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Summary: Impaired bone quality and increased fracture risk are cardinal features of the skeleton in diabetes mellitus. Hyperglycemia-induced oxidative stress is proposed as a potential underlying mechanism, but the precise pathogenic mechanism remains incompletely understood. In this investigation, osteoblasts under high glucose exhibited heightened levels of reactive oxygen species, impaired mitochondrial membrane potential, and profound inhibition of late-stage osteoblast differentiation. Further analyses uncovered that high glucose resulted in the downregulation of the PINK1/Drp1 pathway in osteoblasts, consequently leading to impaired mitophagy. Conversely, the upregulation of PINK1/Drp1 pathway activated mitophagy, which restored the differentiation capacity of osteoblasts. Notably, in an STZ-induced diabetic mouse model, BMP9 upregulated the expression of PINK1/Drp1 in the bone tissue, leading to an improvement in bone quality and bone mineral density. These findings suggest that the PINK1/Drp1 pathway might be a potential therapeutic target to enhance osteogenic differentiation and treat diabetic osteoporosis.

Sodium-ion batteries (SIBs) are promising alternatives to replace lithium-ion batteries as future energy storage batteries because of their abundant sodium resources, low cost, and high charging efficiency. In order to match the high energy capacity and density, designing an atomically doped carbonous material as the anode is presently one of the important strategies to commercialize SIBs. In this work, we report the preparation of high-performance dual-atom-doped carbon (C) materials using low-cost corn starch and thiourea (CH4N2S) as the precursors. The electronegativity and radii of the doped atoms and C are different, which can vary the embedding properties of sodium ions (Na+) into/on C. As sulfur (S) can effectively expand the layer spacing, it provides more channels for embedding and de-embedding Na+. The synergistic effect of N and S co-doping can remarkably boost the performance of SIBs. The capacity is preserved at 400 mAh g −1 after 200 cycles at 500 mA g−1; more notably, the initial Coulombic efficiency is 81%. Even at a high rate of high current of 10 A g−1, the cell capacity can still reach 170 mAh g−1. More importantly, after 3000 cycles at 1 A g−1, the capacity decay is less than 0.003% per cycle, which demonstrates its excellent electrochemical performance. These results indicate that high-performance carbon materials can be prepared using low-cost corn starch and thiourea.

Ruscogenin (RUS), first isolated from Ruscus aculeatus, also a major steroidal sapogenin of traditional Chinese herb Radix Ophiopogon japonicus, has been found to exert significant anti-inflammatory and anti-thrombotic activities. Our previous studies suggested that ruscogenin remarkably inhibited adhesion of leukocytes to a human umbilical vein endothelial cell line (ECV304) injured by tumor necrosis factor-Α (TNF-Α) in a concentration-dependent manner. Yet the underlying mechanisms remain unclear. In this study, the in vivo effects of ruscogenin on leukocyte migration and celiac prostaglandin E2 (PGE2) level induced by zymosan A were studied in mice. Furthermore, the effects of ruscogenin on TNF-Α-induced intercellular adhesion molecule-1 (ICAM-1) expression and nuclear factor-κB (NF-κB) activation were also investigated under consideration of their key roles in leukocyte recruitment. The results showed that ruscogenin significantly suppressed zymosan A-evoked peritoneal total leukocyte migration in mice in a dose-dependent manner, while it had no obvious effect on PGE2 content in peritoneal exudant. Ruscogenin also inhibited TNF-Α-induced over expression of ICAM-1 both at the mRNA and protein levels and suppressed NF-κB activation considerably by decreasing NF-κB p65 translocation and DNA binding activity. These findings provide some new insights that may explain the possible molecular mechanism of ruscogenin and Radix Ophiopogon japonicus for the inhibition of endothelial responses to cytokines during inflammatory and vascular disorders. Keywords:: ruscogenin, endothelial cell, adhesion, intercellular adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB)

Background: Preβ1-high-density lipoprotein (preβ1-HDL), plays an important role in reverse cholesterol transport and exhibits potent risk for coronary artery disease (CAD). However, the association of plasma preβ1-HDL and cholesterol ester transfer protein (CETP) levels in CAD patients and the relationship of preβ1-HDL with extent of CAD are debatable. Methods: Preβ1-HDL and CETP levels were measured by enzymed-linked immunosorbent assay (ELISAs) in 88 acute coronary syndromes (ACS), 79 stable coronary artery disease (SCAD) patients and 85 control subjects. The correlation analyses, multiple linear regression analyses and logistic regression analyses were performed, respectively. Results: The preβ1-HDL and CETP levels in ACS patients were significantly higher than those in SCAD patients and both of them were higher than controls'. Preβ1-HDL levels were positively associated with CETP (R = 0.348, P = 0.000), the diameter of stenosis (R = 0.253, P = 0.005), the number of vessel disease (R = 0.274, P = 0.002) and Gensini score (R = 0.227, P = 0.009) in CAD patients. Stepwise multiple linear regression analyses showed that CETP was one of the determinants of preβ1-HDL levels. Logistic regression analysis revealed that elevated preβ1-HDL and CETP were potential risk factors for both ACS and SCAD. Conclusion: The elevated preβ1-HDL levels may change with CETP concentrations in CAD patients and were related to the presence and severity of CAD. [ABSTRACT FROM AUTHOR]

Pharmaceuticalcocrystals are an efficient approach to improvethe solubility of insoluble active pharmaceutical ingredients (APIs),while the dissolution profiles of pharmaceutical cocrystals usuallyexhibit a type of “spring and rapid parachute” effectthat influences stability and pharmacodynamic sustainability, in whichthe high apparent solubility induced by the formation of cocrystalscan only be maintained for a short time (usually minutes) in the metastablezone and then decreases rapidly afterwords. Herein we reported thepreparation and structures of two lenalidomide cocrystals with gallicacid (1, 2). After the formation of cocrystals,the intrinsic dissolution rate and apparent solubility of lenalidomidewere found to be enhanced. The high solubility of cocrystals can keepfor 48 h without dropping. The result of phase solubility study indicatesgallic acid (GA) forms a 1:1 complex with lenalidomide (Rev) in aqueoussolution, with a stability constant of 1713.2 L/mol. The multiplehydrogen bonding interactions between GA and Rev are attributed tothe formation of GA-Rev complex in aqueous solution and subsequentlythe constant high solubility of cocrystals. [ABSTRACT FROM AUTHOR]