Protection Efficacy of the Extract of Ginkgo biloba

Repeated high sustained positive Gz (+Gz) exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb) has been reported to have neuroprotective effects and cognition-enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM) was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) but reduce the production of malondialdehyde (MDA). Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system

Identification and characterization of a ribose 2′-O-methyltransferase encoded by the ronivirus branch of Nidovirales.

Peer reviewe

Expression of HER2 in high-grade urothelial carcinoma based on Chinese expert consensus and the clinical effects of disitamab vedotin-tislelizumab combination therapy in the treatment of advanced patients

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab.Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy’s efficacy and safety.Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions.Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC

Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs

ERN: Emergence Rescue Navigation with Wireless Sensor Networks

Navigation with wireless sensor networks (WSNs) can help people escape safely from an emergency. Previous navigation algorithms attempt to find safe and efficient escape paths for individuals under various environmental dynamics but ignore possible congestion caused by the individuals rushing for the exits. Moreover, all the previous works have overlooked the fact that the emergency rescue force can take actions strategically in order to save people out of danger. We propose ERN, Emergence Rescue Navigation algorithm by treating WSNs as navigation infrastructure. ERN takes both pedestrian congestion and rescue force flexibility into account. A directed graph is used to model the emergency regions. Human’s movements are regarded as network flows on the graph. By calculating the maximum flow and minimum cut on the graph, the system can provide firemen rescue commands to eliminate key dangerous areas, which may significantly reduce congestion and save trapped people. We have performed extensive simulations under dynamic environments to evaluate the effectiveness and response time of ERN. Simulation results show that with ERN people in emergency are evacuated much faster and less congestion is observed

Energy Characteristics and Internal Flow Field Analysis of Centrifugal Prefabricated Pumping Station with Two Pumps in Operation

In order to study the hydraulic performance and internal flow field of dual pumps in centrifugal prefabricated pumping station under operation conditions, this paper carried out a numerical calculation based on CFD software for dual pumps in a centrifugal prefabricated pumping station under different flow conditions and verified the internal flow field through test. The results show that the efficiency of centrifugal prefabricated pumping station under design conditions (Qd = 33.93 m3/h) is 63.96%, the head is 8.66 m, the head at the starting point of the saddle area is 10.50 m, which is 1.21 times of the designed head. The efficiency of the high-efficiency zone of the prefabricated pump station is 58.0~63.0%, and the corresponding flow range is 0.62Qd~1.41Qd (21.0~48.0 m3/h). The uniformity of the inlet flow rate of impeller of pump 1 is 74.70%, and that of pump 2 is 75.57%. The flow fields of water pumps on both sides are inconsistent. The results of the flow field indicate that there are severe back flow phenomena at the prefabricated bucket intake, more back flow in the bucket, and many eddies on the side wall. With the increase in flow rate, the eddy structure at the intake expands continuously and moves towards the center area, which has a negative impact on the flow field in the center area. The research results of this paper can provide a theoretical reference for the research and operation of the same type of prefabricated pumping stations

Efficient Emergency Rescue Navigation with Wireless Sensor Networks *

Recently, many applications in wireless sensor networks (WSNs) have been discussed. Navigation with WSNs is among the most heated debated ones. Previous navigation algorithms attempt to find safe and efficient escape paths for individuals under various environmental dynamics but ignore possible congestion caused by the individuals rushing for the exits. Moreover, most previous works have overlooked the fact that the emergency rescue force can take actions strategically in order to save people out of danger. We propose an efficient Emergency Rescue Navigation strategy (ERN) by treating WSNs as navigation infrastructure. Our approach takes both pedestrian congestion and rescue force flexibility into account. A directed graph is used to model the emergency regions. Human’s movements are regarded as network flows on the graph. By calculating the maximum flow and minimum cut on the graph, the system can provide firemen rescue commands to eliminate key dangerous areas, which may significantly reduce congestion and save trapped people. We have performed extensive simulations under dynamic environments to evaluate the effectiveness and response time of our work. Simulation results show that, with our strategy, people in emergency are evacuated much faster and less congestion is observed