摘要：Natural products（NPs） have long been recognized as a valuable resource for drug discovery, and bringing NP-related features to virtual libraries is believed to be an effective way to increase the coverage of druggable chemical space. Here, deep learning-based molecule generative model, which is a recent technique in de novo molecule design, was applied to generate virtual libraries with NP-like properties. Results demonstrated that the model was effective in generating molecules that highly resemble NPs. Moreover, the model was also found to be capable of generating NP-like molecules that were also easy to synthesize, significantly increasing the practical value of the compound library.

摘要：Based on the structure of compound B51（IC_（50） = 37.4 μM）, which was discovered as hit in a previous virtual screen, a series of methylisoxazole/isothiazole amide derivatives were designed and synthesized as BACE1 inhibitors. The methoxyphenylpyrimidone fragment of B51 was transformed into a methoxyphenylmethylisoxazole/isothiazole moiety to reduce the molecular weight while retaining the ability to fit into the S1＇ and S2＇ subpocket of BACE1 as predicted by docking studies. The effects of BACE1 inhibition and the structure-activity relationships were analyzed. Among all 20 designed compounds, 5t exhibited almost 10-fold improved potency（IC_（50） = 5.33 μM） compared to B51 in the BACE1 inhibition assay. Additionally, it has exhibited ＂rapid binding, slow dissociation＂ kinetics in SPR analysis, suggesting a longer inhibitory effect than B51. All acquired methylisoxazole/isothiazole derivatives were small in size and safe to normal cells, which allow them represent a novel scaffold for BACE1 inhibitor design.

摘要：The brown planthopper, Nilaparvata lugens is a pest of cultivated rice through- out Asia and is controlled using insecticides and/or resistant rice varieties. This species has developed resistance to many classes of insecticide and biotypes have developed that are vir- ulent against formerly resistant rice cultivars. Insects use a suite of detoxification enzymes, including cytochrome P450s, glutathione S-transferases and carboxyl/cholinesterases to defend themselves against plant secondary metabolites and pesticides. Pyrosequencing on the Roche 454-FLX platform was used to produce a substantial expressed sequence tag （EST） dataset to complement the existing Sanger sequenced ESTs in GenBank. A total of 78 959 reads were combined with the 37 392 publically available Sanger ESTs; these assembled into 8 911 contigs and 10 620 singletons. Analysis of the distribution of tenta- tive unique genes （TUGs） with the gene ontology for biological processes and molecular functions suggests that the 454 and Sanger EST assembly is broadly representative of the N. lugens transcriptome. The brown planthopper transcriptome was found to contain 31 TUGs encoding P450s, nine encoding glutathione S-transferases and 26 encoding car- boxyl/cholinesterases and many of these are putatively involved in the detoxification of xenobiotics. The Agilent eArray platform was used to construct an oligonucleotide mi- croarray populated with probes for ~ 19 000 unigene sequences, including all those known to encode detoxification enzymes. The genomic resources developed in this study will be useful to the community studying this crop pest and will help elucidate the molecular mechanism underlying insecticide resistance and planthopper adaptation to resistant rice cultivars.

摘要：Pharmaceutical comprehensive study(PCS) is a new system of experimental teaching in China, which integrates multidisciplinary pharmaceutical knowledge and covers the basic process of new drug discovery. To explore the feasibility of this experiment teaching system and mode, we developed PCS as an elective course. The PCS is designed with two sections: pharmaceutical comprehensive design(PCD) and pharmaceutical comprehensive experiment(PCE). The PCD section includes literature review, comprehensive project design and oral examination. PCE can be divided into four parts: synthesis, quantitative determination, pharmacodynamic evaluation, and formulation and quality determination. Course grade was determined by experimental performance, written report, literature review, new project design and oral examination. The learning interest, experimental ability, theoretical level and literature retrieval ability, team spirit and interpersonal skills have been all significantly improved among students taking this course. A survey was administered at the end of the semester to the enrolled students. The responses were reported as percentages, and the feedback was positive. The course was highly recommended by the teaching inspection committee. This new course plays an important role in developing students’ creativity and comprehensive ability. It could help students understand the focus and features of every secondary discipline, as well as establish scientific and reasonable knowledge system. Most students can better understand the process of drug research after this course.

摘要：In the field of Second Language Acquisition （SLA）, motivation has played a crucial role for language learning and teaching. Just as motivation is important in SLA, demotivation constitutes an important factor for both students and teachers. In our previous study, investigating 97 teachers for demotivational factors, the teachers felt demotivated to see students＇ lack of interest and bad attitudes, as well as dissatisfaction with curriculum, teaching material and poor facilities. We concluded further investigation was necessary as to how teachers regain motivation and hopefully toward directed motivational current （DMC）, which not only provides a direction for action, but it also energizes action （D6myei et al, 2016）. In our present study, compared to our previous study which was analyzed quantitatively, we have collected qualitative data from some 34 college teachers investigating when they felt demotivated, what they did to cope with it, and how they regained their motivation. Data was collected, analyzed qualitatively, and factors which may lead to DMC was extracted. It is hoped that this study will be beneficial for facilitating better SLA learning and teaching, and also for teacher training.

摘要：INTRODUCTION: Lateral epicondylosis is a common cause of lateral elbow pain, however, some patients fail conservative management. One reason, many pathologies have similar presentations. There are no valid and reliable clinical tests to differentiate between tendopathy and arthropathy. This single case design looks at the utilization of the humeroradial joint (HRJ) distraction test to diagnose HRJ chondropathy. CASE SUMMARY: 38-year-old male recreational athlete with persistent lateral elbow pain, impaired motion, crepitus and locking. Disability of the Arm Shoulder Hand Questionnaire (DASH): 13.33/100. DASH Sport Module, 68.75/100. Differential Diagnosis: Chondropathy of the HRJ with loose body, based on history of elbow pain and locking, non-capsular pattern of limitation of motion and a positive HRJ distraction test. Intervention: loose body manipulation improved pain free range of motion with continued remarkable HRJ distraction test;referral to orthopedic surgeon. Plain radiographs and CT demonstrated a loose body and marked cartilage thinning within the HRJ. Arthroscopic removal of the loose body and plica resection was performed. Surgical exploration confirmed Grade 3 cartilage lesions within the radial head without involvement of the extensor muscle group. Post-operative physical therapy focused on restoration of accessory joint motion and education on return to functional and recreational activity. OUTCOMES: Full range and normal joint accessory motion, DASH score and DASH Sport Module score reduced to 8.33 and 25, 12-weeks post-operative. CONCLUSION: Arthroscopic exploratory surgery is recommended for chronic lateral elbow pain resistant to conservative management;however, patients who present with pain in the absence of a positive clinical examination and radiographic findings benefit least from arthroscopic evaluation. No clinical test(s) have been validated in the literature to diagnose HRJ lesions. This report is the first to propose the use of a new c

摘要：The application of thermoelectric devices(TEDs)for personalized thermoregulation is attractive for saving energy while balancing the quality of *** that directly attach to human skin remarkably minimized the energy wasted for cooling the entire ***,facing the extreme dynamic geometry change and strain of human skin,conventional TEDs cannot align with the contour of our bodies for the best thermoregulation ***,we designed a kirigami-based wearable TED with excellent water vapor permeability,flexibility,and *** analysis and experimental results reveal that our product can withstand various types of large mechanical deformation without circuit *** stated outcome and proposed facile approach not only reinforce the development of wearable TEDs but also offer an innovative opportunity for different electronics that require high conformability.

摘要：Background: The lower extremity muscle strength has been shown to be weaker in patients with diabetes mellitus, primarily due to the effects of diabetic polyneuropathy, a common diabetic complication. With respect to assessments of the lower extremity muscle strength, reference values for the knee extension force in healthy Japanese subjects have been reported. The clinical significance of applying knee extension force in the assessment of efficacy of exercise therapy and patient education has also been demonstrated, and the use of an individualized approach in physical exercise based on the quantitative assessment of the lower extremity muscle strength is becoming one of the most important strategies for promoting effective rehabilitation. Methods: The study is a multicenter, cross-sectional investigation. We will measure the knee extension force and evaluate the diabetic polyneuropathy in patients with type 2 diabetes using uniform equipment and methodology at all centers. We will compare the knee extension force between the subjects with and without diabetic polyneuropathy and will investigate the associations between the knee extension force and both glycemic control and exercise habits. The trial registration is UMIN CTR (UMIN000002810). Discussion: The lower extremity muscle strength has been insufficiently investigated in Japanese patients with diabetes. This study was designed to establish reference values for the knee extension force in Japanese diabetic patients with and without diabetic polyneuropathy.

摘要：The radial migration of cortical pyramidal neurons(PNs)during corticogenesis is necessary for establishing a multilayered cerebral *** migration defects are considered a critical etiology of neurodevelopmental disorders,including autism spectrum disorders(ASDs),schizophrenia,epilepsy,and intellectual disability(ID).TRIO is a high-risk candidate gene for ASDs and ***,its role in embryonic radial migration and the etiology of ASDs and ID are not fully *** this study,we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born *** investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin(N-cadherin).Also,independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent *** together,our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 *** results suggest the vital roles of the guanine nucleotide exchange factor 1(GEF1)and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners,which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

摘要：Objective To explore and interpret the experiences of pregnant women in Macao region,China during the COVID-19 *** Recruitment advertisements were published through multiple social platforms in Macao region,China.A purposive snowball sampling method was adopted to select *** women who were confirmed as pregnant from January to May 2020 participated in this qualitative *** was collected from November to December 2020 using in-depth personal ***-to-one interviews were conducted by telephone to avoid personal *** analysis was used to perform the data analysis and identify emergent *** Five themes emerged from the data analysis:changes in daily life,psychological distress,unique experiences of pregnancy follow-up,trying to pay attention to health information but also feeling overwhelmed,and change in hygiene behaviors due to fear of *** sub-themes were identified:being confined at home but understanding the reasons,financial pressures and timely support from the government,perceived risk of catching the infection,retaining optimism with various help and support,adequate personal protections,and obsessive hygiene *** During a pandemic,there is a risk of greater individual isolation,particularly for vulnerable groups such as women in *** humanized attention to and support for the residents from the government buffered the adverse impact on the study *** for such events is needed to focus on psychological distress,financial constraints,and prenatal health *** service delivery,such as telemedicine,online counseling,and virtual reality(VR)technology,should be applied to offer pregnant women timely support and avoid a crisis.