Activity

The mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) is inhibition of specific prostaglandin (PG) synthesis by inhibition of cyclooxygenase (COX) enzymes. The two COX isoenzymes show 60% similarity. It is known that the nonspecific side effects of conventional NSAIDs are physiologically caused by inhibition of the COX-1 enzyme. Therefore, the use of COX-2 selective inhibitors is seen to be a more beneficial approach in reducing these negative effects. However, some of the existing COX-2 selective inhibitors show cardiovascular side effects. Therefore, studies on the development of new selective COX-2 inhibitors remain necessary. It is important to develop new COX-2 inhibitors in the field of medicinal chemistry. Accordingly, novel N -acyl hydrazone derivatives were synthesized as new COX-2 inhibitors in this study. The hydrazone structure, also known for its COX activity, is important in terms of many biological activities and was preferred as the main structure in the design of these compounds. A methyl sulfonyl pharmacophore was added to the structure in order to increase the affinity for the polar side pocket present in the COX-2 enzyme. It is known that methyl sulfonyl groups are suitable for polar side pockets. The synthesis of the compounds ( 3a-3j ) was characterized by spectroscopic methods. Evaluation of in vitro COX-1/COX-2 enzyme inhibition was performed by fluorometric method. According to the enzyme inhibition results, the obtained compounds displayed the predicted selectivity for COX-2 enzyme inhibition. Compound 3j showed important COX-2 inhibition with a value of IC 50 =0.143 uM. Interaction modes between the COX-2 enzyme and compound 3j were investigated by docking studies.Solar radiation is a renewable and clean energy source used in photoelectrochemical cells (PEC) to produce hydrogen gas as a powerful alternative to carbon-based fuels. Semiconductors play a vital role in this approach, absorbing the incident solar photons and converting them into electrons and holes. The hydrogen evolution reaction (HER) occurs in the interface of the p-type semiconductor that works as a photocathode in the PEC. Cu-chalcopyrites such as Cu(In, Ga)(Se,S)2 (CIGS) and CuIn(Se,S)2 (CIS) present excellent semiconductor characteristics for this purpose, but drawbacks as charge recombination, deficient chemical stability, and slow charge transfer kinetics, demanding improvements like the use of n-type buffer layer, a protective layer, and a cocatalyst material. HDAC inhibitor Concerning the last one, platinum (Pt) is the most efficient and stable material, but the high price due to its scarcity imposes the search for inexpensive and abundant alternative cocatalyst. The present Minireview highlighted the use of metal alloys, transition metal chalcogenides, and inorganic carbon-based nanostructures as efficient alternative cocatalysts for HER in PEC.

To determine the characteristics of crystalline lens with varying refractive errors and relationship with axial elongation in young school children.

A total of 1465 children aged 6-8years were examined annually for 2years. Each participant underwent a series of ophthalmic examinations, including cycloplegic autorefraction, crystalline lens and axial length measurement. Crystalline lens power was determined, and factors associated with different refractive statuses were investigated.

Crystalline lens power decreased with time; reduction in lens power in Year 1 was greater in children with emmetropia (-0.69±0.59 dioptre [D]) than in those with hyperopia (-0.49±0.56 D) or myopia (-0.45±0.55 D) (p<0.001). Among the emmetropes, there were no differences in loss of crystalline lens power between those who remained emmetropic (-0.63±0.59 D) and those who became myopic at Year 1 (-0.74±0.61 D) and Year 2 (-0.77±0.57 D, p>0.05) visits. Among myopes at Year 1 visit, there was a greater reduction at Year 2 in those who had baseline emmetropia (-0.61±0.51 D) than those who had baseline myopia (-0.26±0.49 D, p<0.001). The trend was similar among children of the same age. There was a significant correlation between changes in lens power and axial elongation in non-myopia (β=-0.954, p<0.001) and new myopia (β=-1.178, p<0.001), but not in established myopia (β=-0.001, p=0.539).

There is accelerated loss of lens power in emmetropia and early stage of myopia. However, this loss is retarded when myopia persists and is accompanied by disappearance of the compensatory effect of lens power against axial elongation. These findings provide new insights into human refractive development.

There is accelerated loss of lens power in emmetropia and early stage of myopia. However, this loss is retarded when myopia persists and is accompanied by disappearance of the compensatory effect of lens power against axial elongation. These findings provide new insights into human refractive development.Unassisted photovoltaic (PV) water splitting to hydrogen system is of great potential for future environmental-friendly fuel production from renewable solar energy. However, industrialization simultaneously requires higher efficiency, sustained stability and a lower cost for the system. In this work, the ultrathin cobalt/iron-molybdenum oxides nanosheet on nickel foam (NF) is prepared for efficient HER and OER, respectively, delivering a relatively low voltage of 1.45 V at 10 mA cm-2 in two-electrodes configuration. Water electrolysis at low voltage driven by electrocatalysts is critical for realizing energy conversion. Integrated with a commercial monocrystalline silicon cell, the H2 area specific activity of 0.47 L m-2 h-1 is achieved with a solar-to-hydrogen efficiency of 15.1% under solar simulator illumination (100 mW cm-2 ) and no performance degradation appeares over 160 h. Such a solar conversion technology demonstrates the potential for long-term and cost-efficient H2 production in large-scale industrialization and provides an exploration for new-type of energy-conversion system.Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease involving arrhythmia in young adults accompanied by structural changes at later stages. In this issue of EMBO Molecular Medicine, Sommariva et al (2021) identified a positive correlation between circulating levels of oxidized low-density lipoproteins (oxLDL) and ACM disease penetrance, which contributes to fibro-fatty cardiac remodeling via the oxLDL/CD36/PPARγ axis. These data identify oxidized low-density lipoproteins as a risk factor for ACM and uncover a novel therapeutic intervention option to block disease pathogenesis.

Kindlin-3 is essential for supporting the bidirectional signaling of integrin αIIbβ3 in platelets by bridging the crosstalk between integrin αIIbβ3 and the cytoplasmic signaling adaptors.

In this study, we identified a previously unrecognized paxillin binding site in the pleckstrin homology (PH) domain of kindlin-3 and verified its functional significance.

Structure-based approaches were employed to identify the paxillin binding site in the PH domain of kindlin-3. In addition, the bidirectional signaling of integrin αIIbβ3 were evaluated in both human and mouse platelets.

In brief, we found that a β1-β2loop in the PH domain of kindlin-3, an important part of the canonical membrane phospholipid binding pocket, was also involved in mediating paxillin interaction. Interestingly, the binding sites of paxillin and membrane phospholipids in the PH domain of kindlin-3 were mutually exclusive. Specific disruption of paxillin binding to the PH domain by point mutations inhibited platelet spreading on immobilized fibrinogen while having no inhibition on soluble fibrinogen binding to stimulated platelets. In addition, a membrane-permeable peptide derived from the β1-β2loop in the PH domain of kindlin-3 was capable of inhibiting platelet spreading and clot retraction, but it had no effect on soluble fibrinogen binding to platelets and platelet aggregation. Treatment with this peptide significantly reduced thrombus formation in mice.

Taken together, these findings suggest that interaction between paxillin and the PH domain of kindlin-3 plays an important role in supporting integrin αIIbβ3 outside-in signaling in platelets, thus providing a novel antithrombotic target.

Taken together, these findings suggest that interaction between paxillin and the PH domain of kindlin-3 plays an important role in supporting integrin αIIbβ3 outside-in signaling in platelets, thus providing a novel antithrombotic target.Mitochondrial dysfunction is considered to be an important factor that leads to aging and premature aging diseases. Transferring mitochondria to cells is an emerging and promising technique for the therapy of mitochondrial deoxyribonucleic acid (mtDNA)-related diseases. This paper presents a unique method of controlling the quality and quantity of mitochondria transferred to single cells using an automated optical tweezer-based micromanipulation system. The proposed method can automatically, accurately, and efficiently collect and transport healthy mitochondria to cells, and the recipient cells then take up the mitochondria through endocytosis. The results of the study reveal the possibility of using mitochondria from fetal mesenchymal stem cells (fMSCs) as a potential source to reverse the aging-related phenotype and improve metabolic activities in adult mesenchymal stem cells (aMSCs). The results of the quantitative polymerase chain reaction analysis show that the transfer of isolated mitochondria from fMSCs to a single aMSC can significantly increase the antiaging and metabolic gene expression in the aMSC. The proposed mitochondrial transfer method can greatly promote precision medicine for cell therapy of mtDNA-related diseases.Purple sweet potato polysaccharide was extracted via hot water, and it was chemically modified by phosphorus oxychloride-pyridine to obtain phosphorylated polysaccharide from purple sweet potato (P-PPSP) with certain degrees of substitution. Furthermore, the structure and antioxidant activity in vitro of PPSP and phosphorylated derivative were compared. The result indicated that the phosphorylation modification product of polysaccharide from purple sweet potato could improve the scavenging effect on hydroxyl radical and superoxide anion of PPSP, significantly. It also could improve the anti-lipid peroxidation ability while fail to improve the reducing ability of PPSP.Heterostructure plays an important role in boosting the overall water splitting (OWS) performance of nonprecious metal electrocatalysts. However, rational design and synthesis of semiconductor heterojunctions especially for Cu-based ones as efficient bifunctional electrocatalysts toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) still face challenges, and the in-depth study of catalytic mechanisms is urgently needed. Herein, n-type cobalt layered double hydroxide nanosheets are assembled on p-type cuprous phosphide nanowire to form p-n junction. This heterostructure with a strong built-in potential (EBI ) of 1.78 V provides enlarged electrochemical active surface area, enhanced active site, facilitated electron separation and transfer, and accelerated formation of superoxide radical. As expected, the heterogeneous electrocatalyst exhibits significantly improved activities for OWS, achieving an overpotential of 111 mV for HER and 221 mV for OER and an applied voltage of 1.575 V for OWS at 10 mA cm-2 in 1 m KOH.