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Immune therapy has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients, yet its efficacy remains limited, underscoring the urgency to identify new therapeutic targets and biomarkers. Here, we investigated the pathological and physiological roles of KIF20A and assess its potential in enhancing HCC treatment efficacy when combined with PD-1 inhibitors. We initially assess KIF20A's oncogenic function using liver-specific KIF20A knockout (Kif20a CKO) mouse models and orthotopic xenografts. Subsequently, we establish a regulatory axis involving KIF20A, FBXW7, and c-Myc, validated through construction of c-Myc splicing mutants. Large-scale clinical immunohistochemistry (IHC) analyses confirm the pathological relevance of the KIF20A-FBXW7-c-Myc axis in HCC. We demonstrate that KIF20A overexpression correlates with poor prognosis in HCC by competitively inhibiting FBXW7-mediated degradation of c-Myc, thereby promoting glycolysis and enhancing tumor proliferation. Conversely, KIF20A downregulation suppresses these effects, impairing tumor growth through c-Myc downregulation. Notably, KIF20A inhibition attenuates c-Myc-induced MMR expression, associated with improved prognosis in HCC patients receiving PD-1 inhibitor therapy. Furthermore, in Kif20a CKO HCC mouse models, we observe synergistic effects between Kif20a knockout and anti-PD-1 antibodies, significantly enhancing immunotherapeutic efficacy against HCC. Our findings suggest that targeting the KIF20A-c-Myc axis could identify HCC patients likely to benefit from anti-PD-1 therapy. In conclusion, we propose that combining KIF20A inhibitors with anti-PD-1 treatment represents a promising therapeutic strategy for HCC, offering new avenues for clinical development and patient stratification.
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Steering on the intrinsic active site of an electrode material is essential for efficient electrochemical biomass upgrading to valuable chemicals with high selectivity. Herein, we show that an in-situ surface reconstruction of a two-dimensional layered CdPS3 nanosheet electrocatalyst, triggered by electrolyte, facilitates efficient 5-hydroxymethylfurfural (HMF) hydrogenation to 2,5-bis(hydroxymethyl)furan (BHMF) under ambient condition. The in-situ Raman spectroscopy and comprehensive post-mortem catalyst characterizations evidence the construction of a surface-bounded CdS layer on CdPS3 to form CdPS3/CdS heterostructure. This electrocatalyst demonstrates promising catalytic activity, achieving a Faradaic efficiency for BHMF reaching 91.3 ± 2.3 % and a yield of 4.96 ± 0.16 mg/h at - 0.7 V versus reversible hydrogen electrode. Density functional theory calculations reveal that the in-situ generated CdPS3/CdS interface plays a pivotal role in optimizing the adsorption of HMF* and H* intermediate, thus facilitating the HMF hydrogenation process. Furthermore, the reconstructed CdPS3/CdS heterostructure cathode, when coupled with MnCo2O4.5 anode, enables simultaneous BHMF and formate synthesis from HMF and glycerol substrates with high efficiency.
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Single-crystal lithium-nickel-manganese-cobalt-oxide (SC-NMC) is attracting increasing attention due to its excellent structural stability. However, its practical production faces challenges associated with complex precursor preparation processes and severe lithium-nickel cation mixing at high temperatures, which restricts its widespread application. Here, a molten-salt-assisted method is proposed using low-melting-point carbonates. This method obviates the necessity for precursor processes and simplified the synthetic procedure for SC-NMC down to a single isothermal sintering step. Multiple characterizations indicate that the acquired SC-LiNi0.6Mn0.2Co0.2O2 (SC-622) exhibits favorable structural capability against intra-granular fracture and suppressive Li+/Ni2+ cation mixing. Consequently, the SC-622 exhibits superior electrochemical performance with a high initial specific capacity (174 mAh g-1 at 0.1 C, 3.0-4.3 V) and excellent capacity retention (87.5% after 300 cycles at 1C). Moreover, this molten-salt-assisted method exhibits its effectiveness in directly regenerating SC-622 from spent NMC materials. The recovered material delivered a capacity of 125.4 mAh g-1 and retained 99.4% of the initial capacity after 250 cycles at 1 C. This work highlights the importance of understanding the process-structure-property relationships and can broadly guide the synthesis of other SC Ni-rich cathode materials.
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Two-electron oxygen reduction reaction (2e- ORR) is of great significance to H2O2 production and reversible nonalkaline Zn-air batteries (ZABs). Multiple oxygen-containing sp2-bonded nanocarbons have been developed as electrocatalysts for 2e- ORR, but they still suffer from poor activity and stability due to the limited and mixed active sites at the edges as well as hydrophilic character. Herein, graphdiyne (GDY) with rich sp-C bonds is studied for enhanced 2e- ORR. First, computational studies show that GDY has a favorable formation energy for producing five-membered epoxy ring-dominated groups, which is selective toward the 2e- ORR pathway. Then based on the difference in chemical activity of sp-C bonds in GDY and sp2-C bonds in CNTs, we experimentally achieved conductive and hydrophobic carbon nanotubes (CNTs) covering O-modified GDY (CNTs/GDY-O) through a mild oxidation treatment combined with an in situ CNTs growth approach. Consequently, the CNTs/GDY-O exhibits an average Faraday efficiency of 91.8% toward H2O2 production and record stability over 330 h in neutral media. As a cathode electrocatalyst, it greatly extends the lifetime of 2e- nonalkaline ZABs at both room and subzero temperatures.
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OBJECTIVES: The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. METHODS: The CthΔskm mice and littermate Cth-floxed (Cthf/f) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle. RESULTS: Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cthf/f mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. DISCUSSION: Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.
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Cistationina gama-Liase , Dieta Hiperlipídica , Hiperglicemia , Resistência à Insulina , Músculo Esquelético , Obesidade , Animais , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , Camundongos , Obesidade/metabolismo , Cistationina gama-Liase/metabolismo , Cistationina gama-Liase/genética , Cistationina gama-Liase/deficiência , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/metabolismo , Camundongos Knockout , Masculino , Metabolismo EnergéticoRESUMO
Background: Nephronophthisis (NPHP) is a rare autosomal recessive inherited tubulointerstitial nephropathy, the most prevalent genetic cause of end-stage renal disease (ESRD) in children. Convincing evidence indicated that the overall prevalence of NPHP in adult-onset ESRD is very likely to be an underestimation. Therefore, understanding the genetic background and clinicopathologic features of adult-onset NPHP is warranted. Case presentation: we reported one intriguing case with concurrent NPHP3 c.2694-2_2694-1delAG (splicing) variant and c.1082C > G (p.S361C) variant. A 48-year-old male was admitted to our hospital, complained about renal dysfunction for 10 years, and found right renal space-occupying lesion for 1 week. One of the most interesting clinical features is adult-onset ESRD, which differs from previous cases. Another discovery of this study is that the NPHP harboring NPHP3 deletion may be associated with clear cell renal cell carcinoma. Conclusion: In conclusion, we report two mutations in the NPHP3 gene that cause NPHP with adult-onset ESRD and renal clear cell carcinoma in a Chinese family, enriching the clinical features of NPHP.
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OBJECTIVE: To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1 500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 µg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. RESULTS: Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×109/L): 1 673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×109/L): 1 350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. CONCLUSIONS: PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.
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Falência Hepática Aguda , Trombopoetina , Humanos , Masculino , Ratos , Animais , Trombopoetina/farmacologia , Interleucina-11/farmacologia , Ratos Sprague-Dawley , Plaquetas , Falência Hepática Aguda/tratamento farmacológico , Amarelo de Eosina-(YS) , AlbuminasRESUMO
RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy. A machine-learning model of 23 m6A genes was constructed. Single-cell analysis revealed a surprising enrichment of IGFBP3 in astrocytes, prompting the exploration of associated signaling pathways. Experimental verification shows that IGFBP3 is significantly enhanced in normal tissues, while immunohistochemical analysis shows that its expression is lower in tumor tissues, indicating its protective effect in HCC and a good prognosis. Importantly, high IGFBP3 expression is associated with better outcomes in patients receiving immunotherapy. Moreover, cytotoxic T lymphocyte (CTL) experiments have confirmed that high expression of IGFBP3 is associated with stronger T cell-killing ability. In summary, the comprehensive evaluation of m6A modification, immune characteristics, and single-cell analysis in this study not only revealed the TME of HCC but also made significant contributions to the progress of personalized HCC immunotherapy targeting IGFBP3. This study provides a solid theoretical foundation for clinical translation and emphasizes its potential impact on developing effective treatment strategies.
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Heterogeneous electrocatalysis closely relies on the electronic structure of the catalytic materials. The ferroelectric-to-paraelectric phase transition of the materials also involves a change in the state of electrons that could impact the electrocatalytic activity, but such correlation remains unexplored. Here, we demonstrate experimentally and theoretically that the intrinsic electrocatalytic activity could be regulated as exampled by hydrogen evolution reaction catalysis over two-dimensional ferroelectric CuInP2S6. The obvious discontinuity in the overpotential and apparent activation energy values for CuInP2S6 electrode are illustrated during the ferroelectric-to-paraelectric phase transition caused by copper displacement around Tc point (318â K), revealing the ferroelectro-catalytic effect on thermodynamics and kinetics of electrocatalysis. When loading Pt single atom on the CuInP2S6, the paraelectric phase one showed an improved hydrogen evolution activity with smaller apparent activation energy over the ferroelectric phase counterpart. This is attributed to the copper hopping between two sulfur planes, which alternate between strong and weak H adsorption at the Pt sites to simultaneously promote H+ reactant adsorption and H2 product desorption.
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Photoelectrochemical (PEC) catalysis provides the most promising avenue for producing value-added chemicals and consumables from renewable precursors. Over the last decades, PEC catalysis, including reduction of renewable feedstock, oxidation of organics, and activation and functionalization of CâC and CâH bonds, are extensively investigated, opening new opportunities for employing the technology in upgrading readily available resources. However, several challenges still remain unsolved, hindering the commercialization of the process. This review offers an overview of PEC catalysis targeted at the synthesis of high-value chemicals from sustainable precursors. First, the fundamentals of evaluating PEC reactions in the context of value-added product synthesis at both anode and cathode are recalled. Then, the common photoelectrode fabrication methods that have been employed to produce thin-film photoelectrodes are highlighted. Next, the advancements are systematically reviewed and discussed in the PEC conversion of various feedstocks to produce highly valued chemicals. Finally, the challenges and prospects in the field are presented. This review aims at facilitating further development of PEC technology for upgrading several renewable precursors to value-added products and other pharmaceuticals.
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Intestinal ischemia-reperfusion (I/R) injury is a serious disease in medical settings, and gut dysbiosis is a major contributor to its development. Polysaccharides from Agaricus blazei Murill (ABM) showed a range of pharmacological activities, yet no studies assessed the potential of ABM polysaccharides for alleviating intestinal I/R injury. Here, we purified a major polysaccharide (ABP1) from an ABM fruit body and subsequently tested its potential to mitigate intestinal I/R injury in a mouse model of temporary superior mesenteric artery occlusion. The results reveal that ABP1 pretreatment enhances gut barrier function via upregulation of the expression of tight junction proteins such as ZO-1 and occludin. Additionally, ABP1 intervention reduces the recruitment of neutrophils and the polarization of M1 macrophages and limits inflammation by blocking the assembly of the NLRP3 inflammasome. Moreover, the role of ABP1 in regulating the gut microbiota was confirmed via antibiotic treatment. The omics data reveals that ABP1 reprograms gut microbiota compositions, characterized by a decrease of Proteobacteria and an increase of Lachnospiraceae and Lactobacillaceae, especially the SCFA-producing genera such as Ligilactobacillus and Blautia. Overall, this work highlights the therapeutic potential of ABP1 against intestinal I/R injury, which mainly exhibits its effects via regulating the gut microbiota and suppressing the overactivated inflammation response.
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Agaricus , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Camundongos , Animais , Polissacarídeos/farmacologia , Inflamação/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , IsquemiaRESUMO
BACKGROUND: It has been found that a variety of host disease states can exacerbate intestinal inflammation, leading to disruption of intestinal barrier function. Changes in the composition of the intestine microbiota, which affect downstream metabolites in turn, ultimately react against the host. OBJECTIVES: We revealed the mechanism of berberine as an intestinal protective agent in rats with renal ischemia-reperfusion injury acute kidney injury (AKI). METHODS: HE staining was performed to evaluate the pathological changes in the colon and kidney. 16 S rRNA analysis was performed to assess the intestinal microbiota. Intestine TLR4/NF-κB expression was assessed by western blot. Q-RT-PCR was performed to detect TLR4 in intestine and IL-6 and KIM-1 gene expression in the kidney. SPSS 22.0 was used to compare the data. RESULTS: Rats with AKI exhibited increased relative abundances of Proteobacteria and Bacteroidetes and decreased relative abundances of Lactobacillus, Ruminococcus and Lachnospiraceae belonging to the phylum Firmicutes. The Sirt1-NF-κB-TLR4 pathway was involved in the occurrence process, accompanied by intestinal inflammation and oxidation. Berberine reversed the appeal change. CONCLUSION: Berberine inhibits the intestinal biological barrier of Proteobacteria, reduces LPS production, exerts an anti-inflammatory effect, and delays the progression of AKI.
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Injúria Renal Aguda , Berberina , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Ratos , Animais , NF-kappa B/metabolismo , Berberina/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Inflamação/tratamento farmacológicoRESUMO
Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
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Near-neutral zinc-air batteries (ZABs) have garnered significant research interest due to their high energy density, exceptional electrochemical reversibility, and adaptability to ambient air. However, these batteries suffer from substantial electrochemical polarization, low energy efficiency, and poor rate performance. In this study, a mesoporous carbon (meso-C) with a high specific surface area (1081 m2 g-1 ) and abundant porous structure for the cathode of near-neutral ZABs using a scalable synthesis method is prepared. The meso-C-based cathode is endowed with stable hydrophobicity and abundant electrochemical active sites, which considerably improve the energy efficiency, rate performance, and cycle life of the battery compare to commercial carbon black-based cathode when applied to near-neutral ZABs with 1 mol kg-1 (1 m) zinc acetate and 1 m zinc trifluoromethanesulfonate electrolytes. Additionally, the mesopores of meso-C facilitate the construction of better three-phase reaction interfaces and contribute to better electrochemical reversibility. The work presents a general and scalable approach for carbon materials in the cathode of near-neutral ZABs.
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PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B , Nucleotídeos , Interleucina-8 , Citocinas/metabolismo , Antivirais/uso terapêuticoRESUMO
The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn2+ component allows real-time dynamic visualization of the ALG-Mn hydrogel at the tumor site via magnetic resonance imaging. To the best of knowledge, the proposed ALG-Mn hydrogel represents the minimalist biocompatible platform for imaging-guided synergistic MWA and CDT toward achieving complete tumor clearance.
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Manganês , Neoplasias , Humanos , Micro-Ondas/uso terapêutico , Hidrogéis , Neoplasia Residual/tratamento farmacológico , Neoplasias/tratamento farmacológico , Imageamento por Ressonância Magnética , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
In situ formation of a stable interphase layer on zinc surface is an effective solution to suppress dendrite growth. However, the fast transport of bivalent Zn-ions within the solid interlayer remains very challenging. Herein, we engineer the SEI components and enable superior kinetics of Zn metal batteries under harsh conditions through regulating the sequence of interfacial chemical reaction. With the differences in chemical reactivity of trimethyl phosphate co-solvent and trifluoromethanesulfonate anions in the Zn2+-solvation shell, Zn3(PO4)2 and ZnF2 are successively generated on Zn metal surface to form a gradient ZnF2-Zn3(PO4)2 interphase. Mechanistic studies reveal the outer ZnF2 facilitates Zn2+ desolvation and inner Zn3(PO4)2 serves as channels for fast Zn2+ transport, contributing to long-term cycling at subzero temperatures. Impressively, the gradient SEI enables a high lifespan over 7000 hours in Zn symmetric cell and a capacity retention of 86.1% after 12000 cycles in Zn-KVOH full cell at -50 °C.
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INTRODUCTION: Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population. METHODS AND ANALYSIS: This prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des-γ-carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD's clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD's discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD. ETHICS AND DISSEMINATION: This trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally. TRIAL REGISTRATION NUMBER: NCT05626985.
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Carcinoma Hepatocelular , DNA Tumoral Circulante , Hepatite C , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/diagnóstico , Metilação , alfa-Fetoproteínas , Estudos Prospectivos , Neoplasias Hepáticas/diagnóstico , Biomarcadores , Cirrose Hepática , Estudos Observacionais como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Non-alkaline zinc-air batteries (ZABs) that use reversible O2 /ZnO2 chemistry exhibit excellent stability and superior reversibility compared to conventional alkaline ZABs. Unlike alkaline ZABs, ZnO2 discharge products are generated on the surface of the air cathodes in non-alkaline ZABs, requiring more gas-liquid-solid three-phase reaction interfaces. However, the kinetics of reported ZABs based on carbon black (CB) is far from satisfactory due to the insufficient reaction areas. The rational structural design of the air cathode is an effective way to increase active surfaces to further enhance the performance of non-alkaline ZABs. In this study, multi-walled carbon nanotubes (MW-CNTs) with unique mesoporous structures and high pore volumes are selected to replace CB in the air cathode preparation. Due to the larger electrochemically active surface area, superior hydrophobicity, and uniform electroconductibility of MW-CNTs-based cathodes, primary ZABs exhibit high specific capacity (704 mAh gZn-1 ) with a Zn utilization ratio of 85.85% at 1.0 mA cm-2 , excellent discharge rate performance, and negligible self-discharge. Furthermore, rechargeable ZABs also demonstrate outstanding rate capability and excellent cycling stability at various current densities. This work provides a fundamental understanding of the criteria for the cathode design of non-alkaline ZABs, thus opening a new pathway for more sustainable ZABs.