Hypoxia is a common characteristic of solid tumors, especially in hepatocellular carcinoma (HCC). Hypoxia-inducible factors (HIFs), particularly HIF-1α, mediate metabolic adaptation, which is crucial for survival of hypoxic cells. Branched-chain amino transferase 1 (BCAT1) catalyzes the reversible transamination reaction between branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs), involving the inter-conversion of α-ketoglutarate (α-KG) and glutamate. We investigate and delineate the mechanisms by which BCAT1 consumes α-KG and stabilizes HIF-1α, suppressing α-KG-dependent oxygen dehydrogenase, prolyl hydroxylase-domain protein (PHD), inducing HIF-1α-mediated metabolic reprogramming and promoting hypoxic survival of HCC. We evaluate the potency of a BCAT1 inhibitor, ERG245, as a single or combination treatment with tyrosine kinase inhibitor (TKI) in vivo. We further validate the over-expression and correlation of BCAT1 and HIF-1α downstream metabolic genes in HCC clinical samples. Our results indicate that BCAT1 benefits HCC growth through HIF-1α-induced metabolic reprogramming. Targeting BCAT1 will provide an effective therapeutic strategy for HCC patients.

Live cell imaging of EML4-overexpressing A549 cells in wound healing assay.

Sample information and analysis in the internal cohort.

Differences between m6A level-derived patient subtypes.

Organophosphate flame retardants (OPFRs), widely used in consumer products as flame retardants and plasticizers, pose significant health risks, yet their high-risk sources in urban PM2.5 are understudied. In this study, we investigated the atmospheric prevalence of 13 traditional and 13 novel OPFRs in Shenzhen, a dynamic urban hub in southern China, using multiseason PM2.5 sampling paired with advanced analytical techniques, including atmospheric pressure gas chromatography mass spectrometry and liquid chromatography-tandem mass spectrometry. Concentrations of traditional and novel OPFRs in PM2.5 were 5062.2 +/- 1618.0 pg m(-3) (range: 2562.8-9154.7 pg m(-3)) and 3081.3 +/- 1552.8 pg m(-3) (range: 663.3-7607.3 pg m(-3)), respectively. Employing positive matrix factorization with source-specific markers, we identified six emission sources, with plastic processing and waste disposal dominating, contributing 61.0% and 51.6% to traditional and novel OPFRs, respectively, and increasing to 71.9% and 63.0% during the wet season. Although inhalation risks from coexposure to traditional and novel OPFRs in PM2.5 were generally low, chlorinated OPFRs from these sources posed elevated risks. Toxicity prediction further revealed that certain novel aryl-OPFRs, such as isodecyl diphenyl phosphate (IDDPP) and bis(2,4-di-tert-butylphenyl) phosphate (B2,4DtBPP), may induce more severe adverse health effects associated with estrogen receptor disruption and oxidative stress than traditional OPFRs. These findings underscore the urgent need to address high-risk novel OPFRs and their dominant emission sources, offering critical insights for mitigating air pollution and safeguarding public health in rapidly urbanizing regions.

Summary and gene enrichment of hyper-, hypo-, NL-specific and tumor-specific methylated genes.

Abstract Metabolic adaptations upon intrinsic and environmental stressors enable cancer cells to resist treatment and sustain proliferation. Understanding of adaptive rewiring and compensatory mechanisms is a pivotal strategy to develop effective treatment options. Statins are receiving increasing attention in the prevention of colorectal cancer (CRC), but the biological mechanism is elusive. Here, we demonstrate that six statins show effective tumor repression capacity in a dose-dependent manner. We next observe that administration of statin alone is not sufficient to induce programmed cell death because inhibitors of ferroptosis, apoptosis, necroptosis, and autophagy fail to rescue the cell viability. To further understand the therapeutic vulnerability, untargeted metabolic analysis is employed to detect the reprogramming metabolites. Pathway analysis shows glutathione metabolism is significantly perturbed. Meanwhile, dramatic increases of cysteine and gamma-glutamylcysteine are widely observed while the reduced glutathione (GSH) and oxidized glutathione (GSSG) levels are decreased, linked to redox imbalance and ferroptosis. Western blotting shows statins have similar effects as RSL3 on increasing the expression of glutamate-cysteine ligase catalytic subunit (GCLC), which catalyzes the rate-limiting step of GSH synthesis, and its inhibition is associated with ferroptosis induction. In contrast, CRC cells show increasing reliance on glutathione peroxidase 4 (GPX4) upon statins treatment when compare to RSL3. Collectively, compensatory upregulation of GCLC indicates combinations of statins and GCLC inhibitors may enhance antiproliferative efficacy of targeting GSH metabolism. Citation Format: Jieqing FENG, Jianming LI, Hong YAN, Zongwei CAI. Repurposing statins activates compensatory glutathione metabolism as synergistic vulnerability in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4707.

Organoids are three-dimensional multicellular structures generated from stem cells through self-organization, which recapitulate key architectural and functional features of native human organs. By bridging the gap between conventional in vitro models and in vivo systems, organoids provide a physiologically relevant platform for studying human development and disease. Compared with traditional two-dimensional cultures, organoids better preserve cellular diversity, tissue-specific functions, and long-term genetic stability, enabling scalable expansion for biobanking and high-throughput applications. In contrast to animal models, they allow more precise genetic manipulation, real-time imaging, and direct investigation of human-specific biological processes. Owing to these advantages, organoids have become powerful tools across multiple biomedical fields, including disease modeling, vaccine evaluation, regenerative medicine, drug discovery, and personalized therapy, where they enable more accurate mechanistic studies and therapeutic assessment.

Aristolochic acids (AAs) and the herbs containing them are recognized human carcinogens. Emerging evidence indicates that AAs are also food and environmental contaminants, posing significant risks to human health. This study developed a highly sensitive AA detection method by combining automated in-injector denitration with HPLC coupled with fluorescence detection (HPLC-FLD). The method converts non-fluorescing AAs into fluorescing aristolic acids (ARs) through a dithionite-mediated reaction directly within the HPLC injector port. Following validation for accuracy and precision, this method was applied to measure AAs in herbal medicine and soil samples collected from an herbal cultivation field. This approach, featuring automated in-injector derivatization, offers improved sensitivity and resolution, and selectivity while being less labor-intensive than existing methods for AAs analysis, obviating the need for sample enrichment or cleanup. The adaptable derivatization strategy also shows promise for the sensitive detection of other chemical species with appropriate derivatization agents.

As green alternatives of developed pesticides, diamide insecticides (DAIs) now are new choice to protect crops in China. Extensive applications inevitably lead to their considerable releasing into the environment, especially aquatic system through agricultural runoff. However, large-scale investigation of their pollution characteristics in surface water is still rare. In this work, a nationwide survey elucidated the widespread occurrence of DAIs in rivers across 9 major Chinese basins, with their median concentrations from 0.96 ng/L (Chlorantraniliprole, CTP) to 17 ng/L (Cyantraniliprole, CYTP). While CYTP is the predominant contaminant in riverine water, While CYTP is the predominant contaminant in riverine water, its regional pollution features were different, which was associated with local applied crop-specific insecticides. Noteworthily, broflanilide (BFA) was the DAI with the highest screening-level ecological concern especially for dwelling midges (Chironomus dilutus), even though its pollution level is not the most serious. This pattern indicates that ecological risk is not determined by environmental concentration alone, but is strongly influenced by compound-specific toxicity. Furthermore, in comparison to adults, children showed modeled cumulative waterborne exposure about 2.4 times that of adults cumulative waterborne exposure of DAIs under the modeled raw source-water ingestion scenario, although all calculated Hazard Quotients (HQ) remained below 1. This work provides a preliminary nationwide snapshot of DAIs pollution in Chinese surface water. The spatial heterogeneities of contamination patterns and potential exposure risks both highlights the urgent need to study the in vivo and in vitro biological impacts of DAIs in the future.

Sample information and gene list of NL-specific, tumor-specific and common methylated genes.

Phthalates, such as butyl benzyl phthalate (BBP), are widely detected in the environment and confirmed to exhibit estrogenic effects. However, their health risks toward breast tumor (BT) under real environmental conditions remained unclear. This study systematically investigated BBP-related health risks for BT by integrating in vitro assays with chronic exposure mouse models at environmentally relevant concentrations. The mechanisms were further investigated using metabolomics and lipidomics approaches. In vitro experiments demonstrated BBP and its metabolites (monobutyl phthalate and monobenzyl phthalate) enhanced 4T1 cell proliferation (cell viability ratio ≥1.2). In animal experiments, tumor volumes in the Low-dose (0.2 mg/kg/day) and High-dose (20 mg/kg/day) groups increased to 2.82-fold and 4.84-fold of the control group, respectively. Integrated metabolomics and lipidomics analysis revealed that BBP induced glycerolipids (GLs) hydrolysis into fatty acids (FAs), while upregulating fatty acid β-oxidation and TCA cycle activity. Acetyl-CoA derived from β-oxidation enhanced TCA cycle flux, which provided energy for pyrimidine metabolism and promoted tumor growth. This study firstly provided comprehensive assessment of BBP's health risks for BT under realistic exposure scenarios, offering mechanistic insights to support phthalate regulation and environmental management.

Characteristics of m6A peaks and methodological comparison for m6A level calculation.

The quantitative characterization of multiple exposure routes to quaternary ammonium compounds (QACs) remains underexplored. In this study, paired samples of indoor dust, bulk air, hand wipes, silicone wristbands, and urine were collected from 109 adults residing in urban homes from South China in 2023. First, seven urinary biomarkers, including hydroxylated and carboxylated metabolites of C10-C14 benzylalkyldimethylammonium compounds (BACs), were identified using a combined in silico and in vitro workflow. Then, 23 QACs, including 6 C8-C18 BACs, 6 dialkyldimethylammonium compounds (C8-C18 DADMACs), 6 alkyltrimethylammonium compounds (C8-C18 ATMACs), and 5 emerging QACs, were ubiquitously detected in various environmental matrices, including dust (median ∑QAC concentrations of 39.6 μg/g), bulk air (130 pg/m3), hand wipes (1420 ng for two hands), and silicone wristbands (225 ng/g), respectively. A significantly positive correlation was observed between the logarithmically transformed masses of QACs detected in silicone wristbands and those from dust, bulk air, and hand wipes (r: 0.564, p < 0.01). Moreover, urinary hydroxylated and carboxylated C10- and C12-BACs were significantly correlated with corresponding parent compounds in wristbands (r: 0.481-0.607, p < 0.01). Finally, back calculation from urinary exposure biomarkers revealed that ingestion of surface residues was the dominant exposure route for C10-, C12-, and C14-BACs, accounting for 3.7%, 49.6%, and 18% of total exposure, respectively. The findings from this study propose suitable urinary exposure biomarkers and silicone wristbands as useful indicators for accurate internal and external exposure assessment, respectively, and highlight the importance of ingestion of surface residues as a major exposure route.

As bioactive compounds, chiral amino acids (AAs) have been demonstrated to play pivotal roles in different physiological processes, thereby influencing human health. The assessment of the relative enantiomeric ratio through analytical methods is essential for indicating the abnormal status of disease progression, which drives the development of effective methods for resolving and identifying enantiomers. This work presents a robust strategy for the ultrahigh-resolution analysis of chiral AAs using MALDI-TIMS-MS. By employing a chiral derivatization process using S-NIFE and stabilizing the soft chain of the derivatization reagent with bimetal ion addition, the separation of 19 pairs of proteinogenic AAs was successfully achieved. This method not only demonstrates outstanding separation capability but also proves its efficiency in determining enantiomeric ratios, extending its applicability to real sample analysis.

Live cell imaging of EML4-overexpressing H358 cells in wound healing assay.