Advanced Science
·
2026
·
IF 14.1
Shuo Zhang,Yujie Zhang,Jiansheng He,Shunlian Li,Qingyan Ma,Qiao Li,Yudan Zhang,Yiyang Wang,Shaobo Ma,Songyan Jin,Chune Li,Xueyong Xie,Hang Zhang,Junze Deng,Xueqin Song,Daocheng Wu,Xiancang Ma,Feng Zhu
Inflammatory bowel diseases (IBDs) are frequently accompanied by anxiety and depression, largely driven by perturbed gut-brain axis signaling. However, current oral therapies remain constrained by the spatial and functional separation between intestinal inflammation and central nervous system dysfunction. Here, we present a comprehensive gut-brain dual region integrated therapeutic strategy based on functionalized Bifidobacterium longum hydrogel (INPs@BL@Gel), in which baicalin and tyrosine are coordinated with Fe(III) to form infinite coordination polymers (ICPs), coated with inulin, assembled onto Bifidobacterium longum (BL), and subsequently encapsulated within a pH- and matrix metalloproteinase-responsive silk fibroin-gelatin hydrogel. INPs@BL@Gel exhibits high drug-loading, effective gastric protection, inflammation-triggered release, and long-term intestinal colonization. Within the inflamed intestine, BL and components synergistically suppress inflammatory responses, restore gut microbiota homeostasis, and promote intestinal barrier repair through multi-target integrated therapy. Importantly, BL combined with components markedly enhances the production of beneficial neuroactive metabolites such as homovanillic acid and short-chain fatty acids, which integratedly regulate neuroinflammation, preserve synaptic function, and facilitate blood-brain barrier repair via the gut-brain axis. In vivo studies demonstrate that INPs@BL@Gel not only exerts potent therapeutic efficacy against colitis and effectively alleviates associated depression, but also reshapes the gut microbiota and restores barrier integrity, achieving a remarkable comprehensive therapeutic effect.
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Scientific Reports
·
2026
·
IF 4.9
Zhao Zihao,Li Minqian,Teng Hongbo,Wang Xv,Shi Mengqi,He Zhongmei,Zong Ying,Chen Weijia,Geng Jianan,Zhou Jia,Zhao Yan
To establish the standardized processing technology of velvet antler stir-fried with Polygonatum sibiricum juice, elucidate the core mechanism underlying the enhanced anti-non-alcoholic fatty liver disease (NAFLD) efficacy of the processed product, and identify the key bioactive components. Taking protein content as the screening index, this study optimized the processing parameters of Polygonatum sibiricum -Prepared Cervus elaphus Velvet Antler (PC-PR) using single-factor experiments combined with response surface methodology (RSM). The in vivo pharmacodynamic efficacy was validated in a high-fat diet-induced NAFLD rat model. Multi-omics technologies were integrated to screen for core differential proteins enriched after processing. The in vitro activity of the target component was verified in an oleic acid-induced inflammatory model of HepG2 cells, and Western blot (WB) analysis was employed to decipher its molecular regulatory mechanism. A standardized processing technology for PC-PR was successfully established, which induced specific alterations in the compositional profile of velvet antler. The processed product significantly improved blood glucose, body weight, liver function, and lipid metabolism indicators in NAFLD model rats, with superior efficacy compared to non-optimally processed velvet antler. Multi-omics screening and in vitro experiments confirmed that Q28237 is a core bioactive component specifically enriched after processing, exhibiting potent lipid-lowering and anti-inflammatory activities. Mechanistic studies revealed that Q28237 alleviates the pathological progression of NAFLD by constructing a “component-pathway-phenotype” regulatory network, which involves inhibiting the overactivation of epidermal growth factor receptor (EGFR), promoting the activation of the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway, and activating estrogen receptor1 (ESR1) to exert synergisticanti-inflammatory effects.
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DRUG METABOLISM AND DISPOSITION
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2026
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IF 3.6
Jie Dai,Yufen Liao,Xueqian Cheng,Qing Zhang,Tingmin Ye,Dandan Yang,Chunlei Zhang,Ying Peng,Weiwei Li,Jiang Zheng
Tinospora sagittata is a widely used medicinal herb whose safety has raised increasing concerns in recent years. Fibleucin (FBL), a furanoditerpenoid isolated from Tinospora sagittata , has not been systematically evaluated for its safety and toxicological mechanisms despite its presence as a major bioactive constituent in this medicinal plant. To address this toxicological knowledge gap, we comprehensively investigated the hepatotoxicity and/or metabolic activation of FBL in vivo (mice) and in vitro (mouse and human liver microsomal incubations as well as primary mouse hepatocytes). Oral administration of FBL (single intragastric dose) dose-dependently elevated serum ALT, AST, ALP, blood ammonia, and total bile acid levels in mice, accompanied by hepatocellular degeneration, necrosis, and inflammatory infiltration. Pretreatment with the CYP3A inhibitor ketoconazole (100 mg/kg) markedly alleviated the liver injury induced by FBL. LC-MS/MS analysis of mouse liver microsomal incubations and primary hepatocyte exposure (1.0–50 μM FBL) revealed that FBL was bioactivated to an electrophilic intermediate reactive to thiols and amines. Similar observation was obtained in human liver microsomal incubations. The reactive intermediate was found to react with nucleophilic sites of hepatic glutathione and proteins to form the corresponding conjugates and adducts. The observed adduction correlated with the liver injury and cytotoxicity induced by FBL. Chemical synthesis was carried out to probe the mechanism of toxic action. The mechanistic investigation suggests that FBL was metabolized to the corresponding cis -2-butene-1,4-dial intermediate responsible for the GSH depletion and protein adduction.
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Cell Reports Medicine
·
2026
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IF 14
Zifan Pei,Yifan Yin,Nailin Yang,Shumin Sun,Nan Jiang,Fangyi Yu,Xiaofen Zhang,Jihu Nie,Youdong Chen,Longxiao Li,Jie Wu,Fei Gong,Minming Chen,Wei Liu,Liang Cheng
Clinical evidence has suggested that persistent STAT3 activation and alteration in lipid metabolism correlate with pathological progression in patients with breast cancer, driving resistance to chemotherapy. Herein, we show that H 2 S, an endogenous gas signaling molecule, sensitizes breast cancer to chemotherapy by suppressing STAT3 signaling-mediated lipid metabolism and improves tumor immunogenicity. Moreover, we further identify Ni 2+ as immune agonist for potent metalloimmunotherapy. The construction of an activable nanoplatform enables the controllable delivery of metal ions and H 2 S gas, which triggers pyroptosis and mobilizes multiple immune cells to elicit systemic anti-tumor immunity in combination with chemotherapy. Moreover, the synergy with αPD-1 inhibits the progression of both primary and metastatic tumors. Our work highlights the potential of bioactive gas transmitters and nutrient metal ions for reversing the dual dilemmas of chemoresistance and low immunogenicity in breast cancer and thus provides a nanosensitization strategy to synergize with multiple clinical treatment modalities.
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Micromachines
·
2026
·Vol. 17
·期 4
·408
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IF 3.5
Yaqiang Ji,Junfeng Huang,Weibin Yin,Junrui Xiang,Yongquan Liu,Yongjun Huang,Jingsheng Hong,Long Li
Bifunctional materials present a promising route to develop advanced devices, yet the dual performance of CoNi2S4nanosheets anchored on a porous scaffold is seldom reported. Herein, we propose a rational fabrication strategy to construct a three-dimensional hierarchical electrode via the in-situ growth of densely aligned CoNi2S4nanosheets on a conductive fabric scaffold. This integrated porous architecture concurrently offers an ultrahigh specific surface area, efficient mass transport, and rapid electron conduction. As a supercapacitor, the electrode achieves a high areal capacitance of 3198 mF cm−2at 4 mA cm−2and retains 98.1% of its initial capacitance after 1000 cycles at 20 mA cm−2. As a non-enzymatic glucose sensor, it exhibits outstanding selectivity (<4.1% interference), high sensitivity (1049 μA mM−1cm−2), a wide linear range (1–8 mM), and a low detection limit (1 μM). These results highlight the significant potential of this binder-free, scaffold-supported nanosheet design for advancing integrated energy storage and biosensing systems.
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ADVANCED MATERIALS
·
2026
·Vol. 38
·期 20
·e19832
·
IF 29.1
Dechao Gan,Xiaoyu Xie,Fei Long,Haoran Chen,Qiqing Li,Zexuan Sui,Wang Wang,Dabing Li,Yulei Chang
The second near-infrared window (NIR-II, 1000–2000 nm) provides an ideal window for multichannel photoluminescence lifetime imaging (mPLI) because of its exceptional tissue penetration depth and minimal scattering. However, the inevitable spectral crosstalk that is caused by the broad and overlapping emissions of traditional luminescent materials (e.g., organic dyes and quantum dots) has restricted the scalability of mPLI channels. Herein, we developed a series of Ln 3+ -doped (Ln = Nd, Er, Tm, or Ho) stratified nanoparticles (Ln-SNPs) that enable highly efficient multiwavelength NIR-II luminescence. These nanoparticles can be further engineered into concentration-mediated Yb 3+ energy relay nanoparticles to enable the precise tuning of the luminescence lifetime across the 1060–2050 nm range, thereby expanding the NIR-II imaging channels in mPLI. Notably, the engineered Tm-SNPs exhibit optimized downshifting emission at ∼1850 nm (NIR-IIc subwindow) with distinguishable luminescence lifetimes that span three orders of magnitude at similar emission intensities. This advancement establishes a powerful toolkit for multidimensional information encryption and multiplexed bioimaging applications.
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Advanced Healthcare Materials
·
2026
·
IF 11
Hong Jiang,Qin-Xie Xie,Tianzhao Tian,Qingqing Yang,Peipei Qian,Jia-Yi Liu,Wending Yan,Shengfeng Huang,Cui Shao,Wei Yi,Yifa Chen,Xu-Jia Hong
The complex tumor microenvironment (TME), characterized by coexisting normoxic and hypoxic regions, demands oxygen-adaptive nanomedicines for multimodal therapy. Herein, GTPZ is presented, an oxygen-adaptive covalent organic framework (COF)-based nanoplatform that can achieve quadruple-modal synergistic therapy through the integration of chemodynamic therapy (CDT), photothermal therapy (PTT), Type I/II photodynamic therapy (PDT), and hypoxia-activated chemotherapy. Remarkably, GTPZ exhibits a record-high photothermal conversion efficiency of 72% among COF-based nanomedicines, enabling spatiotemporal control over hypoxia-activated tirapazamine (TPZ) release to generate cytotoxic radicals. Besides, GTPZ dynamically adapts to oxygen gradients by activating Type II PDT in normoxia and switching to Type I PDT in hypoxia, with phototherapy-induced oxygen depletion amplifying TPZ activation, exhibiting high oxygen-adaptive ability. In MCF-7 models, GTPZ achieves high tumor suppression through synergistic lipid peroxidation, cell cycle arrest, and ferroptosis. This work provides a paradigm for designing intelligent nanomedicines capable of dynamically adapting to TME.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Biyao Zhao,Xiaoyu Wu,Xuwen Ye,Fangyi Jia,Yuanyuan Wang
The determination of acetylcholinesterase (AChE) activity and organophosphorus pesticides plays a critical role in disease diagnosis, drug screening, and food safety monitoring. In this study, we report a multifunctional UiO-66@MnO 2 nanocomposite that integrates both oxidase-mimicking activity and intrinsic fluorescence, enabling dual-mode colorimetric and fluorescence sensing. MnO 2 nanosheets anchored on the surface of the UiO-66 not only catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) but also efficiently quenched the fluorescence of UiO-66 via Förster resonance energy transfer. Upon the addition of acetylthiocholine and AChE, the enzymatic generated thiocholine reduces MnO 2 , resulting in disassembly of the nanocomposite. This triggers a “turn-off” colorimetric signal and a “turn-on” fluorescence response, enabling sensitive detection of AChE with detection limits as low as 0.076 mU/mL (colorimetric) and 3.8 mU/mL (fluorescence). Furthermore, taking advantage of the inhibitory effect of organophosphorus pesticides on AChE activity, the proposed platform was further successfully extended to detect dipterex, achieving detection limits of 0.032 μM (colorimetric) and 1.1 μM (fluorescence). Moreover, the dual-mode nanozyme sensor was successfully validated in complex biochemical samples, highlighting its considerable potential for applications in bioanalysis, food safety monitoring, and environmental surveillance.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2026
·Vol. 78
·期 3
·
IF 3.7
Cheng Yawei,Li Gengliang,Li Yang,Ma Yugang,Xia Yujie,Zhang Chunye,Wang Xingchen
ObjectivesConventional pharmacotherapies afford only modest renoprotection in diabetic nephropathy (DN). Oleanolic acid (OA), a pentacyclic triterpenoid abundant in Traditional Chinese Medicine (TCM), mitigates DN, but its mechanism remains unclear. This study aimed to verify the hypothesis that OA protects podocytes by modulating autophagy, thereby exploring the potential therapeutic mechanism of OA in attenuating DN.MethodsHigh glucose-injured MPC5 podocytes were treated with OA to evaluate its impact on autophagy. Podocytes were further treated with graded concentrations of OA, rapamycin (an autophagy inducer), or 3-methyladenine (an autophagy inhibitor). Cell viability was quantified using the Cell Counting Kit-8 assay. Nuclear morphology was visualized by DAPI staining, autophagosomes were enumerated by transmission electron microscopy, and the expression of autophagy-related genes was determined by quantitative reverse transcription polymerase chain reaction. These complementary approaches were used to assess high-glucose-induced podocyte injury and the capacity of OA to enhance autophagy and attenuate cellular damage.Key findingsThe effective concentration window for OA was established at 5–10 μM. Within this concentration range, podocyte viability was significantly increased, accompanied by a higher autophagosome count and elevated expression of autophagosomal markers.ConclusionsOleanolic acid alleviates high glucose-induced podocyte injury by robustly activating autophagy, underscoring its potential as a sustainable therapeutic strategy for DN, along with other active compounds derived from TCM.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2026
·
IF 3.6
Jiyong Wu,Jing Nie,Huina Wu,Dongbo Wang,Yamei Li,Minyan Liang,Huimei Qian,Yong Wang
Platinum-based chemotherapeutics remain clinically indispensable for treating various malignancies despite causing severe side effects, with ototoxicity being particularly limiting. This study reports the synthesis and evaluation of platinum(IV) prodrugs incorporating the hearing-protective ligand RG108. Among the synthesized mono- and di-substituted cisplatin and oxaliplatin derivatives, compound 4 exhibited exceptional antitumor activity with an IC 50 value of 0.07 ± 0.08 µM in FaDu cells. Mechanistic investigations revealed that the enhanced anti-tumor effect was primarily mediated via the EZH2/SLC47A2 regulatory axis. These prodrugs significantly mitigated ototoxicity, preserving cochlear hair cell viability, stabilizing auditory brainstem response thresholds, and maintaining cochlear basement membrane morphology. Our findings establish a framework for designing dual-functional platinum agents that synergize antitumor efficacy with organoprotective properties, addressing critical hearing loss limitations of conventional platinum chemotherapy while maintaining robust therapeutic outcomes. Graphical
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Microbiology Spectrum
·
2026
·
IF 4.1
Yuwei Qiu,Xu Dong,Dan Cao,Xiuzhi Jiang,Zhongkang Ji,Pusheng Xu,Yi Li,Kaijing Xu,Ying Zhang
Mycobacterium avium-intracellulare complex (MAC) infections are the most common nontuberculous mycobacterial infections, and ethambutol (EMB) is one of the main therapeutic agents used to treat MAC infections. However, the EMB resistance profile and its resistance mechanisms in M. avium remain poorly understood. This study determined the minimum inhibitory concentration (MIC) of 40 M. avium clinical strains, revealing that 97.5% (39/40) of the strains were intermediate (MIC = 4 µg/mL) or resistant (MIC ≥ 8 µg/mL) to EMB. One susceptible clinical isolate strain 245 (MIC = 2 µg/mL) was picked for EMB-resistant mutant isolation, and a total of 121 resistant mutants were isolated and subjected to whole-genome sequencing or Sanger sequencing. Integrated analysis revealed that 94.21% (114/121) of the mutants carried mutations in the ubiA gene, which encodes decaprenylphosphoryl-β-D-5-phosphoribose (DPPR) synthase—an enzyme involved in cell wall biosynthesis that has been associated with high-level EMB resistance in Mycobacterium tuberculosis. Complementation with the wild-type ubiA gene restored EMB susceptibility in EMB-resistant mutants and clinical strain 322 (EMB MIC = 64 µg/mL) with ubiA mutation, reducing the MICs from 32 to 4 μg/mL and from 64 to 8 μg/mL, respectively. This study indicates that the ubiA mutation is the major mechanism of EMB resistance in M. avium, which should facilitate the development of molecular tests for rapid detection of resistance in this organism.
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PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Huimao Liu,Dan Yang,Hanyan Cheng,Lijuan Cao,Xu Song,Xun Zhou,Yuanfeng Zou,Lixia Li,Renyong Jia,Dongmei Zhang,Mingyue Li,Zhongqiong Yin
Resveratrol (RSV), a dietary polyphenol widely present in traditional medicinal plants and foods, exhibits antioxidant and anti-inflammatory properties that are relevant to ethnopharmacological strategies for protecting against environmental neurotoxicants. Given increasing real-world co-exposure to lead (Pb) and cadmium (Cd), elucidating RSV's capacity to preserve gut–brain axis (GBA) homeostasis has direct translational relevance for populations relying on phytochemical interventions. Sprague–Dawley rats were randomized into control, Pb–Cd model, and RSV treatment groups (10, 20, or 40 mg/kg). For 4 weeks, rats received Pb (300 mg/L) and Cd (50 mg/L) in drinking water with daily RSV. Cognitive function was assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO-1/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; and short-chain fatty acids (SCFAs) by GC-MS. Neurotransmitters (5-HT, GABA, SP, VIP) and cytokines (IL-6, IL-1β, TNF-α) were measured by ELISA. RSV improved spatial learning, reduced EB extravasation, preserved synaptic ultrastructure and proteins (BDNF, SYN, PSD-95), and restored intestinal architecture with increased ZO-1/Occludin. RSV attenuated cytokine release, normalized goblet cells, reversed dysbiosis by restoring Lactobacillaceae/Prevotellaceae, and increased acetate, propionate, and butyrate. It reinstated 5-HT and GABA while reducing SP and restoring VIP across serum, colon, and hippocampus. RSV attenuated Pb–Cd–associated neurotoxicity and was accompanied by improved intestinal and BBB-related readouts, partial normalization of gut microbiota features and SCFA levels, and preservation of synaptic and neurotransmitter-related markers, consistent with a link to gut–brain axis function. This study is among the first to test RSV in a Pb–Cd co-exposure model using a multi-dose regimen with integrated behavioral, barrier, microbial, and neurochemical endpoints.
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