Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS induced DNA double strand breaks at transcription initiation region.

BACKGROUND: The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. METHODS: We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). RESULTS: The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. CONCLUSION: These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Study of the molecular structure of proteins in fermented Maize-Soybean meal-based rations based on FTIR spectroscopy.

This research investigates the dynamic alterations that occur in protein molecular structure during the fermentation process of feed. Fourier transform infrared spectroscopy (FTIR), coupled with deconvolution, second derivative and curve-fitting methodologies, was employed to comparatively analyse the protein molecular structures in fermented feed. At the 48-h fermentation mark, the α-helix and ß-sheet contents reached their peaks, while the random coil and ß-turn contents were at their lowest. Simultaneously, the ß-sheet/α-helix ratio was minimized. FTIR spectroscopy emerged as a comprehensive tool, revealing the nuanced changes in molecular structure throughout the fermentation process of corn-soybean meal feed. When integrated with spectral quantitative analysis, it provides a novel perspective for evaluating the nutritional value of fermented feed.

Variable eIF4E-binding sites and their synergistic effect on cap-independent translation in a novel IRES of wheat yellow mosaic virus RNA2 isolates.

Some viral proteins are translated cap-independently via the internal ribosome entry site (IRES), which maintains conservative characteristic among different isolates of the same virus species. However, IRES activity showed a 7-fold variance in RNA2 of wheat yellow mosaic virus (WYMV) HC and LYJN isolates in this study. Based on RNA structure probing and mutagenesis assay, the loosened middle stem of H1 and the hepta-nucleotide top loop of H2 in the LYJN isolate synergistically ensured higher IRES activity than that in the HC isolate. In addition, the conserved top loop of H1 ensured basic IRES activity in HC and LYJN isolates. WYMV RNA2 5'-UTR specifically interacted with the wheat eIF4E, accomplished by the top loop of H1 in the HC isolate or the top loop of H1 and H2 in the LYJN isolate. The high IRES activity of the WYMV RNA2 LYJN isolate was regulated by two eIF4E-binding sites, which showed a synergistic effect mediated by the proximity of the H1 and H2 top loops owing to the flexibility of the middle stem in H1. This report presents a novel evolution pattern of IRES, which altered the number of eIF4E-binding sites to regulate IRES activity.

Combining microbiome and pseudotargeted metabolomics revealed the alleviative mechanism of Cupriavidus sp. WS2 on the cadmium toxicity in Vicia unijuga A.Br.

Cadmium (Cd) pollution is one of the most severe toxic metals pollution in grassland. Vicia unijuga (V. unijuga) A.Br. planted nearby the grassland farming are facing the risk of high Cd contamination. Here, we investigated the beneficial effects of a highly Cd tolerant rhizosphere bacterium, Cupriavidus sp. WS2, on Cd contaminated V. unijuga. Through plot experiments, we set up four groups of treatments: the control group (without WS2 or Cd), the Cd group (with only Cd addition), the WS2 group (with only WS2 addition), and the WS2/Cd group (with WS2 and Cd addition), and analyzed the changes in physiological indicators, rhizosphere microorganisms, and stem and leaf metabolites of V. unijuga. Results of physiological indicators indicated that Cupriavidus sp. WS2 had strong absorption and accumulation capacity of Cd, exogenous addition of strain WS2 remarkably decreased the Cd concentrations, and increased the plant heights, the biomass, the total protein concentrations, the chlorophyll contents and the photosynthetic rate in stems and leaves of V. unijuga under Cd stress. Cd treatment increased the abundance of Cd tolerant bacterial genera in rhizosphere microbiome, but these genera were down-regulated in the WS2/Cd group. Pseudotargeted metabolomic results showed that six common differential metabolites associated with antioxidant stress were increased after co-culture with WS2. In addition, WS2 activated the antioxidant system including glutathione (GSH) and catalase (CAT), reduced the contents of oxidative stress markers including malondialdehyde (MDA) and hydrogen peroxide (H2O2) in V. unijuga under Cd stress. Taken together, this study revealed that Cupriavidus sp.WS2 alleviated the toxicity of V. unijuga under Cd exposure by activating the antioxidant system, increasing the antioxidant metabolites, and reducing the oxidative stress markers.

MXene-enhanced ePatch with antibacterial activity for wound healing.

Prudent wound-healing strategies hold great potential in expediting tissue renovation and regeneration. Despite the widespread adoption of hydrogels as preferred carriers for wound healing patches, achieving optimal mechanical compatibility and superior wound performance remains a formidable challenge. Consequently, meticulous attention must be given to the formulation of hydrogel structure and materials design to overcome these hurdles. In response, we have developed an ePatch composed of polyacrylamide (PAAM) as the primary hydrogel structure, augmented with MXene, silver nanowires (AgNWs), and resveratrol to act as sustained-release agents, structural enhancers, and antibacterial agents, respectively. Notably, the ePatch exhibited exceptional wound-fitting capabilities and impressive mechanical stretchability (with a relative standard deviation [RSD] of only 1.36% after 55 stretches) and Young's modulus. In contrast to the commercial 3M Tegaderm, the ePatch demonstrated superior wound healing properties, with the inclusion of MXene into PAAM/AgNWs playing a pivotal role in expanding the ePatch's potential use across various interconnected fields.

Construction of a Delivery Platform for Vaccine Based on Modified Nanotubes: Sustainable Prevention against Plant Viral Disease, Simplified Preparation Method, and Protection of Plasmid.

Control of plant viral diseases through cross-protection conferred by an attenuated vaccine is an important strategy for plant protection. However, the mutated site of an attenuated vaccine may not be stably inherited, while viruses have evolved efficient repair mechanisms for the maintenance of genomic integrity. Here, the wide host range and broad selection of mutation sites in cucumber mosaic virus (CMV) enabled construction of an attenuated vaccine through insertional mutation of the CMV 2b protein. CMV-R2E was stably inherited in tobacco for more than 10 generations and had a high relative control efficacy of CMV. Then, the use of polyetherimide (PEI)-modified functionalized carboxylated single-walled carbon nanotubes (PSWNTs) was investigated for vaccine delivery to address the problems of poor stability, complex procedure on field application, and exacting storage conditions with Agrobacterium inoculation. After co-incubating at a 1:300 ratio for 30 min, the vaccine and PSWNTs combined to form pCMV-R2E@PSWNTs, which resulted in a significant increase in the average height of the nanoparticles from 6.56 to 72.34 nm. The relative control efficacy of pCMV-R2E@PSWNTs to CMV was found to be 90.37%. Furthermore, the protective effect of PSWNTs on plasmids was investigated under various environmental conditions and the potential plant toxicity of pCMV-R2E@PSWNTs was assessed, providing a theoretical basis for field application of the vaccine nano-delivery system. A highly effective, stable viral vaccine for plants was thus developed and combined with nanocarriers to address the problems of field application. This approach has the potential to enable wider use of attenuated vaccines for sustainable prevention against plant viral disease in the field.

A General Deep Learning Method for Computing Molecular Parameters of a Viscoelastic Constitutive Model by Solving an Inverse Problem.

Prediction of molecular parameters and material functions from the macroscopic viscoelastic properties of complex fluids are of great significance for molecular and formulation design in fundamental research as well as various industrial applications. A general learning method for computing molecular parameters of a viscoelastic constitutive model by solving an inverse problem is proposed. The accuracy, convergence and robustness of a deep neural network (DNN)-based numerical solver have been validated by considering the Rolie-Poly model for modeling the linear and non-linear steady rheometric properties of entangled polymer solutions in a wide range of concentrations. The results show that as long as the DNN could be trained with a sufficiently high accuracy, the DNN-based numerical solver would rapidly converge to its solution in solving an inverse problem. The solution is robust against small white noise disturbances to the input stress data. However, if the input stress significantly deviates from the original stress, the DNN-based solver could readily converge to a different solution. Hence, the resolution of the numerical solver for inversely computing molecular parameters is demonstrated. Moreover, the molecular parameters computed by the DNN-based numerical solver not only reproduce accurately the steady viscoelastic stress of completely monodisperse linear lambda DNA solutions over a wide range of shear rates and various concentrations, but also predict a power law concentration scaling with a nearly same scaling exponent as those estimated from experimental results.

Variations and driving mechanisms of desertification in the southeast section of the China-Mongolia-Russia Economic Zone.

Desertification seriously restricts sustainable development in the arid-semiarid areas of the eastern section of the China-Mongolia-Russia Economic Zone, especially in China and Mongolia. In this study, the potential range of desertification was bounded. Spatio-temporal dynamics from 2000 to 2020 were analyzed using best-performing indices (fvc, albedo and LST). Further analysis focused on the driving factors resulting in desertification. The research showed that the potential range of desertification accounted for 50.99 % of the entire region, mainly distributed in central and western parts of Inner Mongolia, and central and southern parts of Mongolia. From 2000 to 2020, desertification in the entire study area improved, with a 2.23 % decrease in the area of severe and extremely severe desertification. Among the studied countries, the grades of desertification in China decreased over the years of study; the area of desertification in Mongolia expanded. The study also indicated that the restoration regions were affected mainly by climatic factor sand human activities, and the degradation area was driven primarily by human activities. Therefore, it is essential to formulate a reasonable land policy for desertification control.

Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: a meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) confers anti-inflammatory efficacy, which has been suggested to be effective for patients with osteoarthritis (OA). However, previous studies evaluating the influence of n-3 PUFAs supplementation in patients with OA showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively evaluate the influence of n-3 PUFAs on symptom and joint function of patients with OA. METHODS: Relevant randomized controlled trials (RCTs) were obtained by searching PubMed, Embase, and Cochrane Library databases. A random-effects model was employed to combine the results. RESULTS: Nine RCTs with 2070 patients with OA contributed to the meta-analysis. Pooled results showed that n-3 PUFAs supplementation could significantly relieve the arthritis pain as compared to placebo (standardized mean difference [SMD]: - 0.29, 95% confidence interval [CI] - 0.47 to - 0.11, p = 0.002, I2 = 60%). Besides, supplementation with n-3 PUFAs was also associated with improved joint function (SMD: - 0.21, 95% CI - 0.34 to - 0.07, p = 0.002, I2 = 27%). Subgroup analysis showed consistent results of studies with arthritis pain and joint function evaluated by the Western Ontario-McMaster University Osteoarthritis Index and other scales (p for subgroup difference = 0.33 and 0.34, respectively). No severe treatment-related adverse events (AEs) were observed in the included patients, and the incidence of overall AEs was similar between groups (odds ratio: 0.97, 95% CI 0.64-1.45, p = 0.86, I2 = 0%). CONCLUSIONS: Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA.

Manipulating the Dynamic Adaptivity of a Fluid Interface to Maintain the Multipotency of Mesenchymal Stromal Cells.

The native extracellular matrix is highly dynamic with continuous mutual feedback between cells being responsible for many important cell function regulators. However, establishing bidirectional interaction between complex adaptive microenvironments and cells remains elusive. Herein an adaptive biomaterial based on lysozyme monolayers self-assembled at a perfluorocarbon FC40-water interface is reported. The dynamic adaptivity of interfacially assembled protein nanosheets is modulated independently of bulk mechanical properties by covalent crosslinking. This provides a scenario to establish bidirectional interactions of cells with liquid interfaces of varying dynamic adaptivity. This is found that growth and multipotency of human mesenchymal stromal cells (hMSCs) are enhanced at the highly adaptive fluid interface. The multipotency retention of hMSCs is mediated by low cell contractility and metabolomic activity involving the continuous mutual feedback between the cells and materials. Consequently, an understanding of the cells' response to dynamic adaptivity has substantial implications for regenerative medicine and tissue engineering.

Time-Concentration Superposition for Linear Viscoelasticity of Polymer Solutions.

The concentration dependence of linear viscoelastic properties of polymer solutions is a well-studied topic in polymer physics. Dynamic scaling theories allow qualitative predictions of polymer solution rheology, but quantitative predictions are still limited to model polymers. Meanwhile, the scaling properties of non-model polymer solutions must be determined experimentally. In present paper, the time-concentration superposition (TCS) of experimental data is shown to be a robust procedure for studying the concentration scaling properties of binary and ternary polymer solutions. TCS can not only identify whether power law scaling may exist or not, and over which concentration range, but also unambiguously estimate the concentration scaling exponents of linear viscoelastic properties for a range of non-model polymer solutions.

Altitude-dependent metabolite biomarkers reveal the mechanism of plateau pika adaptation to high altitudes.

The harsh environment in the Tibetan plateau, the highest place in the world, poses thermoregulatory challenges and hypoxic stress to animals. The impacts of plateau environment on animal physiology and reproduction include external factors such as strong ultraviolet radiation and low temperature, and internal factors such as animal metabolites and gut microbiota. However, it remains unclear how plateau pika adapt to high altitudes through the combination of serum metabolites and gut microbiota. To this end, we captured 24 wild plateau pikas at the altitudes of 3400, 3600, or 3800 m a.s.l. in a Tibetan alpine grassland. Using the machine learning algorithms (random forest), we identified five biomarkers of serum metabolites indicative of the altitudes, that is, dihydrotestosterone, homo-l-arginine, alpha-ketoglutaric-acid, serotonin, and threonine, which were related to body weight, reproduction, and energy metabolism of pika. Those metabolic biomarkers were positively correlated with Lachnospiraceae_ Agathobacter, Ruminococcaceae, or Prevotellaceae_Prevotella, suggesting the close relationship between metabolites and gut microbiota. By identifying the metabolic biomarkers and gut microbiota analysis, we reveal the mechanisms of adaptation to high altitudes in plateau pika.

Concentration Scaling on Linear Viscoelastic Properties of Cellular Suspensions and Effects of Equilibrium Phase Behavior.

Concentration scaling on linear viscoelastic properties of cellular suspensions has been studied by rheometric characterisation of Phormidium suspensions and human blood in a wide range of volume fraction under small amplitude oscillatory shear experiments. The rheometric characterisation results are analysed by the time-concentration superposition (TCS) principle and show a power law scaling of characteristic relaxation time, plateau modulus and the zero-shear viscosity over the concentration ranges studied. The results show that the concentration effect of Phormidium suspensions on their elasticity is much stronger than that of human blood due to its strong cellular interactions and a high aspect ratio. For human blood, no obvious phase transition could be observed over the range of hematocrits studied here and with respect to a high-frequency dynamic regime, only one concentration scaling exponent could be identified. For Phormidium suspensions with respect to a low-frequency dynamic regime, three concentration scaling exponents in the volume fraction Region I (0.36≤ϕ/ϕref≤0.46), Region II (0.59≤ϕ/ϕref≤2.89) and Region III (3.11≤ϕ/ϕref≤3.44) are identified. The image observation shows that the network formation of Phormidium suspensions occurs as the volume fraction is increased from Region I to Region II; the sol-gel transition takes place from Region II to Region III. In combination with analysis of other nanoscale suspensions and liquid crystalline polymer solutions reported in the literature, it is revealed that such a power law concentration scaling exponent depends on colloidal or molecular interactions mediated with solvent and is sensitive to the equilibrium phase behaviour of complex fluids. The TCS principle is an unambiguous tool to give a quantitative estimation.

Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism.

Swainsonine induced liver inflammation in livestock; however, the underlying mechanisms, especially the role of bile acids (BAs), in the pathogenesis remained elusive. Here, our results showed that swainsonine induced hepatic inflammation via changing BA metabolism and gut microbiota in mice. Swainsonine significantly upregulated the levels of deoxycholic acid (DCA) and taurine-ß-muricholic acid (T-ß-MCA) in the serum and liver of mice due to the markedly increased genus Clostridium and the decreased genus Lactobacillus in the gut. As antagonists of the farnesoid X receptor (FXR), elevated DCA and T-ß-MCA inhibited hepatic Fxr gene expression and thus suppressed FXR-SHP signaling and activated hepatic Cyp7a1 gene expression, which induced a significant upregulation of the total BA level in serum, contributing to liver inflammation. These findings offer new insights into the underlying mechanisms in which swainsonine induced liver inflammation in mice via the gut-liver axis and suggest that gut microbiota and its metabolite BAs may be underlying triggering factors.

Kynurenic acid mediates bacteria-algae consortium in resisting environmental cadmium toxicity.

Cadmium (Cd2+) is a toxic heavy metal in the environment, posing severe damage to animal health and drinking water safety. The bacteria-algae consortium remediates environmental Cd2+ pollution by secreting chelating reagents, but the molecular mechanisms remain elusive. Here, we showed that Cellulosimicrobium sp. SH8 isolated from a Cd2+-polluted lake could interact with Synechocystis sp. PCC6803, a model species of cyanobacteria, in strengthening Cd2+ toxicity resistance, while SH8 or PCC6803 alone barely immobilized Cd2+. In addition, the SH8-PCC6803 consortium, but not SH8 alone, could grow in a carbon-free medium, suggesting that autotrophic PCC6803 enabled the growth of heterotrophic SH8. Totally, 12 metabolites were significantly changed when SH8 was added to PCC6803 culture in the presence of Cd2+ (PCC6803/Cd2+). Among them, kynurenic acid was the only metabolite that precipitated Cd2+. Remarkably, adding kynurenic acid increased the growth of PCC6803/Cd2+ by 14.1 times. Consistently, the expressions of kynA, kynB, and kynT genes, known to be essential for kynurenic acid synthesis, were considerably increased when SH8 was added to PCC6803/Cd2+. Collectively, kynurenic acid secreted by SH8 mitigates Cd2+ toxicity for algae, and algae provide organic carbon for the growth of SH8, unveiling a critical link that mediates beneficial bacteria-algae interaction to resist Cd2+.

Pseudotargeted metabolomics revealed the adaptive mechanism of Draba oreades Schrenk at high altitude.

Strong ultraviolet radiation and low temperature environment on Gangshika Mountain, located in the eastern part of the Qilian Mountains in Qinghai Province, can force plants to produce some special secondary metabolites for resisting severe environmental stress. However, the adaptive mechanism of Draba oreades Schrenk at high altitude are still unclear. In the current study, Draba oreades Schrenk from the Gangshika Mountain at altitudes of 3800 m, 4000 m and 4200 m were collected for comprehensive metabolic evaluation using pseudotargeted metabolomics method. Through KEGG pathway enrichment analysis, we found that phenylpropanoid biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism related to the biosynthesis of flavonoids were up-regulated in the high-altitude group, which may enhance the environmental adaptability to strong ultraviolet intensity and low temperature stress in high altitude areas. By TopFc20 distribution diagram, the content of flavonoids gradually increased with the elevation of altitude, mainly including apigenin, luteolin, quercetin, hesperidin, kaempferol and their derivatives. Based on the random forest model, 10 important metabolites were identified as potential biomarkers. L-phenylalanine, L-histidine, naringenin-7-O-Rutinoside-4'-O-glucoside and apigenin related to the flavonoids biosynthesis and plant disease resistance were increased with the elevation of altitude. This study provided important insights for the adaptive mechanism of Draba oreades Schrenk at high altitude by pseudotargeted metabolomics.

Oroxin B alleviates osteoarthritis through anti-inflammation and inhibition of PI3K/AKT/mTOR signaling pathway and enhancement of autophagy.

Background: Osteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA. Methods: In vitro, primary mice chondrocytes were stimulated with IL-1ß along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice's knee joints were obtained for subsequent histological staining and analysis. Results: OB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1ß-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1ß, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß) markers were downregulated after the administration of OB in IL-1ß-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1ß could be inhibited by OB. Additionally, the autophagy process impaired by IL-1ß could be rescued by OB. What's more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models. Conclusions: The study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.

Molecular Characteristics of Subgenomic RNAs and the Cap-Dependent Translational Advantage Relative to Corresponding Genomic RNAs of Tomato spotted wilt virus.

Tomato spotted wilt virus (TSWV) causes severe viral diseases on many economically important plants of Solanaceae. During the infection process of TSWV, a series of 3'-truncated subgenomic RNAs (sgRNAs) relative to corresponding genomic RNAs were synthesized, which were responsible for the expression of some viral proteins. However, corresponding genomic RNAs (gRNAs) seem to possess the basic elements for expression of these viral proteins. In this study, molecular characteristics of sgRNAs superior to genomic RNAs in viral protein expression were identified. The 3' ends of sgRNAs do not cover the entire intergenic region (IGR) of TSWV genomic RNAs and contain the remarkable A-rich characteristics. In addition, the 3' terminal nucleotides of sgRNAs are conserved among different TSWV isolates. Based on the eIF4E recruitment assay and subsequent northern blot, it is suggested that the TSWV sgRNA, but not gRNA, is capped in vivo; this is why sgRNA is competent for protein expression relative to gRNA. In addition, the 5' and 3' untranslated region (UTR) of sgRNA-Ns can synergistically enhance cap-dependent translation. This study further enriched the understanding of sgRNAs of ambisense RNA viruses.