N6-methyladenosine RNA modification regulates cotton drought response in a Ca2+ and ABA-dependent manner.

N6 -methyladenosine (m6 A) is the most prevalent internal modification present in mRNAs, and is considered to participate in a range of developmental and biological processes. Drought response is highly regulated at the genomic, transcriptional and post-transcriptional levels. However, the biological function and regulatory mechanism of m6 A modification in the drought stress response is still poorly understood. We generated a transcriptome-wide m6 A map using drought-resistant and drought-sensitive varieties of cotton under different water deficient conditions to uncover patterns of m6 A methylation in cotton response to drought stress. The results reveal that m6 A represents a common modification and exhibit dramatic changes in distribution during drought stress. More 5'UTR m6 A was deposited in the drought-resistant variety and was associated with a positive effect on drought resistance by regulating mRNA abundance. Interestingly, we observed that increased m6 A abundance was associated with increased mRNA abundance under drought, contributing to drought resistance, and vice versa. The demethylase GhALKBH10B was found to decrease m6 A levels, facilitating the mRNA decay of ABA signal-related genes (GhZEP, GhNCED4 and GhPP2CA) and Ca2+ signal-related genes (GhECA1, GhCNGC4, GhANN1 and GhCML13), and mutation of GhALKBH10B enhanced drought resistance at seedling stage in cotton. Virus-induced gene silencing (VIGS) of two Ca2+ -related genes, GhECA1 and GhCNGC4, reduced drought resistance with the decreased m6 A enrichment on silenced genes in cotton. Collectively, we reveal a novel mechanism of post-transcriptional modification involved in affecting drought response in cotton, by mediating m6 A methylation on targeted transcripts in the ABA and Ca2+ signalling transduction pathways.

Transcriptome and metabolome profiling of interspecific CSSLs reveals general and specific mechanisms of drought resistance in cotton.

In order to understand the molecular mechanism of cotton's response to drought during the flowering and boll stage, transcriptomics and metabolomics were carried out for two introgression lines (drought-tolerant line: T307; drought-sensitive line: S48) which were screened from Gossypium hirsutum cv. 'Emian22' with some gene fragments imported from Gossypium barbadense acc. 3-79, under drought stress by withdrawing water at flowering and boll stage. Results showed that the basic drought response in cotton included a series of broad-spectrum responses, such as amino acid synthesis, hormone (abscisic acid, ABA) signal transduction, and mitogen-activated protein kinases signal transduction pathway, which activated in both drought-tolerant and drought-sensitive lines. However, the difference of their imported fragments and diminished sequences triggers endoplasmic reticulum (ER) protein processing, photosynthetic-related pathways (in leaves), and membrane solute transport (in roots) in drought-tolerant line T307, while these are missed or not activated in drought-sensitive line S48, reflecting the different drought tolerance of the two genotypes. Virus-induced gene silencing assay of drought-tolerant differentially expressed heat shock protein (HSP) genes (mainly in leaf) and ATP-binding cassette (ABC) transporter genes (mainly in roots) indicated that those genes play important role in cotton drought tolerant. Combined analysis of transcriptomics and metabolomics highlighted the important roles of ER-stress-related HSP genes and root-specific ABC transporter genes in plants drought tolerance. These results provide new insights into the molecular mechanisms underlying the drought stress adaptation in cotton.

Genome-wide identification of MAPK cascade genes reveals the GhMAP3K14-GhMKK11-GhMPK31 pathway is involved in the drought response in cotton.

The mitogen-activated protein kinase (MAPK) cascade pathway, which has three components, MAP3Ks, MKKs and MPKs, is involved in diverse biological processes in plants. In the current study, MAPK cascade genes were identified in three cotton species, based on gene homology with Arabidopsis. Selection pressure analysis of MAPK cascade genes revealed that purifying selection occurred among the cotton species. Expression pattern analysis showed that some MAPK cascade genes differentially expressed under abiotic stresses and phytohormones treatments, and especially under drought stress. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments showed extensive interactions between different MAPK cascade proteins. Virus-induced gene silencing (VIGS) assays showed that some MAPK cascade modules play important roles in the drought stress response, and the GhMAP3K14-GhMKK11-GhMPK31 signal pathway was demonstrated to regulate drought stress tolerance in cotton. This study provides new information on the function of MAPK cascade genes in the drought response, and will help direct molecular breeding for improved drought stress tolerance in cotton.

Neuroprotective effects of triterpenoid saponins from Medicago sativa L. against H2O2-induced oxidative stress in SH-SY5Y cells.

Medicago sativa L. is a forage legume plant widely distributed in all continents. Six new triterpenoid saponins, Medicagosides A-F (1-6) and five known ones (7-11) were isolated from M. sativa. Their structures were determined via HRESIMS, 1D and 2D NMR analysis. Biologically, all the isolates displayed neuroprotective activities against H2O2-induced damage in SH-SY5Y cells. Among them, compounds 1, 3-5 and 10 exhibited striking neuroprotective activities at 100 µM, restoring cell viability range from 79.66% to 89.03%, relative to 79.46% (100 µM) of Trolox used as the positive control.

Nocardioides phosphati sp. nov., an actinomycete isolated from a phosphate mine.

A Gram-staining-positive, non-spore-forming and non-motile strain, designated WYH11-7T, was isolated from a phosphate mine in Yunnan Province, PR China. The taxonomic position of WYH11-7T was investigated by polyphasic approaches. Phylogenetic analyses based on 16S rRNA gene sequences indicated that WYH11-7T represents a member of the genus Nocardioides. WYH11-7T was closely related to Nocardioidesjensenii DSM 20641T, Nocardioidesdubius DSM 19084T and Marmoricolaterrae DSM 27141T, and had pairwise 16S rRNA gene sequence similarities of 97.4, 97.2 and 97.0 %, respectively. DNA-DNA relatedness values between WYH11-7T and related type strains N. jensenii DSM 20641T and N. dubius DSM 19084T were found to be 17.6±4.9 and 14.6±3.1 %, respectively. The respiratory menaquinone of WYH11-7T was MK-8 (H4) while the major fatty acids were C18 : 1ω9c, C16 : 0, C17 : 0, C17 : 1ω8c, C18 : 1 10-methyl and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and two unidentified phospholipids. Whole-cell hydrolysates contained mannose, ribose, glucose and galactose along with ll-diaminopimelic acid as the diagnostic diamino acid in the peptidoglycan. The DNA G+C content was 71.2 mol%. Phenotypic, phylogenetic and chemotaxonomic data indicated that strain WYH11-7T represents a novel species of the genus Nocardioides, for which the name Nocardioidesphosphatisp. nov. is proposed. The type strain is WYH11-7T (=CGMCC 4.7371T=DSM 104026T).

Cu Regulating the Bifunctional Activity of Co-O Sites for the High-Performance Rechargeable Zinc-Air Battery.

The rational design of cost-effective and highly active electrocatalysts becomes the crucial energy storage technology to boost the kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), which hinders the large-scale application of metal-air batteries under the situation of increasingly pressing energy anxiety. Herein, the Co-based ZIF introduced the moderate amount of Cu2+-derived Cu/Co metal nanoparticles (NPs) embedded in carbon frameworks after high-temperature calcination. The Co-O bond on the surface of Co nanoparticles is modulated by adjacent Cu nanoparticles with the surface Cu-O bonds. The resulted increase of the Co2+/Co3+ ratio in 0.1CuCo-NC enhances the ORR/OER bifunctional catalytic kinetics along with the ΔE of 0.639 V. In situ Raman spectra of the catalyst on the three-electrode system as well as in the driven zinc-air battery (ZAB) show that the Co-O active sites regulated by Cu nanoparticles with Cu-O bonds maintain a periodic lattice expansion and compression during discharging and charging. The zinc-air battery based on 0.1CuCo-NC has a peak power density of up to 198.3 mW cm-2, a mass-specific capacity of 798.2 mAh g-1, and a cycling stability of 923 h at room temperature. This work makes up the research gap of a Co-based metal-organic framework (MOF)-derived catalyst regulated by a transition metal.

GhL1L1 regulates the contents of unsaturated fatty acids by activating the expression of GhFAD2 genes in cotton.

Edible oils with high unsaturated fatty acids, particularly oleic acid, are beneficial to human health. Cotton is one of the top five oil crops in the world, but the mechanism of high-quality oil synthesis and regulatory networks in cotton are largely unclear. Here, we identified Leafy cotyledon1-like 1 (GhL1L1), a NF-YB subfamily gene that is specifically expressed during somatic embryogenesis and seed maturation in cotton. Overexpression of GhL1L1 regulates the contents of unsaturated fatty acids in cotton, especially in the seeds, which is associated with altered expression of the cotton fatty acid biosynthesis-related genes. GhL1L1 synergistically enhanced the expression of GhFAD2-1A by binding to the G-box in its promoter, leading to an increase in the content of linoleic acid. Furthermore, this activation could be enhanced by GhNF-YC2 and GhNF-YA1 by form a transcriptional complex. Collectively, these results contribute to provide new insights into the molecular mechanism of oil biosynthesis in cotton and can facilitate genetic manipulation of cotton varieties with enhanced oil content.

Single-Cell Transcriptome Atlas and Regulatory Dynamics in Developing Cotton Anthers.

Plant anthers are composed of different specialized cell types with distinct roles in plant reproduction. High temperature (HT) stress causes male sterility, resulting in crop yield reduction. However, the spatial expression atlas and regulatory dynamics during anther development and in response to HT remain largely unknown. Here, the first single-cell transcriptome atlas and chromatin accessibility survey in cotton anther are established, depicting the specific expression and epigenetic landscape of each type of cell in anthers. The reconstruction of meiotic cells, tapetal cells, and middle layer cell developmental trajectories not only identifies novel expressed genes, but also elucidates the precise degradation period of middle layer and reveals a rapid function transition of tapetal cells during the tetrad stage. By applying HT, heterogeneity in HT response is shown among cells of anthers, with tapetal cells responsible for pollen wall synthesis are most sensitive to HT. Specifically, HT shuts down the chromatin accessibility of genes specifically expressed in the tapetal cells responsible for pollen wall synthesis, such as QUARTET 3 (QRT3) and CYTOCHROME P450 703A2 (CYP703A2), resulting in a silent expression of these genes, ultimately leading to abnormal pollen wall and male sterility. Collectively, this study provides substantial information on anthers and provides clues for heat-tolerant crop creation.

Ox-LDL induced profound changes of small non-coding RNA in rat endothelial cells.

Introduction: Atherosclerosis (AS) is a common cardiovascular disease with a high incidence rate and mortality. Endothelial cell injury and dysfunction are early markers of AS. Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of AS. Ox-LDL promotes endothelial cell apoptosis and induces inflammation and oxidative stress in endothelial cells. Small non-coding RNAs (sncRNAs) mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), microRNAs (miRNAs) and repeat-associated RNAs. Studies have shown that small non-coding RNAs play an increasingly important role in diseases. Methods: We used ox-LDL to treat rat endothelial cells to simulate endothelial cell injury. The expression changes of sncRNA were analyzed by small RNA high-throughput sequencing, and the expression changes of piRNA, snoRNA, snRNA, miRNA and repeat-associated RNA were verified by quantitative polymerase chain reaction (qPCR). Results: Small RNA sequencing showed that 42 piRNAs were upregulated and 38 piRNAs were downregulated in endothelial cells treated with ox-LDL. PiRNA DQ614630 promoted the apoptosis of endothelial cells. The snoRNA analysis results showed that 80 snoRNAs were upregulated and 68 snoRNAs were downregulated in endothelial cells with ox-LDL treatment, and snoRNA ENSRNOT00000079032.1 inhibited the apoptosis of endothelial cells. For snRNA, we found that 20 snRNAs were upregulated and 26 snRNAs were downregulated in endothelial cells with ox-LDL treatment, and snRNA ENSRNOT00000081005.1 increased the apoptosis of endothelial cells. Analysis of miRNAs indicated that 106 miRNAs were upregulated and 91 miRNAs were downregulated in endothelial cells with ox-LDL treatment, and miRNA rno-novel-136-mature promoted the apoptosis of endothelial cells. The repeat RNA analysis results showed that 4 repeat RNAs were upregulated and 6 repeat RNAs were downregulated in endothelial cells treated with ox-LDL. Discussion: This study first reported the expression changes of sncRNAs in endothelial cells with ox-LDL treatment, which provided new markers for the diagnosis and treatment of endothelial cell injury.

Comprehensive non-coding RNA analysis reveals specific lncRNA/circRNA-miRNA-mRNA regulatory networks in the cotton response to drought stress.

Root and leaf are essential organs of plants in sensing and responding to drought stress. However, comparative knowledge of non-coding RNAs (ncRNAs) of root and leaf tissues in the regulation of drought response in cotton is limited. Here, we used deep sequencing data of leaf and root tissues of drought-resistant and drought-sensitive cotton varieties for identifying miRNAs, lncRNAs and circRNAs. A total of 1531 differentially expressed (DE) ncRNAs was identified, including 77 DE miRNAs, 1393 DE lncRNAs and 61 DE circRNAs. The tissue-specific and variety-specific competing endogenous RNA (ceRNA) networks of DE lncRNA-miRNA-mRNA response to drought were constructed. Furthermore, the novel drought-responsive lncRNA 1 (DRL1), specifically and differentially expressed in root, was verified to positively affect phenotypes of cotton seedlings under drought stress, competitively binding to miR477b with GhNAC1 and GhSCL3. In addition, we also constructed another ceRNA network consisting of 18 DE circRNAs, 26 DE miRNAs and 368 DE mRNAs. Fourteen circRNA were characterized, and a novel molecular regulatory system of circ125- miR7484b/miR7450b was proposed under drought stress. Our findings revealed the specificity of ncRNA expression in tissue- and variety-specific patterns involved in the response to drought stress, and uncovered novel regulatory pathways and potentially effective molecules in genetic improvement for crop drought resistance.

The GhMAP3K62-GhMKK16-GhMPK32 kinase cascade regulates drought tolerance by activating GhEDT1-mediated ABA accumulation in cotton.

INTRODUCTION: Drought is the principal abiotic stress that severely impacts cotton (Gossypium hirsutum) growth and productivity. Upon sensing drought, plants activate stress-related signal transduction pathways, including ABA signal and mitogen-activated protein kinase (MAPK) cascade. However, as the key components with the fewest members in the MAPK cascade, the function and regulation of GhMKKs need to be elucidated. In addition, the relationship between MAPK module and the ABA core signaling pathway remains incompletely understood. OBJECTIVE: Here we aim to elucidate the molecular mechanism of cotton response to drought, with a focus on mitogen-activated protein kinase (MAPK) cascades activating ABA signaling. METHODS: Biochemical, molecular and genetic analysis were used to study the GhMAP3K62-GhMKK16-GhMPK32-GhEDT1 pathway genes. RESULTS: A nucleus- and membrane-localized MAPK cascade pathway GhMAP3K62-GhMKK16-GhMPK32, which targets and phosphorylates the nuclear-localized transcription factor GhEDT1, to activate downstream GhNCED3 to mediate ABA-induced stomatal closure and drought response was characterized in cotton. Overexpression of GhMKK16 promotes ABA accumulation, and enhances drought tolerance via regulating stomatal closure under drought stress. Conversely, RNAi-mediated knockdown of GhMKK16 expression inhibits ABA accumulation, and reduces drought tolerance. Virus-induced gene silencing (VIGS)-mediated knockdown of either GhMAP3K62, GhMPK32 or GhEDT1 expression represses ABA accumulation and reduces drought tolerance through inhibiting stomatal closure. Expression knockdown of GhMPK32 or GhEDT1 in GhMKK16-overexpressing cotton reinstates ABA content and stomatal opening-dependent drought sensitivity to wild type levels. GhEDT1 could bind to the HD boxes in the promoter of GhNCED3 to activate its expression, resulting in ABA accumulation. We propose that the MAPK cascade GhMAP3K62-GhMKK16-GhMPK32 pathway functions on drought response through ABA-dependent stomatal movement in cotton.

A DNA Plasmid-Based Approach for Efficient Synthesis of Sacbrood Virus Infectious Clones within Host Cells.

RNA viruses are often cited as a significant factor affecting the populations of both domestic honey bees and wild pollinators. To expedite the development of effective countermeasures against these viruses, a more comprehensive understanding of virus biology necessitates extensive collaboration among scientists from diverse research fields. While the infectious virus clone is a robust tool for studying virus diseases, the current methods for synthesizing infectious clones of bee-infecting RNA viruses entail the in vitro transcription of the viral genome RNA in 8-10 kb, presenting challenges in reproducibility and distribution. This article reports on the synthesis of an infectious clone of the Chinese variant sacbrood virus (SBV) using a DNA plasmid containing an Autographa californica multiple nucleopolyhedrovirus (AcMNPV) immediate-early protein (IE1) promoter to trigger transcription of the downstream viral genome within hosts. The results demonstrate that the IE1-SBV plasmid can synthesize SBV clones in a widely used lepidopteran immortal cell line (Sf9) and honey bee pupae. Furthermore, the negative strand of the clone was detected in both Sf9 cells and honey bee pupae, indicating active infection and replication. However, the transfection of Sf9 cells was observed in only a limited proportion (less than 10%) of the cells, and the infection did not appear to spread to adjacent cells or form infective virions. The injection of honey bee pupae with 2500 ng of the IE1-SBV plasmid resulted in high infection rates in Apis cerana pupae but low rates in A. mellifera pupae, although the dosage was comparatively high compared with other studies using in vitro transcribed viral RNA. Our findings suggest that the synthesis of bee-infecting RNA viruses using DNA plasmids is feasible, albeit requiring additional optimization. However, this method holds substantial potential for facilitating the production of clones with various sequence modifications, enabling the exploration of viral gene functions and biology. The ease of distributing infectious clones in DNA plasmid form may foster collaboration among scientists in applying the clone to bee biology, ecology, and behavior, ultimately offering a comprehensive approach to managing virus diseases in the future.

Effect of Shixiao San on inflammatory factors and pain in rats with endometriosis.

ETHNOPHARMACOLOGICAL RELEVANCE: In the practice of traditional Chinese medicine, endometriosis is believed to be caused by blood stasis and is characterised by dysmenorrhea, which is difficult to control. Shixiao San (SXS) has a long history of use in the treatment of gynaecological diseases. The prescriptions composed of SXS include Typhae Pollen and Faeces Trogopterori, both of which have anti-inflammatory activity. In addition, Typhae Pollen can be used to treat many kinds of blood stasis diseases. AIM OF THE STUDY: The purpose of the present study was to investigate the effect of SXS on pain relief in rats with endometriosis and to preliminarily explore its mechanism of action in alleviating pain. MATERIAL AND METHODS: Ten rats received sham operation as the Sham group, and 30 endometriosis model rats were randomly divided into three groups: the Model, Shixiao San-Low (SXS-L), and Shixiao San-High (SXS-H) groups. The rats were administered the appropriate treatment via intragastric gavage for 4 weeks. The thermal radiation pain and mechanical pain thresholds of the rats were measured every 7 days after treatment. Finally, the distribution density of nerve fibres in endometrial tissue, the inflammatory infiltration of the dorsal root ganglion (DRG), the expression of TRPV1 in the DRG, and the expression of IL-1ß, TNF-α, and IL-6 in ectopic tissue were measured. RESULTS: After SXS treatment, the growth of ectopic tissue in rats with endometriosis was significantly suppressed, their thermal radiation pain and mechanical pain thresholds increased, the density of nerve fibres and the expression of inflammatory factors in ectopic tissues reduced, and inflammatory cells infiltration in the DRG of the animals alleviated. Meanwhile, the expression of TRPV1 in the DRG was downregulated in rats with endometriosis. CONCLUSIONS: SXS could possibly inhibit the development of endometriosis and relieve pain in patients with endometriosis by reducing inflammatory responses in ectopic tissue and the DRG.

ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis.

Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.

Cooperative Set Aggregation of Second-Order Multiagent Systems: Approximate Projection and Prescribed Performance.

This paper studies the cooperative set aggregation problem for second-order multiagent systems by utilizing the approximate projection algorithm. First, an aggregation law that uses the approximate projection is proposed, where the feasible set of the approximate projection points is established based on an Euclidean distance with respect to the targeted set and a deviated angle with respect to the exact projection point. Under the proposed law, the position vectors of all the agents are shown to reach an agreement in the intersection of their individual targeted sets and the velocity vector of each agent is shown to converge to zero. Then, a time-dependent performance bound is set for the norm of the weighted error of the relative positions among neighboring agents and the absolute velocity of the agent, and a performance-guaranteed aggregation controller is designed to guarantee the prescribed transient performance. During the process of aggregation, the norm of the weighted error is shown to not exceed the performance bound. The convergence conditions of the proposed algorithms with respect to the control strength and the terms induced by the approximate projection are obtained by using the techniques of convex analysis and Lyapunov stability. Simulations are provided to validate the theoretical results.

Structural characteristics of Medicago Sativa L. Polysaccharides and Se-modified polysaccharides as well as their antioxidant and neuroprotective activities.

Medicago Sativa L., a nutrient-rich plant used as feed for cattle and sheep, is widely planted globally. This study investigated the structural characteristics and activities of three kinds of novel polysaccharides (APS1, APS2 and APS3) isolated from the stems of M. sativa as well as its two selenium modified products (Se-APS2 and Se-APS3). APS1 (Mw = 13.4 KDa) and APS2 (Mw = 11.2 KDa) were composed of rhamnose, arabinose, mannose and galactose with different molar ratio, APS3 (Mw = 18.6 KDa) was composed of rhamnose, arabinose, fructose, mannose and galactose. All APS1-3 contained 1 â†’ 3 : 1 â†’ 6 : 1 â†’ 4 : 1 â†’ 2 glycosidic bonds in a ratio of 0.74:0.09:0.05:0.12, 0.34:0.20:0.36:0.10 and 0.63:0.17:0.06:0.14, respectively. The selenium content of Se-APS2 (Mw = 9.0 KDa) and Se-APS3 (Mw = 10.2 KDa) were 1.05 and 2.57 µg/mg, respectively. Their surface morphology and thermal stability were determined by scanning electron microscope (SEM) and thermal analysis (TGA), respectively. Further, the antioxidant and neuroprotective activities of the three natural polysaccharides and two Se-polysaccharides were studied. Interestingly, Se-polysaccharides not only exhibited higher antioxidant activity, but also higher neuroprotective activity compared to natural polysaccharides.

Network pharmacology and RNA sequencing studies on triterpenoid saponins from Bupleurum chinense for the treatment of breast cancer.

Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. Bupleurum chinense DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both in vitro and in vivo experiments. Saikosaponin compounds are the characteristic constituent of B. chinense, which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of B. chinense. In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3'',6''-O-diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6''-O-acetylsaikosaponin-b1 (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of B. chinense against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, etc. More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.

Cluster Synchronization of Coupled Genetic Regulatory Networks With Delays via Aperiodically Adaptive Intermittent Control.

In this paper, we study the cluster synchronization of coupled genetic regulatory networks with time-varying delays via aperiodically adaptive intermittent control on some nodes. The network is intermittently coupled and the intra-cluster coupling strength is adaptively adjusted. The graph of the coupling topology of each cluster is only required to have a directed spanning tree. Two cases of delays are considered. In the first case, by using the switching Lyapunov-based function and Razumikhin-type technique, the cluster synchronization criterion is presented which indicates that the cluster synchronization is realized via the aperiodically adaptive intermittent control. The second case is investigated by using the switching Lyapunov functional. Both the cluster synchronization criteria are established by the Linear Matrix Inequalities (LMIs), the lower bound of the aperiodical time span, and the maximum uncontrolled ratio. It is shown that the results are applicable to both the situations that the upper bound of the delay is larger and smaller than the lower bound of the aperiodical coupling and control width. Numerical simulations are carried out to illustrate the theoretical results.

Common carotid artery dissection caused by radiotherapy: A case report.

In the present study, a case of acute cerebral infarction with radiation-induced carotid artery dissection is reported. Carotid artery dissection is generally asymptomatic at the early stages. Due to the non-specific clinical manifestations of carotid artery dissection, a detailed inquiry of the past history of a patient has a critical role in making a diagnosis of radiation-induced common carotid artery dissection. Onset of acute ischemic stroke is the predominant manifestation, and for patients with a history of head-and-neck radiotherapy, dissection should be considered. The condition may progress rapidly, and result in a poor prognosis. Therefore, a correct early diagnosis and initiation of appropriate therapy may lead to rapid recovery, and influence the overall prognosis.