Facilitating the Electrochemical Oxidation of ZnS through Iodide Catalysis for Aqueous Zinc-Sulfur Batteries.

Aqueous zinc-sulfur (Zn-S) batteries show great potential for unlocking high energy and safety aqueous batteries. Yet, the sluggish kinetic and poor redox reversibility of the sulfur conversion reaction in aqueous solution challenge the development of Zn-S batteries. Here, we fabricate a high-performance Zn-S battery using highly water-soluble ZnI2 as an effective catalyst. In situ experimental characterizations and theoretical calculations reveal that the strong interaction between I- and the ZnS nanoparticles (discharge product) leads to the atomic rearrangement of ZnS, weakening the Zn-S bonding, and thus facilitating the electrochemical oxidation reaction of ZnS to S. The aqueous Zn-S battery exhibited a high energy density of 742 Wh kg(sulfur) -1 at the power density of 210.8 W kg(sulfur) -1 and good cycling stability over 550 cycles. Our findings provide new insights about the iodide catalytic effect for cathode conversion reaction in Zn-S batteries, which is conducive to promoting the future development of high-performance aqueous batteries.

Reversal of Enantioselectivity for the Desymmetrization of meso-1,2-Diols Catalyzed by Pyridine-N-oxides.

The desymmetrization of meso-vic-diols with a reversal of enantioselectivity catalyzed by chiral pyridine-N-oxides with l-proline as a single source of chirality is reported. With chiral 3-substituted ArPNO C2c and 2-substituted 4-(dimethylamino)pyridine-N-oxide C3b as catalysts, a wide range of monoesters were obtained with satisfactory results with a complete and controlled switch in stereoselectivity (up to 97:3 and 1:99 er). Chiral six-membered carbocyclic uracil nucleosides were generated with excellent enantioselectivities after derivatization. A series of control experiments and density functional theory (DFT) calculations supported that the reaction proceeded in a bifunctional activated manner, where the N-oxide groups and N-H proton of the amides were vital for catalytic reactivity and stereocontrol. The DFT calculation also supported the distance-directed switching of enantioselectivity, in which the l-prolinamide moiety moved from the C3 to C2 position on the pyridine ring, resulting in the H-bond interaction between the amide N-H and OH group of meso-vic-diol also shifted from one hydroxyl group to another.

COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity.

Renal fibrosis relies on multiple proteins and cofactors in its gradual development. Copper is a cofactor of many enzymes involved in renal microenvironment homeostasis. We previously reported that intracellular copper imbalance occurred during renal fibrosis development and was correlated with fibrosis intensity. In this study, we investigated the molecular mechanisms of how copper affected renal fibrosis development. Unilateral ureteral obstruction (UUO) mice were used for in vivo study; rat renal tubular epithelial cells (NRK-52E) treated with TGF-ß1 were adapted as an in vitro fibrotic model. We revealed that the accumulation of copper in mitochondria, rather than cytosol, was responsible for mitochondrial dysfunction, cell apoptosis and renal fibrosis in both in vivo and in vitro fibrotic models. Furthermore, we showed that mitochondrial copper overload directly disrupted the activity of respiratory chain complex IV (cytochrome c oxidase), but not complex I, II and III, which hampered respiratory chain and disrupted mitochondrial functions, eventually leading to fibrosis development. Meanwhile, we showed that COX17, the copper chaperone protein, was significantly upregulated in the mitochondria of fibrotic kidneys and NRK-52E cells. Knockdown of COX17 aggravated mitochondrial copper accumulation, inhibited complex IV activity, augmented mitochondrial dysfunction and led to cell apoptosis and renal fibrosis, whereas overexpression of COX17 could discharge copper from mitochondria and protect mitochondrial function, alleviating renal fibrosis. In conclusion, copper accumulation in mitochondria blocks complex IV activity and induces mitochondrial dysfunction. COX17 plays a pivotal role in maintaining mitochondrial copper homeostasis, restoring complex IV activity, and ameliorating renal fibrosis.

Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in Caenorhabditis elegans.

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected in Caenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR in C. elegans. The results indicate that genistein substantially extended the lifespan of C. elegans under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in C. elegans under hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2 and upregulated the expression of daf-16, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, and eat-2, whereas it downregulated the expression of age-1 and daf-2 in C. elegans; similarly, it upregulated the expression of daf-16, sod-3, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, jnk-1 skn-1, and eat-2, whereas it downregulated the expression of age-1, daf-2, gst-4, and hsp-12.6 in C. elegans at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2 conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2 conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects in C. elegans via insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization.

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0-time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation.

Excessive Zinc Ion Caused PC12 Cell Death Correlating with Inhibition of NOS and Increase of RAGE in Cells.

Zinc ion (Zn2+) is an important functional factor; however, excessive Zn2+ can be toxic. To understand the neurotoxicity of excessive Zn2+ and the underlying mechanism, PC12 cells were treated with excessive Zn2+ and Zn2+ plus N, N, N', N'-Tetrakisethylenediamine (TPEN), a zinc ion chelator agent. Trypan blue and 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays were used to test cell viability; the relative kits were used to detect the activity of NOS synthase and the content of the receptor for advanced glycation end product (RAGE) in cells. We observed that excessive zinc caused PC12 cell damage and that TPEN partially reversed cell damage caused by excessive zinc. In addition, excessive zinc decreased total nitric oxide synthase (TNOS) activity in cells, in which constitutive nitric oxide synthase (cNOS) activity was significantly reduced; however, inducible nitric oxide synthase (iNOS) activity was extremely promoted. Moreover, excessive zinc upregulated the expression of RAGE, and TPEN effectively reversed the increase in RAGE induced by excessive zinc ions. Therefore, we concluded that excessive zinc caused PC12 cell damage, correlating with the inhibition of NOS and increase of RAGE induced in cells.

[Research progress of bone marrow edema-like lesions in knee osteoarthritis].

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.

Development and evaluation of 1-deoxynojirimycin sustained-release delivery system: In vitro and in vivo characterization studies.

We aimed to establish a 1-Deoxynojirimycin (DNJ) sustained-release delivery system to improve the hypoglycemic effect of DNJ. We used a transdermal diffusion meter in an in vitro orthogonal experiment to determine the optimal composition of the DNJ sustained-release transdermal system. Based on the in vitro analysis results, a sustained-release patch was prepared, and its pharmacokinetics and other properties were determined in vivo. The results showed that 30% hydroxypropyl methylcellulose (K100M ), 14% carboxymethyl cellulose sodium and 26% oleic acid-azone compound as the matrix material, drug excipient, and penetration enhancer, respectively, produced an optimal DNJ sustained-release delivery system. In vitro release tests showed that the system slowly released DNJ within 12 hr, conforming to the Higuchi equation. In vivo experiments showed that the prepared patch had good hypoglycemic activity and continuously released DNJ within 10 hr. In vivo pharmacokinetic study results showed that compared to conventional patches, the prepared patch exhibited significantly different maximum concentration (Cmax ), time to achieve Cmax (Tmax ), and area under the curve from 0 to time t (AUC[0-t] ) as well as improved pharmacokinetics. In conclusion, the prepared DNJ patch has high stability, a sustained-release effect, and relatively good pharmacokinetics and is a safe dosage form that does not cause skin irritation.

Research progress of bone marrow edema-like lesions in knee osteoarthritis / 中国骨伤

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.

Curcumin anti-diabetic effect mainly correlates with its anti-apoptotic actions and PI3K/Akt signal pathway regulation in the liver.

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

Elevated intracellular copper contributes a unique role to kidney fibrosis by lysyl oxidase mediated matrix crosslinking.

Copper ions play various roles in mammalian cells, presumably due to their involvement in different enzymatic reactions. Some studies indicated that serum copper correlates with fibrosis in organs, such as liver and lung. However, the mechanism is unknown. Here, we explored the role of copper in kidney fibrosis development and possible underlying mechanisms. We found that copper transporter 1 (CTR1) expression was increased in the kidney tissues in two fibrosis models and in patients with kidney fibrosis. Similar results were also found in renal tubular epithelial cells and fibroblast cells treated with transforming growth factor beta (TGF-ß). Mechanistically, the upregulation of CTR1 required Smads-dependent TGF-ß signaling pathway and Smad3 directly binded to the promoter of CTR1 in renal fibroblast cells using chromatin immunoprecipitation. Elevated CTR1 induced increase of copper intracellular influx. The elevated intracellular copper ions activated lysyl oxidase (LOX) to enhance the crosslinking of collagen and elastin, which then promoted kidney fibrosis. Reducing intracellular copper accumulation by knocking down CTR1 ameliorated kidney fibrosis in unilateral ureteral obstruction induced renal fibrosis model and renal fibroblast cells stimulated by TGF-ß. Treatment with copper chelator tetrathiomolybdate (TM) also alleviated renal fibrosis in vivo and in vitro. In conclusion, intracellular copper accumulation plays a unique role to kidney fibrosis by activating LOX mediated collagen and elastin crosslinking. Inhibition of intracellular copper overload may be a potential portal to alleviate kidney fibrosis.