Dynamic investigation of hypoxia-induced L-lactylation.

The recently identified histone modification lysine lactylation can be stimulated by L-lactate and glycolysis. Although the chemical group added upon lysine lactylation was originally proposed to be the L-enantiomer of lactate (K), two isomeric modifications, lysine D-lactylation (K) and N-ε-(carboxyethyl) lysine (K), also exist in cells, with their precursors being metabolites of glycolysis. The dynamic regulation and differences among these three modifications in response to hypoxia remain poorly understood.

Targeting S100A8/A9-NCF1 Axis in Tumor microenvironment to Prevent Tumor Metastasis by Self-assembled Peptide Nanofibers.

Immunosuppressive microenvironment plays a crucial role in driving and accelerating tumor metastasis. S100A8/A9, produced by myeloid-derived suppressor cells, is a potential therapeutic target for metastatic cancer due to its role in promoting premetastatic niche formation. Previous studies have revealed that the S100A9-targeted peptide (H6, MEWSLEKGYTIK) fused to the Fc region of mouse IgG2b antibodies exhibits antitumor effects; however, the mechanism remains unclear.

RNA Editing Analysis Reveals Methyl Jasmonic Acid Regulation of Fucoxanthin and Fatty Acid Metabolism in .

is a marine diatom with significant biotechnological potential, particularly in producing high-value bioactive compounds such as fucoxanthin and unsaturated fatty acids, which possess significant pharmaceutical and nutraceutical properties. However, the naturally low yields of these compounds present a major challenge for large-scale production. Methyl jasmonic acid (MeJA), a plant-derived signaling molecule, has been shown to enhance the biosynthesis of these metabolites in .

Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012.

Oncogenic TFE3 fusions drive OXPHOS and confer metabolic vulnerabilities in translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by TFE3 gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic nature of most other renal cancers. Reliance on this TFE3 fusion-driven OXPHOS programme renders tRCCs vulnerable to NADH reductive stress, a metabolic stress induced by an imbalance of reducing equivalents.

Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration.

Self-Assembly Nanomedicine Initiating Cancer-Immunity Cycle with Cascade Reactions for Boosted Immunotherapy.

Immune checkpoint blockade (ICB) therapy has been extensively integrated into cancer clinical management. However, its overall response rate is limited due to the stagnating cancer-immunity cycle (CIC) caused by the immunosuppressive tumor microenvironment (TME). Here, a multi-pronged nanomedicine, defined as LCCS, was constructed by the self-assembly of lactate oxidase, catalase, chlorin e6, and sorafenib.

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Assessment of the safety and gut microbiota modulation ability of an infant formula containing Bifidobacterium animalis ssp. lactis CP-9 or Lactobacillus salivarius AP-32 and the effects of the formula on infant growth outcomes: insights from a four-month clinical study in infants under two months old.

Background: Breast milk is a natural treasure for infants, and its microbiota contains a rich array of bacterial species. When breastfeeding is not possible, infant formula with probiotics can be used as a sole source or as a breast milk supplement. The main aim of this study was to evaluate the growth outcomes and tolerance of infants consuming an infant formula containing Bifidobacterium animalis ssp.

Chemical Coordination of Acetic Acid to Improve Photovoltaic Performance and Long-Term Stability of Sn-Pb Perovskite Solar Cells.

Mixed Tin-Lead perovskite solar cells (Sn-Pb PSCs) with a narrow band gap (NBG) are significant for single-junction and all-perovskite tandem solar cells due to their low toxicity and ideal band gap. Nevertheless, the performance and stability of the device are adversely affected by the uncontrollable crystallization and ion migration processes. Acetic acid (HAc) is introduced into the perovskite precursor solution as a multifunctional additive to enhance the film crystallization process and restrain ion migration in the device.

Tau pathway-based gene analysis on PET identifies CLU and FYN in a Korean cohort.

Introduction: The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort.

Methods: We analyzed data for 146 older adults from the well-established Korean AD continuum cohort (Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; KBASE).

Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.

The nonribosomal peptide synthetase (NRPS) is a highly precise molecular assembly machinery for synthesizing structurally diverse peptides, which have broad medicinal applications. Withinthe NRPS, the condensation (C) domain is a core catalytic domain responsible for the formation of amide bonds between individual monomer residues during peptide elongation. This review summarizes various aspects of the C domain, including its structural characteristics, catalytic mechanisms, substrate specificity, substrate gating function, and auxiliary functions.

GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.

The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th differentiation.

Tin-Lead Perovskite Solar Cells with Preferred Crystal Orientation by Buried Interface Approach.

Mixed tin-lead perovskite solar cells (PSCs) have garnered much attention for their ideal bandgap and high environmental research value. However, poly (3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS), widely used as a hole transport layer (HTL) for Sn-Pb PSCs, results in unsatisfactory power conversion efficiency (PCE) and long-term stability of PSCs due to its acidity and moisture absorption. A synergistic strategy by incorporating histidine (HIS) into the PEDOT: PSS HTL is applied to simultaneously regulate the nucleation and crystallization of perovskite (PVK).

Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs.

A simple model for predicting the hydraulic conductivity of MICP-treated sand.

In this research paper, we introduce a novel and sustainable approach for forecasting the hydraulic conductivity of sand layers subjected to microbial-induced carbonate precipitation (MICP) to mitigate the diffusion of toxic pollutants. The proposed model uniquely integrates the impact of varying CaCO contents on the void ratio and estimates the average particle size of CaCO crystals through scanning electron microscopy (SEM) analysis. By incorporating these parameters into the K-C equation, a simplified predictive model is formulated for assessing the hydraulic conductivity of MICP-treated sand layers.

Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions.

Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population.

Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial.

Background: Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)-based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a first-in-human, phase 1/2 clinical trial conducted in 3 parts.

Methods: In parts 1 to 3 of this stratified observer-blind study, adults aged ≥18 years were randomly assigned to receive a single dose (6.