Computation-Enabled Structure-Based Discovery of Potent Binders for Small-Molecule Aptamers.

Aptamers, functional nucleic acids recognized for their high target-binding affinity and specificity, have been extensively employed in biosensors, diagnostics, and therapeutics. Conventional screening methods apply evolutionary pressure to optimize affinity, while counter-selections are used to minimize off-target binding and improve specificity. However, aptamer specificity characterization remains limited to target analogs and experimental controls.

Structurally Diverse New Metabolites from Three Hadal Trench-Derived Microorganisms.

Two new tetraene lactone derivatives ( and ), two new α-pyrone derivatives ( and ), three compounds reported as natural products for the first time [an α-pyrone derivative (), an indole-diketopiperazine alkaloid (), and a β-amino acid derivative ()], and 11 known compounds (, -), were obtained from microorganisms isolated from hadal trench sediments in the Pacific Ocean. Their structures were determined using NMR, HRESIMS, optical rotatory dispersion (ORD) spectra, NMR calculations followed by DP4+ analysis, electronic circular dichroism (ECD) calculations, X-ray crystallography analysis, and advanced Marfey's and modified Mosher eater methods. Microbial broth dilution assay suggested that compounds - and had weak antibacterial effects.

Regulation of Alternative Splicing by PARP1 in HTR-8/Svneo Cells: Implications for Placental Development and Spontaneous Abortion.

Objective: Alternative splicing affects gene expression during placental development. The present study aimed to identify poly (ADP-ribose) polymerase 1 (PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.

Methods: Decidual tissues were collected from women with induced abortion and spontaneous abortion.

Talaketides A-G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027.

Seven novel linear polyketides, talaketides A-G (1-7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A-E (1-5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure.

Blue photoluminescence of wide-bandgap polystyrenesulfonate materials.

For the first time, polystyrene sulfonic acid solution (PSS) was observed to emit blue fluorescence. The photoluminescence (PL) behavior of PSS under different concentrations, pH values and magnetic field strengths was investigated, revealing the diversity and tunability of its PL properties. PSS possesses remarkable down-conversion properties and strong responsiveness to external magnetic fields.

Ultrathin Self-Assembled Monolayer for Effective Silicon Solar Cell Passivation.

Passivation technology is crucial for reducing interface defects and impacting the performance of crystalline silicon (c-Si) solar cells. Concurrently, maintaining a thin passivation layer is essential for ensuring efficient carrier transport. With an ultrathin passivated contact structure, both Silicon Heterojunction (SHJ) cells and Tunnel Oxide Passivated Contact (TOPCon) solar cells achieve an efficiency surpassing 26%.

Single-cell mapping of peripheral blood mononuclear cells reveals key transcriptomic changes favoring coronary artery lesion in IVIG-resistant Kawasaki disease.

Background: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) poses a considerable challenge to patients and their families due to its severe complications. Previous researches have highlighted the critical role of immune disorders in its pathogenesis. However, fragmented studies based on isolated cases hinder a comprehensive understanding of this deadly illness.

Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology.

Obesity and type 2 diabetes mellitus (T2DM) impact more than 2.5 billion adults worldwide, necessitating innovative therapeutic approaches. Unimolecular polypharmacology, which involves designing single molecules to target multiple receptors or pathways simultaneously, has revolutionized treatment strategies.

Absence of PNET formation and normal longevity in a mouse model of Mahvash disease.

Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (), induces significant pancreatic hyperglucagonemia, resulting in α-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as , harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wild-type (WT) and mice exhibited no discernible difference in appearance or weight, adult mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol.

Research on fine co-focus adjustment method for segmented solar telescope.

For segmented telescopes, achieving fine co-focus adjustment is essential for realizing co-phase adjustment and maintenance, which involves adjusting the millimeter-scale piston between segments to fall within the capture range of the co-phase detection system. CGST proposes using a SHWFS for piston detection during the co-focus adjustment stage. However, the residual piston after adjustment exceeds the capture range of the broadband PSF phasing algorithm( ± 30μm), and the multi-wavelength PSF algorithm requires even higher precision in co-focus adjustment.

Dimerization and antidepressant recognition at noradrenaline transporter.

The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology. Dysfunction of noradrenaline transporter has been implicated in numerous neuropsychiatric diseases, including depression and attention deficit hyperactivity disorder. Here we report cryo-electron microscopy structures of noradrenaline transporter in apo and substrate-bound forms, and as complexes with six antidepressants.

Association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a retrospective cohort study in lean Chinese individuals.

There is limited research on the association between the alanine aminotransferase to high-density lipoprotein cholesterol ratio (ALT/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD). The purpose of the current research was to look into the connection between the ALT/HDL-C ratio and the risk of NAFLD in lean Chinese individuals. Between January 2010 and December 2014, 11,975 non-obese people participated in this prospective cohort research.

The crystal structure of human ferroptosis suppressive protein 1 in complex with flavin adenine dinucleotide and nicotinamide adenine nucleotide.

Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation of lipids within cellular membranes. Ferroptosis plays a crucial role in physiological and pathological situations and has attracted the attention of numerous scientists. Ferroptosis suppressive protein 1 (FSP1) is one of the main regulators that negatively regulates ferroptosis through the GPX4-independent FSP1-CoQ10-NAD(P)H axis and is a potential therapeutic target for ferroptosis-related diseases.

Association between estimated glomerular filtration rate and reversion to normoglycemia in people with impaired fasting glucose: a 5-year retrospective cohort study.

Objectives: The present body of evidence regarding the correlation between the estimated glomerular filtration rate (eGFR) and the reversal of impaired fasting glucose (IFG) to normoglycemia remains constrained. Consequently, the objective of our study is to examine the relationship between eGFR and the restoration of normoglycemia in individuals with IFG.

Methods: This retrospective cohort study consecutively collected data from 24,541 non-selective participants with IFG at Rich Healthcare Group in China from January 2010 to 2016.