Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Bicyclol mitigates lipopolysaccharide-induced acute lung injury through myeloid differentiation factor 88 inhibition.

Acute lung injury (ALI) remains a significant clinical challenge due to the absence of effective treatment alternatives. This study presents a new method that employs a screening platform focusing on MyD88 affinity, anti-inflammatory properties, and toxicity. This platform was used to evaluate a 300-compound library known for its anti-inflammatory potential. Among the screened compounds, Bicyclol emerged as a standout, exhibiting MyD88 binding and a significant reduction in LPS-stimulated pro-inflammatory factors production in mouse primary peritoneal macrophages. By targeting MyD88, Bicyclol disrupts the MyD88/TLR4 complex and MyD88 polymer formation, thereby mitigating the MAPKs and NF-κB signaling pathways. In vivo experiments further confirmed Bicyclol's efficacy, demonstrating alleviated ALI symptoms, decreased inflammatory cytokines level, and reduced inflammatory cells presence in lung tissues. These findings were associated with a decrease in mortality in LPS-challenged mice. Overall, Bicyclol represents a promising treatment option for ALI by specifically targeting MyD88 and limiting inflammatory responses.

Hypericin Alleviates Chronic Kidney Disease-induced Left Ventricular Hypertrophy by Regulation of FGF23-FGFR4 Signaling Pathway.

ABSTRACT: Chronic kidney disease (CKD) is a significant global health threat that imposes a substantial burden on both individuals and societies. CKD frequently correlates with cardiovascular events, particularly left ventricular hypertrophy (LVH), which contributes to the high mortality rate associated with CKD. Fibroblast growth factor 23 (FGF23), a hormone primarily involved in regulating calcium and phosphorus metabolism, has been identified as a major risk factor for LVH in CKD patients. Elevated serum FGF23 levels are known to induce LVH and myocardial fibrosis by activating the fibroblast growth factor receptor 4 (FGFR4) signal pathway. Therefore, targeting FGFR4 and its downstream signaling pathways holds potential as a treatment strategy for cardiac dysfunction in CKD. In our current study, we have discovered that Hypericin, a key component derived from Hypericum perforatum , has the ability to alleviate CKD-related LVH by targeting the FGFR4/phospholipase C gamma 1 (PLCγ1) signaling pathway. Through in vitro experiments using rat cardiac myocyte H9c2 cells, we observed that Hypericin effectively inhibits FGF23-induced hypertrophy and fibrosis by suppressing the FGFR4/PLCγ1/calcineurin/nuclear factor of activated T-cell (NFAT3) signaling pathway. In addition, our in vivo studies using mice on a high-phosphate diet and rat models of 5/6 nephrectomy demonstrated that Hypericin has therapeutic effects against CKD-induced LVH by modulating the FGFR4/PLCγ1/calcineurin/NFAT3 signaling pathway. In conclusion, our research highlights the potential of Hypericin as a candidate for the treatment of CKD-induced cardiomyopathy. By suppressing the FGFR4/PLCγ1 signaling pathway, Hypericin shows promise in attenuating LVH and myocardial fibrosis associated with CKD.

Hydrogen production by traditional and novel alkaline water electrolysis on nickel or iron based electrocatalysts.

Hydrogen production through alkaline water electrolysis holds great promise as a scalable solution for renewable energy storage and conversion. The development of non-precious metal-based electrocatalysts with low-overpotential for alkaline water electrolysis is essential to decrease the cost of electrolysis devices. Although the Ni-based and Fe-based electrocatalysts have been commercially employed in the cathodic hydrogen evolution reaction (HER) and anodic oxygen evolution reaction (OER), it is imperative to persistently pursue the advancement of highly efficient electrocatalysts with enhanced current density and fast kinetics. This feature article overviews the progress of NiMo HER cathodes and NiFe OER anodes in the traditional alkaline water electrolysis process for hydrogen production, including the detailed mechanisms, preparation strategies, and structure-function relationship. Moreover, recent advances of Ni-based and Fe-based electrodes in the process of novel alkaline water electrolysis, involving small energetic molecule electro-oxidation and redox mediator decoupled water electrolysis, are also discussed for hydrogen production with low cell voltage. Finally, the perspective of these Ni-based and Fe-based electrodes in the mentioned electrolysis processes is proposed.

Zn and N co-doped three-dimensional honeycomb-like carbon featured with interconnected nano-pools for dendrite-free zinc anode.

The zinc-ion battery (ZIB) has been extensively researched as one of the promising electrochemical power sources. However, the problem of Zn-dendrite formation during repeated plating and stripping process seriously hinders the development of ZIBs. Herein, three-dimensional (3D) honeycomb-like porous carbon (HPC) with co-doping of zinc and nitrogen is prepared through confining growth of nanoscale zeolite imidazole framework-8 (ZIF-8) on the well-designed nano-pools walls of HPC followed by pyrolysis at 600 ℃ to obtain the final product ZnN/HPC-600, which exhibits large surface area and abundant zincophilic interfaces, ensuring homogeneous distribution of electronic field and low polarization during cycling process. Importantly, ZnN/HPC-600 facilitates the uniform distribution and migration of Zn2+ in this nano-pools structure, avoiding the growth of dendritic Zn crystal during charging stage. The symmetric and asymmetric cells with Zn/ZnN/HPC-600 anodes are assembled, demonstrating excellent cycling reversibility, good rate performance and long-term stability. Besides, a Zn||MnO2 full cell with Zn/ZnN/HPC-600 anode also exhibits robust cycling stability, fast reaction kinetics and almost 100 % coulombic efficiency. This work offers a novel and efficient carbonaceous nano-pools strategy to realize dendrite-free zinc anode in ZIBs.

Carbon Coated and Nitrogen Doped Hierarchical NiMo-Based Electrocatalysts with High Activity and Durability for Efficient Borohydride Oxidation.

Sodium borohydride is a promising candidate as hydrogen storage material. The direct borohydride fuel cell (DBFC) as an energy conversation device has attracted intensive attention owing to the low theoretical potential of borohydride oxidation reaction (BOR, -1.24 V vs SHE) on the anode. In this paper, the hierarchical sea urchin-like NiMoN@NC coated by thin carbon layer with optimal BH4- adsorption characteristic was synthesized as a superior electrocatalyst toward BOR. In 1 M NaOH-0.05 M NaBH4, the BOR working potentials are only -55 and 44 mV at the current densities of 10 and 200 mA cm-2 on NiMoN@NC, respectively. Furthermore, the membrane-free DBFC using NiMoN@NC as anodic electrocatalyst shows a maximum power density of 67 mW cm-2 at room temperature with appreciative stability. This well-designed carbon coated and nitrogen doped transition-metal material with hierarchical nano/microstructure as a highly efficient electrocatalyst shows promising potential and bright prospects in electrocatalysis research and practical application for energy conversion systems of DBFC.