Cell Death & Disease
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2026
·
IF 12.2
Ao Liyan,Chen Zhiqiang,Zhang Jingliang,Wang Qi,Luo Jin,Li Zhuoran,Jiao Qilong,Ning Bobin,Peng Shiyuan,Hu Wenhao,Jia Yuqi,Ci Weimin,Wang Baojun,Dong Zhouhuan,Zhang Xu,Niu Shaoxi
Prostate cancer is a highly heterogeneous malignancy, with distinct subtypes displaying unique molecular and metabolic profiles. This study identifies a compensatory shift in α-ketoglutarate (α-KG) metabolism in prostate cancer, where the tumor relies on IDH1 to incorporate citrate into the TCA cycle. IDH1 inhibition, leads to lower α-KG levels. Since α-KG is required for HIF-1α hydroxylation, IDH1 inhibition stabilizes HIF-1α, which subsequently upregulates c-Fos. C-Fos enhances GLUD1 transcription, promoting the conversion of glutamate to α-KG as a compensatory mechanism. Additionally, c-Fos upregulates downstream effectors, including FOXC1 and SOX2, driving neuroendocrine differentiation in prostate cancer. Targeting α-KG-metabolizing enzymes, such as IDH1 or GLUD1, presents promising therapeutic strategies for prostate cancer subtypes by inhibiting tumor proliferation and inducing oxidative stress, thus sensitizing tumors to ferroptosis. Overall, these findings uncover a metabolic adaptation in response to IDH1 inhibition and highlight the pivotal role of c-Fos in mediating this compensatory pathway, offering new insights into potential metabolic targets for prostate cancer treatment and ferroptosis-based therapies.
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Nature Microbiology
·
2026
·
IF 18.7
Ye Meng,Liu Xinyu,Peng Zhengxiong,Li Shuaichao,Jia Xiaoyu,Yang Xiyuchen,Jiang Shan,Wang Feng,Yang Xiaobing,Yu Juping,Liu Wei,Gao Xiangdong
Engineered therapeutic microbes for intestinal inflammation must be capable of gut colonization, sensitive detection of disease-associated biomarkers and targeted delivery of therapeutic molecules. Examples of microbes displaying all three characteristics are limited. Here we engineered Bacteroides thetaiotaomicron , a human gut commensal bacterium with colonization ability, colonic tropism and innate anti-inflammatory properties, as a chassis to create programmable bacterial strains termed Btbots. We developed genetic circuits that were integrated into the bacterial chromosome to sense two intestinal inflammation biomarkers, deoxycholic acid (DCA) and nitric oxide (NO), and to enhance surface display and secretion of therapeutic molecules in response. Btbots with these biosensors were developed that either display trefoil factor-3 to facilitate mucosal repair or secrete interleukin-35 to suppress inflammation. These Btbots sensed DCA and NO biomarkers and released therapeutic agents, alleviating colitis and modulating the gut microenvironment and microbiota in mouse models. This work establishes a proof of concept for localized sensing and consequent therapeutic molecule release for gastrointestinal applications, whose clinical potential awaits further investigation.
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高影响因子
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2026
·Vol. 42
·期 6
·304
·
IF 4.7
Lu Lingqing,Zhang Rongrong,Jie Wenli,Zhou Hang,Yang Yi,He Yunxue,Ren Mingzheng,Zhou Lihong
Temperature is a key environmental factor affecting fungal growth, reproduction, and metabolism. In this study, the industrially important fungus Aspergillus cristatus was investigated by integrating physiological phenotyping with liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to systematically characterize its morphological traits, antioxidant activity, and untargeted metabolic profiles at 20 °C, 25 °C, 30 °C, and 35 °C. The results showed that approximately 30 °C was the most favorable temperature for the growth of Aspergillus cristatus . Metabolomic analysis indicated that Aspergillus cristatus exhibited a pattern of metabolic redirection under different temperature conditions, reflecting a multilayered and coordinately changing metabolic mode associated with temperature adaptation. At low temperatures (20 °C and 25 °C), unsaturated lysophospholipids, such as PC O-18:2, accumulated substantially, suggesting their involvement in membrane adaptation, whereas high temperature was associated with changes in specific phospholipid molecules. In terms of oxidative stress defense, flavonoid- and phenolic-related metabolites showed more prominent changes under low and optimal temperatures, whereas glutathione-related metabolites increased significantly at high temperature, indicating a greater reliance on glutathione-associated antioxidant defense. Regarding energy and osmotic balance, reserve carbohydrates accumulated at the optimal temperature, consistent with coordination between growth and stress resistance, whereas high-temperature stress was associated with a shift toward sugar alcohol accumulation and a metabolic pattern consistent with metabolic deceleration. This study presents the metabolic changes of Aspergillus cristatus under different temperature conditions from a systems-level metabolic perspective and suggests that Aspergillus cristatus may adapt to environmental change by coordinating growth-related metabolism with stress defense-related metabolism. In addition, these findings may provide a reference for future studies on fermentation regulation and stress resistance in Aspergillus cristatus .
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Nature Communications
·
2026
·
IF 18.1
Wang Wei,Tang Yonghua,Su ZhuiZhui,Liu Huanmin,Liu You-Nian,Tang Dingguo,Zhou Peng
Photocatalytic carbon–carbon coupling offers a route for converting plastic-derived chemicals into valuable multi-carbon products, yet uncontrolled coupling of intermediate limits efficiency and selectivity. Here, we report atomically dispersed barium species on titanium dioxide that act as frustrated Lewis pairs, enabling efficient and selective generation intermediates during the co-oxidation of ethylene glycol and methanol toward lactic acid. The barium species create interstitial states near the Fermi level, enhancing charge separation and surface redox activity. Meanwhile, barium sites promote the formation of transient •CHOHCH 2 OH radicals from ethylene glycol, while lattice O generates stable *CH 3 intermediates from methanol. Their directed cross-coupling yields lactic acid at rate of 2.04 ± 0.08 mmol g –1 h –1 with 81.8 ± 2.4 % carbon selectivity, alongside H 2 evolution at 5.85 ± 0.23 mmol g –1 h –1 . In this work, we show an alkaline-earth frustrated Lewis pairs for selective solar-driven cross-coupling reaction.
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Systems Microbiology and Biomanufacturing
·
2026
·Vol. 6
·期 3
·98
·
IF 3.5
Li Caimei,Shen Wei,Yang Haiquan,Zhou Li,Xia Yuanyuan,Chen Xianzhong
Salidroside, the key active component of Rhodiola , possesses anti-hypoxia and anti-fatigue properties, making it valuable in medicine, health products, and cosmetics. This study focuses on efficiently synthesizing salidroside using a dual-enzyme cascade system with sucrose synthase AtSUS3 and glycosyltransferase AtUGT85A1 from Arabidopsis thaliana . This system facilitates the regeneration of UDPG and the conversion of tyrosol into salidroside. First, the two key enzymes AtSUS3 and AtUGT85A1 were expressed and purified with optimized His‑tag positions. Solubility enhancement via tag fusion and linker engineering yielded the fusion proteins TSu and ES85 with desirable activity. Subsequently, semi‑rational design on the poorly thermostable ES85 using the FireProt platform generated an S324R mutant with significantly improved thermostability. Ultimately, a recombinant strain TSR85 co‑expressing both enzymes was constructed. A one‑pot system employing this strain achieved 13.61 g/L salidroside with a conversion rate of 90% within 10 h (space‑time yield 1.36 g/L/h). This study thus integrates solubility enhancement, thermostability engineering, and one‑pot catalysis into a balanced, practical, and industrially relevant platform for salidroside biosynthesis.
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Nature Communications
·
2026
·
IF 18.1
Zheng Nengzhan,Zhu Yanfei,Ji Haocheng,Wang Junxiong,Wu Zhuozhao,Ji Guanjun,Shi Ruyu,Li Bo,Zhou Guangmin
Direct recycling of spent lithium-ion batteries is an essential approach to address challenges related to energy security and resource sustainability. However, previous direct recycling methods could only restore spent electrode materials to their original state, limiting their ability to meet rapidly advancing performance benchmarks. Herein, we present a promising upcycling strategy that reconstructs degraded ternary layered positive electrode materials into Li-rich oxides, thereby achieving with substantial capacity advantages. Microstructure characterizations and theoretical calculations demonstrate that intrinsic vacancy defects in the degraded materials provide energetically favorable atomic-scale diffusion pathways for exogenous lithium-ions, mediating the conversion of the layered R-3m structure into the C2/m phase and the formation of Li 2 TMO 3 -type domains. With activated anion redox reactions, it attains a specific capacity increase from 100 to over 274 mAh g −1 at 0.1 C and maintains 92.5% capacity retention over 300 cycles at 0.5 C. The strategy has been scaled to kilogram-level production, achieving a specific energy of 377 Wh kg −1 in a 14 Ah-level pouch cell. This result validates the upcycling approach, bridging laboratory research and industrial manufacturing of high-energy-density batteries via sustainable recycling.
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Journal of Translational Medicine
·
2026
·Vol. 24
·期 1
·539
·
IF 9.7
Gao Yuan-Yuan,Sun Wen-Shuang,Sun Zi-Ying,Wang Jun-Rui,Lv Zhong-Yang,Li Yu-Jia,Tian Hao-Yuan,Bao Zheng-Yang,Qiu Xin-Ran,Wang Zheng,Zheng Shi-Zhong,Shao Jiang-Juan,Zhang Zi-Li,Meng Jia
Background Tendinopathy is a prevalent orthopaedic condition characterized by disrupted tendon homeostasis, with oxidative stress being a key contributing mechanism. Although the natural compound 18-β-Glycyrrhetinic acid (GA) exhibits antioxidant properties and is a therapeutic candidate for tendinopathy, its precise molecular mechanism remains unclear. This study aimed to elucidate how GA alleviates tendinopathy, with a focus on its role in regulating the HMGB1-cGAS-STING axis and NLRP3 inflammasome activation in the context of oxidative stress. Methods We employed single-cell RNA sequencing (scRNA-seq) of clinical samples, proteomics of animal tissues, and comprehensive pharmacological assays to investigate the mechanisms of tendinopathy. Furthermore, the rat tendinopathy model and H 2 O 2 -induced oxidative stress model of tendon stem cells (TSCs) were used to validate the protective effects of GA. Results We found that GA significantly reduced oxidative stress and subsequent inflammation, thereby mitigating collagen disruption in rats with tendinopathy. Notably, scRNA-seq revealed that the proportion of TSCs increased significantly during tendinopathy, which were particularly susceptible to reactive oxygen species (ROS). TSCs from oxidative damage and inhibited activation of the NLRP3 inflammasome by suppressing the cGAS-STING pathway. Mechanistically, GA promoted cGAS degradation by enhancing its interaction with the mitochondrial E3 ubiquitin ligase Mul1. This effect was mediated through high-mobility group box 1 (HMGB1), as GA disrupted the HMGB1-cGAS interaction. Specifically, GA induced methylation of HMGB1 at lysine 43, a modification essential for its activity. This methylation was catalyzed by the methyltransferase DOT1L, which was upregulated and directly bound by GA. Collectively, GA alleviates tendinopathy by targeting the DOT1L-HMGB1-cGAS axis to resolve oxidative stress and inflammation. Conclusion Collectively, our findings provide new insights into how oxidative stress accelerates tendinopathy progression. Moreover, they delineate the mechanism by which GA in mitigates oxidative damage and inflammation in TSCs by inhibiting the co-localization of HMGB1 and cGAS. Overall, this study offers scientific support for further developing GA as a promising therapeutic agent for tendinopathy treatment. Graphical The alternative text for this image may have been generated using AI.
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Nature Communications
·
2026
·
IF 18.1
Chen Litong,Su Benxing,Zhong Geng,Wang Jing,Ji Yongxiang,Zhou Zhongzeng,He Xuecheng,Xu Tailin
Wearable sweat biosensors enable noninvasive molecular monitoring, but reliable and comfortable on-demand sweat induction remains challenging. We developed a soft, skin-conformal wearable device that integrates ultrasound-assisted sweat generation with electrochemical sensing. Low-frequency ultrasound enhanced transdermal delivery of carbachol from a hydrogel reservoir, inducing localized sweat secretion under resting conditions without electrical current or skin penetration. Under the matched 15-min experimental window used here, ultrasound-induced sweating showed lower observed skin irritation and more favorable user-rated comfort than the tested iontophoresis setting. Integrated sensors measured uric acid, pH and K+ in ultrasound-induced sweat, and sweat uric acid showed a positive correlation with serum levels in a preliminary human study. These results support wearable ultrasound as a low-irritation strategy for controlled sweat generation and downstream biomarker tracking under resting conditions.
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Journal of Biological Engineering
·
2026
·Vol. 20
·期 1
·84
·
IF 6.3
Liu Chang,Zhang Hongwei,Xing Wanbin,Na Rina,Meng Xuanyu,Huang Sichen,Wang Linlin,Cao Guoqiang,Wang Pengchao
Background 2-phenylethanol (2-PE) is a high-value aromatic alcohol. Its bioproduction is limited by pathway bottlenecks, limited by a rate-limiting decarboxylation step, product toxicity, and volatilization. We sought to build an efficient Escherichia coli ( E. coli ) platform by optimizing the segment of the Ehrlich route that converts L-phenylalanine (L-Phe) to 2-PE, together with a food-grade soybean-oil overlay for in situ product recovery (ISPR). Results Whole-cell assays showed that phenylpyruvate decarboxylation was the main bottleneck when the yeast decarboxylase Aro10 was used. A phylogeny-guided screen identified Lactococcus lactis KivD as a superior substitute in E. coli . After replacing Aro10 with KivD and tuning expression, leveraging endogenous glutamate dehydrogenase (GDH) for NAD(P)H recycling enabled sufficient cofactor regeneration, yielding 49.5 mM 2-PE from 50 mM L-Phe with 99.0% conversion. At the shake-flask scale, a fed-batch L-Phe feeding strategy coupled with a 2:1 soybean-oil overlay for in situ product removal reduced toxicity and volatilization losses, producing 130 mM 2-PE (15.9 g/L). Using soybean oil as an ISPR phase effectively sequestered 2-PE from the aqueous phase, minimizing volatilization and increasing the overall recovered yield to 94.2% based on L-Phe consumption. Conclusions Replacing the rate-limiting decarboxylation step with KivD, balancing redox through cofactor recycling, and coupling the pathway to a mild oil-overlay recovery increased flux and enabled high-titer 2-PE in E. coli . The workflow of bottleneck substitution plus biocompatible in situ recovery can be transferred to related aromatic alcohols and provides a foundation for de novo routes and high-cell-density fermentations that target still higher titers. Graphical The alternative text for this image may have been generated using AI.
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT
·
2026
·
IF 2.2
He Xiaotong,Dou Qiumei,Huang Xi,Zhang Xinyu,Zheng Ziqi,Wang Yingzi,Yang Quan,Gao Hongyang
Dendrobium officinale regenerated plants were divided into a normal control group (Normal), a hyperhydricity group (HH), and a silicon-treated hyperhydricity group (HH and Si); and the study investigated how silicon mitigates hyperhydricity by regulating water metabolism, photosynthetic pigments, antioxidant system, ethylene-polyamine metabolism, stomatal morphology, and molecular mechanisms. The results revealed significant differences between the HH group and the Normal group. The HH group exhibited a substantial increase in free water content, as well as reduced photosynthetic pigment content, diminished antioxidant enzyme activity, elevated ethylene levels, lower polyamine concentrations, and impaired stomatal regulation. In contrast, the HH and Si group exhibited recovered free water content to Normal group levels, markedly increased photosynthetic pigments, enhanced antioxidant capacity, reduced ethylene content, elevated polyamine levels, and restored stomatal function. Furthermore, silicon supplementation suppressed the expression of ethylene synthesis genes and increased that of polyamine synthesis genes. These findings indicated that silicon alleviates hyperhydricity in D. officinale regenerated plants through multifaceted mechanisms. Specifically, silicon mitigated the adverse effects of hyperhydricity by: (1) restoring cellular water balance and minimizing structural damage from free water accumulation; (2) recovering photosynthetic pigment content and boosting antioxidant enzyme activity; and (3) rebalancing ethylene-polyamine antagonism to improve stomatal function. This study provided a theoretical foundation and technical framework for managing hyperhydricity in D. officinale regenerated plants.
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JOURNAL OF MATERIALS SCIENCE
·
2026
·Vol. 61
·期 25
·18185-18209
·
IF 4.4
Li Ying,Qin Jiaying,Zhou Yiqing,Fang Baoru,Wang Ke,Wu Shang,Qian Huifeng,Xing Guiying,Li Xiudong,Ye Zhiqiu,Yu Zhangsen
Doxorubicin (DOX) is a highly effective first-line chemotherapeutic agent for various tumors. However, its clinical utility is limited by fatal dose-dependent cardiomyopathy, primarily attributed to excessive reactive oxygen species (ROS) production and mitochondrial damage. Herein, we developed ultrasmall Prussian blue nanoparticles (SPB) possessing multiple antioxidant enzyme-like activities for the prevention and treatment of doxorubicin-induced cardiomyopathy (DIC). These nanoparticles function by efficiently scavenging ROS and preserving mitochondrial integrity. In vitro studies in cardiomyocytes demonstrated that SPB effectively eliminated ROS, reversed mitochondrial membrane potential loss, enhanced mitochondrial complex I activity, promoted ATP production, attenuated mitochondrial dysfunction, and inhibited cardiomyocyte apoptosis. In a breast cancer-bearing mouse model, SPB administration protected cardiac function and reduced myocardial fibrosis without compromising the antitumor efficacy of DOX. Mechanistically, SPB upregulated antioxidant-related proteins to reduce oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway. Acute toxicity experiments showed that SPB could be safely administered via the tail vein at a dose of 75 mg/kg, which is substantially above the effective therapeutic dose. In conclusion, these findings demonstrate that SPB confers robust cardioprotection during DOX chemotherapy and holds considerable promise for clinical translation. Graphical Ultrasmall Prussian blue nanoparticles (SPB), synthesized via a green chemistry method with excellent biocompatibility, can effectively protect the heart function of chemotherapy tumor-bearing mice by scavenging reactive oxygen species generation, activating the Keap1-Nrf2/HO-1 signal pathway and protecting mitochondrial functions, reducing the degree of myocardial fibrosis without weakening the chemotherapy efficacy of DOX.
The alternative text for this image may have been generated using AI.
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Surface Science and Technology
·
2026
·Vol. 4
·期 1
·46
·
IF 7
Wang Zian,Wang Yanan,Luo Rifang,Wang Yunbing
Surface-induced thrombosis restricts the clinical safety of blood-contacting devices. Although surface heparinization is a widely commercialized strategy for enhancing hemocompatibility, current methods (e.g., covalent grafting, Layer-by-Layer assembly) suffer from complex procedures or insufficient stability. Herein, we introduce a facile, one-step strategy to construct robust anticoagulant coatings driven by a salt-concentration gradient. By utilizing 4 mol/L NaCl to screen electrostatic interactions between polyethyleneimine (PEI) and heparin, a homogeneous precursor slurry was prepared. During a simple immersion-withdrawal process, rapid salt diffusion at the interface triggers immediate liquid–liquid phase separation, inducing the dense coacervation of polyelectrolyte complexes onto substrates. The resulting coating exhibits exceptional stability via physical entanglement, retaining 73% of heparin after 16 days of physiological incubation. Furthermore, the coating demonstrated a negligible hemolysis rate (0.32%), suppressed platelet adhesion by 98%, and reduced ex vivo thrombus formation by 90%. This scalable assembly paradigm offers a highly effective solution for cardiovascular implant functionalization.
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危险品化学品经营许可证（带存储）