Molecular Property Prediction Based on Multi-Level Graph Self-Supervised Pretraining and Multi-Grain Finetuning.

Molecular property prediction is crucial for advancing medical research in areas like retrosynthesis analysis and drug discovery. The challenge of obtaining accurate molecular property labels has led to the use of pretrained Graph Neural Networks (GNNs) with self-supervised learning methods. However, traditional approaches often fail to capture detailed chemical structural and functional information, particularly within molecular functional groups, and do not adequately address relationships across molecular graph layers.

Comparison of treatment patterns, efficacy and safety between generic and branded atorvastatin users in China: a multicenter, retrospective propensity score-matched cohort study.

Background: To evaluate and compare the treatment patterns, effectiveness, and safety of generic and branded atorvastatin in China.

Methods: This multicenter, retrospective cohort study collected and analyzed data from patients who initiated atorvastatin therapy for the first time across 16 hospitals between 2020 and 2022. Treatment patterns included adherence, persistence, switching, augmentation.

Soluble E-cadherin Drives Brain Metastasis in Inflammatory Breast Cancer.

Unlabelled: The brain is a common site of relapse in inflammatory breast cancer (IBC), an E-cadherin positive, aggressive form of breast cancer. We found that elevated serum levels of soluble E-cadherin (sEcad), an 80-kDa fragment of E-cadherin, in patients with metastatic IBC correlated with poorer outcomes and increased rates of brain metastases. In our effort to understand the underlying mechanism, we discovered that sEcad binds to XIAP, an inhibitor of cell death, activating the pro-survival NF-kβ signaling in tumor cells.

Comparative metabolomics profiling reveals the aroma and nutritional diversity of eight wild edible plants.

Wild edible plants are important yet undervalued vegetables, due to limited knowledge of their bioactive components and nutritional/functional potential. In this study, we used full-spectrum metabolomics and machine learning to analyze the aroma-related and nutritional components of eight common wild edible plants from Southwest China. The results showed broad differences in the metabolic profiles of these wild edible plants, with Houttuynia cordata and Aralia elata presenting unique metabolic patterns.

Comparison of Efficacy and Safety of Endoscopic Breast-Conserving Surgery Versus Conventional Breast-Conserving Surgery in Elderly Patients With Breast Cancer: Insights From a Single-Center Retrospective Analysis.

Aim: Breast-conserving surgery (BCS) has been increasingly favored by elderly breast cancer patients to preserve their quality of life. This study compares the efficacy and safety of endoscopic versus conventional BCS in elderly patients, focusing on operative and aesthetic outcomes.

Methods: A retrospective analysis was conducted on 261 elderly breast cancer patients (age ≥70) treated from January 2020 to January 2022.

Facile N═N Bond Cleavage of Cis-Azobenzene with Bis-silylenes.

The very different features of cooperative disilicon(II)-mediated N═N bond activation of trans- vs. cis-azobenzene are reported, employing two bis-silylenes with distinct intramolecular Si···Si distances, PhN(LSi:)₂ 1 (L = PhC(BuN)₂, Si···Si: 2.9 Å) and XT(LSi:)₂ 2 (XT = 9,9-dimethyl-xanthene-4,5-diyl, Si···Si: 4.

Combined anti-PD-L1 and anti-VEGFR2 therapy promotes the antitumor immune response in GBM by reprogramming tumor microenvironment.

Inhibitors of programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) are commonly used in the clinic, but they are beneficial for only a minority of glioblastoma multiforme (GBM) patients. GBM has significant immunosuppressive properties, and there are many immunosuppressive cells and dysfunctional effector T cells in the tumor microenvironment (TME), which is one of the important reasons for the failure of clinical treatment of GBM. Here, we have identified P21 activated kinase 4 (PAK4) as a pivotal immune suppressor in the TME.

A single-dose, four-cycle, fully repetitive crossover bioequivalence of dabigatran etexilate in Chinese.

Purpose: Among healthy Chinese subjects, two capsules of dabigatran etexilate were tested for bioequivalence.

Method: Fifty healthy subjects were recruited for each of the fasting and postprandial trials in a randomized, two-sequence, open-label, four-cycle, fully replicated trial design of a single 150 mg dose of either the test or the reference formulation of dabigatran etexilate capsules in the fasting and postprandial states. The blood concentration of dabigatran at different time points after administration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Ion suppression correction and normalization for non-targeted metabolomics.

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and sensitivity. Here we report a method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) library plus companion algorithms to: 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We evaluate the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reversed-phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices.

WRAD core perturbation impairs DNA replication fidelity promoting immunoediting in pancreatic cancer.

It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in the context of oncogenic stress. Here, we identify the WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator of DNA replication in pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that the WRAD core interacts with the replisome complex, with disruption of DPY30 resulting in DNA re-replication, DNA damage, and chromosomal instability (CIN) without affecting cancer cell proliferation.

Ultra-Fast Multi-Organ Proteomics Unveils Tissue-Specific Mechanisms of Drug Efficacy and Toxicity.

Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present UFP-MS, an ultra-fast mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively.

A Novel Modified ZIF-8 Nanoparticle with Enhanced Interfacial Compatibility and Pervaporation Performance in a Mixed Matrix Membrane for De-Alcoholization in Low-Concentration Solutions.

This study investigated the enhancement in bioethanol recovery from mixed matrix membranes (MMMs) by functionalizing zeolite framework-8 (ZIF-8) with imidazolate. This study focused on the separation of ethanol from low-concentration ethanol/water mixtures (typical post-fermentation concentrations of 5-10 wt%). Specifically, ZIF-8 was modified by the shell-ligand exchange reaction (SLER) with 5,6-dimethylbenzimidazole (DMBIM), resulting in ZIF-8-DMBIM particles with improved hydrophobicity, organophilicity, larger size, and adjustable pore size.

Disilicon-Mediated Carbon Monoxide Activation: From a 1,2,3-Trisila- to 1,3-Disilacyclopentadienes with Hypercoordinate λSi-λC Double Bonds.

The facile reaction of the SiPh-bridged bis-silylene (LSi:)SiPh (L=PhC(NBu)) with diphenylacetylene affords the unprecedented 1,2,3-trisilacyclopentadiene (LSi)(PhC)SiPh 1 with a hypercoordinate λSi-λSi double bond. Compound 1 is very oxophilic and consumes three molar equivalents of inert NO to form the bicyclic oxygenation product 2 through O-atom insertion in the Si=Si and Si-Si bonds. Strikingly, 1 can completely split the C≡O bonds of carbon monoxide under ambient conditions (1 atm, room temperature), yielding the 1,3-disilacyclopentadiene 3, representing the first hypercoordinate example of a cyclosilene with a λSi-λC double bond.

Promotion of aromatic amino acids of extracellular polymeric substance targeted transformation via sulfite mediated iron redox cycling in sludge solid-liquid separation.

Highly hydrophilic extracellular polymeric substance (EPS) with gel-like structure seriously plagues the development of sludge deep dewatering. Oxysulfur radicals-based oxidation driven by iron-bearing mineral proposes a promising strategy for effective EPS decomposition. However, the transformation and involved interaction mechanisms of aromatic proteins are still controversial due to the complex EPS structure.

Characterization and Flame-Retardant Properties of Cobalt-Coordinated Cyclic Phosphonitrile in Thermoplastic Polyurethane Composites.

Halogen-free organophosphorus flame retardants have promising application prospects due to their excellent safety and environmental protection properties. A cobalt-coordinated cyclic phosphonitrile flame retardant (Co@CPA) was synthesized via a hydrothermal method using hexachlorocyclotriphosphonitrile (HCCP), 5-amino-tetrazolium (5-AT), and cobalt nitrate hexahydrate (Co(NO)2∙6HO) as starting materials. The structure was characterized using Fourier transform infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA).

Synergetic conditioning via oxalic acid enhanced Fe/CaO and skeleton construct to achieve deep dewatering of sewage sludge.

Extracellular polymeric substance (EPS) with highly hydrophilic groups and sludge with high compressibility are determined sludge dewaterability. Herein, Fe catalyzed calcium peroxide (CaO) assisted by oxalic acid (OA) Fenton-like process combined with coal slime was applied to improve sludge dewaterability. Results demonstrated that the sludge treated by 0.

A Combined Manual Annotation and Deep-Learning Natural Language Processing Study on Accurate Entity Extraction in Hereditary Disease Related Biomedical Literature.

We report a combined manual annotation and deep-learning natural language processing study to make accurate entity extraction in hereditary disease related biomedical literature. A total of 400 full articles were manually annotated based on published guidelines by experienced genetic interpreters at Beijing Genomics Institute (BGI). The performance of our manual annotations was assessed by comparing our re-annotated results with those publicly available.

Contribution to the knowledge of the genus Nephelomilta Hampson, 1900(Lepidoptera, Erebidae, Arctiinae) from China with descriptions of two new species.

New information on the genus Nephelomilta Hampson, 1900 from China is reported. Two new species are described from southwestern China: N. medogensis Huang, Volynkin & Saldaitis, sp.

RAD54L2-mediated DNA damage avoidance pathway specifically preserves genome integrity in response to topoisomerase 2 poisons.

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons.