Advanced Science
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2026
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IF 14.1
Tingting Wu,Yajing Liu,Shuman Wang,Xiaoming Bai,Luyun Zhang,Yuwei Liu,Zhiwen Fu,Chen Shi
Mesenchymal stem cell (MSC)-based therapies hold great promise for tissue regeneration, yet precise spatiotemporal regulation of their bioactivity remains challenging. Here, we report a light-switchable MSC system (MSC-UCNPs) enabled by intracellular upconversion nanoparticles (UCNPs), which allowed remote control of exosome biogenesis and regenerative function. Upon 980 nm near-infrared irradiation, intracellular UCNPs emitted localized 365 nm ultraviolet light without compromising MSC viability. The generated UVA stimulus activated the ROS/HEXB/LAMP1 signaling cascade, suppressing lysosome–multivesicular body fusion and thereby markedly enhancing exosome production (increased to 2.7-fold). The MSC-derived exosomes exerted autocrine effects to promote MSC proliferation and osteogenic differentiation, while also facilitating osteoblast maturation via activating the Wnt/β-catenin pathway. To facilitate in vivo application, an injectable hydrogel composed of sodium alginate, calcium alginate, and hyaluronic acid was constructed through electrostatic interactions for the localized delivery of MSC-UCNPs. Positron emission tomography–computed tomography (PET-CT) imaging confirmed the in vivo light-switchable behavior of MSC-UCNPs, allowing on-demand enhancement of in situ exosome release. Benefiting from the synergistic regenerative effects of MSCs and their exosomes, this light-responsive MSC platform achieved robust cranial bone regeneration with a 3.2-fold greater bone volume fraction compared to the control group.
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Journal of Materiomics
·
2026
·
IF 10.6
Xiao Ma,Zhihao Dong,Weichen Zhang,Ying Jiang,Xu Cheng,Limin Guo,Peiyao Zhao,Xiaohui Wang
Piezoelectric actuators are widely used industrial electronic devices. In recent years, driven by environmental concerns, lead-free piezoelectric materials, particularly KNN-based ceramics, have gained increasing attention. In this study, Mn-doped KNN piezoelectric ceramics were synthesized by the conventional solid-state reaction method and sintered in a reducing atmosphere. By employing a synergistic strategy involving defect dipoles and ferroelectric domain switching, a giant converse piezoelectric coefficient of 2676 pm/V and a strain of 0.67% are achieved in the KNNM ceramics under an electric field of 2.5 kV/mm. In our ceramic samples, no obvious strain enhancement attributable to electrobending is observed. The ceramic exhibits excellent thermal stability, with performance degradation of less than 10% from room temperature to 170 °C, and maintains favorable performance after 2 million fatigue cycles. Considering the combination of excellent piezoelectric properties, high temperature stability, superior fatigue resistance, and reduction resistance, KNNM ceramics are expected to facilitate the development of lead-free piezoelectric actuators compatible with base-metal internal electrodes.
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Cells
·
2026
·Vol. 15
·期 12
·1071
·
IF 6
Shuyue Cheng,Zeyue Mu,Feng Zhang,Jianyou Song,Jiapeng Shao,Yunqi Yan,Anastasios A Daskalakis,Yunjie Wang,Bin Zhang,Yashuang Jiang,Le Wang,Fang Liu
Background: Mitochondrial dysfunction is a central event in the pathogenesis of ischemic stroke. The roles of specific mitochondrial complex subunits, such as NDUFA4 and NDUFB3, in cerebral ischemia–reperfusion injury remain poorly defined. This study aims to investigate the dynamic expressions and functional impact of NDUFA4 and NDUFB3 in ischemic stroke. Methods: A transient middle cerebral artery occlusion (MCAO) model was established in male C57BL/6J mice. Label-free quantitative proteomics and Western blotting were employed to analyze protein expression in the ischemic penumbra. Highly differentiated PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) or glutamate excitotoxicity to mimic ischemic injury in vitro. The functional consequences of NDUFB3 knockdown and overexpression were assessed by measuring ATP levels, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptosis. The involvement of the JNK-mediated mitochondrial apoptotic pathway was also examined. Results: Proteomic analysis revealed a significant upregulation of NDUFA4 and NDUFB3 in the ischemic penumbra of MCAO mice, as verified by western blot. In highly differentiated PC12 cells, both OGD/R and glutamate exposure induced a time-dependent increase in these proteins in mitochondrial fractions. Functional studies demonstrated that NDUFB3 knockdown significantly rescued OGD/R-induced mitochondrial dysfunction, as indicated by restored ATP production, reduced ROS generation, and stabilized ΔΨm. Furthermore, NDUFB3 silencing attenuated apoptosis by inhibiting JNK phosphorylation and decreasing BAX levels. Conversely, overexpression of NDUFB3 alone was sufficient to induce mitochondrial abnormalities, including loss of ΔΨm and elevated oxidative stress in highly differentiated PC12 cells. Conclusions: Ischemic injury triggers the upregulation of mitochondrial complex subunits NDUFA4 and NDUFB3. While this may initially act as a compensatory response, our findings identify NDUFB3 as a critical mediator of ischemic stroke pathology, whose overexpression drives mitochondrial dysfunction and apoptosis. In contrast, the suppression of NDUFB3 provides protection against ischemic injury. Therefore, NDUFB3 may be a potential candidate therapeutic target for reducing mitochondrial damage in ischemic stroke, but this role requires further validation in additional experimental and translational models.
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Pharmaceutics
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2026
·Vol. 18
·期 7
·796
·
IF 6.9
Yijie Li,Chuan Chen,Yuxin Feng,Jiahe Zou,Yuqiao Qi,Weidong Huang,Yuekang Xu,Jinyao Li
Background/Objectives: In situ vaccines that directly release endogenous tumor antigens in situ to elicit anti-tumor immune responses without exogenous antigen preparation have emerged as a promising cancer immunotherapy strategy, due to their enhanced safety by local immunization that minimizes systematically adverse reactions. However, the anti-tumor efficacy of most in situ vaccines is affected by their limited access to tumors in distant sites and the toxicity of the adjuvants contained.Methods: To overcome these shortcomings, the present study explored the feasibility of utilizing extracellular vesicles from the probiotic bacteriaLactococcus lactisas both immune activators and drug carriers, which were formulated into nanoparticles to target distant tumors.Results: Using confocal microscopy and flow cytometry, we confirmed that theLactococcus lactis-derived extracellular vesicles possess adjuvant activity that promoted the maturation of dendritic cells without affecting their viability or apoptosis rate. Moreover, theLactococcus lactis-derived extracellular vesicles, both alone and when carrying the drug doxorubicin, could target and accumulate in solid tumor tissues via the enhanced permeability and retention effect. Interestingly, compared to healthy cells, theLactococcus lactis-derived extracellular vesicles tended to be taken up more by tumor cells and readily released their encapsulated doxorubicin in the acidic tumor environment, which resulted in their enhanced reactive oxygen species production and immunogenic cell death. Ultimately, systemic administration ofLactococcus lactis-derived extracellular vesicle-encapsulated doxorubicin greatly increased the anti-tumor efficacy by boosting the number of infiltrating dendritic cells and CD8+T cells in the tumor tissues and doxorubicin-mediated immunogenic cell death.Conclusions: Collectively, this study demonstrated that the probioticLactococcus lactis-derived extracellular vesicles are both safer adjuvants and effective drug carriers with immunostimulatory activity and tumor-targeting capability, shedding an interesting light on this vaccine design platform for future cancer immunotherapy.
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Food Chemistry-X
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2026
·
IF 9.2
Zifu Shao,Chunyan Gao,Zhixiong Shi
Para- phenylenediamines (PPDs) and their quinone derivatives (PPD-Qs) are ubiquitous in the environment, while data on their occurrence in foods are scarce. In this study, twelve PPDs and PPD-Qs were measured in infant formula, and their daily intakes and health risks for infants were assessed. In the tested 141 samples, the median levels of ∑PPDs and ∑PPD-Qs were 2538 and 80.34 pg/g (powder), respectively. N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD) was detected in most samples, with a median level of 2125 pg/g. However, most other PPDs and all PPD-Qs presented low detection frequencies of <40%, with mean levels of <80 pg/g. Formulas for infants of 0–6 months had significantly higher levels of 6PPD than those for older infants. Estimated daily intakes (EDIs) of ∑PPDs and ∑PPD-Qs via formula feeding were < 200 and < 10 ng/kg bw/day, respectively, for infants, and formula feeding may represent an important dietary exposure pathway for infants.
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Frontiers in Immunology
·
2026
·
IF 7
Xiaokun Shen,Haitao Cao,Fujie Li,Wenya Wang,Xingshu Qi,Yarui Zhou,Bo Li,Qingjie Fan,Tao Yang,Shinan Li
Liver fibrosis is a major global health challenge, and it is an independent risk factor for the development of hepatocellular carcinoma (HCC). Several methods have been explored to improve liver fibrosis progression, but effective preventive and therapeutic strategies remain limited. Natural killer (NK) cells can limit the activation of hepatic stellate cells (HSCs), but they have exhibited impaired antifibrotic properties in liver fibrosis, and the underlying mechanisms are not well understood. In this study, we found that CD36 was markedly upregulated in NK cells from mice with liver fibrosis. The CD36 expression was negatively correlated with activation markers of NK cells. The CD36- NK cells exhibited elevated cytotoxic cytokine production and enhanced antifibrotic activity against HSCs. The adoptive transfer of CD36- NK cells alleviated liver fibrosis progression. Mechanistically, CD36 induced reactive oxygen species (ROS) and lipid peroxidation. These consequently triggered ferroptosis in NK cells. The blockage of CD36 or inhibition of ferroptosis in NK cells effectively restored their antifibrotic properties against HSCs. In summary, our findings demonstrated that the antifibrotic properties of NK cells were regulated by CD36. These results provide evidence that targeting CD36 could restore NK cell function for liver fibrosis immunotherapy.
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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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iScience
·
2026
·
IF 4.5
Zehua Zhang,Ziwen Yu,Haiqun Shi,Tong Ding,Yan Shi,Jianyuan Zhao,Ke Cai,Feng Wang
Maternal sucralose exposure during pregnancy has been demonstrated to interfere embryonic development, yet limited studies have investigated its potential hazards on fetal cardiogenesis. In the present study, we employed a mice model to investigate the impact of sucralose exposure in early pregnancy on the risk of heart defects in offspring. Pregnant C57BL/6J mice received either control or sucralose water. The incidence of heart defects in the sucralose group was 13.86%, significantly higher than that in the control group. Transcriptional downregulation of cardiogenic genes involving Gata4 , Nkx2.5 , Tbx5 , and Tbx20 were confirmed, potentially due to increased CREB phosphorylation. N-acetylcysteine (NAC) reduced CREB phosphorylation, partially reversed sucralose-induced suppression of cardiogenic genes, and reduced the incidence of heart defects from 16.67% to 4.81%. Our study demonstrates that sucralose exposure during early pregnancy increases the risk of heart defects via transcriptional suppression of cardiogenic genes, while NAC potentially functions as a protective factor.
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RESPIRATORY RESEARCH
·
2026
·Vol. 27
·期 1
·103
·
IF 5.7
Ge Shaobo,Li Rui,Li Yuer,Liu Jin,Yao Shiyuan,Zhang Rui,Sun Yuanliang,Zhang Tao,Zhang Jie,Zhang Ming
Background Oxidative stress contributes to airway mucus hypersecretion in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although reactive oxygen species modulator 1 (ROMO1) is involved in mitochondrial oxidative stress, its role in airway mucus hypersecretion in COPD remains unclear. Methods The protein expression of ROMO1 and mucin5AC (MUC5AC) in human airway epithelium was determined by immunohistochemistry. The effects of ROMO1 on mitochondrial injury and MUC5AC expression in cigarette smoke extract (CSE)-treated airway epithelial cells were evaluated by a series of experimental techniques, including real-time PCR, western-blot and immunofluorescent staining. Results Protein expression of ROMO1 and MUC5AC was significantly elevated in the airway epithelium of COPD patients compared with the controls. The mRNA and protein expression of ROMO1 and MUC5AC were significantly increased in concentration- and time-dependent manners when airway epithelial cells were treated with CSE. ROMO1 silencing significantly suppressed 7.5% CSE-induced mitochondrial structure damage, mitochondrial membrane potential loss, intracellular ATP depletion, mitochondrial reactive oxygen species production, signal transducer and activator of transcription 6 (STAT6) phosphorylation, and MUC5AC expression in airway epithelial cells. Moreover, pretreatment with either a mitochondrial-targeted antioxidant or STAT6 inhibitor significantly inhibited the up-regulated expression of p-STAT6/STAT6 and MUC5AC in airway epithelial cells stimulated with 7.5% CSE. Conclusion Our findings suggest that ROMO1 contributes to airway mucus hypersecretion in COPD by mediating MUC5AC expression in airway epithelial cells via the mitochondrial ROS-STAT6 pathway, thereby highlighting its potential clinical value as a therapeutic target.
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Nature Communications
·
2026
·
IF 18.1
Zhang Yong,Qi Ying,Zhou Haiqing,Zhang Yan,Sun Jingying,Ma Wenqi,Hu Jiayi,Feng Ligang,Yu Fang
Glycerol electrooxidation emerges as an electrochemically cogent paradigm to supplant the sluggish oxygen evolution reaction in water electrolysis. However, most non-precious catalysts still suffer from large electrolytic voltage and poor stability when operating at industrially relevant current densities. Here, we develop a heterostructure catalyst by immobilizing abundant cobalt phosphide (CoP) nanoparticles on conductive cobalt nitride (Co 2 N 0.67 ) support, which results in the construction of a strong built-in electric field at the heterointerface. The optimal catalyst demonstrates effective bifunctional catalytic performance, yielding an industrial-level current density of 500 mA cm −2 at low potentials of −141 mV and 1.44 V for hydrogen evolution and glycerol oxidation, respectively. When integrated into a flow cell system, this catalyst maintains good stability for 260 hours at 1 A cm −2 (1.67 V) while preserving > 85% Faradaic efficiency for formate production. Both theoretical and experimental analyses substantiate that the built-in electric field drives directional electron transfer from CoP to Co 2 N 0.67 , forming an electron-deficient region at the CoP interface that enriches OH* species, and an electron-rich region at the Co 2 N 0.67 interface, facilitating hydrogen adsorption, thereby expediting the glycerol and H* co-adsorption process. Multiple in-situ spectroscopic characterizations verify the existence of a combined direct/indirect oxidation mechanism for glycerol electrooxidation. This discovery sets the stage for low-voltage hydrogen production by hybrid water splitting using the excess electrical power whenever and wherever available.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2026
·
IF 3.4
Zhe Chen,Zhenye Luo,Ting Xia,Xiaomei Tan
Gegen Qinlian decoction (GQD), a traditional Chinese medicine used to treat infectious diarrhea, forms self-precipitates (GQD-P) during decoction. Although GQD-P and the supernatant (GQD-S) share an identical chemical composition, their physicochemical properties and in vivo behavior are not yet fully understood. This study aimed to investigate the physicochemical, in vitro , and in vivo properties of GQD-P, and to elucidate its unique role in the decoction's holistic efficacy. The morphology and pH-dependent dissolution of GQD-P were analyzed. Components in GQD, GQD-S, and GQD-P were quantified using HPLC, while pharmacokinetics of nine components were compared in rats administered GQD, GQD-S, or GQD-P using UPLC-MS/MS. GQD-P consisted of nanospheres whose dissolution was markedly enhanced under acidic, but not enzymatic, conditions. Baicalin and berberine were the main components of the primary precipitate framework. GQD-P components showed significantly prolonged MRT 0-t and T 1/2 , and delayed T max compared to GQD-S. The whole decoction exhibited a biphasic profile combining features of both phases, with GQD-P acting as a pH-triggered, sustained-release reservoir. Together with the rapid-release supernatant, it creates a biphasic system prolonging systemic exposure and collectively underpins the comprehensive efficacy of GQD.
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Journal of Neuroinflammation
·
2026
·Vol. 23
·期 1
·90
·
IF 11.5
Tang Fenglin,Li Yufeng,Bai Xue,Zhu Zhongmou,Dong Hongwei,Chen Jianhui,Ye Bo,Yuan Meng,Wu Qilong,Fu Weishan,Zhang Yuan,Wang Chao
Alzheimer’s disease (AD) is the most common neurodegenerative disorder, with circadian rhythm disturbances strongly linked to its pathogenesis. The choroid plexus (ChP) is a circadian-regulated structure in the brain ventricles, but the role of the core clock gene brain and muscle ARNT-like protein 1 ( BMAL1 ) in ChP in relation to AD pathology remains unclear. Here, we report that knockdown of Bmal1 in ChP epithelial cells of 5xFAD mice alleviates amyloid-β (Aβ) pathology, primarily by improving the function of astrocytes and border-associated macrophages (BAMs), with the latter potentially mediated by the upregulation of the secreted protein glutathione peroxidase 3 (GPX3), which reduces lipid peroxidation in BAMs. Collectively, our findings establish the ChP-driven BMAL1-GPX3 axis as a new Aβ clearance mechanism, with GPX3 representing a promising therapeutic target. These findings provide new mechanistic insights into AD and suggest innovative treatment approaches.
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