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.
View Article and Find Full Text PDFBackground: 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.
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.
View Article and Find Full Text PDFPROTACs 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFDuck 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.
View Article and Find Full Text PDFHyperbaric 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.
View Article and Find Full Text PDFA 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBioengineering (Basel)
October 2024
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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFNPJ Parkinsons Dis
September 2024
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.
View Article and Find Full Text PDFEfficient 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.
View Article and Find Full Text PDFPrevious 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.
View Article and Find Full Text PDFSheng Wu Yi Xue Gong Cheng Xue Za Zhi
August 2024
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.
View Article and Find Full Text PDFHeterogeneity 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.
View Article and Find Full Text PDFInfection 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.
View Article and Find Full Text PDFSewage 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.
View Article and Find Full Text PDFCactus 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.
View Article and Find Full Text PDFUnderstanding 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.
View Article and Find Full Text PDFDespite 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.
View Article and Find Full Text PDFIntroduction: 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.