ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2026
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IF 12.2
Zhendong Yang,Tingyu Li,Wenyuan Su,Wangjing Zhai,Zhengzhe Wan,Yong Liang,Ting Ruan,Guibin Jiang
The activation of peroxisome proliferator-activated receptor γ (PPARγ) represents a primary biological mechanism underlying the adverse effects of environmental adipogens. However, a holistic understanding of the composition profiles of PPARγ agonists in complex environmental matrices remains elusive. In this study, an integrated workflow of knowledge-based suspect screening combined with in vitro bioassays enabled the comprehensive identification and prioritization of the main contributing components in indoor dust from Chinese residential areas. All mixed dust extracts activated PPARγ within the exposure concentration range (7.8 × 10–2–10 mg dust/mL assay medium). A total of 123 putative agonists covering 35 structural categories were found, among which 30 chemicals were verified as specific PPARγ agonists through reference standards and in vitro assays. These agonists could explain up to 84% of the effect in the mixed dust extracts, with phthalates (31% ± 19%), fatty acids (12% ± 9%), quaternary ammonium compounds (2% ± 1%), and hydrocarbon surfactants (2% ± 1%) being the major contributors. The concentration addition model was validated to effectively characterize the combined effects of these PPARγ agonists via the artificial mixture experiments. These results suggest that the workflow holds promise for the overall perception of bioactive components related to toxicological end points in environmental samples.
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EXPERIMENTAL NEUROLOGY
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2026
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IF 4.8
Zhenyu Wu,Xufang Huo,Yubing Huang,Taowu Gong,Pengcheng Zhao,Yuhang Zhu,Qingfan Zeng
Although hypertension (HYP) consistently predicts cognitive decline, the precise pathogenic cascade within the brain remains elusive. Here we interrogated whether the PPARγ/ACSL3 axis governs HYP-elicited hippocampal ferroptosis and consequent cognitive dysfunction. This study aimed to explore the role of the PPARγ/ACSL3 axis in HYP-induced neuronal ferroptosis and cognitive impairment. In the HYP rat model, behavioral tests (Morris water maze and Y-maze tests) demonstrated that rats in the hypertensive group had a significant decline in learning and memory. Mechanistically, the AngII-AT1R axis was found to be activated in the hippocampus, accompanied by typical ultrastructural features of ferroptosis, increased iron accumulation, elevated oxidative stress, and downregulation of PPARγ, ACSL3, and key ferroptosis defense proteins (GPX4, XCT, and FPN1). In vitro, ACSL3 overexpression alleviated AngII-induced neuronal ferroptosis. Furthermore, the PPARγ agonist rosiglitazone attenuated lipid peroxidation and iron overload by transcriptionally upregulating ACSL3, a direct regulatory relationship confirmed by dual-luciferase reporter assay. In conclusion, under hypertensive conditions, BRAS activation inhibits the PPARγ/ACSL3 axis via the AngII-AT1R pathway, aggravates lipid peroxidation and ferroptosis in hippocampal neurons, and ultimately contributes to cognitive decline. This study provides new experimental evidence for the mechanism research and therapeutic target exploration of HYP-related cognitive impairment.
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FOOD AND CHEMICAL TOXICOLOGY
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2026
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IF 3.2
Yuchen Zheng,Zijia Liu,Zijie Zhao,Chao Sheng,Wenzhuo Li,Duo Tang,Yunlu Ning,Renhang Zhou,Ao Li,Zhixiang Zhou
As an emerging contaminant, nanoplastics (NPs) are widespread in the food chain and environment, raising concerns about their potential toxicity. However, their effects on lipid metabolic homeostasis and the underlying mechanisms remain unclear. This study used polystyrene nanoplastics (PS-NPs), common in food packaging, to examine their impact on adipogenic differentiation and lipid synthesis. Our research results indicated that after 10 days of oral exposure, PS-NPs significantly accumulated in the adipose tissue of mice. Within the exposure concentration range of 1-100 μg/mL, PS-NPs significantly increased the expression of genes related to adipogenesis, accelerated mitotic clonal expansion (MCE) during early differentiation, and enhanced triglyceride (TG) accumulation in mouse 3T3-L1 preadipocytes, leading to adipogenic differentiation and lipogenesis. These effects were positively correlated with the exposure concentration. Protein quantification and immunofluorescence revealed that PS-NPs promoted the nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ). Molecular dynamics simulations confirmed that PS-NPs bind to the nuclear localization signal (NLS) region of PPARγ. These findings suggested a new molecular mechanism in which PS-NPs influence PPARγ′s subcellular localization through NPs-protein interactions, triggering adipogenic programs. This study provides valuable insights for the safety assessment and toxicology of nanoplastics.
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Nature Communications
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2025
·Vol. 16
·期 1
·1-12
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IF 15.7
Tian Ran,Zhang Tong,Dong Hao,Seim Inge,Yang Guang
Blubber is a hydrostatic pressure-resistant and insulating vascularized layer of subcutaneous adipose tissue beneath the skin found in cetaceans, pinnipeds, and sirenians. Little is known about the molecular genetics of blubber formation, and it is unclear when the blubber observed today began to develop during the evolution of the marine mammal groups. Here we screen for genes lost in cetaceans and find that ADRB3 (β 3 -adrenergic receptor), a gene essential for adipose tissue lipolysis and thermogenesis, acquired inactivating mutations in crown cetaceans 20 million years after its downstream effector uncoupling protein 1 ( UCP1 ) gained partial loss-of-function mutations in semi-aquatic stem cetaceans. Both in vivo and in vitro experiments indicate that cetacean ADRB3 is not functional, suggesting that crown cetaceans abolished cold-induced non-shivering thermogenesis to favor lipid storage for thermal insulation. Our study supports that cetacean blubber evolved stepwise along their transition to an aquatic environment and implies that ADRB3 loss was critical for the radiation and dispersal of toothed and baleen whales.
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ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Huijun Yu,Xiao Xu,Xian Wang,Xiaonan Qiu,Qinxin Wang,Mengke Lu,Fengyi Du,Qi Guo,Miaomiao Zhang
Photothermal therapy (PTT) faces critical limitations due to tumor hypoxia, intrinsic resistance, and metastasis. To address these challenges, we developed a trimodal nanoplatform (R-R/PB@PPy NEs) by synergizing Prussian blue (PB)/polypyrrole (PPy) nanozymes, tumor suppressor reactivation, and immune modulation. Through Fe3+ -mediated one-step oxidative polymerization, PB and PPy were integrated into a hybrid nanozyme and further functionalized with rosiglitazone (PPAR-γ agonist) and rutin (tumor-targeting ligand). The R-R/PB@PPy NEs achieved a photothermal conversion efficiency of 31.6% and catalase/superoxide dismutase-like enzymatic activity, persistently alleviating hypoxia via oxygen generation. Simultaneously, AKT/mTOR-mediated PTEN upregulation suppressed tumor proliferation and metastasis. Rutin-mediated tumor targeting enhanced drug accumulation at tumor sites, which synergistically amplified immunogenic cell death induction, promoting dendritic cell maturation and cytotoxic T-cell infiltration. In vivo, this platform completely inhibited 4T1 tumor growth, eradicated lung metastasis, and prevented recurrence (0% at 56 days) with an 80% long-term survival rate and no systemic toxicity. By unifying catalytic nanozyme design, PTEN-driven sensitization, and immune activation, this study establishes an interdisciplinary strategy to overcome resistance in PTT, offering a translatable approach for precision cancer therapy through tumor microenvironment modulation.
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PHYTOMEDICINE
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2026
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IF 8.3
Chong Gao,Wei Liu,Sai-Hu Liu,Shuang Zheng,Chen-Yu Wang,Xu Dai,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background Reprogramming of aerobic glycolysis occurs with HSCs activation and is associated with regression of liver fibrosis. Trigonelline (TRG), a plant alkaloid extracted from Trigonella foenum-graecum L seeds, has a variety of pharmacological effect. Purpose The current study investigated the hepatoprotective effect and mechanism of TRG against hepatic fibrosis by regulating glycolysis. Methods Anti-hepatic fibrosis effects of TRG were detected in thioacetamide (TAA)-induced hepatic fibrosis mice. HSCs or LX-2 were stimulated with TGF-β or conditioned medium (CM) from LPS-stimulated THP-1, then incubated with TRG, phloretin (PHL), rosiglitazone (RGZ), siRNA Glut-1 or plasmid with Glut-1. Results TRG significantly reduced serum transaminase levels, liver histopathological changes, excessive collagen deposition, inflammatory response, and neutrophil recruitment in TAA-induced mice. TAA increased hepatic Glut-1, HIF-1α and key enzymes of glycolysis expressions, while TRG completely reversed this effect. TRG also obviously regulated the combination of Glut-1 and HIF-1α to affect glycolysis in activated HSCs. TRG could inhibit α-SMA, IL-6, IL1R1, and HIF-1α expressions accompanying inhibition of Glut-1, function as PHL (Glut-1 inhibitor). Glut-1 silencing weakened α-SMA, IL-6, IL1R1, and HIF-1α expressions and enhanced the effect of TRG in activated LX-2. TRG inhibited LX-2 activation caused by Glut-1 overexpression, even demonstrated in interaction between LX-2 and macrophages. Further, TRG shown that improved fibrogenesis and inflammatory response by inhibiting Glut-1 compared with PHL in vivo . Conclusion TRG could ameliorate hepatic fibrosis through inhibiting ECM excessive deposition and inflammatory response. Inhibiting Glut-1-HIF-1α axis and glycolysis was a potential therapeutic strategy for TRG ameliorating liver microenvironment, further against hepatic fibrosis.
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BIOMATERIALS
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2026
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IF 13.6
Jin Li,Mengyi Yang,Rui Xing,Jingmei Pan,Xing Guo,Shaobing Zhou
Ischemic stroke therapy remains challenging due to a detrimental post-reperfusion inflammatory cascade that exacerbates neuronal damage, a process critically mediated by neutrophils and microglia. Neutrophils infiltrate the brain to release pro-inflammatory factors and neutrophil extracellular traps (NETs), while microglia become activated and amplify neuroinflammation. However, both cell types possess phenotypic plasticity that allows for immunomodulation toward repair. To address this, we developed a biomimetic nanoparticle strategy designed to reprogram these immune cells. Specifically, we encapsulated rosiglitazone into mPEG-PLA nanoparticles and further coated them with platelet membranes, obtaining a targeted nanoplatform termed pmPELA@R. In a mouse model of middle cerebral artery occlusion (MCAO), the platelet membrane coating markedly enhanced neutrophil targeting and improved brain accumulation of pmPELA@R. The released rosiglitazone activated PPAR-γ to polarize neutrophils toward the N2 phenotype and suppressed NETosis. Concurrently, the lactate generated from PLA degradation promoted microglial M2 polarization via enhanced histone lactylation. This dual modulation synergistically shifted the inflammatory microenvironment toward a reparative state, leading to enhanced neural tissue recovery. Our findings present a novel nanotherapeutic approach for precise immunomodulation in ischemic stroke.
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Journal of Bioresources and Bioproducts
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2025
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IF 13
Shuang Qi,Hui Yang,Tian Fang,Tingwei Zhang,Bo Jiang,Sehrish Manan,Chaofeng Zhang,Peng Wang,Caoxing Huang,Wenjuan Wu,Yongcan Jin
Lignin, a natural and renewable aromatic biopolymer, has gained attention in various biomedical applications due to its diverse structure, excellent biocompatibility, and antioxidant activity. However, the effects of lignin with tailored molecular weight on treating type 2 diabetes mellitus (T2DM) remain largely unexplored. In this study, a series of heterogeneous natural phenolic kraft lignin (KL) with tailored molecular weights, derived through an anti-sugar strategy, were prepared by continuous fractionation. The lignin fractions were categorized as F1, F2, and F3, corresponding to high, medium, and low molecular weights, respectively. Their therapeutic effects on T2DM were evaluated using a fractionated lignin culture cell model and intravenous injection into the tail vein of diabetic rats. The results demonstrated that lignin's protective effects in attenuating T2DM progression were molecular weight-dependent. Specifically, F3 reduced fasting blood glucose, reversed insulin resistance, and improved insulin sensitivity by mitigating oxidative stress and inflammatory responses. Mechanistic investigations revealed that F3 positively regulated glucose and lipid metabolism, inhibited hepatic gluconeogenesis, and enhanced hepatic glycogen synthesis by activating the insulin receptor substrate 1/phosphoinositide 3-kinase/protein kinase B (IRS1/PI3K/AKT) signaling pathway. Results revealed that lignin exerts its therapeutic effects on T2DM in a molecular weight-dependent manner, with IRS1/PI3K/AKT signaling as a potential underlying mechanism. This highlights lignin with a defined molecular weight as a promising candidate for T2DM treatment.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Yin Zhuang,Xiangying Sun,Siting Deng,Ya Wen,Qiujin Xu,Quanquan Guan
Background Bisphenol A (BPA) is known to exhibit endocrine disrupting activities and is associated with adiposity. We examined the obesogenic effect of prenatal BPA exposure in the present study. Methods Pregnant ICR mice were exposed to vehicle or BPA via the drinking water at a dose of 0.5 μg/kg·d throughout the gestation. Obesity-related indexes were investigated in the 12-wk-old offspring. Primary mouse embryonic fibroblasts (MEFs) collected from treated embryos were used to test effects of BPA on adipocyte differentiation. Results Offspring presented a significantly higher rate of weight gain than the control, with impaired insulin sensitivity and increased adipocyte size. Differentiation of MEFs from BPA-treated mice showed a higher propensity for the adipocyte commitment as well as up-regulation of genes enriched in lipid biosynthesis. TGF-β signaling pathway was found to modulate obesogenic effect of BPA in MEF model, but estrogen signaling pathway had no effect. Conclusions The present study provides strong evidence of the association between prenatal exposure to low dose of BPA and a significant increase in body weight in the offspring mice with a critical role played by TGF-β signaling pathway. The potential interactions modulating the binding of BPA and TGF-β that activate its obesogenic effects need to be examined.
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Marine Drugs
·
2023
·Vol. 21
·期 5
·270
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IF 5.4
Zhuling Shao,Yingying Tian,Shan Liu,Xiao Chu,Wenjun Mao
Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present study, a homogeneous exopolysaccharide from the fermented broth of the mangrove endophytic fungusPenicillium janthinellumN29, designated as PJ1-1, was obtained. The results of chemical and spectroscopic analyses showed that PJ1-1 was a novel galactomannan with a molecular weight of about 10.24 kDa. The backbone of PJ1-1 was composed of →2)-α-d-Manp-(1→, →4)-α-d-Manp-(1→, →3)-β-d-Galf-(1→ and →2)-β-d-Galf-(1→ units with partial glycosylation at C-3 of →2)-β-d-Galf-(1→ unit. PJ1-1 had a strong hypoglycemic activity in vitro, evaluated using the assay of α-glucosidase inhibition. The anti-diabetic effect of PJ1-1 in vivo was further investigated using mice with type 2 diabetes mellitus induced by a high-fat diet and streptozotocin. The results indicated that PJ1-1 markedly reduced blood glucose level and improved glucose tolerance. Notably, PJ1-1 increased insulin sensitivity and ameliorated insulin resistance. Moreover, PJ1-1 significantly decreased the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, enhanced the level of serum high-density lipoprotein cholesterol and alleviated dyslipidemia. These results revealed that PJ1-1 could be a potential source of anti-diabetic agent.Keywords:mangrove endophytic fungus;exopolysaccharide;structure;anti-diabetic activity
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Foods
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2023
·Vol. 12
·期 3
·539
·
IF 5.2
Zixian He,Zhiwei Liu,Haihuan Xie,Pengjie Luo,Xiangmei Li
Herein, an ultrasensitive lateral flow immunoassay (LFIA), based on metal-organic framework-decorated polydopamine (PCN-224@PDA) was first established to detect multiple sulfonylureas (SUs) in functional foods. The PCN-224@PDA was synthesized using the one-pot hydrothermal method and covalently coupled with SUs antibodies, and the coupling rate was up to 91.8%. The detection limits of the developed PCN-224@PDA-LFIA for multiple SUs in functional teas and capsules were 0.22–3.72 μg/kg and 0.40–3.71 μg/kg, and quantification limits were 0.75–8.19 μg/kg and 1.03–9.08 μg/kg, respectively. The analytical sensitivity was 128-fold higher than that of similar methods reported so far. The recovery rates ranged from 83.8 to 119.0%, with coefficients of variation of 7.6–14.4%. The parallel analysis of 20 real samples by LC-MS/MS confirmed the reliability of the proposed method. Therefore, our work offers novel, ultrasensitive, and rapid technical support for on-site monitoring of SUs in functional foods.Keywords:sulfonylureas;metal-organic frameworks;polydopamine;lateral flow immunoassay;functional foods
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BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Jingyi Hu,Yiheng Tong,Zhaofeng Shen,Yanan Li,Cheng Cheng,Ryan Au,Feng Xu,Yajun Liu,Lei Zhu,Hong Shen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae , maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun , is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli ( E. coli, family of Enterobacteriaceae ) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae . Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.
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