Deeply functional identification of TCS1 alleles provides efficient technical paths for low-caffeine breeding of tea plants

Caffeine is an important functional component in tea,which has the effect of excitement and nerve stimulation,but excessive intake can cause insomnia and dysphoria.Therefore,the production of tea with low-caffeine content can meet the consumption needs of certain people.Here,in addition to the previous alleles of the tea caffeine synthase(TCS1)gene,a new allele(TCS1h)from tea germplasms was identified.Results of in vitro activity analysis showed that TCS1h had both theobromine synthase(TS)and caffeine synthase(CS)activities.Site-directed mutagenesis experiments of TCS1a,TCS1c,and TCS1h demonstrated that apart from the 225th amino acid residue,the 269th amino acid also determined the CS activity.GUS histochemical analysis and dual-luciferase assay indicated the low promoter activity of TCS1e and TCS1f.In parallel,insertion and deletion mutations in large fragments of alleles and experiments of site-directed mutagenesis identified a key cis-acting element(G-box).Furthermore,it was found that the contents of purine alkaloids were related to the expression of corresponding functional genes and alleles,and the absence or presence and level of gene expression determined the content of purine alkaloids in tea plants to a certain extent.In summary,we concluded TCS1 alleles into three types with different functions and proposed a strategy to effectively enhance low-caffeine tea germplasms in breeding practices.This research provided an applicable technical avenue for accelerating the cultivation of specific low-caffeine tea plants.

Magnetic Damping Properties of Single-Crystalline Co_(55)Mn_(18)Ga_(27) and Co_(50)Mn_(18)Ga_(32) Films

We investigate the structural,static magnetic and damping properties in two Mn-deficient magnetic Weyl semimetal Co-Mn-Ga(CMG) alloy films,i.e.,Co_(55)Mn_(18)Ga_(27)(CMG1) and Co_(50)Mn_(18)Ga_(32)(CMG2),which were epitaxially grown on MgO(001) substrates.CMG1 has a mixing phase of B2and L21,larger saturation magnetization(M_(s) ~760 emu/cm^(3)),stronger in-plane magnetic anisotropy.CMG2 has an almost pure B2phase,smaller M_(s)(~330 emu/cm^(3)),negligible in-plane magnetic anisotropy.Time-resolved magneto-optical Kerr effect results unambiguously demonstrate an obvious perpendicular standing spin wave(PSSW) mode in addition to the Kittel mode for both of the CMG films.The intrinsic damping constant is about 0.0055 and 0.015 for CMG1 and CMG2,respectively,which are both significantly larger than that of the stoichiometric CMG(i.e.,Co_(2)MnGa)film reported previously.In combination with the first-principles calculations,the intrinsic damping properties of the Mn-deficient CMG films can be well explained by considering the increase of density of states at the Fermi level,reduction of M_(s),and excitation of the PSSW mode.These findings provide a new clue to tuning the magnetic damping of the magnetic Weyl semimetal film through slight off-stoichiometry.

Characterization of microRNAs in serum： a novel class of biomarkers for diagnosis of cancer and other diseases

在各种各样的纸巾的 microRNAs (miRNAs ) 的 Dysregulated 表示与许多疾病被联系了，包括癌症。这里，我们证明 miRNAs 在象老鼠，老鼠，牛的胎儿，小牛，和马那样的人和另外的动物的浆液和血浆是在场的。在浆液的 miRNAs 的层次在一样的种类的个人之中稳定、可再现、一致。采用 Solexa，我们定序健康中国题目的所有浆液 miRNAs 并且分别地在男、女的题目发现超过 100 和 91 浆液 miRNAs。我们也为肺癌症， colorectal 癌症，和糖尿病识别了浆液 miRNAs 的特定的表示模式，提供证据那浆液 miRNAs 为各种各样的疾病包含指纹。癌症特定的浆液 miRNAs 由 Solexa 获得了的二个非小的房间肺进一步在 75 个健康施主和 152 个癌症病人的独立审判被验证，用量的反向的抄写聚合酶链反应试金。通过这些分析，我们断定浆液 miRNAs 能为各种各样的癌症和另外的疾病的察觉用作潜在的 biomarkers。

Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products

最近的婴儿的公式奶粉污染事件证明了在牛奶质量控制的经典标记或标准在识别鈥渕a nipulated 鈥 ? 是不够的差质量的牛奶。在现在的学习，我们第一次证明奶牛牛奶包含大量 microRNAs ( miRNAs )并且牛奶特定的 miRNAs 的唯一的表示侧面能为未加工的牛奶和牛奶相关的商业产品的质量控制用作新奇指示物和可能的新标准，例如液体牛奶和粉状的公式牛奶。用定序的 Solexa，首先，我们系统地在未加工的牛奶屏蔽了 miRNA 表示并且在未加工的牛奶识别了 245 miRNAs 的一个总数。不同于层次在哺乳的不同时期是其表达式将近相同的另外的经典 biomarkers，单个 miRNAs 能显著地在哺乳过程期间被改变，含有那 miRNAs 可以是更精确的指示物反映牛奶的优秀改变。第二，使用 TaqMan 基于探查的 miRNA 量的 RT-PCR ，我们进一步识别了七 miRNAs 重要地在整个哺乳过程，和更多有相对一致的表情，这七牛奶特定的 miRNAs 的表示侧面能为区别用作理想的 biomarker 差质量或从纯未加工的牛奶的 鈥渕a nipulated 鈥?牛奶，象为商业乳制品的质量控制一样，例如液体，牛奶和粉状的公式挤。一起，我们的调查结果为为决定未加工的牛奶或牛奶相关的商业产品的质量理解牛奶 miRNAs 和一个新潜在的标准的生理的角色提供一个基础。

PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARy-dependent pathway

Peroxisome 激活 proliferator 的受体鲸鱼群妈(PPAR γ) coactivator-1 高山哈(PGC-1 α) coactivates 多重抄写因素并且调整几个代谢过程。Thecurrent 学习在人的上皮的卵巢的癌症房间在 apoptosis 的正式就职调查了 PGC-1 α的角色。在人的卵巢和人的卵巢的上皮的肿瘤之间的 PGC-1 α信使 rna 水平被量的 RT-PCR 检验。更少的 PGC-1 α表示与正常卵巢相比在恶意的肿瘤的表面上皮被发现。在人的上皮的卵巢的癌症房间线 Ho-8910 的 PGC-1 α的 Overexpression 通过 Bcl-2 和 Bax 表示的协调规定导致了房间 apoptosis。Microarray 分析证实 PGC-1 α戏剧性地在 Ho-8910 房间影响了 apoptosis 相关的基因。 Mitochondrial 功能的试金证明 apoptosis 的正式就职通过由细胞色素 c.Furthermore 的版本的终端阶段，导致的 apoptosis 部分是，然而并非完全，由 PPAR γa ntagonist ( GW9662 )堵住了的 PGC-1 α-，并且由 siRNA 的 PPAR γ 表示的抑制也在 Ho-8910 房间禁止了 PGC-1 α- inducedapoptosis 。这些数据建议 PGC-1 α通过 aPPAR γ - 依赖者小径施加了它的效果。我们的调查结果显示 PGC-1 α涉及 apoptotic signaltransduction 小径， PGC-1 α的 down 规定可以是在支持上皮的卵巢的癌症生长和前进的一个关键点。

薯蓣丸对化疗4T1乳腺癌小鼠T淋巴细胞亚群的影响

目的评价薯蓣丸对化疗后4T1乳腺癌小鼠免疫功能的影响,并探讨其作用机制。方法随机将32只BALB/c小鼠分为对照组、模型组、化疗组、中药组,每组8只。除对照组外,其余组注射4T1细胞悬液复制荷瘤模型。成瘤后第1天化疗组、中药组小鼠予以多西他赛治疗,1次/7 d,共21 d;注射多西他赛后第2天对中药组小鼠行中药灌胃,1次/d,共21 d。治疗完成后处死小鼠取脾脏研磨,用流式细胞仪检测小鼠脾脏中CD4^+、CD8^+、CD4^+CD25^+Foxp3^+调节性T细胞(Treg)表达水平。结果与模型组比较,化疗组、中药组CD4^+、CD8^+、CD4^+CD25^+Foxp3^+Treg细胞表达水平降低,CD4^+/CD8^+比值升高(P<0.05);与化疗组比较,中药组CD4^+细胞表达水平、CD4^+/CD8^+比值升高,CD4^+CD25^+Foxp3^+Treg细胞表达水平降低(P<0.05)。结论薯蓣丸能改善化疗后乳腺癌小鼠免疫功能。

Toolbox of teaching strategies

A teaching strategy is a method, which can help students to gain knowledge, deliver information, and improve their learning. Different learning environments, such as clinical teaching, online teaching, and face-to-face traditional learning environments, require different teaching strategies for students. Choosing teaching strategies for a course is very important for nurse educators because various factors should be taken into account to make students meet the learning outcomes. The use of modern technologies in teaching strategies can improve students’ competencies and confidences. The purpose of this article is to create a toolbox integrating ten teaching strategies that can be used in different teaching environments.

scPlant:A versatile framework for single-cell transcriptomic data analysis in plants

Single-cell transcriptomics has been fully embraced in plant biological research and is revolutionizing our understanding of plant growth,development,and responses to external stimuli.However,single-cell tran-scriptomic data analysis in plants is not trivial,given that there is currently no end-to-end solution and that integration of various bioinformatics tools involves a large number of required dependencies.Here,we pre-sent scPlant,a versatile framework for exploring plant single-cell atlases with minimuminput data provided by users.The scPlant pipeline is implemented with numerous functions for diverse analytical tasks,ranging from basic data processing to advanced demands such as cell-type annotation and deconvolution,trajec-tory inference,cross-species data integration,and cell-type-specific gene regulatory network construc-tion.In addition,a variety of visualization tools are bundled in a built-in Shiny application,enabling explo-ration of single-cell transcriptomic data on the fly.

Numerical Analysis of Explosion Characteristics of Vent Gas From 18650 LiFePO_(4)Batteries With Different States of Charge

The combustion and explosion characteristics of lithium-ion battery vent gas is a key factor in determining the fire hazard of lithium-ion batteries.Investigating the combustion and explosion hazards of lithium-ion batteries vent gas can provide guidance for rescue and protection in explosion accidents in energy storage stations and new energy vehicles,thereby promoting the application and development of lithium-ion batteries.Based on this understanding and combined with previous research on gas production from lithium-ion batteries,this article conducted a study on the combustion and explosion risks of vent gas from thermal runaway of 18650 LFP batteries with different states of charge(SOCs).The explosion limit of mixed gases affected by carbon dioxide inert gas is calculated through the“elimination”method,and the Chemkin-Pro software is used to numerically simulate the laminar flame speed and adiabatic flame temperature of the battery vent gas.And the concentration of free radicals and sensitivity coefficients of major elementary reactions in the system are analyzed to comprehensively evaluate the combustion explosion hazard of battery vent gas.The study found that the 100%SOC battery has the lowest explosion limit of the vent gas.The inhibitory elementary reaction sensitivity coefficient in the reaction system is lower and the concentration of free radicals is higher.Therefore,it has the maximum laminar flame speed and adiabatic flame temperature.The combustion and explosion hazard of battery vent gas increases with the increase of SOC,and the risk of explosion is the greatest and most harmful when SOC reaches 100%.However,the related hazards decrease to varying degrees with overcharging of the battery.This article provides a feasible method for analyzing the combustion mechanism of vent gas from lithium-ion batteries,revealing the impact of SOC on the hazardousness of battery vent gas.It provides references for the safety of storage and transportation of lithium-ion batteries,safety protection of energy storage stations,and the selection of related fire extinguishing agents.

Horizontal transfer of microRNAs: molecular mechanisms and clinical applications

A new class of RNA regulatory genes known as microRNAs(miRNAs)has been found to introduce a whole new layer of gene regulation in eukaryotes.The intensive studies of the past several years have demonstrated that miRNAs are not only found intracellularly,but are also detectable outside cells,including in various body fluids(e.g.serum,plasma,saliva,urine and milk).This phenomenon raises questions about the biological function of such extracellular miRNAs.Substantial amounts of extracellular miRNAs are enclosed in small membranous vesicles(e.g.exosomes,shedding vesicles and apoptotic bodies)or packaged with RNA-binding proteins(e.g.high-density lipoprotein,Argonaute 2 and nucleophosmin 1).These miRNAs may function as secreted signaling molecules to influence the recipient cell phenotypes.Furthermore,secreted extracellular miRNAs may reflect molecular changes in the cells from which they are derived and can therefore potentially serve as diagnostic indicators of disease.Several studies also point to the potential application of siRNA/miRNA delivery as a new therapeutic strategy for treating diseases.In this review,we summarize what is known about the mechanism of miRNA secretion.In addition,we describe the pathophysiological roles of secreted miRNAs and their clinical potential as diagnostic biomarkers and therapeutic drugs.We believe that miRNA transfer between cells will have a significant impact on biological research in the coming years.

Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF,and the neutralization of miR-150 attenuate tumor development

Tumor-associated macrophages(TAMs)mostly exhibit M2-like(alternatively activated)properties and play posi-tive roles in angiogenesis and tumorigenesis.Vascular en-dothelial growth factor(VEGF)is a key angiogenic factor.During tumor development,TAMs secrete VEGF and other factors to promote angiogenesis;thus,anti-treatment against TAMs and VEGF can repress cancer development,which has been demonstrated in clinical trials and on an experimental level.In the present work,we show that miR-150 is an oncomir because of its promotional effect on VEGF.MiR-150 targets TAMs to up-regulate their secre-tion of VEGF in vitro.With the utilization of cell-derived vesicles,named microvesicles(MVs),we transferred an-tisense RNA targeted to miR-150 into mice and found that the neutralization of miR-150 down-regulates miR-150 and VEGF levels in vivo and attenuates angiogenesis.There-fore,we proposed the therapeutic potential of neutralizing miR-150 to treat cancer and demonstrated a novel,natu-ral,microvesicle-based method for the transfer of nucleic acids.

MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6

Osteosarcoma is the most common primary sarcoma of bone, and it is a leading cause of cancer death among adolescents and young adults. However, the molecular mechanism underlying osteosarcoma carcinogenesis remains poorly understood. Recently, cyclin-dependent kinase 6 （CDK6） was identified as an important onco- gene. We found that CDK6 protein level, rather than CDK6 mRNA level, is much higher in osteosarcoma tissues than in normal adjacent tissues, which indicates a post-transcriptional mechanism involved in CDK6 regulation in osteosarcoma. MiRNAs are small non- coding RNAs that repress gene expression at the post- transcriptional level and have widely been shown to play important roles in many human cancers. In this study, we investigated the role of miR-29b as a novel regulator of CDK6 using bioinformatics methods. We demon- strated that CDK6 can be downregulated by miR-29b via binding to the 3＇-UTR region in osteosarcoma cells. Furthermore, we identified an inverse correlation between miR-29b and CDK6 protein levels in osteosar- coma tissues. Finally, we examined the function of miR- 29b-driven repression of CDK6 expression in osteosarcoma cells. The results revealed that miR-29b acts as a tumor suppressor of osteosarcoma by targeting CDK6 in the proliferation and migration processes. Taken together, our results highlight an important role for miR-29b in the regulation of CDK6 in osteosarcoma and may open new avenues for future osteosarcoma therapies.

Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum

Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns.Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles(MVs).In the present study,we found that the MVs from colostrum contain signifi cantly higher levels of several immune-related miRNAs.We hypothesized that the colostrum MVs may transfer the immune-related miR-NAs into cells,which contribute to its immune modulatory feature.We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs.We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect.Moreover,we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects.Taken together,these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which co-lostrum modulates body immune response.

An artificial intelligence based method for evaluating power grid node importance using network embedding and support vector regression

The identification of important nodes in a power grid has considerable benefits for safety. Power networks vary in many aspects, such as scale and structure. An index system can hardly cover all the information in various situations. Therefore, the efficiency of traditional methods using an index system is case-dependent and not universal. To solve this problem, an artificial intelligence based method is proposed for evaluating power grid node importance. First, using a network embedding approach, a feature extraction method is designed for power grid nodes, considering their structural and electrical information. Then, for a specific power network, steady-state and node fault transient simulations under various operation modes are performed to establish the sample set. The sample set can reflect the relationship between the node features and the corresponding importance. Finally, a support vector regression model is trained based on the optimized sample set for the later online use of importance evaluation. A case study demonstrates that the proposed method can effectively evaluate node importance for a power grid based on the information learned from the samples. Compared with traditional methods using an index system, the proposed method can avoid some possible bias. In addition, a particular sample set for each specific power network can be established under this artificial intelligence based framework, meeting the demand of universality.

miR-181b functions as an oncomiR in colorectal cancer by targeting PDCDZ

Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and conse- quently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken toge- ther, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.

The protective role of myeloid-derived suppressor cells in concanavalin A-induced hepatic injury

The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells （MDSCs） could prevent the concanavalin A （ConA）- induced hepatitis through suppressing T cell proliferation. We observed an increase in the frequencies of MDSCs in mouse spleen and liver at early stage of ConA treatment, implicating that the MDSCs might be involved in the initial resistance of mice against ConA- mediated inflammation. Subpopulation analysis showed that the MDSCs in liver of ConA-induced mice were mainly granulocytic MDSCs. Adoptive transfer of the bone marrow-derived MDSCs into ConA-treated mice showed that the MDSCs migrated into the liver and spleen where they suppressed T cell proliferation through ROS pathway. In addition, the frequencies of MDSCs in mice were also significantly increased by the treatment with immune suppressor glucocorticoids. Transfer of MDSCs into the regulatory T cell （Treg）- depleted mice showed that the protective effect of MDSCs on ConA-induced hepatitis is Treg-independent. In conclusion, our results demonstrate that MDSCs possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease.

Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

MTUS1 （microtubule-associated tumor suppressor 1） has been identified that can function as a tumor sup- pressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b （miR-19a/b） promote prolifer- ation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell prolif- eration and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to pro- mote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first cluesregarding the roles of miR-19a/b, which appear to func- tion as oncomirs in lung cancer by downregulating MTUSI.

Identification of microRNA-like RNAs in Ophiocordyceps sinensis

Ophiocordyceps sinensis is well known as a traditional Chinese medicine and has widely been used for over 2,000 years to stimulate immune system, decrease blood pressure and to inhibit tumor growth. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less studied until the discovery of microRNA-like RNA(milRNA). High-throughput sequencing and bioinformatics approaches were used to identify conserved and novel milRNAs in O. sinensis. 40 conserved milRNAs were identified, while 23 pre-miRNA candidates encoding 31 novel milRNAs were predicted. Furthermore, the potential target genes of milRNAs in human were predicted and gene ontology analysis was applied to these genes. Enrichment analysis of GO-represented biological process showed that target genes of both conserved and novel milRNAs are involved in development, metabolic and immune processes, indicating the potential roles of milRNAs of O. sinensis in pharmacological effects as health food and traditional Chinese medicine. This study is the first report on genome-wide analysis of milRNAs in O. sinensis and it provides a useful resource to further study the potential roles of milRNAs as active components of O. sinensis in health food or traditional Chinese medicine.