整合mRNA转录本与基因组信息的基因组选择方法研究

基因组预测已成为畜禽、作物遗传评估和人类疾病风险预测的主要技术,但经典的基因组预测方法在性状遗传调控机制等生物学先验信息的整合方面有一定的不足。本研究提出一种将mRNA转录本信息整合应用于复杂性状表型预测的方法。基于国际上广泛应用于数量遗传学研究的果蝇群体,对本研究提出的新方法进行准确性评估。结果显示,整合mRNA转录本,可有效提高部分性状基因组预测准确性,但对部分性状的表型预测准确性没有改善。与GBLUP相比,雄性果蝇D-香芹酮嗅觉反应(dCarvone)准确性由0.256提高到0.274,提高幅度7%。雄性果蝇咖啡因耐受反应(cafe)准确性由0.355提高到0.401,提高幅度13%。雄性果蝇百草枯耐受反应(survival_paraquat)准确性由0.101提高到0.138,提高幅度36%。雌性果蝇1-已醇嗅觉反应(1hexanol)准确性由0.147提高到0.210,提高幅度43%。综上所述,对于部分性状,通过整合mRNA转录本可有效提高基因组预测准确性(提高幅度为7%~43%)。对于部分性状,整合mRNA转录本并考虑互作效应可进一步提高预测准确性。

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARSCoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P4503A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after recovery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12e18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Effects of fertilization and container-type on nutrient uptake and utilization by four subtropical tree seedlings

Seedling quality is important for subtropical tree species endangered by the degradation of natural habitats in southern China.At present,the cultural regime for raising these seedlings involving fertilizer levels and size of container is not clear.In this study,seedlings of three endangered species,red-seed tree(Ormosia hosiei),Zhejiang phoebe(Phoebe chekian gensis),and Zhejiang camphor(Cinnamomum japonicum)were evaluated along with red-bark oak(Cyclobalanopsis gilva)as a reference,a species which is not endangered.Seedlings were raised in 2.8,3.6,5.1,and 6.3 L containers and fertilizer applied at 1.0,2.0,3.0 and 4.0 kg m-3.Seedling height and leaf biomass increased in response to higher fertilizer levels while larger containers resulted in greater stem and root biomass.Root biomass of endangered species seedlings did not respond to neither treatments.Zhejiang phoebe seedlings responded to nitrogen and phosphorus uptake but red-seed tree seedlings were unaffected by any nutrient levels.Red-bark oak seedlings had high nitrogen-use efficiency.Based on the results,it is recommended using at least 5.1 L containers to culture Zhejiang phoebe and Zhejiang camphor seedlings with fertilizer at 3.0 kg m-3.Red-bark oak and red-seed tree seedlings should be cultured with 2.0 kg m-3 in smaller containers.

Common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma

Objective:Intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma(HCC)are clinically disparate primary liver cancers with etiological and biological heterogeneity.In Thailand,both cancer types represent the primary cause of cancer-related deaths and are a major public health concern.

Orientation and choice of Hanwei symbolic word

Universal feature of human symbolic thinking makes the symbol words exist in Chinese language vocabulary dimensional systems, expressing the symbolic significance in addition to expressing the concept, they both have a commonality when they are chose, but also has differences. This paper discusses on the Orientation and choice of Hanwei symbolic word.

Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment

Bone morphogenetic protein(BMP-2)has been approved by the FDA to promote bone regeneration,but uncertain osteogenic effect and dose-dependent side effects may occur.Osteoimmunomodulation plays an important role in growth factor-based osteogenesis.Here,we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2.We observed that the expression level of local IL-1βdid not increase with the dose of BMP-2 in the mouse osteogenesis model.A low dose of BMP-2 could not promote new bone formation,but trigger the release of IL-1βfrom M1 macrophages.As the dose of BMP-2 increased,the IL-1βexpression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2,and new bone tissues formed,even excessively.Anti-inflammatory drugs(Dexamethasone,Dex)promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation.Thus,we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands,including IL-1βand IL-1Ra.The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.

静电纺丝纤维滤材表征及其气液过滤性能

以聚丙烯腈与二甲基甲酰胺为原料配制纺丝溶液,采用静电纺丝技术制备玻璃纤维/聚丙烯腈纤维/玻璃纤维三层复合滤材,研究了纺丝溶液浓度与纺丝电压等参数对纤维形貌及尺寸的影响,分析了复合滤材的过滤性能.结果表明,控制不同纺丝溶液浓度可得形貌不同的纤维,且溶液浓度越大纤维尺寸越大;纺丝电压对纤维形貌的影响较小,但增加纺丝电压使静电纺纤维层的孔径减小.相比玻璃纤维滤材,复合滤材过滤效率明显提升,稳态效率最大可提升21%,最易穿透粒径效率最大可提升39%,但复合滤材孔径较小时,过程压降增加了一段跳跃阶段,纳米纤维层表面形成液膜,使复合滤材稳态压降升高.

不同操作压力下的气液过滤特性分析

根据ISO-12500标准建立了压缩空气滤芯性能检测系统,将操作压力由0.1 MPa升至0.7 MPa,分析了操作压力对亲油型和疏油型两种滤芯内的液体分布、滤材饱和度和过程压降的影响.结果表明,操作压力对疏油型滤芯的过程压降、液体运移与饱和度有显著影响,操作压力每上升0.2MPa,滤芯初始压降上升0.32kPa,各操作压力下滤芯润湿压降（平衡压降与初始压降的差）为4.5-5.1 kPa,0.7 MPa时最后1层滤材饱和度比0.1 MPa时上升了71%,饱和度沿气体流动方向呈凹型分布,小面积润湿区域增多,稳态压降前出现短暂跃升阶段,可能加剧滤芯二次夹带,导致过滤器下游管道内液滴数增多,降低过滤器效率;操作压力对亲油型滤芯的初始压降影响显著,操作压力每上升0.2 MPa,初始压降上升0.39 kPa;操作压力对液体运移与饱和度影响较小,不同操作压力下各层滤材饱和度的分布规律相同,液体分布无明显差异.

基于光学测量的异形纤维润湿性差异研究

气液聚结过滤在过程工业领域具有广泛应用,纤维材料润湿性是影响聚结元件过滤性能的关键因素。基于光学测量法,本工作开展了单根三角形、三叶形和十字形纤维表面的液体润湿性差异研究,分析了液体接触角及体积的变化过程,考察了液体类型、纤维倾斜角度及异形度对润湿性的影响。结果表明,液体表面张力越小,接触角越小,润湿性越强,但液体的挥发性易导致实际接触角大于理论接触角。三甘醇、癸二酸二辛酯和硅油的接触角基本不随时间发生变化,水和乙醇的接触角随时间逐渐减小且由于乙醇挥发速率较高,导致减小速率更大。液体接触角随异形纤维的倾斜角度呈"V"形分布,即存在极小值点(倾斜角度为30°),使纤维润湿性达到最佳。当纤维异形度增大时,不同液体间的接触角差异缩小、整体润湿性提高,表明在制备预过滤层或排液层材料时,宜选择异形度较高的纤维。

温度对OPC装置在线检测颗粒物的影响

以球形SiO2颗粒为研究对象搭建高温测试实验台,用光学粒子计数器(OPC)测定了25800℃下的颗粒数及其累计分布,并进行扫描电镜(SEM)和X射线衍射(XRD)分析,研究了高温对颗粒物在线检测结果的影响。结果表明,随加热温度升高,SiO2颗粒的粒径先变小后增大再变小,但颗粒物形状未发生变化;XRD衍射峰强度整体变弱,2θ≈25.5o处的衍射峰宽化并移动,晶胞体积先增大后变小。根据SiO2晶胞体积与晶体介电常数的关系可排除加热使颗粒物粒径变化,温度升高导致SiO2颗粒晶体内部结构变化、晶体折射率变化,使测量结果存在23个粒径通道的误差,影响测量精度。

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels

Osteochondral repair remains a major challenge in current clinical practice despite significant advances in tissue engineering.In particular,the lateral integration of neocartilage into surrounding native cartilage is a difficult and inadequately addressed problem that determines the success of tissue repair.Here,a novel design of an integral bilayer scaffold combined with a photocurable silk sealant for osteochondral repair is reported.First,we fabricated a bilayer silk scaffold with a cartilage layer resembling native cartilage in surface morphology and mechanical strength and a BMP-2-loaded porous subchondral bone layer that facilitated the osteogenic differentiation of BMSCs.Second,a TGF-β3-loaded methacrylated silk fibroin sealant(Sil-MA)exhibiting biocompatibility and good adhesive properties was developed and confirmed to promote chondrocyte migration and differentiation.Importantly,this TGF-β3-loaded Sil-MA hydrogel provided a bridge between the cartilage layer of the scaffold and the surrounding cartilage and then guided new cartilage to grow towards and replace the degraded cartilage layer from the surrounding native cartilage in the early stage of knee repair.Thus,osteochondral regeneration and superior lateral integration were achieved in vivo by using this composite.These results demonstrate that the new approach of marginal sealing around the cartilage layer of bilayer scaffolds with Sil-MA hydrogel has tremendous potential for clinical use in osteochondral regeneration.

Biocompatibility and bone regeneration of PEO/Mg-Al LDH-coated pure Mg:an in vitro and in vivo study

Forming a stable anti-corrosion surface layer on magnesium(Mg)and its alloys has become a major challenge in developing a desirable degradable medical implant in bone.In this study,a porous MgO layer was first formed on Mg by plasma electrolytic oxidation(PEO),and then a Mg-Al layered double hydroxide(LDH)layer was prepared to seal the porous structure of the PEO layer(LDH-2h and LDH-12h)via hydrothermal treatment.The bilayer structure composite coating,which can effectively resist the penetration of surrounding media,is similar to plain Chinese tiles.The in vitro results revealed that compared with other coatings,the LDH-12h composite coating can reduce the release of Mg ions and induce a milder change in pH when immersed in phosphate-buffered saline(PBS).In vitro rat bone marrow stem cell(rBMSC)culture suggested that the LDH-12h composite coating is favorable for cell activity,proliferation and could improve the osteogenic activity of rBMSCs.A subcutaneous implantation test revealed that the as-prepared sample showed enhanced corrosion resistance and histocompatibility in vivo,especially in the LDH-12h group.Moreover,LDH-12h had the lowest rate of degradation and the closest combination with the new bone after being inserted into a rat femur for 12 weeks with no major organ dysfunction.In summary,the asprepared PEO/Mg-Al LDH composite coating is able to improve the corrosion resistance and biocompatibility of Mg and to enhance osteogenic activity in vivo,suggesting its promising prospects for orthopedic applications.

Preservation of alveolar ridge height through mechanical memory: A novel dental implant design

Irreversible marginal bone loss can hinder recovery around dental implants.Insufficient alveolar osteogenesis and stress concentration during chewing contribute to marginal bone resorption and can result in implant failure.A biomaterial with a micropore-channel structure was developed using 3D printing technology.This design facilitated bony ingrowth and provided similar mechanical stimulation at the implant neck during mastication to a natural tooth.The micropore channels provided a guiding structure for bone mesenchymal stem cell proliferation and differentiation without the need for growth factors.Specifically,this was achieved through mechanical transduction by F-actin remodeling and the activation of Yes-associated protein(YAP).The implants were verified in a canine dental implant surgery model,which demonstrated the promising use of biomaterialbased dental implants in future clinical applications.

A rapidly magnetically assembled stem cell microtissue with“hamburger”architecture and enhanced vascularization capacity

With the development of magnetic manipulation technology based on magnetic nanoparticles(MNPs),scaffold-free microtissues can be constructed utilizing the magnetic attraction of MNP-labeled cells.The rapid in vitro construction and in vivo vascularization of microtissues with complex hierarchical architectures are of great importance to the viability and function of stem cell microtissues.Endothelial cells are indispensable for the formation of blood vessels and can be used in the prevascularization of engineered tissue constructs.Herein,safe and rapid magnetic labeling of cells was achieved by incubation with MNPs for 1 h,and ultrathick scaffold-free microtissues with different sophisticated architectures were rapidly assembled,layer by layer,in 5 min intervals.The in vivo transplantation results showed that in a stem cell microtissue with trisection architecture,the two separated human umbilical vein endothelial cell(HUVEC)layers would spontaneously extend to the stem cell layers and connect with each other to form a spatial network of functional blood vessels,which anastomosed with the host vasculature.The“hamburger”architecture of stem cell microtissues with separated HUVEC layers could promote vascularization and stem cell survival.This study will contribute to the construction and application of structural and functional tissues or organs in the future.

Co_(1-x)S embedded in porous carbon derived from metal organic framework as a highly efficient electrocatalyst for oxygen evolution reaction

Developing active, robust, and cost-efficient electrocatalysts is critical for oxygen evolution reaction(OER). Here, a novel composite catalyst of Co_(1-x)S embedded in porous dodecahedron carbon hybrid was synthesized by a two-step conversion protocol of a cobalt-based metal-organic framework(ZIF-67). The porous dodecahedron Co_(1-x)S@C composite catalyst was prepared by direct oxidation of ZIF-67 followed by sulfurization reaction. The Co_(1-x)S@C composite exhibit superior OER performance, including a low overpotential of 260 mV for 10 mA/cm2, a small Tafel slope of ~85 mV/dec, outstanding stability over 80 h and almost 100% Faradaic efficiency. The various material characterizations indicate that the excellent activity and strong stability of Co_(1-x)S@C might be attributed to good conductivity of Co_(1-x)S, mesoporous nanostructure, and synergistic effect of Co_(1-x)S encapsulated within porous carbon. This work provides a novel strategy for designing and synthesizing advanced composite

CuS/RGO hybrid by one-pot hydrothermal method for efficient electrochemical sensing of hydrogen peroxide

In this study,a non-enzymatic hydrogen peroxide sensor was successfully fabricated on the basis of copper sulfide nanoparticles/reduced graphene oxide（CuS/RGO） electrocatalyst.Using thiourea as reducing agent and sulfur donor,CuS/RGO hybrid was synthesized through a facile one-pot hydrothermal method,where the reduction of GO and deposition of CuS nanoparticles on RGO occur simultaneously.The results confirmed that the CuS/RGO hybrid helps to prevent the aggregation of CuS nanoparticles.Electrochemical investigation showed that the as-prepared hydrogen peroxide sensor exhibited a low detection limit of 0.18μmol/L（S/N = 3）,a good reproducibility（relative standard deviation（RSD） of4.21%）,a wide linear range（from 3 to 1215 μmol/L） with a sensitivity of 216.9 μA L/mmol/cm-2 under the optimal conditions.Moreover,the as-prepared sensor also showed excellent selectivity and stability for hydrogen peroxide detection.The excellent performance of CuS/RGO hybrid,especially the lower detection limit than certain enzymes and noble metal nanomaterials ever reported,makes it a promising candidate for non-enzymatic H2O2 sensors.

Transparent conducting properties of c-axis-oriented NaxCoO2 epitaxial thin films

Transparent conducting oxides （TCOs） have attracted in- tensive attention because of their broad application in pho- toelectric devices such as solar cells, light-emitting diodes, and flat-panel displays. Current TCOs used in industry, including tin （IV） oxide （SnOz）, indium oxide （In203）, indium tin oxide （ITO）, and zinc oxide （ZnO）, are primarily n-type semiconductors [1-3]. Suitable p-type TCOs are still being researched. In the past several decades, delafossite-type compounds CuMO2 （M = Cr, A1, Ga, Fe, Sc, Y） as well as NiO, Cr203, and MoO3 have been extensively studied as potential p-type TCO candidates [4-8].

先天性白内障术后配戴渐变多焦镜14年跟踪随访一例

患者,女,2004年1月出生,家长发现患儿瞳孔发白来陆军军医大学第一附属医院眼科就诊。双眼裸眼视力无追踪运动,裂隙灯显微镜检查显示双眼晶状体混浊(+++)。诊断:双眼先天性白内障。患者于2005年1月在我院完善相关术前检查后实施双眼白内障针吸术+后囊膜切开+前段玻璃体切除术(1岁),术后配戴框架眼镜,右眼+20.0 D,左眼+20.0 D,半年后植入人工晶状体,术后配戴渐变多焦镜矫正。

BioNetSim:a Petri net-based modeling tool for simulations of biochemical processes

BioNetSim,a Petri net-based software for modeling and simulating biochemistry processes,is developed,whose design and implement are presented in this pa-per,including logic construction,real-time access to KEGG(Kyoto Encyclopedia of Genes and Genomes),and BioModel database.Furthermore,glycolysis is simulated as an example of its application.BioNetSim is a helpful tool for researchers to download data,model biological network,and simulate complicated biochemistry processes.Gene regulatory networks,metabolic pathways,signaling pathways,and kinetics of cell interaction are all available in BioNetSim,which makes modeling more efficient and effective.Similar to other Petri net-based softwares,BioNetSim does well in graphic application and mathematic construction.Moreover,it shows several powerful predominances.(1)It creates models in database.(2)It realizes the real-time access to KEGG and BioModel and transfers data to Petri net.(3)It provides qualitative analysis,such as computation of constants.(4)It generates graphs for tracing the concentration of every molecule during the simulation processes.