Synthesis of Novel Benzofuran Spiro-2-Pyrrolidine Derivatives via [3+2] Azomethine Ylide Cycloadditions and Their Antitumor Activity.

A synthetic strategy of a three-component spiro-pyrrolidine compound based on benzofuran via an [3+2] azomethine ylide cycloaddition reaction is reported herein. Under mild optimal conditions, this reaction can quickly produce potentially bioactive compounds with a wide range of substrates, high yield, and simple operation. The desired products were obtained with a yield of 74-99% and a diastereomeric ratio (dr) of >20:1.

CAPE activates AMPK and Foxo3 signaling to induce growth inhibition and ferroptosis in triple-negative breast cancer.

Purpose: Approximately 20% of all breast cancer cases are classified as triple-negative breast cancer (TNBC), which represents the most challenging subtype due to its poor prognosis and high metastatic rate. Caffeic acid phenethyl ester (CAPE), the main component extracted from propolis, has been reported to exhibit anticancer activity across various tumor cell types. This study aimed to investigate the effects and mechanisms of CAPE on TNBC.

Enhancing Stability and Catalytic Activity of d-Allulose 3-Epimerase through Multistrategy Computational Design and Cross-Regional Advantageous Mutations.

d-Allulose 3-epimerase (DAEase) derived from has excellent properties in the catalytic production of d-allulose, a rare sugar with unique biological functions. However, the industrial application of DAEase (Cb-DAEase) for d-allulose production is hindered by its low enzyme activity, poor long-term thermostability, and pH tolerance. In this study, we identified potential noncatalytic residues in Cb-DAEase using methods such as proline substitution, surface charge engineering, and surface residue prediction.

CRISPR/Cas9-mediated GhFT-targeted mutagenesis prolongs indeterminate growth and alters plant architecture in cotton.

The shift from vegetative to reproductive growth is an important developmental transition that affects flowering and maturation, architecture, and ecological adaptability in plants. The florigen-antiflorigen system universally controls flowering and plant architecture, and changes to the ratio of these components alter this transition and disrupt growth. The genes FT (FLOWERING LOCUS T), encoding the florigen protein FT, and CETS [CENTRORADIALIS (CEN)/TERMINAL FLOWER1 (TFL1)/SELF-PRUNING (SP)], encoding antiflorigen proteins, have opposing roles.

PGRN protects against serum deprivation-induced cell death by promoting the ROS scavenger system in cervical cancer.

Progranulin (PGRN), an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells.

Development of a novel fluorescent probe for the Selective and sequential imaging of fluoride and hypochlorite.

Fluoride (F) are common in the environment and are beneficial in moderate amounts but can be harmful at high concentrations, leading to conditions such as fluorosis influenced by reactive oxygen species (ROS), including hypochlorite (ClO). This study introduces PZ-DT, a novel fluorescent probe with a phenothiazine core, designed for the sequential detection of F and ClO. PZ-DT emits orange-red fluorescence with a Stokes shift greater than 200 nm upon F detection, demonstrating excellent selectivity and sensitivity, boasting a quantum yield of 19.

Investigations on improved Box-Cox sparsity measures for machine condition monitoring.

Sparsity measures are commonly utilized as health indicators for machine condition monitoring. Recently, with the assistance of Box-Cox transformation, kurtosis and negative entropy have been smoothly extended to form Box-Cox sparsity measures (BCSMs). However, traditional BCSMs do not generate sparsity measures that outperform negative entropy, which means it is meaningless to some extent.

Industrial hemp (Cannabis sativa L.) adapts to cadmium stress by reshaping rhizosphere fungal community.

Increasing evidence indicates that plants under environmental stress can actively seek the help of microbes ('cry-for-help' hypothesis). However, empirical evidence underlying this strategy is limited under metal-stress conditions. Here, we employed integrated microbial community profiling in cadmium (Cd) polluted soil and culture-based methods to investigate the three-way interactions between the industrial hemp (Cannabis Sativa L.

Enhancing Mechanical Durability and Long-Term Stability in Organic Solar Cells via Flexible Linker-Sequential Block Copolymerized Donors.

Multi-component copolymerized donors (MCDs) hold great promise for improving both the efficiency and mechanical robustness of flexible organic solar cells (f-OSCs) owing to their facile molecular tunability and advantageous one-pot copolymerization. However, despite the excellent crystallinity imparted by their highly conjugated polymer backbone, MCDs often struggle to retain photovoltaic performance under large external deformations, limiting their applicability in wearable devices. Herein, we developed a novel series of flexible linker-sequential block MCDs (Fs-MCDs), specifically PM6-Cl-b-D18-Cl-BTB, PM6-Cl-b-D18-Cl-BTH, and PM6-Cl-b-D18-Cl-BTD, by precisely incorporating flexible functional groups into the conjugated polymer skeleton.

COVID-AMD database for coronavirus-infected animal models with comparative analysis tools.

Respiratory infections caused by coronaviruses have posed serious and unpredictably public health threats; reliable animal models continue to be essential for advancing our understanding of the virus's transmission, pathophysiology, and immunological mechanisms. In response to the critical need for centralized resources in coronavirus research, the COVID-AMD database (Coronavirus Disease Animal Model Database, https://www.uc-med.

The immune function of thioester-containing proteins in typical invertebrate disease vectors.

Disease vectors, such as arthropods, primarily rely on innate immunity to counteract pathogen invasions, typically through the recognition and binding of pathogen-associated molecular patterns (PAMPs) by the host's pattern recognition receptors (PRRs). As a conserved immune effector gene family from insects to mammals, the complement system may play an essential role in combating pathogenic microorganisms. In arthropods, the complement proteins are often referred to as thioester-containing proteins (TEPs) because thioester motifs are one of the essential functional domains of the first proteins characterized within the C3 and AM family.

Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma.

Sirtuin 6 (SIRT6), a member of the SIRT family, plays essential roles in the regulation of metabolism, inflammation, aging, DNA repair, and cancer development, making it a promising anticancer drug target. Herein, we present our use of proteolysis-targeting chimera (PROTAC) technology to formulate a series of highly potent and selective SIRT6 degraders. One of the degraders, , induced the near-complete degradation of SIRT6 in both SK-HEP-1 and Huh-7 cell lines and more potently inhibited hepatocellular carcinoma (HCC) cell proliferation than the parental inhibitors.

Multiple Resonance Quasi-fluorescence from BN-Doped Aromatic Compounds Modified with "Naphthalene" Units Approaches the BT.2020 Green Light Standard.

Developing fluorophores that conform to the Broadcast Service Television 2020 (BT.2020) standard presents a formidable challenge. Here, we propose an innovative approach that integrates two and three-boron/nitrogen (BN2)-embedded [4]helicene subunits with naphthalene, resulting in the synthesis of two novel narrowband bright green quasi-fluorescent emitters, NT-2B and NT-3B for ultra-high-definition displays.

PLXNA1 confers enzalutamide resistance in prostate cancer via AKT signaling pathway.

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR).

Formation mechanism of off-flavor and the inhibition regulatory strategies in the algal oil-loaded emulsions-a review.

Algal oil rich in docosahexaenoic acid is easily oxidized and degraded to produce volatile short-chain compounds, leading to the deterioration of product flavor. Currently, the emulsion delivery of algal oil provides a promising approach to minimize oxidative deterioration and conceal its off-flavor. However, algal oil emulsions would also experience unanticipated oxidation as a result of the large specific surface area between the aqueous phase and the oil phase.

Ubiquitination of NS1 Confers Differential Adaptation of Zika Virus in Mammalian Hosts and Mosquito Vectors.

Arboviruses, transmitted by medical arthropods, pose a serious health threat worldwide. During viral infection, Post Translational Modifications (PTMs) are present on both host and viral proteins, regulating multiple processes of the viral lifecycle. In this study, a mammalian E3 ubiquitin ligase WWP2 (WW domain containing E3 ubiquitin ligase 2) is identified, which interacts with the NS1 protein of Zika virus (ZIKV) and mediates K63 and K48 ubiquitination of Lys 265 and Lys 284, respectively.

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS.

Background: Hypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism.