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This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
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Abelmoschus , Diabetes Mellitus , Nefropatias Diabéticas , Flavonas , Resistência à Insulina , Podócitos , Ratos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Abelmoschus/química , Ratos Sprague-Dawley , Transição Epitelial-Mesenquimal , Flavonas/farmacologia , Espécies Reativas de OxigênioRESUMO
Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
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Abelmoschus , Diabetes Mellitus , Nefropatias Diabéticas , Flavonas , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Flavonas/farmacologia , Estresse do Retículo Endoplasmático , Nefropatias Diabéticas/tratamento farmacológico , ApoptoseRESUMO
The low-cost, high-abundance and durable layered double hydroxides (LDHs) have been considered as promising electrocatalysts for oxygen evolution reaction (OER). However, the easy agglomeration of lamellar LDHs in the aqueous phase limits their practical applications. Herein, a series of ternary NiCoFe LDHs were successfully fabricated on nickel foam (NF) via a simple electrodeposition method. The as-prepared Ni(Co0.5 Fe0.5 )/NF displayed an unique nanoarray structural feature. It showed an OER overpotential of 209â mV at a current density of 10â mA cm-2 in alkaline solution, which was superior to most systems reported so far. As evidenced by the XPS and XAFS results, such excellent performance of Ni(Co0.5 Fe0.5 )/NF was attributed to the higher Co3+ /Co2+ ratio and more defects exposed, comparing with Ni(Co0.5 Fe0.5 )-bulk and Ni(Co0.5 Fe0.5 )-mono LDHs prepared by conventional coprecipitation method. Furthermore, the ratio of Co to Fe could significantly tune the Co electronic structure of Ni(Cox Fe1-x )/NF composites (x=0.25, 0.50 and 0.75) and affect the electrocatalytic activity for OER, in which Ni(Co0.5 Fe0.5 )/NF showed the lowest energy barrier for OER rate-determining step (from O* to OOH*). This work proposes a facile method to develop high-efficiency OER electrocatalysts.
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The host-guest interaction can remarkably alter the physiochemical properties of composite materials. It is crucial to clarify the mechanism by revealing the influence of the host on the electronic structure of the guest molecules. Herein, we study the structural variation of polyoxometalates (POMs) after being confined in single-walled carbon nanotubes (SWNT). What we found is that in addition to the reported charge transfer from SWNT to POM, an intramolecular electron transfer within a single POM cluster can be observed in the POM@SWNT composites. Moreover, the charge density on the bridged oxygen of POMs is prominently enhanced. The structural change and electron reconfiguration of POMs upon encapsulation in SWNT significantly speed up electron and ion transport, leading to the improved electrochemical performance for sodium ions storage.
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Polyoxometalates (POMs)-based materials, with high theoretical capacities and abundant reversible multi-electron redox properties, are considered as promising candidates in lithium-ion storage. However, the poor electronic conductivity, low specific surface area and high solubility in the electrolyte limited their practical applications. Herein, a double-shelled hollow PMo12 -SiO2 @N-C nanofiber (PMo12 -SiO2 @N-C, where PMo12 is [PMo12 O40 ]3- , N-C is nitrogen-doped carbon) was fabricated for the first time by combining coaxial electrospinning technique, thermal treatment and electrostatic adsorption. As an anode material for LIBs, the PMo12 -SiO2 @N-C delivered an excellent specific capacity of 1641â mA h g-1 after 1000 cycles under 2â A g-1 . The excellent electrochemical performance benefited from the unique double-shelled hollow structure of the material, in which the outermost N-C shell cannot only hinder the agglomeration of PMo12 , but also improve its electronic conductivity. The SiO2 inner shell can efficiently avoid the loss of active components. The hollow structure can buffer the volume expansion and accelerate Li+ diffusion during lithiation/delithiation process. Moreover, PMo12 can greatly reduce charge-resistance and facilitate electron transfer of the entire composites, as evidenced by the EIS kinetics study and lithium-ion diffusion analysis. This work paves the way for the fabrication of novel POM-based LIBs anode materials with excellent lithium storage performance.
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Core-multishelled structures with controlled chemical composition have attracted great interest due to their fascinating electrochemical performance. Herein, a metal-organic framework (MOF)-on-MOF self-templated strategy is used to fabricate okra-like bimetal sulfide (Fe7 S8 /C@ZnS/N-C@C) with core-double-shelled structure, in which Fe7 S8 /C is distributed in the cores, and ZnS is embedded in one of the layers. The MOF-on-MOF precursor with an MIL-53 core, a ZIF-8 shell, and a resorcinol-formaldehyde (RF) layer (MIL-53@ZIF-8@RF) is prepared through a layer-by-layer assembly method. After calcination with sulfur powder, the resultant structure has a hierarchical carbon matrix, abundant internal interface, and tiered active material distribution. It provides fast sodium-ion reaction kinetics, a superior pseudocapacitance contribution, good resistance of volume changes, and stepwise sodiation/desodiation reaction mechanism. As an anode material for sodium-ion batteries, the electrochemical performance of Fe7 S8 /C@ZnS/N-C@C is superior to that of Fe7 S8 /C@ZnS/N-C, Fe7 S8 /C, or ZnS/N-C. It delivers a high and stable capacity of 364.7 mAh g-1 at current density of 5.0 A g-1 with 10 000 cycles, and registers only 0.00135% capacity decay per cycle. This MOF-on-MOF self-templated strategy may provide a method to construct core-multishelled structures with controlled component distributions for the energy conversion and storage.
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To observe the multi-targeted therapeutic effects of Huangkui Capsules(HKC)on insulin resistance(IR)and urine microalbumin in the early diabetic kidney disease(DKD)patients. The case data from the 83 DKD patients at G2 and A2 stage were collected respectively and analyzed retrospectively. According to the different treatment,all patients were divided into the control(A)group(40 cases)and the treated(B)group(43 cases). Among them,the A group patients were received "routine basic treatment";the B group patients were received "routine basic treatment+HKC". For the 2 group patients,firstly,the baseline parameters before receiving the treatment were compared respectively,and then,the changes of the total scores of traditional Chinese medicine(TCM) syndromes and the indicators of IR,urine protein,renal function,blood lipids and safety after receiving the treatment for 8 weeks were compared,respectively. Furthermore,for the all patients,the correlation analysis between IR and urine protein or IR and the total scores of TCM syndromes was carried out,respectively. The results showed that,for the B group patients received "routine basic treatment",their total scores of TCM syndromes,urine protein indicators including urine microalbumin(micro-UAlb) and urine microalbumin/urinary creatinine(UACR),IR indicators including fasting serum insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly improved,respectively. For the all DKD patients,before and after the treatment,the main IR indicators(FIN and HOMA-IR)were positively correlated with urine protein indicators(micro-UAlb and UACR). The main IR indicators(FIN and HOMA-IR) were also positively correlated with the total scores of TCM syndromes. In addition,2 treatments had no significant effects on renal function,blood lipids and safety indicators in the all DKD patients. Overall, "routine basic treatment+HKC" can ameliorate IR and reduce urine microalbumin in the early DKD patients. Its therapeutic targets may be not only proteinuria,but also IR,which is the upstream risk factor of proteinuria.
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Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Resistência à Insulina , Albuminúria , Cápsulas , Humanos , Insulina , Rim , Estudos RetrospectivosRESUMO
In the kidney, pericyte is the major source of myofibroblast (MyoF) in renal interstitium. It is reported that pericyte-myofibroblast transitionï¼PMTï¼is one of the important pathomechanisms of renal interstitial fibrosisï¼RIFï¼. Among them, the main reasons for promoting RIF formation include pericyte recruitment, activation and isolation, as well as the lack of pericyte-derived erythropoietin. During the PMT startup process, pericyte activation and its separation from microvessels are controlled by multiple signal transduction pathways, such as transforming growth factor-ßï¼TGF-ßï¼pathway, vascular endothelial growth factor receptor (VEGFR) pathway and platelet derived growth factor receptor (PDGFR) pathway;Blocking of these signaling pathways can not only inhibit PMT, but also suppress renal capillaries reduction and further alleviate RIF. In clinic, many traditional Chinese medicine compound prescriptions, single traditional Chinese herbal medicine (CHM) and their extracts have the clear effects in alleviating RIF, and some of their intervention actions may be related to pericyte and its PMT. Therefore, the studies on PMT and its drug intervention will become the main development direction in the research field of anti-organ fibrosis by CHM.
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Medicamentos de Ervas Chinesas/farmacologia , Rim/citologia , Miofibroblastos/citologia , Pericitos/citologia , Fibrose , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The aim of this paper was to explore the effects and possible mechanisms in vitro of tea polyphenols (TP) delaying human glomerular mesangial cells (HGMCs) senescence induced by high glucose (HG). HGMCs were cultured in vitro and divided into the normal group (N, 5.5 mmol·L⻹ glucose), the mannitol group(MNT, 5.5 mmol·L⻹ glucose plus 24.5 mmol·L⻹ mannitol), the high dose of D-glucose group (HG, 30 mmol·L⻹ glucose), the low dose of TP group (L-TP, 30 mmol·L⻹ glucose plus 5 mg·L⻹ TP) and the high dose of TP group (H-TP, 30 mmol·L⻹ glucose plus 20 mg·L⻹ TP), which were cultured in 5% CO2 at 37 °C, respectively. Firstly, the effects of TP on the cell morphology of HGMCs were observed after 72 h-intervention. Secondly, the cell cycle, the positive rate of senescence-associated-ß-galactosidase (SA-ß-gal) staining and the telomere length were detected, respectively. Finally, the protein expressions of p53, p21 and Rb in the p53-p21-Rb signaling pathway were investigated, respectively. And the expressions of p-STAT3 and miR-126 were examined severally. The results indicated that HG not only arrested the cell cycle in G1 phase but also increased the positive rate of SA-ß-gal staining, and shortened the telomere length. HG led to the protein over-expressions of p53, p21 and Rb and HGMCs senescence by activating the p53-p21-Rb signaling pathway. In addition, L-TP delayed HGMCs senescence by improving the cell cycle G1 arrest, reducing SA-ß-gal staining positive rate and lengthening the telomere length. L-TP reduced the protein over-expressions of p53, P21 and Rb induced by HG and inhibited the telomere-p53-p21-Rb signaling pathway. Moreover, the expression of p-STAT3 was increased and the expression of miR-126 was decreased in HGMCs induced by HG. L-TP reduced the expression of p-STAT3 and increased the expression of miR-126 in HGMCs. In conclusion, HG could induce HGMCs senescence by activating the telomere-p53-p21-Rb signaling pathway in vitro. L-TP could delay HGMCs senescence through regulating STAT3/miR-126 expressions and inhibiting the telomere-p53-p21-Rb signaling pathway activation. These findings could provide the effective interventions in clinic for preventing and treating renal cell senescence in diabetic kidney disease.
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Células Mesangiais , Células Cultivadas , Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21 , Glucose , Humanos , MicroRNAs , Polifenóis , Fator de Transcrição STAT3 , Chá , Telômero , Proteína Supressora de Tumor p53RESUMO
To develop a cost-effective, high-viscosity asphalt for porous asphalt pavement, we utilized SBS, tackifier, and solubilizer as the main raw materials, identified the optimal composition through an orthogonal experiment of three factors and three levels, and prepared a low-cost high-viscosity asphalt. We compared its conventional and rheological properties against those of rubber asphalt, SBS modified asphalt, and matrix asphalt, employing fluorescence microscopy and Fourier transform infrared spectroscopy for microstructural analysis. The results indicate that the optimal formula composition for high-viscosity asphalt was 4-5% styrene-butadiene-styrene (SBS) + 1-2% tackifier +0-3% solubilizer +0.15% stabilizer. The components evenly dispersed and the performances were enhanced with chemical and physical modification. Compared with SBS modified asphalt, rubber asphalt, and matrix asphalt, the softening point, 5 °C ductility, and 60 °C dynamic viscosity of high-viscosity asphalt were significantly improved, while the 175 °C Brookfield viscosity was equivalent to SBS modified asphalt. In particular, the 60 °C dynamic viscosity reaches 383,180 Pa·s. Rheological tests indicate that the high- and low-temperature grade of high-viscosity asphalt reaches 88-18 °C, and that high-viscosity asphalt has the best high-temperature resistance to permanent deformation and low-temperature resistance to cracking. It can save about 30% cost compared to commercially available high-viscosity asphalt, which is conducive to the promotion and application of porous asphalt pavement.
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To study the rheological and aging properties of vegetable oil-based polyurethane (V-PU) modified asphalt, V-PU terminated with an -NCO group was synthesized from renewable castor oil, and liquefied MDI-100LL and 10-40 wt% V-PU modified asphalts were prepared. Temperature classification, multiple stress creep recovery (MSCR), and linear amplitude scanning (LAS) tests were carried out. The results showed that the modulus, the creep recovery rate (R), and the yield stress and yield strain of the V-PU modified asphalts significantly increased in the order: 0 wt% < 10 wt% < 20 wt% < 40 wt% < 30 wt%, while the phase angle and the unrecoverable creep compliance (Jnr) changed in the opposite order, and the high temperature grade of 30 wt% V-PU modified asphalt was 4 grades higher than that of the base asphalt, which indicated that the addition of V-PU enhanced the fatigue, permanent deformation, and recovery deformation resistance. The 30 wt% sample exhibited phase inversion had the best performance. Comprehensive FTIR, GPC, and fluorescence microscopy analyses showed that the molecular weight significantly increased and the V-PU molecules agglomerated after aging. The excess -NCO groups of V-PU prepolymer react with water in the air and the active hydrogen in the asphalt system and finally form a cross-linked three-dimensional network structure with the asphalt to improve performance. The mechanism of intramolecular cementation reaction and the aging process of V-PU modified asphalt was creatively derived.
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BACKGROUND: Long-term peritoneal exposure to high glucose in the peritoneal dialysis (PD) solution may potentiate the development of peritoneal fibrosis in PD patients. The most important factor leading to peritoneal fibrosis may be injury of human peritoneal mesothelial cells (HPMC). Little is known about senescence of HPMC. It has been reported that Tanshinone IIA can ameliorate fibrosis. Whether Tanshinone IIA may delay senescence and protect HPMC against high glucose is not clear. The aim of this study is to investigate the protective role of Tanshinone IIA in senescence of HPMC induced by high glucose. METHODS: HPMC were isolated and cultured with Roswell Park Memorial Institute 1640 medium containing high glucose concentrations (2.5%) and Tanshinone IIA (50 µmol/L and 100 µmol/L). The effects of high glucose and Tanshinone IIA on cellular senescence of HPMC were examined by observing cell generation, growth rate, cell cycle, positive rate of senescence-associated ß-galactosidase (SA-ß-gal) staining, telomere length, and expression of p16 and p21. RESULTS: Compared with the control cells, HPMC cultured in high glucose showed decreased cell generations by four to five and suppression of growth rate, and the cell cycle was stopped at G1 phase. The positive rate of SA-ß-gal staining was increased; the telomere length was shortened; and the expressions of p16 and p21 were increased. The characteristics in morphology of senescent cells appeared earlier. Tanshinone IIA may delay the process of senescence of HPMC induced by high glucose by increasing cell generations and growth rate, decreasing the rate of G1 phase and the positive rate of SA-ß-gal staining, lengthening the telomere, and decreasing the expression of p16 and p21. CONCLUSIONS: Tanshinone IIA may protect HPMC through delaying cellular senescence induced by high glucose.
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Abietanos/farmacologia , Senescência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Peritônio/citologia , Peritônio/efeitos dos fármacos , Células Cultivadas , Glucose/administração & dosagem , Humanos , Fatores de TempoRESUMO
Integrated, timely data about pavement structures, materials and performance information are crucial for the continuous improvement and optimization of pavement design by the engineering research community. However, at present, pavement structures, materials and performance information in China are relatively isolated and cannot be integrated and managed. This results in a waste of a large amount of effective information. One of the significant development trends of pavement engineering is to collect, analyze, and manage the knowledge assets of pavement information to realize intelligent decision-making. To address these challenges, a knowledge graph (KG) is adopted, which is a novel and effective knowledge management technology and provides an ideal technical method to realize the integration of information in pavement engineering. First, a neural network model is used based on the principle of deep learning to obtain knowledge. On this basis, the relationship between knowledge is built from siloed databases, data in textual format and networks, and the knowledge base. Second, KG-Pavement is presented, which is a flexible framework that can integrate and ingest heterogeneous pavement engineering data to generate knowledge graphs. Furthermore, the index and unique constraints on attributes for knowledge entities are proposed in KG-Pavement, which can improve the efficiency of internal retrieval in the system. Finally, a pavement information search engine based on a knowledge graph is constructed to realize information interaction and target information matching between a webpage server and graph database. This is the first successful application of knowledge graphs in pavement engineering. This will greatly promote knowledge integration and intelligent decision-making in the domain of pavement engineering.
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Reconhecimento Automatizado de Padrão , Ferramenta de Busca , Engenharia , Conhecimento , Redes Neurais de ComputaçãoRESUMO
Tip-based photoemission spectroscopic techniques have now achieved subnanometer resolution that allows visualization of the chemical structure and even the ground-state vibrational modes of a single molecule. However, the ability to visualize the interplay between electronic and nuclear motions of excited states, i.e., vibronic couplings, is yet to be explored. Herein, we theoretically propose a new technique, namely, tip-enhanced fluorescence excitation (TEFE). TEFE takes advantage of the highly confined plasmonic field and thus can offer a possibility to directly visualize the vibronic effect of a single molecule in real space for arbitrary excited states in a given energy window. Numerical simulations for a single porphine molecule confirm that vibronic couplings originating from Herzberg-Teller (HT) active modes can be visually identified. TEFE further enables high-order vibrational transitions that are normally suppressed in the other plasmon-based processes. Images of the combination vibrational transitions have the same pattern as that of their parental HT active mode's fundamental transition, providing a direct protocol for measurements of the activity of Franck-Condon modes of selected excited states. These findings strongly suggest that TEFE is a powerful strategy to identify the involvement of molecular moieties in the complicated electron-nuclear interactions of the excited states at the single-molecule level.
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Polyoxometalate (POM)-based materials are considered as promising candidates for lithium-ion batteries (LIBs) due to their stable and well-defined molecular structure and reversible multielectron redox properties. Currently, POM-based electrode materials suffer from high interfacial resistance and low uniformity. Herein, we reported a self-supported POM-based anode material for LIBs by electrodepositing H3PMo12O40 (PMo12) and aniline on carbon cloth (CC) for the first time. The as-prepared polyaniline (PANi)-PMo12/CC composite exhibited an excellent reversible capacity of 1092 mA h g-1 for 200 cycles at 1 A g-1. Such an outstanding performance was attributed to the rapid electron transfer and Li+ diffusion stemming from the exposure of more active sites by the self-supported structure, the strong electrostatic interaction, and electronic structure reconfiguration between the active PMo12 cluster and conductive PANi polymer. This work provides insight into the electronic structure engineering of highly efficient LIB anode materials.
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Polyoxometalates (POMs) have shown great potential in sodium-ion batteries (SIBs) due to their reversible multielectron redox property and high ionic conductivity. Currently, POM-based SIBs suffer from the irreversible trapping and sluggish transmission kinetics of Na+. Herein, a series of POMs/metal-organic frameworks (MOFs)/graphene oxide (GO) (MOFs = MIL-101, MIL-53, and MIL-88B; POM = [PMo12O40]3-, denoted as PMo12) composites are developed as SIB anode materials for the first time. Unlike MIL-101 with large pore structures, the pores in flexible MIL-53 and MIL-88B swell spontaneously upon the accommodation of PMo12. Particularly, the PMo12/MIL-88B/GO composites deliver an excellent specific capacity of 214.2 mAh g-1 for 600 cycles at 2.0 A g-1, with a high initial Coulombic efficiency (ICE) of 51.0%. The so-called "breathing effect" of flexible MOFs leads to the relatively tight confinement space for PMo12, which greatly modulates its electronic structure, affects the adsorption energy of Na+, and eventually reduces the trapping of sodium ions. Additionally, the straight and multidimensional channels in MIL-88B significantly accelerate ion diffusion, inducing favored energetic kinetics and thus generating high-rate performance.
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Background: Fucoidan (FPS) has been widely used to treat renal fibrosis (RF) in patients with diabetic kidney disease (DKD); however, the precise therapeutic mechanisms remain unclear. Recently, research focusing on inflammation-derived podocyte pyroptosis in DKD has attracted increasing attention. This phenomenon is mediated by the activation of the nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to RF during DKD progression. Therefore, we designed a series of experiments to investigate the ameliorative effects of FPS on RF in DKD and the mechanisms that are responsible for its effect on NLRP3 inflammasome-mediated podocyte pyroptosis in the diabetic kidney. Methods: The modified DKD rat models were subjected to uninephrectomy, intraperitoneal injection of streptozotocin, and a high-fat diet. Following induction of renal injury, the animals received either FPS, rapamycin (RAP), or a vehicle for 4 weeks. For in vitro research, we exposed murine podocytes to high glucose and MCC950, an NLRP3 inflammasome inhibitor, with or without FPS or RAP. Changes in the parameters related to RF and inflammatory podocyte injury were analyzed in vivo. Changes in podocyte pyroptosis, NLRP3 inflammasome activation, and activation of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/NLRP3 signaling axis involved in these changes were analyzed in vivo and in vitro. Results: FPS and RAP ameliorated RF and inflammatory podocyte injury in the DKD model rats. Moreover, FPS and RAP attenuated podocyte pyroptosis, inhibited NLRP3 inflammasome activation, and regulated the AMPK/mTORC1/NLRP3 signaling axis in vivo and in vitro. Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro. Conclusion: We confirmed that FPS, similar to RAP, can alleviate RF in DKD by inhibiting NLRP3 inflammasome-mediated podocyte pyroptosis via regulation of the AMPK/mTORC1/NLRP3 signaling axis in the diabetic kidney. Our findings provide an in-depth understanding of the pathogenesis of RF, which will aid in identifying precise targets that can be used for DKD treatment.
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Chemo/chemodynamic synergistic therapy is a promising strategy to improve the antitumor effect. However, hypoxia and a limited amount of hydrogen peroxide (H2O2) in the tumor microenvironment (TME) severely restrict the therapeutic efficacy of this combined treatment. Herein, we report biodegradable doxorubicin (Dox)-loaded copper-metformin (Met) nanoscale coordination polymers (Dox@Cu-Met NPs), which exert a chemo/chemodynamic synergistic therapeutic effect by reducing oxygen (O2) consumption to promote H2O2 accumulation in the tumor. Inside tumor cells, Met can inhibit the consumption of O2 to relieve tumor hypoxia by suppressing mitochondrial respiration. The alleviated-tumor hypoxia can not only elevate H2O2 content via the Dox-activated cascade reaction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and superoxide dismutase (SOD), but also improve the efficacy of Dox. More importantly, the depletion of glutathione (GSH) accompanies the whole treatment process, which can realize the conversion of Cu2+ to Cu+ and boost reactive oxygen species (ROS) accumulation to improve chemodynamic therapy (CDT) efficacy. Meanwhile, Met is expected to cut off the energy supply by inhibiting respiration, leading to starvation therapy. In vivo investigations demonstrate that tumor growth is significantly inhibited through the enhanced chemo/chemodynamic synergistic treatment. This work provides a new paradigm for cancer therapy using an economical and straightforward method to construct a synergistic nanomedicine platform.
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Cobre/química , Portadores de Fármacos/química , Peróxido de Hidrogênio/metabolismo , Metformina/química , Nanoestruturas/química , Consumo de Oxigênio/efeitos dos fármacos , Polímeros/química , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Metabolismo Energético/efeitos dos fármacos , Humanos , Células MCF-7 , NADPH Oxidases/metabolismo , Superóxido Dismutase/metabolismo , Hipóxia Tumoral/efeitos dos fármacosRESUMO
A new Pd/Ce based metal-organic framework is designed and synthesized as a self-sacrificial template for fabrication of an efficient catalyst for CO oxidation. The catalyst obtained by thermal annealing at 700 °C (Pd/CeO2@NC-700) is composed of N-doped carbon with embedded Pd and CeO2 nanoparticles, which are highly dispersed and closely connected in the N-doped carbon; the high Pd loading (33.7 wt%) and the coupling between Pd and the CeO2 phase synergistically boost the CO oxidation performance. The Pd/CeO2@NC-700 catalyst exhibits a 100% conversion temperature of 89 °C and excellent long-term stability. By combining structural characterization with density functional theory calculations, two possible CO oxidation pathways of TPB and TOP are revealed, in which the adsorbed O2 directly dissociates to O* atoms and activates CO* molecules. The transfer of O* between Pd and Ce (TPB) or Pd and Pd (TOP) facilitates the formation of intermediates and finally results in the production of CO2. This work provides a new insight into the development of novel efficient catalysts for CO oxidation based on metal-organic frameworks.
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Recently, anode materials with synergistic sodium storage mechanisms of conversion combined with alloying reactions for sodium ion batteries (SIBs) have received widespread attention due to their high theoretical capacities. In this work, through reacting with an appropriate concentration of Sb3+ ions and a simple carbonization process, hollow ZnSe/Sb2Se3 microspheres encapsulated in nitrogen-doped carbon (ZnSe/Sb2Se3@NC) are progressively synthesized based on a cation-exchange reaction, using polydopamine-coated ZnSe (ZnSe@PDA) microspheres as the precursor. Benefiting from the synergistic effects between the unique structure and composition characteristics, when serving as an anode material for SIBs, they result in higher sodium diffusion coefficients (8.7 × 10-13-3.98 × 10-9 cm2 s-1) and ultrafast pseudocapacitive sodium storage capability. Compared with ZnSe@NC and Sb2Se3@NCs exhibit, ZnSe/Sb2Se3@NC exhibits more stable capacity (438 mA h g-1 at a current of 0.5 A g-1 after 120 cycles) and superior rate performance (316 mA h g-1 at 10.0 A g-1). Our work provides a convenient method to construct high performance anodes with tunable composition and structure for energy storage.