摘要:
Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC. Tweetable abstract: Triple-negative breast cancer is the most malignant subtype of BC. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to increase SLC7A11 expression. POU2F2 upregulated PTPRG-AS1 to inhibit ferroptosis in triple-negative breast cancer by miR-376c-3p/SLC7A11. Plain language summary: Triple-negative breast cancer (TNBC) is a kind of breast cancer with high recurrence and low survival rates. Activation of the ferroptosis pathway can inhibit BC proliferation and distant metastasis. Therefore, identifying effective biomarkers and molecular mechanisms of ferroptosis in TNBC is important for its earlier detection and therapy. PTPRG-AS1 is a new type of lncRNA discovered in recent years that is increased in various diseases and is related to prognosis. In the present study, the authors found that POU2F2 promoted PTPRG-AS1 transcription. PTPRG-AS1 knockdown activated ferroptosis in TNBC and inhibited proliferation. Mechanistically, PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11, thereby inhibiting ferroptosis and promoting TNBC development. These results indicate that PTPRG-AS1 is a possible therapeutic target in TNBC.
摘要:
To investigate the strengthening effects and mechanisms of bioaugmentation on the microbial remediation of uranium-contaminated groundwater via bioreduction coupled to biomineralization, two exogenous microbial consortia with reducing and phosphate-solubilizing functions were screened and added to uranium-contaminated groundwater as the experimental groups (group B, reducing consortium added; group C, phosphate-solubilizing consortium added). β-glycerophosphate (GP) was selected to stimulate the microbial community as the sole electron donor and phosphorus source. The results showed that bioaugmentation accelerated the consumption of GP and the proliferation of key functional microbes in groups B and C. In group B, Dysgonomonas, Clostridium_sensu_stricto_11 and Clostridium_sensu_stricto_13 were the main reducing bacteria, and Paenibacillus was the main phosphate-solubilizing bacteria. In group C, the microorganisms that solubilized phosphate were mainly unclassified_f_Enterobacteriaceae. Additionally, bioaugmentation promoted the formation of unattached precipitates and alleviated the inhibitory effect of cell surface precipitation on microbial metabolism. As a result, the formation rate of U-phosphate precipitates and the removal rates of aqueous U(VI) in both groups B and C were elevated significantly after bioaugmentation. The U(VI) removal rate was poor in the control group (group A, with only an indigenous consortium). Propionispora, Sporomusa and Clostridium_sensu_stricto_11 may have played an important role in the removal of uranium in group A. Furthermore, the addition of a reducing consortium promoted the reduction of U(VI) to U(IV), and immobilized uranium existed in the form of U(IV)-phosphate and U(VI)-phosphate precipitates in group B. In contrast, U was present mainly as U(VI)-phosphate precipitates in groups A and C. Overall, bioaugmentation with an exogenous consortium resulted in the rapid removal of uranium from groundwater and the formation of U-phosphate minerals and served as an effective strategy for improving the treatment of uranium-contaminated groundwater in situ.
作者机构:
[Xu, Xiaoding; Xu, Ya; Xu, Lei; Cao, Yuan] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China.;[Xu, Xiaoding; Xu, Ya; Xu, Lei; Cao, Yuan] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou Key Lab Med Nanomat, Guangzhou 510120, Peoples R China.;[Xu, Xiaoding; Xu, Ya; Xu, Lei; Cao, Yuan] Sun Yat Sen Mem Hosp, Nanhai Translat Innovat Ctr Precis Immunol, Foshan 528200, Peoples R China.;[Li, Rong; Xu, Xiaoding] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构:
[Xu, XD ] S;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China.;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou Key Lab Med Nanomat, Guangzhou 510120, Peoples R China.;Sun Yat Sen Mem Hosp, Nanhai Translat Innovat Ctr Precis Immunol, Foshan 528200, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词:
cancer therapy;delivery;nucleic acid;polymeric nanoparticles;redox responsive
摘要:
Redox‐responsive polymeric nanoparticles (NPs) are widely used for nucleic acid drug delivery and cancer therapy. Herein, the important signaling pathways regulating tumor redox status are summarized and the recent development of redox‐responsive NPs for nucleic acid delivery and cancer therapy is systemically reviewed. The future development of NPs‐mediated nucleic acid delivery and their challenges in clinical translation are also discussed. Abstract Cancer development and progression of cancer are closely associated with the activation of oncogenes and loss of tumor suppressor genes. Nucleic acid drugs (e.g., siRNA, mRNA, and DNA) are widely used for cancer therapy due to their specific ability to regulate the expression of any cancer‐associated genes. However, nucleic acid drugs are negatively charged biomacromolecules that are susceptible to serum nucleases and cannot cross cell membrane. Therefore, specific delivery tools are required to facilitate the intracellular delivery of nucleic acid drugs. In the past few decades, a variety of nanoparticles (NPs) are designed and developed for nucleic acid delivery and cancer therapy. In particular, the polymeric NPs in response to the abnormal redox status in cancer cells have garnered much more attention as their potential in redox‐triggered nanostructure dissociation and rapid intracellular release of nucleic acid drugs. In this review, the important genes or signaling pathways regulating the abnormal redox status in cancer cells are briefly introduced and the recent development of redox‐responsive NPs for nucleic acid delivery and cancer therapy is systemically summarized. The future development of NPs‐mediated nucleic acid delivery and their challenges in clinical translation are also discussed.
作者机构:
[Huang, Haobo; Wu, Mingxin; Liu, Zhican; Zeng, Jianping; Zhang, Lingling; Zhu, Yunlong] Xiangtan Cent Hosp, Dept Cardiol, Xiangtan 411100, Peoples R China.;[Wu, Mingxin; Liu, Zhican; Zeng, Jianping; Zhu, Yunlong] Univ South China, Grad Collaborat Training Base Xiangtan Cent Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhu, Yunlong] Cent South Univ, Dept Cardiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.;[Peng, Ke] Xiangtan Cent Hosp, Dept Sci Res, Xiangtan 411100, Peoples R China.;[Yang, Wenbin] Xiangtan Cent Hosp, Med Dept, Xiangtan 411100, Peoples R China.
通讯机构:
[Wu, MX ; Zhang, LL; Peng, K ] X;Xiangtan Cent Hosp, Dept Cardiol, Xiangtan 411100, Peoples R China.;Univ South China, Grad Collaborat Training Base Xiangtan Cent Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Xiangtan Cent Hosp, Dept Sci Res, Xiangtan 411100, Peoples R China.
摘要:
This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35kg/m(2), subjects were divided into the mildly obese group (BMI, 30-35kg/m(2)) and non-obese group (BMI < 30kg/m(2)). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32-0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47-1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.
期刊:
JOURNAL OF SUPERCRITICAL FLUIDS,2024年205:106145 ISSN:0896-8446
通讯作者:
Ge, FH;Wang, WG
作者机构:
[Fang, Ting; Ge, Fahuan; Ge, FH; Zhou, Dan; Duan, Minghui; Zhou, Xue] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.;[Wang, Weiguo; Duan, Minghui] Univ South China, Hengyang 421000, Hunan, Peoples R China.;[Fang, Ting; Ge, Fahuan; Ge, FH; Zhou, Dan] Guangdong Engn Res Ctr Supercrit Fluid Extract Tra, Guangzhou 510006, Peoples R China.;[Shi, Qinglong] Natl Engn Res Ctr Pharmaceut Proc Technol Tradit C, Guangzhou, Peoples R China.
通讯机构:
[Ge, FH ] S;[Wang, WG ] U;Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.;Univ South China, Hengyang 421000, Hunan, Peoples R China.;Guangdong Engn Res Ctr Supercrit Fluid Extract Tra, Guangzhou 510006, Peoples R China.
关键词:
High-pressure supercritical CO 2 extraction;Astaxanthin;Haematococcus pluvialis;Kinetics
摘要:
Astaxanthin derived from Hematococcus pluvialis (H. pluvialis) exhibits potent capacity in scavenging free radicals and quenching active oxygen. However, the conventional extraction of Astaxanthin from H. pluvialis involves the use of a substantial amount of organic reagents, leading to environmental pollution and low extraction efficiency. In this work, a high-pressure supercritical CO2 extraction (H-SFE) was applied to extract astaxanthin from H. pluvialis. Influential parameters of H-SFE were optimized by single factor, orthogonal test and kinetics experiments. Extraction pressure is a critical component influencing the extraction efficiency of SFE. Increased pressure results in increased supercritical CO2 density and thus increased solubility of substances and enhanced component extraction. The extraction yield of astaxanthin at 65 MPa was 1.25 times and 2.32 times higher than that at 45 MPa and 25 MPa, respectively. The H-SFE extraction yield of astaxanthin was 20%−70% higher than that of ultrasonic-assisted extraction (UAE) and organic solvent extraction (OSE).
通讯机构:
[Tian, H; Peng, Q; Liao, QJ ; Zhou, YJ] C;Cent South Univ, Hunan Canc Hosp, Hunan Key Lab Canc Metab, Changsha 410013, Hunan, Peoples R China.;Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China.;Univ South China, Hengyang 421001, Hunan, Peoples R China.;Publ Serv Platform Tumor Organoids Technol, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
摘要:
Human papillomavirus (HPV) is a class of envelope-free double-stranded DNA virus. HPV infection has been strongly associated with the development of many malignancies, such as cervical, anal and oral cancers. The viral oncoproteins E6 and E7 perform central roles on HPV-induced carcinogenic processes. During tumor development, it usually goes along with the activation of abnormal signaling pathways. E6 and E7 induces changes in cell cycle, proliferation, invasion, metastasis and other biological behaviors by affecting downstream tumor-related signaling pathways, thus promoting malignant transformation of cells and ultimately leading to tumorigenesis and progression. Here, we summarized that E6 and E7 proteins promote HPV-associated tumorigenesis and development by regulating the activation of various tumor-related signaling pathways, for example, the Wnt/β-catenin, PI3K/Akt, and NF-kB signaling pathway. We also discussed the importance of HPV-encoded E6 and E7 and their regulated tumor-related signaling pathways for the diagnosis and effective treatment of HPV-associated tumors.
摘要:
Land-based uranium resources are becoming scarce because of the widespread development and use of nuclear energy. Therefore, to make up for the shortage of uranium resources, a new chitosan/carboxymethyl-β-cyclodextrin/quaternary ammonium salt-functionalized amidoxime carbon adsorbent (CSAOCF) was designed and synthesized for extracting uranium from seawater. Experimental studies show that the adsorption of uranium by CSAOCF is a spontaneous endothermic reaction and chemical adsorption. The theoretical maximum adsorption capacity of uranium can reach 726mg/g at 308K and pH=6. Moreover, the adsorption efficiency and selectivity of CSAOCF for uranium were significantly improved after the introduction of the carboxymethyl group, and the selection and partition coefficient of CSAOCF for uranium and vanadium increased from 16-fold to 30-fold under the same conditions. This indicates that there is a synergistic effect between carboxyl and amidoxime groups, which can promote the adsorption of uranium by CSAOCF. Furthermore, CSAOCF exhibits good oil resistance and can be reused more than five times. Therefore, CSAOCF containing carboxymethyl and amidoxime functional groups can considerably improve the selective adsorption of uranium and has great potential in the extraction of uranium from seawater.
摘要:
Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.
摘要:
Soil surface carbon dioxide (CO2) fluxes hold significant implications for comprehending carbon cycling, global climate change, and ecosystem functioning. Accurate understanding and quantification of this flux are crucial for assessing the carbon dynamics of ecosystems and predicting the impacts of climate change. In this study, we analyzed the variation pattern of CO2 concentration within the accumulated chamber from Fick's law, accounting for diffusion gradient effect and considering leakage effect. We developed a simple model to measure the soil surface CO2 flux, and used the model to calculate the values of CO2 fluxes on a specific soil surface. Comparing the fitting results of the proposed nonlinear model with traditional linear models for the measurement data, we found that the linear model underestimated by at least 18%, even up to 45%. Overall, our research indicates that the proposed model exhibits significant advancement and higher predictive reliability, successfully evaluating soil surface CO2 flux.
作者机构:
[Chen, Nan; Yuan, Tie-chui; Li, Zhi-you] Cent South Univ, State Key Lab Powder Met, Changsha 410083, Peoples R China.;[Teng, Hao; Chen, Long-wei] Univ South China, Coll Mech Engn, Hengyang 421001, Peoples R China.
通讯机构:
[Li, ZY ] C;[Teng, H ] U;Cent South Univ, State Key Lab Powder Met, Changsha 410083, Peoples R China.;Univ South China, Coll Mech Engn, Hengyang 421001, Peoples R China.
摘要:
With high-energy wet ball milling M2 high-speed steel (HSS) powder and ferrovanadium alloy, an in-situ synthesized core-shell MC carbides reinforced M2 HSS was prepared via vacuum sintering. The phase, morphology and composition distribution of the milled composite powders, and the evolution of the sintered microstructure with the temperature and the associated mechanical properties before and after heat treatment were investigated. The ground powders were fully refined into lamellae and aggregates with V-element evenly distributed inside. Almost full densification (similar to 99.2% relative density) of the modified M2 steel was achieved at 1180 degree celsius by supersolidus liquid phase sintering. Near-spherical MC carbides and irregular M6C carbides were dispersed within the HSS matrix, and the MC developed a core-shell structure due to the solidification of the sintering liquid. Both the matrix grains and carbides of the sintered alloy had been refined by heat treatment, reaching satisfactory bending strength of 3580 MPa and hardness of HRC58, and enhancing the scratch resistance significantly.
期刊:
European Journal of Medicinal Chemistry,2024年263:115956 ISSN:0223-5234
通讯作者:
Mi, Pengbing;Yuan, Zhonghua;Zheng, X;Lin, YW
作者机构:
[Tan, Yan; Yuan, Zhonghua; Mi, Pengbing; Jiang, Jinhuan; Chen, Limei; Luo, Jianxiong; Zheng, Xing; Ye, Shiying; Lin, Yuqing; Zheng, X] Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu; Mi, Pengbing] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xing] Hunan Vocat Coll Sci & Technol, Dept Pharm, Changsha 410004, Hunan, Peoples R China.;[Lv, You] Shaanxi Univ Sci & Technol, Coll Bioresources Chem & Mat Engn, Xian 710021, Shaanxi, Peoples R China.
通讯机构:
[Yuan, ZH; Mi, PB; Lin, YW ; Zheng, X ] U;Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.
关键词:
Human monoamine oxidase B inhibitor;Thiochromone;Thiochromone S,S-dioxide
摘要:
Developing new scaffolds for highly potent and selective inhibitors of human Monoamine Oxidase B (hMAO-B) is a crucial objective in enhancing the efficacy and safety in the clinical treatment of neurodegenerative diseases. In this study, we have identified a series of C-3 isoxazole-substituted thiochromone S,S-dioxide derivatives that exhibit strong inhibitory activity against hMAO-B. The strategy of oxidizing thiochromone to thiochromone S,S-dioxide solves the key defect of extreme insolubility observed for thiochromone analogues. In addition, the sulfone group contributes extra hydrogen(H)-bonding interactions with Tyr435, which significantly increases the activity of thiochromone S,S-dioxide derivatives against hMAO-B. Furthermore, the presence of isoxazole group provides potential H-bonding interaction and electrostatic interaction with the residue of Tyr326, while the rigid aryl ring introduces a potential steric conflict with Phe208 of hMAO-A to improve both potency and selectivity. In our investigations, several compounds (9c, 10c, 10e, 10g, 10l and 10m) demonstrate remarkable single-digit nanomolar potency. These compounds exhibit favorable cytotoxicity profiles in both differentiated SH-SY5Y and HVSMC cells, without apparent cardiotoxic effects. Moreover, compounds 10e and 10h do not lead to an increase in ROS levels in differentiated SH-SY5Y cells, further demonstrating their potential as safe and effective hMAO-B inhibitors. These findings indicate that the C-3 isoxazole substituted thiochromone S,S-dioxide analogues are potential leading compounds for the development of selective inhibitors with high potency.
期刊:
Reliability Engineering & System Safety,2024年243:109827 ISSN:0951-8320
通讯作者:
Ohl, JP
作者机构:
[Jiadong, Qiu] Univ South China, Sch Resources Environm & Safety Engn, Hengyang 421001, Peoples R China.;[Ohl, Joy P.] NanoStructuraCivis Lab Adv Smart Mat Civil Engn, Tokyo, Japan.;[Tran, Trung-Tin] Swinburne Vietnam FPT Univ, Dept Informat Technol, Da Nang, Vietnam.
通讯机构:
[Ohl, JP ] N;NanoStructuraCivis Lab Adv Smart Mat Civil Engn, Tokyo, Japan.
关键词:
Clay compressibility;Artificial neural network;Metaheuristic algorithms;Prediction accuracy;Practical engineering;Reliability systems
摘要:
This study aims at predicting clay compressibility (clay compressibility) for foundation design with unprecedented reliability and safety. To achieve this goal, we set forth several scientific objectives to enhance the ac-curacy of clay compressibility predictions and ensure the robustness of our models. Firstly, we explored an updated dataset comprising diverse clay types, focusing on the intricate relationship between clay compressibility and essential soil properties. By incorporating particle size distribution, the ratio between liquid limit (wLL) and plasticity index (PI), and the ratio between void ratio (eLL) and wLL, our objective was to gain a comprehensive understanding of clay behavior, facilitating more accurate predictions. Secondly, we employed Artificial Neural Networks (ANNs) as our primary modeling tool. ANNs, with their capacity to discern complex patterns within data, formed the foundation of our predictive model. Our scientific objective was to harness the power of ANNs to capture subtle relationships among input variables, thereby ensuring a robust foundation for clay compressibility predictions. To further refine our predictions, our third objective was to optimize the ANN model. We utilized five distinct metaheuristic algorithms-Bird Swarm Algorithm (BSA), Dragonfly Optimization (DO), Elephant Herding Optimization (EHO), Jaya Algorithm (JA), and Whale Optimization Algorithm (WOA). Our aim was to fine-tune the ANN model's parameters using these algorithms, capitalizing on their strengths to achieve superior predictive performance. Additionally, our study aimed to pioneer the development and eval-uation of hybrid models for forecasting clay compressibility. By integrating the ANN model with the meta-heuristic algorithms (BSA-ANN, DO-ANN, EHO-ANN, JA-ANN, and WOA-ANN), our objective was to create hybrid frameworks that synergistically combined the strengths of both approaches. We rigorously evaluated these hybrid models, ensuring their efficacy and reliability in practical engineering applications. Crucially, we validated our models through practical engineering scenarios. For this purpose, we prepared 30 new soil samples mirroring real-world conditions. Our objective was to apply the developed models to these samples, affirming their effectiveness and reliability in actual foundation design applications. In pursuit of identifying the most accurate and reliable predictive model, our final objective focused on the BSA-ANN model. Remarkably, this model demonstrated an exceptional accuracy of 99.8%. Our objective was to establish the BSA-ANN model as the preferred choice for practical engineering applications, ensuring high reliability and safety in foundation design.
摘要:
BACKGROUND: Potassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers. OBJECTIVE: To evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects. METHOD: A single-center open two-cycle trial was conducted on 12 healthy subjects who received a single oral dose of 120 mg of bismuth potassium citrate. The plasma concentration of bismuth was determined using a validated inductively coupled plasma mass spectrometry (ICP‒MS) method. The pharmacokinetic parameters, including maximum serum concentration (C(max)) and area under the curve concentration-time curve (AUC(0-t) and AUC(0-∞)), and safety were evaluated via noncompartment analysis. RESULTS: The ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for C(max), AUC(0-t), and AUC(0-∞) were 44.8%, 55.5%, and 64.4%, respectively; the bilateral 95% confidence intervals (Cis) for these parameters were 20.2-99.6%, 24.1-127.5%, and 23.7-175.0%, respectively, and the non-inferior limits for these parameters were 169.4%, 198.8%, and 200.5%, respectively. The upper limits of the one-sided 97.5% confidence interval for the least squares geometric mean ratio (T/R) were lower than the non-inferior limits. No serious adverse reactions or adverse reactions leading to detachment were observed among the subjects. CONCLUSION: The concentration of bismuth in the blood of healthy subjects in the T formulation was not greater than that in the R formulation. Similarly, the safety of oral administration of 120 mg of bismuth potassium citrate formulations to healthy subjects was good. The trial registration number (TRN) was [2018] 013, 6 December 2018.
期刊:
Applied Radiation and Isotopes,2024年205:111145 ISSN:0969-8043
通讯作者:
Xie, SB
作者机构:
[Xie, Shuibo; Mai, Yingqing; Wang, Guohua; Zhang, Haibo] Univ South China, Sch Civil Engn, Hengyang 421001, Peoples R China.;[Xie, Shuibo] Univ South China, Key Discipline Lab Natl Def Biotechnol Uranium Min, Hengyang 421001, Peoples R China.;[Wang, Shuiyun] Nonferrous Met Design & Res Inst, Changsha 410000, Peoples R China.;[Xie, Shuibo] Univ South China, 28 Changshen Rd, Zhengxiang Dist, Hengyang 421001, Peoples R China.
通讯机构:
[Xie, SB ] U;Univ South China, 28 Changshen Rd, Zhengxiang Dist, Hengyang 421001, Peoples R China.
关键词:
Acid wastewater;Adsorption;PT-CS;U(VI)
摘要:
With sodium tripolyphosphate (STPP) as cross-linker, Persimmon tannin-chitosan microspheres (PT-CS) were synthesized by hydrothermal for removing U(VI) from acidic effluent. The batch experiments indicated that PT-CS adsorbed U(VI) most effectively at pH 1.5, the maximum adsorption capacity for PT-CS was 245mg/g. Compared to pure CS dissolved at pH 3, PT-CS still maintain high stability at pH 1. Moreover, single system of common metal ions in rare earth wastewater only slightly affected the adsorption of uranium at pH 1.5, but this process was inhibited about 30% at pH 5. Those results indicated that the selectivity of PT-CS for uranium removal could be controlled by regulating the pH and there are excellent potentials for PT-CS using in acid metal water treatment. Its adsorption selectivity and ability to adapt different condition was demonstrated with uraniferous rare earth wastewater treatment. The adsorption for PT-CS to U(VI) were well fitted for both Langmuir isothern and pseudo-secondary kinetic model equations, and that meant chemisorption dominated the removal process. Spectroscopic analyses confirmed that the adsorption of U(VI) occurred via surface complexation by -OH and ion exchange with Na(+). Therefore, this study provides a high-efficiency, low-cost, valuable and highly adaptable method for the treatment of acidic uranium-containing effluents.
摘要:
In the classical route of synthesizing of avanafil, the last step of the reaction uses EDCI and HOBT as an acid and amine binding agent. HOBT may contain residues of hydrazine, and potential mutagenic impurities containing acylhydrazide structures may be formed. The intermediate product (M6) of avanafil was synthesized by 6 steps using diethyl ethoxylmethylmalonate and S-methyl isothiourea semisulfide as starting materials. The potentially genotoxic impurity E (Imp-E) of avanafil was given by the reaction of M6 and hydrazine sulfate acid amine, yield of 20%. The single crystal of Imp-E was cultivated by solvent volatilization method, and its structure was analyzed by high resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectroscopy (NMR). The Flack parameter of Imp-E was -0.03(3) by X-ray single crystal diffraction analysis, and the absolute configuration of Imp-E was determined as S configuration. The intramolecular / intermolecular hydrogen bonds of Imp-E make the molecules maintain a stable arrangement in space.
关键词:
cancer therapy;cellular metabolism;ferroptosis inducer;ferroptosis
摘要:
Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron-dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.
期刊:
Annals of Clinical and Translational Neurology,2024年11(1):57-66 ISSN:2328-9503
通讯作者:
Zhou, HC
作者机构:
[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha 410013, Peoples R China.;[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Inst Pain Med, Changsha 410013, Peoples R China.;[Chen, Li] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Anesthesiol, Changsha 410028, Peoples R China.;[Zhou, Haocheng; Huang, Dong] Cent South Univ, Hunan Key Lab Brain Homeostasis, Changsha 410013, Peoples R China.;[Huang, Yuzhao] Cent South Univ, Xiangya Hosp 3, Dept Orthopaed, Changsha 410013, Hunan, Peoples R China.
通讯机构:
[Zhou, HC ] C;Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha, Peoples R China.;Cent South Univ, Inst Pain Med, Changsha, Peoples R China.
摘要:
AIM: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain. It is necessary to identify the responders of SCS analgesia before implantation. The aim of this study is to investigate the relationship between the cortical dynamics and SCS analgesia responders in pain management. METHODS: Resting-state EEG recording was performed in patients who underwent short-term implantation of spinal cord stimulation for pain therapy. We then did spectral analysis to capture the pattern of cortical oscillation between neuromodulation therapy analgesia responders and nonresponders. RESULTS: About 58.3% (14 out of 24) of participants were considered as analgesia responders, with average visual analogue scores reduction of 4.8 ± 1.0 after surgery, and 2.1 ± 0.7 for the nonresponder subgroup, respectively. The alpha oscillation was significantly enhanced in responder cohort compared with nonresponders. We also observed an increasing spectral power of gamma band in responders. Furthermore, the attenuation of pain severity was significantly correlated with the global alpha oscillation activity (r = 0.60, P = 0.002). Likely, positive and significant correlation was found between the pain relief and gamma activity (r = 0.58, P = 0.003). CONCLUSIONS: Distinct pattern of neural oscillation is associated with the analgesic effect of spinal cord stimulation in pain management, enhancement of cortical alpha and gamma oscillation may be a predictor of analgesia responders.
摘要:
The herbicide glyphosate, N-(phosphonomethyl)glycine, has been widely used in the past 40 years, and has had many adverse effects on human health. Here, we constructed a convenient "on-off-on" fluorescent platform for detection of glyphosate via Cu(2+) modulated squaraine dye fluorescence quenching. The squaraine dye F-0 exhibited strong fluorescence, which could be quenched by the addition of Cu(2+). However, the addition of glyphosate restored the fluorescence intensity of F-0 due to the formation of a Cu(2+)-glyphosate complex. F-0 was utilized as a fluorescent probe for the quantitative detection of glyphosate, with the lowest detection limit of 13.16 nmol L(-1). Furthermore, this method demonstrated high selectivity and anti-interference capabilities. The successful monitoring of glyphosate in real samples was achieved using this detection strategy.
摘要:
A novel polyvinyl alcohol-carbon nanotube containing an imidazolyl ionic liquid/chitosan composite hydrogel (termed CBCS) was prepared for highly selective uranium adsorption from seawater. The results show that CBCS has good adsorption properties for uranium within the pH range of 5.0-8.0. Kinetics and thermodynamics experiments show that the theoretical maximum adsorption capacity of CBCS to U(VI) is 496.049mg/g (288K, pH=6.0), indicating a spontaneous exothermic reaction. Mechanism analysis shows that the hydroxyl group, amino group, and CN bond on the surface of CBCS directly participate in uranium adsorption and that the dense pores on the surface of CBCS play an important role in uranium adsorption. The competitive adsorption experiment shows that CBCS has excellent uranium adsorption selectivity. In addition, CBCS exhibits good reusability. After five adsorption-desorption cycles, the uranium adsorption rate of CBCS can still reach >98%. Hence, CBCS has excellent potential for uranium extraction from seawater.
摘要:
There is a body of evidence to suggest that chronic stress modulates neurochemical homeostasis, alters neuronal structure, inhibits neurogenesis and contributes to development of mental disorders. Chronic stress-associated mental disorders present common symptoms of cognitive impairment and depression with complex disease mechanisms. P-coumaric acid (p-CA), a natural phenolic compound, is widely distributed in vegetables, cereals and fruits. p-CA exhibits a wide range of health-related effects, including anti-oxidative-stress, anti-mutagenesis, anti-inflammation and anti-cancer activities. The current study aims to evaluate the therapeutic potential of p-CA against stress-associated mental disorders. We assessed the effect of p-CA on cognitive deficits and depression-like behavior in mice exposed to chronic restraint stress (CRS); we used network pharmacology, biochemical and molecular biological approaches to elucidate the underlying molecular mechanisms. CRS exposure caused memory impairments and depression-like behavior in mice; p-CA administration attenuated these CRS-induced memory deficits and depression-like behavior. Network pharmacology analysis demonstrated that p-CA was possibly involved in multiple targets and a variety of signaling pathways. Among them, the protein kinase A (PKA) - cAMP-response element binding protein (CREB) - brain derived neurotrophic factor (BDNF) signaling pathway was predominant and further characterized. The levels of PKA, phosphorylated CREB (pCREB) and BDNF were significantly lowered in the hippocampus of CRS mice, suggesting disruption of the PKA-CREB-BDNF signaling pathway; p-CA treatment restored the signaling pathway. Furthermore, CRS upregulated expression of proinflammatory cytokines in hippocampus, while p-CA reversed the CRS-induced effects. Our findings suggest that p-CA will offer therapeutic benefit to patients with stress-associated mental disorders.