Network pharmacology- and molecular docking-based analyses of the antihypertensive mechanism of Ilex kudingcha

Herein, network pharmacology was used to identify the active components in Ilex kudingcha and common hypertension-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and molecular docking was performed to verify molecular dynamic simulations. Six active components in Ilex kudingcha were identified; furthermore, 123 target genes common to hypertension were identified. Topological analysis revealed the strongly associated proteins, with RELA, AKT1, JUN, TP53, TNF, and MAPK1 being the predicted targets of the studied traditional Chinese medicine. In addition, GO enrichment analysis revealed significant enrichment of biological processes such as oxidative stress, epithelial cell proliferation, cellular response to chemical stress, response to xenobiotic stimulus, and wound healing. Furthermore, KEGG enrichment analysis revealed that the genes were particularly enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, and other pathways. Molecular docking revealed that the key components in Ilex kudingcha exhibited good binding potential to the target genes RELA, AKT1, JUN, TP53, TNF, and IL-6. Our study results suggest that Ilex kudingcha plays a role in hypertension treatment by exerting hypolipidemic, anti-inflammatory, and antioxidant effects and inhibiting the transcription of atherosclerosis-related genes

Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants

CcGSDMEa functions the pore-formation in cytomembrane and the regulation on the secretion of IL-lβ in common carp (Cyprinus carpio haematopterus)

GSDME is the only direct executor of caspase-dependent pyroptosis in both canonical and non-canonical inflammasomes known to date in fish, and plays an important role in anti-bacterial infection and inflammatory response. In order to determine the regulation of GSDMEa on antibacterial infection in innate immune response, the CcGSDMEa gene in common carp (Cyprinus carpio haematopterus) was first identified and characterized, and then its function related to immune defense was investigated. Our results showed that the expressions of CcGSDMEa at the mRNA and protein levels were both significantly increased after Aeromonas hydrophila intraperitoneal infection at the early stage than that in the control group. We found that CcGSDMEa could be cleaved by inflammatory caspase (CcCaspase-1b) and apoptotic caspases (CcCaspase-3a/b and CcCaspase-7a/b). Interestingly, only the CcGSDMEa-NT (1-252 aa) displayed bactericidal activity to Escherichia coli and could punch holes in the membrane of HEK293T cells, whereas CcGSDMEa-FL (1-532 aa) and CcGSDMEa-CT (257-532 aa) showed no above activity and pore-forming ability. Overexpression of CcGSDMEa increased the secretion of CcIL-1β and the release of LDH, and could reduce the A. hydrophila burdens in fish. On the contrary, knockdown of CcGSDMEa reduced the secretion of CcIL-1β and the release of LDH, and could increase the A. hydrophila burdens in fish. Taken together, the elevated expression of CcGSDMEa was a positive immune response to A. hydrophila challenge in fish. CcGSDMEa could perform the pore-formation in cell membrane and the regulation on the secretion of IL-lβ, and further regulate the bacterial clearance in vivo. These results suggested that CcGSDMEa played an important role in immune defense against A. hydrophila and could provide a new insight into understanding the immune mechanism to resist pathogen invasion in teleost

Genome of Crucihimalaya himalaica, a close relative of Arabidopsis, shows ecological adaptation to high altitude

Crucihimalaya himalaica is a close relative of Arabidopsis with typical Qinghai–Tibet Plateau (QTP) distribution. Here, by combining short- and long-read sequencing technologies, we provide a de novo genome sequence of C. himalaica. Our results suggest that the quick uplifting of the QTP coincided with the expansion of repeat elements. Gene families showing dramatic contractions and expansions, as well as genes showing clear signs of natural selection, were likely responsible for C. himalaica’s specific adaptation to the harsh environment of the QTP. We also show that the transition to self-pollination of C. himalaica might have enabled its occupation of the QTP. This study provides insights into how plants might adapt to extreme environmental conditions

Effect of Cationic/Anionic Diffusion Dominated Passive Film Growth on Tribocorrosion

Tribocorrosion behaviours of nickel (Ni) and niobium (Nb) in sodium sulfate (Na2SO4) solution under potentiodynamic and potentiostatic conditions were studied. Under the potentiodynamic condition, the passivation was early broken, accompanied by a sharp increase in frictional coefficient on Nb. The current was more fluctuant, and larger material loss appeared at the higher potential in the potentiostatic condition. However, these phenomena did not occur for Ni, and it even showed lower material loss at the higher potential in the potentiostatic tribocorrosion test. The differences in tribocorrosion behaviour had a close relationship to the passive film growth mechanism, which decided the passive film/metal interface structure. Nb with anionic diffusion dominated mechanism in passive growth would cause the accumulation of oxygen vacancies at the passive film/metal interface. This may weaken the adhesion between the metal and the passive film. However, with the cationic diffusion dominated passive film growth on Ni, cation vacancies concentrated at the passive film/tribo-film interface, and this did not affect the adhesion between metal and passive film. Ni or other passive elements with the cationic diffusion-dominated mechanism in passive film growth were recommended as the alloying element for improving the tribocorrosion resistance of alloys

Tribocorrosion investigation of 316L stainless steel: the synergistic effect between chloride ion and sulfate ion

Tribocorrosion is a failure phenomenon which involves synergistic effect of electrochemical corrosion and mechanical wear. It usually results into early failure of mechanical components than simple wear and corrosion. Chloride (Cl ^− ) and sulfate ions $\left({{\rm{SO}}}_{4}^{{\rm{2}}-}\right)$ are often found together in corrosive media. In this study, the synergistic effect of Cl ^− and ${{\rm{SO}}}_{4}^{{\rm{2}}-}$ on tribocorrosion of 316L stainless steel was studied by changing the ratio of ${{\rm{SO}}}_{4}^{{\rm{2}}-}$ /Cl ^− in corrosive solution from 0.31 M : 0 to 0 : 0.62 M. The stainless steel was worn against with a ZrO _2 sphere. The coefficient of friction (COF), material loss volume, surface micro-topographies and surface chemical composition in different solutions were compared to explore the synergism between ${{\rm{SO}}}_{4}^{{\rm{2}}-}$ and Cl ^− . The results indicated that the mix of Cl ^− and ${{\rm{SO}}}_{4}^{{\rm{2}}-}$ reduced material loss volume by a quarter when compared with that in pure Na _2 SO _4 or NaCl solution. More than half of material loss was caused by the synergism between wear and corrosion in mixing solutions. The synergistic effect between ${{\rm{SO}}}_{4}^{{\rm{2}}-}$ and Cl ^− could promote the transmission of metal into oxides. This had two effects on tribocorrosion. First, the existence of oxides would cause abrasion which accelerated wear-affected corrosion and enhanced mechanical wear (corrosion-affected wear). On the other side, the transmission of metal into oxides benefited for the formation of tribo-film. The flexible stainless steel needed to coordinate deformation with the tribo-film which had relatively low deformability. This aggravated deformation of stainless steel and promoted surface work-hardening effect. It was helpful for stainless steel to resist wear, thus, the corrosion-affected wear was decreased

Effect of Cationic/Anionic Diffusion Dominated Passive Film Growth on Tribocorrosion

Tribocorrosion behaviours of nickel (Ni) and niobium (Nb) in sodium sulfate (Na2SO4) solution under potentiodynamic and potentiostatic conditions were studied. Under the potentiodynamic condition, the passivation was early broken, accompanied by a sharp increase in frictional coefficient on Nb. The current was more fluctuant, and larger material loss appeared at the higher potential in the potentiostatic condition. However, these phenomena did not occur for Ni, and it even showed lower material loss at the higher potential in the potentiostatic tribocorrosion test. The differences in tribocorrosion behaviour had a close relationship to the passive film growth mechanism, which decided the passive film/metal interface structure. Nb with anionic diffusion dominated mechanism in passive growth would cause the accumulation of oxygen vacancies at the passive film/metal interface. This may weaken the adhesion between the metal and the passive film. However, with the cationic diffusion dominated passive film growth on Ni, cation vacancies concentrated at the passive film/tribo-film interface, and this did not affect the adhesion between metal and passive film. Ni or other passive elements with the cationic diffusion-dominated mechanism in passive film growth were recommended as the alloying element for improving the tribocorrosion resistance of alloys

Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome

Introduction Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of signaling pathways is etiological in cancer cells. Thus, we speculated that the pathway activity of neuroblastoma contains more prognostic information and therapeutic targets. Methods Using a footprint-based method, we calculated the activity of fourteen pathways in neuroblastoma. Through stepwise Cox regression analyses, we established a three-gene prognostic signature whose predictive performance was evaluated by external validation. Combining a single-cell sequencing dataset, the most active pathways in high-risk neuroblastoma were found. Results We found that several pathway activities were correlated with neuroblastoma outcomes. We built a three-gene model comprising DLK1, FLT3, and NTRK1, which exhibited superior internal and external performances. We created a nomogram that combines clinical characteristics to aid in the selection and visualization of high-risk neuroblastoma patients. Furthermore, by integrating a single-cell sequencing dataset, we found that estrogen and MAPK were the most active pathways in high-risk neuroblastoma. Conclusion Our findings suggest that pathway-related therapies may hold promise for the treatment of high-risk neuroblastoma

Development of Strong and Tough β-TCP/PCL Composite Scaffolds with Interconnected Porosity by Digital Light Processing and Partial Infiltration

Strong and tough β-TCP/PCL composite scaffolds with interconnected porosity were developed by combining digital light processing and vacuum infiltration. The composite scaffolds were comprised of pure β-TCP, β-TCP matrix composite and PCL matrix composite. The porous β-TCP/PCL composite scaffolds showed remarkable mechanical advantages compared with ceramic scaffolds with the same macroscopic pore structure (dense scaffolds). The composite scaffolds exhibited a significant increase in strain energy density and fracture energy density, though with similar compressive and flexural strengths. Moreover, the composite scaffolds had a much higher Weibull modulus and longer fatigue life than the dense scaffolds. It was revealed that the composite scaffolds with interconnected porosity possess comprehensive mechanical properties (high strength, excellent toughness, significant reliability and fatigue resistance), which suggests that they could replace the pure ceramic scaffolds for degradable bone substitutes, especially in complex stress environments

Control effects of different herbicides on Spartina alterniflora

As an invasive species, Spartina alterniflora has caused serious harm to many coastal wetland ecosystems, and its prevention and control have become the top priority of coastal wetland protection. To explore the difference in the control effects of different herbicides on S. alterniflora and optimize the chemical control technology, four experiments were carried out in this study, namely, different herbicides, different doses, different dilution ratios, and mowing + herbicide. The results showed that (1) 75 days after the application of herbicide, the control effects of high doses of glyphosate (8.0 kg ha−1), cyhalofop-butyl (0.8 kg ha−1) or imazameth (0.4 kg ha−1) were only 25%-38%, and the control effects of lower doses were worse; (2) Haloxyfop-R-methyl could permanently kill S. alterniflora. Applying 0.30 kg ha−1 and 0.45 kg ha−1 of haloxyfop-R-methyl in June, the control efficacy was >95% in the first year and 84%–99% in the third year. In addition, there was no significant difference in weed control effect when the same dose of Haloxyfop-R-methyl was sprayed twice on June 8 and July 28 or once on June 8; (3) The mixed application of two of the four herbicides, namely, glyphosate, cyhalofop-butyl, imazameth and Haloxyfop-R-methyl, did not improve the control effect on S. alterniflora; (4) When the herbicide stock solution was diluted 58–461 times with water, Haloxyfop-R-methyl had a very good control effect on S. alterniflora; (5) Spraying Haloxyfop-R-methyl immediately after mowing could not effectively control S. alterniflora, and the regeneration of S. alterniflora was serious in the second year; and (6) Compared with the S. alterniflora area without herbicide application, there was no significant change in the species and quantity of macrobenthos one month after herbicide application. However, in the third year after herbicide application, S. alterniflora near the study area failed to invade the area where the herbicide was applied, indicating that residual toxins were likely to remain in the soil. In summary, haloxyfop-R-methyl can effectively control S. alterniflora, and haloxyfop-R-methyl application can be used as an optional method to eliminate newly invaded small areas of S. alterniflora, but it is not recommended to use herbicides in large areas. In the future, it is necessary to strengthen the monitoring of herbicide residues in soil and water and comprehensively assess the impact of herbicides on the environment and organisms to provide sufficient technical support for the use of herbicides to control S. alterniflora