摘要：Monoclonal antibodies(mAbs)are widely utilized as therapeutic drugs for various diseases,such as cancer,autoimmune diseases,and infectious *** the avian-derived B cell line DT40,we previously developed an antibody display technology,namely,the ADLib system,which rapidly generates antigen-specific ***,we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human *** libraries were first constructed by replacing endogenous immunoglobulin genes with designed human *** these libraries,clones producing full-length human IgGs against distinct antigens can be isolated,as exemplified by the selection of antagonistic *** advantage of avian biology,effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting,quickly affording mAbs with improved affinities and ***,we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody ***,our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells,indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.

摘要：Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease(AD). We analyzed by an inverse docking procedure(INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE,PSEN, IDE, CASP, calpain and TNF-a, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

摘要：The green alga Tetraselmis subcordiformis has been widely used as a quality live food for aquaculture species, and also has been studied as a model organism for the photo-biological production of hydrogen. We attempted to quantify the relationship between T. subcordiformis specific growth rate （SGR） and three important environmental factors （temperature, salinity, and pH） using the central composite design and response surface method under laboratory conditions. The results showed that the linear effects of temperature and salinity were significant （P〈0.05）, and they were equally important in impacting T. subcordiformis specific growth; the linear effect of pH was not significant （P〉0.05）; the interactive effect of temperature and pH was significant （P〈0.05）, whereas the temperature ~ salinity and salinity x pH interactions were not significant （P〉0.05）; all of the quadratic effects of the three factors were significant （P〈0.05）. A model equation for specific growth rate with the three factors was established, with the unadjusted and predictive R2 as high as 0.990 and 0.921, respectively, suggesting that the model was a very good fit and that it could be used to predict SGR. Through optimizing the reliable model, an optimal 3-factor combination of 25~C/35 of salinity/pH 7.9 was obtained, at which the maximum specific growth rate （0.65） was recorded, with a desirability value of 93.8%. These experimental results could serve as guidelines for increasing T. subcordiformis production efficiency.

摘要：The presence of anti-p53 antibody in serum is a biomarker for cancer. However, its high sensitivity detection is still an issue in cancer diagnosis. To tackle this challenge, we used fd phage, a human-safe bacteria-specific virus nanofiber that can be mass-produced by infecting host bacteria in an error-free manner, and genetically engineered it to display a peptide capable of recognizing and capturing anti-p53 antibody on its side wall. We employed the resultant phage nanofibers as a capture probe to develop a modified version of the enzyme- linked immunosorbent assay （ELISA） method, termed phage-ELISA. We compared it to the traditional ELISA method for the detection of anti-p53 antibody, p53-ELISA, which uses recombinant wild-type p53 protein to capture anti-p53 antibody. We applied phage-ELISA to detect anti-p53 antibody in an experimental group of 316 patients with various types of malignant tumors. We found that a detection rate of 17.7% （56 positive cases） was achieved by phage-ELISA, which was comparable to the detection rate of 20.6% for p53-ELISA （65 positive cases）. However, when both phage and p53 were combined to form antibody-capturing probes for phage/p53-ELISA, a detection rate of 30.4% （96 positive cases） was achieved. Our work showed that owing to the combined capture of the anti-p53 antibody by both phage nanofibers and p53, the phage/p53-ELISA achieved the highest diagnostic accuracy and detection efficiency for the anti-p53 antibody in patients with various types of cancers. Our work suggests that a combination of nanofibers and antigens, both of which capture antibody, could lead to increased detection sensitivity, which is useful for applications in the life sciences, clinical medicine, and environmental sciences.

摘要：Protein chemical synthesis usually relies on the use of native chemical ligation that couples peptide thioester with a Cys-peptide. A limitation of this method is the difficulty of finding an appropriate Cys ligation site in many synthetic targets. To overcome this problem, the ligation-desulfurization approach has been developed. This approach involves the use of a thiol-containing amino acid as the ligation partner. After the sequence assembly is completed, the thiol group is removed through a desulfurization reaction to generate the standard amino acids. Currently this strategy has been applied to the ligations at a number of amino acids including Ala, Phe, Val, Lys, Thr, Leu, Pro and Gin. The present article reviews the design and svnthesis of these thiol-containing amino acids for native chemical libation at non-Cys sites.

摘要：Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions. We found that dozens of brain regions provide dense inputs to or receive dense inputs from PVN BDNF neurons, including several known weight control regions and several novel regions that might be functionally important for the BDNF-mediated regulation of energy ***, several regions show very dense reciprocal connections with PVN BDNF neurons, including the lateral septum, the preoptic area, the ventromedial hypothalamic nucleus, the paraventricular thalamic nucleus, the zona incerta, the lateral parabrachial nucleus, the subiculum, the raphe magnus nucleus, and the raphe pallidus nucleus. These strong anatomical connections might be indicative of important functional connections. Therefore, we provide an outline of potential neural circuitry mediated by PVN BDNF neurons, which might be helpful to resolve the complex obesity network.

摘要：Critics have pointed at new technologies as cutprits in the decline of civic life, neighboring and social capital construction in Western societies. When applied to community design and ptanning processes, technologies can empower residents to actively engage in decision-making, foster connections across social groups, with positive consequences on life and sociatization in public spaces. What kind of participation do technotogies foster？ And is it the kind that bridges social and ideotogical divides？ The 2012 community design process for Hawthorne Park in Medford, Oregon illustrates many of the challenges and opportunities connected to the use of new technologies in design. In the process, technologies were instrumental in enlisting a larger-than-usual number of residents to participate in the design of the park. Blogs and online questionnaires were successful in gathering people＇s thoughts on the design choices being made, but also favored a limited, intermittent form of engagement. The results are synthesized in principles for the successful integration of web-based technologies in future community design efforts： adaptability, fuji participation, nuanced participation and the need for links to the physical realm.

摘要：Background： Recently, optogenetics based on genetically encoded photosensitive proteins has emerged as an innovative technology platform to revolutionize manipulation of cellular behavior through fight stimulation. It has enabled user defined control of various cellular behaviors with spatiotemporal precision and minimal invasiveness, creating unprecedented opportunities for biomedical applications. Results： This article reviews current advances in optogenetic networks designed for the treatment of human diseases. We highlight the advantages of these optogenetic networks, as well as emerging questions and future perspectives. Conclusions： Various optogenetic systems have been engineered to control biological processes at all levels using light and applied for numerous diseases, such as metabolic disorders, cancer, and immune diseases. Continued development of optogenetic modules will be necessary to precisely control of gene expression magnitude towards clinical medical practice in the context of real-world problems.

摘要：AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21^CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h. RESULTS： The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21^CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21^CIP1/WAF1 the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells. CONCLUSION： Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21^CIP1/WAF1 activation in SNU-16 cells.

摘要：The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic *** adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to *** a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment *** this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is *** by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and *** study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm *** indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis *** thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation ***,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to *** microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.