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Odontogenesis-associated phosphoprotein (ODAPH) is a recently discovered enamel matrix protein. Our previous study demonstrated that knockouting out Odaph in mice resulted in enamel hypomineralization. To further investigate the effect of Odaph on enamel mineralization, we constructed an Odaph overexpression mouse model, controlled by an amelogenin promoter. Our histological analysis of OdaphTg mice revealed that the enamel layer was thinner than in WT mice. An uneven, thinner enamel layer was confirmed using micro-computed tomography (uCT). It was subsequently found that the Tomes' processes lost their normal morphology, resulting in the loss of the enamel prism structure. These results indicate that Odaph overexpression in ameloblasts led to enamel dysplasia. In conjunction with this, Odaph overexpression hindered Amelx secretion, and may result in endoplasmic reticulum stress. Interestingly, uCT revealed that enamel had higher mineral density at the secretory stage; due to this, we did the histological staining for the mineralization-related proteins Alkaline phosphatase (ALPL) and Runt-related transcription factor 2 (RUNX2). It was observed that these proteins were up-regulated in OdaphTg mice versus WT mice, indicating that Odaph overexpression led to abnormal enamel mineralization. To confirm this, we transfected ameloblast-like cell line (ALC) with Odaph overexpression lentivirus in vitro and identified that both Alpl and Runx2 were strikingly upregulated in OE-mus-Odaph versus OE-NC cells. We concluded that the ectopic overexpression of Odaph in ameloblasts led to abnormal enamel mineralization. In summary, Odaph profoundly influences amelogenesis by participating in enamel mineralization. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis (HF) is a process that occurs during the progression of several chronic liver diseases, for which there is a lack of effective treatment options. Carthamus tinctorius L. (CTL) is often used in Chinese or Mongolian medicine to treat liver diseases. However, its mechanism of action remains unclear. In the present study, CTL was used to treat rats with CCl4-induced HF. The histopathological, biochemical and HF markers of the livers of the rats were analyzed, and CTL-infused serum was used to treat hepatic stellate cells (HSCs) in order to detect the relevant markers of HSC activation. Protein expression pathways were detected both in vitro and in vivo. Histopathological results showed that CTL significantly improved CCl4-induced liver injury, reduced aspartate aminotransferase and alanine aminotransferase levels, promoted E-cadherin expression, and decreased α-smooth muscle actin (SMA), SOX9, collagen I and hydroxyproline expression. Moreover, CTL-infused serum was found to decrease α-SMA and collagen I expression in HSCs. Further studies showed that CTL inhibited the activity of the PI3K/Akt/mTOR pathway in the rat livers. Following the administration of the PI3K agonist 740Y-P to HSCs, the inhibitory effect of CTL on the PI3K/Akt//mTOR pathway was blocked. These results suggested that CTL can inhibit HF and HSC activation by inhibiting the PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR‐23a‐5p underling this pathological process is largely not clear. The purpose of this study was to investigate the role of miR‐23a‐5p in hepatic fibrosis and HSC activation. Methods: The content of miR‐23a‐5p in hepatic fibrosis induced by N‐nitrosodimethylamine (NDMA) and HSC activation induced by platelet‐derived growth factor (PDGF) was detected by qRT‐PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT‐PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual‐luciferase reporter system verifies the interaction between miR‐23a‐5p with PTEN or miR‐23a‐5p with lncRNA LOC102551149 in HSC‐T6. siRNA and miRNA mimic transfer to HSC‐T6 to detect the function of lncRNA LOC102551149 and miR‐23a‐5p on HSC activation. Results: After hepatic fibrosis and HSC activation happened, the expression of miR‐23a‐5p was up‐regulated, whereas anti‐miR‐23a‐5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR‐23a‐5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR‐23a‐5p through base pairing, and siRNA LOC102551149 or exogenous miR‐23a‐5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. Conclusion: We demonstrate mechanism pathway of miR‐23a‐5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis. [ABSTRACT FROM AUTHOR]

The traffic during rush hour in metropolises is always in heavy congestion, so the wagon trucks of logistic transportation are mostly forbidden during rush hour. In fact, quite a few logistic transportations are fulfilled by converted passenger vehicles. This paper aims to model the logistic companies' behaviors and see through the effect of their cooperation modes on the companies and on the whole traffic conditions. The logistic companies decide their transportation pricing, warehouse using and route choosing separately or as a group (cooperation) to compete with others. It is also assumed that the heavy freight vehicles, light freight vehicles and the auto vehicles share the same network. Three models based on variational inequalities are proposed to describe the companies' behaviors when there is no cooperation, simple cooperation and deep cooperation, respectively, and the modified diagonalization method is used to solve these models. The total transportation demand is elastic, which depends on the users' choice of logistics company and further depends on all the companies' prices, warehouse and route choices. The goodness of different coalitions to the companies and the whole traffic system is well investigated in the numerical examples. [ABSTRACT FROM AUTHOR]

In this paper, the problem of simultaneous fault detection and control (SFDC) for a 3-phase 4-wire converter with neutral bridge arm, which is commonly used in the application of smart grid and distributed generation, is considered. By employing a detector/controller module consisting of a dynamic observer and a state feedback controller based on the dynamic observer, a multi-objective H ∞ optimization SFDC framework is established to achieve the fault detection and control objectives simultaneously. Extended linear matrix inequalities (LMIs) characterizations are obtained as the strict conditions for solvability of the SFDC problem. The proposed method can reduce the designing conservativeness and overcome the shortcoming of existing SFDC methods by applying the superiority of dynamic observer. The achievable performance is analyzed quantitatively and the effectiveness of our designing method was illustrated and verified both in simulation and the hardware-in-the-loop(HIL) simulation which is conducted in a real-time simulation platform built by StarSim and MT respectively. • A SDFC problem with the dynamic observer is established. • This method provides strict LMI condition for observer parameter and controller gain. • With introduced variables and linear transformation, design conservatism is reduced. • Conducted software simulation and hardware in the loop simulation in real time. [ABSTRACT FROM AUTHOR]

Human infections caused by Brucella (called brucellosis) are among the most common zoonoses worldwide with an estimated 500,000 cases each year. Since chronic Brucella infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As a facultative intracellular bacterium, Brucella is strictly parasitic in the host cell. Here, we performed proteomic and transcriptomic and metabolomic analyses on Brucella infected patients, mice and cells that provided an extensive "map" of physiological changes in brucellosis patients and characterized the metabolic pathways essential to the response to infection, as well as the associated cellular response and molecular mechanisms. This is the first report utilizing multi‐omics analysis to investigate the global response of proteins and metabolites associated with Brucella infection, and the data can provide a comprehensive insight to understand the mechanism of Brucella infection. We demonstrated that Brucella increased nucleotide synthesis in the host, consistent with increased biomass requirement. We also identified IMPDH2, a key regulatory complex that controls nucleotide synthesis during Brucella infection. Pharmacological targeting of IMPDH2, the rate‐limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits B. abortus growth both in vitro and in vivo. Through screening a library of natural products, we identified oxymatrine, an alkaloid obtained primarily from Sophora roots, is a novel and selective IMPDH2 inhibitor. In further in vitro bacterial inhibition assays, oxymatrine effectively inhibited the growth of B. abortus, which was impaired by exogenous supplementation of guanosine, a salvage pathway of purine nucleotides. This moderately potent, structurally novel compound may provide clues for further design and development of efficient IMPDH2 inhibitors and also demonstrates the potential of natural compounds from plants against Brucella. [ABSTRACT FROM AUTHOR]

Objective: Long‐term and high exposure to UV radiation can lead to the development of skin photoaging diseases. Therefore, there is an ongoing need for more natural and safe drugs to prevent or treat skin photoaging diseases. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database were used to collect the active compounds and corresponding targets of Cnidii Fructus, Arnebiae Radix, Angelicae Sinensis Radix, Poria, and Borneolum. The GeneCards database and the NCBI Gene database were used to collect the targets of skin photoaging diseases. The STRING database was used to construct a protein–protein interaction network formed by the intersecting targets of drugs and diseases. The Metascape database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the targets. Molecular docking between active compounds and targets was verified by Autodock. After that, the skin photoaging model of mice was established and treated with MP gel. The skin characterization on the back of mice was observed, and the ameliorative effect of MP gel on skin photoaging was evaluated by histological and epidermal thickness assays. The MDA content and SOD activity were measured. Caspase‐3 expression in mouse skin tissues was detected by immunohistochemistry, quantitative real‐time polymerase chain reaction assay, and Western blot. Results: The results of network pharmacology experiments showed that the natural drugs have multi‐component, multi‐target therapeutic disease characteristics. The results of animal studies showed that MP gel improved the health of photoaged skin, promoted skin structural integrity, had antioxidant properties and significantly inhibited caspase‐3 expression. Conclusion: The experimental validation of the results of the preliminary network pharmacology analysis was carried out in animal experiments, which confirmed part of the mechanism of action of MP gel in the prevention and treatment of skin photoaging. [ABSTRACT FROM AUTHOR]

Gamete and embryo transport is an important function of the oviduct. This transport involves both smooth muscle contraction and epithelial cell secretions, the former of which is mediated by prostaglandins (PGs) and their receptors. Our aim was to study the regulation of prostaglandin E 2 and prostaglandin F 2α receptors (EP 2 , EP 4 , and FP receptor) by estradiol in bovine oviduct smooth muscle. EP 2 , EP 4 , and FP receptor mRNA and protein expression was investigated using real-time RT-PCR and Western blot analyses, respectively. To evaluate the contraction or relaxation of cultured bovine oviductal smooth muscle tissue, peristalsis was used to assess contractile activity. EP 2 , EP 4 , and FP receptor mRNA and protein expression was increased in oviductal smooth muscle tissue after treatment with different concentrations of estradiol for various durations. The expression of all receptors peaked at an estradiol concentration of 10 −11 mol/L after 8 h of treatment, whereas no increase in expression was observed after fulvestrant (a selective antagonist of E 2 receptor) treatment, indicating that E 2 interacts with specific E 2 nuclear receptors to regulate EP 2 , EP 4 , and FP receptor expression. Although PGF 2α and PGE 2 induced both contraction and relaxation, no significant differences were found in contractility between the estradiol-treated and control groups, with both groups of cultured smooth muscle strips showing similar vitality. In conclusion, estradiol increases EP 2 , EP 4 , and FP receptor mRNA and protein expression in bovine oviductal smooth muscle when added for different periods of time and at different concentrations. Additionally, E 2 is transported intracellularly and interacts with specific E 2 nuclear receptors to regulate their expression. [ABSTRACT FROM AUTHOR]

Brucellosis is a worldwide zoonotic disease caused by Brucella spp. Human infection often results from direct contact with tissues from infected animals or by consumption of undercooked meat and unpasteurised dairy products, causing serious economic losses and public health problems. The male genitourinary system is a common involved system in patients with brucellosis. Among them, unilateral orchitis and epididymitis are the most common. Although the clinical and imaging aspect of orchi-epididymitis caused by brucellosis have been widely described, the cellular and molecular mechanisms involved in the damage and the immune response in testis and epididymis have not been fully elucidated. In this review, we first summarised the clinical characteristics of Brucella epididymo-orchitis and the composition of testicular and epididymal immune system. Secondly, with regard to the mechanism of Brucella epididymoorchitis, we mainly discussed the process of Brucella invading testis and epididymis in temporal and spatial order, including i) Brucella evades innate immune recognition of testicular PRRs；ii) Brucella overcomes the immune storm triggered by the invasion of testis through bacterial lipoproteins and virulence factors, and changes the secretion mode of cytokines; iii) Brucella breaks through the blood-testis barrier with the help of macrophages, and inflammatory cytokines promote the oxidative stress of Sertoli cells, damaging the integrity of BTB; iv) Brucella inhibits apoptosis of testicular phagocytes. Finally, we revealed the structure and sequence of testis invaded by Brucella at the tissue level. This review will enable us to better understand the pathogenesis of orchi-epididymitis caused by brucellosis and shed light on the development of new treatment strategies for the treatment of brucellosis and the prevention of transition to chronic form. Facing the testicle with immunity privilege, Brucella is like Bruce Lee in the movie Game of Death, winning is survival while losing is death. We summarized the clinical features and pathological changes of Brucellaepididymoorchitis. Our research reveals the pathogenesis of Brucella epididymoorchitis, which mainly includes the subversion of testicular immune privilege by Brucella and a series of destructive reactions derived from it. As a basic framework and valuable resource, this study can promote the exploration of the pathogenesis of Brucella and provide reference for determining new therapeutic targets for brucellosis in the future. [ABSTRACT FROM AUTHOR]

Objective: The aim of this investigation was to study the effects of Runt‐related transcription factor 2 (Runx2) on the junctional epithelium and alveolar bone. Methods: The attachment level of the junctional epithelium and the resorption of alveolar bone were analyzed by histology and scanning electron microscopy. The expression of amelotin was determined by immunohistochemistry, Western blot, and real‐time PCR. The ultrastructure of the dentogingival interface was observed by transmission electron microscopy. Results: The cKO mice demonstrated remarkable attachment loss, epithelial hyperplasia, and alveolar bone loss. The relative protein and mRNA expression of amelotin was increased in the junctional epithelium of the cKO mice. The attachment apparatus of the cKO mice showed ultrastructural deficiency. Conclusions: Loss of Runx2 led to the junctional epithelium and alveolar bone defects in mice. Runx2 may play a crucial role in maintaining the integrity of the dentogingival junction and the normal structure of alveolar bone. [ABSTRACT FROM AUTHOR]

[Display omitted] The rational design of cost-effective oxygen evolution reaction (OER) electrocatalysts is important for the future global energy supply but remains a formidable challenge. Herein, Cl-doped boron-rich carbon nanocomposites embedded with NiFe alloys (FexNiy@ClBC) were constructed via a facile mechanochemical-assisted strategy for use as an OER electrocatalyst. Combination of the unique Cl-doped boron-rich carbon species with the NiFe alloy optimized the electronic structure and surface properties. Meanwhile, Density flooding theory (DFT) calculations confirmed that the Fe1Ni2@ClBC catalyst weakened the strong adsorption of *O and *OOH intermediates due to the introduction of Cl, which reduced the ΔGmax of the OER process and led to a more favorable reaction kinetics. As a result, this catalyst exhibited a remarkable OER performance with a low overpotential (259 mV at 10 mA cm−2, 296 mV at 50 mA cm−2) and a small Tafel slope (49 mV dec−1). The Fe1Ni2@ClBC catalyst exhibited a considerable stability under harsh alkaline conditions for over 40 h because of its external highly robust porous carbon shell. This work contributes to the understanding of nonmetallic heteroatom-doped carbon materials and should inspire the design of low-cost alloy electrocatalysts. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fe-doped multiphase Ni(OH) 2 successfully achieved by Fe2+/Fe3+ modulation. • Formation of a closely bound interface in multiphase catalysts. • Enhanced active Ni3+ species formation and optimized intermediate free energies. • Multiphase Fe-α,β-Ni(OH) 2 –2 catalyst exhibited an outstanding OER performance. The exploration of catalysts for oxygen evolution reaction (OER) using the advantages of interface engineering is an attractive strategy for achieving highly efficient electrochemical water splitting. In this study, Fe-doped multiphase nickel hydroxide (Fe-α,β-Ni(OH) 2) was successfully prepared with a unique interface by modulating the Fe2+ and Fe3+ ratios in a feasible one-step hydrothermal process. This multiphase catalyst powder significantly contributed to the OER performance, with a low overpotential of 259 mV at 10 mA cm−2 (grown on carbon cloth substrates, 260 mV at 100 mA cm−2) and excellent catalytic stability during the 70-h OER process under extreme conditions. Based on the experimental and theoretical results, the unique interface between the Fe-α-Ni(OH) 2 and Fe-β-Ni(OH) 2 phases optimized the adsorption free energies of oxygen-containing intermediates and accelerated the formation of Ni3+ active species during the OER, leading to a large electrochemically active surface area (ECSA), which considerably enhanced the OER performance. This study provides novel insight into interface engineering and the design of high-performance OER catalysts based on earth-abundant transition-metal elements. [ABSTRACT FROM AUTHOR]