摘要：Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical *** has also been employed in various advanced industrial *** development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative ***,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and *** this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D ***,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced ***,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting *** review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue *** paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide ***,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.

摘要：Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer *** of this pathway by MEK inhibition is an efficient therapeutic approach of *** the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK *** acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.

摘要：Fragment-based drug discovery （FBDD） has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad （Asp228 and Asp32） of D-site amyloid precursor protein cleaving enzyme 1 （BACE1）. A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 pM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/$2＇ pockets well.

摘要：Reimbursement policy for outpatient chronic diseases is an important part of the basic medical insurance scheme in China. The reimbursement policy for outpatient chronic diseases in basic medical insurance for urban residents of provincial capitals in China were analyzed from the perspectives of disease types, benefits package, qualification and health service access. Proposals to improve policy design, establish standardized disease inclusion criteria and set reasonable benefits package, strengthen management and complete supporting policy, strengthen policy coordination were put forward according the existing problems such as fragmented policy, great difference in disease types and benefit package, supervision difficulty, incomplete policy framework and lack of policy coordination.

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：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：Objective： To provide guidance for future randomized controlled trials （RCTs） based on a review con- cerning acupuncture for treating polycystic ovary syndrome （PCOS）. Methods： A comprehensive literature search was conducted in October 2015 using MEDLINE, EMBASE, SCISEARCH, Cumulative Index to Nursing and Allied health Literature, the Cochrane Menstrual Disorders and Subfertility Group trials register, Allied and Complementary Medi- cine （AMED）, China National Knowledge Infrastructure （CNKI）, and the Wanfang databases. RCTs comparing either acupuncture with no/sham/pharmacological intervention or a combination of acupuncture and conventional therapy with conventional therapy in the treatment of PCOS were included in this review. A quality evaluation was performed for each of the included studies. Results： Thirty-one RCTs were included in the review and were divided into four categories according to the type of intervention used in the comparator or control group. Menstrual frequency, hor- mones, anthropometrics, insulin sensitivity, blood lipids, and fertility were used as the main measurements to assess the effects of acupuncture on the patients with PCOS. Thirty trials, except for one, showed an improvement in at least one of the indicators of PCOS after acupuncture treatment. However, normalizing the methodological and reporting format remains an issue. Conclusions： Based upon this review of current clinical trials concerning acupuncture for treating PCOS, we provide guidelines for better clinical trial design in the future.

摘要：A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linked *** inhibitory activities were assayed against recombinant human ST3Gal I and ST6Gal I by using the Schmidt’s HPLC-based *** synthetic compound 15 g showed moderate inhibitory *** findings implied that carbamate might serve as a bioisosteric replacement for a phosphate group in sialyltransferase inhibitor design to improve the membrane permeability.

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：Three series of novel anti-immunodeficiency virus 1 （HIV-1） dual （RT/1N） inhibitors were rationally designed by introducing a functioning diketo acid （DKA） into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance （SPR）, and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.