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• A comprehensive parametric study of 544 numerical models for hybrid I-girders under uniform bending is carried out. • The design method of cross-section behaviour for hybrid I-girders in AASHTO specification and Eurocode 3 are assessed. • The design moment expression of the Direct Strength Method is proposed for the cross-section resistance design of hybrid I-girders. • The design approach of the Continuous Strength Method for hybrid I-girders is derived through rigorous analytical analysis. Hybrid steel I-girders, characterised by different strength grades for the flange and web, offer the potential to optimise material utilisation in various loading scenarios. The current American and European standards for steel bridges (AASHTO specification and Eurocode 3) have incorporated specific provisions for the design of hybrid I-girders with the web strength grade lower than the flange. Based on the data obtained from the validated numerical investigation, the limiting slenderness ratio for cross-section classification and applicability of the designated bending moment resistance (flexural strength) in standards are assessed. The assessment results reveal that the compact/Class 1 sections with flange yield strength of 690 N /mm2 fail to meet the current codified ductility requirement, and the non-compact flange slenderness limits in AASHTO specification are demonstrated to be excessively lenient. A reduction factor of 1.2 is suggested to narrow down the Class 1 width-to-thickness ratio in Eurocode 3 for I-girders with compression flange steel grade equivalent to S690. Furthermore, the design moment expression of the Direct Strength Method (DSM) is proposed for the cross-section resistance design of hybrid I-girders, and the design approach for the Continuous Strength Method (CSM) is also derived through analytical analysis. Instead of addressing the slenderness of the flange and web individually, the DSM and CSM adopt the concept of overall cross-section slenderness, which allows for a more accurate consideration of the flange-web interaction and offers the potential to streamline the calculation process for cross-section resistance. The statistical and reliability analyses indicate that all the design methods could achieve the reasonable moment resistance predictions for the cross-section resistance of hybrid I-girders. [ABSTRACT FROM AUTHOR]

Liver fibrosis (LF) is a pathological process of the liver that threatens human health. Currently, effective treatments are still lacking. Esculin, a prominent constituent found in the Fraxinus rhynchophylla. (bark), Aesculus hippocastanum. (bark), and Cichorium intybus. (herb), has been shown to possess significant anti-inflammatory, antioxidant, and antibacterial properties. However, to date, there have been no studies investigating its potential efficacy in the treatment of LF. The study aims to investigate the therapeutic effect of esculin on LF and elucidate its potential molecular mechanism. Carbon tetrachloride (CCl 4) was injected intraperitoneally to induce LF in mice, and transforming growth factor β1 (TGF-β1) was injected to induce LX-2 cells to investigate the improvement effect of esculin on LF. Kit, histopathological staining, immunohistochemistry (IHC), immunofluorescence (IF), polymerase chain reaction (PCR), and western blot (WB) were used to detect the expression of fiber markers and nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway in liver tissue and LX-2 cells. Finally, molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) were used to verify the targeting between Nrf2 and esculin. Esculin significantly inhibited CCl 4 -induced hepatic fibrosis and inflammation in mice. This was evidenced by the improvement of liver function indexes, fibrosis indicators, and histopathology. Additionally, esculin treatment prominently reduced the levels of pro-inflammatory factors, oxidative stress, and liver Fe2+ in CCl 4 -induced mice. In vitro studies also showed that esculin treatment significantly inhibited TGF-β1-induced LX-2 cell activation and decreased alpha-smooth muscle actin (α-SMA) and collagen I expression. Mechanism experiments proved that esculin can activate the Nrf2/GPX4 signaling pathway and inhibit liver ferroptosis. However, when LX-2 cells were treated with the Nrf2 inhibitor (ML385), the therapeutic effect of esculin significantly decreased. This study is the first to demonstrate that esculin is a potential natural active ingredient in the treatment of LF, which can inhibit the activation of hepatic stellate cells (HSC) and improve LF. Its therapeutic effect is related to the activation of the Nrf2/GPX4 signaling pathway. Schematic diagram of the model for the effect of esculin on liver fibrosis. Esculin reduces hepatic stellate cell ferroptosis and inhibits its activation by activating the Nrf2/GPX4 signaling pathway, thereby reducing the severity of liver fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation on cold-formed steel rectangular and square hollow sections (RHSs and SHSs) with subsequent heat-treatment under combined compression and cyclic lateral loads. A total of 25 specimens designed with different parameters, including slenderness ratios (b/t and d/t) and axial load ratio (n) ranging from 0 to 0.5 were tested. Material tests were carried out to confirm the material ductility requirements stated in Eurocode being reached. Failure modes, moment-rotation curves, secant stiffness, energy dissipation and plastic hinge length presented were analysed. In addition, deformation capacity was evaluated in terms of maximum and ultimate rotations. The comparison results between plastic rotation limits proposed by design codes and the test results indicate that AISC 341-16 is more suitable for the design of cold formed hollow sections with moderate heat treatment under this investigation, though the recommended reduction factor of axial load might be conservative. • Cyclic behaviour of cold-formed hollow section with subsequent heat-treatment was investigated. • Twenty-five beam-column specimens were tested under axial load with monotonic and cyclic lateral load. • Secant stiffness and energy dissipation capacity were evaluated. • Comparison among test results and plastic rotation limits from current design codes. [ABSTRACT FROM AUTHOR]

The effective fermentation of organic waste for polyhydroxyalkanoate (PHA) production is crucial for waste pollution prevention and comprehensive utilization. Glycerol, a common component of organic waste and a by-product of biodiesel production, can serve as a valuable raw material for PHA synthesis. This study explored the potential of metal-organic frameworks (MOFs), specifically MOF-808, to enhance the PHA production by Cupriavidus necator (C. necator) and Bacillus cereus (B. cereus) using glycerol as the substrate. Our results demonstrated that the addition of MOF-808 significantly promoted PHA synthesis without altering the PHA composition. Notably, the proportion of PHA to cell dry weight (CDW) increased significantly (P < 0.05) in both C. necator (from 17.17% to 30.43%) and B. cereus (from 11.30% to 37.93%), with a shortened growth period observed in the latter. The enhanced superproton transport properties of MOF-808 elevated the ATP energy supply level, regulated coenzyme A metabolism, and modulated the PHA synthesis pathway in the bacterial strains. Additionally, MOF-808 improved the utilization of the PHA precursor acetyl-CoA by C. necator , and enhanced the PHA production in B. cereus by facilitating cell growth and PHA synthesis in two distinct stages. Importantly, the recovered MOF-808 structure remained stable, enabling potential recycling. This study provides compelling evidence for the enhancement of PHA production and offers valuable insights into the utilization of organic waste as a valuable resource. [Display omitted] • Enhancement of MOF-808 on PHA production by C. necator and B. cereus was studied. • MOF-808 forms hydrogen bond network to increase ATP energy supply for PHA synthesis. • The proton gradient is heightened, and coenzyme A is activated by the abundant H+. • MOF-808 accelerates the B. cereus growth and diverts the carbon flow of C. necator. • This study provides new idea for improving PHA production from organic waste. [ABSTRACT FROM AUTHOR]

This paper presents a numerical investigation on the local buckling behaviour of high strength steel (HSS) and hybrid I-sections under axial compression, which has not been comprehensively discussed in previous literature. Three sectional steel combinations, featuring different web strength grades (Q690, Q460, and Q355) and using HSS Q690 flange plates, were studied. Through the validated numerical method, parametric studies on the effect of web strength grade, boundary condition and plate slenderness were carried out. The design specifications in European, Australian, and American codes were evaluated using the results of 243 numerical models and collated test data. In addition, the continuous strength method (CSM), direct strength method (DSM), and Kato's method, which can account for element interaction were extended to design for the local buckling behaviour of HSS and hybrid I-sections subjected to axial compression. Assessment results showed that ANSI/AISC 360-16 provides more accurate results than Eurocode 3 and AS 4100. Statistical and reliability results demonstrated the satisfactory reliability level of the proposed design expressions for CSM, DSM, and Kato's design methods. This paper provides insight into the local buckling behaviour and mechanism behind plate interaction of hybrid I-sections. • Three web strength grades-Q690, Q460 and Q355 are considered for welded I-sections with Q690 flange. • A parametric study of 243 numerical models for welded I-sections under axial compression is carried out. • Critical plate element governs the local buckling behaviour of welded I-sections in compression. • Normalised ultimate loads of welded I-sections are marginally affected by the web strength grade. • Newly developed design methods, including the direct strength method, the continuous strength method, and the method by Kato are extended. [ABSTRACT FROM AUTHOR]

Highlights • A hysteretic model for steel piers considering the local buckling of steel plates is proposed. • The model provides an efficient and practical seismic response calculation methodology for steel piers. • The effectiveness of the proposed model under cyclic loads is verified. • The circular and box section single-column Q345qC constructed steel piers are taken as examples. • The empirical formulas with high reliability of the degradation parameter in the proposed hysteretic model are established. Abstract The pier is a vital structural component of bridges and thus critically considered in the seismic design. In order to provide an accurate and efficient methodology in the analysis of seismic response, a hysteretic model considering the effect of local buckling of steel plates is proposed for steel piers. In the hysteretic model, the Giuffre-Menegotto-Pinto hysteresis model is employed to establish the hysteresis curve equation, and the energy-based Ibarra-Krawinkler degradation rule is followed to describe the deterioration rule of structural bearing capacity and stiffness. In this study, a widely used Chinese steel Q345qC was taken as an example to illustrate the proposed model for steel piers. At first, the seismic performance of steel piers under horizontal cyclic load was analyzed. Then, the empirical formulae of the vital limit state points for evaluating the structural seismic performance were established, and further the identification of the decisive parameter (degradation parameter) of the hysteretic model was carried out. Morever, the verification on the effectiveness of the proposed model was verified, and the results showed its applicability and accuracy for steel piers under horizontal cyclic loads. Finally, the application of the proposed model in the seismic calculation of steel piers was interpreted. [ABSTRACT FROM AUTHOR]

[Display omitted] • The improvement of PHA metabolic pathways in C. necator and B. cereus were studied. • C. necator has better PHA synthesis ability and substrate versatility than B. cereus. • Lactate has active amino acid pathway and aminobutyric acid pathway in PHA synthesis. • PHA was inhibited by the carbon competition or limited by the amount of acetyl-CoA. • This study enhances the understanding of PHA synthesis of organic solid waste. The production of polyhydroxyalkanoate (PHA) from organic solid waste is a research hotspot. However, the allocation and conversion mechanism of different carbon resources between precursor routes and PHA metabolism remains unclear. We compared the PHA synthesis of dominant functional bacteria, Cupriavidus necator (C. necator) and Bacillus cereus (B. cereus), and replenished the metabolic pathways of primitive components (glucose, glycerin, lactic acid and propionic acid). The results showed that the PHA accumulation ability of C. necator (11.8%∼36.5%) was better than that of B. cereus (10.1%∼24.5%). C. necator had a faster rate of cell growth and PHA synthesis than B. cereus , which showed advantages in production efficiency. Most of the carbon of glucose flowed to the direct poly-3-hydroxybutyrate synthesis pathway. The carbon competition inhibited the PHA production from glycerin in C. necator, and cysteine metabolism was an effective pathway for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis in B. cereus. There were active amino acid pathway and aminobutyric acid pathway in the utilization of lactic acid in C. necator and B. cereus , respectively. The yield of copolymer was limited by acetyl-CoA in propionic acid system. This study laid the foundation for exploring the PHA synthesis from the components of organic solid waste. [ABSTRACT FROM AUTHOR]

Polysaccharide, as a promising candidate to meet the medication requirement of ulcerative colitis (UC), is increasingly attracting extensive interest. Dendrobium officinale has been widely used to treat gastrointestinal sickness in the clinical treatment of Traditional Chinese Medicine. However, it remains largely unknown whether polysaccharides (DOPS) from Dendrobium officinale can treat UC. The purpose of this paper is to confirm therapeutic action of DOPS to UC and explored its underlying mechanisms. We noted that DOPS could dramatically improve clinical signs and symptoms, decrease mortality, alleviate colonic pathological damage, and reestablish the balance of pro- and anti-inflammatory cytokines in DSS-induced acute UC mice. Moreover, DOPS treatment could also markedly suppress the activation of NLRP3 inflammasome and β-arrestin1 in vivo and in vitro . This study showed that DOPS possesses appreciable therapeutic effect to treat experimental acute UC mice. Its mechanism could be related to inhibition of NLRP3 inflammasome and β-arrestin1 signaling pathways. [ABSTRACT FROM AUTHOR]

The aim of this paper was to prepare purified fractions of polysaccharides from Monetaria moneta Linnaeus and further compare their characteristics and antioxidant activities. Firstly, three novel purified fractions, named MM-P1, MM-P2 and MM-P3, were successfully prepared by a DEAE-Sepharose fast-flow column. Then, their characteristics were compared using chemical testing, FT-IR, GC and HPGPC. The results suggested that MM-P3 had higher molecular weights than MM-P1 and MM-P2. MM-P1 was consisted of glucose, MM-P2 was consisted of glucose and xylose, and MM-P3 was comprised of glucose, xylose and mannose. Differed from MM-P1 and MM-P2, MM-P3 had sulfuric radical and uronic acid groups. Finally, their antioxidant activities were also compared. We found that MM-P3 exhibited better antioxidant bioactivities than MM-P1 and MM-P2. The data demonstrated that three purified fractions derived from different adsorption capacity of DEAE-Sepharose fast-flow column possessed different structural characteristics and antioxidant activity. [ABSTRACT FROM AUTHOR]

It has been known that thin plate can carry loads considerably more than the buckling loads. This phenomenon is defined as the post-buckling behaviour, which is affected by material properties, geometric dimensions and boundary conditions of the plate. Hybrid I-section is a design concept where flanges are made of high strength steel and web is made of lower steel grade. In order to investigate the effect of slender web on the local buckling and post buckling of hybrid I-section under pure compression, experimental studies of twelve fixed-ended I-section stub columns with slender web were conducted. Tensile coupon tests and initial local geometric imperfection measurement were carried out before stub column tests. Experimental and theoretical methods for determining the critical local buckling load of plate elements were discussed, followed by a post-test finite element analysis to investigate the effects of stub column length and sectional steel combination on the buckling behaviour. Based on the experimental and numerical results, it was observed that for specimens which web plate failed by elastic local buckling, the ultimate test loads are affected by the web strength grade, indicating that the unbuckled portion of slender web plate still provides the post-buckling strength for I-section stub columns even after yielding. By comparing the existing design methods with the numerical ultimate loads, it was found that the Eurocode 3 gives the less scattered predictions than the North American code, Australian code and Chinese code, as well as the existing direct strength method and continuous strength method. • 12 I-section stub column tests with slender web are conducted. • Three steel grades are considered for the web plate of I-section. • Critical local buckling load of plate elements is evaluated. • The current codified design methods are assessed. • The existing direct strength method continuous strength method are assessed. [ABSTRACT FROM AUTHOR]

• Four high strength steel (HSS) and eight hybrid I-sections were studied. • Welding effect on the material properties was investigated. • Residual stress measurements were conducted for HSS and hybrid I-sections. • A new residual stress distribution model is proposed. High strength steel (HSS) I-sections are gaining increasing popularity compared with conventional strength steel counterparts, mainly due to its higher strength-to-weight ratio. Meanwhile, there has been growing interest in hybrid I-sections, which are made of different strength steels for flange and web plates, because of the increased need of maximising material utilization. This study investigates the welding effect on the material properties and residual stresses of welded HSS and hybrid I-sections. Tensile tests of coupons machined from both virgin plates and within the welded I-sections were carried out, followed by a metallographic analysis of welding position. It was found that the welding effect on the mechanical behaviour of steel materials varies, depending on the chemical composition and microstructure. Residual stress measurements for HSS and hybrid I-sections covering four web slenderness were conducted. The measurement results demonstrate that the effect of steel strength grade of constitutive plates on residual stress distribution of I-sections is negligible, and a new residual stress distribution model is proposed for welded HSS and hybrid I-sections examined in this study. [ABSTRACT FROM AUTHOR]

• 15 hybrid welded T-section stub columns were tested under axial compression. • Material properties and residual stresses were measured. • Numerical models were developed. • Extensive parametric studies were carried out. • Design codes and design approaches of DSM and CSM were evaluated and compared. Comprehensive experimental and numerical investigations on hybrid T-section stub columns under compressive load were performed and are presented in this paper. The hybrid welded T-section stub columns comprise high strength steel Q690 flange and normal strength steel Q355 web. Material property studies were implemented through tensile coupon tests. Residual stress in membrane type was measured and recorded and its impact on structural performance was also assessed. Initial local geometric imperfection measurements were conducted for all the specimens. In conjunction with experimental studies, numerical investigation was performed to generate more test specimens extending the range of cross-section dimensions by which test data pool can be supplemented. The Eurocode of EN 1993-1-1, EN 1993-1-5 and EN 1993-1-12, the North American code of ANSI/AISC 360-16 and the Australian code of AS 4100 together with design approaches of Direct Strength Method and Continuous Strength Method were examined for its applicability for cross-section classification and compression resistance predictions of hybrid T-sections. Overall, the current specified limits were applicable for hybrid welded T-section and strength predictions from design codes were comparatively consistent and reliable. Strength predictions from Direct Strength Method and Continuous Strength Method were relatively appropriate though overly conservative predictions were provided for cross-section with large slenderness. In this study, modifications on the Direct Strength Method and Continuous Strength Method are proposed, which is shown to provide accurate predictions at cross-sectional level in a reliable manner. [ABSTRACT FROM AUTHOR]

Phlorizin is a member of the chalcone class of organic compounds and was originally extracted from apples. Intensive studies about phlorizin have been conducted. The aim of this study was to determine the therapeutic effects of phlorizin on diet-induced obese mice and to investigate the underlying mechanism. The results show that phlorizin has a beneficial impact on body weight and fat mass, alleviates lipid metabolism and glucose homeostasis. Brown adipose tissue (BAT) temperature was increased and morphological abnormalities were improved in obese mice after phlorizin treatment. Phlorizin activates the Tyk2/STAT3 signalling pathway, up-regulates the protein expression of UCP1, PPARα, PPARγ, C/EBPβ and PRDM16, as well as increases BAT activity which contributes to antiobesity effects. This study suggests that phlorizin activates the Tyk2/STAT3 signalling pathway to induce thermogenesis in BAT and phlorizin has the therapeutic potential in treating obesity and comorbidity. [ABSTRACT FROM AUTHOR]

Comprehensive experimental and numerical investigations on mechanical properties of Q690 and Q460 high strength steel (HSS) sections and stub column behaviour of the 14 hybrid HSS welded T-section stub column specimens are presented in this paper. A total of six coupon specimens were longitudinally and transversely machined from HSS Q690 and Q460 steel parent plates respectively. Furthermore, initial local geometric imperfections measurements were also carried out. In parallel with the experimental investigation on stub column behaviour, extensive numerical studies were carried out by developing finite element (FE) models to replicate the experimental tests results. The validation of the FE models was confirmed against the obtained experimental data. To supplement the experimental data, validated FE models were used in the parametric studies, by which numerical specimens with a larger range of cross-section dimensions can be generated. Subsequently, cross-section classification slenderness limits for outstand plate elements under compressive load set out in structural steel design codes of EN 1993-1-12, ANSI/AISC 360-16, AS 4100 were evaluated against the experimental and numerical data. In addition to the design codes, design methods such as direct strength method (DSM) and continuous strength method (CSM) were also assessed to evaluate the applicability and suitability for hybrid HSS welded T-section stub columns. It was found that the current codified slenderness limits in EN 1993-1-12, ANSI/AISC 360-16 as well as AS 4100 for slender/non-slender outstand flat elements can generally be adopted for hybrid HSS welded T-section under compression. CSM provide under-estimated compressive resistance in comparison to the design codes and DSM for slender sections. • 14 experimental tests of hybrid HSS welded T-section stub columns have been performed. • Numerical models for hybrid HSS welded T-section stub columns have been developed. • Extensive parametric studies have been carried out. • Design codes as well as design approaches of DSM and CSM have been assessed. [ABSTRACT FROM AUTHOR]

An enzyme-amplified magnetic immunosensor was developed for the sensitive and selective detection of ractopamine (RAC) in fodder using a quartz crystal microbalance (QCM). Magnetic capture probes were prepared by immobilizing β-cyclodextrins (β-CD) on Fe 3 O 4 nanoparticles in order to enrich RAC. PowerVision (PV), a kind of enzyme–polymer complex with a high enzyme-to-antibody ratio, served as a signal label. Horseradish peroxidase (HRP) on the immnunocomplex, which arises from sandwich-type immunoreactions, causes 3,3′,5,5′-tetramethylbenzidine (TMB) to produce large amounts of sedimentation with a mass proportional to RAC. The large amounts of HRP on the PV greatly amplify the QCM sensor's signal. Under optimum conditions, the differences of the QCM frequency (Δ f ) are proportional to the concentration of RAC over the range from 0.03 to 25 ng mL −1 . The limit of detection was 0.01 ng mL −1 . More importantly, this assay's results in swine fodder samples were consistent with those of ELISA, with recoveries between 92.3% and 110%. Due to its high sensitivity, portability and selectivity, the immunosensor achieved reliable quantification of RAC in real fodder samples and has the potential to become an on-site screening tool to enhance food safety. [ABSTRACT FROM AUTHOR]

• 16 Experimental tests have been performed. • Numerical models for HSS welded T-section have been developed. • Extensive parametric studies have been carried out. • Design methods from design codes, and from DSM and CSM have been assessed. This paper presents a comprehensive experimental and numerical investigation into the material properties and stub column behaviour of Q690 high strength steel (HSS) welded T-sections. A total of 16 concentrically loaded stub column tests were performed. The Q690 HSS welded T-sections were fabricated from 6 mm and 10 mm thick plates, delivered in quenched and tempered (QT) conditions by means of gas metal arc welding (GMAW). Material properties measurements were carried out on the coupon specimens taken from the parent plates. Initial local geometric imperfection measurements were conducted. In conjunction with experimental tests, finite element (FE) models were developed to replicate the test results and failure modes. Afterwards, the validated FE models were adopted to conduct parametric studies to supplement the experimental data by generating further structural performance data covering a broader range of cross-section slenderness. Cross-section slenderness limits set out in design codes such as EN 1993-1-12, ANSI/AISC 360-16, AS 4100 and design methods of DSM as well as CSM were evaluated against the experimental and numerical data. It was found that the current limits are generally accurate and safe in three design codes and the cross-section slenderness of DSM is accurate and comparably conservative. Cross-section capacities predictions obtained from EN 1993-1-12, ANSI/AISC 360-16, AS 4100, DSM and CSM were also compared with the tests and numerical results. It is shown that the established local buckling design provisions in EN 1993-1-12 and ANSI/AISC 360-16 result in more precise and consistent predictions compared with AS 4100, DSM and CSM. [ABSTRACT FROM AUTHOR]

Local buckling behaviour of welded high strength steel (HSS) I-sections subjected to bending is crucial for structural designs, and has been found to be affected by the interactive effect between flanges and web. To realize accurate designs considering the local buckling behaviour, the continuous strength method (CSM), direct strength method (DSM) and the method from Kato, all of which incorporate the element interaction, have been developed for hot-rolled or cold-formed structures fabricated with conventional strength steel, aluminium or stainless steel. This paper aims to extend these methods for the design of welded HSS I-sections subject to bending. The results of 593 HSS material tensile tests and 40 tests on HSS I-beams are collated. 526 numerical models are generated to expand the data pool for this study using the validated finite element method. Underpinned by the collection of test data and numerical data generated from an extensive parametric study, the design expressions based on the CSM, DSM and the method from Kato, applicable to HSS I-sections under bending, are proposed. The statistical and reliability analysis indicate that the proposed CSM, DSM and Kato's method provide more satisfactory strength predictions than the codified design rules in Eurocode 3 and AISC specification. In comparison with the proposed CSM and DSM, the predictions based on the modified Kato's method show higher accuracy, which may be attributed to the separate consideration for the effect of flange and web slenderness in Kato's expression. • A parametric study of high strength steel (HSS) I-beam numerical data is conducted. • The continuous strength method (CSM) material model for HSS is established. • The CSM is extended to the design for local buckling behaviour of HSS I-beam. • The direct strength method is extended to the design for local buckling behaviour of HSS I-beam. • The method from Kato is extended to the design for local buckling behaviour of HSS I-beam. [ABSTRACT FROM AUTHOR]

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is characteristic of genetically extensive variation. The objective of the present study was to analyze the molecular variation and evolution of porcine reproductive and respiratory syndrome virus in China based on the complete genomic sequences of three highly pathogenic Chinese PRRSV strains isolated in 2006 and the sequences of the amplified Nsp2, ORF5 and ORF7 genes from clinical specimens during 2006–2008. Full-length genome sequencing and phylogenetic analysis showed that the three strains (JXwn06, BJsy06 and NX06) had a unique 30-amino-acid discontinuous deletion in Nsp2, and were classified into the same subgroup that consisted of the most Chinese strains isolated during 2006–2007, the pandemic period of atypical PRRS. The evolution analysis suggested that the emergence of the highly pathogenic PRRSV in China experienced a gradual variation and evolution accumulation progress from Chinese domestic virus. The variation analysis of the amplified 41 Nsp2, 59 ORF5 and 59 ORF7 genes indicated that the diversity of PRRSV strain existed in the field, and the highly pathogenic PRRSV strain with the 30-amino-acid deletion in Nsp2 was the dominating virus in China in recent years. Our data contribute to the understanding of molecular variation and epidemiology surveillance of PRRSV in China. [Copyright &y& Elsevier]

Background: Patients with inflammatory bowel disease are at increased risks of developing ulcerative colitis-associated colorectal cancer (CAC). Vitexin can suppress the proliferation of colorectal carcinoma cells in vitro orin vivo. However, different from colorectal carcinoma, CAC is more consistent with the transformation from inflammation to cancer in clinical chronic IBD patients. Therefore, we aim to investigated that vitexin whether possess benefic effects on CAC mice.Purpose: We aimed to determine the beneficial effects of vitexin on CAC mice and reveal its underlying mechanism.Methods: The mouse CAC model was induced by Azoxymethane and dextran sodium sulfate (AOM/DSS) and CAC mice were treated with vitexin. At the end of this study, inflammatory cytokines of IL-1β, IL-6, TNF-α, IL-10 as well as nitric oxide (NO) were detected by kits after long-term treatment of vitexin. Pathological changes and macrophage polarization were determined by H&E and immunofluorescence in adjacent noncancerous tissue and carcinomatous tissue respectively of CAC mice.Results: Our results showed that oral administration of vitexin could significantly improve the clinical signs and symptoms of chronic colitis, relieve colon damage, regulate colonic inflammatory cytokines, as well as suppress tumor incidence and tumor burden. Interesting, vitexin caused a significant increase in serum level of NO and a higher content of NO in tumor tissue. In addition, vitexin significantly decreased M1 phenotype macrophages in the adjacent noncancerous tissue, while markedly up-regulated M1 macrophage polarization in the tumor tissue in the colon of CAC mice.Conclusion: Vitexin can attenuate chronic colitis-associated carcinogenesis induced by AOM/DSS in mice and its protective effects are partly associated with its alternations in macrophage polarization in the inflammatory and tumor microenvironment . [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a prevailing and deadly complication of sepsis coupled with increasing incidence and fatality rate. Annexin A3 (ANXA3) has been unraveled to be upregulated during sepsis. This study purposed to assess the role and the mechanism of ANXA3 in sepsis-induced ALI. After the construction of mouse model of sepsis, the pathological changes of mice lung tissues were estimated by H&E staining. ANXA3 expression in mice lung tissues and serum was examined. The degree of pulmonary edema and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed. In lipopolysaccharide (LPS)-induced mouse ALI model in vitro, CCK-8 assay measured cell viability and flow cytometry analysis detected cell apoptosis. Besides, ELISA assay detected the release of inflammatory cytokines. Western blot analyzed the expression of proteins associated with inflammation, apoptosis and extracellular-signal-regulated kinase (ERK)/ETS-like gene 1 (ELK1) signaling. Results revealed that ANXA3 was overexpressed in the lung tissues and serum of septic mice. Following the knockdown of ANXA3, sepsis-induced lung injury was alleviated, manifested as reduced lung edema, decreased inflammatory cell infiltration and inhibited cell apoptosis. Additionally, ANXA3 silence blocked ERK/ELK1 signaling both in sepsis mouse models and in vitro model of ALI induced by lipopolysaccharide (LPS). Moreover, the inhibitory effects of ANXA3 silencing on ERK/ELK1 signaling activation, the viability damage, inflammation and apoptosis in LPS-induced mouse ALI model in vitro were partially reversed by ERK activator. Collectively, depletion of ANXA3 exerted suppressive effects on the inflammation and apoptosis in sepsis-induced ALI through blocking ERK/ELK1 signaling. • ANXA3 expression was raised in the lung tissues and serum of septic mice. • ANXA3 depletion alleviated lung tissue damage in septic mice. • ANXA3 depletion reduced inflammation and apoptosis in septic mice. • ANXA3 depletion inhibited ERK/ELK1 signaling in the lung tissues of septic mice. • Interference with ANXA3 inactivated ERK/ELK1 signaling to mitigate LPS-elicited inflammatory response and apoptosis in MLE-12 cells. [ABSTRACT FROM AUTHOR]

Protein phosphorylation is an important link in a variety of signaling pathways, and most of the important life processes in cells involve protein phosphorylation. Based on the amino acid residues of phosphorylated proteins, protein kinases can be categorized into the following families: serine/threonine protein kinases, tyrosine-specific protein kinases, histidine-specific protein kinases, tryptophan kinases, and aspartate/glutamyl protein kinases. Of all the protein kinases, most are serine/threonine kinases, where serine/threonine protein kinases are protein kinases that catalyze the phosphorylation of serine or threonine residues on target proteins using ATP as a phosphate donor. The current socially accepted classification of serine/threonine kinases is to divide them into seven major groups: protein kinase A, G, C (AGC), CMGC, Calmodulin-dependent protein kinase (CAMK), Casein kinase (CK1), STE, Tyrosine kinase (TKL) and others. After decades of research, a preliminary understanding of the specific classification and respective functions of serine/threonine kinases has entered a new period of exploration. In this paper, we review the literature of the previous years and introduce the specific signaling pathways and related therapeutic modalities played by each of the small protein kinases in the serine/threonine protein kinase family, respectively, in some common cardiovascular system diseases such as heart failure, myocardial infarction, ischemia-reperfusion injury, and diabetic cardiomyopathy. To a certain extent, the current research results, including molecular mechanisms and therapeutic methods, are fully summarized and a systematic report is made for the prevention and treatment of cardiovascular diseases in the future. [Display omitted] • Integrate the serine/threonine kinase system with the cardiovascular system and detail its molecular mechanism in the cardiovascular system. • Based on the description of the molecular mechanisms, animal and cellular experiments are utilized to support them. • This paper briefly lists the existing and potential drugs that are currently clinically targeting their molecular mechanisms. • Listed kinase families more closely associated with cardiovascular disease: AGC Protein Family; CMGC Protein Family; CAMK Protein Family. • By systematically describing the molecular mechanisms, cellular and animal experimental evidence, and clinically available drugs, it provides a theoretical basis for the future development of therapeutic drugs targeting serine/threonine kinases. [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation on the material properties variation and residual stress distribution within the high strength steel (HSS) hexagonal hollow sections. Three different fabrication routes encompassing welding or combinations of welding and press-braking were employed for fabricating the HSS hexagonal sections. HSS plates of grade Q690 with two thicknesses of 6 mm and 10 mm were used. A total of 76 tensile coupons extracted from the parent plates and the hexagonal hollow sections with different fabrication routes were tested to obtain the static material properties of the parent steel plates and the material properties variation for the hexagonal hollow sections. A new material model describing the material properties for the flat portion was proposed while the existing material model for cold-formed steel was modified for the materials at the press-braked corners. In addition, residual stresses measurements for five HSS hexagonal sections with different fabrication routes and varying section slenderness were subsequently performed. Sectioning method was adopted in this study with 74 strips extracted and more than 898 strain readings obtained. Results of the residual stress distributions and the magnitudes are presented and discussed. Based on the measurement results, predictive models for residual stresses were developed and can be applied to estimate residual stresses for predicting the structural behaviour of the HSS hexagonal hollow sections. [Display omitted] • Material property variations within the HSS hexagonal cross sections is investigated • Non-destructive inspections were performed • 898 residual stress measurements were carried out • Predictive models for residual stress distribution of HSS hexagonal hollow sections were proposed [ABSTRACT FROM AUTHOR]

The main damage caused by earthquakes to single-column circular-section steel piers is the bulged deformation at the bottom, generated by local instability. The refined shell-based finite element (FE) model can accurately simulate the deformational behavior, but it is still cumbersome and time-consuming to apply to the engineering design currently. Further, the existing simplified methods cannot be used in seismic response analyses under horizontal bidirectional earthquakes. Therefore, this paper uses the multi-shear spring (MSS) mechanical model as the basic model and proposes an MSS calculation model for circular-section steel piers. This model is applicable for horizontal bidirectional seismic response analysis and considers the local instability effect of steel plates. In this study, the load–deformation relationship of the modified Menegotto-Pinto model is employed in all directions as the hysteresis curve equation of the springs. The basic parameters of the corresponding models for different structures are determined according to the calculation results of the refined-shell models. In addition, the Ibarra-Krawinkler degradation rule is employed to simulate the degradation process of structural bearing capacity and stiffness, and the degradation parameters are identified. The pseudostatic and seismic time-history response analyses of steel piers with different width-to-thickness ratios verify that the proposed model has reliable calculation accuracy and greatly improved efficiency. The research in this paper provides a practical calculation method for the seismic response analysis of steel bridge piers. [Display omitted] • The modified M–P hysteresis model shows excellent simulation accuracy. • The I–K degradation rule can truly describe the decrease in structural bearing capacity and stiffness. • The proposed model can take into account the local instability effects and horizontal bidirectional seismic action. [ABSTRACT FROM AUTHOR]

Numerical simulation of flow and heat transfer for a 3 in. (0.075 m) diameter liquid encapsulant full float zone (LEFZ) growth of single-crystal GaAs was conducted using the finite-element method. Convective and conductive heat transfers, radiative heat transfer between diffuse surfaces and the Navier–Stokes equations for both melt and encapsulant as well as the interface position are all combined and solved simultaneously. The effect of the thickness of encapsulant, rotation rate of crystal and feed rod on the flow and heat transfer as well as on the growing and melting interface shape were investigated. [Copyright &y& Elsevier]

• Vitexin could alleviate liver injury caused by ulcerative colitis. • Vitexin could inhibit the activation of TLR4/NF-κB signaling pathway. • Vitexin could be a promising drug for liver injury induced by acute ulcerative colitis. As one of commonly used herbs with dual-purpose of drug and food, it has been reported that vitexin has hepatoprotective effects. However, the protective effects of vitexin on colitis-induced liver injury as well as the underlying molecular mechanisms remain unclear. The purpose of the current study was to investigate the effects and mechanisms of vitexin on liver injury induced by acute ulcerative colitis in mice. In this study, the mice model of acute ulcerative colitis was induced by 4 % dextran sodium sulphate (DSS). And then, the degree of liver injury in colitis mice was evaluated, the hepatic ALT, AST, TC and TG levels were measured by specific determination kits, the levels of TNF-α, IL-6 and IL-1β were examined by ELISA, the expressions of TLR4/NF-κB pathway related protein were detected by western blot analysis. The results indicated that hepatic histopathological changes induced by DSS were normalized by vitexin treatment, administration of vitexin decreased the liver levels of ALT and TC in mice with liver injury and reduced the release amounts of DSS-induced pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Furthermore, we found that vitexin inhibited the activation of TLR4/NF-κB signaling pathway induced by DSS. In conclusion, vitexin possess hepatoprotective activities against colitis-induced liver injury, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis. [ABSTRACT FROM AUTHOR]

This paper presents an in-depth numerical investigation into the local buckling behaviour and develops advanced machine learning (ML) -based design methods for high strength steel (HSS) welded I-section beams for predicting the ultimate bending moment resistance under bending. Though HSS welded I-sections are commonly used in construction industry, the interaction effect between the flange and web plates as well as the relatively simplified design formulae result in limited accuracy of ultimate bending moment prediction and complex endeavour is involved for sections subject to local buckling. Finite element models are firstly developed and validated against the collected experimental test data, after which an extensive parametric study is carried out covering a larger range of cross-section slenderness and steel grades. Five ML models including Linear regressor (LR), Support vector regressor (SVR), Artificial neural network (ANN), Random forest regressor (RFR) and Boosting algorithm (XGBoost) were subsequently developed based on the test dataset (experimental and numerical data) to train and test the ML models. Though the current design codes of EN 1993-1-12 and AISC 360-16 can generally provide accurate cross-section classifications with appropriate slenderness limits, the ultimate bending moment resistance predictions are overconservative, particularly for slender sections. The developed ML models outperformed the codified design methods with notable improvements and can be employed in predicting the ultimate bending moment resistance of HSS welded I-section beams under bending. • Finite element modelling of high strength steel I-section is presented. • An extensive parametric study comprising 548 numerical models is carried out. • Slenderness limits specified in existing design codes are assessed. • Five machine learning models for predicting ultimate bending moment resistance is developed. • The performance of the developed machine learning models is evaluated. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear. We aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro. Pharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1β and TNF-α were detected by ELISA. ASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome. Our results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD. • Asperuloside (ASP) alleviates HFD-induced NAFLD through suppressing lipid deposition and inflammatory. • ASP affects the protein level of p-AMPK and NLRP3 in HepG2 cells. • ASP attenuates lipid deposition through suppressing AMPK/SREBP-1 signaling pathway. • ASP attenuates inflammation through suppressing NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Neuropathic pain was regarded as a main form of chronic pain condition that remains difficult to treat. Conventional pharmacotherapy for neuropathic pain responsed vary and side effects limited their compliance. These prompted us to find new alternatives. In this study, we investigated the effect of troxerutin on treatment of CCI-induced neuropathic pain. Results showed that troxerutin significantly reversed mechanical allodynia and thermal hyperalgesia. In L4–6 spinal cord, troxerutin reduced the expression of INF-γ, IL-1β, TNF-α, and activation of NF-κB(p65). Immunofluorescence results showed that troxerutin significantly inhibited microglia activation induced by CCI surgery. Further, troxerutin treatment significantly induced AMPK activation and inhibited CCI-induced SIRT1 decrease. However, AMPK inhibitor compound C and SIRT1 inhibitor EX527 inhibited analgesic effect of troxerutin in CCI mice. This demonstrated the involvement of AMPK/SIRT1 pathway in anti-allodynic effect of troxerutin in CCI mice. Troxerutin could be developed as a potential therapeutic agent for neuropathic pain. [ABSTRACT FROM AUTHOR]