摘要:
Nanomedicine is revolutionizing precision medicine, providing targeted, personalized treatment options. Lipid-based nanomedicines offer distinct benefits including high potency, targeted delivery, extended retention in the body, reduced toxicity, and lower required doses. These characteristics make lipid-based nanoparticles ideal for drug delivery in areas such as gene therapy, cancer treatment, and mRNA vaccines. However, traditional bulk synthesis methods for LNPs often produce larger particle sizes, significant polydispersity, and low encapsulation efficiency, which can reduce the therapeutic effectiveness. These issues primarily result from uneven mixing and limited control over particle formation during the synthesis. Microfluidic technology has emerged as a solution, providing precise control over particle size, uniformity, and encapsulation efficiency. In this mini review, we introduce the state-of-the-art microfluidic systems for lipid-based nanoparticle synthesis and functionalization. We include the working principles of different types of microfluidic systems, the use of microfluidic systems for LNP synthesis, cargo encapsulation, and nanomedicine delivery. In the end, we briefly discuss the clinical use of LNPs enabled by microfluidic devices.
摘要:
Cervical cancer (CC) is a significant global health issue and remains one of the leading causes of cancer-related mortality in women. Radiotherapy is a crucial treatment modality for CC; however, tumor heterogeneity and resistance to radiotherapy often result in suboptimal outcomes for some patients, including recurrence and metastasis. Periostin (POSTN), a matricellular protein within the tumor microenvironment, has been implicated in the promotion of tumor progression and treatment resistance, particularly through mechanisms such as epithelial-mesenchymal transition (EMT). Despite this, the role of POSTN in radiotherapy resistance in CC patients remains underexplored. Therefore, in this study, we investigated the prognostic significance of POSTN expression in CC patients undergoing radical radiotherapy and explored potential mechanisms underlying radiotherapy resistance. We analyzed data from 92 CC patients in The Cancer Genome Atlas (TCGA) and 153 patients from our institution, assessing POSTN expression levels through mRNA analysis and immunohistochemistry (IHC). Our findings revealed that high POSTN expression was significantly associated with advanced tumor stages, poorer radiotherapy outcomes, and worse overall survival (OS). Additionally, multivariate Cox regression analysis identified POSTN as an independent prognostic factor for CC patients undergoing radical radiotherapy. A prognostic nomogram integrating POSTN expression and clinicopathological features demonstrated superior predictive accuracy for OS. Drug sensitivity analysis suggested that high POSTN expression may be linked to resistance to multiple chemotherapeutic agents. Furthermore, weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified EMT as a top enriched pathway in patients with high POSTN expression, suggesting it may play a critical role in radiotherapy resistance. Subsequently, in vitro experiments confirmed that POSTN knockdown significantly inhibited HeLa cell proliferation, invasion, and enhanced radiosensitivity, while promoting apoptosis. These findings indicate that high POSTN expression is a risk factor for poor prognosis in CC patients undergoing radical radiotherapy, and targeting POSTN may improve radiotherapy efficacy by reducing tumor proliferation and resistance.
摘要:
Bacterial infectious diseases pose a serious threat to the safety of human life. It is urgent to development a simple, rapid, efficient and safe precise diagnostic methods and synergistic therapy techniques for combating bacteria. Herein, we synthesize CuInSe 2 quantum dots with near-infrared (NIR) emission peak at 1190 nm upon excitation at 808 nm and shifted to 1026 nm after the incorporation of ZnS. Then, Vancomycin was modified on the hydrophilic CuInSe 2 /ZnS quantum dots to obtain a fluorescent nano biological probe (Van-CuInSe 2 /ZnS) that can target Staphylococcus aureus, which was used to monitor the bacterial infection process in vivo in real time. Moreover, the nanosystem possesses excellent photothermal conversion properties, and biocompatibility, which enables precise, targeted NIR-II fluorescent imaging of bacterial inflammation in vivo as well as effectively cure subcutaneous bacterial infection and wound bacterial infection in mice. It shows great potential in the treatment of bacterial infectious diseases.
Bacterial infectious diseases pose a serious threat to the safety of human life. It is urgent to development a simple, rapid, efficient and safe precise diagnostic methods and synergistic therapy techniques for combating bacteria. Herein, we synthesize CuInSe 2 quantum dots with near-infrared (NIR) emission peak at 1190 nm upon excitation at 808 nm and shifted to 1026 nm after the incorporation of ZnS. Then, Vancomycin was modified on the hydrophilic CuInSe 2 /ZnS quantum dots to obtain a fluorescent nano biological probe (Van-CuInSe 2 /ZnS) that can target Staphylococcus aureus, which was used to monitor the bacterial infection process in vivo in real time. Moreover, the nanosystem possesses excellent photothermal conversion properties, and biocompatibility, which enables precise, targeted NIR-II fluorescent imaging of bacterial inflammation in vivo as well as effectively cure subcutaneous bacterial infection and wound bacterial infection in mice. It shows great potential in the treatment of bacterial infectious diseases.
期刊:
Journal of Cleaner Production,2025年492:144883 ISSN:0959-6526
通讯作者:
Jiajie Zhang
作者机构:
[Chuqiao Wang; Chaowei Kang; Shuiming Liu; Shan Huang; Yuying Hu; Jiajie Zhang] School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, 330013, China;[Xizi Long] Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Shuai Zhang] Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control (AEMPC), Collaborative Innovation Center of Atmospheric Environment and Equipment Technology (CIC-AEE'T), Nanjing University of Information Science & Technology, Naning, 210044, China
通讯机构:
[Jiajie Zhang] S;School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, 330013, China
摘要:
Suppressing temperature stratification is crucial for pilot-scale methanogenic reactor (MR) in two-phase anaerobic digestion. In this study, computational fluid dynamics was utilized to simulate changes in temperature distribution under various heating and hydraulic stirring conditions within the MR. Elevating heating temperature accelerated the process of the MR reaching the set temperature (35.5 °C). However, excessively high heating temperature led to significant temperature differences. The maximum temperature difference varied from 2.15 °C to 4 °C when heating temperature ranged from 45 °C to 75 °C, respectively. Hydraulic stirring effectively mitigated temperature distribution, reducing the maximum temperature difference from 3 °C to 1 °C at stirring speed of 0.31 m/s when heating temperature was maintained at 55 °C. The standard deviation of the temperatures at points P1-P5 and the average temperature decreased from 0.22 at 0.11 m/s to 0.076 at 0.31 m/s. Consequently, cumulative biogas production of the MR increased from 8.085 m³ to 12.975 m³ after implementing hydraulic stirring. Microbial community analysis revealed that methanogens were more susceptible to the effects of temperature distribution compared to bacteria. This study provides guidance for practical project implementations.
Suppressing temperature stratification is crucial for pilot-scale methanogenic reactor (MR) in two-phase anaerobic digestion. In this study, computational fluid dynamics was utilized to simulate changes in temperature distribution under various heating and hydraulic stirring conditions within the MR. Elevating heating temperature accelerated the process of the MR reaching the set temperature (35.5 °C). However, excessively high heating temperature led to significant temperature differences. The maximum temperature difference varied from 2.15 °C to 4 °C when heating temperature ranged from 45 °C to 75 °C, respectively. Hydraulic stirring effectively mitigated temperature distribution, reducing the maximum temperature difference from 3 °C to 1 °C at stirring speed of 0.31 m/s when heating temperature was maintained at 55 °C. The standard deviation of the temperatures at points P1-P5 and the average temperature decreased from 0.22 at 0.11 m/s to 0.076 at 0.31 m/s. Consequently, cumulative biogas production of the MR increased from 8.085 m³ to 12.975 m³ after implementing hydraulic stirring. Microbial community analysis revealed that methanogens were more susceptible to the effects of temperature distribution compared to bacteria. This study provides guidance for practical project implementations.
摘要:
In this work, a multifunctional Pd@Au nanoframe hydrogel was designed to detect uric acid (UA) for in situ monitoring of wound infection and enhance wound healing by a chemo-photothermal strategy. In acidic conditions, the Pd@Au nanoframe hydrogels show high peroxidase-like activity by catalyzing H(2)O(2) to produce reactive oxygen species (ROS) to damage RNAs of bacteria and enhance antibacterial activity. Under Near-infrared (NIR) laser irradiation, the Pd@Au nanoframe hydrogels exhibit photothermal conversion performance; i.e., the color of Pd@Au nanoframe hydrogel solution varies from deep blue (0 s, 25.4 °C) to red (300 s, 50.1 °C) in infrared thermography. After loading the antibacterial mupirocin (M), the as-obtained M Pd@Au nanoframe hydrogels show a maximum cumulative release rate exceeding 90% for mupirocin, as controlled by NIR laser irradiation. In antimicrobial experiments in vitro, M Pd@Au nanoframe hydrogels exhibit NIR laser-driven antibacterial ability; i.e., 98% Escherichia coli are effectively killed in 10 min. After coating rabbit wounds with a UA sensing patch of M Pd@Au nanoframe hydrogels, wound status can be monitored in real time by detecting UA concentration, leading to rapid wound healing in 4 days by a new synergistic effect of chemo-photothermal strategy. This approach successfully confirms a closed-loop strategy, i.e., real-time monitoring the status of a wound and efficiently perform chemo-photothermal wound therapy, for wound healing by combining functional hydrogels, NIR laser irradiation, and pharmaceutical antibacterials.
作者机构:
[Qiuhua Zhou; Xiangsheng Tian; Yujun Ning; Yuwei Mao; Weichao Zhao; Dingxin Long] School of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China;Department of nutrition, The First People's Hospital of Chenzhou, Chenzhou 423000, China;[Yiquan Ou] School of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China<&wdkj&>Department of nutrition, The First People's Hospital of Chenzhou, Chenzhou 423000, China
通讯机构:
[Dingxin Long] S;School of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China
摘要:
Objective To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms.
To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms.
Methods Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR + Rg1, Rg1), IR + Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 d, followed by single-dose irradiation of 5 Gy X-ray irradiation (2 Gy/min) for the IR and IR + Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis.
Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR + Rg1, Rg1), IR + Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 d, followed by single-dose irradiation of 5 Gy X-ray irradiation (2 Gy/min) for the IR and IR + Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis.
Results Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ± 1.62 vs. IR + Rg1: 33.93 ± 2.20, t = −13.23, P < 0.05), and reduced sperm malformation rates (IR: 46.33 ± 2.18 vs. IR + Rg1: 39.00 ± 1.67, t = 7.33, P < 0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ± 0.28 vs. IR + Rg1: 1.81 ± 0.18, t = 1.40, P < 0.05) and modulated serum testosterone (IR: 4.47 ± 0.23 vs. IR + Rg1: 6.65 ± 0.09, t = −2.18, P < 0.05), GnRH (IR: 24.37 ± 0.92 vs. IR + Rg1: 32.98 ± 1.33, t = −8.61, P < 0.05), and FSH levels (IR: 1.41 ± 0.11 vs. IR + Rg1: 2.69 ± 0.21, t = −1.28, P < 0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice.
Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ± 1.62 vs. IR + Rg1: 33.93 ± 2.20, t = −13.23, P < 0.05), and reduced sperm malformation rates (IR: 46.33 ± 2.18 vs. IR + Rg1: 39.00 ± 1.67, t = 7.33, P < 0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ± 0.28 vs. IR + Rg1: 1.81 ± 0.18, t = 1.40, P < 0.05) and modulated serum testosterone (IR: 4.47 ± 0.23 vs. IR + Rg1: 6.65 ± 0.09, t = −2.18, P < 0.05), GnRH (IR: 24.37 ± 0.92 vs. IR + Rg1: 32.98 ± 1.33, t = −8.61, P < 0.05), and FSH levels (IR: 1.41 ± 0.11 vs. IR + Rg1: 2.69 ± 0.21, t = −1.28, P < 0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice.
Conclusions Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.
Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.
摘要:
Microcystin LR (MC-LR) pollution is a serious threat to aquatic ecosystems and public health in China and is an environmental problem that urgently needs to be solved. However, few studies have investigated the anaerobic degradation pathway and related molecular biological mechanisms of MC-LR. In this study, a bacterium capable of degrading MC-LR with a degradation efficiency of 0.303 µg/mL/d under anaerobic conditions was isolated from water. The strain was identified as Alcaligenes and named Alcaligenes faecalis D04. Two new anaerobic degradation products, one pentapeptide (Adda-Glu-Mdha-Ala-Leu) and one tripeptide (Adda-Glu-Mdha), were identified by chromatography and mass spectrometry, and two new anaerobic degradation pathways for microcystins were proposed. This study revealed a new connection between related functional genes ( mblH , ridA , paaA , livI , soxR , gltD , marR , etc.) and bacterial degradation functions through the analysis of multiomics data. Real-time quantitative PCR analysis verified that the expression trends of the differentially expressed genes were consistent with the transcriptomic data. Our study aimed to elucidate the anaerobic degradation pathway and molecular regulatory mechanism of MC-LR in Alcaligenes faecalis D04, which offers important practical significance for microbial strategies to prevent and regulate microcystin contamination.
Microcystin LR (MC-LR) pollution is a serious threat to aquatic ecosystems and public health in China and is an environmental problem that urgently needs to be solved. However, few studies have investigated the anaerobic degradation pathway and related molecular biological mechanisms of MC-LR. In this study, a bacterium capable of degrading MC-LR with a degradation efficiency of 0.303 µg/mL/d under anaerobic conditions was isolated from water. The strain was identified as Alcaligenes and named Alcaligenes faecalis D04. Two new anaerobic degradation products, one pentapeptide (Adda-Glu-Mdha-Ala-Leu) and one tripeptide (Adda-Glu-Mdha), were identified by chromatography and mass spectrometry, and two new anaerobic degradation pathways for microcystins were proposed. This study revealed a new connection between related functional genes ( mblH , ridA , paaA , livI , soxR , gltD , marR , etc.) and bacterial degradation functions through the analysis of multiomics data. Real-time quantitative PCR analysis verified that the expression trends of the differentially expressed genes were consistent with the transcriptomic data. Our study aimed to elucidate the anaerobic degradation pathway and molecular regulatory mechanism of MC-LR in Alcaligenes faecalis D04, which offers important practical significance for microbial strategies to prevent and regulate microcystin contamination.
摘要:
In this research, a new synthesis approach was developed for an adsorbent, namely the phosphorylated ZIF-8/bamboo charcoal/chitosan/tannic acid (P-ZBCT) composite, for the efficient adsorption of uranyl ions from wastewater at low dosages. Impressively, the uranium adsorption rate of P-ZBCT reaches up to 98 % at a low dosage of 0.056 g/L in a 10-mg/L uranium solution, outperforming most reported uranium adsorption materials. The theoretical maximum adsorption capacity of P-ZBCT for uranium at 308 K and pH 6.0 is 2357.69 mg/g, with uranium adsorption being a spontaneous endothermic chemical reaction. Mechanistic analysis reveals that surface functional groups such as P O, amino group, and C N play a pivotal role in uranium adsorption. A competitive adsorption experiment shows that zinc is the most competitive with uranium adsorption; however, the partition coefficient of U is 11 times that of zinc, indicating that the absorption of uranium is more selective than that of other metal ions, such as zinc. Adsorption treatment using P-ZBCT successfully reduces the uranium content in real uranium tailings–containing pond wastewater to 34 μg/L. P-ZBCT demonstrates exceptional recycling performance, maintaining an adsorption rate of 85 % even after 10 sorption–desorption cycles. Therefore, P-ZBCT exhibits significant potential for efficiently extracting uranium from low-concentration uranium-containing wastewater.
In this research, a new synthesis approach was developed for an adsorbent, namely the phosphorylated ZIF-8/bamboo charcoal/chitosan/tannic acid (P-ZBCT) composite, for the efficient adsorption of uranyl ions from wastewater at low dosages. Impressively, the uranium adsorption rate of P-ZBCT reaches up to 98 % at a low dosage of 0.056 g/L in a 10-mg/L uranium solution, outperforming most reported uranium adsorption materials. The theoretical maximum adsorption capacity of P-ZBCT for uranium at 308 K and pH 6.0 is 2357.69 mg/g, with uranium adsorption being a spontaneous endothermic chemical reaction. Mechanistic analysis reveals that surface functional groups such as P O, amino group, and C N play a pivotal role in uranium adsorption. A competitive adsorption experiment shows that zinc is the most competitive with uranium adsorption; however, the partition coefficient of U is 11 times that of zinc, indicating that the absorption of uranium is more selective than that of other metal ions, such as zinc. Adsorption treatment using P-ZBCT successfully reduces the uranium content in real uranium tailings–containing pond wastewater to 34 μg/L. P-ZBCT demonstrates exceptional recycling performance, maintaining an adsorption rate of 85 % even after 10 sorption–desorption cycles. Therefore, P-ZBCT exhibits significant potential for efficiently extracting uranium from low-concentration uranium-containing wastewater.
摘要:
BACKGROUND: This retrospective multicenter study is aimed at evaluating the diagnostic accuracy and influence factors of serum des-gamma-carboxy prothrombin (DCP) as a diagnostic biomarker of hepatocellular carcinoma (HCC). METHODS: Clinical data were collected from 4555 subjects with DCP tests, composed of primary liver cancer (PLC), metastatic liver cancer (MLC), chronic hepatitis (CH), liver cirrhosis (LC), benign liver diseases (BLD), biliary tract diseases (BTD), non-liver cancers (NLC), and non-liver benign diseases (NLBD). The clinical data collected included medical history, treatment records, various serum tests, and imaging examination. RESULTS: Serum DCP was measured with Abbott agents in each center. In HCC, serum DCP concentration was at 9086.00 ± 366.10 mAU/mL, higher than that in other diseases (p < 0.05). At 40.00 mAU/mL recommended by instruction, positive rates of serum DCP were at 85.11% in HCC, 30.12% in intrahepatic cholangiocellular carcinoma (ICC), 31.65% in MLC, 13.95% in BLD, 18.14% in CH, 27.87% in LC, 15.75% in BTD, 35.29% in NLC, and 20.00% in NLBD. In this study, the diagnostic specificity of serum DCP in HCC was affected by liver function. In HCC, serum AFP concentrations also increased compared to non-HCC diseases (p < 0.05), but specificity varied with agents from different providers. Serum DCP decreased after the surgical removal of HCC, but remained elusive in systemic treatment. CONCLUSION: Serum DCP may serve as an optimal biomarker for the diagnosis of HCC, but its accuracy appears influenced by liver function; attention needs to be paid to the liver function of patients for false positivity.
摘要:
Polycyclic aromatic hydrocarbons (PAHs), especially pyrene, are hazardous pollutants with serious health risks. Effective detection methods for PAHs are essential for environmental monitoring. In this study, we construct a simple, efficient method to detect pyrene derivatives in water. A squaraine dye (J3-Ad) with dual host-guest sites was synthesized and paired with a β-cyclodextrin dimer (H2-CD) to regulate host-guest interactions. In the presence of pyrenes, J3-Ad monomers in the the J3-Ad/H2-CD mixture (JH-AC) are displaced by pyrenes and self-assemble into H-aggregates, resulting in a ~135 nm absorption spectral shift. The transformation was confirmed through Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS), and Density Functional Theory (DFT) analysis. The system showed high sensitivity, with detection limits of 1.76 nmol/L for pyrene and 60.02 nmol/L for 1-hydroxypyrene (1-OHP), along with strong anti-interference and reliable colorimetric recognition. A smartphone-based, real-time detection platform was developed for visual monitoring of pyrene in soil and vegetables. Pyrene in tap water and river water, as well as 1-OHP in urine, were successfully detected, with recovery rates and a relative standard deviation (RSD) of less than 10.14%. This work provides a sensitive, rapid, and visual method for tracking PAH pollution, offering significant potential for practical, on-site environmental applications.
Polycyclic aromatic hydrocarbons (PAHs), especially pyrene, are hazardous pollutants with serious health risks. Effective detection methods for PAHs are essential for environmental monitoring. In this study, we construct a simple, efficient method to detect pyrene derivatives in water. A squaraine dye (J3-Ad) with dual host-guest sites was synthesized and paired with a β-cyclodextrin dimer (H2-CD) to regulate host-guest interactions. In the presence of pyrenes, J3-Ad monomers in the the J3-Ad/H2-CD mixture (JH-AC) are displaced by pyrenes and self-assemble into H-aggregates, resulting in a ~135 nm absorption spectral shift. The transformation was confirmed through Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS), and Density Functional Theory (DFT) analysis. The system showed high sensitivity, with detection limits of 1.76 nmol/L for pyrene and 60.02 nmol/L for 1-hydroxypyrene (1-OHP), along with strong anti-interference and reliable colorimetric recognition. A smartphone-based, real-time detection platform was developed for visual monitoring of pyrene in soil and vegetables. Pyrene in tap water and river water, as well as 1-OHP in urine, were successfully detected, with recovery rates and a relative standard deviation (RSD) of less than 10.14%. This work provides a sensitive, rapid, and visual method for tracking PAH pollution, offering significant potential for practical, on-site environmental applications.
通讯机构:
[Wang, FD ; Min, JX ] Z;Zhejiang Univ, Affiliated Hosp 2, State Key Lab Expt Hematol, Sch Publ Hlth,Sch Med, Hangzhou 310058, Peoples R China.;Zhejiang Univ, Affiliated Hosp 1, Inst Translat Med, Sch Med, Hangzhou 310058, Peoples R China.;Univ South China, Affiliated Hosp 1, Basic Med Sci, Hengyang Med Sch,Sch Pharmacol,Sch Publ Hlth, Hengyang 421001, Peoples R China.;Xinxiang Med Univ, Sch Publ Hlth, Sch Basic Med Sci, Xinxiang 453003, Peoples R China.
关键词:
5,15-DiHETE;5,15-dihydroxyeicosatetraenoic acid;ACSL4;HIF1α;acyl-coenzyme A synthetase long-chain family member 4;adipose tissue;ferritin;ferrology;ferroptosis;ferroptotic signaling;hypoxia-inducible factor-1α;iron metabolism;obesity
摘要:
Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function and activity. Here, we find a lower ferroptotic signature in the adipose tissue of individuals and mice with obesity. We further find that activation of ferroptotic signaling by a non-lethal dose of ferroptosis agonists significantly reduces lipid accumulation in primary adipocytes and high-fat diet (HFD)-fed mice. Notably, adipocyte-specific overexpression of acyl-coenzyme A synthetase long-chain family member 4 ( Acsl4 ) or deletion of ferritin heavy chain ( Fth ) protects mice from HFD-induced adipose expansion and metabolic disorders via activation of ferroptotic signaling. Mechanistically, we find that 5,15-dihydroxyeicosatetraenoic acid (5,15-DiHETE) activates ferroptotic signaling, resulting in the degradation of hypoxia-inducible factor-1α (HIF1α), thereby derepressing a thermogenic program regulated by the c-Myc-peroxisome proliferator-activated receptor gamma coactivator-1 beta (Pgc1β) pathway. Our findings suggest that activating ferroptosis signaling in adipose tissues might help to prevent and treat obesity and its related metabolic disorders.
Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function and activity. Here, we find a lower ferroptotic signature in the adipose tissue of individuals and mice with obesity. We further find that activation of ferroptotic signaling by a non-lethal dose of ferroptosis agonists significantly reduces lipid accumulation in primary adipocytes and high-fat diet (HFD)-fed mice. Notably, adipocyte-specific overexpression of acyl-coenzyme A synthetase long-chain family member 4 ( Acsl4 ) or deletion of ferritin heavy chain ( Fth ) protects mice from HFD-induced adipose expansion and metabolic disorders via activation of ferroptotic signaling. Mechanistically, we find that 5,15-dihydroxyeicosatetraenoic acid (5,15-DiHETE) activates ferroptotic signaling, resulting in the degradation of hypoxia-inducible factor-1α (HIF1α), thereby derepressing a thermogenic program regulated by the c-Myc-peroxisome proliferator-activated receptor gamma coactivator-1 beta (Pgc1β) pathway. Our findings suggest that activating ferroptosis signaling in adipose tissues might help to prevent and treat obesity and its related metabolic disorders.
摘要:
Construct a sensitive and rapid detection fluorescence biosensor with the assistance of exonuclease III to achieve efficient detection of Hg(2+). Nucleic acid aptamer H0 specifically recognizes Hg(2+), and under the action of exonuclease III, H0 bound to Hg(2+) is hydrolyzed, which in turn fails to trigger the catalytic hairpin self-assembly amplification reaction, resulting in a decrease in the number of double-stranded DNA bound to the fluorescent dye SYBR Green I in the solution, and a decrease in the fluorescence intensity. The results showed that the concentration of Hg(2+) showed a good linear relationship with the fluorescence intensity of the sensing system within the range of 3.8-10pmol/L, and the detection limit was 0.53pmol/L. The recoveries of Xiangjiang River water used for the analysis of the actual samples were in the range of 99.57-103.58%, and the relative standard deviations of the determined values were 2.4-3.7%. The method is simple, sensitive, specific, cost-effective and can be applied to water samples.
摘要:
BACKGROUND: This study investigates the application of a machine learning model that integrates radiomic features and dosiomic features to predict hematologic toxicity (HT) in patients with advanced cervical cancer undergoing concurrent chemoradiotherapy (CCRT). Two integration methods based on SHapley Additive exPlanations (SHAP) values for dual-radiomic features were compared. METHODS: Clinical information, planning CT images, and dose distribution files from 205 patients with advanced cervical cancer treated with CCRT were retrospectively collected. Patients were categorized by HT severity, with 80% of the data used for training and 20% for testing. Radiomic features and dosiomic features were extracted from the same regions of interest, and SHAP-based feature selection was employed. Extreme gradient boosting models were developed using two feature selection schemes: single-step and multi-step. Sensitivity, specificity, and area under the curve (AUC) values on the test set were used to evaluate model performance. RESULTS: For the single-step feature selection scheme, the best hybrid model achieved an AUC of 0.79, sensitivity of 0.67, and specificity of 0.72. For the multi-step feature selection scheme, the best hybrid model achieved an AUC of 0.81, sensitivity of 0.75, and specificity of 0.83. Furthermore, the hybrid models outperformed those using radiomic or dosiomic features alone. CONCLUSIONS: Combining radiomic and dosiomic features improves classification performance in predicting HT in patients with advanced cervical cancer undergoing CCRT, with the multi-step SHAP-based feature selection scheme offering additional advantages. These models hold promise for optimizing patient treatment strategies.
摘要:
Due to the wide uses of plastic products, nanoplastics are ubiquitous contaminants in the environment. Hence, extensive studies used various models to evaluate the toxicity of nanoplastics. In the present study, we developed yellow mealworm (Tenebrio molitor) as an alternative model to investigate the acute toxicity of nanoplastics. Our results showed that microinjection with 500 mg/kg nanoplastics significantly increased death rate of yellow mealworms after 24 or 48 h, with 100 nm particles being more effective compared with 20 nm ones. Meanwhile, dose-dependent increase of death rate was observed in yellow mealworms after injection with 2-200 mg/kg 100 nm nanoplastics. Exposure to 2 mg/kg 100 nm but not 20 nm nanoplastics also led to hyperactivity of yellow mealworms. Both types of nanoplastics altered metabolite profiles, that 20 nm nanoplastics significantly up-regulated and down-regulated 9 and 12 metabolites, whereas 100 nm nanoplastics significantly up-regulated and down-regulated 16 and 25 metabolites, respectively. Enrichment analysis revealed that 100 nm but not 20 nm nanoplastics significantly affected alpha-linolenic acid metabolism (ko00592) and purine metabolism (ko00230). For the metabolites belonging to these pathways, 100 nm nanoplastics significantly up-regulated stearidonic acid but down-regulated guanine. Combined, these results revealed size-dependent effects of nanoplastics on acute toxicity, hyperactivity and metabolite profile changes in yellow mealworms. These results also indicated the potential uses of yellow mealworms as a cheap and simple model to evaluate the toxicity of nanoplastics.
期刊:
FRONTIERS IN ENDOCRINOLOGY,2025年16:1571076 ISSN:1664-2392
作者机构:
[Lv, Ziquan; Xu, Xinyue] School of Public Health, University of South China, Hengyang, Hunan Province, China;[Tang, Zhi] School of Public Health, Guangdong Medical University, Dongguan, China;[Liang, Yin; Jia, Guixuan; Guo, Yajie] Department of Emergency Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China;[Peng, Changfeng; Wu, Yuxuan; Hu, Xiaoxiao; Chen, Ying; Liu, Guangnan; Wang, Dan] Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong Province, China;[Sang, Dan] Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
摘要:
Background: Bisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subjected to either a normal chow diet (ND) or a high-fat diet (HFD).Methods: Mice were exposed to BPAF at a concentration of 100 μg/kg every other day for five months under different dietary conditions, and body weight, rectal temperature, and food intake were monitored regularly. After the mice were sacrificed, the hepatic lipid metabolism was analyzed by measuring serum, hepatic lipids and performing hepatic metabolomics; energy metabolism was elucidated by assessing thermogenic pathways in brown adipose tissue (BAT) and factors affecting ingestion in the hypothalamus; the development and pathways of obesity were indicated by exploring lipogenesis and lipolysis pathways and fat accumulation in white adipose tissue (WAT).Results: Histomorphometric analyses indicated that BPAF exposure induced drived fat deposition in white adipose tissue through adipocyte hypertrophy-mediated pathways in eWAT of ND and HFD mice, accompanied by weight gain in HFD mice. Energy metabolism analysis showed that BPAF exposure decreased resting body temperature and reduced thermogenic factor expression in BAT of ND and HFD mice, which may affect energy expenditure. Hepatic metabolomics analysis suggested that BPAF exposure interfered with hepatic lipid metabolism in ND and HFD mice, with elevated levels of hepatic triglycerides, total cholesterol, and free fatty acids in HFD mice. Transcript analysis revealed altered expression levels of genes regulating lipid metabolism in white adipose tissue of ND and HFD mice, with a down-regulation observed in p-HSL protein expression, indicative of a potential inhibition effects of BPAF on lipolysis signaling pathway.Conclusion: Chronic BPAF exposure differentially exacerbates fat deposition in mice fed normal or high-fat diets via affecting lipid metabolism. Given the widespread prevalence of obesity and the pervasive environmental presence of BPAF, our findings provide valuable insights into the metabolic toxicity of BPAF, thereby raise further concern on the safe utilization and precision prevention of this unique chemical.
作者机构:
[Lu, Hongyu; Li, Xingli; Yu, Han; Shi, Rui; Du, Wanqing; "Wang, Bingjie; Zhong, Liyuan] Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Furong Laboratory, Xiangya School of Public Health, Central South University, 172# Tongzipo Road, Changsha, Hunan 410013, China;[Guo, Jiaojiao] Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China;[Zhou, Wen; Zhu, Yinghong; He, Nihan] Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, China;[Yang, Fei] School of Public Health, University of South China, Hengyang, Hunan 421001, China;[Yang, Fei] Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410013, China
通讯机构:
[Feng, Xiangling] H;Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Furong Laboratory, Xiangya School of Public Health, Central South University, 172# Tongzipo Road, Changsha, Hunan 410013, China. Electronic address:
摘要:
The recurrence of drug-resistant and expensive treatment drugs are major causes of the low survival rate of multiple myeloma (MM) patients. Exploring a safe, effective, low-cost and novel drug treatment for MM is a promising strategy to relieve the burden of MM patients. In this study, we found that prodigiosin could inhibit MM cell proliferation and induce MM cell apoptosis, however, it had a lesser cytotoxic effect on normal B cells within the IC 50 range of MM cells. In addition, prodigiosin could inhibit the growth of xenograft MM cells in mice. Transcriptomics and targeted amino acid metabolomics confirmed that prodigiosin could regulate amino acid metabolism, and decrease in amino acid utilization by down-regulated aminoacyl tRNA synthetases expression, resulting in slower growth of MM. In conclusion, prodigiosin exerts anticancer effects on MM cells by interfering with the use of amino acids, indicating its potential novel therapeutic application in MM.
The recurrence of drug-resistant and expensive treatment drugs are major causes of the low survival rate of multiple myeloma (MM) patients. Exploring a safe, effective, low-cost and novel drug treatment for MM is a promising strategy to relieve the burden of MM patients. In this study, we found that prodigiosin could inhibit MM cell proliferation and induce MM cell apoptosis, however, it had a lesser cytotoxic effect on normal B cells within the IC 50 range of MM cells. In addition, prodigiosin could inhibit the growth of xenograft MM cells in mice. Transcriptomics and targeted amino acid metabolomics confirmed that prodigiosin could regulate amino acid metabolism, and decrease in amino acid utilization by down-regulated aminoacyl tRNA synthetases expression, resulting in slower growth of MM. In conclusion, prodigiosin exerts anticancer effects on MM cells by interfering with the use of amino acids, indicating its potential novel therapeutic application in MM.
期刊:
FRONTIERS IN ONCOLOGY,2025年15:1524308 ISSN:2234-943X
通讯作者:
Zuo, JH
作者机构:
[Zuo, JH; Deng, Yuqi; Zuo, Jianhong; Wang, Yajie; Chen, Lili] Univ South China, Sch Publ Hlth, Dept Hlth Inspection & Quarantine, Hengyang, Peoples R China.;[Zuo, JH; Zuo, Jianhong; Li, Jiale; Yang, Jinsai] Univ South China, Comp Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Luo, Xinyu; Zuo, JH; Zuo, Jianhong; Zhang, Chaohui] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang, Peoples R China.;[Zuo, JH; Qiu, Jieya; Zuo, Jianhong; Long, Rou; Tang, Guiyang] Univ South China, Hengyang Med Sch, Transformat Res Lab, Hengyang, Hunan, Peoples R China.;[Zuo, JH; Zuo, Jianhong] Univ South China, Affiliated Hosp 3, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构:
[Zuo, JH ] U;Univ South China, Sch Publ Hlth, Dept Hlth Inspection & Quarantine, Hengyang, Peoples R China.;Univ South China, Comp Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Transformat Res Lab, Hengyang, Hunan, Peoples R China.
关键词:
alcohol use;burden of disease;colorectal cancer;high body mass index (high BMI);smoking
摘要:
BACKGROUND: Colorectal cancer (CRC) ranks among the highest in incidence and mortality rates globally. A significant portion of Colorectal cancer cases and deaths can be attributed to modifiable risk factors, with smoking, alcohol use, and high body mass index (BMI) being the three most prominent. However, the impact of these risk factors on Colorectal cancer across regions, genders, and age groups remains insufficiently characterized. METHODS: Utilizing data from the Global Burden of Disease (GBD) study 2019, restrictive cubic splines (RCS) and quantile regression analyses are applied to explore the relationship between the Socio-Demographic Index (SDI) and ASMR or ASDR. Additionally, gender differences, changes across different SDI levels, and age group trends in smoking, alcohol use, and high BMI over the 30-year period are analyzed. The Bayesian age-period-cohort (BAPC) model is employed to predict mortality trends from 2020 to 2030, aiming to explore the epidemiological and sociodemographic transitions in the Colorectal cancer disease burden attributed to smoking, alcohol use, and high BMI. RESULTS: In 2019, the number of colorectal cancer deaths globally attributable to risk factors as smoking, alcohol consumption, and obesity increased to 142,931, 52,495, and 85,882 cases respectively, collectively accounting for approximately one-third of all Colorectal cancer-related deaths. Notably, there is an upward trend in early-onset Colorectal cancer mortality associated with these factors. DISCUSSION: To reduce the burden of Colorectal cancer, it is recommended to enhance health education, promote smoking cessation and alcohol moderation, and increase the coverage and participation in Colorectal cancer screening, which are crucial for lowering Colorectal cancer mortality rates. These findings are vital for the development of public health policies and intervention measures to reduce the global disease burden. They provide guidance for Colorectal cancer prevention across different regions, genders, and age groups worldwide.
摘要:
This study reveals the transformation of the Super Uranyl-binding Protein (SUP) gene with high uranium selectivity and binding affinity into Deinococcus Radiodurans, a genetically modified bacterium with high uranium adsorption capacity and resistance to radiation. The optimal adsorption conditions and mechanism of Deino-SUP for uranium under different environmental conditions were investigated. The results demonstrated the successful construction of Deino-SUP, a recombinant strain with excellent uranium adsorption capacity and radiation resistance. The adsorption of uranium by Deino-SUP is mainly controlled by chemisorption, and the adsorption rate of uranium by Deino-SUP is better than that by Deino-wt.
作者机构:
[Long, Xizi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Key Lab Typ Environm Pollut & Hlth Hazards Hunan, Hengyang 421001, Peoples R China.;[Li, Wei-Peng; Li, WP; Ho, Chia-Lun; Long, Xizi; Okamoto, Akihiro] Natl Inst Mat Sci, Int Ctr Mat Nanoarchitecton, Tsukuba, Ibaraki 3050044, Japan.;[Kataoka-Hamai, Chiho; Ho, Chia-Lun; Okamoto, Akihiro] Natl Inst Mat Sci, Res Ctr Macromol & Biomat, 1-1 Namiki, Tsukuba, Ibaraki 3050044, Japan.;[Ho, Chia-Lun; Okamoto, Akihiro] Hokkaido Univ, Grad Sch Chem Sci & Engn, Sapporo, Hokkaido 0608628, Japan.;[Li, Wei-Peng; Huang, Wei-Lun] Natl Cheng Kung Univ, Ctr Appl Nanomed, Tainan 701, Taiwan.
通讯机构:
[Li, WP; Okamoto, A ] N;Natl Inst Mat Sci, Int Ctr Mat Nanoarchitecton, Tsukuba, Ibaraki 3050044, Japan.;Natl Inst Mat Sci, Res Ctr Macromol & Biomat, 1-1 Namiki, Tsukuba, Ibaraki 3050044, Japan.
关键词:
Liposome;Outer-membrane vesicles;Extracellular electron transport;Cytochrome;Shewanella oneidensis MR-1
摘要:
Extracellular vesicles are pivotal in intercellular communication and hold significant promise for medical applications. However, limitations in their mass production and challenges in replicating their complex functions with artificial liposomes necessitate innovative solutions. We functionalize liposomes by combining the scalable production advantages of artificial liposomes with the vesicle fusion and formation mechanisms of bacteria. By incubating the gram-negative Shewanella oneidensis MR-1, known for its electrochemically active outer membrane cytochromes (OMCs), with liposomes containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine for 24 hours, we achieved a substantial yield of membrane-integrated liposomes (MILs) incorporating OMCs. Circular dichroism spectroscopy confirmed the preservation of redox activity and strong inter-heme exciton coupling in the OMCs. These components were successfully delivered to Escherichia coli K-12 by incubation with MILs, retaining their functionality. Furthermore, the slow membrane exchange process did not result in cellular viability loss or lysis, allowing for the recycling of microbial cells and minimizing contaminants from lysed cells, which is advantageous for scaling up. Building on our previous work where MIL-coated titanium dioxide nanoparticles significantly enhanced radical production and effectively treated orthotopic liver tumors in vivo , our methodology to generate the MIL has promising potential to spearhead novel integrations of synthetic and biological systems for medical technologies.
Extracellular vesicles are pivotal in intercellular communication and hold significant promise for medical applications. However, limitations in their mass production and challenges in replicating their complex functions with artificial liposomes necessitate innovative solutions. We functionalize liposomes by combining the scalable production advantages of artificial liposomes with the vesicle fusion and formation mechanisms of bacteria. By incubating the gram-negative Shewanella oneidensis MR-1, known for its electrochemically active outer membrane cytochromes (OMCs), with liposomes containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine for 24 hours, we achieved a substantial yield of membrane-integrated liposomes (MILs) incorporating OMCs. Circular dichroism spectroscopy confirmed the preservation of redox activity and strong inter-heme exciton coupling in the OMCs. These components were successfully delivered to Escherichia coli K-12 by incubation with MILs, retaining their functionality. Furthermore, the slow membrane exchange process did not result in cellular viability loss or lysis, allowing for the recycling of microbial cells and minimizing contaminants from lysed cells, which is advantageous for scaling up. Building on our previous work where MIL-coated titanium dioxide nanoparticles significantly enhanced radical production and effectively treated orthotopic liver tumors in vivo , our methodology to generate the MIL has promising potential to spearhead novel integrations of synthetic and biological systems for medical technologies.
作者机构:
[Wang, Yuyan; Yang, F; Zeng, Ying; Pan, Jiafeng; Ren, Xiaoya; Yang, Fei] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Qiu, Jun] Hunan Childrens Hosp, Pediat Res Inst Hunan Prov, Changsha 410007, Peoples R China.
通讯机构:
[Yang, F ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
摘要:
Microcystin-lr (MC-LR) is one of the most toxic and ubiquitous microcystins (MCs) released by cyanobacteria. Exposure to MC-LR can cause multiple organ damage and even death of the organism. Therefore, creating highly sensitive and dependable methods for detecting trace MC-LR is crucial. Herein, we developed a novel fluorescence aptasensor aided by exonuclease III (Exo III) for the highly sensitive detection of MC-LR. In the presence of MC-LR, the affinity interaction between MC-LR and aptamer A was triggered, leading to the release of blocker B. This unbound blocker can initiate Exo III-mediated signal amplification to digest the probe H, thereby recovering the fluorescence signal for readout. The proposed Exo III-assisted sensing platform demonstrated remarkable sensitivity and selectivity, achieving a limit of detection (LOD) of 0.37 ng L(-1). Furthermore, it is robust and has been effectively utilized on water samples, achieving acceptable recovery rates (95.04-107.01%). With excellent sensitivity, high selectivity, efficient signal amplification, and fluorescence readout, the proposed biosensor offered a new and reliable alternative for the detection of trace MC-LR in the environment and the early warning of algal toxins.