Objective To observe the effect of transplantation of telomerase immortalized human neural progenitor cells to acute injured canine spinal cord by using MR diffusion tensor imaging (DTI).Methods Telomerase immortalized human neural progenitor cells with expression of green fluorescent protein were prepared for transplantation. Eight adult canines with left spinal cord hemisection at the level of T13 were examined by MR diffusion tensor imaging four times sequentially: prior to injury, one week after injury, one week after transplantation (two weeks after injury), and four weeks after transplantation. Results The ADC values of the injured spinal cord were (1.00?0.15)?10 -3 mm2/s, (1.65?0.45)?10 -3 mm2/s, (1.44?0.48)?10 -3 mm2/s, and (1.43?0.26) ?10 -3 mm2/s, respectively. There was statistically significant difference between the data obtained at different times (F=6.038, P=0.005). The FA values of the injured spinal cord were 0.59?0.11, 0.30?0.17, 0.36?0.25, and 0.34?0.11, respectively. There was also statistically significant difference between the data obtained at different times ( F=5.221,P=0.009). The ADC values of the intact spinal cord were (1.01?0.17)?10 -3 mm2/s, (1.32?0.06)?10 -3 mm2/s, (1.10?0.24)?10 -3 mm2/s, and (1.14?0.22) ?10 -3 mm2/s, respectively. There was no statistically significant difference between the data obtained at different times ( F=1.303,P=0.306). The FA values of the intact spinal cord were 0.60?0.09, 0.38?0.25, 0.46?0.15, and 0.50?0.21, respectively. There was also no statistically significant difference between the data obtained at different times (F=2.797,P=0.072).Conclusion DTI can provide useful information for spinal cord injury and regeneration in experimental spinal cord injury.

Objective:To explore the effect of combining functional electric stimulation (FES) with upper limb cycle training in rehabilitating upper limb motor function and ability in the activities of daily living after a stroke.Methods:Sixty hemiplegic stroke survivors were randomly divided into an experimental group and a control group. In addition to conventional rehabilitation therapy, the experimental group underwent 20 minutes of MOTOmed upper limb cycle training every day while receiving FES. The control group received only the 20 minutes of cycle training. Before and after 4 weeks, Brunnstrom staging was used to quantify hand and upper extremity functioning. The Fulg-Meyer assessment upper extremity scale (FMA-UE) and the modified Barthel index (MBI) were also used before the training and after 1, 2, 3 and 4 weeks of the treatments.Results:After 4 weeks of treatment, significant differences were observed in the average BS scores of both groups compared with before the intervention. The average hand and upper limb stages of the experimental group were significantly better than the control group′s averages. Significant improvement was also observed in the average FMA-UE and MBI scores of both groups after only one week, with significantly greater improvement in the experimental group.Conclusions:Supplementing upper limb cycle training with FES can significantly improve the upper limb motor function and ability in the activities of daily living of stroke survivors. It is more effective than the MOTOmed exercise alone.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December,2019.Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving,and driven by adaptation to the new host and environments is still under debate.Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,and providing guidance for disease control and treatments.Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30,2021,we demonstrate with popula-tion genetic evidence that during the course of SARS-CoV-2 pandemic in humans,1)SARS-CoV-2 genomes are overall conserved under purifying selection,especially for the 14 genes related to viral RNA replication,transcription,and assembly;2)ongoing positive selection is actively driving the evolution of 6 genes(e.g.,S,ORF3a,and N)that play critical roles in molecular processes involving pathogen-host interactions,including viral invasion into and egress from host cells,and viral inhi-bition and evasion of host immune response,possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution.According to an established haplotype phylogenetic relation-ship of 138 viral clusters,a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters,of which multiple mutations potentially conferring alterations in viral transmis-sibility,pathogenicity,and virulence of SARS-CoV-2 are highlighted,warranting attention.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.