The Effects of Combined Low Frequency Repetitive Transcranial Magnetic Stimulation and Motor Imagery on Upper Extremity Motor Recovery Following Stroke

Objective: To investigate the effects of low frequency transcranial magnetic stimulation (LF-rTMS) combined with motor imagery (MI) on upper limb motor function during stroke rehabilitation.Background: Hemiplegic upper extremity activity obstacle is a common movement disorder after stroke. Compared with a single intervention, sequential protocol or combination of several techniques has been proven to be better for alleviating motor function disorder. Non-invasive neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) have been verified to augment the efficacy of rehabilitation.Methods:Participants were randomly assigned to 2 intervention cohorts: (1) experimental group (rTMS+MI group) was applied at 1 Hz rTMS over the primary motor cortex of the contralesional hemisphere combined with audio-based MI; (2) control group (rTMS group) received the same therapeutic parameters of rTMS combined with audiotape-led relaxation. LF-rTMS protocol was conducted in 10 sessions over 2 weeks for 30 min. Functional measurements include Wolf Motor Function Test (WMFT), the Fugl-Meyer Assessment Upper Extremity (UE-FMA) subscore, the Box and Block Test (BBT), and the Modified Barthel index (MBI) were conducted at baseline, the second week (week 2) and the fourth week (week 4).Results: All assessments of upper limb function improved in both groups at weeks 2 and 4. In particular, significant differences were observed between two groups at end-intervention and after intervention (p < 0.05). In these findings, we saw greater changes of WMFT (p < 0.01), UE-FMA (p < 0.01), BBT (p < 0.01), and MBI (p < 0.001) scores in the experimental group.Conclusions: LF-rTMS combined with MI had a positive effect on motor function of upper limb and can be used for the rehabilitation of upper extremity motor recovery in stroke patients

Curcumin Reduces Cognitive Deficits by Inhibiting Neuroinflammation through the Endoplasmic Reticulum Stress Pathway in Apolipoprotein E4 Transgenic Mice.

Apolipoprotein E4 (ApoE4) is the main genetic risk factor for Alzheimer's disease (AD), but the exact way in which it causes AD remains unclear. Curcumin is considered to have good therapeutic potential for AD, but its mechanism has not been clarified. This study aims to observe the effect of curcumin on ApoE4 transgenic mice and explore its possible molecular mechanism. Eight-month-old ApoE4 transgenic mice were intraperitoneally injected with curcumin for 3 weeks, and the Morris water maze test was used to evaluate the cognitive ability of the mice. Immunofluorescence staining, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to examine the brain tissues of the mice. Curcumin reduced the high expression of ApoE4 and the excessive release of inflammatory factors in ApoE4 mice. In particular, the expression of marker proteins of endoplasmic reticulum (ER) stress was significantly increased in ApoE4 mice, while curcumin significantly reduced the increase in the expression of these proteins. Collectively, curcumin alleviates neuroinflammation in the brains of ApoE4 mice by inhibiting ER stress, thus improving the learning and cognitive ability of transgenic mice

Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

The pharmacokinetic profile of a drug can be different when delivered as a nanosuspension compared with a true solution, which may in turn affect the therapeutic effect of the drug. The goal of this study was to prepare itraconazole nanosuspensions (ITZ-Nanos) stabilized by an amphipathic polymer, polyethylene glycol-poly (benzyl aspartic acid ester) (PEG-PBLA), by the precipitation-homogenization, and study the pharmacokinetic profile of the ITZ-Nanos. The particle size and morphology of nanosuspensions were determined by Zetasizer and field emission scanning electron microscope (SEM), respectively. The dissolution profile was evaluated using a paddle method according to Chinese Pharmacopoeia 2015. The level of ITZ in plasma and tissues was measured by a HPLC method. The optimized ITZ-Nanos had an average particle size of 268.1 ± 6.5 nm and the particles were in a rectangular form. The dissolution profile of ITZ-Nanos was similar to that of commercial ITZ injections, with nearly 90% ITZ released in the first 5 min. The ITZ-Nanos displayed different pharmacokinetic properties compared with the commercial ITZ injections, including a decreased initial drug concentration, increased plasma half-life and mean residence time (MRT), and increased concentration in the liver, lung, and spleen. The ITZ-Nanos can change the in vivo distribution of ITZ and result in passive targeting to the organs with mononuclear phagocyte systems (MPS)

N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals

Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129 which increases compactness between HA monomers thus stabilizes the trimeric structure. Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts

H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation

Highly pathogenic avian influenza H5N1 virus has swept west across the globe and caused serious debates on the roles of migratory birds in virus circulation since the first large-scale outbreak in migratory birds of Lake Qinghai, 2005. In May 2006, another outbreak struck Lake Qinghai and six novel strains were isolated. To elucidate these QH06 viruses, the six isolates were subjected to whole-genome sequencing. Phylogenetic analyses show that QH06 viruses are derived from the lineages of Lake Qinghai, 2005. Five of the six novel isolates are adjacent to the strain A/Cygnus olor/Croatia/1/05, and the last one is related to the strain A/duck/Novosibirsk/02/05, an isolate of the flyway. Antigenic analyses suggest that QH06 and QH05 viruses are similar to each other. These findings implicate that QH06 viruses of Lake Qinghai may travel back via migratory birds, though not ruling out the possibility of local circulation of viruses of Lake Qinghai

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Accelerated Degradation Process Analysis Based on the Nonlinear Wiener Process with Covariates and Random Effects

It is assumed that the drift parameter is dependent on the acceleration variables and the diffusion coefficient remains the same across the whole accelerated degradation test (ADT) in most of the literature based on Wiener process. However, the diffusion coefficient variation would also become obvious in some applications with the stress increasing. Aiming at the phenomenon, the paper concludes that both the drift parameter and the diffusion parameter depend on stress variables based on the invariance principle of failure mechanism and Nelson assumption. Accordingly, constant stress accelerated degradation process (CSADP) and step stress accelerated degradation process (SSADP) with random effects are modeled. The unknown parameters in the established model are estimated based on the property of degradation and degradation increment, separately for CASDT and SSADT, by the maximum likelihood estimation approach with measurement error. In addition, the simulation steps of accelerated degradation data are provided and simulated step stress accelerated degradation data is designed to validate the proposed model compared to other models. Finally, a case study of CSADT is conducted to demonstrate the benefits of our model in the practical engineering

pH Drives Differences in Bacterial Community β-Diversity in Hydrologically Connected Lake Sediments

As microorganisms are very sensitive to changes in the lake environment, a comprehensive and systematic understanding of the structure and diversity of lake sediment microbial communities can provide feedback on sediment status and lake ecosystem protection. Xiao Xingkai Lake (XXL) and Xingkai Lake (XL) are two neighboring lakes hydrologically connected by a gate and dam, with extensive agricultural practices and other human activities existing in the surrounding area. In view of this, we selected XXL and XL as the study area and divided the area into three regions (XXLR, XXLD, and XLD) according to different hydrological conditions. We investigated the physicochemical properties of surface sediments in different regions and the structure and diversity of bacterial communities using high-throughput sequencing. The results showed that various nutrients (nitrogen, phosphorus) and carbon (DOC, LOC, TC) were significantly enriched in the XXLD region. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant bacterial phyla in the sediments, accounting for more than 60% of the entire community in all regions. Non-metric multidimensional scaling analysis and analysis of similarities confirmed that β-diversity varied among different regions. In addition, the assembly of bacterial communities was dominated by a heterogeneous selection in different regions, indicating the important influence of sediment environmental factors on the community. Among these sediment properties, the partial least squares path analysis revealed that pH was the best predictor variable driving differences in bacterial communities in different regions, with higher pH reducing beta diversity among communities. Overall, our study focused on the structure and diversity of bacterial communities in lake sediments of the Xingkai Lake basin and revealed that high pH causes the β-diversity of bacterial communities in the sediment to decrease. This provides a reference for further studies on sediment microorganisms in the Xingkai Lake basin in the future

Monitoring k-Nearest Neighbor Queries Over Moving Objects

Many location-based applications require constant monitoring of k-nearest neighbor (k-NN) queries over moving objects within a geographic area. Existing approaches to this problem have focused on predictive queries, and relied on the assumption that the trajectories of the objects are fully predictable at query processing time. We relax thi

Occurrence and risk assessment of triclosan in freshwater lakes in the middle Yangtze River basin (Wuhan, Central China)

Triclosan (TCS) is an endocrine disrupting chemical which is commonly used as a disinfectant in pharmaceuticals and personal care products (PPCP's). Since early 2020, the worldwide outbreak of COVID-19 has increased the use of PPCP's, so the occurrence and impact of TCS on freshwater lakes should be considered. However, little attention has been given to the effect of TCS on freshwater lakes in China. This study is the first attempt at a risk assessment focusing on the temporal and spatial occurrence of TCS in freshwater lakes in the middle Yangtze River basin. The surface water and sediments of Donghu Lake and Liangzi Lake (Wuhan, Central China) were collected from October 2020 to August 2021. The maximum concentrations of TCS were 466 ​ng/L and 239 ​ng/L in surface water, 71 ​ng/g and 25 ​ng/g (dry weight) in sediments of Donghu Lake and Liangzi Lake, respectively. Significant temporal and spatial differences of TCS were observed within and between the lakes, with the highest concentrations measured in winter. Furthermore, higher concentrations of TCS were observed in areas that are more impacted by human activities. There was a significant positive correlation between TCS and nitrogen in the surface water. A risk assessment using the risk quotient (RQ) method showed that a potentially high risk (RQ ​> ​1) was found only in surface waters from Donghu Lake, and that the sediments posed a lower risk than the surface waters. These results provide timely data on the temporal and spatial occurrence of TCS in freshwater lakes in China following the outbreak of COVID-19 and demonstrate a possible high risk of exposure to TCS for aquatic biota