ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage

MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.

A comparison of mapping strategies from DDC to CLC

Purpose: This study aims to discuss the strategies for mapping from Dewey Decimal Classification(DDC) numbers to Chinese Library Classification(CLC) numbers based on co-occurrence mapping while minimizing manual intervention.Design/methodology/approach: Several statistical tables were created based on frequency counts of the mapping relations with samples of USMARC records,which contain both DDC and CLC numbers. A manual table was created through direct mapping. In order to find reasonable mapping strategies,the mapping results were compared from three aspects including the sample size,the choice between one-to-one and one-to-multiple mapping relations,and the role of a manual mapping table.Findings: Larger sample size provides more DDC numbers in the mapping table. The statistical table including one-to-multiple DDC-CLC relations provides a higher ratio of correct matches than that including only one-to-one relations. The manual mapping table cannot produce a better result than the statistical tables. Therefore,we should make full use of statistical mapping tables and avoid the time-consuming manual mapping as much as possible.Research limitations: All the sample sizes were small. We did not consider DDC editions in our study. One-to-multiple DDC-CLC relations in the records were collected in the mapping table,but how to select one appropriate CLC number in the matching process needs to be further studied.Practical implications: The ratio of correct matches based on the statistical mapping table came up to about 90% by CLC top-level classes and 76% by the second-level classes in our study. The statistical mapping table will be improved to realize the automatic classification of e-resources and shorten the cataloging cycle significantly.Originality/value: The mapping results were investigated from different aspects in order to find suitable mapping strategies from DDC to CLC while minimizing manual intervention.The findings have facilitated the establishment of DDC-CLC mapping system for practical applications.

Estimation of Ecological Compensation Standards in the Yellow River Basin

It is crucial to establish a reasonable ecological compensation mechanism for the Yellow River Basin.This study uses a calculating model to estimate the value of the total cost of ecological protection in the upstream.On this basis,an apportion model is used to reach the ecological compensation standard value of each province in the midstream and downstream.The results provide a scientific reference for the ecological compensation standards in the Yellow River Basin.

基于劈裂环的光学天线研究

光学天线是一个新兴领域,可以与自由空间电磁波发生相互作用,把光场限制在亚波长的尺寸,促使天线狭缝处电场的局域增强。光学天线的提出使得在亚波长尺寸下调控光场成为可能,在光学成像、光学传感、纳米光学等领域具有广泛的应用。本文将对劈裂环天线进行深入研究,在电场作用下劈裂环将产生两种共振模式,分别是低频的电感–电容(LC)共振和高频的偶极共振,在天线表面形成环形振荡电流和线性振荡电流。两种共振模式可以很好地实现电场局域增强。

New techniques and strategies in drug discovery

Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug discovery.In this roadmap,several representative techniques and strategies are highlighted to show recent advances in this filed.(A)A DOX protocol has been developed for accurate protein-ligand binding structure prediction,in which first principle method was used to rank the binding poses.Validation against crystal structures have found that DOX prediction achieved an impressive success rate of 99%,indicating significant improvement over molecular docking method.(B)Virtual target profiling is a compound-centric strategy enabling a parallel implementation of interrogating compounds against various targets in a single screen,which has been used in hit/lead identification,drug repositioning,and mechanism-of-action studies.Current and emerging methods for virtual target profiling are briefly summarized herein.(C)Research on targeted autophagy to treat diseases has received encouraging progress.However,due to the complexity of autophagy and disease,experimental and in silico methods should be performed synergistically for the entire process.This part focuses on in silico methods in autophagy research to promote their use in medicinal research.(D)Histone deacetylases(HDACs)play important roles in various biological functions through the deacetylation of lysine residues.Recent studies demonstrated that HDACs,which possess low deacetylase activities,exhibited more efficient defatty-acylase activities.Here,we review the defatty-acylase activity of HDACs and describe examples for the design of isoform selective HDAC inhibitor.(E)The FDA approval of three kinase allosteric inhibitors and some others entering clinical study has spurred considerable interests in this targeted drug discovery area.(F)Recent advances are reviewed in structure-based design of novel antiviral agents to combat drug resistance.(G)Since nitric oxide(NO)exerts anticancer activity depending on its concentration,optimal levels of NO in cancer cells is desirable.In this minireview,we briefly describe recent advances in the research of NO-based anticancer agents by our group and present some opinions on the future development of these agents.(H)The field of photoactivation strategies have been extensively developed for controlling chemical and biological processes with light.This review will summarize and provide insight into recent research advances in the understanding of photoactivatable molecules including photoactivatable caged prodrugs and photoswitchable molecules.

HIV-1 Vif suppresses antiviral immunity by targeting STING

HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling activates innate immunity to produce type I interferon(IFN).The HIV-1 nonstructural protein viral infectivity factor(Vif)is essential in HIV-1 replication,as it degrades the host restriction factor APOBEC3G.However,whether and how it regulates the host immune response remains to be determined.In this study,we found that Vif inhibited the production of type I IFN to promote immune evasion.HIV-1 infection induced the activation of the host tyrosine kinase FRK,which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif(ITIM)of Vif and enhanced the interaction between Vif and the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN.Mechanistically,the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited the K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162.However,the FRK inhibitor D-65495 counteracted the phosphorylation of Vif to block the immune evasion of HIV-1 and antagonize infection.These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING.These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection.

Two-step phase manipulation by tailoring chemical bonds results in high-performance GeSe thermoelectrics

In thermoelectrics,phase engineering serves a crucial function in deter-mining the power factor by affecting the band degeneracy.However,for low-symmetry compounds,the mainstream one-step phase manipulation strategy,depending solely on the valley or orbital degeneracy,is inadequate to attain a high density-of-states effective mass and exceptional zT.Here,we employ a distinctive two-step phase manipulation strategy through stepwise tailoring chemical bonds in GeSe.Initially,we amplify the valley degeneracy via CdTe alloying,which elevates the crystal symmetry from a covalently bonded orthorhombic to a metavalently bonded rhombohedral phase by significantly suppressing the Peierls distortion.Subsequently,we incorporate Pb to trigger the convergence of multivalence bands and further enhance the density-of-states effective mass by moderately restraining the Peierls distortion.Additionally,the atypical metavalent bonding in rhombohedral GeSe enables a high Ge vacancy concentration and a small band effective mass,leading to increased carrier concentration and mobility.This weak chemical bond along with strong lattice anharmonicity also reduces lattice thermal conductivity.Consequently,this unique property ensemble contributes to an outstanding zT of 0.9 at 773 K for Geo.8oPbo.2oSe(CdTe)o.25.This work underscores the pivotal role of the two-step phase manipulation by stepwise tailoring of chemical bonds in improving the thermoelectric performance of p-bonded chalcogenides.

Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents

To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,S2 was 30-fold more water-soluble,and over 10-fold more potent in inhibition of platelet aggregation,as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage,in comparison with NB P.Additionally,S2 was more active than its three moieties alone or in combination,suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties.Importantly,in vivo studies indicated that S2 not only possessed good pharmacokinetic profile,but also improved NBP distribution in rodent brain,suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1(GLUT1)on blood-brain barrier(BBB),promoting it to penetrate through BBB.Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke,warranting further study.

Bronchoscopic transparenchymal nodule access in the diagnosis and management of pulmonary nodules

To the Editor:Transthoracic needle aspiration(TTNA)and bronchoscopy have been the preferred methods for the sampling of pulmonary nodules suspected of lung cancer.However,despite having a higher diagnostic accuracy,TTNA has been associated with a high rate of pneumothorax.Moreover,conventional bronchoscopy with a low rate of pneumothorax has exhibited a low diagnostic yield for peripheral pulmonary nodules,particularly for nodules<2 cm in size or those without a bronchus leading directly to them.Thus,Herth et al[1]developed a novel bronchoscopy technique called bronchoscopic transparenchymal nodule access(BTPNA)under the guidance of Archimedes Virtual Bronchoscopic Navigation(VBN)System for the purpose of accessing pulmonary nodules using a transparenchymal approach without relying on the airway to approach the lesion.Here,we systematically reviewed evidence regarding BTPNA to provide general guidance on the safe implementation and development of this novel approach.