Design, synthesis, and biological evaluation of 2-substituted-pyridin-4-yl macrocyclic derivatives as new selective HPK1 inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T-cell receptor (TCR) signaling and a promising therapeutic target in immunotherapy. Herein, based on the reported HPK1 inhibitor Compound K, a series of 2-substituted-pyridin-4-yl macrocyclic HPK1 inhibitors was designed and synthesized through structure-based drug design and macrocyclization strategies. Detailed SAR studies led to the discovery of compound 2 t, which exhibits excellent HPK1 inhibitory activity (IC = 1.

Study on the cocrystal of arginine and acetylsalicylic acid using vibrational spectroscopy and DFT calculations.

Drug repositioning and reuse is a cost-effective strategy for the development of new drugs, and drug co-crystal is a fast and effective technical means. Acetylsalicylic acid is a BCS II drug, which has the limitations of high permeability and low solubility, and the safety and efficacy of the drug have been greatly affected. Co-crystallization with other forming agents is considered to be a promising technical means, which can not only increase the solubility, but also improve the dissolution rate and stability.

Effects of neutron, γ-ray, and neutron-γ-ray mixed radiations on chromosomal aberrations in peripheral blood lymphocytes of two males.

This study aimed to explore the relative biological effectiveness (RBE) of monoenergetic neutrons and the interactions of mixed radiation by investigating the biological effects of neutron, 137Cs γ-ray, and neutron-γ-ray mixed radiations on chromosomal aberrations in human peripheral blood lymphocytes. Human peripheral blood lymphocytes were treated with neutrons from the Intensive Deuterium and Tritium Neutron Source Science Facility and a gamma source from the 137Cs γ-ray source of the Chinese Academy of Sciences for follow-up experimental results. The chromosomal aberrations were analyzed in lymphocytes exposed to neutron, 137Cs γ-ray, and mixed radiations, and the RBE values of neutron radiation were calculated.

Hydrophobic Silica Aerogel with Higher Flame Retardancy, Thermal Radiation Shielding, and High-Temperature Insulation Properties Through Introduction of TiO.

SiO aerogels have garnered significant attention for thermal insulation applications due to their exceptional hydrophobicity and thermal resistance. However, the organic functional groups enabling hydrophobicity introduce flammability concerns, limiting their safe implementation in high-temperature environments. This study presents a novel TiO doping strategy (SA/TiO) that simultaneously enhances thermal safety while preserving the material's intrinsic advantages.

A retrospective study on predicting clinically significant prostate cancer via a bi-parametric ultrasound-based deep learning radiomics model.

Purpose: This study aimed to establish and evaluate a model utilizing bi-parametric ultrasound-based deep learning radiomics (DLR) in conjunction with clinical factors to anticipate clinically significant prostate cancer (csPCa).

Methods: We retrospectively analyzed 232 participants from our institution who underwent both B-mode ultrasound and shear wave elastography (SWE) prior to prostate biopsy between June 2022 and December 2023. A random allocation placed the participants into training and test cohorts with a 7:3 distribution.

AhFAD3-A01 enhances α-linolenic acid content in Arabidopsis and peanut.

Alpha-linolenic acid (ALA, C18:3) is an essential fatty acid integral to human growth and development. Despite its significance, the ALA content in peanut seeds-a major global oilseed crop-is notably low. This study employed bioinformatics analysis, tissue expression, and promoter function evaluations to investigate AhFAD3, which encodes the microsomal omega-3 fatty acid desaturase that is directly responsible for ALA accumulation through converting linoleic acid (LA) to ALA.

Association between recreational physical activity and depressive symptoms in adults with diagnosed sleep disorders: an analysis of NHANES 2007-2018 data.

Objective: This study aimed to examine the relationship between recreational physical activity and depressive symptoms in adults diagnosed with sleep disorders, and to explore the potential of recreational physical activity as a practical intervention to alleviate depressive symptoms.

Methods: Data were drawn from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, including a cohort of 3,164 adults with diagnosed sleep disorders. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9), while recreational physical activity was assessed via metabolic equivalents (METs).

Creation of fragrant peanut using CRISPR/Cas9.

Targeted knockout of the betaine aldehyde dehydrogenase genes AhBADH1 and AhBADH2 using CRISPR/Cas9 produced peanut mutant lines with significantly elevated 2-acetyl-1-pyrroline levels and a strong aroma, marking the first creation of fragrant peanut lines.

Predicting clinically significant prostate cancer in elderly patients: A nomogram approach with shear wave elastography.

Purpose: This study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa).

Methods: 290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non-prostate cancer tissue, as determined by pathology findings.

Chloroplast and whole-genome sequencing shed light on the evolutionary history and phenotypic diversification of peanuts.

Cultivated peanut (Arachis hypogaea L.) is a widely grown oilseed crop worldwide; however, the events leading to its origin and diversification are not fully understood. Here by combining chloroplast and whole-genome sequence data from a large germplasm collection, we show that the two subspecies of A.

Improved Proton Conductivity of Chitosan-Based Composite Proton Exchange Membrane Reinforced by Modified GO Inorganic Nanofillers.

Non-fluorinated chitosan-based proton exchange membranes (PEMs) have been attracting considerable interest due to their environmental friendliness and relatively low cost. However, low proton conductivity and poor physicochemical properties have limited their application in fuel cells. In this work, a reinforced nanofiller (sulfonated CS/GO, S-CS/GO) is accomplished, for the first time, via a facile amidation and sulfonation reaction.

Byakangelicin alleviates sepsis-associated acute kidney injury by inhibiting inflammation and apoptosis.

Inflammation and apoptosis are common in many pathological conditions. Studies have shown that many natural compounds can regulate the signal pathways related to inflammation and apoptosis and can prevent sepsis-associated acute kidney injury (SA-AKI). Several studies have reported the potential anti-inflammatory effect of byakangelicin (BK), a component from the roots of Angelica gigas.

Identification of two major QTLs for pod shell thickness in peanut (Arachis hypogaea L.) using BSA-seq analysis.

Background: Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST.

Results: An F segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST.

Gut microbiota of two invasive fishes respond differently to temperature.

Temperature variation structures the composition and diversity of gut microbiomes in ectothermic animals, key regulators of host physiology, with potential benefit to host or lead to converse results (i.e., negative).

Effects of Neutron and Gamma Rays Combined Irradiation on the Transcriptional Profile of Human Peripheral Blood.

We studied the effects of neutrons, neutrons and γ rays, and γ rays exposures on the transcription spectrum in human peripheral blood of three healthy adult men. Samples were irradiated with 1.42 Gy 2.

Research on the Relationship between the Amylopectin Structure and the Physicochemical Properties of Starch Extracted from Glutinous Rice.

Glutinous rice has very low amylose content and is a good material for determining the structure and physicochemical properties of amylopectin. We selected 29 glutinous rice varieties and determined the amylopectin structure by high-performance anion exchange chromatography with the pulsed amperometric detection method. We also determined the correlation between amylopectin structure and the physicochemical properties of starch extracted from these varieties.

Hydrogen sulfide inhibits human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG4B.

Hydrogen sulfide (H S) is a redox gasotransmitter. It has been shown that H S has a key role in host antiviral defense by inhibiting interleukin production and S-sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H S can play an antiviral role by regulating autophagy.

ESTABLISHMENT OF THE IN VITRO DOSE-RESPONSE CALIBRATION CURVE FOR X-RAY-INDUCED MICRONUCLEI IN HUMAN LYMPHOCYTES.

The cytokinesis-block micronucleus assay has proven to be a reliable technique for biological dosimetry. This study aimed to establish the dose-response curve for X-ray-induced micronucleus. Peripheral blood samples from three healthy donors were irradiated with various doses and scoring criteria by the micronuclei (MN) in binucleated cells.

Mechanically strong polyimide aerogels cross-linked with low-cost polymers.

Polyimide aerogels were prepared using low-cost polymers with different structure capped polyamide oligomers serving as cross-linking agents. To investigate the effects of the anhydride density on cross-linker chain units and side groups of cross-linkers on their properties and microstructures, two kinds of polymers from maleic anhydride, endic anhydride, and styrene were prepared by simple radical polymerization. The polyimide aerogels exhibit densities as low as 0.

Implementing an Air Suction Effect Induction Strategy to Create Super Thermally Insulating and Superelastic SiC Aerogels.

Silicon carbide (SiC) aerogels are promising thermal insulators that are lightweight and possess high thermal stability. However, their application is hindered by their brittleness. Herein, an air suction effect induction (ASEI) strategy is proposed to fabricate a super thermally insulating SiC aerogel (STISA).

Improvement of the Thermal Insulation Performance of Silica Aerogel by Proper Heat Treatment: Microporous Structures Changes and Pyrolysis Mechanism.

A simple heat treatment method was used to optimize the three-dimensional network structure of the hydrophobic aerogel, and during the heat treatment process at 200-1000 °C, the thermal conductivity of the aerogel reached the lowest to 0.02240 W/m·K between 250 °C and 300 °C, which was mainly due to the optimization of microstructure and pyrolysis of surface groups. Further Fluent heat-transfer simulation also confirmed the above results.

High Performance and Self-Humidifying of Novel Cross-Linked and Nanocomposite Proton Exchange Membranes Based on Sulfonated Polysulfone.

The introduction of inorganic additive or nanoparticles into fluorine-free proton exchange membranes (PEMs) can improve proton conductivity and have considerable effects on the performance of polymer electrolyte membrane fuel cells. Based on the sol-gel method and in situ polycondensation, novel cross-linked PEM and nanocomposite PEMs based on a sulfonated polysulfone (SPSU) matrix were prepared by introducing graphene oxide (GO) polymeric brushes and incorporating Pt-TiO nanoparticles into an SPSU matrix, respectively. The results showed that the incorporation of Pt-TiO nanoparticles could obviously enhance self-humidifying and thermal stability.