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1.
Int J Biol Sci ; 20(8): 3008-3027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904013

RESUMO

SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.


Assuntos
Carcinoma de Células Renais , Movimento Celular , Proliferação de Células , Histona-Lisina N-Metiltransferase , Neoplasias Renais , Humanos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Movimento Celular/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Linhagem Celular Tumoral , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fatores Associados à Proteína de Ligação a TATA/genética , Metilação , Fator de Transcrição TFIID/metabolismo , Fator de Transcrição TFIID/genética , Regulação Neoplásica da Expressão Gênica
2.
Nat Commun ; 15(1): 4675, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824139

RESUMO

H2O dissociation plays a crucial role in solar-driven catalytic CO2 methanation, demanding high temperature even for solar-to-chemical conversion efficiencies <1% with modest product selectivity. Herein, we report an oxygen-vacancy (Vo) rich CeO2 catalyst with single-atom Ni anchored around its surface Vo sites by replacing Ce atoms to promote H2O dissociation and achieve effective photothermal CO2 reduction under concentrated light irradiation. The high photon flux reduces the apparent activation energy for CH4 production and prevents Vo from depletion. The defects coordinated with single-atom Ni, significantly promote the capture of charges and local phonons at the Ni d-impurity orbitals, thereby inducing more effective H2O activation. The catalyst presents a CH4 yield of 192.75 µmol/cm2/h, with a solar-to-chemical efficiency of 1.14% and a selectivity ~100%. The mechanistic insights uncovered in this study should help further the development of H2O-activating catalysts for CO2 reduction and thereby expedite the practical utilization of solar-to-chemical technologies.

3.
ACS Nano ; 18(20): 13035-13048, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38728209

RESUMO

We report a solvothermal method for the synthesis of an oxygen vacancy-enriched ZrO2 photocatalyst with Co single atoms and Ni clusters immobilized on the surface. This catalyst presents superior performance for the reduction of CO2 in H2O vapor, with a CO yield reaching 663.84 µmol g-1 h-1 and a selectivity of 99.52%. The total solar-to-chemical energy conversion efficiency is up to 0.372‰, which is among the highest reported values. The success, on one hand, depends on the Co single atoms and Ni clusters for both extended spectrum absorption and serving as dual-active centers for CO2 reduction and H2O dissociation, respectively; on the other hand, this is attributed to the enhanced photoelectric and thermal effect induced by concentrated solar irradiation. We demonstrate that an intermediate impurity state is formed by the hybridization of the d-orbital of single-atom Co with the molecular orbital of H2O, enabling visible-light-driven excitation over the catalyst. In addition, Ni clusters play a crucial role in altering the adsorption configuration of CO2, with the localized surface plasmon resonance effect enhancing the activation and dissociation of CO2 induced by visible-near-infrared light. This study provides valuable insights into the synergistic effect of the dual cocatalyst toward both efficient photothermal coupling and surface redox reactions for solar CO2 reduction.

4.
Chem Asian J ; 19(12): e202400208, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38607325

RESUMO

Due to the serious ecological problems caused by the high CO2 content in the atmosphere, reducing atmospheric CO2 has attracted widespread attention from academia and governments. Among the many ways to mitigate CO2 concentration, the capture and comprehensive utilization of CO2 through chemical methods have obvious advantages, whose key is to develop suitable adsorbents and catalysts. Frustrated Lewis pairs (FLPs) are known to bind CO2 through the interaction between unquenched Lewis acid sites/Lewis base sites with the O/C of CO2, simultaneously achieving CO2 capture and activation, which render FLP better potential for CO2 utilization. However, how to construct efficient FLP targeted for CO2 utilization and the mechanism of CO2 activation have not been systematically reported. This review firstly provides a comprehensive summary of the recent advances in the field of CO2 capture, activation, and transformation with the help of FLP, including the construction of homogeneous and heterogeneous FLPs, their interaction with CO2, reaction activity, and mechanism study. We also illustrated the challenges and opportunities faced in this field to shed light on the prospective research.

5.
Front Immunol ; 15: 1361231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545095

RESUMO

Introduction: Nocardia seriolae adversely impacts a diverse range of fish species, exhibiting significant pathogenic characteristics that substantially impede the progress of aquaculture. N. seriolae infects in fish has a long incubation period, and clinical symptoms are not obvious in the early stages. There is presently no viable and eco-friendly approach to combat the spread of the disease. According to reports, N. seriolae primarily targets macrophages in tissues after infecting fish and can proliferate massively, leading to the death of fish. Interferon-gamma (IFN-γ) is a crucial molecule that regulates macrophage activation, but little is known about its role in the N. seriolae prevention. Methods: IFN-γ was first defined as largemouth bass (Micropterus salmoides, MsIFN-γ), which has a highly conserved IFN-γ characteristic sequence through homology analysis. The recombinant proteins (rMsIFN-γ) were obtained in Escherichia coli (E. coli) strain BL21 (DE3). The inflammatory response-inducing ability of rMsIFN-γ was assessed in vitro using monocytes/macrophages. Meanwhile, the protective effect of MsIFN-γ in vivo was evaluated by N. seriolae infection largemouth bass model. Results: In the inflammatory response of the monocytes/macrophages activated by rMsIFN-γ, various cytokines were significantly increased. Interestingly, interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-a) increased by 183- and 12-fold, respectively, after rMsIFN-γ stimulation. rMsIFN-γ improved survival by 42.1% compared with the control. The bacterial load in the liver, spleen and head kidney significantly decreased. rMsIFN-γ was also shown to better induce increased expression of IL-1ß, TNF-α, hepcidin-1(Hep-1), major histocompatibility complex I (MHCI), and MHC II in head kidney, spleen and liver. The histopathological examination demonstrated the transformation of granuloma status from an early necrotic foci to fibrosis in the infection period. Unexpectedly, the development of granulomas was successfully slowed in the rMsIFN-γ group. Discussion: This work paves the way for further research into IFN-γ of largemouth bass and identifies a potential therapeutic target for the prevention of N. seriolae.


Assuntos
Bass , Nocardiose , Nocardia , Animais , Interferon gama , Escherichia coli , Nocardiose/prevenção & controle , Nocardiose/veterinária , Proteínas Recombinantes
6.
Funct Integr Genomics ; 23(4): 326, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880458

RESUMO

Renal cell carcinoma (RCC) is the most lethal of the urologic malignancies. We previously discovered that DAB2IP, a novel Ras GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. In this study, we determined the biological functions of DAB2IP in clear cell RCC (ccRCC) and its potential mechanisms of action. Correlations between DAB2IP expression level and ccRCC tumor size and patient survival were analyzed, and the results showed that ccRCC patients with high DAB2IP mRNA level exhibited smaller tumor size and better survival than the patients with low DAB2IP. Compared to control, DAB2IP knockdown significantly increased cell proliferation, promoted cell cycle progression in G1/S phase, and decreased p27 expression. Mechanism studies demonstrated that loss of DAB2IP promoted p27 protein phosphorylation, cytosolic sequestration, and subsequently ubiquitination-mediated degradation in ccRCC cells. Further studies confirmed that the proline-rich domain in C terminal (CPR) of DAB2IP suppressed AKT phosphorylation and p27 phosphorylation on S10. Hence, DAB2IP is essential for p27 protein stabilization in ccRCC, which is at less partly mediated by PI3K/AKT signaling pathway.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Proliferação de Células/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Linhagem Celular Tumoral , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo
8.
Nat Commun ; 14(1): 5277, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644027

RESUMO

Phase separation is a universal physical transition process whereby a homogeneous mixture splits into two distinct compartments that are driven by the component activity, elasticity, or compositions. In the current work, we develop a series of heterogeneous colloidal suspensions that exhibit both liquid-liquid phase separation of semiflexible binary polymers and liquid crystal phase separation of rigid, rod-like nanocellulose particles. The phase behavior of the multicomponent mixture is controlled by the trade-off between thermodynamics and kinetics during the two transition processes, displaying cholesteric self-assembly of nanocellulose within or across the compartmented aqueous phases. Upon thermodynamic control, two-, three-, and four-phase coexistence behaviors with rich liquid crystal stackings are realized. Among which, each relevant multiphase separation kinetics shows fundamentally different paths governed by nucleation and growth of polymer droplets and nanocellulose tactoids. Furthermore, a coupled multiphase transition can be realized by tuning the composition and the equilibrium temperature, which results in thermotropic behavior of polymers within a lyotropic liquid crystal matrix. Finally, upon drying, the multicomponent mixture undergoes a hierarchical self-assembly of nanocellulose and polymers into stratified cholesteric films, exhibiting compartmentalized polymer distribution and anisotropic microporous structure.

9.
J Mol Graph Model ; 118: 108349, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36198249

RESUMO

This work provides a molecular scale insight into non-phosgene synthesis based on the reaction of dimethylhexane-1,6-dicarbamate from 1,6-hexamethylenediamine, urea and methanol with computational electronic method. By exploring almost all possible reaction modes and comparing the effective barrier of each channel, this work analyzes the optimal reaction mechanism for both non-catalytic and self-catalytic systems. The mechanism without catalysis has a high effective free energy barrier (FEB) of 47.0 kcal mol-1. As for self-catalytic system, after sorting out the reaction pathway network, an effective FEB of 24.6 kcal mol-1 is confirmed which corresponds to dissociation of urea.


Assuntos
Metanol , Ureia , Teoria da Densidade Funcional , Catálise
10.
J Mol Model ; 29(1): 30, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36585991

RESUMO

CONTEXT: Isomerization processes between glucose and fructose catalyzed by four different organic ligands are investigated with quantum chemistry methods in this study. These organic ligands are the carboxylic pendant group, sulfonic pendant group, amino pendant group, and 1H-imidazole ligand. After guessing and verifying a variety of elementary reactions, transition states and energy barriers that are relevant to the optimum pathways have been confirmed. The effective barriers under the catalysis of the carboxylic pendant group, sulfonic pendant group, amino pendant group, and 1H-imidazole ligand are 97.5 kJ mol-1, 134.7 kJ mol-1, 146.7 kJ mol-1, and 167.7 kJ mol-1, respectively. Then, based on the conclusions of the non-solvation model, the effective barriers in solvents are briefly investigated. The implicit model predicts that solvents bring little improvement or setback to catalyzed reaction models. The explicit model shows that the proton transfer with the participant of water molecules can improve the catalytic performance of Lewis bases in these reactions. The detailed reaction mechanism combing and reliable reaction templates provided in this work will be useful for catalysis designs for glucose transformation to fructose. METHODS: This work used the computational level of ωB97M-D3BJ/def2-SVP and the software package of ORCA 4.2. For solvent effects, energies of the gas phase were corrected by the combination of C-PCM and SMD.


Assuntos
Frutose , Glucose , Humanos , Isomerismo , Glucose/química , Frutose/química , Ligantes , Solventes/química , Imidazóis , Catálise
11.
Research (Wash D C) ; 2022: 9890686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349337

RESUMO

Conductive polymer fibers/wires (CPFs) are important materials in modern technologies due to their unique one-dimension geometry, electrical conductivity, and flexibility. However, the advanced applications of current CPFs are limited by their low electrical conductivities (<500 S/m) and poor interfacial interactions between conductive fillers (e.g., graphite) and polymers. Therefore, in current electrical applications, metal wires/foils like copper and aluminum are the most frequently utilized conductive fibers/wires instead of the inferior conductive CPFs. This work successfully addresses the heavy phase segregation between polymers and conductive inorganic materials to obtain semiliquid metal polymer fibers (SLMPFs) which exhibit an ultrahigh electrical conductivity (over 106 S/m), remarkable thermal processability, and considerable mechanical performance (Young's modulus: ~300 MPa). Semiliquid metal (gallium-tin alloy) with tunable viscosities is the key to achieve the excellent miscibility between metals and polymers. Both the rheological results and numerical simulations demonstrate the critical viscosity matching for the successful preparation of the fibers. More importantly, the fibers are adapted with classic polymer melt-processing like melt injection, which indicates the scalable production of the highly conductive fibers. The SLMPFs are highly promising substitutes for metal wires/fibers in modern electrical applications such as electricity transmission, data communication, and underwater works.

12.
Front Endocrinol (Lausanne) ; 13: 989030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246885

RESUMO

Background: Bladder cancer is the most common leading cause of mortality around the world. Previous studies have indicated that genetic factors are significantly associated with bladder cancer progression-for instance, the CYP2C8 gene is involved in bladder cancer progression. However, little is known about the impact of CYP2C8 genetic polymorphisms on bladder cancer risk. We aimed to detect the association between CYP2C8 variations and bladder cancer susceptibility. Methods: This study included 550 healthy subjects and 217 bladder cancer patients. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the correlation of CYP2C8 polymorphisms with bladder cancer risk. Multifactor dimensionality reduction (MDR) was carried out to investigate the influence of single-nucleotide polymorphism (SNP)-SNP interactions on bladder cancer. Results: Our study showed that two SNPs were significantly associated with an increased risk of bladder cancer (rs1934951: OR 1.96, 95% CI 1.37-2.82, p = 2.67E-04; rs17110453: OR 1.89, 95% CI 1.35-2.67, p = 2.53E-04). On the contrary, two SNPs identified in the study had protective effects on bladder cancer (rs1934953: OR 0.26, 95% CI 0.14-0.47, p = 1.20E-05; rs2275620: OR 0.40, 95% CI 0.21-0.76, p = 0.005). The MDR analysis suggested that the combination of rs1934953, rs1934951, rs2275620, and rs17110453 was the best model to predict bladder cancer (CVC 10/10, testing accuracy 0.6720, p < 0.0001). Conclusion: There was a significant association between CYP2C8 polymorphisms (rs1934953, rs1934951, rs2275620, and rs17110453) and susceptibility to bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Citocromo P-450 CYP2C8/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética
13.
Artigo em Inglês | MEDLINE | ID: mdl-36212952

RESUMO

Objective: Currently, cumulative evidence has shown that loss of NEK2 function suppresses tumor growth. However, complete studies on the regulatory role of NEK2 in clear-cellrenal-cell carcinoma (ccRCC) are rarely reported. Methods: The GEPIA database was used for information mining to analyze the gene expression differences between ccRCC tumor and normal tissues. At the same time, we analyzed the protein expression of NEK2 in clinical ccRCC samples and ccRCC cell lines. We detected the effect of NEK2 on the biological behavior of ccRCC at the cell level and further verified the biological effect of NEK2 on ccRCC cells in vivo by nude mouse tumorigenesis experiment. The expression of WNT/ß-cateninpathway-related proteins and downstream proteins related to cell function were detected by Western blotting. Results: Using the GEPIA database, we observed that NEK2 expression level in ccRCC tissues was significantly higher than that in normal kidney tissues and was also related to tumor grade. The survival time of patients with ccRCC with high NEK2 expression was shorter than that of patients with low NEK2 expression. Compared with adjacent carcinoma and normal renal tubular epithelial cells, NEK2 levels were highly expressed in ccRCC tissues and ccRCC cell lines. NEK2 interference restrained ccRCC cell growth, migration, and invasion. NEK2 regulated the malignant behavior of ccRCC cells through the WNT/ß-catenin pathway. Nude mouse tumorigenesis assay results showed that the transplanted tumors from NEK2 silenced mice grew more slowly and were smaller in size than those from control mice. Conclusions: NEK2 elevation may be associated with poor prognosis in ccRCC, and NEK2 enhances ccRCC cell proliferation, migration, and invasion ability by activating the WNT/ß-catenin signaling pathway.

14.
Front Chem ; 10: 1041843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304745

RESUMO

The activation and conversion of the CO2 molecule have always been the most vexing challenge due to its chemical inertness. Developing highly active catalysts, which could overcome dynamic limitations, has emerged as a provable and effective method to promote CO2 activation-conversion. Herein, ETS-10 zeolite-based catalysts, with active nickel species introduced by in situ doping and impregnation, have been employed for CO2 methanation. Conspicuous CO2 conversion (39.7%) and perfect CH4 selectivity (100%) were achieved over the Ni-doped ETS-10 zeolite catalyst at 280°C. Comprehensive analysis, which include X-ray diffraction, N2 adsorption-desorption, SEM, TEM, H2 chemisorption, CO2 temperature programmed desorption, and X-ray photoelectron spectroscopy, was performed. Also, the results indicated that the resultant hierarchical structure, high metal dispersion, and excellent CO2 adsorption-activation capacity of the Ni-doped ETS-10 zeolite catalyst played a dominant role in promoting CO2 conversion and product selectivity.

15.
Anal Methods ; 14(37): 3680-3685, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36063084

RESUMO

Upconversion nanocrystals (UCNCs) have emerged as a new type of fluorescent probe for sensing applications. Herein, we designed a 980 nm excited upconversion luminescence system, composed of core-shell-structured NaYF4 : Yb,Er@NaYF4 : Yb nanocrystals (csUCNCs) and the triethylenetetramine-Cu complex (complex-I), for quantitative detection of sulfide ions. Taking advantage of the specific recognition of complex-I toward S2-, the as-formed compound (complex-II) exhibits excellent spectral overlap not only in the range of fluorescence emissions of UCNCs but also in the excitation wavelength for UCNCs; fluorescence quenching of UCNCs occurs where the complex-II acts as the energy acceptor. Due to the electrostatic repulsion between positively charged ligand-free csUCNCs and complex-I, the fluorescence quenching is based on the primary and secondary inner filter effect rather than the fluorescence resonance energy transfer process. The detection limit of S2- for the upconversion-based system is calculated to be 2.7 µM, exhibiting higher detection sensitivity over the single complex-I compound measured by the spectrophotometric method. Moreover, no significant variation in upconversion luminescence is observed upon the addition of other interfering ions, showing the excellent selectivity of this nanoprobe toward S2-.


Assuntos
Corantes Fluorescentes , Fluoretos , Fluoretos/química , Luminescência , Sulfetos , Trientina
16.
Polymers (Basel) ; 14(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36080735

RESUMO

Thermal management has become an important requirement for many types of electrical equipment due to the development of integrated circuits. In this study, modified and reduced graphene fillers were synthesized in two steps, and then epoxy resin was filled through the evaporation of the solvent. The interfacial thermal resistance between the filler and matrix material was lowered by including amino groups to improve graphene compatibility in the epoxy resin. Furthermore, the reduction procedure was shown to have the potential to fix graphene oxide flaws, thereby improving thermal stability, electrical conductivity, and thermal conductivity of the composites. As a result, the thermal conductivity of the composite reached 1.7 W/mK, which is 750% higher than that of pure epoxy resin, and it was still insulated.

17.
Biomater Sci ; 10(20): 5912-5924, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36040793

RESUMO

The efficacy of free radical-based therapeutic strategies is severely hindered by nonspecific accumulation, premature release and glutathione (GSH) scavenging effects. Herein, a tumor microenvironment-responsive MPDA/AIPH@Cu-TA@HA (abbreviated as MACTH) nanoplatform was constructed by coating Cu2+ and tannic acid (TA) on the surface of azo initiator (AIPH)-loaded mesoporous polydopamine (MPDA) nanoparticles and further modifying them with hyaluronic acid (HA) to achieve tumor-specific photothermal/thermodynamic/chemodynamic synergistic therapy (PTT/TDT/CDT). Once accumulated and internalized into cancer cells through CD44 receptor-mediated active targeting and endocytosis, the HA shell of MACTH would be preliminarily degraded by hyaluronidase (HAase) to expose the Cu-TA metal-phenolic networks, which would further dissociate in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Cu2+ and AIPH. On the one hand, the released Cu2+ could deplete the overexpressed GSH via redox reactions and produce Cu+, which in turn catalyzes endogenous H2O2 into highly cytotoxic hydroxyl radicals (˙OH) for CDT. On the other hand, the local hyperthermia generated by MACTH under 808 nm laser irradiation could not only augment CDT efficacy through accelerating the Cu+-mediated Fenton-like reaction, but also trigger the decomposition of AIPH to produce biotoxic alkyl radicals (˙R) for TDT. The consumption of GSH and accumulation of oxygen-independent free radicals (˙OH/˙R) synergistically amplified intracellular oxidative stress, resulting in substantial apoptotic cell death and significant tumor growth inhibition. Collectively, this study provides a promising paradigm for customizing stimuli-responsive free radical-based nanoplatforms to achieve accurate and efficacious cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Compostos de Diazônio , Glutationa/metabolismo , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase , Peróxido de Hidrogênio/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Oxigênio , Piridinas , Taninos , Termodinâmica , Microambiente Tumoral
18.
Br J Clin Pharmacol ; 88(12): 5317-5325, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35818959

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitor is a new drug class approved for treating dyslipidemias. Herein, we aimed to investigate the safety profiles of PCSK9 inhibitors (alirocumab and evolocumab) using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We included adverse event (AE) reports regarding alirocumab and evolocumab submitted to the FAERs between 2015Q3 to 2021Q1. Disproportionality analyses, including reporting odds ratio (ROR), were performed to detect risk signals from the FAERs data to identify potential drug-AE associations. A signal was considered when the lower limit of the 95% confidence interval of ROR exceeded 1 and ≥3 AEs were reported. The definition relied on system organ class and preferred terms established by the Medical Dictionary for Regulatory Activities. RESULTS: The FAERS database documented 31 475 reports regarding PCSK9 inhibitors (alirocumab and evolocumab) from July 1, 2015, to March 31, 2021. Although some differences were detected, alirocumab and evolocumab shared considerably similar safety profiles. The most significant RORs and most common reports were injection-site reactions (eg, injection-site pain, bruising, haemorrhage, erythema), muscle-related AEs (eg, myalgia, back pain, arthralgia, muscle spasms), influenza-like illness, pain and headache. CONCLUSION: Data mining of the FAERs is useful for examining PCSK9 inhibitor-induced AEs. Herein, our findings were largely consistent with clinical experience and could help clinicians improve the safety of PCSK9 inhibitors in clinical practice.


Assuntos
Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Humanos , Estados Unidos/epidemiologia , United States Food and Drug Administration , Mineração de Dados , Dor
19.
Fish Shellfish Immunol ; 127: 155-165, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35716969

RESUMO

The reduction of fishmeal in aquafeeds has been the concern of researchers. Replacing fishmeal with plant proteins affects intestinal function and inflammation, but the interaction between the intestinal responses and gut microbiota remains unclear. In this study, juvenile channel catfish (Ictalurus punctatus) was fed with four diets in which enzymatic rice protein (RP) replaced fishmeal at levels of 0 (FM), 2.5% (RP2.5), 5.0% (RP5.0), and 7.5% (RP7.5) for 8 weeks to solve the problem mentioned above. Quantification of intestinal morphology showed that 2.5% or 5.0% RP significantly increased villus length and goblet cell number, accompanied by higher activities of intestinal trypsin, alkaline phosphatase (AKP), and Na+/K+-ATPase (NKA) in RP2.5 group (P < 0.05). In contrast, 7.5% RP slightly damaged the intestinal mucosa and significantly reduced the activities of amylase, AKP, and NKA, as well as decreased serum complement 4 (C4) and immunoglobulin M (IgM). Noteworthy, RT-qPCR showed that 2.5% RP significantly down-regulated intestinal mRNA expression level of il8, while up-regulated mif, tlr4, tlr7, tgfß3, and cldn2. In contrast, 7.5% RP up-regulated the mRNA expression levels of il1ß, il8, and mif, while down-regulated cldn3d. Analysis of gut microbiota showed that 2.5% RP increased the relative abundance of Bacteroidetes and significantly activated potential functions of gut microbiota involved in carbohydrate metabolism. The 7.5% RP increased the diversity of the gut microbiota, accompanied by a significant increase in the relative abundance of conditionally pathogenic bacteria such as Vibrio, Serratia, and Aeromonas (classified as Proteobacteria). Notably, Vibrio was the biomarker species with the greatest difference between the FM and RP7.5 groups (genus level). Correlation analysis indicated that Vibrio may affect immunity through the C4 pathway and further lead to gut inflammation and digestive impairment. Taken above, these results indicated that RP could affect intestinal morphology, digestion, and inflammation, and interact with the composition and potential function of gut microbiota. The low RP supplement (2.5%) improved intestinal morphology and digestion, while high supplement (7.5%) disrupted gut microbiota homeostasis, resulting in damage to intestinal mucosa and inflammatory response.


Assuntos
Microbioma Gastrointestinal , Ictaluridae , Oryza , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas Alimentares , Digestão , Ictaluridae/genética , Inflamação/veterinária , Interleucina-8 , RNA Mensageiro
20.
J Colloid Interface Sci ; 613: 224-233, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35033768

RESUMO

High-valence metal doping and abundant grain boundaries (GBs) have been proved to be effective strategies to promote the oxygen evolution reaction (OER). However, the reasonable design of the two to facilitate OER collaboratively is challenging. Herein, a convenient and novel one-step molten salt decomposition strategy is proposed to fabricate segregated-Mo doped nickle nitrate hydroxide with substantial GBs on MoNi foam (Mo-NNOH@MNF). When processed in molten salt, the Mo species on the conductive substrate migrates unevenly to the surface of Mo-NNOH@MNF, which not only induces the formation of abundant GBs to modulate electronic structure, but also improves the intrinsic activity as high-valence dopants, synergistically elevating OER activity. As verification, the optimized Mo-NNOH@MNF-10h exhibits low overpotential of 150 mV at 10 mA cm-2, which can be attributed to the reduced valence charge transition energy of Ni by high-valence Mo dopant, coupled with the fine-tuning of d-band center bond and corresponding local electron density by induced GBs and Mo doping, as DFT calculations revealed. Moreover, the intrinsic robustness and strong adhesion ensure the long-term stability of 6 h at 500 mA cm-2. This work provides a promising molten salt decomposition approach to synthesize advanced materials with unique structures.

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