Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.

鸟类羽色性别二态性形成机制研究进展

鸟类羽毛颜色普遍存在性别二态性,即雄性羽色相对于雌性更鲜艳,这种现象的产生可能与环境对性别的选择效应或性别间的种内竞争有关。鸟类羽毛颜色性别二态性的生理因素及遗传调控机制一直备受关注。了解两性二态性特征的形成机制,有助于深入了解两性的交配策略及种群的行为和进化过程。研究表明,ASIP、MC1R、TYRP1和BCO2等基因能调控鸟类羽色性别二态性的形成,主要通过控制黑色素或胡萝卜素产生或降解的速率和类型,或通过调控色素生物合成途径。本文综述了影响鸟类羽色性别二态性的生物学意义、直接原因(化学性颜色、物理性颜色)、性激素对鸟类羽色性别二态性的影响,以及部分关键基因调控鸟类羽色性别二态性形成的分子机制,以期为深入理解鸟类羽色性别二态性的形成机制研究提供参考。

An event-related potential observation of preposition processing in Chinese: Is N280 a specific component for Chinese prepositions?

BACKGROUND： Studies have shown that closed-class words, such as prepositions and conjunctions, induce a left anterior negativity （N280）, indicating that N280 should be a specific component of the word category. OBJECTIVE： To observe if Chinese prepositions and verbs exhibit different linguistic functions, to determine whether they are processed by different neural systems, and to verify that N280 is a specific component. DESIGN, TIME AND SETTING： The observed neurolinguistics experiment was performed at Xuzhou Normal University between November and December 2006. PARTICIPANTS： Sixteen undergraduate students, comprising 8 females and 8 males, with no mental or neuropathological history, were selected. METHODS： A total of 15 verbs and prepositions were used as linguistic stimuli, and each verb and preposition was combined to produce four correct phrase collocations and four incorrect ones. MAIN OUTCOME MEASURES： Event-related potentials were recorded in the subjects while they read correct or incorrect phases flashed upon a video screen. RESULTS： Both verbs and prepositions elicited negativity at the frontal site in a 230-330 ms window, as well as at the fronto-temporal and central sites in a 350-500 ms window. Neither exhibited significant differences in peak [F（1, 15） = 0.144, P = 0.710] and latency [F（1, 15） = 0.144, P= 0.710]. Both verbs and prepositions elicited negativity at the left and right hemisphere in a 270-400 ms window. CONCLUSION： There was no significant difference between Chinese prepositions and verbs in the neural system process and N280 was not the specific component for closed-class words.

Anti-tumor Activity of Derivatives of Protopanaxadiol Prepared with Acid Anhydrides

[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was subjected to structural modification and reacted with acid anhydrides to prepare derivatives,in order to improve the anti-tumor activity of protopanaxadiol.None of the five compounds designed and synthesized had been reported in the literature,and they were novel compounds.The anti-tumor activity of the derivatives was studies using MTS method.Taking cisplatin and paclitaxel as positive control drugs,the bioactivity of the compounds 1-5 on anti-tumor cell lines(HL-60 cells,SMMC-7721 cells,A-549 cells,MCF-7 cells and SW480 cells)in vitro was screened.[Results]The compound 5 showed inhibitory effect on HL-60 cells,SMMC-7721 cells and A-549 cells.[Conclusions]The acid anhydride esterification method is simple to operate and easy to control.This study has reference value for the structural modification and anti-tumor activity research of protopanaxadiol from P.notoginseng(Burk.)FH Chen.

Albumin-based multidrug delivery system enriched in Golgi apparatus against metastatic breast cancer

Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired toxicity.Cyclooxygenase-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)synthesis.This drug combination strategy is still required to be improved due to some unsatisfactory clinical trial results.Intricate processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi apparatus.Hence,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and metastasis.Since COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the synergy.In this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 cells.Owing to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.