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The never-ending emergence of SARS-CoV-2 variations of concern (VOCs) has challenged the whole world for pandemic control. In order to develop effective drugs and vaccines, one needs to efficiently simulate SARS-CoV-2 spike receptor binding domain (RBD) mutations and identify high-risk variants. We pretrain a large protein language model on approximately 408 million protein sequences and construct a high-throughput screening for the prediction of binding affinity and antibody escape. As the first work on SARS-CoV-2 RBD mutation simulation, we successfully identify mutations in the RBD regions of 5 VOCs and can screen millions of potential variants in seconds. Our workflow scales to 4096 NPUs with 96.5% scalability and 493.9x speedup in mixed precision computing, while achieving a peak performance of 366.8 PFLOPS (reaching 34.9% theoretical peak) on Pengcheng Cloudbrain-II. Our method paves the way for simulating coronavirus evolution in order to prepare for a future pandemic that will inevitably take place. Our models are released at https://github.com/ZhiweiNiepku/SARS-CoV-2_mutation_simulation to facilitate future related work.
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The intestinal microbiota refers to the microbial group that exists in the intestine, and its composition disorder may affect human health. Many studies have found that intestinal microbiota and their metabolites may be closely related to the pathologies of Alzheimer′s disease (AD) through the gut-brain axis. This article will review the roles and possible mechanisms of lipopolysaccharide, functional bacterial amyloid proteins and bile acids, which are common metabolites of intestinal microbiota, in the pathogenesis of AD, and provide valuable information for exploring the pathogenesis of AD.
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The fluorescence and photosensitivity properties of NaYb1-x F4:Tm x 3+ nanoparticles were optimized to develop noninvasive near-infrared fluorescence imaging-guided photodynamic therapy. The emission at 800 nm from Tm3+ presented an exponential increase with an increase in the Tm3+ doping concentration from 0 to 2%. The photosensitivity properties of NaYb1-x F4:Tm x 3+ nanoparticles were also studied via the chemoprobe method, which used a reactive oxygen quencher, 1,3-diphenylisobenzofuran (DPBF). With the increase in the doping concentration of Tm3+, the generation rate of reactive oxygen species in NaYb1-x F4:Tm x 3+ nanoparticles decreased linearly at a rate of 0.3. The doping concentration of Tm3+ had two opposite effects on the 800 nm emission and generation rates of reactive oxygen species. The competitive relationship was discussed and an optimal value for the Tm3+ doping concentration of approximately 1% was determined. At this concentration, the energy of the Yb3+ excited state can be fully utilized, and the fluorescence and photosensitivity properties are an effective combination.
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At present, the treatment methods of lymphoma mainly include the combined chemotherapy, hematopoietic stem cell transplantation, immunotherapy and new targeted therapies, but the treatment-related drug resistance, recurrence, extranodal and central nervous system infiltration, and leukemia transformation are still intractable problems that need to be solved in clinical practice. Studies have shown that cytokines are expressed to varying degrees in patients with lymphoma, which are significantly related to the progression of lymphoma, poor prognosis, chemotherapy response, and drug resistance. It has been confirmed that interleukin 6 (IL-6) and IL-10 are highly expressed in all types of lymphoma, and IL-10 is highly expressed in the cerebrospinal fluid of central nervous system lymphoma, all of which indicate a poor prognosis. This article reviews the role of cytokines in the development, treatment and prognosis of lymphoma.
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Calmodulin,as an important signaling regulatory protein,widely exists in eukaryotic cells and participates in a variety of physiological activities.Alzheimer's disease (AD) is a typical neurodegenerative diseasemostly affecting the old people.Senile plaques (SP) caused by amyloid protein deposition and neurofibrillary tangles (NTF) caused by over-phosphorylation of Tau protein in the brain are the two major neuropathological hallmarks of AD.Neuronal apoptosis induced by dysregulation of calcium homeostasis also plays a significant role during this pathological process.Recent studies have found that calcium and its downstream receptor,calmodulin,are closely associated with the pathogenesis and progress of Alzheimer's disease.This article reviews the current development and the latest research progress on the effects of calmodulin on β-amyloid protein generation and deposition,neurofibrillary tangle formation,synaptic plasticity in AD around the world,comprehensively discusses the role of calmodulin in the pathogenesis of Alzheimer's disease.
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Kinect-like depth sensors have been widely used in rehabilitation systems. However, single depth sensor processes limb-blocking, data loss or data error poorly, making it less reliable. This paper focus on using two Kinect sensors and data fusion method to solve these problems. First, two Kinect sensors capture the motion data of the healthy arm of the hemiplegic patient; Second, merge the data using the method of Set-Membership-Filter (SMF); Then, mirror this motion data by the Middle-Plane; In the end, control the wearable robotic arm driving the patient's paralytic arm so that the patient can interactively and initiatively complete a variety of recovery actions prompted by computer with 3D animation games.
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Reabilitação/instrumentação , Jogos de Vídeo , Algoritmos , Simulação por Computador , Humanos , Modelos Teóricos , Movimento , Estatística como AssuntoRESUMO
Objective To identify the genotype of the APP/tau/PS1 triple transgenic Alzheimer's disease (AD) mice,and investigate the pathological changes of tau protein in the pathogenic process.Methods Using specific primers of PS1,APP,tau gene,the genotypes of the triple transgenic AD mice were identified.Expression of tau protein in hippocampal tissue of mouse model aged 2,4,8 month was detected by immunohistochemistry.The expression of tau and its hyperphosphorylation in different sites in the hippocampal tissue and different month old mice was detected by Western blotting.Results PCR amplification fragment of 960 bp,530 bp and 400 bp of transgenic mouse genome were the expected size of APP,PS1,tau,respectively.Expression of tau in hippocampal CA3 region was increased obviously in the 8 month old mice.Compared with the normal wild-type mice,the expressions of tau and phosphorylation of pS262,pS404 and pS202 were increased significantly in hippocampus tissue of the transgenic mice (P＜0.01).Expression of tau were significantly higher in 8-and 12-monthsold mice than in 2 months-old mice (P ＜ 0.01).Phosphorylation level of pS404 and Ps202 was significantly increased since 2-months-old in transgenic mouse compared to the wild type mouse (P＜0.01),and in 8-monthold mice,there was also a significant increase as compared to that in 2 month-old mice (P＜0.01).As to the phosphorylation level of pSs262,the significant increase did not appear until 12 months old in transgenic mouse as compared to the wild type mouse (P＜0.01).Conclusions The triple transgenic mice can stably express the APP/tau/PS1 gene.The transgenic animals can be a useful model with the pathological features of tau of AD.The phosphorylation level of tau in different site increases in different time,which will provide useful research reference in Alzheimer's disease pathology and medication research.
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@#Objective To investigate the effect of exposure to 0.25 T, 0.35 T, 0.42 T static magnetic fields (SMF) on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). Methods Primary bone marrow MSCs were obtained from Sprague-Dawley rats and screened by adhesive method. MSCs were exposed to 0.25 T, 0.35 T, 0.42 T SMF continuously and 24 h intermittently respectively.The cell proliferation activity was detected by Cell Counting Kit (CCK-8) assay. The osteogenic differentiation markers including alkaline phosphatase (ALP) activity and osteocalcin were analyzed after continuously exposure to 0.35 T SMF. Results Compared with the control group, the proliferation activity of SMF-treated cells significantly decreased, especially on the 7th day (P<0.001) after continuous exposure,and on the 2nd to 8th day in 0.25 T, 0.35 T SMF intermittent exposure groups (P<0.001). Both the alkaline phosphatase activity and the level of osteocalcin significantly increased in MSCs after continuous exposure to 0.35 T SMF (P<0.05). Conclusion Continuous or intermittent exposure to 0.25 T, 0.35 T and 0.42 T SMF could effectively inhibit the proliferation of MSCs. Continuous exposure to 0.35 T SMF could enhance the osteogenic differentiation of MSCs.
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BACKGROUND:Poly(D,L-lactide-co-glycolide)(PLGA)may produce lactic acid and glycolic acid when PLGA degrades,thus leading to the acid accumulation and inducing the inflammatory reaction locally.OBJECTIVE:To investigate the effect of lysine,histidine and arginine on regulating the acid accumulation of PLGA copolymer during the degradation.DESIGN:Repeated measurement and experiment.TIME AND SETTING:The experiments were performed in the College of Bioengineering.Chongqing University from July 2006 to August 2007.MATERIALS:PILGA(80:20)was produced by Sigma(USA);Lysine,histidine and arginine(purlty>99%)were purchased from Sigma(USA);Chitosan(deacetylation degree:85%)was purchased from Chengdu Kelong Chemical Reagent Factory;Algin(viscosity:1.05-1.15)was purchased from Tianiin Damao Chemical Reagent Factory.METHODS:Lysine,histidine and arginine were added into PLGA with the proportion of 5%(w/v)and 10%(w/v)respectively.The resultant film sample was put into a bottle with tri-distilled-water for 2-month degradation at 37℃.The pH value of degradation solution was detected by pH meter;Each film sample was taken out and lyophilized 12 hours to get its dry weight and calculate mass loss ratio.Each variety of the solution was sampled three specimens,the average pH value,average initial weight and average finial weight of these three specimens were taken as the indices at each sampling time point,respectively.Accordingly,the regulation effect of basic amino acid was comparexl with that of algin,chitosan and NaHCO3.MAIN OUTCOME MEASURES:The changes of pH value of degradation solution;the mass loss ratio of the composite.RESULTS:Each basic additive could relieve the acid accumulation,among them,NaHCO3 was the strongest,while algin and chitosan showed a lowest capacity,basic amino acid was moderate;The suitable regulation effect could be achieved at a level of 5%lysine.CONCLUSION:Basic amino acid can effectively regulate the acid accumulation after PLGA degrades,and the optimal concentration of lysine is 5%.
