Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

Microstructure and Mechanical Properties of Novel High-Strength, Low-Activation Wx(TaVZr)100-x (x = 5, 10, 15, 20, 25) Refractory High Entropy Alloys.

In this work, novel high-strength, low-activation Wx(TaVZr)100-x (x = 5, 10, 15, 20, 25) refractory high entropy alloys (RHEAs) were prepared by vacuum arc melting. Their microstructure, compressive mechanical properties, hardness, and fracture morphology were investigated and analyzed. The results show that the RHEAs possess a disordered BCC phase, ordered Laves phase, and Zr-rich HCP phase. Their dendrite structures were observed, and the distribution of dendrites became gradually more dense with an increase in W content. The RHEAs demonstrate high strength and hardness, with these properties being higher than in most reported tungsten-containing RHEAs. For example, the typical W20(TaVZr)80 RHEA has a yield strength of 1985 MPa and a hardness of 636 HV, respectively. The improvement in terms of strength and hardness are mainly due to solid solution strengthening and the increase in dendritic regions. During compression, with the increase in the applied load, the fracture behavior of RHEAs changed from initial intergranular fractures to a mixed mode combining both intergranular and transgranular fractures.

Recent Advances in W-Containing Refractory High-Entropy Alloys-An Overview.

During the past decade, refractory high-entropy alloys (RHEA) have attracted great attention of scientists, engineers and scholars due to their excellent mechanical and functional properties. The W-containing RHEAs are favored by researchers because of their great application potential in aerospace, marine and nuclear equipment and other high-temperature, corrosive and irradiated fields. In this review, more than 150 W-containing RHEAs are summarized and compared. The preparation techniques, microstructure and mechanical properties of the W-containing RHEAs are systematically outlined. In addition, the functional properties of W-containing RHEAs, such as oxidation, corrosion, irradiation and wear resistance have been elaborated and analyzed. Finally, the key issues faced by the development of W-containing RHEAs in terms of design and fabrication techniques, strengthening and deformation mechanisms, and potential functional applications are proposed and discussed. Future directions for the investigation and application of W-containing RHEAs are also suggested. The present work provides useful guidance for the development, processing and application of W-containing RHEAs and the RHEA components.

Longevity factor FOXO3a: A potential therapeutic target for age-related ocular diseases.

The forkhead box protein O3 (FOXO3a) belongs to the subgroup O of the forkhead transcription factor family and plays an important role in regulating the aging process by participating in the regulation of various life processes, including cell cycle arrest, apoptosis, autophagy, oxidative stress, and DNA repair. The eye is an organ that is affected by aging earlier. However, the functional role and potential clinical applications of FOXO3a in age-related eye diseases have not received widespread attention and lacked comprehensive and clear clarification. In this review, we demonstrated the relationship between FOXO3a and visual system health, summarized the functional roles of FOXO3a in various eye diseases, and potential ocular-related therapies and drugs targeting FOXO3a in visual system diseases through a review and summary of relevant literature. This review indicates that FOXO3a is an important factor in maintaining the normal function of various tissues in the eye, and is closely related to the occurrence and development of ophthalmic-related diseases. Based on its vital role in the normal function of the visual system, FOXO3a has potential clinical application value in related ophthalmic diseases. At present, multiple molecules and drugs targeting FOXO3a have been reported to have the potential for the treatment of related ophthalmic diseases, but further clinical trials are needed. In conclusion, this review can facilitate us to grasp the role of FOXO3a in the visual system and provide new views and bases for the treatment strategy research of age-related eye diseases.