A Smart Pesticide-Controlled Release Platform with Dual Stimuli-Responsive Functions for Enhanced Treatment of Plant Black Shank.

Realizing controllable input of botanical pesticides is conducive to improving pesticide utilization, reducing pesticide residues, and avoiding environmental pollution but is extremely challenging. Herein, we constructed a smart pesticide-controlled release platform (namely, SCRP) for enhanced treatment of tobacco black shank based on encapsulating honokiol (HON) with mesoporous hollow structured silica nanospheres covered with pectin and chitosan oligosaccharide (COS). The SCRP has a loading capacity of 12.64% for HON and could effectively protect HON from photolysis. Owing to the pH- and pectinase-sensitive property of the pectin, the SCRP could smartly release HON in response to a low pH or a rich pectinase environment in the black shank-affected area. Consequently, the SCRP effectively inhibits the infection of P. nicotianae on tobacco with a controlled rate for tobacco black shank of up to 87.50%, which is mainly due to the SCRP's capability in accumulating ROS, changing cell membrane permeability, and affecting energy metabolism. In addition, SCRP is biocompatible, and the COS layer enables SCRP to show a significant growth-promoting effect on tobacco. These results indicate that the development of a stimuli-responsive controlled pesticide release system for plant disease control is of great potential and value for practical agriculture production.

Correction: RNAi-Mediated Silencing of Atp6i and Atp6i Haploinsufficiency Prevents Both Bone Loss and Inflammation in a Mouse Model of Periodontal Disease.

[This corrects the article DOI: 10.1371/journal.pone.0058599.].

Synergistic Lewis and Brønsted Acid Sites Promote OH* Formation and Enhance Formate Selectivity: Towards High-efficiency Glycerol Valorization.

As a sustainable valorization route, electrochemical glycerol oxidation reaction (GOR) involves in formation of key OH* and selective adsorption/cleavage of C-C(O) intermediates with multi-step electron transfer, thus suffering from high potential and poor formate selectivity for most non-noble-metal-based electrocatalysts. So, it remains challenging to understand the structure-property relationship as well as construct synergistic sites to realize high-activity and high-selectivity GOR. Herein, we successfully achieve dual-high performance with low potentials and superior formate selectivity for GOR by forming synergistic Lewis and Brønsted acid sites in Ni-alloyed Co-based spinel. The optimized NiCo oxide solid-acid electrocatalyst exhibits low reaction potential (1.219 V@10 mA/cm2) and high formate selectivity (94.0 %) toward GOR. In situ electrochemical impedance spectroscopy and pH-dependence measurements show that the Lewis acid centers could accelerate OH* production, while the Brønsted acid centers are proved to facilitate high-selectivity formation of formate. Theoretical calculations reveal that NiCo alloyed oxide shows appropriate d-band center, thus balancing adsorption/desorption of C-O intermediates. This study provides new insights into rationally designing solid-acid electrocatalysts for biomass electro-upcycling.

Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = - 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = - 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.

Extracellular and intracellular effects of bioactive glass nanoparticles on osteogenic differentiation of bone marrow mesenchymal stem cells and bone regeneration in zebrafish osteoporosis model.

Bioactive glass nanoparticles (BGNs) are well-recognized multifunctional biomaterials for bone tissue regeneration due to their capability to stimulate various cellular processes through released biologically active ions. Understanding the correlation between BGN composition and cellular responses is key to developing clinically usable BGN-based medical devices. This study investigated the influence of CaO content of binary SiO2-CaO BGNs (CaO ranging from 0 to 10 mol%) on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo bone regeneration in zebrafish osteoporosis model. The results showed that BGNs could promote osteogenic differentiation of rBMSCs by indirectly releasing active ions or directly interacting with rBMSCs by internalization. In both situations, BGNs of a higher CaO content could promote the osteogenic differentiation of rBMSCs to a greater extent. The internalized BGNs could activate the transcription factors RUNX2 and OSX, leading to the expression of osteogenesis-related genes. The results in the zebrafish osteoporosis model indicated that the presence of BGNs of higher CaO contents could enhance bone regeneration and rescue dexamethasone-induced osteoporosis to a greater extent. These findings demonstrate that BGNs can stimulate osteogenic differentiation of rBMSCs by releasing active ions or internalization. A higher CaO content facilitates osteogenesis and bone regeneration of zebrafish as well as relieving dexamethasone-induced osteoporosis. The zebrafish osteoporosis model can be a potent tool for evaluating the in vivo bone regeneration effects of bioactive materials. STATEMENT OF SIGNIFICANCE: Bioactive glass nanoparticles (BGNs) are increasingly used as fillers of nanocomposites or as delivery platforms of active ions to regenerate bone tissue. Various studies have shown that BGNs can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by releasing active ions. However, the correlation between BGN composition and cellular responses and in vivo bone regeneration effect has still not been well investigated. Establishment of a suitable in vivo animal model for investigating this correlation is also challenging. The present study reports the influence of CaO content in binary SiO2-CaO BGNs on osteogenic differentiation of BMSCs extracellularly and intracellularly. This study also demonstrates the suitability of zebrafish osteoporosis model to investigate in vivo bone regeneration effect of BGNs.

Para-perirenal fat thickness is associated with reduced glomerular filtration rate regardless of other obesity-related indicators in patients with type 2 diabetes mellitus.

PURPOSE: To investigate the relationship between estimated glomerular filtration rate (eGFR) and para-perirenal fat thickness in comparison with other indices of adiposity in type 2 diabetes mellitus (T2DM). METHODS: This single-center, retrospective and cross-sectional study evaluated 337 patients with T2DM. The obesity-related indicators including height, weight, body surface area (BSA), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), para-perirenal fat thickness (PRFT), total abdominal fat (TAF), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT). eGFR was calculated by CKD-EPI equation. The correlation between eGFR and obesity-related indicators was performed by pearson or spearman correlation analysis and multivariate linear regression. RESULTS: 337 subjects (mean age, 60.2 ± 11.6 years; 195 males, 57.9%) were evaluated. eGFR was negatively correlated with height, weight, BMI, PRFT, TAF, SAT, and VAT, among which the correlation between eGFR and PRFT was the strongest (r = -0.294, p< 0.001). eGFR remained the strongest correlation with PRFT in the subgroup separated by sex (r = -0.319 in the male subgroup, and -0.432 in the female subgroup, respectively, p < 0.001). Age and PRFT were the independent predictive factors for eGFR. PRFT was the best predictor of chronic kidney disease (CKD) in T2DM (AUC = 0.686, p = 0.001, 95% CI: 0.582-0.791). CKD in T2DM can be predicted well by linking age with PRFT (AUC = 0.708, p<0.001, 95% CI = 0.605-0.812). CONCLUSIONS: PRFT is more closely related to glomerular filtration rate than other obesity-related indicators in T2DM. The model combining age with PRFT could predict CKD in T2DM well.

The association between obesity indicators and metabolic risk factors in type-2 diabetic patients.

Rationale and objectives: Obesity, accumulation of adipose tissue, is a global disease that can lead to cardiovascular and metabolic complications. The aim of this study was to investigate the relationship between obesity indicators and metabolic risk factors in type 2 diabetes mellitus (T2DM) patients. Materials and methods: A total of 337 T2DM subjects were included in our study. The metabolic risk factors including diabetes duration, fast plasma glucose (FPG), height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), estimated average glucose (eAG), glycated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (Scr), free fatty acid (FFA), uric acid (UA), cystatin c (cysc), albumin (Alb), urinary albumin creatinine ratio (UACR) were recorded. The obesity indicators included body surface area (BSA), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), para-perirenal fat thickness (PRFT), total abdominal fat (TAF), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT). The association between obesity indicators and metabolic risk factors was investigated by univariate and multivariate analysis. Results: HDL-c was independently associated with WHR and PRFT (ß = -0.126 vs. -0.214, both p < 0.05). TG and Scr were both independently associated with PRFT (ß = 0.173 vs. 0.218, both p < 0.01, respectively). UA was independently associated with BSA (ß = 0.172, p < 0.01) and PRFT (ß = 0.151, p < 0.01). cysc, Alb and UACR were independently associated with WC (ß = 0.274 vs. 0.204 vs. 0.182, all p < 0.01). Conclusion: In T2DM patients, obesity indicators were significantly associated with metabolic risk factors.

Major vault protein (MVP) suppresses aging- and estrogen deficiency-related bone loss through Fas-mediated apoptosis in osteoclasts.

Osteoclasts (OCs), derived from monocyte/macrophage lineage, are key orchestrators in bone remodeling. Targeting osteoclast apoptosis is a promising approach to cut down excessive osteoclast numbers, and thus slow down the rate of bone mass loss that inevitably occurs during aging. However, the therapeutic target of apoptosis in osteoclasts has not been fully studied. Our previous work generated Mvpf/fLyz2-Cre mice, conditionally depleting major vault protein (MVP) in monocyte lineage, and identified MVP as a bone protector for its negative role in osteoclastogenesis in vivo and in vitro. Here, we observed a notable decline of MVP in osteoclasts with aging in mice, encouraging us to further investigate the regulatory role of osteoclast MVP. Then, Mvpf/fLyz2-Cre mice were exploited in two osteoporosis contexts, aging and abrupt loss of estrogen, and we revealed that conditional knockout of MVP inhibited osteoclast apoptosis in vivo and in vitro. Moreover, we reported the interaction between MVP and death receptor Fas, and MVP-Fas signaling cascade was identified to positively regulate the apoptosis of osteoclasts, thus preventing osteoporosis. Collectively, our comprehensive discovery of MVP's regulatory role in osteoclasts provides new insight into osteoclast biology and therapeutic targets for osteoporosis.

Co-application of chitooligosaccharides and arbuscular mycorrhiza fungi reduced greenhouse gas fluxes in saline soil by improving the rhizosphere microecology of soybean.

Soil salinization can affect the ecological environment of soil and alter greenhouse gas (GHG) emissions. Chitooligosaccharides and Arbuscular mycorrhizal fungi (AMF) reduced the GHG fluxes of salinized soil, and this reduction was attributed to an alteration in the rhizosphere microecology, including changes in the activities of ß-glucosidase, acid phosphatase, N-acetyl-ß-D-glucosidase, and Leucine aminopeptidase. Additionally, certain bacteria species such as paracoccus, ensifer, microvirga, and paracyclodium were highly correlated with GHG emissions. Another interesting finding is that foliar spraying of chitooligosaccharides could transport to the soybean root system, and improve soybean tolerance to salt stress. This is achieved by enhancing the activities of antioxidant enzymes, and the changes in amino acid metabolism, lipid metabolism, and membrane transport. Importantly, the Co-application of chitooligosaccharides and Arbuscular mycorrhiza fungi was found to have a greater effect compared to their application alone.

Macrophage MVP regulates fracture repair by promoting M2 polarization via JAK2-STAT6 pathway.

OBJECTIVE: Major vault protein (MVP) is vital in various macrophage-related inflammatory diseases. However, the effects of MVP on macrophage polarization during fracture repair are still unknown. METHODS: We used Mvpflox/floxLyz2-Cre mice (myeloid-specific MVP gene knockout, abbreviated as MacKO) and Mvpflox/flox (abbreviated as MacWT) mice to compare their fracture healing phenotype. Next, we traced the changes in macrophage immune status in vivo and in vitro. We further explored the effects of MVP on osteogenesis and osteoclastogenesis. Finally, we re-expressed MVP in MacKO mice to confirm the role of MVP in fracture healing. RESULTS: The lack of MVP in macrophages impaired their transition from a pro-inflammatory to an anti-inflammatory phenotype during fracture repair. The increased secretion of pro-inflammatory cytokines by macrophages promoted their osteoclastic differentiation and impaired BMSC osteogenic differentiation, ultimately leading to impaired fracture repair in MacKO mice. Last, adeno-associated virus (AAV)-Mvp tibial injection significantly promoted fracture repair in MacKO mice. CONCLUSIONS: Our findings showed MVP has a previously unknown immunomodulatory role in macrophages during fracture repair. Targeting macrophage MVP may represent a novel therapeutic method for fracture treatment.

Integrated Cascade Nanozyme Remodels Chondrocyte Inflammatory Microenvironment in Temporomandibular Joint Osteoarthritis via Inhibiting ROS-NF-κB and MAPK Pathways.

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease with no complete cure at present. Notably, the inflammatory microenvironment in TMJ OA is modulated by oxidative stress, which impacts cartilage metabolism, chondrocyte apoptosis, inflammatory cytokine release, and extracellular matrix (ECM) synthesis. Thus, it is reasoned that reducing excess reactive oxygen species (ROS) in the chondrocyte microenvironment may be an effective therapeutic strategy for TMJ OA. Recently, cascade nanozymes, including Pt@PCN222-Mn, have been exploited to treat ROS-associated diseases. Nevertheless, cascade nanozymes are not employed for TMJ OA therapy. To fill this gap, it is explored whether the Pt@PCN222-Mn cascade nanozyme could be applied to the treatment of TMJ OA. The in vitro results demonstrate that the Pt@PCN222-Mn nanozyme can inhibit the production of inflammatory factors, the degradation of ECM, and the apoptosis of chondrocytes by inhibiting the ROS-nuclear factor kappa-B (NF-κB_ and mitogen-activated protein kinase signaling pathways. The in vivo results further demonstrate that the Pt@PCN222-Mn nanozyme can delay the progression of TMJ OA in the rat unilateral anterior crossbite model. It is believed that insightful perspectives on the application of nanozymes in TMJ OA will be provided here.

IRF4 as a novel target involved in malignant transformation of oral submucous fibrosis into oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) in the context of oral submucous fibrosis (OSF) has a high incidence owing to undefined pathogenesis. Identifying key genes and exploring the underlying molecular mechanisms involved in the conversion of OSF into OSCC are in urgent need. Differentially expressed genes (DEGs) between OSCC and OSF were dug from GEO databases and a total of 170 DEGs were acquired. Functional association of DEGs were analyzed by GO and KEGG. Protein-protein interactions (PPIs) analysis was carried out and candidate biomarkers were identified by Gene co-expression analysis and Cox analyses. Hub genes were confirmed by qRT-PCR in tissues and cell lines, of which we found that IRF4 mRNA was successively up-regulated from Normal to OSF and then to OSCC and associated with immune infiltrating levels. In addition, Immunohistochemical (IHC) and Immunofluorescence (IF) assays were conducted to validate the consistent upregulation of IRF4 and the oncogene role of IRF4 in OSF and OSCC at translation level. IRF4 may be indicative biomarker in transformation of OSF into OSCC. High IRF4 expression contribute to increased immune infiltration of OSCC and may provide a novel diagnostic marker for OSCC patients translated from OSF.

AMF colonization affects allelopathic effects of Zea mays L. root exudates and community structure of rhizosphere bacteria.

Arbuscular mycorrhizal fungi (AMF) widely exist in the soil ecosystem. It has been confirmed that AMF can affect the root exudates of the host, but the chain reaction effect of changes in the root exudates has not been reported much. The change of soil microorganisms and soil enzyme vigor is a direct response to the change in the soil environment. Root exudates are an important carbon source for soil microorganisms. AMF colonization affects root exudates, which is bound to have a certain impact on soil microorganisms. This manuscript measured and analyzed the changes in root exudates and allelopathic effects of root exudates of maize after AMF colonization, as well as the enzymatic vigor and bacterial diversity of maize rhizosphere soil. The results showed that after AMF colonization, the contents of 35 compounds in maize root exudates were significantly different. The root exudates of maize can inhibit the seed germination and seedling growth of recipient plants, and AMF colonization can alleviate this situation. After AMF colonization, the comprehensive allelopathy indexes of maize root exudates on the growth of radish, cucumber, lettuce, pepper, and ryegrass seedlings decreased by 60.99%, 70.19%, 80.83%, 36.26% and 57.15% respectively. The root exudates of maize inhibited the growth of the mycelia of the pathogens of soil-borne diseases, and AMF colonization can strengthen this situation. After AMF colonization, the activities of dehydrogenase, sucrase, cellulase, polyphenol oxidase and neutral protein in maize rhizosphere soil increased significantly, while the bacterial diversity decreased but the bacterial abundance increased. This research can provide a theoretical basis for AMF to improve the stubble of maize and the intercropping mode between maize and other plants, and can also provide a reference for AMF to prevent soil-borne diseases in maize.

The value of cardiac CT in the diagnosis of unroofed coronary sinus syndrome.

BACKGROUND: Unroofed coronary sinus syndrome (UCSS) is a rare cardiovascular malformation with nonspecific clinical manifestations that easily causes misdiagnosis and missed diagnosis. The aim of this study is to present the different features of UCSS by various CCT (cardiac CT) postprocessing techniques and evaluate the diagnostic advantages of CCT. METHODS: 9 UCSS patients who were diagnosed by imaging and undergone both CCT and transthoracic echocardiography (TTE) were included in this study, and their CCT images were reviewed. The UCSS images were classified by multiplanar reformations, maximum intensity projection, volume rendering and cinematic rendering. The size of CS roof defect was also measured. RESULTS: Only 4 of 9 CCT confirmed UCSS patients were detected by TTE (4/9, 44.4%), the sensitivity of TTE was lower compared to CCT by Fisher's exact test (P < 0.05). UCSS was classified according to the Kirklin and Barratt Boyes's method, including 1 case was classified as type I, 4 cases as type II, 1 case as type III, 2 cases as type IV, 1 case as type V (variant type), and TTE was undiagnosed in all type III-V patients. Additionally, CCT showed 12 extra malformations in these patients, only 5 of them were found by TTE (5/12, 41.7%), and TTE missed all extracardiac malformations. The mean size of CS roof defect was 3.04 ± 1.57 cm. CONCLUSIONS: CCT with various postprocessing technologies has excellent value in diagnosing and differentiating subtypes of UCSS, measuring size of coronary sinus defect, describing accompanying cardiovascular abnormalities.

Dual RNA and 16S ribosomal DNA sequencing reveal arbuscular mycorrhizal fungi-mediated mitigation of selenate stress in Zea mays L. and reshaping of soil microbiota.

Excessively high concentrations of selenium (Se) in soil are toxic to crop plants, and inoculation with arbuscular mycorrhizal fungi (AMF) can reverse Se stress in maize (Zea mays L.). To investigate the underlying mechanisms, maize seedlings were treated with sodium selenate (5 mg Se[VI] kg-1) and/or AMF (Funneliformis mosseae and Claroideoglomus etunicatum). Dual RNA sequencing in mycorrhiza and 16 S ribosomal DNA sequencing in soil were performed. The results showed that Se(VI) application alone decreased plant dry weight, but increased plant Se concentration, total Se content (mainly selenocysteine), and root superoxide content. Inoculation with either F. mosseae or C. etunicatum increased plant dry weight, decreased Se accumulation and selenocysteine proportion, enhanced root peroxidase activity, and alleviated oxidative stress in Se(VI)-treated plants. Inoculation also downregulated the expression of genes encoding Se transporters, assimilation enzymes, and cysteine-rich receptor-like kinases in Se(VI)-stressed plants, similar to plant-pathogen interaction and glutathione metabolism related genes. Conversely, genes encoding selenium-binding proteins and those related to phenylpropanoid biosynthesis were upregulated in inoculated plants under Se(VI) stress. Compared with Se(VI)-free plants, Se tolerance index, symbiotic feedback percentage on plant dry weight, and root colonization rate were all increased in inoculated plants under Se(VI) stress, corresponding to upregulated expression of 'key genes' in symbiosis. AMF inoculation increased bacterial diversity, decreased the relative abundances of selenobacteria related to plant Se absorption (e.g., Proteobacteria and Firmicutes), and improved bacterial network complexity in Se(VI)-stressed soils. We suggest that stress-mediated enhancement of mycorrhizal symbiosis contributed to plant Se(VI) tolerance, whereas AMF-mediated reshaping of soil bacterial community structure prevented excessive Se accumulation in maize.

Effect of bone-shaped nanotube-hydrogel drug delivery system for enhanced osseointegration.

Anodic titanium dioxide nanotubes (TNT) have a range of beneficial theranostic properties. However, a lack of effective osseointegration is a problem frequently associated with the titanium dental implant surface. Here, we investigated whether bone-shaped nanotube titanium implants could enhance osseointegration via promoting initial release of vascular endothelial growth factor 165 (VEGF165) and dual release of recombinant human bone morphogenetic protein-2 (rhBMP-2). Thus, we generated cylindrical-shaped nanotubes (TNT1) and bone-shaped nanotubes (TNT2) through voltage-varying and time-varying electrochemical anodization methods, respectively. Additionally, we prepared rhBMP-2-loaded cylindrical-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F1) and rhBMP-2-loaded bone-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F2) drug delivery systems. We evaluated the characteristics and release kinetics of the drug delivery systems, and then analyzed the cytocompatibility and osteogenic differentiation of these specimens with mesenchymal stem cells (MSCs) in vitro. Finally, we utilized a rat femur defect model to test the bone formation capacity of nanotube-hydrogel drug delivery system in vivo. Among these different nanotubes structures, the bone-shaped one was the optimum structure for growth factor release.

Major Vault Protein Prevents Atherosclerotic Plaque Destabilization by Suppressing Macrophage ASK1-JNK Signaling.

BACKGROUND: Macrophages are implicated in atherosclerotic plaque instability by inflammation and degradation of extracellular matrix. However, the regulatory mechanisms driving these macrophage-associated processes are not well understood. Here, we aimed to identify the plaque destabilization-associated cytokines and signaling pathways in macrophages. METHODS: The atherosclerotic models of myeloid-specific MVP (major vault protein) knockout mice and control mice were generated. Atherosclerotic instability, macrophage inflammatory signaling, and active cytokines released by macrophages were examined in vivo and in vitro by using cellular and molecular biological approaches. RESULTS: MVP deficiency in myeloid cells exacerbated murine plaque instability by increasing production of both MMP (matrix metallopeptidase)-9 and proinflammatory cytokines in artery wall. Mechanistically, expression of MMP-9 was mediated via ASK1 (apoptosis signal-regulating kinase 1)-MKK-4 (mitogen-activated protein kinase kinase 4)-JNK (c-Jun N-terminal kinase) signaling in macrophages. MVP and its α-helical domain could bind with ASK1 and inhibit its dimerization and phosphorylation. A 62 amino acid peptide (MVP-[686-747]) in the α-helical domain of MVP showed a crucial role in preventing macrophage MMP-9 production and plaque instability. CONCLUSIONS: MVP may act as an inhibitor for ASK1-JNK signaling-mediated MMP-9 production in macrophages and, thereby, attenuate unstable plaque formation. Our findings suggest that suppression of macrophage ASK1-JNK signaling may be a useful strategy antagonizing atherosclerotic diseases.

Mycorrhizal symbiosis promotes the nutrient content accumulation and affects the root exudates in maize.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are a group of important symbiotic microorganisms found in ecosystems. Maize is the second most produced food crop globally. To investigate the mechanisms by which mycorrhizal symbiosis improves maize yields, the effects of mycorrhizal symbiosis on root vigor, nutrient accumulation in various tissues, and root exudates were investigated. We propose the following hypothesis: The secretion of organic acids in root exudates has antagonistic or synergistic effects, which are related to the rhizosphere environment. AMF symbiosis will enhance this effect. RESULT: Rhizophagus aggreatus, Claroideoglomus etunicatum, and Funneliformis mosseae were used to inoculate maize plants separately; meanwhile, maize was inoculated with the above three fungi together for another processing. The plant tissues were sampled at five growth stages: V12 (twelve-leaf), VT (Tassel), R1 (Silking), R2 (Blister), and R4 (Dough stage). The root vigor, and nutrient content in different maize organs and organic acids in root exudates were determined in these stages. The results show that mycorrhizal symbiosis significantly improved the root vigor of maize, especially for plants inoculated with F. mosseae. AMF symbiosis significantly increased N, P, and K accumulation. Mixed inoculation with arbuscular mycorrhizal fungi significantly promoted the accumulation of N and K in maize. P accumulation was significantly promoted by C. etunicatum inoculation. Mycorrhizal symbiosis reduced the levels of protocatechuic, vanillic, citric, and ferulic acid in maize root exudates and increased the levels of p-hydroxybenzoic and caffeic acid. Except for syringic, chlorogenic and succinic acid, the levels of other organic acids in root exudates were higher in plants inoculated with F. mosseae than in other treatments. CONCLUSION: This study demonstrates that mycorrhizal symbiosis improves root vigor and promotes nutrient accumulation at various sites; in addition, mycorrhizal symbiosis affects the content of organic acids in root exudates.

Biocompatible Nanotube-Strontium/polydopamine-arginine-glycine-aspartic acid coating on Ti6Al4V enhances osteogenic properties for biomedical applications.

Titanium (Ti) alloys, particularly Ti6 Al4 V, are the most commonly used biomedical implant material. Ti alloys are biologically inert, so there have been continuous efforts to improve their osteogenic properties and clinical performance. Since TiO2 nanotubes (NT) appear to be excellent drug platforms, and strontium reportedly enhances osteogenesis, we constructed a TiO2 nanotube coating on the surface of Ti6 Al4 V and immersed it in Sr (OH)2 solution in order to incorporate Sr into TiO2 nanotubes (NT-Sr). The results of field emission scanning electron microscope and X-ray diffraction analysis verified the fabrication of NT-Sr. We next added polydopamine (PDA) and cyclo- (arginine-glycine-aspartic acid-phenylalanine-cysteine) [c(RGDfC)] peptides to further promote biocompatibility of the implant. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the existence of PDA and c(RGDfC). Mesenchymal stem cells (MSCs) were planted on Ti, NT, NT-Sr, NT-Sr/PDA, and NT-Sr/PDA-RGD surfaces. The adhesion and differentiation of MSCs on different surfaces were evaluated. The mRNA expression of alkaline phosphatase, runt-related transcription factor 2 (Runx2) and type I collagen (Col I) of different groups were also tested. Finally, we observed that the NT-Sr/PDA-RGD group showed significantly better performance than other groups in terms of the differentiation and osteogenesis-related gene expression of MSCs. Thus, the NT-Sr/PDA-RGD complex may be an important modification strategy for Ti, as it shows excellent osteogenic potential.

Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.

Osteosarcoma (OS) is the most common primary bone tumor. Its high mortality rate and metastasis rate seriously threaten human health. Currently, the treatment has reached a plateau, hence we urgently need to explore new therapeutic directions. In this paper, we found that Trio was highly expressed in osteosarcoma than normal tissues and promoted the proliferation, migration, and invasion of osteosarcoma cells. Furthermore, Trio inhibited osteosarcoma cells' osteogenic differentiation in vitro and accelerated the growth of osteosarcoma in vivo. Given Trio contains two GEF domains, which have been reported as the regulators of RhoGTPases, we further discovered that Trio could regulate osteosarcoma progression and osteogenic differentiation through activating RhoGTPases. In summary, all our preliminary results showed that Trio could be a potential target and prognostic marker of osteosarcoma.