Spatial 3D genome organization reveals intratumor heterogeneity in primary glioblastoma samples.

Glioblastoma (GBM) is the most prevalent malignant brain tumor with poor prognosis. Although chromatin intratumoral heterogeneity is a characteristic feature of GBM, most current studies are conducted at a single tumor site. To investigate the GBM-specific 3D genome organization and its heterogeneity, we conducted Hi-C experiments in 21 GBM samples from nine patients, along with three normal brain samples.

Chain length of fatty acid determines the reassembly behaviors of starch-lipid complexes following microwave heat-moisture treatment.

Food postprocessing can induce the structural changes of starch-lipid complexes, however, how the chain length of fatty acids affects their reassembly behaviors during postprocessing has not been researched. Accordingly, starch-lipid complexes containing varying chain lengths of fatty acids were prepared and the changes in their structures and digestibility were investigated during microwave heat-moisture treatment. After treatment, the contents of complexed lipids, complex index, and single helix in the complexes increased, and the values were lower for complexes containing longer-chain fatty acids.

Incorporating preoperative and intraoperative data to predict postoperative pneumonia in elderly patients undergoing non-cardiothoracic surgery: The online two-stage prediction tool.

Background: Prior research on postoperative pneumonia (POP) risk models focused on preoperative factors but overlooked intraoperative variables vital for precision. These models also neglected the higher-risk elderly population. This study seeks to develop and evaluate preoperative and combined models to predict POP risk in elderly patients undergoing non-cardiothoracic surgery.

Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation.

During homeostasis and regeneration, satellite cells, the resident stem cells of skeletal muscle, have distinct metabolic requirements for fate transitions between quiescence, proliferation and differentiation. However, the contribution of distinct energy sources to satellite cell metabolism and function remains largely unexplored. Here, we uncover a role of mitochondrial fatty acid oxidation (FAO) in satellite cell integrity and function.

Size-effect induced controllable Cu-Cu sites for ampere-level nitrate electroreduction coupled with biomass upgrading.

The synergistic Cu-Cu sites is regarded as the active species towards NH synthesis from the nitrate electrochemical reduction reaction (NORR) process. However, the mechanistic understanding and the roles of Cu and Cu remain exclusive. The big obstacle is that it is challenging to effectively regulate the interfacial motifs of Cu-Cu sites.

Morphology Effect of Puffball Spores on Hemostasis: A Promising Solution for Hemostatic Challenges.

Hemostatic materials play a crucial role in wound healing by promoting blood concentration or releasing procoagulant factors. While hydrophilic hemostatic materials are effective, they may cause excessive blood loss and difficulty removing from the wound. Conversely, hydrophobic hemostatic materials avoid these issues but may hinder blood concentration and the release of procoagulant factors due to their water-repellent nature.

Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates.

Alzheimer's disease (AD), the most prevalent form of dementia, disproportionately affects the elderly population. While aging is widely recognized as a major risk factor for AD, the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood. In our previous work, the neuropathological changes in the brains of aged cynomolgus monkeys (≥18 years old) following parenchymal cerebral injection of amyloid-β oligomers (AβOs) have been characterized.

Cavity oscillation drives pattern formation in early mammalian embryos.

During the second cell fate in mouse embryos, the inner cell mass (ICM) segregates into the spatially distinct epiblast (EPI) and primitive endoderm (PrE) layers. The mechanism driving this pattern formation, however, remains unresolved. Here, we report that, concomitant with the segregation process of EPI/PrE precursors starting from mid-blastocyst, the blastocyst cavity begins to oscillate cyclically with rapid contraction yet slow expansion, triggering a phase transition in the ICM to a fluid-like state.

Capilliposide A relieved dry age-related macular degeneration through ROS/SIRT1/P53 signaling pathway.

Age-related macular degeneration (AMD) is the main cause of vision impairment in the elderly, which still lacks efficient treatment. Capilliposide A (LC-A), a saponin-type anti-inflammation compound extracted from Lysimachia capillipes Hemsl, were used for investigating its anti-AMD effects. The cell viability of LC-A against ARPE-19 cell lines were detected by CCK8 assay.

MESR4 targets bam to mediate intestinal homeostasis and aging in adult flies.

The Drosophila melanogaster (fruit fly) misexpression suppressor of Ras 4 (MESR4) gene encodes a potential transcription factor and plays critical roles in various biological processes, including embryonic development, lipid metabolism, eye-antennal development, and germline stem cell differentiation. However, whether it is involved in modulating intestinal homeostasis remains elusive. In this study, we provide compelling evidence demonstrating that MESR4 is a bona fide regulator in preventing age-onset intestinal leakage and dysbiosis in adult flies.

Multiomic Analysis of Calf Muscle in Peripheral Artery Disease and Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) has emerged as a significant risk factor that accelerates atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the modulators underlying this exacerbated pathobiology are ill-defined. Recent work has demonstrated that uremic toxins are associated with limb amputation in PAD and have pathological effects in both the limb muscle and vasculature.

Current status of artificial intelligence analysis for the diagnosis of gallbladder diseases using ultrasonography: a scoping review.

Background: Ultrasound (US) is the first-line imaging method for gallbladder diseases (GBDs), with advantages of easy accessibility, real-time dynamic imaging, and no radiation. However, using only visual judgment from US images to stratify the risk of gallbladder (GB) lesions is challenging. In addition, the diagnostic ability of sonographers is highly correlated with their knowledge reserves, clinical experience, and proficiency in operation.

MorPhiC Consortium: towards functional characterization of all human genes.

Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes. The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium aims to address this gap by creating a comprehensive catalogue of the molecular and cellular phenotypes associated with null alleles of all human genes using in vitro multicellular systems.

Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity.

Oncogene amplification is a key driver of cancer pathogenesis. Both breakage fusion bridge (BFB) cycles and extrachromosomal DNA (ecDNA) can lead to high oncogene copy numbers, but the impact of BFB amplifications on intratumoral heterogeneity, treatment response, and patient survival remains poorly understood due to detection challenges with DNA sequencing. We introduce an algorithm, OM2BFB, designed to detect and reconstruct BFB amplifications using optical genome mapping (OGM).

Pioneer factor GATA6 promotes colorectal cancer through 3D genome regulation.

Colorectal cancer (CRC) is one of the most lethal and prevalent malignancies. While the overexpression of pioneer factor GATA6 in CRC has been linked with metastasis, its role in genome-wide gene expression dysregulation remains unclear. Through studies of primary human CRC tissues and analysis of the TCGA data, we found that GATA6 preferentially binds at CRC-specific active enhancers, with enrichment at enhancer-promoter loop anchors.

Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.

Background: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.

Methods: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared.

Efficacy and safety of cisplatin combined with paclitaxel concurrent radiotherapy in patients with locally advanced cervical squamous cell carcinoma.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dual-agent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events.

mRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity.

Unlabelled: The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) and interleukin-2 (IL-2) T-cell responses and neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity on cellular and humoral responses to vaccination were additionally assessed.

Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.

ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.

Deep learning-based synthetic CT for dosimetric monitoring of combined conventional radiotherapy and lattice boost in large lung tumors.

Purpose: Conventional radiotherapy (CRT) has limited local control and poses a high risk of severe toxicity in large lung tumors. This study aimed to develop an integrated treatment plan that combines CRT with lattice boost radiotherapy (LRT) and monitors its dosimetric characteristics.

Methods: This study employed cone-beam computed tomography from 115 lung cancer patients to develop a U-Net +  + deep learning model for generating synthetic CT (sCT).

Network Pharmacology Combined With Metabolomics Reveals the Mechanism of Yangxuerongjin Pill Against Type 2 Diabetic Peripheral Neuropathy in Rats.

Purpose: This study aims to explore the mechanism of Yangxuerongjin pill (YXRJP) in the treatment of diabetic peripheral neuropathy (DPN) by network pharmacology and metabolomics technology combined with animal experiments, and to provide scientific basis for the treatment of DPN.

Methods: In this study, network pharmacology analysis was applied to identify the active compounds, core targets and signal pathways, which might be responsible for the effect of DPN. The DPN model was established by high-fat diet combined with streptozotocin (STZ) injection, and the rats were given administration for 12 weeks.

Functional characterization and protein engineering of a O-methyltransferase involved in benzylisoquinoline alkaloid biosynthesis of Stephania tetrandra.

Benzylisoquinoline alkaloids (BIAs) are the primary active components of Stephania tetrandra. However, the molecular mechanisms underlying BIA biosynthesis in S. tetrandra remain poorly understood.

Saccharomyces cerevisiae inactivation during water disinfection by underwater plasma bubbles: Preferential reactive species production and subcellular mechanisms.

The escalating challenges posed by water resource contamination, especially exacerbated by health concerns associated with microbial fungi threats, necessitate advanced disinfection technologies. Within this context, non-thermal plasma generated within bubble column reactors emerges as a promising antifungal strategy. The effects of direct plasma bubbles within different discharge modes and thus-produced plasma activated water (PAW) on the inactivation of Saccharomyces cerevisiae are investigated.

Chromatin hubs drive key regulatory networks in leukemia.

In this issue of Molecular Cell, Gambi, Boccalatte, Hernaez, et al. apply multiomics followed by genetic engineering to define then characterize epigenetic hubs that regulate processes crucial for T-ALL and use this insight to offer new avenues for therapeutic targeting.