CYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NAD/NADH ratio.

Background: Glioblastoma multiforme (GBM) exhibits a cellular hierarchy with a subpopulation of stem-like cells known as glioblastoma stem cells (GSCs) that drive tumor growth and contribute to treatment resistance. NAD(H) emerges as a crucial factor influencing GSC maintenance through its involvement in diverse biological processes, including mitochondrial fitness and DNA damage repair. However, how GSCs leverage metabolic adaptation to obtain survival advantage remains elusive.

Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.

Histone lysine-specific demethylase 1 (LSD1) is overexpressed in various solid and hematological tumors, suggesting its potential as a therapeutic target, but there are currently no LSD1 inhibitors available on the market. In this study we employed a computer-guided approach to identify novel LSD1/EGFR dual inhibitors as a potential therapeutic agent for non-small cell lung cancer. Through a multi-stage virtual screening approach, we found L-1 and L-6, two compounds with unique scaffolds that effectively inhibit LSD1 with IC values of 6.

Sulfur chains glass formed by fast compression.

Due to the sulfur's atoms' propensity to form molecules and/or polymeric chains of various sizes and configuration, elemental sulfur possesses more allotropes and polymorphs than any other element at ambient conditions. This variability of the starting building blocks is partially responsible for its rich and fascinating phase diagram, with pressure and temperature changing the states of sulfur from insulating molecular rings and chains to semiconducting low- and high-density amorphous configurations to incommensurate superconducting metallic atomic phase. Here, using a fast compression technique, we demonstrate that the rapid pressurisation of liquid sulfur can effectively break the molecular ring structure, forming a glassy polymeric state of pure-chain molecules (Am-S).

Network pharmacology and molecular docking to explore mechanisms of clozapine-induced cardiac arrest.

Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.

Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.

Temperature-sensitive driving assembled fluorescence hydrogel based dual-mode sensor for adsorbing and detecting of heavy metal cadmium ions in food and water.

The denatured bovine serum albumin (dBSA) is coupled with the CdTe/CdS quantum dot and the resulting CdTe/CdS@dBSA complex is assembled and retained in the poly(n-isopropyl acrylamide) (PNIPAM) hydrogel via regulating temperature and pH to form the CdTe/CdS@dBSA-PNIPAM fluorescence hydrogel substrate, which is able to adsorb and sense cadmium ions (Cd). Based on this fluorescence hydrogel, a fluorescence and colorimetric dual-mode detection system is established to quantitatively detect Cd with a limit of detection (LOD) of 2.88 nM for fluorescence detection and 11.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

Competing Hexagonal and Square Lattices on a Spherical Surface.

The structural properties of packed soft-core particles provide a platform to understand the cross-pollinated physical concepts in solid-state and soft-matter physics. Confined on a spherical surface, the traditional differential geometry also dictates the overall defect properties in otherwise regular crystal lattices. Using molecular dynamics simulation of the Hertzian model as a tool, we report here the emergence of new types of disclination patterns: domain and counter-domain defects, when hexagonal and square patterns coexist.

Intramolecular Repulsive Interactions Enable High Efficiency of NIR-II Aggregation-Induced Emission Luminogens for High-Contrast Glioblastoma Imaging.

Strategies to acquire high-efficiency luminogens that emit in the second near-infrared (NIR-II, 1000-1700 nm) range are still rare due to the impediment of the energy gap law. Herein, a feasible strategy is pioneered by installing large-volume encumbrances in a confined space to intensify the repulsive interactions arising from overlapping electron densities. The experimental results, including smaller coordinate displacement, reduced reorganization energy, and suppressed internal conversion, demonstrate that the repulsive interactions assist in the inhibition of radiationless deactivation.

Engineering extracellular vesicles for targeted therapeutics in cardiovascular disease.

Extracellular vesicles (EVs) are nanosized particles secreted by cells that play crucial roles in intercellular communication, especially in the context of cardiovascular diseases (CVDs). These vesicles carry complex cargo, including proteins, lipids, and nucleic acids, that reflects the physiological or pathological state of their cells of origin. Multiomics analysis of cell-derived EVs has provided valuable insights into the molecular mechanisms underlying CVDs by identifying specific proteins and EV-bound targets involved in disease progression.

Deciphering network dysregulations and temporo-spatial dynamics in disorders of consciousness: insights from minimum spanning tree analysis.

Objectives: The neural mechanism associated with impaired consciousness is not fully clear. We aim to explore the association between static and dynamic minimum spanning tree (MST) characteristics and neural mechanism underlying impaired consciousness.

Methods: MSTs were constructed based on full-length functional magnetic resonance imaging (fMRI) signals and fMRI signal segments within each time window.

Alterations of synaptic plasticity and brain oscillation are associated with autophagy induced synaptic pruning during adolescence.

Adolescent brain development is characterized by significant anatomical and physiological alterations, but little is known whether and how these alterations impact the neural network. Here we investigated the development of functional networks by measuring synaptic plasticity and neural synchrony of local filed potentials (LFPs), and further explored the underlying mechanisms. LFPs in the hippocampus were recorded in young (21 ~ 25 days), adolescent (1.

Nutrition, production, and processing of virgin omega-3 polyunsaturated fatty acids in dairy: An integrative review.

With improving living standards, functional and healthy foods are accounting for an increased share in human food. The development of dairy products that are rich in virgin omega-3 polyunsaturated fatty acids (n-3 PUFAs) has become a topic of interest. Virgin n-3 PUFA milk can provide high-quality protein and calcium, as well as provide n-3 PUFAs to improve human health.

CuO-Superlattices Induced Oxygen Vacancy for Localized Surface Plasmon Resonance.

Metallic oxide can induce localized surface plasmon resonance (LSPR) through creating vacancies, which effectively achieve high carrier concentrations and offer advantages such as versatility and tunability. However, vacancies are typically created by altering the stoichiometric ratio of elements through doping, and it is challenging to achieve LSPR enhancement in the visible spectral range. Here, we have assembled CuO-superlattices to induce a high concentration of oxygen vacancies, resulting in LSPR within the visible spectrum.

Time-series single-cell transcriptomic profiling of luteal-phase endometrium uncovers dynamic characteristics and its dysregulation in recurrent implantation failures.

Understanding human endometrial dynamics in the establishment of endometrial receptivity remains a challenge, which limits early diagnosis and treatment of endometrial-factor infertility. Here, we decode the endometrial dynamics of fertile women across the window of implantation and characterize the endometrial deficiency in women with recurrent implantation failure. A computational model capable of both temporal prediction and pattern discovery is used to analyze single-cell transcriptomic data from over 220,000 endometrial cells.

HDAC6 deacetylates TRIM56 to negatively regulate cGAS-STING-mediated type I interferon responses.

Histone deacetylase HDAC6 has been implicated in regulating antiviral innate immunity. However, its precise function in response to DNA virus infection remains elusive. Herein, we find that HDAC6 deficiency promotes the activation of cGAS-STING signaling and type I interferon (IFN) production, both in vitro and in vivo, resulting in a decrease in HSV-1 infection.

Subtilisin-like protease 4 regulates cold tolerance through cell wall modification in rice.

Rice is susceptible to cold temperatures, especially during the seedling stage. Despite extensive research into the cold tolerance mechanisms of rice, the number of cloned genes remains limited. Plant subtilisin-like proteases (SUBs or SBTs) are protein-hydrolyzing enzymes which play important roles in various aspects of plant growth as well as the plant response to biotic and abiotic stress.

A stable open-shell peri-hexacene with remarkable diradical character.

[n]Peri-acenes ([n]PA) have attracted great interest as promising candidates for nanoelectronics and spintronics. However, the synthesis of large [n]PA (n > 4) is extremely challenging due to their intrinsic open-shell radical character and high reactivity. Herein, we report the successful synthesis and isolation of a derivative (1) of peri-hexacene in crystalline form.

Mismatch prime editing gRNA increased efficiency and reduced indels.

Prime editing enables precise and efficient genome editing, but its efficacy is hindered by pegRNA's 3' extension, forming secondary structures due to high complementarity with the protospacer. The continuous presence of the prime editing system also leads to unintended indel formation, raising safety concerns for therapeutic applications. To address these challenges, we develop a mismatched pegRNA (mpegRNA) strategy that introduces mismatched bases into the pegRNA protospacer, reducing complementarity and secondary structure formation, and preventing sustained activity.

2D MoS-based reconfigurable analog hardware.

Biological neural circuits demonstrate exceptional adaptability to diverse tasks by dynamically adjusting neural connections to efficiently process information. However, current two-dimension materials-based neuromorphic hardware mainly focuses on specific devices to individually mimic artificial synapse or heterosynapse or soma and encoding the inner neural states to realize corresponding mock object function. Recent advancements suggest that integrating multiple two-dimension material devices to realize brain-like functions including the inter-mutual connecting assembly engineering has become a new research trend.

Discovery of novel sulfonamide derivatives containing pinacolone moieties as fungicide candidates against Botrytis cinerea.

Background: Botrytis cinerea is one of the most serious plant diseases and severely threatens agricultural production. The rapidly intensifying resistance makes most commercial chemical fungicides lose control efficacy. Developing new fungicides with novel structures and modes of action is an effective measure to solve this problem.

Review on synthesis of lactic acid and lactates from biomass derived carbohydrates via heterogeneous catalysis.

The utilization of renewable lignocellulosic biomass resources is a promising solution to deal with the deficit of fossil resources and the associated environmental concerns. Among diverse biomass-derived products, lactic acid (LA) stands out as one of the most successful commodities and also a platform to connect raw biomass feedstocks with value-added chemicals and degradable polymers. Herein, we critically review the recent advances in the design and development of base, acid, and multifunctional catalytic systems for the conversion of different carbohydrates to LA and alkyl lactates via chemical routes.

Copper-Catalyzed Oxidative Arylation and Hydroxylation of Indolin-2-ones for Direct Construction of Tetrasubstituted Carbon Centers.

This study introduces a novel methodology for the direct construction of tetrasubstituted centers, utilizing secondary C(sp)-H and C(sp)-H substrates, specifically indolin-2-ones and indoles, through an innovative oxidative cross-coupling reaction. Facilitated by a straightforward copper salt catalyst, this reaction proceeds efficiently at a mild temperature of 40 °C under operationally streamlined conditions. Emphasizing sustainability, this method is notably enhanced by employing air (molecular oxygen) as an eco-friendly oxidant.

RecA deletion disrupts protein homeostasis, leading to deamidation, oxidation, and impaired glycolysis in .

is a foodborne pathogen linked to severe infections in infants and often associated with contaminated powdered infant formula. The RecA protein, a key player in DNA repair and recombination, also influences bacterial resilience and virulence. This study investigated the impact of deletion on the pathogenicity and environmental stress tolerance of BAA-894.

Magnesium/methanol-d1: a practical reductive deuteration system for the deuterium labeling of α,β-unsaturated esters, nitriles and amides.

The use of magnesium and methanol in the reduction of various functional groups has been well established. In this study, we present a reductive deuteration system using Mg/CHOD, which successfully facilitates the conversion of α,β-unsaturated esters, amides, and nitriles to their saturated counterparts. This protocol achieves good yields and high degrees of deuterium incorporation, while avoiding defunctionalization in the presence of various functional groups.