Rapid and accurate intraoperative pathologic diagnosis is essential for intraoperative decision-making, improving patient prognosis, and avoiding reoperation. This study developed a unique rapid pathological diagnosis and staging technique for intraoperative tissue sections based on lipidomic relevance, using two-photon fluorescence (TPF) imaging assisted by a lipid-targeted carbonized polymer dot (CPD) probe (∼8 nm) and multiple classification algorithms, including machine learning and deep convolutional networks. This platform enables ultrabright TPF imaging in response to lipid microenvironments and can be completed within 10 min. Its feasibility was validated through rapid diagnostics of intraoperative frozen sections of breast tissues. Due to abnormal levels of lipid metabolism, normal breast tissues and pathologically staged I-III cancerous tissues were well distinguishable, and the sensitivities and specificities for pathologic diagnosis were all above 90%. The combination of CPD and TPF microscopy provides a rapid and accurate method for detecting lipidomes in pathological frozen sections, marking a significant advancement over hematoxylin and eosin (H&E)-staining-based pathological diagnosis in terms of speed, ease of operation, and relevance to chemical components. This study is vital for advancing lipidome-related research and enhancing the understanding of the lipidomic atlas.

Emerging pollutants 6PPD and its oxidation product 6PPD-Q enter the environment via rubber product abrasion, with scarce toxicological data for risk assessment. This study compared their toxicity and mechanisms on zebrafish glucolipid metabolism at environmentally relevant and sublethal concentrations. Both induced developmental malformations dose-dependently, with 120hpf larvae LC50 of 991.6 μg/L (6PPD) and 165.2 μg/L (6PPD-Q), showing 6PPD-Q has higher teratogenicity and lethality. RNA-seq and bioinformatics revealed shared differentially expressed genes (DEGs) enrichment in ether lipid, glycerophospholipid, glycerolipid metabolism, and insulin signaling pathways, indicating common disruption of glucose-lipid homeostasis. Oil red o(ORO) staining and assays confirmed hepatic lipid accumulation (elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), reduced high-density lipoprotein cholesterol (HDL-C)) and glucose metabolism disorders (hyperglycemia, decreased insulin, lactate accumulation, etc.), suggesting insulin resistance and suppressed tricarboxylic acid cycle (TCA) cycle. Energy metabolism was dysfunctional (reduced adenosine triphosphate (ATP), impaired mitochondrial membrane potential (ΔΨm)), inhibiting swimming vitality, with more severe disturbances in 6PPD-Q group. PPI network analysis and RT-qPCR showed 6-PPD disrupts glucolipid metabolism via phospholipase A2(PLA2)-mediated pathways, while 6PPD-Q acts through PLA2, phospholipase D1(PLD1), and lysophosphatidylcholine acyltransferases (LPCATs). This study confirms their induction of glucolipid metabolic disorders with distinct mechanisms, providing a basis for environmental health risk assessment and related strategies.

Osteosarcoma (OS) is a highly aggressive bone tumor with rapid progression and high metastatic potential. Current clinical diagnosis relies mainly on imaging and biopsy, which are limited in detecting early pathological abnormalities and are unsuitable for real-time or repeated monitoring. Viscosity, a key biophysical parameter of the tumor microenvironment (TME), is closely linked to metabolic activity and signal transduction; abnormal viscosity changes may serve as sensitive indicators of OS progression and microenvironmental remodeling. The endoplasmic reticulum (ER), an essential organelle involved in protein folding, lipid metabolism, calcium homeostasis, and stress responses, plays a critical role in tumor adaptation and progression. Accordingly, monitoring ER-associated viscosity may provide valuable pathological information. Herein, we developed Ost-V, an ER-localized viscosity-responsive fluorescent probe based on an alkenyl indole scaffold. Ost-V exhibited viscosity-dependent fluorescence activation, good chemical stability, broad pH tolerance, favorable photostability, and low cytotoxicity. In living cells, Ost-V produced stronger fluorescence signals in OS cells than in normal cells and sensitively responded to intracellular viscosity elevation. Co-localization imaging confirmed preferential ER accumulation. In a subcutaneous OS xenograft model, ex vivo imaging showed that Ost-V can visualize viscosity changes in OS tumor tissues with low background interference from major organs. These results indicate that Ost-V is a promising molecular imaging tool for monitoring ER-associated viscosity alterations in the OS microenvironment, offering a potential strategy for early diagnosis and progression assessment of OS.

As pervasive environmental contaminants, nanoplastics (NPs) have garnered increasing concern due to their potential health hazards. However, the impact of gestational and lactational exposure to NPs on offspring vascular structural injury remains unexplored. In this study, we used BALB/c mice to model gestational and lactational exposure to 100 nm polystyrene nanoplastics (PS-NPs) at doses of 0.1, 1, and 10 mg/L. Our findings revealed that PS-NPs exposure significantly reduced offspring body weight in both sexes. Histopathological analysis demonstrated that exposure induced multiorgan damage in offspring at postnatal day 21 (PND 21), with partial recovery by PND 90. Critically, PS-NPs exposure induced cardiovascular toxicity in offspring, which included acute vascular injuries (disordered elastic fibers and evident calcium salt deposition) at PND 21 that were largely resolved by PND 90, alongside more persistent issues of abnormal lipid deposition in the aortic root and dyslipidemia observed at both time points. Integrated biomarker response indices, principal component analysis, and hierarchical clustering confirmed dose-dependent toxicity in PS-NPs-exposed offspring. In vitro studies further showed that PS-NPs induced lipid accumulation in three major cardiovascular cell types: endothelial cells, smooth muscle cells, and macrophages. Our study firstly reveals that maternal PS-NPs exposure throughout gestation and lactation induces vascular injury and lipid deposition in mouse offspring, indicating that PS-NP pollution represents a critical environmental risk factor for offspring cardiovascular adverse outcomes later in life.

Five isonitrogenous (35%) diets with different lipid contents were prepared by adding 0%, 3%, 6%, 9%, and 12% soybean oil (SO) as the single lipid source (with groups designated SO0, SO3, SO6, SO9, and SO12, respectively), followed by a 12-week feeding experiment in juvenile gibel carp (Carassius gibelio) (initial weight: 11.76 ± 0.09 g). The final weight (FW), weight gain rate (WGR), and specific growth rate (SGR) were significantly higher in gibel carp fed diets containing 6%-12% SO than those of others (p  < 0.05), while the feed conversion ratio (FCR) was significantly reduced in the SO6 group (p  < 0.05). Muscle crude fat and polyunsaturated fatty acid (PUFA) levels significantly increased as the dietary SO content increased (p < 0.05). Meanwhile, muscle crude protein was present in notably higher amounts in fish receiving 6%-9% SO (p < 0.05). Serum low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (T-CHO) continuously increased with increasing SO levels (p < 0.05). Histopathological abnormalities were observed in the local regions of the hepatopancreas after supplementation with 9%-12% SO. Most genes involved in lipid metabolism were upregulated to varying degrees (p < 0.05) as dietary SO content increased, especially lipogenic genes. About 4481 differentially expressed genes (DEGs) were screened in the hepatopancreas between the SO12 and SO0 group, primarily linking to metabolism-related pathways, including steroid biosynthesis. Conclusively, the available content of SO as the sole fat source in diets for juvenile gibel carp was found to be 6%-9%, within which the optimal SO inclusion was 6.37% according to FCR-based regression analysis. Excessive supplementation of dietary SO (12% or beyond) could expedite hepatic lipid metabolism, particularly lipogenesis, by stimulating steroidogenesis, thereby evoking fat over-accumulation, lipid metabolism disorders, and other adverse effects in gibel carp. These results provide synthetic data for better understanding the advantages, disadvantages, and relevant mechanisms of SO-based feed for gibel carp and for optimizing SO-based aquafeeds in farmed fish.

Children's health and well-being are cross-cutting indicators of sustainable development and underpin society's long-term development potential and productivity. The Shanghai Child and Adolescent Health Cohort (SCAHC) was established with a focus on the sociodemographic, environmental and biological determinants of children's growth and development.

BackgroundMaternal weight before, during, and after pregnancy is associated with postpartum metabolic health; however, the independent contributions of these weight indicators remain insufficiently examined.ObjectivesThis study assessed the associations of pre-pregnancy Body Mass Index (BMI), gestational weight gain (GWG), and postpartum weight retention (PPWR) with metabolic outcomes.DesignWe analyzed data from a prospective cohort of pregnant women followed to 6 months postpartum in the United Arab Emirates (UAE).MethodsA total of 256 women were recruited during their third trimester of gestation from Primary Health Clinics and Mother and Child Centers. Weight information was obtained for three time points: before pregnancy, at delivery, and 6 months postpartum. Blood biomarkers (lipids, insulin, glucose, and inflammatory markers) were measured at 6 months postpartum. Multivariate logistic regression assessed the associations between weight indicators and each metabolic outcome, as well as with having ≥3 abnormal/elevated outcomes, based on the population median of three.ResultsPre-pregnancy overweight/obesity (59.4%) was significantly associated with elevated insulin (OR=3.91, CI: 1.36-11.24), interleukin-6 (OR=5.11, CI: 1.71-15.28), CRP (OR=5.34, CI: 1.58-18.01), LDL (OR=2.89, CI: 1.08-7.74) and total cholesterol (OR=3.05, CI: 1.14-8.15). Among participants, 85.1% had inappropriate GWG, and 73.2% retained some weight postpartum. GWG was associated only with elevated TNF-α, while PPWR was linked to elevated fasting serum glucose. The odds of having ≥3 metabolic abnormalities were significantly higher among women with elevated pre-pregnancy BMI (OR=3.44, CI: 1.36-8.68).ConclusionAmong the three weight indicators examined, pre-pregnancy BMI showed the most consistent associations with postpartum metabolic biomarkers. These findings suggest that achieving a healthy weight before pregnancy may be an important target for reducing cardiometabolic risk.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and its rising incidence poses a growing burden on productivity and healthcare systems, particularly in the context of global population aging. Despite substantial advances in research, the pathogenesis of PD remains incompletely understood, and no curative or effective preventive therapies are currently available. Emerging evidence suggests a potential link between fatty acid (FA) metabolism and PD pathogenesis, positioning the modulation of FA metabolic pathways as a promising therapeutic strategy. This review examines the interplay between FA metabolism and key pathological processes, including oxidative stress, neuroinflammation, and the abnormal aggregation of alpha-synuclein, within the context of PD. By integrating these perspectives, the article aims to advance understanding of disease mechanisms and identify novel opportunities for prevention, early diagnosis, and targeted treatment.

Bruton's tyrosine kinase inhibitors (BTKIs) have become the first-line treatment for B-cell malignancies such as chronic lymphocytic leukemia, significantly improving patient outcomes. However, hypertension is a common and critical cardiovascular adverse effect of BTKIs, with incidence rates ranging from 23% to 75%. For some patients, traditional antihypertensive therapy is ineffective, creating significant risks to cardiovascular safety and the sustainability of the treatment plan. Current reviews have primarily addressed general BTKI cardiotoxicity or isolated signaling pathways, failing to systematically analyze how the proprotein convertase subtilisin/kexin type 9 (PCSK9)/Notch3 pathway coordinates hypertension. Furthermore, current reviews lack comprehensive integration of individual susceptibility and mechanism-targeted strategies. Thus, this review systematically evaluates the epidemiological characteristics, molecular mechanisms, individual risk-modifying factors, and management strategies of BTKI-related hypertension by searching the PubMed, Embase, and Web of Science databases (up to 2025). Key findings suggest that BTKIs induce endothelial dysfunction and increase peripheral mechanisms through multiple mechanisms. These agents promote vascular inflammation, remodeling, and altered lipid metabolism by upregulating PCSK9, abnormally activating Notch3 signaling, increasing renin-angiotensin-aldosterone system activity, and driving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-reactive oxygen species-mediated oxidative stress. Additionally, off-target inhibition of TEC/interleukin 2-inducible T-cell kinase contributes to these adverse vascular effects. Disease risk is further modified by Notch3/PCSK9 gene polymorphisms and clinical features such as existing cardiovascular disease and advanced age. Clinical management primarily relies on traditional antihypertensive drugs such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, as well as calcium channel blockers. In contrast, novel intervention strategies such as PCSK9 inhibitors and curcumin show potential advantages. To our knowledge, this review systematically elaborates the core role of the PCSK9/Notch3 signaling pathway in BTKI-related hypertension, integrating the "mechanism - susceptibility - intervention" three-dimensional network, providing a theoretical basis for precise risk stratification and individualized treatment, and promoting the dual optimization of cardiovascular protection and anti-tumor therapy.