RESUMO
Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.
Assuntos
Carcinoma de Células Renais , Imunoterapia , Neoplasias Renais , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/genética , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Animais , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Imunoterapia/métodos , Camundongos , Proliferação de Células/efeitos dos fármacos , Movimento Celular , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Progressão da Doença , Prognóstico , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lithium-sulfur batteries (LSBs) are considered next-generation energy storage and conversion solutions owing to their high theoretical specific capacity and the high abundance/low-cost of sulfur-based cathode materials. However, LSBs still encounter significant challenges, including the low conductivities of sulfur-based materials, severe volumetric expansion of sulfur during the discharge process, and the persistent "shuttle effect" of polysulfides. In recent years, a tremendous amount of research has been conducted to address the above challenges by developing coating and compositing materials and corresponding fabrication strategies for sulfur-based cathode materials. In this study, the surface coating, compositing materials, and fabrication methodologies of LSB cathodes are comprehensively reviewed in terms of advanced materials, structure/component characterization, functional mechanisms, and performance validation. Some technical challenges are analyzed in detail, and possible future research directions are proposed to overcome the challenges toward practical applications of lithium-sulfur batteries.
RESUMO
Doping metals and constructing heterostructures are pivotal strategies to enhance the electrocatalytic activity of metal-organic frameworks (MOFs). Nevertheless, effectively designing MOF-based catalysts that incorporate both doping and multiphase interfaces poses a significant challenge. In this study, a one-step Co-doped and Co3O4-modified Ni-MOF catalyst (named Ni NDC-Co/CP) with a thickness of approximately 5.0 nm was synthesized by a solvothermal-assisted etching growth strategy. Studies indicate that the formation of the Co-O-Ni-O-Co bond in Ni NDC-Co/CP was found to facilitate charge density redistribution more effectively than the Co-O-Ni bimetallic synergistic effect in NiCo NDC/CP. The designating Ni NDC-Co/CP achieved superior oxygen evolution reaction (OER) activity (245 mV @ 10 mA cm-2) and robust long stability (100 h @ 100 mA cm-2) in 1.0 M KOH. Furthermore, the Ni NDC-Co/CP(+)||Pt/C/CP(-) displays pregnant overall water splitting performance, achieving a current density of 10 mA cm-2 at an ultralow voltage of 1.52 V, which is significantly lower than that of commercial electrolyzer using Pt/C and IrO2 electrode materials. In situ Raman spectroscopy elucidated the transformation of Ni NDC-Co to Ni(Co)OOH under an electric field. This study introduces a novel approach for the rational design of MOF-based OER electrocatalysts.
RESUMO
Although lithium-sulfur (Li-S) batteries have attracted strong consideration regarding their fundamental mechanism and energy applications, the inferior cycling performance and low reaction rate caused by the "shuttling effect" and the sluggish reaction kinetics of lithium polysulfides (LiPSs) impede their practical application. In this work, graphitic C3N4 (g-C3N4) assembled with highly-dispersed nitrogen-containing carbon quantum dots (CQDs) is designed as a cooperative catalyst to accelerate the reaction kinetics of LiPS conversion, the precipitation of Li2S during discharging, and insoluble Li2S decomposition during the charging process. Meanwhile, the introduction of CQDs improves the conductivity of the g-C3N4 substrate, showing great significance for the construction of high-performance electrocatalysts. As a result, the as-obtained composite shows efficient adsorption and electrochemical conversion of LiPSs, and the Li-S batteries assembled with CQDs/g-C3N4 exhibit an initial specific capacity of 1300.0 mA h g-1 at the current density of 0.1C and retain 582.3 mA h g-1 after 200 cycles. The electrode with the modified composite displays a greater capacity contribution of Li2S precipitation (175.7 mA h g-1), indicating an enhanced catalytic activity of g-C3N4 decorated by CQDs. The rational design of CQDs/g-C3N4 as a sulfur host could be an effective strategy for developing high performance Li-S batteries.
RESUMO
2D metal-organic frameworks (MOFs) have emerged as potential candidates for electrocatalytic oxygen evolution reactions (OER) due to their inherent properties like abundant coordination unsaturated active sites and efficient charge transfer. Herein, a versatile and massively synthesizable self-etching assembly strategy wherein nickel-iron foam (NFF) acts as a substrate and a metal ion source. Specifically, by etching the nickel-iron foam (NFF) surface using ligands and solvents, Ni/Fe metal ions are activated and subsequently reacted under hydrothermal conditions, resulting in the formation of self-supporting nanosheet arrays, eliminating the need for external metal salts. The obtained 33 % NiFeMOF/NFF exhibits remarkable OER performance with ultra-low overpotentials of 188/231â mV at 10/100â mA cm-2, respectively, outperforming most recently reported catalysts. Besides, the built 33 % NiFeMOF/NFF(+)||Pt/C(-) electrolyzer presents low cell voltages of 1.55/1.83â V at 10/100â mA cm-2, superior to the benchmark RuO2 (+)||Pt/C(-), implying good industrialization prospects. The excellent catalytic activity stems from the modulation of the electronic spin state of the Ni active site by the introduction of Fe, which facilitates the adsorption process of oxygen-containing intermediates and thus enhances the OER activity. This innovative approach offers a promising pathway for commercial-scale sustainable energy solutions.
RESUMO
Bimetallic metal-organic framework (BMOF) exhibits better electrocatalytic performance than mono-MOF, but deciphering the precise anchoring of foreign atoms and revealing the underlying mechanisms at the atomic level remains a major challenge. Herein, a novel binuclear NiFe-MOF with precise anchoring of Fe sites is synthesized. The low-crystallinity (LC)-NiFe0.33 -MOF exhibited abundant unsaturated active sites and demonstrated excellent electrocatalytic oxygen evolution reaction (OER) performance. It achieved an ultralow overpotential of 230 mV at 10 mA cm-2 and a Tafel slope of 41 mV dec-1 . Using a combination of modulating crystallinity, X-ray absorption spectroscopy, and theoretical calculations, the accurate metal sequence of BMOF and the synergistic effect of the active sites are identified, revealing that the adjacent active site plays a significant role in regulating the catalytic performance of the endmost active site. The proposed model of BMOF electrocatalysts facilitates the investigation of efficient OER electrocatalysts and the related catalytic mechanisms.
RESUMO
We have previously found that a mixture exposure of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand-receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE-47 (50 µM) or Cd (5 µM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co-treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N-acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved-caspase-3 and gasdermin E N-terminal (GSDME-NT), while caspase-8, caspase-3, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE-47 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME-dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.
Assuntos
Cádmio , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Cádmio/toxicidade , Caspase 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Éter , Células Epiteliais/metabolismoRESUMO
OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION: 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.
Assuntos
Variações do Número de Cópias de DNA , Epilepsia Resistente a Medicamentos , Lactente , Feminino , Masculino , Humanos , Criança , Recém-Nascido , Pré-Escolar , Epilepsia Resistente a Medicamentos/genética , Estudos Retrospectivos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Although Pt is a widely adopted commercial catalyst for the hydrogen evolution reaction (HER), its practical application is greatly limited by its prohibitive cost and high energy barrier for H2O dissociation in alkaline media. Herein, an ultrafine Pt-based catalyst decorated with oxygenophilic Ni-sites is rationally designed and successfully synthesized with Pt5(GS)10 (HGS = l-reduced glutathione) nanocluster precursor. The optimized Ni-decorated Pt catalyst (Ni-Pt-C-500) with ultrafine nanoparticles (about 1.6 nm) exhibits a low overpotential (14.0 mV) at 10 mA cm-2 and a mild Tafel slope of 20.8 mV dec-1 in the HER, which is superior to its undecorated counterpart (Pt-C-500), the commercial 20 wt% Pt/C catalyst and most of the previously reported Pt-based electrocatalysts. Experimental observations and theoretical calculations indicate that H2O could be spontaneously adsorbed to Ni-sites of the Ni-Pt-C-500 catalyst. Mechanistic studies reveal that Ni-sites promote HER by accelerating the kinetic of H2O cleavage and optimizing the electronic structure of Pt. This work paves a new avenue for designing other ultrafine hybrid electrocatalysts based on metal nanoclusters to enhance catalytic reaction kinetics.
RESUMO
Fe-N-C catalysts with single-atom Fe-N4 configurations are highly needed owing to the high activity for oxygen reduction reaction (ORR). However, the limited intrinsic activity and dissatisfactory durability have significantly restrained the practical application of proton-exchange membrane fuel cells (PEMFCs). Here, we demonstrate that constructing adjacent metal atomic clusters (ACs) is effective in boosting the ORR performance and stability of Fe-N4 catalysts. The integration of Fe-N4 configurations with highly uniform Co4 ACs on the N-doped carbon substrate (Co4 @/Fe1 @NC) is realized through a "pre-constrained" strategy using Co4 molecular clusters and Fe(acac)3 implanted carbon precursors. The as-developed Co4 @/Fe1 @NC catalyst exhibits excellent ORR activity with a half-wave potential (E1/2 ) of 0.835â V vs. RHE in acidic media and a high peak power density of 840â mW cm-2 in a H2 -O2 fuel cell test. First-principles calculations further clarify the ORR catalytic mechanism on the identified Fe-N4 that modified with Co4 ACs. This work provides a viable strategy for precisely establishing atomically dispersed polymetallic centers catalysts for efficient energy-related catalysis.
RESUMO
Diabetes mellitus (DM) is the most widely recognized metabolic illness with expanding morbidity among ongoing years. Its high incapacity rate and death rate badly affect individuals' quality of life. Increasing proofs backed the relationship between metal exposures with the risk of DM, but the methodological boundedness cannot clarify the complexity of the internal relationship of metal mixtures. We fitted the logistic regression model, weighted quantile sum regression model, and Bayesian kernel machine regression model to assess the relationship between the metal exposures with DM in adults who participated in the National Health and Nutrition Examination Survey 2013-2016. The metals (lead, cadmium, and copper) levels were significantly higher among diabetic compared to the healthy controls. In the logistic regression model established for each single metal, lead and manganese were associated with DM in both unadjusted and mutually adjusted models (highest vs. lowest concentration quartile). When considering all metal as a mixed exposure, we found a generally positive correlation between metal mixtures with DM (binary outcome) and glycohemoglobin (HbA1c) levels (continuous outcome). Exposure to metal mixtures was associated with an increased risk of DM and elevated levels of HbA1c.
Assuntos
Diabetes Mellitus , Qualidade de Vida , Humanos , Adulto , Estudos Transversais , Hemoglobinas Glicadas , Inquéritos Nutricionais , Teorema de Bayes , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Metais/toxicidadeRESUMO
Nonuniform microstretching (NUMS) naturally occurs in real bone tissues in vivo, but its profound effects have not been identified yet. In order to explore the biological effects of NUMS and static stretch (uniform stretch [US]) on cells, a new "musical dish" device was developed. Musical signal was used to provide NUMS to cells. More stress fibers, arranging along the long axis of cells, were formed throughout the cells under NUMS, compared with US and untreated control group, although cell morphology did not show any alteration. Whole transcriptome sequencing revealed enhanced osteogenic differentiation of cells after NUMS treatment. Cells in the NUMS group showed a higher expression of bone-related genes, while genes related to stemness and other lineages were down-regulated. Our results give insights into the biological effects of NUMS and US on stem cell osteogenic differentiation, suggesting beneficial effects of micromechanical stimulus for osteogenesis. The newly developed device provides a basis for the development of NUMS derived rehabilitation technology to promote bone healing.
RESUMO
Objective: To explore the effect of music in pain perception and the molecular mechanism. Methods: Mice were separated to control, music, music + inhibitor, and saline group. Percentage pain reduction of mice in each group was determined. The contents of 5-HT, Glu, and NE in cerebrospinal fluid of mice in the four groups were determined by HPLC. FISH was used to analyze the distribution characteristics of GRIK5 in hippocampal tissues. The protein expressions of GRIK5, NMDA 1, and TRPC1 in the hippocampal tissues were determined via western blot. Results: Mice exposed to music showed a higher percentage of pain reduction compared to model animals, while injection of GRIK5 inhibitor weakened the effect of music. It increased the contents of 5-HT, Glu, and NE in mouse models of depression. The fluorescence signal in music group was significantly stronger than saline group. Music remarkably increased the expression of GRIK5, DLG4, NMDA 1, and TRPC1 proteins when compared with saline group. Conclusion: Music promoted the secretion of Glu. The glutaminergic pathway sensed Glu, subsequently activated GRIK5, DLG4, and NMDA 1 proteins to excite dopaminergic neurons, and finally promoted the production of 5-HT.
Assuntos
Ácido Glutâmico , Música , Animais , Depressão/metabolismo , Depressão/terapia , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Camundongos , N-Metilaspartato/metabolismo , Dor/metabolismo , Percepção da Dor , Serotonina/metabolismoRESUMO
The volatile organic compounds (VOCs) in four Chinese freshwater fishes (i.e., Hypophthalmichthys molitrix (H), Aristichthys nobilis (A), Lateolabrax japonicus (L), Parabramis pekinensis (P)) were separated using gas chromatography-ion mobility spectrometry (GC-IMS) and ultrafast gas chromatography electronic-nose (uf-GC E-nose). Principal component analysis (PCA) was applied to distinguish the VOCs identified from the four freshwater fishes in both raw and cooked states. Twenty compounds were identified from the spectral database of GC-IMS, including five aldehydes, eight alcohols, six ketones, and three esters. In addition, using GC E-nose, 32 compounds were isolated by the first column MTX-5, and 24 compounds were isolated by the second column MXT-1701. PCA results showed that the four fishes could be well discriminated against. The odor profiles of raw and cooked fishes were clearly different. This study demonstrated that specific signals provided from GC-IMS could differentiate freshwater fishes. GC-IMS and uf-GC E-nose could be developed further to distinguish aquatic products based on VOCs. PRACTICAL APPLICATIONS: Two new methods, gas chromatography-ion mobility spectrometry (GC-IMS) and ultrafast gas chromatography electronic-nose (uf-GC E-nose), were used to analyze the volatile organic compounds (VOCs) in four Chinese freshwater fishes at raw and cooked status. GC-IMS has the characteristics of fast detection speed and high sensitivity. The accuracy of the qualitative analysis of the compounds is better with GC-IMS (larger data volume, leading to a better in-depth statistical analysis). Uf-GC E-nose could provide a nondestructive, fast, relatively low cost, and trustworthy way for flavor analysis. According to the techniques, the established fingerprints of VOCs provided an additional tool for food analysis.
Assuntos
Espectrometria de Mobilidade Iônica , Compostos Orgânicos Voláteis , Animais , China , Nariz Eletrônico , Eletrônica , Peixes , Água Doce , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Mobilidade Iônica/métodos , Compostos Orgânicos Voláteis/análiseRESUMO
BACKGROUND: Cardiorenal syndrome (CRS) is a condition that defines disorders of the heart and kidneys whereby "acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other". Early diagnosis of its biomarkers has a significant impact on the treatment and prognosis of the CRS. Elevated serum NGAL and NT-proBNP levels are independent risk factors for predicting heart and kidney disease. Therefore, we proposed early detection of type 1 CRS using serum NGAL in combination with NT-proBNP. OBJECTIVE: This study intended to investigate the clinical value of serum NGAL in combination with NT-proBNP in the early diagnosis of type 1 CRS. METHODS: In this paper, 80 patients with type 1 CRS and 80 healthy controls admitted to our hospital from January 2019 to August 2020 were retrospectively included, and the predictive value of single index and combined indices for predicting CRS were judged by calculating the correlation between serum NGAL, NT-proBNP and the creatinine levels and plotting receiver operating characteristic (ROC) curves. RESULTS: There was no difference in baseline data between the control and patient groups. Serum NGAL and NT-proBNP in the patient group were significantly higher than those in the control group, and were positively correlated with changes in blood creatinine. The ROC curves showed that serum NGAL and NT-proBNP independently had a high predictive value for CRS, and the combination of the two had a better predictive value. CONCLUSION: Serum NGAL in combination with NT-proBNP is of high clinical value for the early diagnosis of type 1 CRS.
RESUMO
BACKGROUND: The main cause of chronic renal allograft dysfunction (CRAD) still remains unclear. Insulin resistance (IR) may be a potential inducement, but there is insufficient evidence about this association. We aimed to establish a rat model of CRAD complicated with IR and to explore the function and pathologic changes of the renal allograft induced by IR. METHODS: F344-to-Lewis rats of CRAD were fed a high-fat diet to induce IR. They were divided into 3 groups: IR (CRAD+IR), CRAD, and control (CTL). Serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to evaluate the renal function. The Homeostasis Model Assessment (HOMA)-IR index was detected by comparing the values of fasting serum insulin levels (FINS) with fasting blood glucose levels (FBG). The pathologic analysis was conducted by the degree of renal lesions including glomerular lesions, renal tubular lesions, hemorrhage, inflammatory cell infiltration, fibrillation, and hyperplasia of the renal interstitium. RESULTS: In the second, third, and fourth month after surgery, serum levels of Scr and BUN in the IR group were reduced more than those in the CRAD group, while they were both higher compared to the CTL group, suggesting that renal function in the CRAD group was declined. The HOMA-IR in the IR group was greater than that in the CRAD and CTL groups, showing that simple high-fat diet feeding significantly and steadily increased FINS and FBG in CRAD complicated with IR rats. Pathologic changes indicated that the CRAD rat model was successfully constructed and was still in the early-middle stages of renal lesions 4 months after surgery, yet IR presented a significant effect on CRAD. CONCLUSION: These results indicate that the stable CRAD complicated with IR rat model can be established through a high-fat diet in CRAD rats in 4 months, and IR could be an influencing factor.
Assuntos
Modelos Animais de Doenças , Resistência à Insulina , Transplante de Rim , Disfunção Primária do Enxerto/complicações , Aloenxertos , Animais , Dieta Hiperlipídica/efeitos adversos , Rim/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Transplante HomólogoRESUMO
The in situ tracking of the pyrolysis of a binary molecular cluster [Zn7 (µ3 -CH3 O)6 (L)6 ][ZnLCl2 ]2 is presented with one brucite disk and two mononuclear fragments (L=mmimp: 2-methoxy-6-((methylimino)-methyl)phenolate) to porous carbon using TG-MS from 30 to 900 °C. Following up the spilled gas product during the decomposed reaction of zinc cluster along the temperature rising, and in conjunction with XRD, SEM, BET and other materials characterization, where three key steps were observed: 1)â cleavage of the bulky external ligand; 2)â reduction of ZnO and 3)â volatilization of Zn. The real-time-dependent phase-sequential evolution of the remaining products and the processing of pore forming template transformation are proposed simultaneously. The porous carbon structure featuring a uniform nano-sized pore distribution synthesized at 900 °C with the highest surface area of 1644â m2 g-1 and pore volume of 0.926â cm3 g-1 exhibits the best known capacitance of 662â F g-1 at 0.5â A g-1 .
RESUMO
Changes in the stiffness of chondrocyte extracellular matrix (ECM) are involved in the pathological progression of osteoarthritis (OA). However, the downstream responses of cartilage ECM stiffness are still unclear. YAP (Yes-associated protein) has been extensively studied as a mechanotransducer, we thus hypothesized that by targeting the downstream molecule activity of ECM stiffness could maintain chondrocyte phenotype and prevent cartilage degeneration in OA. Here, we showed that human cartilage matrix stiffened during pathological progression of OA, and the chondrocyte YAP activity was associated with ECM stiffness. We then mimicked the physiological and pathological stiffness of human cartilage by using PDMS-based substrates, and found that YAP was activated in chondrocytes seeded on stiff substrate, gradually losing their phenotype. In addition, it was observed that YAP was also significantly activated in mice OA development, and conditional knockout (cKO) of YAP in mice preserved collagen II expression and protected cartilage from degeneration in the OA model. Furthermore, intra-articular injection of YAP-selective inhibitor, Verteporfin, significantly maintained cartilage homeostasis in mice OA model. This study indicates that the application of mechanotransducer-targeted drugs could be a potential therapeutic approach for cartilage repair in OA.
Assuntos
Cartilagem Articular , Quitosana , Osteoartrite , Animais , Condrócitos , Camundongos , Microesferas , Osteoartrite/tratamento farmacológico , VerteporfinaRESUMO
Controllable structure and defect design are considered as efficient strategies to boost the electrochemical activity and stability of catalysts for the oxygen evolution reaction (OER). Herein, oxygen defect hollow Co3O4/nitrogen-doped carbon (OV-HCo3O4@NC) composites were successfully synthesized using tannic acid-modified ZIF-67 (TAMZIF-67) as the precursor through a one-step pyrolysis. Tannic acid provides abundant oxygen during the pyrolysis process of the modified ZIF-67, which can contribute to the formation of oxygen defects and the construction of a hollow structure. The existence of oxygen defects is shown by X-ray photoelectron spectroscopy and electron paramagnetic resonance, whereas the hollow structure is confirmed by transmission electron microscopy. The optimized OV-HCo3O4@NC shows good electrocatalytic activity and exhibits a low overpotential of 360 mV at a current density of 10 mA cm-2 in 0.1 M KOH due to the hollow structure, abundant oxygen defects, and good electrical conductivity. This work provides valuable insights into the exploration of promising OER electrocatalysts with oxygen defects and special structures.
RESUMO
Some Eastern Asian countries deem pufferfish - especially its muscle - a culinary delight. Herein, molecular mass fingerprinting of soups prepared by Takifugu flavidus, Takifugu obscurus and Takifugu rubripes was established via matrix-assisted laser desorption/ionization - mass spectrometry (MALDI MS). Soup samples were directly analyzed by MALDI MS to collect mass spectra within 0-700â¯Da in a quick way, followed by principal component analysis to distinguish the different soups and to find out the distinctive compounds among the soups. High performance liquid chromatography - tandem MS (HPLC-MS/MS) was applied to identify the compounds. Nineteen compounds were identified from the HPLC-MS/MS data by using METLIN database. Through literature mining, we found that these compounds are closely related to the flavor, nutrition, and safety of pufferfish soups. This method can also be used as a facile way to distinguish between different pufferfish fillets when morphological characters have been damaged or destroyed.