摘要:
Objectives The Shh pathway may shed new light on developing new cell death inhibitors for the therapy of ischemic stroke. We aimed to examine whether the Shh co-reporter SMO or its agonist halcinonide can upregulate Bcl-2 to suppress neuronal cell death, ultimately improving behavioral deficits and reducing cerebral infarction in an ischemic stroke model.
The Shh pathway may shed new light on developing new cell death inhibitors for the therapy of ischemic stroke. We aimed to examine whether the Shh co-reporter SMO or its agonist halcinonide can upregulate Bcl-2 to suppress neuronal cell death, ultimately improving behavioral deficits and reducing cerebral infarction in an ischemic stroke model.
Methods Halcinonide or genetic manipulation of SMO was conducted in PC12 cells to examine their impacts on oxidative or OGD/R stress, and the chemical, along with AAV- SMO or AAV- EGFP were tested in MCAO rats to investigate their potential protective effects against neuronal damages due to cerebral I/R injury. The amounts or activities of L-LA, LDH, ROS, MDA, SOD, MPO, GSSG, and GSH were detected using the corresponding biochemical kits. The levels of TNF-α and IL-6 were analyzed by ELISA.
Halcinonide or genetic manipulation of SMO was conducted in PC12 cells to examine their impacts on oxidative or OGD/R stress, and the chemical, along with AAV- SMO or AAV- EGFP were tested in MCAO rats to investigate their potential protective effects against neuronal damages due to cerebral I/R injury. The amounts or activities of L-LA, LDH, ROS, MDA, SOD, MPO, GSSG, and GSH were detected using the corresponding biochemical kits. The levels of TNF-α and IL-6 were analyzed by ELISA.
Results The results show that halcinonide alleviated neurological score and cerebral infarction, and the abnormal changes in L-LA, LDH, MDA, SOD, MPO, GSH, GSSG, TNF-α, and IL-6 were also reversed in MCAO rats. Through expression or knockout of SMO , we discovered that SMO worked similarly to halcinonide, protecting neuronal cells from oxidative or OGD/R stress, and AAV- SMO prevented cerebral damages of MCAO rats caused by ischemia and reperfusion. Halcinonide inhibited Bcl-2/Bax-mediated apoptosis, at least partially by promoting the Shh signaling pathway through enhancing SMO expression in vivo and in vitro.
The results show that halcinonide alleviated neurological score and cerebral infarction, and the abnormal changes in L-LA, LDH, MDA, SOD, MPO, GSH, GSSG, TNF-α, and IL-6 were also reversed in MCAO rats. Through expression or knockout of SMO , we discovered that SMO worked similarly to halcinonide, protecting neuronal cells from oxidative or OGD/R stress, and AAV- SMO prevented cerebral damages of MCAO rats caused by ischemia and reperfusion. Halcinonide inhibited Bcl-2/Bax-mediated apoptosis, at least partially by promoting the Shh signaling pathway through enhancing SMO expression in vivo and in vitro.
Conclusion This study identified a new target and a candidate chemical for therapy of ischemic stroke, hopefully reducing its morbidity and mortality.
This study identified a new target and a candidate chemical for therapy of ischemic stroke, hopefully reducing its morbidity and mortality.
摘要:
BACKGROUND AND AIM: Long term high-dose erythropoietin (EPO) had been reported inducing the formation of abdominal aortic aneurysm (AAA) in mice. When using this model, we found that EPO treated mice showed significant splenomegaly. This is an interesting phenomenon, and its mechanism has not been reported. Therefore, this study aims to explore its mechanism. METHODS: C57BL/6 mice were given intraperitoneal injection of recombinant human EPO at 10000 IU/kg/day, and the control mice were treated with normal saline (vehicle). After 3 weeks, the spleens were harvested. Pathological changes in histology were observed using Hematoxylin and Eosin (H&E) staining. The differential expression genes (DEGs) were identified using RNA sequencing (RNA-Seq), verified with the real-time quantitative polymerase chain reaction (RT-qPCR). The functional-enrichment analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis were performed to reveal the functional characteristics and related biological pathways of DEGs. Immunohistofluorescence (IHF) and flow cytometry (FCM) were used to detect immune cell subsets and proliferation markers. RESULTS: EPO treatment resulted in splenomegaly, spleen microstructure disorder, splenic corpuscular atrophy, indistinct germinal center, and unclear boundary between white and red pulp structures. RNA-Seq showed that EPO treatment suppressed gene expression associated with immune responses, while promoted cell cycle and DNA replication. IHF and FCM validated that, at the cellular level, T, B, M1 cells were significantly reduced, and M2 cells were significantly decreased after EPO treatment. The proliferation analysis showed that the portion of EDU(+) or Ki-67(+)cells consisted of granulocytes and macrophages, and after EPO treatment, only macrophages showed a significant increase in their number and proportion, while granulocytes did not show a significant response to EPO stimulation. CONCLUSION: Long term high-dose EPO treatment may lead to splenomegaly and immunosuppression of the local immune microenvironment in mice. The mechanism may be related to the increased anti-inflammatory and immunomodulatory functions caused by M2 cells. The study provides, for the first time, the transcriptomic characteristics and immunological of the spleens of EPO treated mice, providing a new perspective for the study of the effects of EPO on mice.
作者:
Ye, Yongjun;Zong, Yifan;Li, Mengyi;Song, Bangzhi
期刊:
Journal of Radioanalytical and Nuclear Chemistry,2025年334(3):2195-2202 ISSN:0236-5731
通讯作者:
Ye, YJ
作者机构:
[Li, Mengyi; Ye, Yongjun; Song, Bangzhi; Zong, Yifan] Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.;[Ye, Yongjun] Univ South China, Key Discipline Lab Natl Def Biotechnol Uranium Min, Hengyang 421001, Peoples R China.
通讯机构:
[Ye, YJ ] U;Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.;Univ South China, Key Discipline Lab Natl Def Biotechnol Uranium Min, Hengyang 421001, Peoples R China.
关键词:
Uranium tailings;The free radon production rate;Temperature;Water-solid mass ratio;Particle size
摘要:
The effect of conventional factors on the free radon production rate above 0 degrees C has been widely studied, but rarely explored under frozen conditions. In order to investigate the effect on the free radon production rate of uranium tailings under frozen and non-frozen conditions, uranium tailings from southern China were selected for screening, and temperature, water-solid mass ratio and particle size were used as influencing factors for research. The stable radon concentration and the free radon production rate of uranium tailings of varying particle sizes at different temperatures (20 degrees C, 0 degrees C, - 10 degrees C, - 20 degrees C) and different water-solid mass ratios (0, 0.14, 0.28) were measured by the homemade radon collection tanks. The experimental results showed that: (1) The free radon production rate decreases with temperature decreases, more significantly under frozen conditions, dropping 3.49-4.16% per 1 degrees C on average. (2) Under non-frozen conditions, the free radon production rate rises with water-solid mass ratio rises, while under frozen conditions, the free radon production rate of uranium tailings first increases and then decreases with the increase of water-solid mass ratio. (3) The larger particle size, the lower the free radon production rate. The free radon production rate of uranium tailings with particle size > 450 mu m is 21.3-81.1% lower than that of uranium tailings with other particle sizes.
作者机构:
[Liu, Xing; Xiao, Xilin; Xiao, XL; Liu, Zhen; Sun, Jie] Univ South China, Sch Publ Hlth, Hengyang Sch Med, Hengyang 421001, Peoples R China.;[Xiao, Xilin; Xiao, XL] Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.;[Xiao, Xilin; Xiao, XL] Univ South China, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
通讯机构:
[Xiao, XL ] U;Univ South China, Sch Publ Hlth, Hengyang Sch Med, Hengyang 421001, Peoples R China.;Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.;Univ South China, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
关键词:
fluorescent sensor;mercury ion detection;silver ion detection;cascade isothermal signal amplification;catalytic hairpin assembly
摘要:
In this study, novel fluorescent DNA biosensors for mercury (Hg2+) and silver (Ag+) ions were developed based on thymine (T)- and cytosine (C)-rich recognition elements in combination with exonuclease III and a mismatch-catalyzed hairpin assembly (MCHA)-based cascade isothermal signal-amplification strategy. In the presence of the respective target analytes, the recognition element terminals form so-called T-Hg2+-T or C-Ag+-C structures, resulting in cleavage by Exo III and the release of the trigger strand for MCHA. This binds to the H1 hairpin, which is fluorescently labeled with carboxyfluorescein (FAM) and tetramethylrhodamine (TAMRA), disrupting fluorescence resonance energy transfer between them and, thus, restoring FAM fluorescence, generating a strong signal at 520 nm. The linear range of the Hg2+ sensor is 0.5 to 3 pM, with a detection limit of 0.07 pM. The recovery range in actual spiked water samples is between 98.5% and 105.2%, with a relative standard deviation (RSD) ranging from 2.0% to 4.2%. The linear range of the Ag+ sensor is 10 to 90 pM, with a detection limit of 7.6 pM. The recovery range in actual spiked water samples is between 96.2% and 104.1%, with an RSD ranging from 3.2% to 6.3%. The cascade isothermal signal amplification strategy effectively enhances sensor sensitivity, while MCHA decreases the false-positive rate. The aptamer sensor exhibits high specificity, is resistant to interference, and can be used for the detection of Hg2+ and Ag+ in environmental water samples.
期刊:
Reliability Engineering & System Safety,2025年256:110794 ISSN:0951-8320
通讯作者:
Zeng, WJ
作者机构:
[Li, Zheng; Chen, Chuqi; Li, Xiaoyu; Wang, Linna; Zeng, Wenjie; Zeng, WJ] Univ South China, Sch Nucl Sci & Technol, Hengyang City 421001, Peoples R China.
通讯机构:
[Zeng, WJ ] U;Univ South China, Sch Nucl Sci & Technol, Hengyang City 421001, Peoples R China.
关键词:
Small pressurized water reactor;Nuclear power plant;Coordinated control system;Uncertainty quantification;Sensitivity analysis
摘要:
Parameter uncertainty is an inherent characteristic of control systems. To assess the impact of parameter uncertainty on the system, the dynamic performance assessment with uncertainty quantification and sensitivity analysis is proposed. The input sample set is obtained by Wilks' method and Latin hypercube sampling, then dynamic simulation and statistics are used to realize the uncertainty quantification of output parameters and the identification of key output parameters. The central composite design and second-order polynomial are used to build the agent model for the Sobol's method. Taking the small pressurized water reactor nuclear power plant as an example, a performance assessment platform of coordinated control system is developed through graphical user interface with fast load decrease conditions. The study shows that all the transient safety parameters except reactor core relative power and secondary-side outlet temperature of once-through steam generator (OTSG) satisfy the technical requirements, and the control system has a certain safety margin. Meanwhile, the adjustment time of reactor core relative power and secondary-side outlet temperature of OTSG is highly sensitive to primary-side flowrate of OTSG under the small range of variable load, and sensitive to the opening pressure of the steam dump valve under the large range of variable load.
Parameter uncertainty is an inherent characteristic of control systems. To assess the impact of parameter uncertainty on the system, the dynamic performance assessment with uncertainty quantification and sensitivity analysis is proposed. The input sample set is obtained by Wilks' method and Latin hypercube sampling, then dynamic simulation and statistics are used to realize the uncertainty quantification of output parameters and the identification of key output parameters. The central composite design and second-order polynomial are used to build the agent model for the Sobol's method. Taking the small pressurized water reactor nuclear power plant as an example, a performance assessment platform of coordinated control system is developed through graphical user interface with fast load decrease conditions. The study shows that all the transient safety parameters except reactor core relative power and secondary-side outlet temperature of once-through steam generator (OTSG) satisfy the technical requirements, and the control system has a certain safety margin. Meanwhile, the adjustment time of reactor core relative power and secondary-side outlet temperature of OTSG is highly sensitive to primary-side flowrate of OTSG under the small range of variable load, and sensitive to the opening pressure of the steam dump valve under the large range of variable load.
通讯机构:
[Gu, WL ] U;Univ South China, Sch Civil Engn, Hengyang, Peoples R China.
关键词:
Solar radiant energy;Non-uniform heat flow;Buoyancy;Secondary flow;Thermal performance
摘要:
Under the focusing characteristics of parabolic trough solar collectors, enhancing secondary flow intensity and shifting the secondary flow vortex center towards the bottom of the absorber can extend the lifespan of the absorber and improve thermal performance. This study combines the Monte Carlo Ray Tracing method (MCRT) and the Finite Volume Method (FVM) to investigate the fluid flow and heat transfer characteristics inside the absorber under non-uniform thermal boundary conditions. The effects of inlet flow rate (Vin), inlet temperature (Tin), and protrusion structures on the secondary flow vortex position are examined. Through numerical analysis, secondary flow intensity (Se), heat transfer coefficient (h), Nusselt number (Nu), and friction factor (f) are calculated. The results show that increasing the Tin significantly enhances secondary flow intensity, thereby improving heat transfer within the absorber. Specifically, when Tin increases from 400.15 to 600.15 K, Se increases by a factor of 7.87, while h increases by 98.96%. Increasing the Vin shifts the secondary flow vortex downward, enhancing heat transfer at the bottom of the absorber. For example, when Vin increases from 100 to 200 L min−1, Se remains largely unchanged, while h increases by 44.68%. Compared to semi-cylindrical protrusions, tetrahedral protrusions are more effective at suppressing the upward shift of the secondary flow vortex, reducing velocity losses caused by fluid-wall interaction, and achieving better heat transfer enhancement. Under conditions of Tin = 500.15 K and Vin = 100 L min−1, the Nu increases by 14.6% for tetrahedral protrusions and 7.3% for semi-cylindrical protrusions, while the f increases by 12.3% and 10.9%, respectively, compared to the smooth absorber.
期刊:
INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES,2025年:1-11 ISSN:1913-2751
通讯作者:
Yan, SY
作者机构:
[Yan, Shiyu; Chen, Lingna; Yan, SY; Yu, Gang] Univ South China, Comp Sch, Hengyang 421001, Peoples R China.;[Yang, Jiaoxing] Univ South China, Affiliated Hosp 1, Hengyang 421001, Peoples R China.
通讯机构:
[Yan, SY ] U;Univ South China, Comp Sch, Hengyang 421001, Peoples R China.
关键词:
Deep Learning technique;Synergistic drug combination;Computational model;Feature extraction
摘要:
Drug combination therapy has shown improved efficacy and decreased adverse effects, making it a practical approach for conditions like cancer. However, discovering all potential synergistic drug combinations requires extensive experimentation, which can be challenging. Recent research utilizing deep learning techniques has shown promise in reducing the number of experiments and overall workload by predicting synergistic drug combinations. Therefore, developing reliable and effective computational methods for predicting these combinations is essential. This paper proposed a novel method called Drug-molecule Connect Cell (DconnC) for predicting synergistic drug combinations. DconnC leverages cellular features as nodes to establish connections between drug molecular structures, allowing the extraction of pertinent features. These features are then optimized through self-augmented contrastive learning using bidirectional recurrent neural networks (Bi-RNN) and long short-term memory (LSTM) models, ultimately predicting the drug synergy. By integrating information about the molecular structure of drugs for the extraction of cell features, DconnC uncovers the inherent connection between drug molecular structures and cellular characteristics, thus improving the accuracy of predictions. The performance of our method is evaluated using a five-fold cross validation approach, demonstrating a 35
$$\%$$
reduction in the mean square error (MSE) compared to the next-best method. Moreover, our method significantly outperformed alternative approaches in various evaluation criteria, particularly in predicting different cell lines and Loewe synergy score intervals.
作者机构:
[Huang, Wenhua; Zhang, Jiankai; Zhan, Jianan; Zhang, JK] Guangdong Med Univ, Sch Basic Med Sci, Dept Human Anat, Zhanjiang 524000, Peoples R China.;[Wang, YL; Wang, Yilin] China Med Univ, Coll Basic Med Sci, Dept Human Anat, Shenyang 110122, Peoples R China.;[Huang, Wenhua; Chen, Qiwei; Zhou, Xi; Zhang, Xianlin] Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Med Biomech, Natl Key Discipline Human Anat, Guangzhou 510515, Peoples R China.;[Huang, Wenhua; Kong, Yueying] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Gong, Haihuan] Guangzhou Med Univ, Affiliated Stomatol Hosp, Guangzhou Key Lab Basic & Appl Res Oral Regenerat, Dept Periodont, Guangzhou 510182, Peoples R China.
通讯机构:
[Huang, WH ; Zhang, JK] G;[Wang, YL ] C;Guangdong Med Univ, Sch Basic Med Sci, Dept Human Anat, Zhanjiang 524000, Peoples R China.;China Med Univ, Coll Basic Med Sci, Dept Human Anat, Shenyang 110122, Peoples R China.;Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Med Biomech, Natl Key Discipline Human Anat, Guangzhou 510515, Peoples R China.
摘要:
Myoelectric biofeedback (EMG-BF) is a widely recognized and effective method for treating movement disorders caused by impaired nerve function. However, existing EMG-feedback devices are almost entirely located in large medical centers, which greatly limits patient accessibility. To address this critical limitation, there is an urgent need to develop a portable, cost-effective, and real-time monitoring device that can transcend the existing barriers to the treatment of EMG-BF. Our proposed solution leverages polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as core materials, ingeniously incorporating wood pulp nano celluloses (CNF-P)-Na(+) to enhance the structural integrity. Additionally, the inclusion of nano-silica particles further augments the sensor's capabilities, enabling the creation of a stress-sensitive mineral ionization hydrogel sensor. This innovative approach not only capitalizes on the superior rheological properties of the materials but also, through advanced 3D printing technology, facilitates the production of a micro-scale structural hydrogel sensor with unparalleled sensitivity, stability, and durability. The potential of this sensor in the realm of human motion detection is nothing short of extraordinary. This development can potentially improve the treatment landscape for EMG-BF offering patients more convenient and efficient therapeutic options.
期刊:
Journal of Cardiovascular Translational Research,2025年:1-15 ISSN:1937-5387
通讯作者:
Dai, Xiaoyan;Peng, Juan;Tang, Zhihan
作者机构:
[Ni Gan; Yanyu Chen; Qiong Xiang; Yuting Cui; Man Li; Yating Zhou] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Wen Zeng] Shaoyang Branch of Key Laboratory for Arteriosclerology of Hunan Province, The Central Hospital of Shaoyang, Shaoyang, 421001, China;[Xi-Long Zheng] Departments of Biochemistry & Molecular Biology and Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;[Xiaoyan Dai] Clinical Research Center, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, China. xdai@usc.edu.cn;[Xiaoyan Dai] Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Hengyang, 421002, China. xdai@usc.edu.cn
通讯机构:
[Peng, Juan; Tang, Zhihan] I;[Dai, Xiaoyan] C;Clinical Research Center, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, China.;Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Hengyang, 421002, China.;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China.
摘要:
Ferroptosis plays a key role in abdominal aortic aneurysm (AAA) development. This study explores whether and how ferroptosis regulates AAA progression. Ferroptosis was confirmed in human AAA tissue. In vitro experiments with primary mouse vascular smooth muscle cells (VSMCs) and abdominal aortic rings revealed that angiotensin II (Ang II) triggered ferroptosis in VSMCs. Ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor, effectively suppressed this effect. Additionally, the ferroptosis inducer erastin and Ang II can both promoted pathological remodeling of abdominal aortic rings, but Fer-1 significantly suppressed these effects. In AAA mouse model, Fer-1 treatment reduced AAA formation. Mechanistically, RNA-sequencing analysis revealed that Fer-1 regulates VSMC contractile function, suppresses inflammation, and mitigates extracellular matrix remodeling. These findings highlight the critical role of VSMC ferroptosis in AAA pathogenesis and demonstrate that ferroptosis inhibition effectively reduces pathological vascular remodeling, making it a promising therapeutic strategy for preventing AAA.
摘要:
In uranium(VI) (U(VI)) photoreduction, it is still a challenge to simultaneously degrade naturally coexisting organics and explore their impact on U(VI) photoreduction. Meanwhile, how to boost the separation and transport capability of photo-induced carriers is also a hot topic of current research. In this work, an ultrathin Bi 2 WO 6 /Bi 2 MoO 6 Z-type heterojunction was developed for the simultaneous treatment of U(VI) and its co-existing organics (tannic acid (TA)). Ultrathin interface engineering increased the contact area and shortened the transmission distance of photo-induced carriers. As a result, ultrathin Bi 2 WO 6 /Bi 2 MoO 6 exhibited highly efficient U(VI) removal rate (95.8 %) and TA degradation rate (97.2 %), which were much higher than those of bulk Bi 2 WO 6 /Bi 2 MoO 6 and single ultrathin Bi 2 WO 6 . In addition, the material possessed excellent stability and recyclability. Importantly, TA not only enhanced U(VI) removal by eliminating holes, but also favored U(VI) removal by serving as a bridge to the catalyst for U(VI) adsorption. Finally, a new mechanism was proposed.
In uranium(VI) (U(VI)) photoreduction, it is still a challenge to simultaneously degrade naturally coexisting organics and explore their impact on U(VI) photoreduction. Meanwhile, how to boost the separation and transport capability of photo-induced carriers is also a hot topic of current research. In this work, an ultrathin Bi 2 WO 6 /Bi 2 MoO 6 Z-type heterojunction was developed for the simultaneous treatment of U(VI) and its co-existing organics (tannic acid (TA)). Ultrathin interface engineering increased the contact area and shortened the transmission distance of photo-induced carriers. As a result, ultrathin Bi 2 WO 6 /Bi 2 MoO 6 exhibited highly efficient U(VI) removal rate (95.8 %) and TA degradation rate (97.2 %), which were much higher than those of bulk Bi 2 WO 6 /Bi 2 MoO 6 and single ultrathin Bi 2 WO 6 . In addition, the material possessed excellent stability and recyclability. Importantly, TA not only enhanced U(VI) removal by eliminating holes, but also favored U(VI) removal by serving as a bridge to the catalyst for U(VI) adsorption. Finally, a new mechanism was proposed.
期刊:
NEW ENGLAND JOURNAL OF MEDICINE,2025年 ISSN:0028-4793
作者机构:
[You, Feng; Zi, Wenjie; Li, Maohua; Li, Linyu; Tian, Yan; Xie, Dongjing; Long, Xingmin; Qiu, Zhongming; Tao, Jian; Jiang, Ling; Meng, Zhaoyou; Zhou, Kai; Li, Fengli] Department of Neurology, Second Affiliated Hospital of Army Medical University (Xinqiao Hospital), Chongqing, China;[Feng, Xinggang; Wu, Yuelu; Cai, Lingyu; Li, Qi; Qiu, Zhongming; Jiang, Bingwu] Department of Neurology, No. 903 Hospital of the People's Liberation Army (PLA) Joint Logistics Support Force, Hangzhou, China;[Yin, Congguo; Sang, Hongfei] Department of Neurology, Hangzhou First People's Hospital and School of Medicine of Westlake University, Hangzhou, China;[Wu, Junxiong; Long, Chen; Wu, Derong; Yuan, Guangxiong] Emergency Department, Xiangtan Central Hospital (Affiliated Hospital of Hunan University), Xiangtan, China;[Yang, Bo; Kong, Zhenyu] Department of Neurology, First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, China
摘要:
BACKGROUND: The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain. METHODS: In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible for thrombolysis to receive either intravenous tenecteplase followed by endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was functional independence (a score of 0 to 2 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 90 days. Secondary outcomes included successful reperfusion before and after thrombectomy. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and death within 90 days. RESULTS: A total of 278 patients were randomly assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. Functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and in 120 patients (44.1%) in the thrombectomy-alone group (unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P = 0.04). A total of 6.1% of the patients in the tenecteplase-thrombectomy group and 1.1% of those in the thrombectomy-alone group had successful reperfusion before thrombectomy, and 91.4% and 94.1%, respectively, had successful reperfusion after thrombectomy. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the patients in the tenecteplase-thrombectomy group and in 6.7% of those in the thrombectomy-alone group; mortality at 90 days was 22.3% and 19.9%, respectively. CONCLUSIONS: Among patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, the percentage of patients with functional independence at 90 days was higher with intravenous tenecteplase plus endovascular thrombectomy than with endovascular thrombectomy alone. (Funded by the Chongqing Science and Health Joint Medical Research Project and others; BRIDGE-TNK ClinicalTrials.gov number, NCT04733742.).
摘要:
BACKGROUND AND OBJECTIVE: Alpha-ketoglutarate (AKG), is a major intermediate metabolite of the tricarboxylic acid cycle, and is closely associated with cardiometabolic disease prognosis. Previous studies indicated that AKG is related to myocardial energy expenditure levels and reflects adverse short-term outcomes in heart failure (HF) patients. In this prospective cohort study, we examined the long-term prognostic value of AKG levels in acute HF (AHF) patients. METHODS: Plasma AKG levels were assessed in patients hospitalized with AHF. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated via multiple Cox regression. All-cause mortality was compared between patients with NT-proBNP < 1000 pg/ml and those with NT-proBNP ≥ 1000 pg/ml via subgroup analysis. RESULTS: Patients with AKG ≥ 9.83 μg/ml had higher heart rates and NT-proBNP and lower left ventricular ejection fraction (LVEF) and systolic blood pressure (SBP). After multiple adjustment, higher AKG was associated with an increased all-cause mortality risk (HR = 1.078, p < 0.001). Compared with AKG < 9.83 μg/ml, AKG ≥ 9.83 μg/ml nearly doubled (HR = 1.929, p < 0.001) and quadrupled (HR = 4.160, p < 0.001) the all-cause mortality risk in patients with NT-proBNP ≥ 1000 pg/ml and those with NT-proBNP < 1000 pg/ml, respectively. CONCLUSIONS AND RELEVANCE: Plasma AKG was independently associated with greater all-cause mortality risk in patients with AHF. Higher AKG levels retained prognostic value for patients with relatively low NT-proBNP.
期刊:
Journal of Environmental Management,2025年386:125756 ISSN:0301-4797
通讯作者:
Zhang, Tao;Yan, Qingyun
作者机构:
[Yan, Qingyun; Fan, Yijun; Yu, Xiaoli; Liu, Shengwei; Ming, Yuzhen; He, Zhili; Su, Erxin; Wu, Kun; Yu, Huang; Liu, Huanping; Liu, Fei; Huang, Zhenyu; Yang, Yufeng; Wang, Cheng; Niu, Mingyang] School of Environmental Science and Engineering, Marine Synthetic Ecology Research Center, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Provincial Observation and Research Station for Marine Ranching in Lingdingyang Bay, China;[Fan, Yijun; Yu, Xiaoli; Liu, Shengwei; Ming, Yuzhen; He, Zhili; Su, Erxin; Wu, Kun; Yu, Huang; Liu, Huanping; Liu, Fei; Huang, Zhenyu; Yang, Yufeng; Wang, Cheng; Niu, Mingyang] ASEAN Belt and Road Joint Laboratory on Mariculture Technology, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China;[Ming, Yuzhen] Department of Ocean Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong 999077, PR China;[Yu, Huang] Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang, Hunan 421001, PR China;[Zhang, Tao] School of Agriculture and Biotechnology, Sun Yat-sen University, Shenzhen, Guangdong 518107, PR China. Electronic address: zhangt47@mail.sysu.edu.cn
通讯机构:
[Yan, Qingyun] A;[Zhang, Tao] S;School of Agriculture and Biotechnology, Sun Yat-sen University, Shenzhen, Guangdong 518107, PR China. Electronic address:;ASEAN Belt and Road Joint Laboratory on Mariculture Technology, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China. Electronic address: yanqingyun@sml-zhuhai.cn
摘要:
Mariculture has expanded significantly in recent decades due to rising seafood demand and its contribution to ocean carbon sequestration. While the mechanisms of carbon sequestration in mariculture are well-established, the roles of microorganisms in sedimentary carbon sequestration have rarely been explored. How microorganisms mediate organic carbon metabolism and their effects on coastal carbon pools remain unclear. Here we tested the carbon fraction and contents, as well as extracellular hydrolase activities in macroalgae culture area, fish or abalone culture area, and control area without mariculture. We profiled microbial community composition and carbon metabolism characteristics in sediments through 16S rRNA gene amplicon sequencing and metagenomics. Our findings revealed that macroalgae culture areas exhibited a significantly greater potential for carbon sequestration than the control area, the concentration of TOC in seawater and the contents of SOC, DOC, and ROC in sediments were significantly ( p < 0.05) increased by 18.93 %, 6.98 %, 33.98 %, and 18.30 % respectively. These results can be attributed to decreased activities of extracellular hydrolase and a lower abundance of carbon-degrading genes. Moreover, metabolic profiling identified taxa from families such as Alteromonadaceae , Pseudomonadaceae , Rhodobacteraceae , Enterobacteriaceae , and Flavobacteriaceae , which are highly metabolically flexible in utilizing a wide range of organic and inorganic energy sources, playing crucial roles in carbon formation. Their respiratory metabolism, such as sulfate reduction, thiosulfate oxidation, and denitrification as well as secondary metabolism products could also affect the formation and persistence of sedimentary carbon pools. Specifically, increased total nitrogen (TN) and nitrate-nitrogen (NO 3 − ) could potentially enhance microbial degradation of organic carbon, decreasing carbon stock within coastal sediments. This study enhanced our understanding of microbial regulation of the organic carbon pool in the mariculture ecosystem.
Mariculture has expanded significantly in recent decades due to rising seafood demand and its contribution to ocean carbon sequestration. While the mechanisms of carbon sequestration in mariculture are well-established, the roles of microorganisms in sedimentary carbon sequestration have rarely been explored. How microorganisms mediate organic carbon metabolism and their effects on coastal carbon pools remain unclear. Here we tested the carbon fraction and contents, as well as extracellular hydrolase activities in macroalgae culture area, fish or abalone culture area, and control area without mariculture. We profiled microbial community composition and carbon metabolism characteristics in sediments through 16S rRNA gene amplicon sequencing and metagenomics. Our findings revealed that macroalgae culture areas exhibited a significantly greater potential for carbon sequestration than the control area, the concentration of TOC in seawater and the contents of SOC, DOC, and ROC in sediments were significantly ( p < 0.05) increased by 18.93 %, 6.98 %, 33.98 %, and 18.30 % respectively. These results can be attributed to decreased activities of extracellular hydrolase and a lower abundance of carbon-degrading genes. Moreover, metabolic profiling identified taxa from families such as Alteromonadaceae , Pseudomonadaceae , Rhodobacteraceae , Enterobacteriaceae , and Flavobacteriaceae , which are highly metabolically flexible in utilizing a wide range of organic and inorganic energy sources, playing crucial roles in carbon formation. Their respiratory metabolism, such as sulfate reduction, thiosulfate oxidation, and denitrification as well as secondary metabolism products could also affect the formation and persistence of sedimentary carbon pools. Specifically, increased total nitrogen (TN) and nitrate-nitrogen (NO 3 − ) could potentially enhance microbial degradation of organic carbon, decreasing carbon stock within coastal sediments. This study enhanced our understanding of microbial regulation of the organic carbon pool in the mariculture ecosystem.
作者:
Like Xie;Sujun Xiao;Qinyi Zhou;Wang Chen;Zhihao Hu;...
期刊:
Journal of Traditional and Complementary Medicine,2025年 ISSN:2225-4110
通讯作者:
Yuan Li
作者机构:
[Like Xie; Sujun Xiao; Qinyi Zhou; Wang Chen; Zhihao Hu; Yizhou Liu; Xiaofeng Ma] Department of Cardiology, Nanhua Hospital affiliated to Nanhua University, 421001, Hengyang, Hunan Province, China;[Yunhui Li] Zhuzhou Central Hospital, General Medicine, 412001, Zhuzhou, Hunan Province, China;[Yuan Li] Health School of Nuclear Industry, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
通讯机构:
[Yuan Li] H;Health School of Nuclear Industry, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
关键词:
HO-1;Keap1;Nrf2;Oxidative stress;ROS
摘要:
Background Anticancer agent doxorubicin is essential for cancer treatment but often causes cardiotoxicity. Tectorigenin has shown potential cardioprotective effects, but underlying mechanisms remain unclear. We aimed to investigate whether Tectorigenin attenuates doxorubicin-induced myocardial injury.
Anticancer agent doxorubicin is essential for cancer treatment but often causes cardiotoxicity. Tectorigenin has shown potential cardioprotective effects, but underlying mechanisms remain unclear. We aimed to investigate whether Tectorigenin attenuates doxorubicin-induced myocardial injury.
Methods Doxorubicin (DOX) was utilized in C57BL/6J mice and cardiomyocytes H9c2, to establish in vivo and in vitro cardiotoxicity models, then treated with Tectorigenin. The levels of ferroptosis-related factors were measured using specific assay kits. The Liperfluo and DHE stainings were used to detect levels of lipid ROS. Cardiac function in rats was assessed using echocardiography. Immunofluorescence staining was used to detect Nrf2 nuclear translocation. ELISA assay was employed to check serum CK-MB, BNP and Tn-T levels. Cardiac injury and fibrosis were evaluated through HE and Masson stainings. Furthermore, TEM was employed to observe mitochondrial ultrastructure. Western blot and immunofluorescence staining were utilized to detect protein levels.
Doxorubicin (DOX) was utilized in C57BL/6J mice and cardiomyocytes H9c2, to establish in vivo and in vitro cardiotoxicity models, then treated with Tectorigenin. The levels of ferroptosis-related factors were measured using specific assay kits. The Liperfluo and DHE stainings were used to detect levels of lipid ROS. Cardiac function in rats was assessed using echocardiography. Immunofluorescence staining was used to detect Nrf2 nuclear translocation. ELISA assay was employed to check serum CK-MB, BNP and Tn-T levels. Cardiac injury and fibrosis were evaluated through HE and Masson stainings. Furthermore, TEM was employed to observe mitochondrial ultrastructure. Western blot and immunofluorescence staining were utilized to detect protein levels.
Results DOX induced ferroptosis in H9c2 cells concentration-dependently and time-dependently, which was alleviated by Tectorigenin treatment. ML385 or K67 abolished Tectorigenin's inhibition on DOX-induced H9c2 cell ferroptosis. Mechanistically, Tectorigenin promoted the expressions of p62 and p-p62, leading to decreased Keap1 expression. This cascade facilitated Nrf2 nuclear translocation and subsequently elevated HO-1 and GPX4 expressions. Moreover, Tectorigenin treatment improved cardiac function, myocardial injury, fibrosis and mitochondrial function in C57BL/6J mice induced by DOX, as well as ferroptosis.
DOX induced ferroptosis in H9c2 cells concentration-dependently and time-dependently, which was alleviated by Tectorigenin treatment. ML385 or K67 abolished Tectorigenin's inhibition on DOX-induced H9c2 cell ferroptosis. Mechanistically, Tectorigenin promoted the expressions of p62 and p-p62, leading to decreased Keap1 expression. This cascade facilitated Nrf2 nuclear translocation and subsequently elevated HO-1 and GPX4 expressions. Moreover, Tectorigenin treatment improved cardiac function, myocardial injury, fibrosis and mitochondrial function in C57BL/6J mice induced by DOX, as well as ferroptosis.
Conclusion Our findings reveal that Tectorigenin attenuates DOX-induced ferroptosis and myocardial damage by activating the p62-Keap1-Nrf2/HO-1/GPX4 axis, this may provide a therapeutic strategy for mitigating cardiotoxicity associated with chemotherapeutic agents.
Our findings reveal that Tectorigenin attenuates DOX-induced ferroptosis and myocardial damage by activating the p62-Keap1-Nrf2/HO-1/GPX4 axis, this may provide a therapeutic strategy for mitigating cardiotoxicity associated with chemotherapeutic agents.
期刊:
Journal of the Franklin Institute,2025年362(1):107397 ISSN:0016-0032
通讯作者:
Wang, H
作者机构:
[Nie, Liang] Univ South China, Sch Elect Engn, Hengyang 421001, Peoples R China.;[Wang, Hui] Liaocheng Univ, Sch Math Sci, Liaocheng 252000, Peoples R China.;[Sun, Yichong] Chinese Univ Hong Kong, Multiscale Med Robot Ctr, Hong Kong 999077, Peoples R China.
通讯机构:
[Wang, H ] L;Liaocheng Univ, Sch Math Sci, Liaocheng 252000, Peoples R China.
摘要:
In this paper, a switched linear parameter-varying (LPV) resilient tracking controller is designed for rigid-body under actuator faults, uncertainties in measurement of scheduling parameters and time-delay in detection of system modes. The nonlinear attitude dynamics of rigid-body is constructed as a switched LPV system in which persistent dwell-time switching rule is used to regulate the switches caused by abrupt and intermittent actuator failures. Thereafter, by constructing a class of both parameter-dependent and time-dependent multiple Lyapunov functions (MLFs), a switched LPV resilient tracking controller is developed in order that the global uniform exponential stability and desired L∞ performance of the underlying system are achieved even with uncertain scheduling parameters, mismatched modes and persistent external disturbances. Furthermore, the nonconvex conditions of control synthesis are converted into parameterized linear matrix inequalities that can be readily resolved via gridding technique. Finally, the availability of the provided approach is evaluated with a numerical simulation.
In this paper, a switched linear parameter-varying (LPV) resilient tracking controller is designed for rigid-body under actuator faults, uncertainties in measurement of scheduling parameters and time-delay in detection of system modes. The nonlinear attitude dynamics of rigid-body is constructed as a switched LPV system in which persistent dwell-time switching rule is used to regulate the switches caused by abrupt and intermittent actuator failures. Thereafter, by constructing a class of both parameter-dependent and time-dependent multiple Lyapunov functions (MLFs), a switched LPV resilient tracking controller is developed in order that the global uniform exponential stability and desired L∞ performance of the underlying system are achieved even with uncertain scheduling parameters, mismatched modes and persistent external disturbances. Furthermore, the nonconvex conditions of control synthesis are converted into parameterized linear matrix inequalities that can be readily resolved via gridding technique. Finally, the availability of the provided approach is evaluated with a numerical simulation.
作者:
M. Ablikim;M. N. Achasov;P. Adlarson;O. Afedulidis;X. C. Ai;...
期刊:
Journal of High Energy Physics,2025年2025(5):1-19 ISSN:1029-8479
通讯作者:
X. X. Ding
作者机构:
[M. Ablikim; G. Chen; Z. Y. Deng; M. C. Du; W. X. Fang; C. D. Fu; T. T. Han; Z. L. Hou; Y. Hu; Y. P. Huang; Q. Ji; R. Kiuchi; G. Li; K. Li; W. G. Li; T. Lin; B. J. Liu; C. X. Liu; F. Liu; H. H. Liu; P. L. Liu; H. L. Ma; Q. M. Ma; Z. P. Mao; F. Z. Qi; J. F. Qiu; J. Y. Shi; G. X. Sun; H. K. Sun; Y. Z. Sun; G. Y. Tang; B. Wang; L. L. Wang; X. N. Wang; Y. Q. Wang; S. P. Wen; L. H. Wu; G. F. Xu; H. X. Yang; T. Yang; B. X. Zhang; J. Y. Zhang; X. M. Zhang; Y. Zhang; Z. D. Zhang; Z. H. Zhang; G. Zhao; L. Zhao; K. Zhu; W. J. Zhu; J. H. Zou] Institute of High Energy Physics, Beijing, People’s Republic of China;Budker Institute of Nuclear Physics SB RAS (BINP), Novosibirsk, Russia;Novosibirsk State University, Novosibirsk, Russia;[P. Adlarson; T. Johansson; K. Schoenning; V. Thoren; M. Wolke] Uppsala University, Uppsala, Sweden;[O. Afedulidis; R. E. de Boer; F. Feldbauer; M. Fritsch; F. Hanisch; F. H. Heinsius; T. Holtmann; F. Hölzken; B. Kopf; M. Kuessner; M. Pelizaeus; U. Wiedner; L. Wollenberg] Bochum Ruhr-University, Bochum, Germany
通讯机构:
[X. X. Ding] P;Peking University, Beijing, People’s Republic of China<&wdkj&>State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing, People’s Republic of China
摘要:
Based on (1.0087 ± 0.0044) × 1010 J/ψ events collected with the BESIII detector at the BEPCII e+e− storage ring, we search for
$$ {K}_S^0 $$
invisible decays via the J/ψ →
$$ \phi {K}_S^0{K}_S^0 $$
process. No significant signal is observed, and the upper limit of the branching fraction of these invisible decays is set at 8.4 × 10−4 at the 90% confidence level. This is the first experimental search for
$$ {K}_S^0 $$
invisible decays.
期刊:
Separation and Purification Technology,2025年352:128172 ISSN:1383-5866
通讯作者:
Yinxiang Chen
作者机构:
[Liu, Cailing; Chen, Yinxiang] School of Resources Environment and Safety Engineering, University of South China, Hengyang 421001, China;[Peng, Yiyang; Wang, Hongqing] Lab of Optoelectronic Technology for Low Dimensional Nanomaterials, School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China;[Xu, Yiguo] Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen 518055, China;[Zhang, Ye] School of Resources Environment and Safety Engineering, University of South China, Hengyang 421001, China<&wdkj&>Lab of Optoelectronic Technology for Low Dimensional Nanomaterials, School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China
通讯机构:
[Yinxiang Chen] S;School of Resources Environment and Safety Engineering, University of South China, Hengyang 421001, China
摘要:
Photocatalytic reduction is a promising way to remove radioactive uranium U(VI) in wastewater. Herein, an S-scheme ZnO@ZnS heterojunction with hollow structure and dual-vacancies of Zn and S (ZnV, SV) is developed. The hollow confined space enhances light trapping ability through multiple light scattering and reflection, while the existence of vacancies extends light absorption, further enhancing the utilization of solar spectrum. Furthermore, the density function theory (DFT) calculations demonstrate that co-sharing of metal atoms at the interface and the ZnV and SV dual-vacancies induce enhanced internal electric field (IEF), leading to facilitated S-scheme charge transfer, thereby resulting in improved retention of redox potential and suppressed carrier recombination dynamics. ZnO@ZnS shows a highest U(VI) removal rate of 96.48% along with a highest U enrichment of 514.33 mg/g, which is 3.6 and 2.7-folds enhanced compared to pristine ZnO and ZnS, respectively. Through various quenching experiments, a potential new mechanism for the catalytic reduction of U(VI) is proposed. Our findings reveal the involvement of h+ in the reaction, highlighting its significant catalytic role in the reduction process. Moreover, ZnO@ZnS performs excellent U(VI) extraction ability in open-air conditions without any sacrificial agents, revealing the great significance for practical applications.
Photocatalytic reduction is a promising way to remove radioactive uranium U(VI) in wastewater. Herein, an S-scheme ZnO@ZnS heterojunction with hollow structure and dual-vacancies of Zn and S (ZnV, SV) is developed. The hollow confined space enhances light trapping ability through multiple light scattering and reflection, while the existence of vacancies extends light absorption, further enhancing the utilization of solar spectrum. Furthermore, the density function theory (DFT) calculations demonstrate that co-sharing of metal atoms at the interface and the ZnV and SV dual-vacancies induce enhanced internal electric field (IEF), leading to facilitated S-scheme charge transfer, thereby resulting in improved retention of redox potential and suppressed carrier recombination dynamics. ZnO@ZnS shows a highest U(VI) removal rate of 96.48% along with a highest U enrichment of 514.33 mg/g, which is 3.6 and 2.7-folds enhanced compared to pristine ZnO and ZnS, respectively. Through various quenching experiments, a potential new mechanism for the catalytic reduction of U(VI) is proposed. Our findings reveal the involvement of h+ in the reaction, highlighting its significant catalytic role in the reduction process. Moreover, ZnO@ZnS performs excellent U(VI) extraction ability in open-air conditions without any sacrificial agents, revealing the great significance for practical applications.
通讯机构:
[Li, YH ] U;[Jiang, YJ ] C;Cent Hosp Yongzhou, Dept Oncol, Yongzhou 425000, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
bioinformatics;biomarker;predictive factor;ribophorin family 1;tumor microenvironment
摘要:
The ribophorin family, including RPN1, has been associated with tumor progression, but its specific role in pan-cancer dynamics remains unclear. Using data from TCGA, GTEx, and Ualcan databases, we investigated the relationship of RPN1 with prognosis, genomic alterations, and epigenetic modifications across various cancers. Differential analysis revealed elevated RPN1 expression in multiple cancer types, indicating a potential prognostic value. Amplification was the predominant mutation type of RPN1 in pan-cancer, with notable correlations with DNA methylation and copy number variation. Gene set variation analysis identified RPN1's involvement in cancer development, immunity, and metabolism. Additionally, RPN1 expression correlated with the tumor microenvironment, immune response factors, and response to anti-tumor therapies. Functional validation in triple-negative breast cancer, glioblastoma, and bladder cancer cell lines demonstrated the role of RPN1 in tumor cell proliferation and migration. Our findings highlight RPN1 as a potential biomarker for cancer diagnosis and treatment response in pan-cancer therapy.