Low expression of GRM4 is associated with poor prognosis and tumor immune infiltration in glioma.

INTRODUCTION: The metabotropic glutamate receptor 4 (mGlu4, GRM4) exhibits significant expression within the central nervous system (CNS) and has been implicated to be correlated with a poor prognosis. OBJECTIVE: This study was aimed to elucidate the relationship between the expression profile of GRM4 and the prognosis of glioma patients. METHODS: RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and China Glioma Genome Atlas (CGGA) repositories were used to evaluate the potential relationship. The value of clinical prognostic about GRM4 was assessed using clinical survival data from CGGA and TCGA. The GEPIA database was used to select genes like GRM4. PPI network was constructed by the database of (STRING), GO and KEGG analyses were performed. TargetScan, TarBase, miRDB, and starBase were used to explore miRNAs that could regulate GRM4 expression. EWAS Data Hub, MethSurv, and MEXPRESS were used for the analysis and relationship between DNA methylation and GRM4 expression and prognosis in glioma. TIMER2.0 and CAMOIP databases were used to assess the association between immune cell infiltration and GRM4. Human GBM cell lines were used to validate the function of GRM4. RESULTS: Our study shows that GRM4 is under expressed among gliomas and accompanied by poorer OS. Multivariate analysis showed that low mRNA expression of GRM4 was an independent factor of prognostic for shorter OS in all glioma patients. MiR-1262 affects the malignant phenotype of gliomas through GRM4. Methylation of DNA plays an important role in the instruction of GRM4 expression, the methylation level of GRM4 in glioma tissue is higher in comparison to normal tissue, and the higher methylation level was accompanied with the worse prognosis. Further analysis showed that GRM4 mRNA expression in GBM linked negatively with common lymphoid progenitor, Macrophage M1, Macrophage, and T cell CD4+ Th2, but not with the tumor purity. Overexpression of GRM4 prevents the migration of human GBM cell lines in vitro. CONCLUSION: GRM4 may have a substantial impact on the infiltration of immune cells and serve as a valuable prognostic biomarker in gliomas.

Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α+ B cells through BAFF/BTK/NF-κB signalling pathway in the pathogenesis of collagen-induced arthritis mice.

Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. We detected the frequencies and counts of PMN-MDSCs, TNF-α+ B cells and Ki67+ B cells in spleen and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, and so on. The mechanism of BAFF regulating B cells was verified through western blot and flow cytometry. PMN-MDSCs accumulated in the spleen and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF-α secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF-α expression, proliferation and apoptosis of B cells in vitro. What's more, BAFF promoted phosphorylation of BTK/NF-κB signalling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF-α expression of B cells. Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF-α expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF-α expression through BTK/NF-κB signalling pathway, which demonstrated a novel pathogenesis of PMN-MDSCs in CIA.

Total glucosides of paeony alleviates experimental Sjögren's syndrome through inhibiting NLRP3 inflammasome activation of submandibular gland cells.

OBJECTIVES: The mechanisms by which total glucosides of paeony (TGP) mitigates Sjögren's syndrome (SS) remains elusive. In the present study, we aim to explore the relationship between the therapeutic effects of TGP in the treatment of SS and NLRP3 inflammasome activation in submandibular gland (SG) cells. METHODS: Female non-obese diabetic (NOD) mice were selected as the model of SS. The mice were divided into PBS and TGP treatment group. For treatment, TGP (400mg·kg-1) was administered intragastrically every day for 4 weeks. The SS-like symptoms and pathological changes of the SG of mice were compared between the PBS and TGP group. The activation of NLRP3 inflammasome in SG was detected by RT-qPCR, immunohistochemistry and western blot. The SG cells stimulated by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activation of NLRP3 inflammasome were treated with or without TGP. Then, NLRP3 inflammasome activation was assessed. The IL-1ß and IL-18 in homogenate of SG, serum and supernatant were detected by ELISA. RESULTS: Compared with balb/c mice, NOD mice showed SS-like symptoms and lymphocyte infiltration in SG, and the expression of NLRP3 inflammasome in SG was significantly increased. The SS-like symptoms were alleviated, and lymphocyte infiltration in SG was reduced, and the level of NLRP3 inflammasome in SG mice was decreased after TGP treatment. TGP also significantly inhibit the activation of NLRP3 inflammasome of SG cells in vitro. CONCLUSIONS: Collectively, our results indicated that TGP alleviates SS through inhibition of the activation of NLRP3 inflammasome of SG. These findings clarified the mechanism underlying the therapeutic effects of TGP on SS, and provided new evidence for the further application of TGP in the treatment of SS.

Insight into the Molecular Mechanism for Enhanced Longevity of Supramolecular Vesicular Photocatalysts.

Supramolecular self-assembly is a promising strategy for stabilizing the photo-sensitive components in photocatalysis. However, the underlying correlation between the enhanced photostability and supramolecular structure at the molecular level has not yet been fully understood. Herein, we develop a biomimetic vesicular membrane-based polyporphyrin photocatalyst exhibiting excellent photocatalytic stability with at least activity time of 240 h in hydrogen generation. Time-domain ab initio modelling together with transient absorption spectroscopy, visual frontier orbitals and Gibbs free energy calculation disclose that the ordered aggregation of porphyrin units in the vesicle membrane facilitates "hot" electron relaxation and the rapid dissipation of photo-generated charges, thereby contributing to the longevity. This work deepens the molecular-level understanding on photostability and photocatalytic mechanism of supramolecular photocatalysts.

Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation.

BACKGROUND: Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun". METHODS: First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins. RESULTS: Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group. CONCLUSIONS: Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.

Three-Dimensional Graphene Networks with Abundant Sharp Edge Sites for Efficient Electrocatalytic Hydrogen Evolution.

To achieve sustainable production of hydrogen (H2 ) through water splitting, establishing efficient and earth-abundant electrocatalysts is of great necessity. Morphology engineering of graphene is now shown to modulate the electronic structure of carbon skeleton and in turn endow it with excellent ability of proton reduction. Three-dimensional (3D) graphene networks with a high density of sharp edge sites are synthesized. Electrocatalytic measurements indicate that the obtained 3D graphene networks can electrocatalyze H2 evolution with an extremely low onset potential of about 18 mV in 0.5 m H2 SO4 solution, together with good stability. A combination of control experiments and density functional theory (DFT) investigations indicates that the exceptional H2 evolution performance is attributed to the abundant sharp edge sites of the advanced frameworks, which are responsible for promoting the adsorption and reduction of protons.

Eosin†Y as a Direct Hydrogen-Atom Transfer Photocatalyst for the Functionalization of C-H Bonds.

Eosin Y, a well-known economical alternative to metal catalysts in visible-light-driven single-electron transfer-based organic transformations, can behave as an effective direct hydrogen-atom transfer catalyst for C-H activation. Using the alkylation of C-H bonds with electron-deficient alkenes as a model study revealed an extremely broad substrate scope, enabling easy access to a variety of important synthons. This eosin Y-based photocatalytic hydrogen-atom transfer strategy is promising for diverse functionalization of a wide range of native C-H bonds in a green and sustainable manner.

Self-Assembled Framework Enhances Electronic Communication of Ultrasmall-Sized Nanoparticles for Exceptional Solar Hydrogen Evolution.

Colloidal quantum dots (QDs) have demonstrated great promise in artificial photosynthesis. However, the ultrasmall size hinders its controllable and effective interaction with cocatalysts. To improve the poor interparticle electronic communication between free QD and cocatalyst, we design here a self-assembled architecture of nanoparticles, QDs and Pt nanoparticles, simply jointed together by molecular polyacrylate to greatly enhance the rate and efficiency of interfacial electron transfer (ET). The enhanced interparticle electronic communication is confirmed by femtosecond transient absorption spectroscopy and X-ray transient absorption. Taking advantage of the enhanced interparticle ET with a time scale of ∼65 ps, 5.0 mL of assembled CdSe/CdS QDs/cocatalysts solution produces 94 ± 1.5 mL (4183 ± 67 µmol) of molecular H2 in 8 h, giving rise to an internal quantum yield of ∼65% in the first 30 min and a total turnover number of >1.64â€¯× 107 per Pt nanoparticle. This study demonstrates that self-assembly is a promising way to improve the sluggish kinetics of the interparticle ET process, which is the key step for advanced H2 photosynthesis.

Torque-speed relationship of the flagellar motor with dual-stator systems in Pseudomonas aeruginosa.

The single polar flagellar motor in Pseudomonas aeruginosa is equipped with two stator systems, MotAB and MotCD, both driven by H+ ions. The torque-speed relationship for flagellar motors with two stator systems has not been explored previously. In this study, we developed a method that utilizes optical trapping and fluorescence labeling to measure the torque-speed relationships for the wild-type P. aeruginosa motor with dual stators and mutant strains with a single stator system, revealing surprising differences in them. Moreover, we found that the MotAB stators exhibit slip-bond behavior in load dependence, contrasting with the catch-bond behavior of the MotCD stators and Escherichia coli stators. Further examination of the solvent isotope and pH effects on the torque-speed relationships of these stator systems provided additional insights into their dynamics. Interestingly, we discovered that the torque of the wild-type motor is similar to the combined torque of motors with MotAB or MotCD stators, indicating an additive contribution from the two stator types in the wild-type motors. These findings underscore the enhanced adaptability of P. aeruginosa to a wide range of external environments with varying load conditions.IMPORTANCEWe developed a novel method to measure the flagellar motor torque-speed relationship by trapping a swimming bacterium using optical tweezers. Using the P. aeruginosa flagellar motor as a model system to investigate motor dynamics with dual stator types, we measured the torque-speed relationships for wild-type motors with dual stator types and mutants with a single type. We found drastic differences that stem from the varying load dependencies of stator stability. These variations enable bacteria to rapidly adjust their stator composition in response to external load conditions. Interestingly, we observed that the torque of the wild-type motor is akin to the cumulative torque of motors with either stator type, indicating an additive contribution from the two stator types in wild-type motors. The methodology we established here can be readily employed to study motor dynamics in other flagellated bacteria.

GPR124 induces NLRP3 inflammasome-mediated pyroptosis in endothelial cells during ischemic injury.

OBJECTIVE: G protein-coupled receptor 124 (GPR124) regulates central nervous system angiogenesis and blood-brain barrier (BBB) integrity, and its deficiency aggravates BBB breakdown and hemorrhagic transformation in ischemic mice. However, excessive GPR124 expression promotes inflammation in atherosclerotic mice. In this study, we aimed to elucidate the role of GPR124 in hypoxia/ischemia-induced cerebrovascular endothelial cell injury. METHODS: bEnd.3 cells were exposed to oxygen-glucose deprivation (OGD), and time-dependent changes in GPR124 mRNA and protein expression were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The effects of GPR124 overexpression or knockdown on the expression of pyroptosis-related genes were assessed at the mRNA and protein levels. Tadehaginoside (TA) was screened as a potential small molecule targeting GPR124, and its effects on pyroptosis-related signaling pathways were investigated. Finally, the therapeutic efficacy of TA was evaluated using a rat model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R). RESULTS: During OGD, the expression of GPR124 initially increased and then decreased over time, with the highest levels observed 1 h after OGD. The overexpression of GPR124 enhanced the OGD-induced expression of NLRP3, Caspase-1, and Gasdermin D (GSDMD) in bEnd.3 cells, whereas GPR124 knockdown reduced pyroptosis. Additionally, TA exhibited a high targeting ability to GPR124, significantly inhibiting its function and expression and suppressing the expression of pyroptosis-related proteins during OGD. Furthermore, TA treatment significantly reduced the cerebral infarct volume and pyroptotic signaling in tMCAO/R rats. CONCLUSIONS: Our findings suggest that GPR124 mediates pyroptotic signaling in endothelial cells during the early stages of hypoxia/ischemia, thereby exacerbating ischemic injury.

Furoic acid-mediated konjac glucomannan/flaxseed gum based green biodegradable antibacterial film for Shine-Muscat grape preservation.

Considering the growing threats to the environment and human health, such as plastic pollution and food spoilage, the development of naturally antibacterial food packaging materials with biodegradable capabilities has recently attracted considerable attention. This work applies the concept of green environmental protection to packaging technology, and a new type of green edible antibacterial packaging film was developed. The basic idea is to incorporate furoic acid (FA), which possesses excellent antibacterial activity, into the flaxseed gum and konjac glucomannan matrix (FK) as a filler to obtain a series of FK-FA bioactive films. This incorporation simultaneously improves the hydrophobicity and UV-barrier ability by 12.28 % and 42.87 %, respectively. Meanwhile, the diameters of the antibacterial zone of the FK-FA0.4% films (composite FK films containing 0.4 % FA) against E. coli and S. aureus increased to 38.98 mm and 36.29 mm from 24.00 mm of pure FK film, respectively. As a consequence, the grape sample sealed with FK-FA0.4% film remained edible on the 18th day of storage, while those packaged with commercial PE film and pure FK were seriously rotted and lost edible value on the 12th day, further confirming the enhanced preservation capacity. Finally, the as-prepared films were established to be biodegradable and were almost completely degraded within 25 days under simulated environmental conditions. Overall, these promising results show the potential of FK-FA films for replacing plastic packaging materials as eco-friendly edible films with prolonged shelf life for active packaging.

Occurrence, formation mechanism, detection methods, and removal approaches for chloropropanols and their esters in food: An updated systematic review.

Chloropropanols, one of the major contaminants in food, and the corresponding esters or glycidyl esters (GEs) are of great concern in terms of product safety due to their potential carcinogenicity. During heat processing, glycerol, allyl alcohol, chloropropanol esters, sucralose, and carbohydrate in mixed foodstuffs are probable precursors of chloropropanol. The standard analytical techniques for chloropropanols or their esters are GC-MS or LC-MS following sample derivatization pretreatment. By comparing modern data against that five-year-old before, it appears that the levels of chloropropanols and their esters/GEs in food products have somewhat decreased. 3-MCPD esters or GEs may yet exceed the permitted intake set, however, especially in newborn formula which requires particularly stringent regulatory measures. Citespace (6.1. R2) software was employed in this study to examine the research focii of chloropropanols and their corresponding esters/GEs in the literature.

The overexpression and clinical significance of TBX15 in human gliomas.

T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.

The pan-genome and local adaptation of Arabidopsis thaliana.

Arabidopsis thaliana serves as a model species for investigating various aspects of plant biology. However, the contribution of genomic structural variations (SVs) and their associate genes to the local adaptation of this widely distribute species remains unclear. Here, we de novo assemble chromosome-level genomes of 32 A. thaliana ecotypes and determine that variable genes expand the gene pool in different ecotypes and thus assist local adaptation. We develop a graph-based pan-genome and identify 61,332 SVs that overlap with 18,883 genes, some of which are highly involved in ecological adaptation of this species. For instance, we observe a specific 332 bp insertion in the promoter region of the HPCA1 gene in the Tibet-0 ecotype that enhances gene expression, thereby promotes adaptation to alpine environments. These findings augment our understanding of the molecular mechanisms underlying the local adaptation of A. thaliana across diverse habitats.

SHIP1 is required for the formation of neutrophil extracellular traps in rheumatoid arthritis.

Aberrant neutrophil extracellular traps (NETs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, the specific pathway leading to NET formation in RA is poorly understood. Therefore, therapies targeting NETs are not available in RA. In this study, we demonstrated Src homology 2 domain-containing inositol phosphatase-1 (SHIP1) function as a hub to regulate NETosis through SHIP1/ p38 MAPK/TNF-α pathway both in vitro and ex vivo and inhibiting SHIP1 expression ameliorated RA symptoms in vivo. Neutrophils from RA patients showed enhanced NETosis as well as increased SHIP1, p38 mitogen-activated protein kinase (MAPK) family expression and tumor necrosis factor-α (TNF-α) expression. Inhibiting SHIP1 in neutrophils using small molecules counteracted the above-mentioned dysregulations and resulted in decrease in NETosis, p38 expression and TNF-α concentration. Consistent with this, SHIP1 agonist led to upregulated p38MAPK and NET formation. Moreover, inhibiting SHIP1 in vivo led to decreased NETosis and showed beneficial therapeutic effects in Collagen-induced arthritis (CIA) mice. Taken together, these results indicated that activation of SHIP1/MAPK/TNF-α pathway was necessary for upregulated NETosis in RA, which provided evidence for targeting SHIP1 in RA treatment.

Trust of Information during the Dissemination of Popular Science Web Videos in the New Media Era.

Web videos have gradually replaced text, voice, pictures, and other information carriers to become an important way of information dissemination in the new media era. As digital technology brings a new dissemination ecology, the original dissemination trust theory and its framework are facing the crisis of explanatory power failure. This paper considers the popular science web video as an object of study. It analyses and interprets the development of popular science web videos based on the evolution of dissemination form and the basic principle of social trust, from perspectives such as mediology, informatics, and sociology. To maintain or improve the trust relationship in web videos, it's necessary to find positive incentive and reverse punishment, and establish a trust certification and regulation mechanism. In this way, active dissemination and sharing of information can be promoted for a more vigorous society and culture. Moreover, this paper explores a new way of web video development from the perspective of trust.

One-Step Scalable Fabrication of Highly Selective Monolithic Zeolite MFI Membranes for Efficient Butane Isomer Separation.

The reproducible fabrication of large-area zeolite membranes for gas separation is still a great challenge. We report the scalable fabrication of high-performance zeolite MFI membranes by single-step secondary growth on the 19-channel alumina monoliths for the first time. The packing density and mechanical strength of the monolithic membranes are much higher for these than for tubular ones. Separation performance of the monolithic membranes toward the butane isomer mixture was comparably evaluated using the vacuum and Wicke-Kallenbach modes. The n-butane permeances and n-butane/i-butane separation factors for the three membranes with an effective area of ∼84 cm2 were >1.0 × 10-7 mol (m2 s Pa)-1 and >50 at 343 K for an equimolar n-butane/i-butane mixture, respectively. We succeeded in scaling up the membrane synthesis with the largest area of 270 cm2 to date which has 1.3 times the area of an industrial 1 m long tubular membrane. Monolith supported zeolite MFI membranes show great potential for industrial n-butane/i-butane separation.

A Network Pharmacology Study to Explore the Underlying Mechanism of Safflower (Carthamus tinctorius L.) in the Treatment of Coronary Heart Disease.

Safflower has long been used to treat coronary heart disease (CHD). However, the underlying mechanism remains unclear. The goal of this study was to predict the therapeutic effect of safflower against CHD using a network pharmacology and to explore the underlying pharmacological mechanisms. Firstly, we obtained relative compounds of safflower based on the TCMSP database. The TCMSP and PubChem databases were used to predict targets of these active compounds. Then, we built CHD-related targets by the DisGeNET database. The protein-protein interaction (PPI) network graph of overlapping genes was obtained after supplying the common targets of safflower and CHD into the STRING database. The PPI network was then used to determine the top ten most significant hub genes. Furthermore, the DAVID database was utilized for the enrichment analysis on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To validate these results, a cell model of CHD was established in EAhy926 cells using oxidized low-density lipoprotein (ox-LDL). Safflower was determined to have 189 active compounds. The TCMSP and PubChem databases were used to predict 573 targets of these active compounds. The DisGeNET database was used to identify 1576 genes involved in the progression of CHD. The top ten hub genes were ALB, IL6, IL1B, VEGFA, STAT3, MMP9, TLR4, CCL2, CXCL8, and IL10. GO functional enrichment analysis yielded 92 entries for biological process (BP), 47 entries for cellular component (CC), 31 entries for molecular function (MF), and 20 signaling pathways, which were obtained from KEGG pathway enrichment screening. Based on these findings, the FoxO signaling pathway is critical in the treatment of CHD by safflower. The in vitro results showed that safflower had an ameliorating effect on ox-LDL-induced apoptosis and mitochondrial membrane potential. The western blot results showed that safflower decreased Bax expression and acetylation of FoxO1 proteins while increasing the expression of Bcl-2 and SIRT1 proteins. Safflower can be used in multiple pathways during CHD treatment and can exert anti-apoptotic effects by regulating the expression of Bax, Bcl-2, and SIRT1/FoxO1 signaling pathway-related proteins.

Pervasive hybridization during evolutionary radiation of Rhododendron subgenus Hymenanthes in mountains of southwest China.

Radiations are especially important for generating species biodiversity in mountainous ecosystems. The contribution of hybridization to such radiations has rarely been examined. Here, we use extensive genomic data to test whether hybridization was involved in evolutionary radiation within Rhododendron subgenus Hymenanthes, whose members show strong geographic isolation in the mountains of southwest China. We sequenced genomes for 143 species of this subgenus and 93 species of four other subgenera, and found that Hymenanthes was monophyletic and radiated during the late Oligocene to middle Miocene. Widespread hybridization events were inferred within and between the identified clades and subclades. This suggests that hybridization occurred both early and late during diversification of subgenus Hymenanthes, although the extent to which hybridization, speciation through mixing-isolation-mixing or hybrid speciation, accelerated the diversification needs further exploration. Cycles of isolation and contact in such and other montane ecosystems may have together promoted species radiation through hybridization between diverging populations and species. Similar radiation processes may apply to other montane floras in this region and elsewhere.

Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice.

BACKGROUND: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. METHODS: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 µl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. RESULTS: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1ß and TNF-α. In addition, NLRP3, Caspase-1 and IL-1ß, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. CONCLUSIONS: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.