Pharmacological Targeting of DHHC9-Mediated STRN4 Palmitoylation to Suppress YAP-Driven Cancer Metastasis.

Protein S-palmitoylation, a dynamic and reversible post-translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signalling. Dysregulation of this modification has emerged as a critical driver of cancer progression. Among the 23 DHHC palmitoyl transferases responsible for catalysing S-palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets.

An Engineered Supramolecular Fluorescent Chemosensor for Multiscale Visualization of Glutamate Dynamics in Living Systems.

Glutamate (Glu) plays a critical role in the brain, and the ability to directly measure glutamate activity is essential for understanding its physiological functions and pathological processes. Herein, we engineered a family of Glu sensors () based on host-guest interactions through the indicator displacement method (IDA) strategy. The optimized supramolecular chemosensor exhibited specificity, sensitivity, signal-to-noise ratio, rapid kinetics (∼145 ms), and photostability, enabling it to be suitable for monitoring Glu dynamics in neuronal organelles, brain tissues, and zebrafish.

Hyperbaric oxygen augments Doxil antitumor efficacy by reducing tumor-induced lactate.

Compared to healthy individuals, cancer patients exhibit significantly elevated lactate. While numerous studies have revealed the critical role of lactate in fostering an immunosuppressive tumor microenvironment, the effects of lactate on cancer nanomedicine (e.g.

KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1.

XPR1 is emerging as the only known inorganic phosphate (Pi) exporter in humans, critical for Pi homeostasis, with its activity stimulated by inositol pyrophosphate InsP8 and regulated by neuronal scaffold protein KIDINS220. Our structural studies reveal that InsP8 specifically activates XPR1 in a stepwise manner, involving profound SYG1/PHO/XPR1 (SPX) domain movements. Each XPR1 subunit functions with four gating states, in which Pi permeates a constriction site via a "knock-kiss-kick" process.

Characteristics of mDIXON-Quant and proton magnetic resonance spectroscopy imaging of thigh skeletal muscles in patients with stroke-related sarcopenia: a prospective case-control study.

Background: This study was performed to investigate the imaging features of mDIXON-Quant and proton magnetic resonance spectroscopy (1H-MRS) of thigh muscles in patients with stroke-related sarcopenia (SRS).

Methods: This prospective case-control study was conducted in 40 patients with SRS, 40 patients without sarcopenia who had a stroke, and 40 healthy volunteers using mDIXON-Quant and 1H-MRS scanning. Skeletal muscle cross-sectional area (CSA) and fat fraction (FF) were analyzed.

Genomic Insights into the Molecular Basis of Broad Host Adaptability of the Entomopathogenic Fungus (Entomophthoromycotina).

(Entomophthorales), a fungal pathogen with a broad insect host range, is a promising candidate for biocontrol applications. We sequenced a strain isolated from a sp. cadaver using PacBio long-read sequencing to elucidate the molecular basis of its wide host adaptability.

Identification of CDK5RAP2 as a causative gene of focal epilepsy without microcephaly.

Objective: The CDK5RAP2 gene, which encodes a regulator of cyclin-dependent kinase activity, plays a vital role in brain development. CDK5RAP2 variants have been previously reported in patients with primary microcephaly-3, with or without epilepsy. This study aimed to investigate the association between CDK5RAP2 and epilepsy.

Age-specific childhood obesity and adult cholelithiasis: association and shared transcriptomic bases.

Objectives: The association between obesity and cholelithiasis has been identified. However, the causal relationship between age-specific childhood obesity and adult cholelithiasis remains unclear. In addition, the biological basis for the association between childhood obesity and adult cholelithiasis is poorly understood, which poses a challenge for preventing adult cholelithiasis in specific biological pathways.

Heterogeneity in prognosis for early-stage hepatocellular carcinoma after hepatectomy: A multicenter analysis of 4,623 patients across five major staging systems.

Background & Aims: Multiple staging systems for hepatocellular carcinoma (HCC) have led to heterogeneous definitions of "early-stage" disease, potentially affecting treatment decisions and outcomes. This study aimed to quantify the prognostic variations among patients undergoing curative hepatic resection for "early-stage" HCC, as defined by five major staging systems.

Methods: In this multicenter study, 4623 patients who underwent curative resection for newly diagnosed HCC (2014-2023) across 11 tertiary hospitals were analyzed.

Microcystin-LR hijacks mitochondrial bioenergetics and Wnt crosstalk: Unveiling a novel dual-pathway mechanism for adipogenesis dysregulation in environmental toxicology.

Cyanobacterial blooms, driven by toxin-producing cyanobacteria, pose significant environmental health risks due to the persistent release of cyanotoxins like microcystin-LR (MC-LR). While much research has focused on its hepatotoxic, nephrotoxic, and neurotoxic effects, its impact on adipose tissue homeostasis remains poorly understood. This study investigates the effects of MC-LR on stromal vascular fraction (SVF) cells, key progenitors in adipogenesis and metabolic regulation.

From waste to flavor enhancer: differential pressure explosion puffing modifies spent coffee grounds for microbial consortia-driven flavor synthesis in craft beer systems.

The high lignocellulosic encapsulation of spent coffee grounds (SCG) severely restricts their substrate accessibility and microbial responsiveness. This study elucidated the regulatory mechanism by which differential pressure explosion puffing (DPEP) optimizes microbial-flavor metabolic networks in SCG beer through the structural remodeling of SCG. Results demonstrated that DPEP significantly enriched Klebsiella abundance, enhancing sugar-phenol synergistic metabolism to promote the synthesis of key flavor compounds, including butyl propionate (fruity), 4-hydroxycinnamic acid (bitter), D-Mannose (caramel), and Indanone (floral).

Dual-layer spectral detector CT electron density imaging: impressive technology for imaging characteristics of ground-glass nodules.

Background: Pulmonary ground-glass nodules (GGNs) are increasingly being detected as manifestations of early lung cancer. However, conventional computed tomography (CT) images may fail to clearly show small lesion details, particularly in the case of small, low-density GGNs, which are often difficult to observe. Limited evidence suggests that dual-layer spectral detector CT (SDCT) electron density imaging (EDI) improves the visualization of ground-glass opacities (GGOs) and increases the detection rate of mixed GGNs (mGGNs).

The impact of post-processing images of abdominal CT small vessels using contrast enhancement boost technique: a retrospective study.

Background: Accurate visualization of small abdominal arteries is crucial for diagnosis, preoperative evaluation, and treatment planning, especially in hepatobiliary and pancreatic diseases. However, due to their small calibers and rapid contrast transit, consistent delineation of these vessels remains challenging in conventional computed tomography (CT) angiography. Recent advancements in image postprocessing, such as contrast enhancement boost (CE-Boost) techniques, offer opportunities to improve vascular conspicuity without additional radiation or contrast agent.

Evolution of CoNi Alloy Electronic Structure Buffered by Carbon Nanolayer to Tune Selective Generation of Reactive Oxygen Species.

Generation of non-radical reactive oxygen species (ROS) via peroxymonosulfate (PMS) activation is desired to drive selective Fenton-like reactions and strongly affected by the electronic structure of catalyst. While the static structure-activity relationship of catalysts is well explored, how the evolution of electronic structure dynamically affects the ROS generation remains poorly understood. This study fabricated carbon nanolayer-supported CoNi alloys (CoNi@CNT) with preset atomic Ni/Co ratio (x/y = 1:3, 2:2, 3:1) to probe the dynamic evolution of electronic structure and its subsequent role for the generation of non-radical ROS.

Integrating multimodal ultrasound imaging for improved radiomics sentinel lymph node assessment in breast cancer.

Background: Accurate preoperative assessment of sentinel lymph node (SLN) is critical for treatment planning in breast cancer (BC). While SLN biopsy (SLNB) remains the gold standard, it is invasive and may be unnecessary for all patients, particularly those with clinically node-negative disease. Combining conventional B-mode ultrasound (BMUS) and color Doppler ultrasound (CDUS) with new techniques like radiomics and deep learning may improve SLN prediction, but this approach has not been widely studied yet.

[Optimization of the baculovirus expression system enhances the expression level of recombinant human keratinocyte growth factor-1 (hKGF-1)].

Human keratinocyte growth factor-1 (hKGF-1), a member of the fibroblast growth factor (FGF) family, plays crucial roles in organ development, cell proliferation, wound healing, and tissue repair, representing one of the most effective and specific growth factors for skin repair. However, obtaining recombinant hKGF-1 remains challenging due to its universally low expression efficiency . This study employs the baculovirus expression system to establish a technological platform that utilizes the economically important insect as a bioreactor for high-efficiency and low-cost expression and production of recombinant human keratinocyte growth factor 1 (hKGF-1) protein, ultimately achieving high-level expression of hKGF-1 in ovary cell line (BmN).

Preoperative ASAP score predicts recurrence and survival following curative hepatic resection for hepatitis B virus-related hepatocellular carcinoma: A multicenter cohort study.

Background & Aims: The ASAP score, integrating age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), has demonstrated value for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. This study sought to assess whether the ASAP score could also predict recurrence and survival following curative resection of HBV-related HCC.

Methods: This multicenter study included patients undergoing curative hepatic resection for HBV-related HCC.

Discovery of Highly Selective and Potent Macrocyclic JAK2 Inhibitors for the Treatment of MPNs.

The development of selective JAK2 inhibitors represents a promising therapeutic strategy for MPNs. Building upon the foundation of our first-generation JAK2 inhibitor, we employed macrocyclization-driven structural optimization to address its off-target limitations. This strategy yielded a novel class of macrocyclic JAK2 inhibitors, with compound emerging as a standout candidate through systematic SAR studies.

Instant enzymes: Systems engineering approach to rapid low cost production of thermostable molecular biology enzymes.

Purified thermostable proteins are essential research reagents, yet their production often involves laborious, stepwise optimization and costly chromatographic methods. These barriers have historically limited in-house protein production to well-equipped labs with significant expertise. A systems engineering approach is presented for streamlined, low-cost production and chromatography-free purification of widely used DNA-modifying enzymes, including Taq DNA Polymerase, Fusion High-Fidelity Polymerase, Thermostable DNA Ligase, and Reverse Transcriptase.

Desensitizing mechanism of thermal processing on pumpkin seed protein: allergen structure alteration and immune reactions in mice.

Background: Pumpkin seeds are commonly consumed nuts. While their allergic potential has been neglected, major allergens existing in pumpkin seed proteins (PS pro) are not clarified yet. Thermal processing has been reported as an effective desensitizing method.

Pre-clinical therapeutics for osteopetrosis caused by PLEKHM1 deficiency Using ex Vivo and in vivo gene Therapies.

Background: Osteopetrosis caused by mutation of Plekhm1 gene is characterized by malignant phenotypes, poor quality of life, and lack of effective treatment. It remains in dispute whether hematopoietic stem cell transplantation (HSCT) is a suitable therapeutic approach for it. In addition, other potential novel therapeutics including gene therapies have not yet been investigated for their efficacies.

Endoplasmic reticulum stress and autophagy as potential therapeutic targets in SERPINF1 mutation-induced type VI osteogenesis imperfecta.

Background: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by recurrent fragile fractures. Mutations in the SERPINF1 gene are known to cause a rare, autosomal recessive form of type VI OI. The pathogenic mechanisms underlying type VI OI caused by mutations in the SERPINF1 gene remain unclear.