-S) anastomosis, has been beneficial in reducing the incidence of postoperative complications and recurrent stroke in patients with moyamoya disease (MMD). However, the safety and efficacy of this unconventional S-S procedure remain unclear. This research aimed to investigate the clinical and hemodynamic outcomes associated with the S-S technique.

Molecular Simulation-Guided Development of a Ractopamine Aptasensor Based on Magnetic Microspheres.

β-Adrenergic agonists are employed in the livestock industry to promote the growth of poultry and livestock. However, due to the frequent lack of scientific guidance in medication administration among farmers, issues such as indiscriminate use, misuse, and noncompliance with withdrawal periods have arisen. These practices result in drug residues, triggering food safety concerns and posing a threat to consumer health.

Navigator motion-resolved MR fingerprinting using implicit neural representation: Feasibility for free-breathing three-dimensional whole-liver multiparametric mapping.

Purpose: To develop a multiparametric free-breathing three-dimensional, whole-liver quantitative maps of water T, water T, fat fraction (FF) and R*.

Methods: A multi-echo 3D stack-of-spiral gradient-echo sequence with inversion recovery and T-prep magnetization preparations was implemented for multiparametric MRI. Fingerprinting and a neural network based on implicit neural representation (FINR) were developed to simultaneously reconstruct the motion deformation fields, the static images, perform water-fat separation, and generate T, T, R*, and FF maps.

Development and Validation of a Machine Learning-Based Risk Prediction Model for Delirium in Older Inpatients: A Prospective Cohort Study.

Aims: To develop and validate a machine learning-based risk prediction model for delirium in older inpatients.

Design: A prospective cohort study.

Methods: A prospective cohort study was conducted.

Insight of protease and PLA activity co-inhibition on jellyfish toxin-induced inflammation and multiple organ dysfunction.

In recent years, global climate change has caused fluctuations in the quantity and activity of phospholipase and proteases prevalent in animal venoms, leading to changes in the patterns of toxic animal injuries and increased treatment difficulties. Herein, this study conducted a screening for inhibitors of jellyfish venom enzyme activity and unexpectedly discovered that Salvianolic acid B (SaB) can inhibit the activities of phospholipase A (PLA) and proteases in jellyfish venom. Compared to protease inhibitor mixtures, this co-inhibition exhibited a more pronounced protective effect on the hemocyte, with 300 μM SaB reducing the hemolytic activity of jellyfish venom from 85 % to 57 %.