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The reaction kinetics of phosphate ore particles reacting with excessive phosphoric acid was investigated. The effects of various operating parameters including reaction temperature (333.15–353.15 K), concentration of phosphoric acid (20–40 ωt% P2O5) and particle size (260, 190, 134, 96, 59 μm) on the reaction performance were investigated first. The results indicated that the reaction rate increased with the increase of reaction temperature, concentration of phosphoric acid, as well as the decrease of particle size. The Drozdov model could be used to describe the reaction behaviors. The activation energy results suggested that the rate-determining step was the diffusion of H+ through the residual layer. The precipitation of insoluble phosphates would cover on the surface and lead to a decrease of dissolution extent. Controlling the product forms is crucial to the improvement of dissolution extent. The specific surface area of the phosphate ore also had a significant impact on the reaction rate and dissolution extent. [ABSTRACT FROM AUTHOR]

The protection of the blood‐brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR‐3064‐5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR‐3064‐5p in exosomes secreted by DCs (DCs‐exo). An SAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL‐IF staining. We found that overexpression of miR‐3064‐5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin‐3, ZO‐1), whereas knockdown of miR‐3064‐5p exerted the opposite effect. Dual‐LUC assay confirmed that miR‐3064‐5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL‐6, IL‐1β, IFN‐γ, and TGF‐β1) levels and apoptosis. The results of the co‐IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs‐exo reduced brain edema, upregulated miR‐3064‐5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs‐exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR‐3064‐5p enhanced the protective effect of DCs‐exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR‐3064‐5p to ameliorate BBB damage after SAH. Mechanistically, miR‐3064‐5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway. [ABSTRACT FROM AUTHOR]

Sorafenib is the first line drug for hepatocellular carcinoma (HCC) therapy. However, HCC patients usually acquire resistance to sorafenib treatment within 6 months. Recent evidences have shown that anticancer drugs with antiangiogenesis effect (e.g. , sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues. Therefore, repolarization of TAMs phenotype could be expected to not only eliminate the influence of TAMs on sorafenib lethality to HCC cells, but also provide an additional anticancer effect to achieve combination therapy. However, immune side effects remain a great challenge due to the non-specific macrophage repolarization in normal tissues. We herein employed a tumor microenvironment (TME) pH-responsive nanoplatform to concurrently transport sorafenib and modified resiquimod (R848-C16). This nanoparticle (NP) platform is made with a TME pH-responsive methoxyl-poly(ethylene glycol)- b -poly(lactic- co -glycolic acid) copolymer. After intravenous administration, the co-delivery NPs could highly accumulate in the tumor tissues and then respond to the TME pH to detach their surface PEG chains. With this PEG detachment to enhance uptake by TAMs and HCC cells, the co-delivery NPs could combinatorially inhibit HCC tumor growth via sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs into tumoricidal M1-like macrophages. Anticancer drugs with antiangiogenesis effect (e.g., sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues to restrict the anticancer effect. In this work, we designed and developed a tumor microenvironment (TME) pH-responsive nanoplatform for systemic co-delivery of sorafenib and resiquimod in hepatocellular carcinoma (HCC) therapy. These co-delivery NPs show high tumor accumulation and could respond to the TME pH to enhance uptake by TAMs and HCC cells. With the sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs, the co-delivery NPs show a combinational inhibition of HCC tumor growth in both xenograft and orthotopic tumor models. [Display omitted] [ABSTRACT FROM AUTHOR]

Germanium-based multi-metallic-oxide materials have advantages of low activation energy, tunable output voltage, and high theoretical capacity. However, they also exhibit unsatisfactory electronic conductivity, sluggish cation kinetics, and severe volume change, resulting in inferior long-cycle stability and rate performance in lithium-ion batteries (LIBs). To solve these problems, we synthesize metal-organic frameworks derived from rice-like Zn2GeO4 nanowire bundles as the anode of LIBs via a microwave-assisted hydrothermal method, minimizing the particle size and enlarging the cation's transmission channels, as well as, enhancing the electronic conductivity of the materials. The obtained Zn2GeO4 anode exhibits superior electrochemical performance. A high initial charge capacity of 730 mAhg−1 is obtained and maintained at 661 mAhg−1 after 500 cycles at 100 mA g−1 with a small capacity degradation ratio of ~0.02% for each cycle. Moreover, Zn2GeO4 exhibits a good rate performance, delivering a high capacity of 503 mA h g−1 at 5000 mA g−1. The good electrochemical performance of the rice-like Zn2GeO4 electrode can be attributed to its unique wire-bundle structure, the buffering effect of the bimetallic reaction at different potentials, good electrical conductivity, and fast kinetic rate. [ABSTRACT FROM AUTHOR]

AMPK plays significant roles in the modulation of metabolic reprogramming and viral infection. However, the detailed mechanism by which AMPK affects viral infection is unclear. The present study aims to determine how AMPK influences white spot syndrome virus (WSSV) infection in shrimp (Marsupenaeus japonicus). Here, we find that AMPK expression and phosphorylation are significantly upregulated in WSSV-infected shrimp. WSSV replication decreases remarkably after knockdown of Ampkα and the shrimp survival rate of AMPK-inhibitor injection shrimp increases significantly, suggesting that AMPK is beneficial for WSSV proliferation. Mechanistically, WSSV infection increases intracellular Ca2+ level, and activates CaMKK, which result in AMPK phosphorylation and partial nuclear translocation. AMPK directly activates mTORC2-AKT signaling pathway to phosphorylate key enzymes of glycolysis in the cytosol and promotes expression of Hif1α to mediate transcription of key glycolytic enzyme genes, both of which lead to increased glycolysis to provide energy for WSSV proliferation. Our findings reveal a novel mechanism by which WSSV exploits the host CaMKK-AMPK-mTORC2 pathway for its proliferation, and suggest that AMPK might be a target for WSSV control in shrimp aquaculture. AMPK and its downstream signaling pathways are implicated in the white spot syndrome virus (WSSV) response of the shrimp Marsupenaeus japonicus, with WSSV using this pathway to promote its proliferation. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. Methods Humanized fragments, consisting of the endothelial cell‐specific K18 promoter, human ST6GAL1‐encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. Results Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. Conclusion A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Abstract Background Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. Methods Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. Results It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. Conclusions Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Introduction: The microbiome inhabiting plant leaves is critical for plant health and productivity. Wild soybean (Glycine soja), which originated in China, is the progenitor of cultivated soybean (Glycine max). So far, the community structure and assembly mechanism of phyllosphere microbial community on G. soja were poorly understood. Methods: Here, we combined a national-scale survey with high-throughput sequencing and microsatellite data to evaluate the contribution of host genotype vs. climate in explaining the foliar microbiome of G. soja, and the core foliar microbiota of G. soja were identified. Results: Our findings revealed that both the host genotype and environmental factors (i.e., geographic location and climatic conditions) were important factors regulating foliar community assembly of G. soja. Host genotypes explained 0.4% and 3.6% variations of the foliar bacterial and fungal community composition, respectively, while environmental factors explained 25.8% and 19.9% variations, respectively. We further identified a core microbiome thriving on the foliage of all G. soja populations, including bacterial (dominated by Methylobacterium-Methylorubrum, Pantoea, Quadrisphaera, Pseudomonas, and Sphingomonas) and fungal (dominated by Cladosporium, Alternaria, and Penicillium) taxa. Conclusion: Our study revealed the significant role of host genetic distance as a driver of the foliar microbiome of the wild progenitor of soya, as well as the effects of climatic changes on foliar microbiomes. These findings would increase our knowledge of assembly mechanisms in the phyllosphere of wild soybeans and suggest the potential to manage the phyllosphere of soya plantations by plant breeding and selecting specific genotypes under climate change. [ABSTRACT FROM AUTHOR]

We study the small mass limit for a class of Hamiltonian systems with multiplicative non-Gaussian Lévy noise. Derivation of the limiting equation depends on the structure of the stochastic Hamiltonian systems, in which a discontinuous noise-induced drift term arises. Firstly, we show that the momentum in the stochastic Hamiltonian system converges to zero when the kinetic energy has polynomial growth. Then, we prove that the stochastic Hamiltonian system with classical kinetic energy converges to the limiting equation in probability, with respect to Skorokhod topology as the mass tends to zero. [ABSTRACT FROM AUTHOR]

Summary: In the optimization process of multi‐objective firefly algorithm, population is easy to fall into local optimum, which leads to poor population distribution and convergence. In order to solve this problem, this article proposes a multi‐objective firefly algorithm with multi‐strategy integration (MOFA‐MSI). First, in order to improve the distribution of population, MOFA‐MSI proposes a cloning strategy, which calculates the distribution degree of individuals in population, clones them according to their distribution degree, and local mutation in the cloned individual produce a new population with good distribution. Then, in order to maintain the convergence of population, a position updating strategy based on non‐dominated sorting is proposed. The new population after local mutation are performed by non‐dominated sorting, and the fireflies with higher rank guide the fireflies with lower rank to fly, and then new population are generated by global mutation after position updated. Finally, the greedy strategy is adopted to select solutions with better distribution and convergence and store them in external files. In the experimental part, different types of test problems are used to test the performance of each algorithm, and MOFA‐MSI is compared with three classical and four new multi‐objective evolutionary algorithms. The results show that MOFA‐MSI is superior to other seven algorithms in terms of the distribution and convergence of population. [ABSTRACT FROM AUTHOR]