Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury.Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway,which may highlight a potential role of WFA for the treatment of ICH.

Ambipolar performance improvement of the C-shaped pocket TFET with dual metal gate and gate–drain underlap

Dual-metal gate and gate–drain underlap designs are introduced to reduce the ambipolar current of the device based on the C-shaped pocket TFET(CSP-TFET).The effects of gate work function and gate–drain underlap length on the DC characteristics and analog/RF performance of CSP-TFET devices,such as the on-state current(I_(on)),ambipolar current(I_(amb)),transconductance(g_(m)),cut-off frequency(f_(T))and gain–bandwidth product(GBP),are analyzed and compared in this work.Also,a combination of both the dual-metal gate and gate–drain underlap designs has been proposed for the C-shaped pocket dual metal underlap TFET(CSP-DMUN-TFET),which contains a C-shaped pocket area that significantly increases the on-state current of the device;this combination design substantially reduces the ambipolar current.The results show that the CSP-DMUN-TFET demonstrates an excellent performance,including high I_(on)(9.03×10^(-4)A/μm),high I_(on)/I_(off)(~10^(11)),low SS_(avg)(~13 mV/dec),and low I_(amb)(2.15×10^(-17)A/μm).The CSP-DMUN-TFET has the capability to fully suppress ambipolar currents while maintaining high on-state currents,making it a potential replacement in the next generation of semiconductor devices.

Discovery and development suggestions of strontium-rich groundwater in Chibi City,China

1.Objectives Chibi City is located along the key development axis of the Beijing-Guangzhou high-speed rail in Hubei Province,and is one of the key towns in the middle reaches of the Yangtze River in China.Karst ground subsidence,groundwater contamination,seasonal water shortage or water shortage are important environmental geological problems that restrict economic and social development in the region.Relying on the discovery of abundant geological heritage landscape resources of Chibi City(Ancient battlefield in the period of the Three Kingdoms,Yangloudong),geothermal resources(Wuhong Mountain hot spring),the discovery of natural mineral water rich in strontium and metasilicate provides more options for the development and utilization of geological resources in Chibi City.Strontium-rich mineral water can strengthen bones,protect hearts,soften blood vessels,and has the function of anti-oxidation,anti-aging and immunity enhancement.It is a kind of high-quality water that is very beneficial to human health.Therefore,identifying its distribution and potential is key to the development of strontium rich mineral water industry in Chibi City.

DC and analog/RF performance of C-shaped pocket TFET(CSP-TFET)with fully overlapping gate

A C-shaped pocket tunnel field effect transistor(CSP-TFET)has been designed and optimized based on the traditional double-gate TFETs by introducing a C-shaped pocket region between the source and channel to improve the device performance.A gate-to-pocket overlapping structure is also examined in the proposed CSP-TFET to enhance the gate controllability.The effects of the pocket length,pocket doping concentration and gate-to-pocket overlapping structure on the DC and analog/RF characteristics of the CSP-TFET are estimated after calibrating the tunneling model in double-gate TFETs.The DC and analog/RF performance such as on-state current(Ion),on/off current ratio(Ion/Ioff),subthreshold swing(SS)transconductance(g;),cut-off frequency(f_(T))and gain-bandwidth product(GBP)are investigated.The optimized CSPTFET device exhibits excellent performance with high I_(off)(9.98×10^(-4)A/μm),high I_(on)/I_(off)(~10^(11)),as well as low SS(~12 m V/dec).The results reveal that the CSP-TFET device could be a potential alternative for the next generation of semiconductor devices.

A dynamic constitutive model of ultra high toughness cementitious composites

In this study,an explicit dynamic constitutive model was established for ultra high toughness cementitious composites(UHTCCs).The model,based on the Holmquist–Johnson–Cook(HJC)model,includes tensile and compressive damage evolution,hydrostatic pressure,strain rate,and the Lode angle effect.The proposed model was embedded in LS-DYNA software and then comprehensive tests were carried on a hexahedral brick element formulation under uniaxial,biaxial,and triaxial stress states to verify its rationality through comparisons with results determined by the HJC and Karagozian&Case(K&C)models.Finally,the proposed model was used to simulate the damage caused to UHTCC targets subjected to blast by embedded explosive and projectile penetration,and predictions were compared with corresponding experimental results.The results of the numerical simulations showed that our proposed model was more accurate than the HJC model in predicting the size of the crater,penetration depth,and the distribution of cracks inside the target following the blast or high-speed impact loading.

Influence of Pin Offset on Microstructure and Mechanical Properties of Friction Stir Welded Mg/Ti Dissimilar Alloys

The influences of pin offset on the formation, microstructure and mechanical properties of friction stir welded joint of Ti6 Al4 V and AZ31 B Mg dissimilar alloys were investigated. The results show that sound joints are obtained at different offsets. With the offset decreasing from 2.5 to 2.1 mm, the number of Ti alloy fragments is increased, and the stir zone(SZ) is enlarged and the grains in SZ become coarser. A hook-like structure is formed at the Mg/Ti interface and its length is increased with the decrease in pin offset. The Al element has an enrichment trend at the Ti alloy side near the Mg/Ti interface when the offset is decreased, which is beneficial to the bonding of the interface. An Al-rich layer with a thickness of 3–5μm forms at the offset of 2.1 mm. All the joints fracture at the interface and present a mixed ductile-and-brittle fracture mode. The joint tensile strength is increased with the offset decreasing from 2.5 to 2.1 mm, and the maximum tensile strength of 175 MPa is acquired at the offset of 2.1 mm.

2-Pyridinylmethyl borrowing:base-promoted C-alkylation of(pyridin-2-yl)-methyl alcohols with ketones via cleavage of unstrained C(sp^(3))-C(sp^(3))bonds

A transition metal-free synthesis of β-(pyridin-2-yl)-methyl ketones,using(pyridin-2-yl)methyl alcohols and ketones through the 2-pyridinylmethyl borrowing strategy,has been disclosed.This approach provides an efficient,available and environmentally benign access,leading to alkylation products with broad functional group tolerance and excellent yields.Meanwhile,the selective cleavage of unactivated C(sp^(3))-C(sp^(3))bonds of common secondary alcohols was achieved with high atom economy.