创伤性颅脑外伤合并急性胃肠功能损伤患者血清中热休克蛋白70水平的变化及意义

背景目前多数研究者们认为在胃肠功能受损时,血清HSP70具有较高的敏感性,为早期肠缺血的敏感指标,但血清中热休克蛋白70(HSP70)在创伤性颅脑外伤(traumatic head injury,TBI)患者的胃肠功能评估中的研究较少,值得进一步研究.目的探究TBI合并急性胃肠功能损伤(acute gastrointestinal impairment,AGI)患者HSP70水平的变化及意义.方法选取2019-03/2020-10期间天津医科大学总医院重症监护病房就诊并住院的TBI合并AGI患者133例作为研究对象,按照改良Glasgow昏迷评分法并结合创伤性颅脑损伤临床分型标准,将研究对象分为轻型63例,中型32例,重型38例;按照AGI分级标准,将研究对象分为AGIⅠ级68例,AGIⅡ级37例,AGIⅢ级17例,AGIⅣ级11例.另选取50例于我院进行常规体检的无颅脑外伤病史、各系统基础疾病者作为对照组.比较不同脑外伤程度及不同AGI分级患者与对照组血清中HSP70水平,并分析TBI合并AGI患者血清HSP70水平与脑损伤程度、AGI分级的相关性,同时分析其单独诊断TBI合并AGI的诊断效能.结果入院当天,随着脑损伤程度的加重,血清HSP70水平也逐渐升高,且各型HSP70水平均显著高于对照组患者,而随着AGI分级的提高,血清HSP70水平也逐渐升高,且各分级HSP70水平均显著高于对照组患者,差异均有统计学意义(P<0.05);入院第3天,各型血清HSP70水平较入院当天数值明显降低,但数值仍高于对照组患者,而各分级血清HSP70水平较入院当天数值明显降低,但数值仍高于对照组患者,差异均有统计学意义(P<0.05);Pearson检验发现,TBI合并AGI患者血清HSP70水平与脑损伤程度、AGI分级均呈显著正相关(r_(s)=0.802、0.836,P<0.01);ROC曲线显示,血清HSP70诊断TBI合并AGI的试验准确性较高,AUC为0.803,95%CI为0.720-0.872.当最佳截断值为258.50 ng/L时,敏感度为80.94%,特异度为87.93%,约登指数为0.501.结论HSP70在TBI合并AGI患者血清中的表达显著上调,可能与疾病发展进程有关,对TBI合并AGI有较高的诊断价值.

Modified Therapeutic Antibodies: Improving Efficacy

The prosperity of the biotherapeutics market reflects the feasibility and effectiveness of therapeutic antibodies for the treatment of cancers,inflammatory disorders,and refractory infections.As drawbacks emerge in clinical trials and practice,such as impeded binding,reduced effector functions,and frequent adverse reactions,modifications of therapeutic antibodies are unprecedently burgeoning in research and development(R&D).These modifications include:①modified glycosylation;②fragment of crystallizable domain(Fc)amino acid alterations;③cross-isotype or cross-subclass exchanges;④antibody–drug conjugates(ADCs);⑤single chain of variable region fragment(scFv)for chimeric antigen receptor T(CAR-T)cells;and⑥bispecific antibodies(bsAbs)in order to promote binding affinity,half-life in circulation,effectiveness toward target cells and,ultimately,to achieve overall improved efficacy.While many achievements have been made around the world in the past decades,China has been playing an active role in this realm,with its great demand for biotherapeutics with R&D potential.This review recapitulates the international progress that has been achieved with modified therapeutic antibodies,and then focuses on that of China in an independent section.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms.The circRNAs are mainly enriched in the central nervous system.However,their function in various physiological and pathological conditions have yet to be determined.Here,we identified circFhit,an exon-intron circRNA expressed in GABAergic neurons,which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain.Moreover,we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R^(+) neurons by promoting the expression of its parental gene Fhit in cis.Mechanistically,circFhit was directly bound to the intronic region of Fhit,and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron.In summary,we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R^(+) neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Novel aqueous rechargeable nickel//bismuth battery based on highly porous Bi_(2)WO6 and Co_(0.5)Ni_(0.5)MoO_(4) microspheres

Developing high performances aqueous rechargeable batteries is imperative and valuable.Herein,a novel aqueous rechargeable nickel//bismuth battery is developed based on highly porous Bi_(2)WO_(6) and Co_(0.5)Ni_(0.5)MoO_(4) microspheres as electrode active materials.Porous Bi_(2)WO6 microspheres assembled from nanosheets as anode active materials can afford a specific capacity of179.2 mAh·g^(-1) at 1 A·g^(-1),rate capability of 74.7%in 1-20 A·g^(-1),and capacity retention of 57.2%for 1500 cycles at 15 A·g^(-1).Owing to the highly porous microsphere with’ribbon’-like and intertwined nanolayers morphology,the screened Co0.5Ni0.5MoO4 cathode active materials present an outstanding specific surface area of 293 m^(2)·g^(-1)and excellent electrochemical performance(such as superior specific capacity of 113.2 mAh·g^(-1) at 1 A·g^(-1),high rate performance of 51.8%in 1-15 A·g^(-1),and good capacity retention of 48.5%for 4600 cycles at15 A·g^(-1)).The corresponding aqueous rechargeable nickel//bismuth battery delivers the maximum energy density and power density of 35.8 Wh·kg^(-1) and3238.5 W·kg^(-1),respectively.The present research would offer a worthwhile guidance for the effective construction of electrode active materials for aqueous rechargeable nickel//bismuth batteries.

GNOM-LIKE 2, Encoding an Adenosine Diphosphate-Ribosylation Factor-Guanine Nucleotide Exchange Factor Protein Homologous to GNOM and GNL1, is Essential for Pollen Germination in Arabidopsis

In flowering plants, male gametes are delivered to female gametophytes by pollen tubes. Although it is important for sexual plant reproduction, little is known about the genetic mechanism that controls pollen germination and pollen tube growth. Here we report the identification and characterization of two novel mutants, gnom-like 2-1 （gnl2-1） and gn12-2 in Arabidopsis thaliana, in which the pollen grains failed to germinate in vitro and in vivo. GNL2 encodes a protein homologous to the adenosine diphosphate-ribosylation factor-guanine nucleotide exchange factors, GNOM and GNL1 that are involved in endosomal recycling and endoplasmic reticulum-Golgi vesicular trafficking. It was prolifically expressed in pollen grains and pollen tubes. The results of the present study suggest that GNL2 plays an important role in pollen germination.

Pollen-Expressed Transcription Factor 2 Encodes a Novel Plant-Specific TFIIB-Related Protein that Is Required for Pollen Germination and Embryogenesis in Arabidopsis

Pollen germination and embryogenesis are important to sexual plant reproduction. The processes require a large number of genes to be expressed. Transcription of eukaryotic nuclear genes is accomplished by three conserved RNA polymerases acting in association with a set of auxiliary general transcription factors （GTFs）, including B-type GTFs. The roles of B-type GTFs in plant reproduction remain poorly understood. Here we report functional characterization of a novel plant-specific TFIIB-related gene PTF2 in Arabidopsis. Mutation in PTF2 caused failure of pollen germination. Pollen-rescue revealed that the mutation also disrupted embryogenesis and resulted in seed abortion. PTF2 is expressed prolifically in developing pollen and the other tissues with active cell division and differentiation, including embryo and shoot apical meristem. The PTF2 protein shares a lower amino acid sequence similarity with other known TFIIB and TFIIB-related proteins in Arabidopsis. It can interact with TATA-box binding protein 2 （TBP2） and bind to the double- stranded DNA （dsDNA） as the other known TFIIB and TFIIB-related proteins do. In addition, PTF2 can form a homodimer and interact with the subunits of RNA polymerases （RNAPs）, implying that it may be involved in the RNAPs transcription. These results suggest that PTF2 plays crucial roles in pollen germination and embryogenesis in Arabidopsis, possibly by regulating gene expression through interaction with TBP2 and the subunits of RNAPs.

MARIS plays important roles in Arabidopsis pollen tube and root hair growth

In flowering plants, male gametes are delivered to female gametes for double fertilization through pollen tubes. Therefore, pollen tube growth is crucial for double fertilization. Despite its importance to sexual reproduction, genetic mechanisms of pollen tube growth remain poorly understood. In this study, we characterized the receptor-like cytoplasmic protein kinase （RLCK） gene, MARLS （MRI） that plays critical roles in pollen tube growth. MRI is preferentially expressed in pollen grains, pollen tubes and roots. Mutation in MRI by a Ds insertion led to a burst of pollen tubes after pollen germination. Pollen-rescue assay by pollen and pollen tubespecific expression of MRI in the mri-4 mutant showed that loss of MRI function also severely affected root hair elongation. MRI protein interacted with the protein kinase OXIDATIVE SIGNAL INDUCIBLEI （OXII） in the in vitro and in vivo assays, which functions in plant defence and root hair development, and was phosphorylated by OXII in vitro. Our results suggest that MRI plays important roles in pollen tube growth and may function in root hair elongation through interaction with OXII.

Polysiloxane Side-chain Liquid Crystalline Polymers Prepared by Alkyne Hydrosilylation

We describe in this work an alkyne-hydrosilylation approach to synthesize a series of novel polysiloxane sidechain LCPs attaching end-on or side-on mesogenic side groups. Their properties are characterized by NMR, FTIR, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetty, polarized optical microscopy and small-angle X-ray scattering. These obtained alkenylsilane linked novel LCPs exhibit higher glass transition temperatures and clearing points, and especially display the tendency of forming smectic phases, in strong contrast with the nematic phases of their comparative conventional alkylsilane linked analogues, which manifests more rigid features of the alkenylsilane linkages and their significant influence on the mesomorphic properties.

AtTMEM18 plays important roles in pollen tube and vegetative growth in Arabidopsis

In flowering plants, pollen tube growth is essential for delivery of male gametes into the female gametophyte or embryo sac for double fertilization. Although many genes have been identified as being involved in the process, the molecular mechanisms of pollen tube growth remains poorly understood. in this study, we identified that the Arabidopsis Transmembrane Protein 18 （AtTMEM18） gene played important roles in pollen tube growth. The AtTMEM18 shares a high similarity with the Transmembrane 18 proteins （TMEM18s） that are conserved in most eukaryotes and may play important roles in obesity in humans. Mutation in the AtTMEM18 by a Ds insertion caused abnormal callose deposition in the pollen grains and had a significant impact on pollen germination and pollen tube growth. AtTMEM18 is expressed in pollen grains, pollen tubes, root tips and other vegetative tissues. The pollen-rescued assays showed that the mutation in AtTMEM18 also caused defects in roots, stems, leaves and transmitting tracts. AtTMEM18-GFP was located around the nuclei. Genetic assays demonstrated that the localization of AtTMEM18 around the nuclei in the generative cells of pollen grains was essential for the male fertility.Furthermore, expression of the rice TM EM18-homologous protein （OsTMEM18） driven by LAT52 promoter could recover the fertility of the Arabidopsis attmem18 mutant. These results suggested that the TMEM18 is important for plant growth in Arabidopsis.

Overexpression of the nuclear protein gene AtDUF4 increases organ size in Arabidopsis thaliana and Brassica napus

Organ size is an important trait of many crops that is influenced by internal and environmental signals and controlled by a combina- tion of factors during organogenesis （I（rizek, 2009）. The final size of plant organs is determined by two successive but overlapping pro- cesses： cell division, which increases cell number, and cell expan- sion, which determines final cell size （Anastasiou and Lenhard, 2007）. Some genes have been identified to control organ size by regulating cell division and for cell expansion in plants.

WBC27,an Adenosine Tri-phosphate-binding Cassette Protein,Controls Pollen Wall Formation and Patterning in Arabidopsis

In flowering plants, the exine components are derived from tapetum. Despite its importance to sexual plant reproduction, little is known about the translocation of exine materials from tapetum to developing microspores. Here we report functional characterization of the arabidopsis WBC27 gene. WBC27 encodes an adenosine tri-phosphate binding cassette （ABC） transporter and is expressed preferentially in tapetum. Mutation of WBC27 disrupted the exine formation. The wbc27 mutant microspores began to degenerate once released from tetrads and most of the microspores collapsed at the uninucleate stage. Only a small number of wbc27-1 microspores could develop into tricellular pollen grains. These survival pollen grains lacked exine and germinated in the anther before anthesis. All of these results suggest that the ABC transporter, WBC27 plays important roles in the formation of arabidopsis exine, possibly by translocation of lipidic precursors of sporopollenin from tapetum to developing microspores.

ABORTED GAMETOPHYTE 1 is required for gametogenesis in Arabidopsis

In flowering plants, the male and female gameto- genesis is a crucial step of sexual reproduction. Although many genes have been identified as being involved in the gametogenesis process, the genetic mechanisms underlying gametogenesis remains poorly understood. We reported here characterization of the gene, ABORTED GAMETOPHYTE 1 （AOGI） that is newly identified as essential for gametogenesis in Arabidopsis thaliana. AOG1 is expressed predominantly in reproductive tissues including the developing pollen grains and ovules. The AOG1 protein shares no significant amino acid sequence similarity with other documented proteins and is located mainly in nuclei of the cells. Mutation in AOG~ caused degeneration of pollen at the uninucleate microspore stage and severe defect in embryo sacs, leading to a significant reduction in male and female fertility.Furthermore, the molecular analyses showed that the aogl mutant significantly affected the expression of several genes, which are required for gametogenesis. Our results suggest that AOG1 plays important roles in gameto- genesis at the stage prior to pollen mitosis 1 （PMI） in Arabidopsis, possibly through collaboration with other genes.

Arabidopsis thaliana NOP10 is required for gametophyte formation

The female gametophyte is crucial for sexual reproduction of higher plants, yet little is known about the molecular mechanisms underlying its development. Here, we report that Arabidopsis thaliana NOP10 （AtNOP10） is required for female gametophyte formation. AtNOP10 was expressed predominantly in the seedling and reproductive tissues, including anthers, pollen grains, and ovules. Mutations in AtNOP10 interrupted mitosis of the functional megaspore during early development and prevented polar nuclear fusion in the embryo sacs. AtNOP10 shares a high level of amino acid sequence similarity with Saccharornycescerevisiae （yeast） NOPIo （ScNOP1o）, an important compo- nent of the H/ACA small nucleolar ribonucleoprotein particles （H/ACA snoRNPs） implicated in 18S rRNA synthe- sis and rRNA pseudouridylation. Heterologous expression of ScNOP10 complemented the mutant phenotype of Atnop10. Thus, AtNOPIo influences functional megaspore mitosis and polar nuclear fusion during gametophyte formation in Arabidopsis.