Evolutionary genetics of pulmonary anatomical adaptations in deep-diving cetaceans.

BACKGROUND: Cetaceans, having experienced prolonged adaptation to aquatic environments, have undergone evolutionary changes in their respiratory systems. This process of evolution has resulted in the emergence of distinctive phenotypic traits, notably the abundance of elastic fibers and thickened alveolar walls in their lungs, which may facilitate alveolar collapse during diving. This structure helps selective exchange of oxygen and carbon dioxide, while minimizing nitrogen exchange, thereby reducing the risk of DCS. Nevertheless, the scientific inquiry into the mechanisms through which these unique phenotypic characteristics govern the diving behavior of marine mammals, including cetaceans, remains unresolved. RESULTS: This study entails an evolutionary analysis of 42 genes associated with pulmonary fibrosis across 45 mammalian species. Twenty-one genes in cetaceans exhibited accelerated evolution, featuring specific amino acid substitutions in 14 of them. Primarily linked to the development of the respiratory system and lung morphological construction, these genes play a crucial role. Moreover, among marine mammals, we identified eight genes undergoing positive selection, and the evolutionary rates of three genes significantly correlated with diving depth. Specifically, the SFTPC gene exhibited convergent amino acid substitutions. Through in vitro cellular experiments, we illustrated that convergent amino acid site mutations in SFTPC contribute positively to pulmonary fibrosis in marine mammals, and the presence of this phenotype can induce deep alveolar collapse during diving, thereby reducing the risk of DCS during diving. CONCLUSIONS: The study unveils pivotal genetic signals in cetaceans and other marine mammals, arising through evolution. These genetic signals may influence lung characteristics in marine mammals and have been linked to a reduced risk of developing DCS. Moreover, the research serves as a valuable reference for delving deeper into human diving physiology.

Baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating ATP-sensitive potassium channels.

Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.

Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale.

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

Unravelling the genetic diversity and population structure of common walnut in the Iranian Plateau.

BACKGROUND: Common walnut (Juglans regia L.) has a long cultivation history, given its highly valuable wood and rich nutritious nuts. The Iranian Plateau has been considered as one of the last glaciation refugia and a centre of origin and domestication for the common walnut. However, a prerequisite to conserve or utilize the genetic resources of J. regia in the plateau is a comprehensive evaluation of the genetic diversity that is conspicuously lacking. In this regard, we used 31 polymorphic simple sequence repeat (SSR) markers to delineate the genetic variation and population structure of 508 J. regia individuals among 27 populations from the Iranian Plateau. RESULTS: The SSR markers expressed a high level of genetic diversity (HO = 0.438, and HE = 0.437). Genetic differentiation among the populations was moderate (FST = 0.124), and genetic variation within the populations (79%) significantly surpassed among populations (21%). The gene flow (Nm = 1.840) may have remarkably influenced the population genetic structure of J. regia, which can be attributed to anthropological activities and wind dispersal of pollen. The STRUCTURE analysis divided the 27 populations into two main clusters. Comparing the neighbor-joining and principal coordinate analysis dendrograms and the Bayesian STRUCTURE analysis revealed the general agreement between the population subdivisions and the genetic relationships among the populations. However, a few geographically close populations dispersed into different clusters. Further, the low genetic diversity of the Sulaymaniyah (SMR) population of Iraq necessitates urgent conservation by propagation and seedling management or tissue culture methods; additionally, we recommend the indispensable preservation of the Gonabad (RGR) and Arak (AKR) populations in Iran. CONCLUSIONS: These results reflected consistent high geographical affinity of the accession across the plateau. Our findings suggest that gene flow is a driving factor influencing the genetic structure of J. regia populations, whereas ecological and geological variables did not act as strong barriers. Moreover, the data reported herein provide new insights into the population structure of J. regia germplasm, which will help conserve genetic resources for the future, hence improving walnut breeding programs' efficiency.

S-nitrosylation of RABG3E positively regulates vesicle trafficking to promote salt tolerance.

Nitric oxide (NO) is a key signaling molecule affecting the response of plants to salt stress; however, the underlying molecular mechanism is poorly understood. In this study, we conducted a phenotype analysis and found that the small GTPase RABG3E (RAB7) promotes salt tolerance in Arabidopsis thaliana. NO promotes the S-nitrosylation of RAB7 at Cys-171, which in turn helps maintain the ion balance in salt-stressed plants. Furthermore, the S-nitrosylation of RAB7 at Cys-171 enhances the enzyme's GTPase activity, thereby promoting vesicle trafficking and increasing its interaction with phosphatidylinositol phosphates-especially phosphatidylinositol-4-phosphate (PI4P). Exogenously applied PI4P increases vesicle trafficking and promotes salt tolerance depending on the S-nitrosylation of RAB7 at Cys-171. These findings illustrate a unique mechanism in salt tolerance, by which NO regulates vesicle trafficking and ion homeostasis through the S-nitrosylation of RAB7 and its interaction with PI4P.

Current knowledge of anthocyanin metabolism in the digestive tract: absorption, distribution, degradation, and interconversion.

Potential roles for anthocyanins in preventing various chronic diseases have been reported. These compounds are highly sensitive to external conditions and are susceptible to degradation, which increases the complexity of their metabolism in vivo. This review discusses anthocyanin metabolism in the digestive tract, phase I and II metabolism, and enterohepatic circulation (EHC), as well as their distribution of anthocyanins in blood, urine, and several organs. In the oral cavity, anthocyanins are partly hydrolyzed by microbiota into aglycones which are then conjugated by glucuronidase. In stomach, anthocyanins are absorbed without deglycosylation via specific transporters, such as sodium-dependent glucose co-transporter 1 and facilitative glucose transporters 1, while in small intestine, they are mainly absorbed as aglycones. High polymeric anthocyanins are easily degraded into low-polymeric forms or smaller phenolic acids by colonic microbiota, which improves their absorption. Anthocyanins and their derivatives are modified by phase I and II metabolic enzymes in cells and are released into the blood via the gastrovascular cavity into EHC. Notably, interconversion can be occurred under the action of enzymes such as catechol-O-methyltransferase. Taking together, differences in anthocyanin absorption, distribution, metabolism, and excretion largely depend on their glycoside and aglycone structures.

Lonicera caerulea (Haskap berries): a review of development traceability, functional value, product development status, future opportunities, and challenges.

Lonicera caerulea is a honeysuckle plant with a long development history. It is defined as a "homology of medicine and food" fruit because it is rich in bioactive substances. By-products (such as pomace, leaves, stems, and flowers), which also have beneficial values, will be produced during processing. Nevertheless, the reuse of derivatives and the further development of new products of Lonicera caerulea are still a challenge. Firstly, this paper traced the development history of Lonicera caerulea and summarized its primary nutrients and bioactive substances, subsequently discussed the research progress and underlying molecular mechanisms of its functional properties, and introduced the application and potential of Lonicera caerulea in the fields of food, health products, cosmetics, medicine, and materials. Finally, this paper put forward the future research direction to promote the development of the Lonicera caerulea industry. To sum up, Lonicera caerulea, as a potential raw material, can be used to produce more functional products. Besides, more in-depth clinical trials are needed to clarify the specific molecular mechanism of the practical components of Lonicera caerulea and improve the rate of development and utilization.HighlightsThe original species of Lonicera caerulea subgroup had appeared on the earth as early as the end of the third century.Lonicera caerulea has been introduced into North America since the 18th century, but the introduction process has not ended until now.Lonicera caerulea widely exists in Eurasia and North America and it has excellent cold tolerance, early maturity and ornamental.The fruits, stems, leaves and flowers of Lonicera caerulea all have bioactive value, but the specific molecular mechanism and utilization need to be improved.Lonicera caerulea has been widely used in food, medicine, health products, cosmetics and materials, but there are still great challenges.

Cyanidin-3-O-glucoside and its phenolic metabolites ameliorate intestinal diseases via modulating intestinal mucosal immune system: potential mechanisms and therapeutic strategies.

The incidence of the intestinal disease is globally increasing, and the intestinal mucosa immune system is an important defense line. A potential environmental cause to regulate gut health is diet. Cyanidin-3-O-glucoside is a natural plant bioactive substance that has shown rising evidence of improving intestinal disease and keeping gut homeostasis. This review summarized the intestinal protective effect of Cyanidin-3-O-glucoside in vivo and in vitro and discussed the potential mechanisms by regulating the intestinal mucosal immune system. Cyanidin-3-O-glucoside and phenolic metabolites inhibited the presence and progression of intestinal diseases and explained from the aspects of repairing the intestinal wall, inhibiting inflammatory reaction, and regulating the gut microbiota. Although the animal and clinical studies are inadequate, based on the accumulated evidence, we propose that the interaction of Cyanidin-3-O-glucoside with the intestinal mucosal immune system is at the core of most mechanisms by which affect host gut diseases. This review puts forward the potential mechanism of action and targeted treatment strategies.

Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3ß Signaling Pathway In Vivo and In Vitro.

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Grazing decreased soil organic carbon by decreasing aboveground biomass in a desert steppe in Inner Mongolia.

The mechanisms through which stocking rates affect soil organic carbon in desert steppe landscapes are not fully understood. To address this research gap, we investigated changes in the biomass of Stipa breviflora plant communities and soils in a desert steppe. Through our research findings, we can establish an appropriate stocking rate for Stipa breviflora desert steppe. The establishment serves as a theoretical foundation for effectively maintaining elevated productivity levels and increasing the carbon sink, thereby offering a valuable contribution towards mitigate climate change. This study examined the effects of different stocking rates on soil organic carbon input, sequestration, and output and found: (1) For soil organic carbon input, the aboveground and litter biomass of plant communities decreased with increasing stocking rate. (2) Grazing treatments did not affect soil organic carbon retention. (3) Regarding soil organic carbon output, the grazing treatments exhibited no significant alteration in soil respiration when compared to the no grazing. In summary, the primary mechanisms through which increasing stocking rates affect the soil organic carbon pool are decreased inputs from plants and increased output through wind erosion. Therefore, decreasing grazing intensity is key to improving soil organic carbon retention in the desert steppe.

Preparation and Performance of Regenerated Al2O3-Coated Cathode Material LiNi0.8Co0.15Al0.05O2 from Spent Power Lithium-Ion Batteries.

In this study, LiNi0.8Co0.15Al0.05O2@x%Al2O3-coated cathode materials were regeneratively compounded by the solid-phase sintering method, and their structural characterization and electrochemical performance were systematically analyzed. The regenerated ternary cathode material precursor synthesized by the co-precipitation method was roasted with lithium carbonate at a molar ratio of 1:1.1, and then completely mixed with different contents of aluminum hydroxide. The combined materials were then sintered at 800 °C for 15 h to obtain the regenerated coated cathode material, LiNi0.8Co0.15Al0.05O2@x%Al2O3. The thermogravimetry analysis, phase composition, morphological characteristics, and other tests show that when the added content of aluminum hydroxide is 3%, the regenerated cathode material, LiNi0.8Co0.15Al0.05O2@1.5%Al2O3, exhibits the highest-order layered structure with Al2O3 coating. This material can better inhibit the production of Ni2+, and improve material structure and electrochemical properties. The first charge-discharge efficiency of the battery assembled with this regenerated cathode material is 97.4%, a 50-cycle capacity retention is 93.4%, and a 100-cycle capacity retention is 87.6%. The first charge-discharge efficiency is far better than that of the uncoated regenerated battery.

Diversity and function of microbial communities in the sand sheath of Agropyron cristatum by metagenomic analysis.

The roots of most gramineous plants are surrounded by a variety of microorganisms; however, few studies have focused on the rhizosheath of psammophytes. Therefore, in this study, we used Illumina HiSeq high-throughput sequencing technology to analyse the composition and functional diversity of microbial communities in the rhizosheath of sand-grown Agropyron cristatum (L.) Gaertn. We found that the number of species and functions of microbial communities gradually decreased from the rhizosheath to the bulk soil. Thus, the microbial composition of the rhizosheath was richer and more diverse, and the abundance of bacteria, including Sphingosinicella, Rhizorhabdus, Friedmanniella, Geodermatophilus, Blastococcus, and Oscillatoria, was higher, and the abundance of fungi, such as Mycothermus, was higher. The abundance of CO2 fixation-related genes (acsA, Pcc, and cbbL) in the carbon cycle; NO3-, NO2-, NH2OH, and N2 transformation genes (nrtP, nirS, hao, and nifK) in the nitrogen cycle; soxB/A/C, Sat, and dsrB genes in the sulphur cycle; and 1-phosphate mannitol dehydrogenase (MtlD) gene and polyketide synthase gene (pks) were higher in the rhizosheath than in the bulk soil, as well as genes related to phosphorus uptake in the phosphorus cycle. Our findings showed that the rhizosheath may host the predominant microbial species related to the formation of a rhizosheath.

CircATIC Contributes to Multiple Myeloma Progression via miR-324-5p-Dependent Regulation of HGF.

Circular RNA (circRNA) 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (circATIC; hsa_circ_0058058) was observed to be upregulated in multiple myeloma (MM) by former article. However, the function and exact mechanism of circATIC in MM development remain barely known. CircRNA-microRNA (miRNA)-messenger RNA (mRNA) axis was established through using bioinformatic databases (starbase, Circinteractome, and microT-CDS). Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay were utilized to verify the target relationship between microRNA-324-5p (miR-324-5p) and circATIC or hepatocyte growth factor (HGF). CircATIC expression was upregulated in MM patients and cell lines. CircATIC interference notably hampered cell proliferation, migration, invasion, and glycolysis and induced cell apoptosis of MM cells. MiR-324-5p was a target of circATIC. CircATIC silencing-mediated effects in MM cells were largely overturned by the knockdown of miR-324-5p. HGF was a target of miR-324-5p, and circATIC upregulated the expression of HGF partly through sponging miR-324-5p in MM cells. MiR-324-5p suppressed the malignant behaviors of MM cells, which were largely counteracted by the overexpression of HGF in MM cells. CircATIC accelerated the proliferation, migration, invasion, and glycolysis and suppressed the apoptosis of MM cells through mediating miR-324-5p/HGF signaling.

TcJAV3-TcWRKY26 Cascade Is a Missing Link in the Jasmonate-Activated Expression of Taxol Biosynthesis Gene DBAT in Taxus chinensis.

Jasmonates (JAs) are the most effective inducers for the biosynthesis of various secondary metabolites. Currently, jasmonate ZIM domain (JAZ) and its interactors, such as MYC2, constitute the main JA signal transduction cascade, and such a cascade fails to directly regulate all the taxol biosynthesis genes, especially the rate-limit gene, DBAT. Another JA signaling branch, JAV and WRKY, would probably fill the gap. Here, TcJAV3 was the closest VQ-motif-containing protein in Taxus chinensis to AtJAV1. Although TcJAV3 was overexpressed in AtJAV1 knockdown mutant, JAVRi17, the enhanced disease resistance to Botrytis cinerea caused by silencing AtJAV1 was completely recovered. The results indicated that TcJAV3 indeed transduced JA signal as AtJAV1. Subsequently, TcWRKY26 was screened out to physically interact with TcJAV3 by using a yeast two-hybrid system. Furthermore, bimolecular fluorescence complementation and luciferase complementary imaging also confirmed that TcJAV3 and TcWRKY26 could form a protein complex in vivo. Our previous reports showed that transient TcWRKY26 overexpression could remarkably increase DBAT expression. Yeast one-hybrid and luciferase activity assays revealed that TcWRKY26 could directly bind with the wa-box of the DBAT promoter to activate downstream reporter genes. All of these results indicated that TcWRKY26 acts as a direct regulator of DBAT, and the TcJAV3−TcWRKY26 complex is actually another JA signal transduction mode that effectively regulates taxol biosynthesis in Taxus. Our results revealed that JAV−WRKY complexes directly regulated DBAT gene in response to JA stimuli, providing a novel model for JA-regulated secondary metabolism. Moreover, JAV could also transduce JA signal and function non-redundantly with JAZ during the regulation of secondary metabolisms.

Network Pharmacology Analysis and Experimental Validation of Kaempferol in the Treatment of Ischemic Stroke by Inhibiting Apoptosis and Regulating Neuroinflammation Involving Neutrophils.

Kaempferol, a natural plant flavonoid compound, has a neuroprotective effect on ischemic stroke, while the specific mechanism remains unclear. In the current study, we applied the comprehensive strategy that combines network pharmacology and experimental evaluation to explore the potential mechanism of kaempferol in the treatment of cerebral ischemia. First, network pharmacology analysis identified the biological process of kaempferol, suggesting that kaempferol may partly help in treating ischemic stroke by regulating apoptosis and inflammatory response. Then, we evaluated the efficacy of kaempferol in the acute stage of ischemic stroke and elucidated its effects and possible mechanisms on cell apoptosis and neuroinflammation involved by neutrophils. The results showed that kaempferol could significantly reduce the modified neurological severity score (mNSS), and reduce the volume of cerebral infarction and the degree of cerebral edema. In terms of anti-apoptosis, kaempferol could significantly reduce the number of TUNEL-positive cells, inhibit the expression of pro-apoptotic proteins and promote the expression of anti-apoptotic proteins. Kaempferol may play an anti-apoptotic role by up-regulating the expression level of the BDNF-TrkB-PI3K/AKT signaling pathway. In addition, we found that kaempferol inhibited neuron loss and the activation of glial cells, as well as the expression level of the inflammatory protein COX-2 and the classic pro-inflammatory signaling pathway TLR4/MyD88/NF-κB in the ischemic brain, reduced MPO activity and neutrophil counts in peripheral blood, and down-regulated neutrophil aggregation and infiltration in the ischemic brain. Western blot revealed that kaempferol down-regulated the activation of the JAK1/STAT3 signaling pathway in neutrophils and ischemic brains. Our study showed that kaempferol inhibited the activation and number of neutrophils in the rat peripheral blood and brain, which may be related to the down-regulation of the JAK1/STAT3 pathway.

Inhibition of Netosis with PAD Inhibitor Attenuates Endotoxin Shock Induced Systemic Inflammation.

Neutrophils play a pivotal role in innate immunity by releasing neutrophils extracellular traps (NETs). Excessive NETs are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases (PAD) mediate histone citrullination and NET formation that, in turn, exacerbate endotoxin shock damages. In this study, we further investigated the molecular mechanism underlying PAD and NETs in endotoxic stress in mice. The control group mice were injected with solvent, the LPS endotoxic shock group mice were intraperitoneally injected with LPS at 35 mg/kg only, while the LPS and PAD inhibitor YW3-56 treatment group mice were injected with YW3-56 at 10 mg/kg prior to the LPS injection. YW3-56 significantly prolonged the survival time of the LPS-treated mice. NETs, cfDNA, and inflammatory factors were detected by ELISA in serum, paitoneal cavity, and lung at 24 h after LPS administration. Lung injuries were detected by immunostaining, and lung tissue transcriptomes were analyzed by RNA-seq at 24 h after LPS administration. We found that YW3-56 altered neutrophil tissue homeostasis, inhibited NET formation, and significantly decreased cytokines (IL-6, TNFα and IL-1ß) levels, cytokines gene expression, and lung tissue injury. In summary, NET formation inhibition offers a new avenue to manage inflammatory damages under endotoxic stress.

ST2825, a Small Molecule Inhibitor of MyD88, Suppresses NF-κB Activation and the ROS/NLRP3/Cleaved Caspase-1 Signaling Pathway to Attenuate Lipopolysaccharide-Stimulated Neuroinflammation.

Neuroinflammation characterized by microglia activation is the mechanism of the occurrence and development of various central nervous system diseases. ST2825, as a peptide-mimetic MyD88 homodimerization inhibitor, has been identified as crucial molecule with an anti-inflammatory role in several immune cells, especially microglia. The purpose of the study was to investigate the anti-neuroinflammatory effects and the possible mechanism of ST2825. Methods: Lipopolysaccharide (LPS) was used to stimulate neuroinflammation in male BALB/c mice and BV2 microglia cells. The NO level was determined by Griess Reagents. The levels of pro-inflammatory cytokines and chemokines were determined by ELISA. The expressions of inflammatory proteins were determined by real-time PCR and Western blotting analysis. The level of ROS was detected by DCFH-DA staining. Results: In vivo, the improved levels of LPS-induced pro-inflammatory factors, including TNF-α, IL-6, IL-1ß, MCP-1 and ICAM-1 in the cortex and hippocampus, were reduced after ST2825 treatment. In vitro, the levels of LPS-induced pro-inflammatory factors, including NO, TNF-α, IL-6, IL-1ß, MCP-1, iNOS, COX2 and ROS, were remarkably decreased after ST2825 treatment. Further research found that the mechanism of its anti-neuroinflammatory effects appeared to be associated with inhibition of NF-κB activation and down-regulation of the NLRP3/cleaved caspase-1 signaling pathway. Conclusions: The current findings provide new insights into the activity and molecular mechanism of ST2825 for the treatment of neuroinflammation.

Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects.

Chrysomycin A (Chr-A), an antibiotic from Streptomyces, is reported to have anti-tumor and anti-tuberculous activities, but its anti-glioblastoma activity and possible mechanism are not clear. Therefore, the current study was to investigate the mechanism of Chr-A against glioblastoma using U251 and U87-MG human cells. CCK8 assays, EdU-DNA synthesis assays and LDH assays were carried out to detect cell viability, proliferation and cytotoxicity of U251 and U87-MG cells, respectively. Transwell assays were performed to detect the invasion and migration abilities of glioblastoma cells. Western blot was used to validate the potential proteins. Chr-A treatment significantly inhibited the growth of glioblastoma cells and weakened the ability of cell migration and invasion by down regulating the expression of slug, MMP2 and MMP9. Furthermore, Chr-A also down regulated Akt, p-Akt, GSK-3ß, p-GSK-3ß and their downstream proteins, such as ß-catenin and c-Myc in human glioblastoma cells. In conclusion, Chr-A may inhibit the proliferation, migration and invasion of glioblastoma cells through the Akt/GSK-3ß/ß-catenin signaling pathway.

Novel Peptide-Based Magnetic Nanoparticle for Mesenchymal Circulating Tumor Cells Detection.

The monitoring of circulating tumor cells (CTCs) has recently served as a promising approach for assessing prognosis and evaluating cancer treatment. We have already developed a CTCs enrichment platform by EpCAM recognition peptide-functionalized magnetic nanoparticles (EP@MNPs). However, considering heterogeneous CTCs generated through epithelial-mesenchymal transition (EMT), mesenchymal CTCs would be missed with this method. Notably, N-cadherin, overexpressed on mesenchymal CTCs, can facilitate the migration of cancer cells. Hence, we screened a novel peptide targeting N-cadherin, NP, and developed a new CTCs isolation approach via NP@MNPs to complement EpCAM methods' deficiencies. NP@MNPs had a high capture efficiency (about 85%) of mesenchymal CTCs from spiked human blood. Subsequently, CTCs were captured and sequenced at the single-cell level via NP@MNPs and EP@MNPs, RNA profiles of which showed that epithelial and mesenchymal subgroups could be distinguished. Here, a novel CTCs isolation platform laid the foundation for mesenchymal CTCs isolation and subsequent molecular analysis.

Grazing intensity changed the activities of nitrogen assimilation related enzymes in desert Steppe Plants.

BACKGROUND: Nitrogen, as a limiting factor for net primary productivity in grassland ecosystems, is an important link in material cycles in grassland ecosystems. However, the nitrogen assimilation efficiency and mechanisms of grassland plants under grazing disturbance are still unclear. This study investigated Stipa breviflora desert steppe which had been grazed for 17 years and sampled the root system and leaf of the constructive species Stipa breviflora during the peak growing season under no grazing, light grazing, moderate grazing and heavy grazing treatments. The activities of enzymes related to nitrogen assimilation in roots and leaves were measured. RESULTS: Compared with no grazing, light grazing and moderate grazing significantly increased the activities of nitrate reductase (NR), glutamine synthetase (GS), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) in leaves, and GS, GOT and GPT in roots of Stipa breviflora, while heavy grazing significantly decreased the activities of GS in leaves and NR in roots of Stipa breviflora. NR, GOT and GPT activities in leaves and roots of Stipa breviflora were positively correlated with nitrogen content, soluble protein, free amino acid and nitrate content. CONCLUSIONS: Grazing disturbance changed the activities of nitrogen assimilation related enzymes of grassland plants, and emphasized that light grazing and moderate grazing were beneficial for nitrogen assimilation by grassland plants. Therefore, establishing appropriate stocking rates is of great significance for material flows in this grassland ecosystem and for the stability and sustainable utilization of grassland resources.