Network pharmacology and molecular docking identify mechanisms of medicinal plant-derived 1,2,3,4,6-penta-O-galloyl-beta-D-glucose treating gastric cancer

Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).

Wide grain 4,encoding an alpha-tubulin,regulates grain size by affecting cell expansion in rice

Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.

一类带有交叉扩散的捕食-食饵模型的正解

该文研究了一类在齐次Dirichlet边界条件下的带有交叉扩散的捕食-食饵模型.首先,根据Leray-Schauder度理论,建立了系统的正解的存在性;其次,当参数m=β且充分大时,分别研究了正则扰动方程和奇异扰动方程的正解的存在性,和借助分歧理论说明奇异系统的正解在a*处爆破;最后,建立了系统正解的多解性.

Simulated annealing spectral clustering algorithm for image segmentation

The similarity measure is crucial to the performance of spectral clustering. The Gaussian kernel function based on the Euclidean distance is usual y adopted as the similarity measure. However, the Euclidean distance measure cannot ful y reveal the complex distribution data, and the result of spectral clustering is very sensitive to the scaling parameter. To solve these problems, a new manifold distance measure and a novel simulated anneal-ing spectral clustering （SASC） algorithm based on the manifold distance measure are proposed. The simulated annealing based on genetic algorithm （SAGA）, characterized by its rapid convergence to the global optimum, is used to cluster the sample points in the spectral mapping space. The proposed algorithm can not only reflect local and global consistency better, but also reduce the sensitivity of spectral clustering to the kernel parameter, which improves the algorithm’s clustering performance. To efficiently apply the algorithm to image segmentation, the Nystrom method is used to reduce the computation complexity. Experimental results show that compared with traditional clustering algorithms and those popular spectral clustering algorithms, the proposed algorithm can achieve better clustering performances on several synthetic datasets, texture images and real images.

Multi-population and diffusion UMDA for dynamic multimodal problems

In dynamic environments,it is important to track changing optimal solutions over time.Univariate marginal distribution algorithm（UMDA） which is a class algorithm of estimation of distribution algorithms attracts more and more attention in recent years.In this paper a new multi-population and diffusion UMDA（MDUMDA） is proposed for dynamic multimodal problems.The multi-population approach is used to locate multiple local optima which are useful to find the global optimal solution quickly to dynamic multimodal problems.The diffusion model is used to increase the diversity in a guided fashion,which makes the neighbor individuals of previous optimal solutions move gradually from the previous optimal solutions and enlarge the search space.This approach uses both the information of current population and the part history information of the optimal solutions.Finally experimental studies on the moving peaks benchmark are carried out to evaluate the proposed algorithm and compare the performance of MDUMDA and multi-population quantum swarm optimization（MQSO） from the literature.The experimental results show that the MDUMDA is effective for the function with moving optimum and can adapt to the dynamic environments rapidly.

A natural allele of TAW1 contributes to high grain number and grain yield in rice

Grain number per panicle (GNP) is a complex trait controlled by quantitative trait loci (QTL),directly determining grain yield in rice.Identifying GNP-associated QTL is desirable for increasing rice yield.A rice chromosome segment substitution line (CSSL),F771,which showed increased panicle length and GNP,was identified in a set of CSSLs derived from a cross between two indica cultivars,R498 (recipient) and WY11327 (donor).Genetic analysis showed that the panicle traits in F771 were semidominant and controlled by multiple QTL.Six QTL were consistently identified by QTL-seq analysis.Among them,the major QTL q PLN10 for panicle length and GNP was localized to a 121-kb interval between markers N802 and N909 on chromosome 10.Based on quantitative real-time PCR and sequence analysis,TAWAWA1(TAW1),a known regulator of rice inflorescence architecture,was identified as the candidate gene for q PLN10.A near-isogenic line,NIL-TAW1,was developed to evaluate its effects.In comparison with the recurrent parent R498,NIL-TAW1 showed increased panicle length (14.0%),number of secondary branches (20.9%) and GNP (22.0%),and the final grain yield per plant of NIL-TAW1 was increased by18.6%.Transgenic experiments showed that an appropriate expression level of TAW1 was necessary for panicle development.Haplotype analysis suggested that the favorable F771-type (Hap 13) of TAW1was introduced from aus accessions and had great potential value in high-yield breeding both in indica and japonica varieties.Our results provide a promising genetic resource for rice grain yield improvement.

Effect of variable number of tandem repeats polymorphism in the human dopamine transporter gene on conflict information processing according to event-related potential

The dopamine transporter （DAT） is responsible for dopamine reuptake from the synaptic cleft. A variable number of tandem repeats polymorphism in the DAT gene is related to DAT availability and has been associated with cognition. With the advantage of high-time resolution, event-related potential is an important method to study the time course of human information processing. Previous results have suggested that dopamine exhibits a close relationship with conflicting information processing. Therefore, the present study assumed that conflicting information processing could be influenced by DAT variable number of tandem repeats polymorphism. To confirm this, the present study analyzed the influence of DAT genotypes on N270, which is presumed to reflect neural activity of conflict information processing in young healthy adults. A S1-S2 matching task was performed in healthy adults with 10/10 genotype （n = 14） and 10/9 genotypes （n = 14）, respectively, when event-related potentials were recorded. Results demonstrated that subjects with the 10/10 genotype exhibited shorter N270 latency and quicker reaction times compared with subjects with the 10/9 genotype. There were no differences in N270 amplitude between the two genotypes. These results suggested that 10/10 genotype subjects more efficiently processed conflict information.

Intraspinal microstimulation A novel technique for the functional recovery of spinal cord injury

Nonspecific neuronal activity elicited by intraspinal microstimulation in the intermediate and ventral gray matter of thoracic spinal segments caudal to a complete spinal cord transection significantly increased the rat hindlimb Basso, Beattie, Bresnahan locomotor score by activating the central pattem generator located in the lumbar spinal cord. However, the best region for intraspinal microstimulation is unclear. Using an incomplete spinal cord injury model at T8, we compared the use of intraspinal microstimulation to activate the spinal cord in rats with a spontaneous recovery group. The intraspinal microstimulation group recovered sooner and showed three kinds of movement： the left hindlimb, the left hindlimb toes, and the paraspinal muscles and tails. These had different microstimulation thresholds. There was mild hyperplasia of the astrocytes surrounding the tips of the microelectrodes and slight inflammatory reactions nearby. These results indicate that implantation of microelectrodes was relatively safe and induced minimal damage to the lumbar-sacral spinal cord. Intraspinal microstimulation in the lumbar sacral spinal cord may improve leg movements after spinal cord injury. Non-specific intraspinal microstimulation may be a novel technique for the recovery of spinal cord injuries.

散发性乳腺癌癌变过程14-3-3σ异常甲基化与其转录水平的关系(英文)

Objective: To study the relationship between 14-3-3 sigma gene promoter hypermethylation and its transcrip-tion levels in sporadic breast carcinogenesis. Methods: Hypermethylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerious and normal tissue, and its mRNA was also detected by real-time PCR based on SYBR Green 1. Results: The hypermethylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Hypermethylation was presented in portions (2/13,18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The hypermethylation change of 14-3-3 sigma gene was markedly related with various types, grades and lymph node metastases (P < 0.05), and no significant differences in methylation frequencies were seen between premenopause and postmenopause (P > 0.05). The hypermethylation of 14-3-3 sigma showed reverse relationship with its mRNA transcription (P < 0.05). Only lymph node metastases was strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5-year survival rate of sporadic breast cancer (P > 0.05). Conclu-sion: Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing the expression of 14-3-3 sigma protein, which plays an important role in the development of sporadic breast carcinomas including various types, grades and lymph node metastases.

An Evolutionary Algorithm Based on a New Decomposition Scheme for Nonlinear Bilevel Programming Problems

In this paper, we focus on a class of nonlinear bilevel programming problems where the follower’s objective is a function of the linear expression of all variables, and the follower’s constraint functions are convex with respect to the follower’s variables. First, based on the features of the follower’s problem, we give a new decomposition scheme by which the follower’s optimal solution can be obtained easily. Then, to solve efficiently this class of problems by using evolutionary algorithm, novel evolutionary operators are designed by considering the best individuals and the diversity of individuals in the populations. Finally, based on these techniques, a new evolutionary algorithm is proposed. The numerical results on 20 test problems illustrate that the proposed algorithm is efficient and stable.

假单胞菌Pseudomonas fluorescens Pf0-1中转录调控因子SpfB负调控DNA磷硫酰化修饰（英文）

【目的】DNA磷硫酰化修饰是DNA骨架上非桥接的氧原子以序列选择性和R-构型被硫取代的一种新型DNA修饰。目前,磷硫酰化修饰在多种细菌、古生菌以及人类致病菌中多有发现,但其分子调控机制尚不清楚。为了全面解析磷硫酰化修饰的调控机制,本文选择荧光假单胞菌Pf0-1为研究对象,开展了其DNA磷硫酰化修饰的调控机制研究。【方法】首先,构建了spfB基因缺失和回补菌株,使用碘能特异性断裂磷硫酰化修饰DNA的方法,研究了该基因缺失对修饰表型的影响。利用cDNA在相邻同方向的基因间隔区进行PCR,确定了磷硫酰化修饰基因簇spf BCDE内的共转录单元。通过荧光定量RT-PCR,分析了spfB基因缺失突变株中磷硫酰化修饰基因的转录量。利用异源表达并纯化得到的重组蛋白SpfB进行了体外功能研究。通过EMSA实验,验证了SpfB蛋白具有与spfB启动子序列结合活性。通过DNase I footprinting实验,精确定位了Spf B蛋白与DNA结合序列。【结果】spf B基因的缺失加剧了磷硫酰化修饰DNA断裂所致电泳条带弥散的表型,spf B基因的回补能够恢复该表型,证明spf B基因负调控磷硫酰化修饰。鉴定了spf基因簇中只含有1个共转录单元,且该共转录单元在?spfB突变株中转录水平明显上升。通过EMSA和DNase I footprint实验,检测了SpfB蛋白与磷硫酰化修饰基因spf BCDE的启动子区域5′-TGTTTGT-3′相结合。【结论】SpfB作为转录调控因子负调控磷硫酰化修饰基因spf BCDE的表达,为解析磷硫酰化修饰的调控机制和全面理解基因组上的部分修饰特征奠定了基础。

OsSPL18 controls grain weight and grain number in rice

Grain weight and grain number are two important traits directly determining grain yield in rice. To date,a lot of genes related to grain weight and grain number have been identified; however, the regulatory mechanism underlying these genes remains largely unknown. In this study, we studied the biological function of OsSPL18 during grain and panicle development in rice. Knockout (KO) mutants of OsSPL18exhibited reduced grain width and thickness, panicle length and grain number, but increased tiller number. Cytological analysis showed that OsSPL18 regulates the development of spikelet hulls by affecting cell proliferation. qRT-PCR and GUS staining analyses showed that OsSPL18 was highly expressed in developing young panicles and young spikelet hulls, in agreement with its function in regulating grain and panicle development. Transcriptional activation experiments indicated that OsSPL18is a functional transcription factor with activation domains in both the N-terminus and C-terminus, and both activation domains are indispensable for its biological functions. Quantitative expression analysis showed that DEP1, a major grain number regulator, was significantly down-regulated in OsSPL18 KO lines.Both yeast one-hybrid and dual-luciferase (LUC) assays showed that OsSPL18 could bind to the DEP1promoter, suggesting that OsSPL18 regulates panicle development by positively regulating the expression of DEP1. Sequence analysis showed that OsSPL18 contains the OsmiR156k complementary sequence in the third exon; 5?RLM-RACE experiments indicated that OsSPL18 could be cleaved by OsmiR156k. Taken together, our results uncovered a new OsmiR156k-OsSPL18-DEP1 pathway regulating grain number in rice.

Epigenetic control on cell fate choice in neural stem cells

Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental cues.NSCs and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during develop-ment.These developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic level.From early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural develop-ment.Here we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.

Loss of Gn1a/OsCKX2 confers heavy-panicle rice with excellent lodging resistance

Significant achievements have been made in breeding programs for the heavy-panicle-type(HPT)rice(Oryza sativa) in Southwest China. The HPT varieties now exhibit excellent lodging resistance,allowing them to overcome the greater pressures caused by heavy panicles. However, the genetic mechanism of this lodging resistance remains elusive. Here, we isolated a major quantitative trait locus, Panicle Neck Diameter 1(PND1), andidentified the causal gene as GRAIN NUMBER 1 A/CYTOKININ OXIDASE 2(Gn1 A/Os CKX2). The null gn1 a allele from rice line R498(gn1 aR498) improved lodging resistance through increasing the culm diameter and promoting crown root development.Loss-of-function of Gn1 a/Os CKX2 led to cytokinin accumulation in the crown root tip and accelerated the development of adventitious roots. Gene pyramiding between the null gn1 aR498 allele with two gain-of-function alleles, STRONG CULM 2(SCM2)and SCM3, further improved lodging resistance.Moreover, Gn1 a/Os CKX2 had minimal influence on overall rice quality. Our research thus highlights the distinct genetic components of lodging resistance of HPT varieties and provides a strategy for tailormade crop improvement of both yield and lodging resistance in rice.

A single nucleotide substitution at 5'-UTR of GSN1 represses its translation and leads to an increase of grain length in rice

Rice grain size is an important trait that affects rice yield and quality, and thus the identification of genes related to grain size is of great significance for improving rice yield and quality. Many genes related to grain size, such as DEP1(Huang et al., 2009),GW5(Liu et al., 2017).

Degradation of ofloxacin using peroxymonosulfate activated by nitrogen-rich graphitized carbon microspheres:Structure and performance controllable study

Nitrogen-rich graphitized carbon microspheres(NGCs)with hierarchically porous were constructed by self-assembly.Under different heat treatment conditions,the structure,morphology and properties of NGCs were studied by using multiple characterization techniques.The results showed that the chemical microenvironments(e.g.surface chemistry,degree of graphitization and defective,etc.)and microstructures properties(e.g.morphology,specific surface area,particle size,etc.)could be delicately controlled via thermal carbonization processes.The degradation of ofloxacin(OFLX)by NGCs activated peroxymonosulfate(PMS)was studied systematically.It was found that the synergistic coupling effect between optimum N or O bonding species configuration ratio(graphitic N and C=O)and special microstructure was the main reason for the enhanced catalytic activity of NGC-800(calcination temperature at 800°C).Electron paramagnetic resonance(EPR)experiments and radical quenching experiments indicated that the hydroxyl(·OH),sulfate(SO4^·-)and singlet oxygen(^1O_(2))were contributors in the NGC-800/PMS systems.Further investigation of the durability of chemical structures and surface active sites revealed that undergo N bonding species configuration reconstruction and cannibalistic oxidation during PMS activation reaction.The used NGC-800 physicochemical properties could be recovered by heat treatment to achieve the ideal catalytic performance.The findings proposed a valuable insight for catalytic performance and controllable design of construction.

Characterization and Fine Mapping of GLABROUS RICE 2 in Rice

Glabrous rice exhibits glabrous leaves and hulls because neither of these structures have trichomes on their surfaces. Glabrous rice varieties have become an important germplasm resource in the rice industry because they have considerable packaging efficiency and can reduce skin itching and dust during harvesting, drying, and packing （Shim et al., 2012; Zhang et al., 2012）.

Effect of Zibushenjing Fang on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency: a mechanistic study

OBJECTIVE: To investigate the effects of Zibushenjing Fang (formula for tonifying the kidney essence) on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency. METHODS: Fifty male Kunming mice were randomly divided into five groups: normal group, model group, Jinkuishenqi Wan group, Zibushenjing Fang high dose group, and Zibushenjing Fang low dose group, with 10 mice in each group. The model of kidney essence insufficiency syndrome was established in all the mice except the normal group by using a cat to threaten the mice and by swimming until exhaustion daily which lasted about 21 days. Mice in the model group were administered 20 mL/ kg -1 · d -1 of normal saline intragastrically. The Jinkuishenqi Wan group was given 2.7 g/kg-1 · d-1 ofa solution of Jinkuishenqi Wan. The Zibushenjing Fang high dose group was given 20 g/kg -1 · d -1 and the Zibushenjing Fang low dose group was given 10 g/kg -1 · d -1 of a solution of Zibushenjing Fang.The general condition of all the groups was observed, including the quantity of food and water intake, swimming time, length of femur, and weight of the femur and musculus quadriceps femoris. The total superoxide dismutase (T-SOD), glutathione peroxi- dase (GSH-Px), and methane dicarboxylic aldehyde (MDA) activities in the brain tissues were detected. RESULTS: Zibushenjing Fang could improve the manifestation of kidney essence insufficiency, increase the quantity of food and water intake, swimming time, femur length, and femur and musculus quadriceps femoris weight. It could also regulate the activities of T-SOD, GSH-Px, and MDA in brain tissue. CONCLUSION: Zibushenjing Fang may play an important role in treating kidney essence insufficiency syndrome by promoting body development and improving brain tissue antioxidation.

Deletion of a Dna K protein gene causes seedling green-revertible albino by retarding chloroplast development in rice

Green-revertible albino mutants are important sources for studying chloroplast structure, chloroplast development, chlorophyll biosynthesis, and plant photosynthesis. In the present study, we characterized a greenrevertible albino mutant gra(k), which was obtained from the tissue-cultured rice Kitaake. The mutant gra(k) exhibited albino on its first three leaves. The leaf color started to turn green at the four-leaf stage. The chlorophyll contents were deeply reduced at the seedling stage, and the chloroplast development was delayed in gra(k). The greenrevertible albino(gra) phenotype of the mutant gra(k) was temperature dependent. The main agronomic traits,including plant height, tilling number per plant, seed setting rate, and thousand-grain weight, slightly decreased in gra(k) comparing to those in the wild-type Kitaake.Genetic analysis showed that the gra phenotype was controlled by a single recessive nucleic gene. By using 5,168 recessive F2individuals derived from the cross of gra(k) 9 Jodan, the locus of the gene Gra(k) was delimited in a DNA region of 200 kb between the makers B-31 and P11 on chromosome 5. Sequencing analysis indicated thatthe three functionally annotated genes, LOC_Os05g23700,LOC_Os05g23720, and LOC_Os05g23740, were all deleted in the 200 kb region in the mutant gra(k). Transgenic test revealed that the gra(k) plants over-expressing LOC_Os05g23740CDS were restored to normal green as the wild-type Kitaake. Our results proved that the deletion of the Dna K protein gene LOC_Os05g23740(encoding the chaperon protein Os Hsp70CP1) led to the gra phenotype in the mutant gra(k).

Adsorption of three pharmaceuticals on two magnetic ion-exchange resins

The presence of pharmaceuticals in aquatic environments poses potential risks to the ecology and human health. This study investigated the removal of three widely detected and abundant pharmaceuticals, namely, ibuprofen（IBU）, diclofenac（DC）, and sulfadiazine（SDZ）, by two magnetic ion-exchange resins. The adsorption kinetics of the three adsorbates onto both resins was relatively fast and followed pseudo-second-order kinetics. Despite the different pore structures of the two resins, similar adsorption patterns of DC and SDZ were observed, implying the existence of an ion-exchange mechanism. IBU demonstrated a combination of interactions during the adsorption process. These interactions were dependent on the specific surface area and functional groups of the resin. The adsorption isotherm fittings verified the differences in the behavior of the three pharmaceuticals on the two magnetic ion-exchange resins. The presence of Cl-and SO2-4suppressed the adsorption amount, but with different inhibition levels for different adsorbates. This work facilitates the understanding of the adsorption behavior and mechanism of pharmaceuticals on magnetic ion-exchange resins.The results will expand the application of magnetic ion-exchange resins to the removal of pharmaceuticals in waters.