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OBJECTIVE: The effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed. METHODS: Adult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis. RESULTS: Rats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota, Proteobacteria, and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas, Alistipes, Aerococcus, Faecalibaculum, and Lachnospiraceae_ND3007_group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas/Faecalibaculum and inflammatory cytokines. CONCLUSION: MSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma.
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Exossomos , Microbioma Gastrointestinal , Fígado , Células-Tronco Mesenquimais , Ratos Wistar , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fígado/metabolismo , Fígado/patologia , Ratos , Masculino , Cicatrização , Macrófagos/metabolismo , Inflamação/metabolismoRESUMO
Aqueous rechargeable zinc ion batteries are promising candidates for grid-scale applications owing to their low cost and high safety. However, they are plagued by the lack of suitable cathode and anode materials. Herein, we report on potassium vanadate (KVO) nanobelts as a promising cathode for an aqueous zinc ion battery, which shows a high discharge capacity of 461 mA h g-1 at 0.2 A g-1 and exhibits a capacity retention of 96.2% over 4000 cycles at 10 A g-1. Furthermore, to enhance the energy efficiency in an aqueous zinc ion battery, a facile and effective method on the anode is demonstrated. The energy efficiency increases from 47.5% for Zn//KVO coupled with the zinc foil anode to 66.5% for AB-Zn//KVO coupled with an acetylene black film improved zinc foil anode at 10 A g-1. The remarkable electrochemical performance makes AB-Zn//KVO a strong candidate for a high-performance aqueous zinc ion battery.
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BACKGROUND: The lack of a suitable transplantation site has become a bottleneck restricting the development of islet transplantation. METHODS: In this study, for the first time, a prevascularized sinus tract (PST) for islet transplantation was constructed in a mouse model by temporarily embedding a 4× silk thread between the liver surface and the attached decellularized human amniotic membrane. After which, the characteristics of the PST and the function of the islet graft within the PST were evaluated. RESULTS: The results showed that PST was lined with granulation tissue, the blood vessel density of the local tissue increased, and proangiogenic proteins were upregulated, which mimics the microenvironment of the islets in the pancreas to a certain extent. Transplantation of ~200 syngeneic islets into the PST routinely reversed the hyperglycemia of the recipient mice and maintained euglycemia for >100 d until the islet grafts were retrieved. The islet grafts within the PST achieved better results to those in the nonprevascularized control groups and comparable results to those under the kidney capsule with respect to glycemic control and glucose tolerance. CONCLUSIONS: By attaching a decellularized human amniotic membrane to the surface of mouse liver and temporarily embedding a 4× silk thread, the PST formed on the liver surface has a favorable local microenvironment and is a potential clinical islet transplantation site.
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Hiperglicemia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Camundongos , Humanos , Animais , Transplante das Ilhotas Pancreáticas/métodos , Fígado/cirurgia , Fígado/metabolismo , Modelos Animais de Doenças , Âmnio , Inflamação/metabolismo , Glicemia/metabolismo , Ilhotas Pancreáticas/cirurgia , Ilhotas Pancreáticas/metabolismo , Sobrevivência de Enxerto , Camundongos Endogâmicos C57BLRESUMO
The effect of different annealing temperatures on the electrochemical performance of potassium ammonium vanadate (KNVO) was investigated, and the annealed KNVO regained H2O from the aqueous electrolyte to achieve an optimal structural water content during activation. In addition, the accompanying oxygen vacancies further promoted Zn2+ diffusion kinetics of the KNVO cathode in AZIBs and achieved excellent rate performance (344 mA h g-1 at 10 A g-1).
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BACKGROUNDS: Advanced schistosomiasis is the late stage of schistosomiasis, seriously jeopardizing the quality of life or lifetime of infected people. This study aimed to develop a nomogram for predicting mortality of patients with advanced schistosomiasis japonica, taking Dongzhi County of China as a case study. METHOD: Data of patients with advanced schistosomiasis japonica were collected from Dongzhi Schistosomiasis Hospital from January 2019 to July 2022. Data of patients were randomly divided into a training set and validation set with a ratio of 7:3. Candidate variables, including survival outcomes, demographics, clinical features, laboratory examinations, and ultrasound examinations, were analyzed and selected by LASSO logistic regression for the nomogram. The performance of the nomogram was assessed by concordance index (C-index), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The calibration of the nomogram was evaluated by the calibration plots, while clinical benefit was evaluated by decision curve and clinical impact curve analysis. RESULTS: A total of 628 patients were included in the final analysis. Atrophy of the right liver, creatinine, ascites level III, N-terminal procollagen III peptide, and high-density lipoprotein were selected as parameters for the nomogram model. The C-index, sensitivity, specificity, PPV, and NPV of the nomogram were 0.97 (95% [CI]: [0.95-0.99]), 0.78 (95% [CI]: [0.64-0.87]), 0.97 (95% [CI]: [0.94-0.98]), 0.78 (95% [CI]: [0.64-0.87]), 0.97 (95% [CI]: [0.94-0.98]) in the training set; and 0.98 (95% [CI]: [0.94-0.99]), 0.86 (95% [CI]: [0.64-0.96]), 0.97 (95% [CI]: [0.93-0.99]), 0.79 (95% [CI]: [0.57-0.92]), 0.98 (95% [CI]: [0.94-0.99]) in the validation set, respectively. The calibration curves showed that the model fitted well between the prediction and actual observation in both the training set and validation set. The decision and the clinical impact curves showed that the nomogram had good clinical use for discriminating patients with high risk of death. CONCLUSIONS: A nomogram was developed to predict prognosis of advanced schistosomiasis. It could guide clinical staff or policy makers to formulate intervention strategies or efficiently allocate resources against advanced schistosomiasis.
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BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.
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Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Inquéritos Nutricionais , Prevalência , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Obesidade/epidemiologiaRESUMO
High-entropy alloys (HEAs) have great potential as accident-tolerant fuel (ATF) cladding. Aluminum-forming duplex (BCC and FCC) stainless-steel (ADSS) is a candidate for ATF cladding, but the multiphase composition is detrimental to its corrosion resistance. In this paper, two single-phase HEAs were prepared by adjusting the content of each element in the ADSS alloy. The two HEAs were designed as Al0.05(CrFeNi)0.95(FCC) and Al0.25(FeCrNi)0.75(BCC). Their corrosion behavior under simulated pressurized water reactor (PWR) primary water was investigated. The corrosion products and corrosion mechanisms of these two HEAs were explored. The results show that the corrosion resistance of HEA alloys containing FCC is better than that of BCC and ADSS alloys. At the same time, the reason why the BCC structure composed of these four elements is not resistant to corrosion is revealed.
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Background: Pancreatic stellate cells (PSCs) play crucial roles in acute/chronic pancreatitis and pancreatic cancer. In this study, bibliometric analysis was used to quantitatively and qualitatively analyze the literature related to PSCs from 1998-2021 to summarize the current trends and research topics in this field. Methods: Relevant literature data were downloaded from the Science Citation Index Expanded Web of Science Core Collection (WoSCC) on April 07, 2021, using Clarivate Analytics. Biblioshiny R packages, VOSviewer, Citespace, BICOMB, gCLUTO, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com) were used to analyze the manually selected data. Results: A total of 958 relevant studies published in 48 countries or regions were identified. The United States of America (USA) had the highest number of publications, followed by the People's Republic of China, Germany, and Japan. Tohoku University (Japan), the University of New South Wales (Australia), the University of Texas MD Anderson Cancer Center (USA), Technical University of Munich (Germany), and University of Rostock (Germany) were the top five institutions with most publications. Nine major clusters were generated using reference co-citation analysis. Keyword burst detection revealed that progression (2016-2021), microenvironment (2016-2021), and tumor microenvironment (2017-2021) were the current frontier keywords. Biclustering analysis identified five research hotspots in the field of PSCs during 1998-2021. Conclusion: In this study, a scientometric analysis of 958 original documents related to PSCs showed that the research topics of these studies are likely in the transition from acute/chronic pancreatitis to pancreatic cancer. The current research trends regarding PSCs are related to pancreatic cancer, such as tumor microenvironment. This study summarizes five research hotspots in the field of PSCs between 1998 and 2021 and thus may provide insights for future research.
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The oxidation behavior of body-centered cubic (bcc) structure Cr20Mn17Fe18Ta23W22 refractory high-entropy alloy (RHEA) and the microdefects induced by hydrogen ions before and after oxidation were investigated. The results revealed that compared with oxidizing Cr20Mn17Fe18Ta23W22 at 800 °C (6.7 °C/min) for 4 h (ST3, Ar:O2 = 3:1), the heating procedure of oxidizing Cr20Mn17Fe18Ta23W22 at 300 °C (6 °C/min) for 2 h and then increased to 800 °C (5 °C/min) for 4 h is more conducive to the production of oxides without spalling on the surface, i.e., HT1 (Ar:O2 = 1:1), HT2 (Ar:O2 = 2:1) and HT3 (Ar:O2 = 3:1) samples. The oxidation of Cr20Mn17Fe18Ta23W22 RHEA is mainly controlled by the diffusion of cations instead of affinities with O. Additionally, HT1 and HT3 samples irradiated with a fluence of 3.9 × 1022 cm-2 hydrogen ions (60 eV) were found to have a better hydrogen irradiation resistance than Cr20Mn17Fe18Ta23W22 RHEA. The microdefects in irradiated Cr20Mn17Fe18Ta23W22 mainly existed as hydrogen bubbles, hydrogen-vacancy (H-V) complexes and vacancy/vacancy clusters. The microdefects in irradiated HT3 were mainly vacancies and H-V complexes, while the microdefects in irradiated HT1 mainly existed as vacancies and vacancy clusters, as large amounts of hydrogen were consumed to react with oxides on the HT1 surface. The oxides on the surface of the HT3 sample were more stable than those on HT1 under hydrogen irradiation.
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OBJECTIVE: We conducted studies to explore the effect of phloretin on glucose uptake, proliferation, and differentiation of human peripheral blood CD4+ T cells and investigated the mechanism of phloretin on inducing Th17/Treg development. METHODS: Naïve CD4+ T cells were purified from peripheral blood of healthy volunteers, stimulated with anti-CD3/CD28 antibodies, and polarized in vitro to generate Th17 or Treg cells. Glucose uptake, proliferation, cell cycle, protein expression (phospho-Stat3, phospho-Stat5), and Th17 and Treg cell numbers were analyzed by flow cytometry. AMP-activated protein kinase (AMPK) signaling was analyzed by western blot. Results and Discussion. Phloretin could inhibit the glucose uptake and proliferation of activated CD4+ T cells. The proliferation inhibition was due to the G0/G1 phase arrest. Phloretin decreased Th17 cell generation and phospho-Stat3 expression as well as increased Treg cell generation and phospho-Stat5 expression in the process of inducing Th17/Treg differentiation. The phosphorylation level of AMPK was significantly enhanced, while the phosphorylation level of mTOR was significantly decreased in activated CD4+ T cells under phloretin treatment. The AMPK signaling inhibitor compound C (Com C) could neutralize the effect of phloretin, while the agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could impact the Th17/Treg balance similar to phloretin during Th17/Treg induction. CONCLUSION: Our results suggest that phloretin can mediate the Th17/Treg balance by regulating metabolism via the AMPK signal pathway.
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Proteínas Quinases Ativadas por AMP/imunologia , Diferenciação Celular/efeitos dos fármacos , Floretina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Diferenciação Celular/imunologia , Humanos , Linfócitos T Reguladores/citologia , Células Th17/citologiaRESUMO
Recently, there has been renewed interest in aqueous Zn-ion batteries. Here, electrochemical and structural changes of hierarchically porous sodium vanadate (NVO) in aqueous Zn-ion batteries are demonstrated. The hierarchically porous NVO cathode exhibits a high power density of 7139 W h kg-1 at 10 A g-1 and excellent long-term cyclability. Moreover, the consequent capacitive- and diffusion-controlled mechanism in Zn/NVO battery chemistry has been first reported. Such a hybrid control mechanism may certainly trigger new opportunities in the rapid development of Zn-ion batteries.
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It is well known that transition metal oxides (TMOs) have attracted extensive attention as promising anodes for next-generation lithium ion batteries (LIBs) owing to their low cost and high theoretical capacities. However, the huge volume changes upon lithiation/delithiation cycling gradually cause drastic particle pulverization in the electrodes, thus leading to fast capacity fading and limiting their practical applications. High-entropy oxides with enhanced electronic conductivity and multiple electrochemically active elements display stepwise lithium storage behaviors, thus efficiently alleviating the volume change induced electrode pulverization problem. Herein, we report the synthesis of a new kind of spinel (Mg0.2Ti0.2Zn0.2Cu0.2Fe0.2)3O4 material via a facile one-step solid state reaction method and subsequent high-energy ball-milling. When used as anodes for LIBs, the submicrometer-sized (Mg0.2Ti0.2Zn0.2Cu0.2Fe0.2)3O4 particles exhibit superior lithium storage properties, delivering a large reversible capacity of 504 mA h g-1 at a current density of 100 mA g-1 after 300 cycles, and notably an exceptional rate capacity of 272 mA h g-1 at 2000 mA g-1. Our work highlights that rational design of high-entropy oxides with different electrochemically active elements and novel structures might be a useful strategy for exploring high-performance LIB anode materials in next-generation energy storage devices.
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Development of suitable cathodes for use in aqueous rechargeable zinc ion batteries has attracted extensive interest. Herein, the electrochemical and structural changes of a novel porous hydrated ammonium vanadate (AVO) cathode in an aqueous ZnSO4-based electrolyte are reported. The AVO/Zn system exhibits a high reversible capacity of 418 mA h g-1, excellent long-term cyclability, and outstanding storage performance. Moreover, an interesting insertion mechanism with ternary carriers in a Zn/AVO aqueous rechargeable zinc-ion battery has been demonstrated for the first time.
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Although 90% of clinical islet transplantations are performed via the portal vein approach, it is still far from the ideal transplant site. Alternative islet transplant sites are promising to reduce the islet dose required to reverse hyperglycemia, thereby improving the efficiency of islet transplantation. The aim of this study was to compare the differences in survival and metabolic function of islet grafts transplanted into the hepatic sinus tract (HST) and the splenic parenchyma (SP). Approximately 300 syngeneic mouse islets were transplanted into the HST (n = 6) and the SP (n = 6) of recipient diabetic mice, respectively. After transplantation, the glycemic control, glucose tolerance, and morphology of islet grafts were evaluated and compared in each group. The nonfasting blood glucose of the two groups of mice receiving islet transplantation gradually decreased to the normal range and sustained for more than 100 d. There is no significant difference in the time required to restore normoglycemia (P > 0.05). The results of the glucose tolerance test showed that the SP group presented a smaller area under the curve than the HST group (P < 0.05). Histopathological results showed that islet grafts in the HST and the SP were characterized with normal islet morphology and robust insulin production. Compared with the HST, islet transplantation in the SP presents better blood glucose regulation, although there is no significant difference in the time required to restore normoglycemia.
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Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/cirurgia , Baço/cirurgia , Animais , Masculino , Camundongos , Distribuição AleatóriaRESUMO
Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.
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Âmnio/química , Técnicas de Cultura de Células/métodos , Diabetes Mellitus Experimental/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante das Ilhotas Pancreáticas/métodos , Substâncias Protetoras/farmacologia , Soro/metabolismo , Extratos de Tecidos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glucose/farmacologia , Teste de Tolerância a Glucose , Humanos , Secreção de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obtenção de Tecidos e Órgãos , Resultado do TratamentoRESUMO
Ultrafine crystalline materials have been extensively investigated as high-rate lithium-storage materials due to their shortened charge-transport length and high surface area. The pseudocapacitive effect plays a considerable role in electrochemical lithium storage when the electrochemically active materials approach nanoscale dimensions, but this has received limited attention. Herein, a series of (Mg0.2Co0.2Ni0.2Cu0.2Zn0.2)O electrodes with different particle sizes were prepared and tested. The ultrafine (Mg0.2Co0.2Ni0.2Cu0.2Zn0.2)O nanofilm (3-5 nm) anodes show a remarkable rate capability, delivering high specific charge and discharge capacities of 829, 698, 602, 498 and 408 mA h g-1 at 100, 200, 500, 1000 and 2000 mA g-1, respectively, and a dominant pseudocapacitive contribution as high as 90.2% toward lithium storage was revealed by electrochemical analysis at a high scanning rate of 1.0 mV s-1. This work offers an approach to tune the lithium-storage properties of (Mg0.2Co0.2Ni0.2Cu0.2Zn0.2)O by size control and gives insights into the enhancement of pseudocapacitance-assisted lithium-storage capacity.
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The human islet amyloid polypeptide (hIAPP), the major component of islet amyloid deposition, is one of the amyloidogenic peptides and has been associated with ß cell loss and dysfunction in type 2 diabetes (T2D). Autophagy plays a central role in the clearance of hIAPP aggregates, thereby diminishing the hIAPP-induced cytotoxicity. Conversely, hIAPP has been reported to have interfering effects on the autophagy. The pentapeptide FLPNF developed in our previous study has been shown to have effects on the level of the downstream proteins of mTOR and autophagy-lysosome pathway. In the present study, the peptide FLPNF-mediated increase in autophagy flux and its underlying mechanisms, as well as its protecting effect on INS-1 cells, were investigated. Autophagy flux in INS-1 cells overexpressing hIAPP (hIAPP-INS-1 cells) markedly increased after exposure to peptide FLPNF for 24 h and peaked at a concentration of 200 µM. Peptide FLPNF enhanced the autophagy by inhibiting the mTORC1 activity. Flow cytometry results showed the peptide FLPNF bind to mammalian target of rapamycin (mTOR), and further molecular docking analysis revealed a direct interaction between peptide FLPNF and the FRB domain of mTOR. Meanwhile, both peptide FLPNF and rapamycin significantly decreased the hIAPP-induced apoptosis, whereas 3-MA increased the apoptosis. Furthermore, peptide FLPNF reduced the hIAPP oligomer and improved the hIAPP-INS-1 cells insulin release function at high glucose concentration. Taken together, the peptide FLPNF decreased the hIAPP oligomer via upregulating autophagy by inhibiting mTORC1 activity, thus protecting the INS-1 cells from hIAPP-induced apoptosis and improving the insulin release function of INS-1 cells.
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A low-cost and eco-friendly system based on a manganese-based complex cathode and zinc anode was demonstrated. The cathode is able to reversibly (de-)insert Zn2+ ions, providing a high capacity of 248 mA h g-1 at 0.1 A g-1. Ex situ TEM and XRD were utilized to determine the electrochemical mechanism of this high capacity cathode. Moreover, the contribution of pre-added Mn2+ in electrolyte to the capacity was revealed, and nearly 18.9% of the capacity is ascribed to the contribution of pre-added Mn2+. With the help of additive, this aqueous rechargeable battery shows outstanding electrochemical property. Its cycling performance is good with 6% capacity loss after 2000 cycles at 4.0 A g-1, highlighting it as a promising system for aqueous rechargeable battery applications.