Minimal active domain of human salivary histatin 1 is efficacious in promoting acute skin wound healing

Dear Editor,The skin barrier can be impaired by acute skin wounds,which may lead to a series of complications.It is essential to accelerate wound healing and rapidly restore the structural integrity and functionality of skin.One of the promising bioactive agents is human salivary histatin 1(Hst1),a 38-amino acid histidine-rich peptide that functions to maintain the homeostasis of oral mucosa with a cellular mechanism of promoting the adhesion,spreading,migration of epithelial cells and thus re-epithelialization[1].In recent years,Hst1 has been shown to be effective against various skin-related cell types,such as fibroblasts,myo-fibroblasts,keratinocytes and endothelial cells.In our latest in-vivo study,Hst1 not only promotes angiogenesis,re-epithelialization and collagen production,but also suppresses inflammation,thereby significantly accelerating acute skin wound healing in mice[2].All these studies show that Hst1 is a potent bioactive agent for accelerating acute skin wound healing.

Active suspension with optimal control based on a full vehicle model

The 7-DOF model of a full vehicle with an active suspension is developed in this paper.The model is written into the state equation style.Actuator forces are treated as inputs in the state equations.Based on the basic optimal control theory,the optimal gains for the control system are figured out.So an optimal controller is developed and implemented using Matlab/Simulink,where the Riccati equation with coupling terms is deduced using the Hamilton equation.The all state feedback is chosen for the controller.The gains for all vehicle variables are traded off so that majority of indexes were up to optimal.The active suspension with optimal control is simulated in frequency domain and time domain separately,and compared with a passive suspension.Throughout all the simulation results,the optimal controller developed in this paper works well in the majority of instances.In all,the comfort and ride performance of the vehicle are improved under the active suspension with optimal control.

Therapeutic targeting of the androgen receptor(AR)and AR variants in prostate cancer

Prostate cancer(PCa)accounted for over 300000 deaths world-wide in 2018.Most of the PCa deaths occurred due to the aggressive castration-resistant PCa(CRPC).Since the androgen receptor(AR)and its ligands contribute to the continued growth of androgendependent PCa(ADPCa)and CRPC,AR has become a well-characterized and pivotal therapeutic-target.Although AR signaling was identified as therapeutic-target in PCa over five-decades ago,there remains several practical issues such as lack of antagonist-bound AR crystal structure,stabilization of the AR in the presence of agonists due to N-terminus and C-terminus interaction,unfavorable large-molecule accommodation of the ligand-binding domain(LBD),and generation of AR splice variants that lack the LBD that impede the discovery of highly potent fail-safe drugs.This review summarizes the AR-signaling pathway targeted therapeutics currently used in PCa and the approaches that could be used in future ARtargeted drug development of potent next-generation molecules.The review also outlines the discovery of molecules that bind to domains other than the LBD and those that inhibit both the full length and splice variant of ARs.

Discovery of novel inhibitors of anti-apoptotic Bcl-2 proteins derived from Bim BH3 domain

The BH3 mimetics targeting the interaction between the BH3-only proteins and their prosurvival Bcl-2family proteins have shown enormous potential as cancer therapeutics. Herein, seven analogues targeting anti-apoptotic Bcl-2 proteins derived from the Bim BH3 domain via sequence simplification and/or modification are described. The in vitro binding affinity on anti-apoptotic Bcl-2 proteins and cell killing activity were evaluated. The results showed that analogues could significantly bind to target proteins and exhibited anti-cancer effect against three cancer cell lines. Of particular interest were the analogue SM-5（KD= 9.48 nmol/L for Bcl-2） and SM-6（KD= 0.08 nmol/L for Bcl-xL）, which exhibited improved binding affinity compared with the lead Bim（KD= 16.90 nmol/L for Bcl-2 and 22.2 nmol/L for Bcl-xL, respectively）. These results indicated that the peptide sequence containing the four hydrophobic side chains occupying pockets within the BH3-recognition cleft of anti-apoptotic Bcl-2 proteins might be the minimum sequence required for the bioactivity and the active core region of Bim. Promising inhibitors of anti-apoptotic Bcl-2 proteins with high bioactivity might be designed based on the active core.

Overexpression of the Wounding-Responsive Gene AtMYB15 Activates the Shikimate Pathway in Arabidopsis

The MYB transcription factor genes play important roles in many developmental processes and various defense responses of plants. The shikimate pathway is a major biosynthetic pathway for the production of three aromatic amino acids and other aromatic compounds that are involved in multiple responses of plants, including protection against UV and defense. Herein, we describe the characterization of the R2R3-MYB gene AtMYB15as an activator of the shikimate pathway in Arabidopsis. The AtMYB15 protein is nuclear localized and a transcriptional activation domain is found in its C-terminal portion. Northern blots showed that AtMYB15 is an early wounding-inducible gene. Resutls of microarray analysis, confirmed using quantitative real-time polymerase chain reaction, showed that overexpression of AtMYB15 in transgenic plants resulted in elevated expression of almost all the genes involved in the shikimate pathway. Bioinformatics analysis showed that one or more AtMYB15-binding AC elements were detected in the promoters of these upregulated genes. Furthermore, these genes in the shikimate pathway were also found to be induced by wounding. These data suggest an important role of AtMYB15as a possible direct regulator of the Arabidopsis shikimate pathway in response to wounding.

Light controlled prebreakdown characteristics of a semi-insulating GaAs photoconductive switch

A 4 mm gap semi-insulating （SI） GaAs photoconductive switch （PCSS） was triggered by a pulse laser with a wavelength of 1064 nm and a pulse energy of 0.5 mJ. In the experiment, when the bias field was 4 kV, the switch did not induce self-maintained discharge but worked in nonlinear （lock-on） mode. The phenomenon is analyzed as follows： an exciton effect contributes to photoconduction in the generation and dissociation of ex- citons. Collision ionization, avalanche multiplication and the exciton effect can supply carrier concentration and energy when an outside light source was removed. Under the combined influence of these factors, the S1-GaAs PCSS develops into self-maintained discharge rather than just in the light-controlled prebreakdown status. The characteristics of the filament affect the degree of damage to the switch.

Construction and Application of Efficient Ac-Ds Transposon Tagging Vectors in Rice

Transposons are effective mutagens alternative to T-DNA for the generation of insertional mutants in many plant species including those whose transformation is inefficient. The current strategies of transposon tagging are usually slow and labor-intensive and yield low frequency of tagged lines. We have constructed a series of transposon tagging vectors based on three approaches： （i） AcTPase controlled by glucocorticoid binding domain/VP16 acidic activation domain/Gal4 DNA-binding domain （GVG） chemical-inducible expression system; （ii） deletion of AcTPase via Cre-lox site-specific recombination that was initially triggered by Ds excision; and （iii） suppression of early transposition events in transformed rice callus through a dual-functional hygromycin resistance gene in a novel Ds element （HPT-Ds）, We tested these vectors in transgenic rice and characterized the transposition events. Our results showed that these vectors are useful resources for functional genomics of rice and other crop plants. The vectors are freely available for the community,