ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.

Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.

Probabilistic assessment of the cumulative risk from dietary heavy metal exposure in Chongqing, China using a hazard-driven approach.

Cumulative risk assessment is significant for evaluating the combined exposure to multiple substances, but its widespread acceptance and application have been limited due to the complexity of clarifying and assessing actual exposure. In this study, we conducted a cumulative risk assessment based on hazard-driven criteria to evaluate the co-exposure to elemental contaminants in the diet of the population in Chongqing Municipality. The cumulative risk was calculated and evaluated using Monte Carlo modeling and the modified Reference Point Index (mRPI) method.

Non-metallic iodine single-atom catalysts with optimized electronic structures for efficient Fenton-like reactions.

In this study, we introduce a highly effective non-metallic iodine single-atom catalyst (SAC), referred to as I-NC, which is strategically confined within a nitrogen-doped carbon (NC) scaffold. This configuration features a distinctive C-I coordination that optimizes the electronic structure of the nitrogen-adjacent carbon sites. As a result, this arrangement enhances electron transfer from peroxymonosulfate (PMS) to the active sites, particularly the electron-deficient carbon.

Neuron-inspired CsPbBr/PDMS nanospheres for multi-dimensional sensing and interactive displays.

Multifunctional materials have attracted tremendous attention in intelligent and interactive devices. However, achieving multi-dimensional sensing capabilities with the same perovskite quantum dot (PQD) material is still in its infancy, with some considering it currently challenging and even unattainable. Drawing inspiration from neurons, a novel multifunctional CsPbBr/PDMS nanosphere is devised to sense humidity, temperature, and pressure simultaneously with unique interactive responses.

NKAPL facilitates transcription pause-release and bridges elongation to initiation during meiosis exit.

Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes.

Liquid-infused nanostructured composite as a high-performance thermal interface material for effective cooling.

Effective heat dissipation remains a grand challenge for energy-dense devices and systems. As heterogeneous integration becomes increasingly inevitable in electronics, thermal resistance at interfaces has emerged as a critical bottleneck for thermal management. However, existing thermal interface solutions are constrained by either high thermal resistance or poor reliability.

Regulation of enzymatic lipid peroxidation in osteoblasts protects against postmenopausal osteoporosis.

Oxidative stress plays a critical role in postmenopausal osteoporosis, yet its impact on osteoblasts remains underexplored, limiting therapeutic advances. Our study identifies phospholipid peroxidation in osteoblasts as a key feature of postmenopausal osteoporosis. Estrogen regulates the transcription of glutathione peroxidase 4 (GPX4), an enzyme crucial for reducing phospholipid peroxides in osteoblasts.

Prevalence and associated factor of verbal abuse against nurses: A systematic review.

Background: Nurses who experience verbal abuse often report negative emotions, which can affect their work status and nurse-patient relationship. However, to the best of our knowledge, no study has summarized the prevalence of verbal abuse among nurses by different perpetrators and related risk factors.

Aim: This review aimed to synthesize the prevalence of verbal abuse among nurses and identify the most common sources and related risk factors.

A Global Relationship Between Genome Size and Encoded Carbon Metabolic Strategies of Soil Bacteria.

Microbial traits are critical for carbon sequestration and degradation in terrestrial ecosystems. Yet, our understanding of the relationship between carbon metabolic strategies and genomic traits like genome size remains limited. To address this knowledge gap, we conducted a global-scale meta-analysis of 2650 genomes, integrated whole-genome sequencing data, and performed a continental-scale metagenomic field study.

Manganese Intercalation Enabling High-Performance Aqueous Fe-VO Batteries.

The aqueous iron ion batteries (AIIBs) are an attractive option for large-scale energy storage applications. However, the inadequate plating and stripping of Fe ions underscore the need to explore more suitable cathode materials. Herein, we optimize the structure of tunnel-like VO nanosheets by introducing Mn ion intercalation as a cathode material to enhance their performance in AIIBs.

Enhancing biosensing of trace tau protein in clinical samples via emergence macroscopic directed aggregation.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that poses a significant risk to human health and well-being. The high cost and invasiveness of neuroimaging and cerebrospinal fluid (CSF) analysis underscores the necessity for accessible early screening via blood samples. In this study, we developed an ultrasound-based strategy for emergent macroscopic that enhances the acoustic response enrichment of specific proteins by introducing functionalized microspheres.

Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial.

Background: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients.

Methods: This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment.

Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.

We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .

New alkaloids from Melodinus fusiformis and their cytotoxic activities.

Four new alkaloids, meloformisine A (1), meloformine B (2), meloformine F (3), meloformine G (4), along with five known alkaloids (5-9) were isolated from the leaves and twigs of Melodinus fusiformis. Their structures were elucidated on the basis of detailed spectroscopic evidence, including 1D and 2D NMR, MS, and single-crystal X-ray diffraction analysis. The structure of 1 was a novel indole alkaloid with an unprecedented 6/5/5/5/5 pentacyclic skeleton.

Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury.

The emergence of cuproptosis, a novel form of regulated cell death, is induced by an excess of copper ions and has been associated with the progression of multiple diseases, including liver injury, cardiovascular disease, and neurodegenerative disorders. However, there are currently no inhibitors available for targeting specific cuproptosis-related pathways in therapy. Here, the compound merestinib (MTB) has been identified as a strong inhibitor of cuproptosis through screening of a kinase inhibitor library.

Immune-cell signatures of persistent inflammation, immunosuppression, and catabolism syndrome after sepsis.

Background: Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear.

Methods: We determined immune-cell signatures of PICS after sepsis at single-cell resolution.

The impact of traditional Chinese medicine kidney-tonifying methods on osteoporosis or bone loss in HR+ breast cancer patients following endocrine therapy.

Objective: This study aims to systematically assess the therapeutic effects of Traditional Chinese Medicine (TCM) kidney-tonifying methods on osteoporosis in HR+ breast cancer patients after endocrine therapy, and to explore their clinical application value.

Methods: This systematic review and meta-analysis adhered to the PRISMA guidelines and aimed to evaluate the impact of TCM kidney-tonifying methods on osteoporosis in HR+ breast cancer patients after endocrine therapy. Literature searches were conducted through October 2024 in databases including CBM, CNKI, Wanfang Data, PubMed, Web of Science, Cochrane Central, VIP, and renowned TCM databases such as TCM Online.

Engineering Defect-Mediated S-scheme heterojunctions in MOF-Derived N-doped NiO porous microrods and ZnInS nanosheets for superior photocatalytic hydrogen evolution.

The development of efficient photocatalysts inspired by natural photosynthesis has drawn considerable interest for sustainable hydrogen (H) production. Among the various strategies for enhancing H evolution, constructing step-scheme (S-scheme) heterojunctions has attracted extensive interest, thanks to their limited charge recombination and enhanced charge transport in comparison to the traditional photocatalytic systems. Herein, we report the engineering of a novel S-scheme heterojunction by integrating ultrathin ZnInS (ZIS) nanosheets with MOF-derived N-doped NiO porous microrods (ZIS/N-NiO) toward superior photocatalytic behaviors.

Polyaniline-ZnTi-LDH heterostructure with d-π coupling for enhanced photocatalysis of pollutant removal.

Heterointerface engineering is an effective strategy to design and construct high-performance photocatalysts. Herein, polyaniline (PANI) nanoparticles and ZnTi layered double hydroxide (ZnTi-LDH) nanosheets were integrated to form organic-inorganic heterostructure (PANI/LDH) via d-π electronic coupling using in-situ polymerization for photocatalytic oxidation/reduction towards tetracycline (TC) and Cr(VI). The photocatalytic activity was closely related to feed amount of aniline (Ani) in the polymerization process, which the abundant PANI nanoparticles were evenly distributed on the surface of ZnTi-LDH nanosheets at the proper Ani feed amount, and thus reinforced d-π electronic coupling at the organic-inorganic interfaces more efficiently.

Discovery of novel dual tubulin and MMPs inhibitors for the treatment of lung cancer and overcoming drug resistance.

Nowadays, hybrid molecule with dual targets activity or effect is regarded as an effective strategy for combating the drug resistance development in cancer therapy. Herein, novel of bifunctional conjugates targeting tubulin and MMPs inhibitors were synthesized. Among them, 15j exhibited robust anticancer activity in vitro and in vivo, with IC values of 0.

Anti-colorectal cancer actions of Glycyrrhiza uralensis Fisch. and its underlying mechanism via HPLC integration and network pharmacological approaches.

Background: The therapeutic and prognostic outcomes for colorectal cancer (CRC) remain unsatisfactory. Among multiple reported bioactive functionalities of Glycyrrhiza uralensis Fisch. one vital recently reported activity is its therapeutic role against numerous cancers but limited information is available related to its underlying key mechanisms and therapeutically active ingredients, especially against CRC treatment.

Extracellular peroxiredoxin 6 released from alveolar epithelial cells as a DAMP drives macrophage activation and inflammatory exacerbation in acute lung injury.

Acute respiratory distress syndrome (ARDS) is featured with acute lung inflammatory injury. Our prospective study found that higher levels of peroxiredoxin 6(PRDX6) were detected in bronchoalveolar lavage (BAL) fluid from ARDS patients. Elevated PRDX6 was also correlated with monocytic activation and poor prognosis in ARDS patients.

Exposure to high-temperature and high-humidity environments associated with cardiovascular mortality.

Aging populations are susceptible to climate change due to physiological factors and comorbidities. Most relevant studies reported the effect of temperature on cardiovascular disease (CVD)-related mortality in aging populations. However, the combined effects of temperature and humidity on CVD-related mortality remain unclear.