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1,3-Dipolar cycloaddition of nonstabilized azomethine ylides derived from α-C-H functionalization of tetrahydroisoquinoline for regio- and diastereoselective synthesis of spirooxindole-pyrrolidines is developed. A three-component reaction of readily available cyclic amine, aryl aldehydes, and olefinic oxindoles provides a pot, atom and step economy (PASE) approach for making spiro-heterocyclic compounds with biological interest.

SET7/9 is a member of the protein lysine methyltransferase family that methylates both histone 3 lysine 4 (H3-K4) and lysine(s) of other non-histone proteins. In recent years, dis-regulation of SET7/9 were frequently detected in various cancer types and SET7/9-mediated methylation has been recognized as an important mechanism that affects cancer initiation and development through regulation of a series of cellular processes. Here we review the currently identified histone and non-histone protein targets of SET7/9 that are closely correlated with human cancer and the function of SET7/9 in regulating the expression and stability of its protein targets. The review also discusses the putative role of SET7/9 as an oncogene or tumor suppressor in the development of various cancer types and the underlying mechanisms, which may help better evaluate the potential of SET7/9 as a novel candidate for cancer therapy.

One-pot two sequential [3 + 2] cycloadditions of azomethine ylides with different dipolarophiles for diastereoselective synthesis of spirooxindole pyrrolizidines are introduced. This one-pot synthesis involving five components generates a highly condensed ring system bearing seven stereocenters diastereoselectively. The new method has high pot, atom, and step economy. Only two equivalents of water are released as a side product.

In this review article, we summarize novel or non-standard strategies and methods for the five-membered carbocycle construction in recent Daphniphyllum alkaloid synthesis.

Cadmium (Cd) is an environmental pollutant produced by industrial activities, which has no known physiological benefits to organisms. In our previous study, the transcriptomic profiles of carp head kidney exposed to Cd was analyzed by genomics technique, and confirmed that miRNAs are important in the head kidney injury of carp induced by Cd, but the specific biological mechanism was unclear. In order to further explore the effect of Cd on carp head kidney lymphocyte damage, we established a model of Cd exposure in vitro. The results showed that Cd could increase the expression of Bax (Bcl-2 associated X protein), Caspase9 (Cysteinyl aspartate specific proteinase 9) and Caspase3 (Cysteinyl aspartate specific proteinase 3), inhibit the expression of Bcl-2 (B cell lymphoma/leukemia 2), and induce apoptosis of carp head kidney lymphocytes. In our previous study, we screened the differentially expressed miRNA in Cd-treated lymphocytes by high-throughput sequencing, and found that there was a significant difference in the expression of miR-9-5p. The expression trend of miR-9-5p in the vitro model was the same as that of high-throughput sequencing. We screened the differentially expressed gene FKBP5 (FK506-binding protein 51) in lymphocytes treated with Cd. It was confirmed by double luciferase reporter gene analysis that FKBP5 was the target gene of miR-9-5p. We established the overexpression/knockdown model of miR-9-5p in carp head kidney lymphocyte in vitro. The results showed that miR-9-5p could inhibit the expression of FKBP5, increase the phosphorylation level of Akt, inhibit apoptosis and improve the cell survival rate in carp head kidney lymphocytes. Together, Cd could down-regulate the expression of miR-9-5p, target up-regulate the expression of FKBP5, inhibit the phosphorylation of Akt, and promote the apoptosis of carp head kidney lymphocytes through mitochondrial pathway.

A sandwich Ti3C2Tx/MoS2−xPx heterostructure with outstanding HER activity and excellent long-term durability was constructed by a hydrothermal and phosphorization approach. The sandwich heterostructure and P doping promote excellent HER performance.

FeCoNiCuxMn (x = 0, 0.1, 0.3, 0.5, 0.7 and 0.9) and FeCoNiCu0.1MnB0.05 high entropy alloys (HEAs) were prepared via an improved swing ball-milling method.

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melanoma–bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovascularization–bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.

Background and Aims Pyroptosis of intestinal epithelial cells is associated with intestinal barrier dysfunction and the intestinal inflammatory symptoms of Crohn's disease (CD). The natural plant monomer, nodakenin (Nod), inhibits NOD-like receptor protein 3 (NLRP3) expression, and this study aimed to evaluate its effect on CD-like colitis, as well as possible mechanisms. Methods Using TNBS intervention mice as CD animal models, the therapeutic effect of Nod on CD-like colitis in mice was explored through disease activity index (DAI) analysis, weight change, histological analysis, inflammatory factor expression and intestinal barrier function. In addition, the direct effect of Nod on the pyroptosis of intestinal epithelial cells was explored by immunofluorescence and western blot detection in LPS-/ATP-induced colon organoid models. Furthermore, through bioinformatics and in vivo and in vitro experimental verification, the potential mechanism by which Nod protects intestinal epithelial cells was explored. Results Nod intervention improved colitis and intestinal barrier function in TNBS-induced mice, as demonstrated by improvements in weight loss, DAI, tissue inflammation score, proinflammatory factor expression, and intestinal permeability. In addition, Nod inhibited the pyroptosis of intestinal epithelial cells in colitis mice and LPS-/ATP-induced colon organoids, as well as the expression of key pyroptosis regulators, such as NLRP3, GSDMD-N, and cleaved-caspase-1. Mechanistically, Nod inhibited the activation of PI3K/Akt signalling a in intestinal epithelial cells in TNBS-induced mice and LPS-/ATP-induced colonic organoids. Conclusions Nod restrained the pyroptosis of intestinal epithelial cells to protect the intestinal barrier of CD-like colitis by inhibiting PI3K/Akt signalling, this may provide a new option for the treatment of Crohn's disease.

Based on the conclusions of small reactor environmental impact assessment and social stability risk assessment of small reactors, this paper conducts a special study on the public communication of small reactors. This article discusses the work content, scope and form of public communication of small reactor, and give suggestions on the scope and form of public publicity, public participation and information disclosure. It is matched with small reactor public communication theoretical system and operation manual. The research on the public communication work of small reactor can provide necessary theoretical basis and technical support for the specific public communication work of small reactor. Provide decision support for local policies and construction departments to implement public communication. It is hoped that this study can provide some reference for the public communication of small reactors in the exploratory stage.

Introduction: Boxing is a global sport, including tactics, body, and mind for intense fighting. Athletes need high strength, speed, endurance, agility, and endurance. Through professional training, athletes’ agility and body control are continuously improved. Objective: To develop special fitness training for professional boxers. This conclusion can provide a reference for boxing education and training. Methods: This paper studies the special training of professional boxers by employing literature materials, expert interviews, and self-experience methods. Analysis of the results is done using mathematical statistics. Results: This paper found several particular boxing training methods, such as high-intensity, intensive and developmental training, through analysis. Conclusion: Professional training has a particular promoting effect on improving the physical fitness and competition level of boxers. Level of evidence II; Therapeutic studies - investigation of treatment outcomes. RESUMO Introdução: O boxe é um esporte global, incluindo táticas, corpo e mente para uma luta intensa. Os atletas precisam de muita força, velocidade, resistência, agilidade e resistência. Através do treinamento profissional, a agilidade e o controle corporal dos atletas são continuamente melhorados. Objetivo: Desenvolver um treinamento especial de aptidão física para boxeadores profissionais. Esta conclusão pode fornecer uma referência para o ensino e treinamento do boxe. Métodos: Este artigo estuda o treinamento especial de boxeadores profissionais empregando materiais de literatura, entrevistas com especialistas e métodos de auto experiência. Faz-se análise dos resultados empregando estatísticas matemáticas. Resultados: Este trabalho encontrou vários métodos particulares de treinamento de boxe, tais como treinamento de alta intensidade, intensivo e de desenvolvimento, através de análise. Conclusão: O treinamento profissional tem um efeito particular de promoção na melhoria da aptidão física e do nível de competição dos boxeadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento. RESUMEN Introducción: El boxeo es un deporte global, que incluye la táctica, el cuerpo y la mente para un combate intenso. Los atletas necesitan mucha fuerza, velocidad, resistencia, agilidad y resistencia. Gracias al entrenamiento profesional, la agilidad y el control corporal de los atletas mejoran continuamente. Objetivo: Desarrollar un entrenamiento físico especial para boxeadores profesionales. Esta conclusión puede servir de referencia para la educación y la formación del boxeo. Métodos: Este trabajo estudia el entrenamiento especial de los boxeadores profesionales empleando materiales bibliográficos, entrevistas con expertos y métodos de auto experiencia. El análisis de los resultados se realiza mediante estadísticas matemáticas. Resultados: Este trabajo encontró varios métodos particulares de entrenamiento de boxeo como el entrenamiento de alta intensidad, intensivo y de desarrollo a través del análisis. Conclusión: El entrenamiento profesional tiene un efecto especial de promoción en la mejora de la condición física y el nivel de competición de los boxeadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The concept of “two birds with one stone” is employed to fabricate a symmetric pseudocapacitor. The Si/Co with optimized content in the MOF-derived N-doped carbon-based electrode can work at an ultra-large potential window of −1.0 to 0.4 V.

To fully exploit the superiority of tubular structures, in this study, we systematically explore the optimal preparation conditions for Ni/Co3O4, including cation species and content, additive species and content, and anion species. Our results reveal that the formation of an initial cobalt nickel acetate hydroxide prism is the key factor and directly affects the final microtubular structure. Moreover, P is subsequently doped into the Ni/Co3O4 lattice to increase the M3+/M2+ molar ratio (M = Co and Ni), promote reaction kinetics, and optimize electronic structure. Consequently, the oxygen evolution reaction performance of P-doped tubular Ni/Co3O4 is significantly higher than that of undoped Ni/Co3O4 and the state-of-the-art RuO2 electrocatalyst.

Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn's disease (CD). A recent study indicated that Epac‐2 protected the intestinal barrier and had anti‐inflammatory effects. The present study examined the function of Epac‐2 in CD‐like colitis. Interleukin‐10 gene knockout (Il‐10 −/−) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac‐2 agonists (Me‐cAMP) or Epac‐2 antagonists (HJC‐0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco‐2 and RAW 264.7 cell co‐culture system were used to analyse the effects of Epac‐2 on the cross‐talk between intestinal epithelial cells and inflammatory cells. Epac‐2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac‐2 activation also decreased Caco‐2 cell permeability in an LPS‐induced cell co‐culture system. Epac‐2 activation significantly suppressed nuclear factor (NF)‐κB/mitogen‐activated protein kinase (MAPK) signalling in vivo and in vitro. Epac‐2 may be a therapeutic target for CD based on its anti‐inflammatory functions and protective effects on the intestinal barrier.

Thermal barrier coating (TBC) applications of 7 wt% yttria stabilized zirconia (7YSZ) must meet low thermal conductivity and excellent high temperature stability. However, the resulting morphology of 7YSZ TBCs fabricated by PS-PVD currently remains poorly studied. The present study addresses this issue by evaluating the microstructure, phase composition, grain distribution, and columnar crystal orientations of 7YSZ coatings fabricated by PS-PVD. The results demonstrate that the growth of YSZ columnar crystals exhibits an obvious preferred orientation [101] that is consistent throughout the entire coating cross-sectional area. The contents of tetragonal phase in the coating is 65.8 %, and the phase has a strongly preferred growth tendency toward . The nano-indentation test shows that the microhardness of the coating increases gradually from bottom to top. In addition, the observed characteristics of 7YSZ particle are evaluated based on the results of numerical simulations of the temperature, velocity, and pressure fields in the plasma jet.

Environmental barrier coatings (EBCs) with great oxidation-resistant performance in steam are needed for efficient protection of silicon carbide-based composites in future advanced gas turbine engines. Besides a dense structure without rapid penetration paths for oxidants and other corrosives, refractory components such as alumina oxide or oxide-containing compounds also help to repel oxygen through coatings, which can ensure a long service life of EBC when used to infiltrate and block pores. However, due to their melting temperature up to nearly 2000 °C, melting and infiltration will damage EBC and matrix. In this work, metallic aluminum first infiltrates into open pores and microcracks at a low temperature of 750 °C, forming a dense structure, and then reacts in situ to form the refractory phases during heat treatment at 1100 °C, which is far below the melting point of refractory components of nearly 2000 °C. The results demonstrate that the structure remained dense after heat treatment. An intermedia layer composed of alumina and ytterbium aluminum garnet was observed due to the diffusion and reaction of oxygen and aluminum. The dense and refractory diffusion-reaction layer prevents the rapid infiltration and diffusion of oxidants in the engine environment to coating and matrix.

Postpartum physical pain is common in clinic, mostly manifested in pain, numbness or weight, swelling and so on of limbs and joints during puerperium, and some of them fail to heal over the years, becoming stubborn “puerperal fever.” Mr. Zhang has been a doctor for more than 30 years. He has superb medical skills and has unique opinions on postpartum diseases. The author is lucky to follow-up. Now, his experience in syndrome differentiation and treatment of postpartum body pain is analyzed as follows, and the tested case is attached.

The vascular eendothelial cells are highly heterogeneous and associated with numerous diseases. Thymosin β4 (Tβ4) plays pleiotropic roles in endothelial cell differentiation, migration and angiogenesis. However, the underlying mechanisms played by Tβ4 in the regulation of endothelial cells have not yet been well investigated. In the present study, Tβ4 -GFP adenovirus, transfected into human umbilical vein endothelial cells (HUVECs), and cell morphology were analyzed by fluorescence microscopy. ELISA was used to determine the concentration of Tβ4 expression. Furthermore, the effects of Tβ4 overexpression on HUVECs proliferation, apoptosis and migration were investigated. Real-time quantitative PCR and western blot were conducted to examine mRNA and protein expression in HUVECs with Tβ4 overexpression. Moreover, the underlying molecular mechanism of Tβ4 in HUVECs function was tested through treatment with LY294002, a PI3K/AKT inhibitor. Overexpression of Tβ4 increased the cell ability of HUVECs, and up-regulated the expression of the proliferation markers PCNA and Cyclin D1. In addition, overexpression of Tβ4 reduced HUVECs apoptosis, both under normoxic and hypoxic conditions. Moreover, overexpression of Tβ4 increased the ability of HUVECs to migrate through the membrane and up-regulated levels of MMP-2 and MMP-9. The use of LY294002 decreased the p-AKT (Ser473) level, which was induced by Tβ4 overexpression. Importantly, LY294002 reduced Tβ4-induced HUVECs proliferation and migration. In conclusion, our results suggest that Tβ4 is a major regulator of HUVECs function by activating the AKT signaling pathway.

Inspired by the self-healing function of biological organisms, Bionic Laser Alloying (BLA) process was adopted to fabricate the bionic self-healing Thermal Barrier Coatings (TBCs). The BLA with different fractions of TiAl3 self-healing agent and Ceria and Yttria-Stabilized Zirconia (CYSZ) on the plasma-sprayed 7YSZ TBCs was carried out by a pulsed Nd: YAG laser. The effect of TiAl3 content on the microstructure, phase composition, and thermal shock behaviors of the bionic self-healing TBCs were investigated. Results indicated that the bionic self-healing TBCs had better thermal shock resistance than that of the as-sprayed TBCs. The thermal shock resistance increased first and then decreased with increasing TiAl3 fraction. The thermal shock resistance of the bionic self-healing TBCs with 15% TiAl3 is triple that of the as-sprayed TBCs. On one hand, the columnar crystals and vertical cracks could improve strain compatibility of TBCs during the thermal shock process; on the other hand, the TiAl3 as a self-healing agent reacted with oxygen in air at high temperature to seal the microcracks, thereby delaying the crack connection.

Environmental barrier coatings (EBCs) effectively protect the ceramic matrix composites (CMCs) from harsh engine environments, especially steam and molten salts. However, open pores inevitably formed during the deposition process provide the transport channels for oxidants and corrosives, and lead to premature failure of EBCs. This research work proposed a method of pressure infiltration densification which blocked these open pores in the coatings. These results showed that it was difficult for aluminum to infiltrate spontaneously, but with the increase of external gas pressure and internal vacuum simultaneously, the molten aluminum obviously moved forward, and finally stopped infiltrating at a depth of a specific geometry. Based on the wrinkled zigzag pore model, a mathematical relationship between the critical pressure with the infiltration depth and the pore intrinsic geometry was established. The infiltration results confirmed this relationship, indicating that for a given coating, a dense thick film can be obtained by adjusting the internal and external gas pressures to drive a melt infiltration.