General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

基于全基因组数据的AI-SNPs筛选及大陆次级区域内群体遗传结构差异研究

在涉及多群体样本的医学研究中,群体遗传结构差异是不容忽视的影响因素之一。利用族源信息单核苷酸多态性遗传标记(ancestry-informative single nucleotide polymorphism,AI-SNP),通过分析群体遗传成分、推断个体遗传背景并对群体样本进行预筛选,可以有效降低群体遗传结构差异对医学研究影响。鉴于已发表的研究多为解析大陆间、大陆次级区域间的群体遗传结构差异,本研究拟基于千人基因组计划(GRCh37.p13)中东亚五群体:日本东京群体(Japanese in Tokyo,JPT)、北京汉族(Han Chinese in Beijing,CHB)、南方汉族(Southern Han Chinese,CHS)、西双版纳傣族(Chinese Dai in Xishuangbanna,CDX)、越南京族(Kinh in Ho Chi Minh City,KHV)的数据,以FST值为标准筛选AI-SNP并分析大陆次级区域内群体遗传结构差异。结果表明,研究涉及的东亚群体可分为三簇:JPT、CHB和CHS、CDX和KHV。利用AI-SNP可成功解析个体的遗传背景,而群体代表性遗传成分占比超过80%的个体具有良好的群体代表性。本研究表明,基于FST值筛选一组AI-SNP用于核验样本遗传背景、筛选群体代表性样本的方法在降低大陆次级区域内群体遗传结构差异对群体相关医学研究的影响中具有实际应用价值。

Hsa_Circ_0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here,we report that hsa_Circ_0000826(Circ_0000826),a circ RNA with significantly reduced expression level in CRC tissues,is associated with a poor prognosis in patients.The silencing of Circ_0000826 promotes the proliferation of CRC cells.Conversely,the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo.Furthermore,Circ_0000826 could target AU-rich element RNA-binding protein 1(AUF1).AUF1,known as heterogeneous nuclear ribonucleoprotein D(hnRNP D),could bind to the c-MYC 3’-UTR and promote c-MYC expression.When Circ_0000826 binds to AUF1,it competitively inhibits the binding of AUF1 to the c-MYC 3’-UTR,which inhibits the c-MYC expression and cell proliferation.These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.

Boosting for Distributed Online Convex Optimization

Decentralized Online Learning(DOL)extends online learning to the domain of distributed networks.However,limitations of local data in decentralized settings lead to a decrease in the accuracy of decisions or models compared to centralized methods.Considering the increasing requirement to achieve a high-precision model or decision with distributed data resources in a network,applying ensemble methods is attempted to achieve a superior model or decision with only transferring gradients or models.A new boosting method,namely Boosting for Distributed Online Convex Optimization(BD-OCO),is designed to realize the application of boosting in distributed scenarios.BD-OCO achieves the regret upper bound O(M+N/MNT)where M measures the size of the distributed network and N is the number of Weak Learners(WLs)in each node.The core idea of BD-OCO is to apply the local model to train a strong global one.BD-OCO is evaluated on the basis of eight different real-world datasets.Numerical results show that BD-OCO achieves excellent performance in accuracy and convergence,and is robust to the size of the distributed network.

Stabilizing layered superlattice MoSe_(2) anodes by the rational solvation structure design for low-temperature aqueous zinc-ion batteries

Aqueous zinc-ion batteries(AZIBs)have attracted widespread attention due to their intrinsic merits of low cost and high safety.However,the poor thermodynamic stability of Zn metal in aqueous electrolytes inevitably cause Zn dendrites growth and interface parasitic side reactions,resulting in unsatisfactory cycling stability and low Zn utilization.Replacing Zn anode with intercalation-type anodes have emerged as a promising alternative strategy to overcome the above issues but the lack of appropriate anode materials is becoming the bottleneck.Herein,the interlayer structure of MoSe_(2) anode is preintercalated with long-chain polyvinyl pyrrolidone(PVP),constructing a periodically stacked p-MoSe_(2)superlattice to activate the reversible Zn^(2+) storage performance(203 mAh g^(−1)at 0.2 A g^(−1)).To further improve the stability of the superlattice structure during cycling,the electrolyte is also rationally designed by adding 1,4-Butyrolactone(γ-GBL)additive into 3 M Zn(CF_(3)SO_(3))_(2),in whichγ-GBL replaces the H2O in Zn^(2+) solvation sheath.The preferential solvation ofγ-GBL with Zn^(2+)effectively reduces the water activity and helps to achieve an ultra-long lifespan of 12,000 cycles for p-MoSe_(2).More importantly,the reconstructed solvation structure enables the operation of p-MoSe_(2)||ZnxNVPF(Na3V2(PO4)2O_(2)F)AZIBs at an ultra-low temperature of−40°C,which is expected to promote the practical applications of AZIBs.

Effects of starch and gelatin encapsulated vitamin A on growth performance,immune status and antioxidant capacity in weaned piglets

To evaluate the effects of gelatin and starch encapsulated vitamin A on growth performance,immune status and antioxidant capacity in weaned piglets,a total of 96 weaned piglets(body weight=9.11±0.03 kg,30-d-old)were randomly allotted to 3 treatments with 4 replications of 8 piglets each.The 3 treatments were control diet(basal diet without addition of vitamin A),gelatin vitamin A diet(basal diet+13,500 IU/kg gelatin encapsulated vitamin A),and starch vitamin A diet(basal diet+13,500 IU/kg starch encapsulated vitamin A),respectively.The results showed that piglets fed starch vitamin A diet had significantly higher final body weight and average daily gain compared to those in control and gelatin vitamin A groups(P<0.05).Gelatin and starch vitamin A supplementation both highly increased serum retinol concentration and immunoglobulin(Ig)M level when compared with the control group(P<0.05).Additionally,serum IgA level and glutathione peroxidase(GSH-Px)activity were significantly increased by gelatin vitamin A diet on d 21 and starch vitamin A diet on d 42,respectively(P<0.05).These results demonstrated that dietary supple mentation of vitamin A could improve immune function and antioxidant capacity in weaned piglets,and starch vitamin A is better than gelatin vitamin A,especially in promoting the growth performance of piglets.

Functional characterization of key polyketide synthases by integrated metabolome and transcriptome analysis on curcuminoid biosynthesis in Curcuma wenyujin

Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids.However,the curcuminoid constituents and their molecular mechanisms are poorly understood,and the relevant curcumin synthases remain unclear.In this study,we comprehensively compared the metabolite profiles of the leaf and tuber tissues of C.wenyujin.A total of 11 curcuminoid metabolites were identified and exhibited differentially changed contents in the leaf and tuber tissues.An integrated analysis of metabolomic and transcriptomic data revealed the proposed biosynthesis pathway of curcuminoid.Two candidate type III polyketide synthases(PKSs)were identified in the metabolically engineering yeasts,indicating that CwPKS1 and CwPKS2 maintained substrate and product specificities.Especially,CwPKS1 is the first type III PKS identified to synthesize hydrogenated derivatives of curcuminoid,dihydrocurcumin and tetrehydrocurcumin.Interestingly,the substitution of the glycine at position 219 with aspartic acid(G219D mutant)resulted in the complete inactivation of CwPKS1.Our results provide the first comparative metabolome analysis of C.wenyujin and functionally identified type III PKSs,giving valuable information for curcuminoids biosynthesis.

Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction

Boosting transcorneal permeability and pharmacological activity of drug poses a great challenge in the field of ocular drug delivery.In the present study,we propose a drug-peptide supramolecular hydrogel based on anti-inflammatory drug,dexamethasone(Dex),and Arg-Gly-Asp(RGD)motif for boosting transcorneal permeability and pharmacological activity via the ligand-receptor interaction.The drug-peptide(Dex-SA-RGD/RGE)supramolecular hydrogel comprised of uniform nanotube architecture formed spontaneously in phosphate buffered saline(PBS,pH=7.4)without external stimuli.Upon storage at 4℃,25℃,and 37℃ for 70 days,Dex-SA-RGD in hydrogel did not undergo significant hydrolysis,suggesting great long-term stability.In comparison to Dex-SA-RGE,Dex-SA-RGD exhibited a more potent in vitro anti-inflammatory efficacy in lipopolysaccharide(LPS)-activated RAW 264.7 macrophages via the inhibition of nuclear factorкB(NF-κB)signal pathway.More importantly,using drug-peptide supramolecular hydrogel labeled with 7-nitro-2,1,3-benzoxadiazole(NBD),the Dex-SA-K(NBD)RGD showed increased performance in terms of integrin targeting and cellular uptake compared to Dex-SA-K(NBD)RGE,as revealed by cellular uptake assay.On topical instillation in rabbit’s eye,the proposed Dex-SA-K(NBD)RGD could effectively enhance the transcorneal distribution and permeability with respect to the Dex-SA-K(NBD)RGE.Overall,our findings demonstrate the performance of the ligand-receptor interaction for boosting transcorneal permeability and pharmacological activity of drug.