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Metallic zinc exhibits immense potential as an anode material for aqueous rechargeable zinc batteries due to its high theoretical capacity, low redox potential, and inherent safety. However, practical applications are hindered by dendrite formation and poor cycling stability. Herein, a facile substitution reaction method is presented to fabricate a 3D leaf-like Cu@Zn composite anode. This unique architecture, featuring a 3D network of leaf-like Cu on a Zn foil surface, significantly reduces nucleation overpotential and facilitates uniform Zn plating/stripping, effectively suppressing dendrite growth. Notably, an alloy layer of CuZn5 forms in situ on the 3D Cu layer during cycling. DFT calculations reveal that this CuZn5 alloy possesses a lower Zn binding energy compared to both Cu and Zn metal, further promoting Zn plating/stripping and enhancing electrochemical kinetics. Consequently, the symmetric Cu@Zn electrode exhibits remarkable cycling stability, surpassing 1300 h at 0.5 mA cm-2 with negligible dendrite formation. Furthermore, full cells comprising Cu@Zn||VO2 exhibit superior capacity and rate performance compared to bare Zn anodes. This work provides a promising strategy for constructing highly stable and efficient Zn anodes for next-generation aqueous zinc batteries.
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N-type PbSe thermoelectric materials encounter challenges in improving the power factor due to the single-band structure near the Fermi level, which obstructs typical band convergence. The primary strategy for enhancing the thermoelectric figure of merit (ZT) for n-type PbSe involves reducing lattice thermal conductivity (κlat) by introducing various defect structures. However, lattice mismatches resulting from internal defects within the matrix can diminish carrier mobility, thereby affecting electrical transport properties. In this study, n-type AgCuTe-alloyed PbSe systems achieve a peak ZT value of ≈1.5 at 773 K. Transmission electron microscopy reveals nanoprecipitates of Ag2Te, the room temperature second phase of AgCuTe, within the PbSe matrix. Meanwhile, a unique semi-coherent phase boundary is observed between the PbSe matrix and the Ag2Te nanoprecipitates. This semi-coherent phase interface effectively scatters low-frequency phonons while minimizing damage to carrier mobility. Additionally, the dynamic doping effect of Cu atoms from the decomposition of AgCuTe within the matrix further optimize the high-temperature thermoelectric performance. Overall, these factors significantly enhance the ZT across the whole temperature range. The ZT value of ≈1.5 indicates high competitiveness compared to the latest reported n-type PbSe materials, suggesting that these findings hold promise for advancing the development of efficient thermoelectric systems.
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Direct analysis of solid samples is always challenging for ionic sensors due to solidified elemental presence and matrix interference. In this work, a "three-phase transforming" technique was first established to make solid sampling elemental sensors and visual detection possible in the future. For Cd transforming from soil samples, a metal ceramic heater (MCH) electrothermal vaporizer (ETV) coupled with a dielectric barrier discharge quartz trap (DBD-QT) was first utilized to fulfill the solid sampling and preconcentration of Cd in soil; for on-site analysis, a colorimetric sensor based on the trithiocyanuric acid (TMT) functionalized gold nanoparticles (AuNPs) was chosen as a chromogenic analysis model. The portable and miniature ETV-DBD apparatus directly introduced Cd from soil and then captured Cd, consuming only <130 W and 4.5 kg weight; finally, only 200 µL water was injected as eluent to dissolve Cd for the following colorimetric detection. Herein, the Cd analyte underwent a "three-phase transforming" from solid (Cd compounds in soil), to aerosol (vaporization and transportation), to solid (Cd oxides trapped on quartz surface) and to liquid (Cd2+ in eluate). Under optimized conditions, the method limit of detection (LOD) reached 0.04 mg/kg Cd (50 mg sample), fulfilling fast monitoring of Cd contamination in soil, with <20 % relative standard deviations (RSDs). The analysis time was <10 min excluding sample digestion and acid application, as well as the interference of Pb2+ on the AuNPs sensor can be eliminated via the "three-phase transforming" process, proving an excellent anti-interference for solid analysis. This "three-phase transforming" processing technique coupled with colorimetric sensor holds a great potential for direct and on-site analysis in solid samples without complicated handling, providing a fantastic methodology for the application of ionic sensors and making solid sampling elemental sensor and visual detection possible.
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Myocardial infarction (MI) is a life-threatening cardiovascular disease that, on average, results in 8.5 million deaths worldwide each year. Timely revascularization of occluded vessels is a critical method of myocardial salvage. However, reperfusion paradoxically leads to the worsening of myocardial damage known as myocardial ischaemia/reperfusion injury (MI/RI). Therefore, reducing the size of myocardial infarction after reperfusion is critical and remains an important therapeutic goal. The susceptibility of the myocardium to MI/RI may be increased by diabetes. Currently, some traditional antidiabetic agents such as metformin reduce MI/RI by decreasing inflammation, inhibiting oxidative stress, and improving vascular endothelial function. This appears to be a new direction for the treatment of MI/RI. Recent cardiovascular outcome trials have shown that several oral antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sodium-glucose-linked transporter-2 inhibitors (SGLT-2is), not only have good antidiabetic effects but also have a protective effect on myocardial protection. This article aims to discuss the mechanisms and effects of oral antidiabetic agents, including GLP-1RAs, DPP-4is, and SGLT-2is, on MI/RI to facilitate their clinical application.
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Inibidores da Dipeptidil Peptidase IV , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Traumatismo por Reperfusão Miocárdica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Administração Oral , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
BACKGROUND: Postmenopausal osteoporosis (PMOP) greatly increases the risk of bone fracture in postmenopausal women, seriously affects the quality of life of patients, and is an important global public health problem. Persistent chronic systemic inflammation may be involved in the change process of PMOP, and many cytokines, such as TNF-alpha and Interleukin-6, play an important role in the inflammatory response. Therefore, This study takes commonly representative inflammatory factors as indicators to better determine their role in PMOP patients by means of databases from multiple studies for use in Meta-analysis.
Method: Systematic review of studies on the relationship between PMOP and markers of inflammation: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Each effect size was expressed with a 95% confidence interval (CI), and I2 quantified the heterogeneity. The final results were aggregated and evaluated using random or fixed effects models. Results: Twenty-one original studies were identified. There were twenty studies involving IL-6 and eleven involving TNF-α. Overall, The levels of IL-6 [MD=23.93, 95% CI (19.65, 28.21)] and TNF-α [MD=2.9, 95% CI (2.37, 3.44)] were increased in PMOP patients compared with postmenopausal women without osteoporosis; The levels of IL-6 [MD=42.4, 95% CI (38.62, 46.19)] and TNF-α [MD=0.40, 95% CI (0.36, 0.44)] were significantly higher than those of premenopausal healthy women. Conclusions: The levels of inflammatory cytokines IL-6 and TNF-α were significantly increased in PMOP patients compared with controls, suggesting that persistent chronic inflammatory reaction exists in PMOP patients, which may be an important cause of aggravated osteoporosis in postmenopausal women. Therefore, the level of IL-6 and TNF-α indexes may be of great significance for the early prevention, diagnosis, treatment and prognosis assessment of PMOP.Assuntos
Interleucina-6 , Osteoporose Pós-Menopausa , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/sangue , FemininoRESUMO
Colloidosomes are microcapsules whose shells are composed of cumulated or fused colloidal particles. When colloidosomes are used for in situ encapsulation, it is still a challenge to achieve a high encapsulation efficiency and controllable release by an effective fabrication method. Herein, we present a highly efficient route for the large-scale preparation of colloidosomes. The biodegradable polylactic acid (PLA) nanoparticles (NPs) as shell materials can be synthesized using an antisolvent precipitation method, and the possible formation mechanism was given through the molecular dynamics (MD) simulation. The theoretical values are basically consistent with the experimental results. Through the use of the modified and unmodified PLA NPs, the colloidosomes with controllable shell porosities can be easily constructed using spray drying technology. We also investigate the mechanism of colloidosomes successfully self-assembled by PLA NPs with various factors of inlet temperature, feed rate, and flow rates of compressed air. Furthermore, avermectin (AVM) was used as a model for in situ encapsulation and a controllable release. The spherical modified colloidosomes encapsulating AVM not only achieve a small mean diameter of 1.57 µm but also realize a high encapsulation efficiency of 89.7% and impermeability, which can be further verified by the MD simulation. AVM molecules gather around and clog the shell pores during the evaporation of water molecules. More importantly, the PLA colloidosomes also reveal excellent UV-shielding properties, which can protect AVM from photodegradation.
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RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.
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The relevance of biopterin metabolism in resistance to immune checkpoint blockade (ICB) therapy remains unknown. We demonstrate that the deficiency of quinoid dihydropteridine reductase (QDPR), a critical enzyme regulating biopterin metabolism, causes metabolite dihydrobiopterin (BH2) accumulation and decreases the ratio of tetrahydrobiopterin (BH4) to BH2 in pancreatic ductal adenocarcinomas (PDACs). The reduced BH4/BH2 ratio leads to an increase in reactive oxygen species (ROS) generation and a decrease in the distribution of H3K27me3 at CXCL1 promoter. Consequently, myeloid-derived suppressor cells are recruited to tumor microenvironment via CXCR2 causing resistance to ICB therapy. We discovered that BH4 supplementation is capable to restore the BH4/BH2 ratio, enhance anti-tumor immunity, and overcome ICB resistance in QDPR-deficient PDACs. Tumors with lower QDPR expression show decreased responsiveness to ICB therapy. These findings offer a novel strategy for selecting patient and combining therapies to improve the effectiveness of ICB therapy in PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/metabolismo , Humanos , Animais , Camundongos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Microambiente Tumoral , Linhagem Celular Tumoral , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos Endogâmicos C57BL , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Feminino , Masculino , Espécies Reativas de Oxigênio/metabolismoRESUMO
N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.