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Objective(s): Ginkgo biloba leaf extract (EGb-761) injection has been widely used as adjuvant therapy for cerebral stroke in China. However, its underlying pharmacological mechanism is not completely understood. The present study aimed to investigate whether the therapeutic effects of EGb-761 are exerted by modulating autophagy flux. Materials and Methods: Ischemic cerebral stroke was prepared in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO/reperfusion rats were then treated with EGb-761 injection once daily for 7 days. Thereafter, the brain tissues in the ischemic penumbra were obtained to detect the key proteins in the autophagic/lysosomal pathway with Beclin1, LC3, (SQSTM1)/p62, ubiquitin, LAMP-1, cathepsin B, and cathepsin D antibodies by western blot and immunofluorescence. Meanwhile, the infarct volume, neurological deficits, and neuronal apoptosis were assessed to evaluate the therapeutic outcomes.Results: The results illustrated that EGb-761 treatment was not only able to promote the autophagic activities of Beclin1 and LC3-II in neurons, but also could enhance the autophagic clearance, as indicated by reinforced lysosomal activities of LAMP-1, cathepsin B, and cathepsin D, as well as alleviating autophagic accumulation of ubiquitin and insoluble p62 in the MCAO+EGb-761 group, compared with those in the MCAO+saline group. Meanwhile, cerebral ischemia-induced neurological deficits, infarct volume, and neuronal apoptosis were significantly attenuated by 7 days of EGb-761 therapy. Conclusion: Our data suggest that EGb-761 injection can elicit a neuroprotective efficacy against MCAO/reperfusion injury, and this neuroprotection may be exerted by enhancement of autophagy flux in neurons in the ischemic penumbra.

Background: Our previous research shows that Curcumin (CUR) attenuates myocardial ischemia-reperfusion injury (MIRI) by reducing intracellular total RNA m6A levels. However, the mechanism remains unknown. Methods: For ischemia-reperfusion (IR), H9c2 cells were cultured for 6 h in serum-free low-glycemic (1 g/L) medium and a gas environment without oxygen, and then cultured for 6 h in high-glycemic (4.5 g/L) medium supplemented with 10% FBS and a 21% oxygen environment. The effects of different concentrations of CUR (5, 10, and 20 µM) treatments on signaling molecules in conventionally cultured and IR-treated H9c2 cells were examined. Results: CUR treatment significantly up-regulated the H2S levels, and the mRNA and protein expression of cystathionine γ-lyase (CSE), and down-regulated the mRNAs and proteins levels of thiosulfate sulfurtransferase (TST) and ethylmalonic encephalopathy 1 (ETHE1) in H9c2 cells conventionally cultured and subjected to IR. Exogenous H2S supply (NaHS and GYY4137) significantly reduced intracellular total RNA m6A levels, and the expression of RNA m6A "writers" METTL3 and METTL14, and increased the expression of RNA m6A "eraser" FTO in H9c2 cells conventionally cultured and subjected to IR. CSE knockdown counteracted the inhibitory effect of CUR treatment on ROS production, promotion on cell viability, and inhibition on apoptosis of H9c2 cells subjected to IR. Conclusion: CUR attenuates MIRI by regulating the expression of H2S level-regulating enzymes and increasing the endogenous H2S levels. Increased H2S levels could regulate the m6A-related proteins expression and intracellular total RNA m6A levels. [ABSTRACT FROM AUTHOR]

The numerical (CFD) method is applied in this paper to investigate the nonuniformity of temperature and airflow filed, the spatial and temporal distribution of coughed droplet under stratum ventilation and mixing ventilation in the negative pressure isolation (NPI) ward. The influence of exhaust terminals number and location on the diffusion process of coughed droplet is analyzed under heating mode. The results show that the relative pollutant concentration in the breathing area of stratum ventilation is lower than that of mixing ventilation. When the air exhaust terminals are high from the ground and the number are small, it is more conducive to reduce the infection risk of medical staff. The deposition rate and suspension rate of stratum ventilation are higher than that of mixing ventilation, and the escape rate is lower. When the number of exhaust outlets is large and the location is high, the nonuniformity coefficient is the smallest and the deposition rate is the largest, which are 0.668, 0.029 and 91.4% respectively. The escape rate is higher when the number of exhaust outlets is small and the location is high, and the suspension rate is higher when the number of exhaust outlets is large and the location is low, which are 27.9% and 1.11% respectively.

Lithium–sulfur batteries (LSB) show excellent potential as future energy storage devices with high energy density, but their slow redox kinetics and the shuttle effect seriously hinder their commercial application. Herein, a 0D@2D composite was obtained by anchoring polar nano-TiO2 onto a 2D layered g-C3N4 surface in situ, and a functional separator was prepared using multi-walled carbon nanotubes as a conductive substrate. Due to their long-range conductivity, multi-walled carbon nanotubes make up for the low conductivity of TiO2@g-C3N4 to some extent. A lithium–sulfur battery prepared with a modified separator exhibited excellent long-term cycle performance, a good lithium ion diffusion rate, and rapid redox kinetics. The initial specific discharge capacity of the composite was 1316 mAh g−1 at 1 C, and a high specific discharge capacity of 569.9 mAh g−1 was maintained after 800 cycles (the capacity decay rate per cycle was only 0.07%). Even at the high current density of 5 C, a specific capacity of 784 mAh g−1 was achieved. After 60 cycles at 0.5 C, the modified separator retained the discharge capacity of 718 mAh g−1 under a sulfur load of 2.58 mg cm−2. In summary, the construction of a heterojunction significantly improved the overall cycle stability of the battery and the utilization rate of active substances. Therefore, this study provides a simple and effective strategy for further improving the overall performance and commercial application of lithium–sulfur batteries. [ABSTRACT FROM AUTHOR]

To design D‐amino acid dehydrogenase (DAADH) for enhanced stability, the interactions of the subunit interfaces of DAADH were analyzed. Interaction network analysis of DAADH indicated that there are only weak interactions between the A and B subunits. Several co‐evolved residue pairs were selected for mutation to enhance interfacial interactions of subunits, and 11 designed DAADHs were obtained. DA06 and DA11 were selected for experimental verification for their salt bridges are 1.4 and 1.2‐fold of that of DAwild, respectively. DA11 can maintain 93% activity in 80°C, while it was only 40% for DAwild. Thermostability study indicated the half‐life of DA11 was 2‐fold of DAwild. Molecular dynamics simulations revealed that the extraordinary stability of the DA11 was due to the formation of extra interfacial salt bridges. The article provides a strategy of mutations outside the active site of enzyme by co‐evolutionary analysis which can reduce the effect of the activity‐thermostability trade‐off. [ABSTRACT FROM AUTHOR]