Rational Design of Lanthanide-Binding Tags to Optimize Magnetic Anisotropy in Paramagnetic Protein NMR.

Due to their exceptional anisotropic magnetic properties, lanthanide ion (Ln) complexes are of great utility in many fields of chemistry, including magnetic materials, biomedical imaging, and nuclear magnetic resonance (NMR) spectroscopy. How to achieve large magnetic anisotropies in the Ln complexes coordinated with open-chain ligands is still a challenge. In this study, we started from the open-chain 4PS-PyMTA ligand and assessed the magnetic anisotropy using installed Ln coordinating pendants by increasing size and rigidity.

Post-marketing safety surveillance of Amivantamab: a real world study based on the FDA adverse event reporting system.

Background: Amivantamab stands as the pioneering bispecific antibody that targets both EGFR and MET, utilized in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations. Nevertheless, a thorough assessment of its safety characteristics in the real-world remains unknown.

Research Design And Methods: The adverse event (AE) reports were collected through a search of the FDA Adverse Event Reporting System (FAERS) database spanning from 2019 Q1 to 2024 Q1, and then disproportionality analysis was utilized.

A generative model for inorganic materials design.

The design of functional materials with desired properties is essential in driving technological advances in areas such as energy storage, catalysis and carbon capture. Generative models accelerate materials design by directly generating new materials given desired property constraints, but current methods have a low success rate in proposing stable crystals or can satisfy only a limited set of property constraints. Here we present MatterGen, a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints.

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.

Balanced hydropower and ecological benefits in reservoir-river-lake system: An integrated framework with machine learning and game theory.

The negative impacts of large hydroelectric reservoirs on downstream ecosystems have attracted worldwide attention. Few attempts have been made to dynamically predict ecological benefits and rationally negotiation in the reservoir-river-lake (RRL) system. This study addresses these gaps by developing an integrated framework with machine learning and game theory to balanced hydropower and ecological benefits.

Matrine relieved DHAV-1-induced hepatocyte excessive interferon and pyroptosis by activating mitophagy.

Duck hepatitis A virus type 1 (DHAV-1) is a significant pathogen affecting ducklings, capable of causing rapid mortality and adversely impacting the development of the duck industry. Matrine, the primary active ingredient in various Chinese herbal medicines, has demonstrated antiviral and anti-inflammatory properties. Nevertheless, the effects and mechanisms of action of matrine against DHAV-1 infection remain unclear.

The interaction of adenosine and dopamine in modulating the consequences of central nervous system oxygen toxicity.

Hyperbaric oxygen (HBO) refers to pure oxygen with a pressure greater than 1 atmospheres absolute (ATA), and when the pressure is too high, it can cause convulsive attacks. Adenosine and dopamine have been shown to be closely associated with HBO-induced convulsion seizures, and their receptors exhibited a coexisting relationship of mutual antagonism on the membrane of nerve cells. We explored the influence of adenosine and dopamine interplay on the occurrence of oxygen convulsion.

On-DNA Three-Component Cycloaddition of Diazo Compounds, Nitrosoarenes, and Alkenes: Syntheses of Isoxazolidines for DNA-Encoded Chemical Libraries.

A DNA-compatible three-component reaction is disclosed for the synthesis of on-DNA polysubstituted isoxazolidines that serve as privileged core scaffolds in numerous natural products and bioactive molecules. This one-pot approach involves the 1,3-dipolar cycloaddition of DNA-tagged styrenes with diazo compounds and nitrosoarenes in an aqueous solution of KOAc. The reaction demonstrates excellent functional group compatibility, providing a conventional protocol for the construction of a DNA-labeled isoxazolidine library.

The benefit and risk of addition of chemotherapy to EGFR tyrosine kinase inhibitors for EGFR-positive non-small cell lung cancer patients with brain metastases: a meta-analysis based on randomized controlled trials.

Background: Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy (ETC) offers more advantages for patients with EGFR-positive non-small cell lung cancer (NSCLC) than using EGFR TKIs alone (ET). However, whether this conclusion applies to patients with brain metastases (BM) remains controversial. This meta-analysis was performed to evaluate the benefits and risks of the two groups.

Application of 3D Printing to Design and Manufacture Pancreatic Duct Stent and Animal Experiments.

Postoperative pancreatic fistula (POPF) is a common and challenging complication following pancreaticoduodenectomy (PD), occurring in 2% to 46% of cases. Despite various pancreaticojejunostomy techniques, an effective method to prevent POPF has not been established. This study aimed to develop and evaluate a novel 3D-printed biodegradable pancreatic duct stent to simplify the surgical process of pancreaticojejunostomy, reduce anastomotic complexity, and minimize postoperative complications.

Structure-Activity Relationship of Potent, Selective, and Orally Bioavailable Molecular Glue Degraders of CK1α.

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). With the aim of understanding and modulating neosubstrate specificity, we recently reported the discovery of SJ3149 (), a selective and potent molecular glue degrader of CK1α, that is active in multiple cancer cell lines. Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders.

Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice.

Circadian disruption often arises prior to the onset of typical motor deficits in patients with Parkinson's disease (PD). It remains unclear whether such a prevalent non-motor manifestation would contribute to the progression of PD. Diffusible oligomeric alpha-synuclein (O-αSyn) is perceived as the most toxic and rapid-transmitted species in the early stages of PD.

Enhanced nitrogen removal for low C/N wastewater via preventing futile carbon oxidation and augmenting anammox.

Efficient carbon use is crucial for biological nitrogen removal. Traditional aerobic processes can waste carbon sources, exacerbating carbon deficiency. This study explores an anaerobic/oxic/anoxic system with sludge double recirculation to improve nitrogen removal in low C/N wastewater.

Untargeted Metabolomics Analysis of Lactic Acid Bacteria Fermented with Regard to Regulated Gut Microbiota in Mice.

Previous studies have shown that (AS) has a beneficial preventive and therapeutic effect on colitis. The fermentation of lactic acid bacteria (LAB) can alter the efficacy of AS by modifying or producing new compounds with potential bioactive properties. However, the specific components and mechanisms that enhance the efficacy are still unclear.

[Research progress on anti-swelling hydrogels in biomedical field].

Hydrogel is a kind of degradable hydrophilic polymer, but excessive hydrophilicity leads to larger volume, lower elastic modulus and looser structure, which further affect its use. Especially in the field of biomedical engineering, excessive swelling of the hydrogel can compress the nerves and improve degradation rate resulting in mismatch of tissue growth and released ions. Therefore, anti-swelling hydrogel has been a research hotspot in recent years.

Individual Deviation-Based Functional Hypergraph for Identifying Subtypes of Autism Spectrum Disorder.

Heterogeneity has been one of the main barriers to understanding and treatment of autism spectrum disorder (ASD). Previous studies have identified several subtypes of ASD through unsupervised clustering analysis. However, most of them primarily depicted the pairwise similarity between individuals through second-order relationships, relying solely on patient data for their calculation.

The synergy effect of matrine and berberine hydrochloride on treating colibacillosis caused by an avian highly pathogenic multidrug-resistant Escherichia coli.

Infection by multidrug-resistant avian pathogenic Escherichia coli (APEC) in chickens always leads to the uselessness of antibiotics, highlighting the need for alternative antibacterial agents. Sophora flavescens and Coptis chinensis have been a classical combination used together in Traditional Chinese Medicine (TCM) formulas to treat diseases with similar symptoms to colibacillosis for an extended period, but the effect of their active ingredients' combination on APEC infection remains unstudied. The objective of this study was to explore the synergistic effect of matrine and berberine hydrochloride on colibacillosis caused by an isolated multidrug-resistant APEC.

Bioenergy recovery and carbon emissions benefits of short-term bio-thermophilic pretreatment on low organic sewage sludge anaerobic digestion: A pilot-scale study.

Sewage sludge in cities of Yangzi River Belt, China, generally exhibits a lower organic content and higher silt contentdue to leakage of drainage system, which caused low bioenergy recovery and carbon emission benefits in conventional anaerobic digestion (CAD). Therefore, this paper is on a pilot scale, a bio-thermophilic pretreatment anaerobic digestion (BTPAD) for low organic sludge (volatile solids (VS) of 4%) was operated with a long-term continuous flow of 200 days. The VS degradation rate and CH yield of BTPAD increased by 19.

Magnetically Driven Cactus Spinelike Superhydrophobic FeO Vertical Array for High-Performance Fog Harvesting.

Cactus spinelike materials have attracted much attention due to high fog harvesting efficiency, but great challenges in structure fabrication and structural controllability still remain. In this study, we proposed a magnetically driven spray-coating method to fabricate a cactus spinelike superhydrophobic FeO vertical array on nonwoven cotton fabric. This method is simple and controllable; a mixture containing magnetic FeO particles and organosilicon resin was atomized into tiny droplets and arranged along the magnetic field lines.

Virtual node graph neural network for full phonon prediction.

Understanding the structure-property relationship is crucial for designing materials with desired properties. The past few years have witnessed remarkable progress in machine-learning methods for this connection. However, substantial challenges remain, including the generalizability of models and prediction of properties with materials-dependent output dimensions.

Development of an Orally Bioavailable LCK PROTAC Degrader as a Potential Therapeutic Approach to T-Cell Acute Lymphoblastic Leukemia.

Despite significant advances over recent years, the treatment of T cell acute lymphoblastic leukemia (T-ALL) remains challenging. We have recently shown that a subset of T-ALL cases exhibited constitutive activation of the lymphocyte-specific protein tyrosine kinase (LCK) and were consequently responsive to treatments with LCK inhibitors and degraders such as dasatinib and dasatinib-based PROTACs. Here we report the design, synthesis and evaluation of SJ45566, a potent and orally bioavailable LCK PROTAC.

Regulatory role of MtrA on dormancy/resuscitation revealed by a novel target gene-mining strategy.

Introduction: The unique dormancy of plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate.

Methods: To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites.

Results And Discussion: The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.