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SBS (styrene–butadiene–styrene block copolymer) is currently the most widely used asphalt modifier, and SBS modified asphalt is usually prepared by high-speed shearing. This paper combines the cavitation effect of ultrasonic to assist in the preparation of SBS modified asphalt, and conducts numerical simulation and rheological properties research on the cavitation bubbles in the molten SBS modified asphalt fluid. The cavitation bubbles in the modified asphalt fluid will expand and contract as the pressure changes inside and outside the bubbles. When the cavitation bubble is compressed to the minimum and the pressure inside the bubble reaches 1.94 × 105Pa, the direction of the velocity vector near the cavitation bubble will change with the expansion and compression of the bubble. The expansion–contraction process of a single cavitation bubble can release 6.41 × 10-7J of energy, thus breaking the long bonds in asphalt and generating a large number of free radicals react with the unsaturated C = C bonds in the SBS molecules. According to the preparation process of modified asphalt, the influence of ultrasonic wave on rheological property of modified asphalt was studied through experiments. The results show that ultrasonic treatment can enhance the elasticity of asphalt and improve the temperature sensitivity of asphalt. With the increase of ultrasonic treatment time, the anti-rutting deformation ability of SBS modified asphalt is greatly improved. At the same temperature, the recovery rate of asphalt also increases with the increase of ultrasonic treatment time, and the non-recoverable compliance (Jnr) decreases Combined with the numerical simulation of cavitation bubbles, the ultrasonic process is added to asphalt production, which is of great significance for the green production of modified asphalt and the improvement of the rheological properties of modified asphalt.

With the intensification of aging population, the prevention or treatment of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, has drawn more and more attention. As a long used traditional Chinese medicine, Uncaria rhynchophylla (Miq.) Jacks., named Gouteng in Chinese, has been reported to have an effective neuroprotective role in neurodegenerative diseases. In this review, the beneficial pharmacological effects and signaling pathways of herbal formulas containing U. rhynchophylla, especially major compounds identified from U. rhynchophylla, such as corynoxine B, corynoxine, rhynchophylline, and isorhynchophylline, in neurodegenerative diseases, were summarized, which not only provide an overview of U. rhynchophylla for the prevention or treatment of neurodegenerative diseases but also give some perspective to the development of new drugs from traditional Chinese medicine.

BackgroundPrevious epidemiological studies have identified a correlation between serum protein levels and Psoriatic Arthritis (PsA). However, the precise nature of this relationship remains uncertain. Therefore, our objective was to assess whether circulating levels of 2,923 plasma proteins are associated with the risk of PsA, utilizing the Mendelian randomization (MR) approach.MethodsTwo-sample MR analysis was performed to assess the causal impact of proteins on PsA risk. Exposure data for plasma proteins were sourced from a genome-wide association study (GWAS) conducted within the UK Biobank Pharma Proteomics Project, which encompassed 2,923 unique plasma proteins. The outcome data for PsA were sourced from the FinnGen study, a large-scale genomics initiative, comprising 3,537 cases and 262,844 controls. Additionally, colocalization analysis, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets.ResultsWe thoroughly assessed the association between 1,837 plasma proteins and PsA risk, identifying seven proteins associated with PsA risk. An inverse association of Interleukin-10 (IL-10) with PsA risk was observed [odds ratio (OR)=0.45, 95% confidence interval (CI), 0.28 to 0.70, PFDR=0.072]. Additionally, Apolipoprotein F (APOF) has a positive effect on PsA risk (OR=2.08, 95% CI, 1.51 to 2.86, PFDR=0.005). Subsequently, we found strong evidence indicating that IL-10 and APOF were colocalized with PsA associations (PP.H4 = 0.834 for IL-10 and PP.H4 = 0.900 for APOF). Phenome-wide association analysis suggested that these two proteins may have dual effects on other clinical traits (PFDR

Summary: ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

Summary: The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

Plant extracts from natural sources are an excellent choice for food additives and natural antioxidants. In this study, the active components of Tulipa edulis were extracted and analysed, and their antioxidant capacity was measured. Then, the crude extract mixture was separated and purified using a Sephadex LH-20 gel, and the antioxidant activity of the purified products was determined. Human umbilical vein endothelial human umbilical vein endothelial cells (HUVEC) cells were treated with 35 mmol/L glucose to construct a model of oxidative stress. Then, the cells were treated with the active component to observe whether the products of T. edulis could have a good protective effect on HUVEC cells induced by glucose. Transcriptome analysis was also performed on HUVEC cells after same treatment to explore the possible mechanism of the component F2 protecting HUVEC cells from oxidative stress induced by high glucose. The results showed that component F2 obtained from T. edulis has strong antioxidant activity. Moreover, F2 can play a strong antioxidant protective role in HUVEC cells. Meanwhile, the gene expression of heme oxygenase 1 (HO-1), γ-glutamyl cysteine ligase catalytic subunit (GCLC) and NAD(P)H quinone oxidoreductase-1 (NQO1) in HUVEC cells was up-regulated after treated with F2. This study provides reference value for the further development and application of T. edulis and the development of functional food.

Abstract The pro-inflammatory state of macrophages, underpinned by their metabolic condition, is essentially affecting their capacity of combating tumor cells. Here we find, via a pooled metabolic gene knockout CRISPR screen that KEAP1 and ACOD1 are strong regulators of the pro-inflammatory state in macrophages. We show that ACOD1 knockout macrophages, generated in our induced pluripotent stem cell-derived CAR-macrophage (CAR-iMAC) platform, are strongly and persistently polarized toward the pro-inflammatory state, which manifests in increased reactive oxygen species (ROS) production, more potent phagocytosis and enhanced cytotoxic functions against cancer cells in vitro. In ovarian or pancreatic cancer mouse models, ACOD1-depleted CAR-iMACs exhibit enhanced capacity in repressing tumors, leading to increased survival. In addition, combining ACOD1-depleted CAR-iMACs with immune checkpoint inhibitors (ICI), such as anti-CD47 or anti-PD1 antibodies, result in even stronger tumor suppressing effect. Mechanistically, the depletion of ACOD1 reduces levels of the immuno-metabolite itaconate, allowing KEAP1 to prevent NRF2 from entering the nucleus to activate an anti-inflammatory program. This study thus lays down the proof of principle for targeting ACOD1 in myeloid cells for cancer immunotherapy and introduces metabolically engineered human iPSC-derived CAR-iMACs cells with enhanced polarization and anti-tumor functions in adoptive cell transfer therapies.

Mulberry leaf tea (MT) is a popular Chinese food with nutrition and medicinal functions. Solid-state fermentation with Eurotium cristatum of MT (FMT) can improve their quality. Differences in chromaticity, taste properties, and flavor characteristics were analyzed to evaluate the improvements of the sensory quality of FMT. After fermentation, the color of the tea infusion changed. The E-tongue evaluation results showed a significant decrease in unpleasant taste properties such as sourness, bitterness, astringency, and aftertaste-bitterness, while umami and saltiness taste properties were enhanced post-fermentation. Aroma-active compounds in MT and FMT were identified and characterized. A total of 25 key aroma-active compounds were screened in MT, and 2-pentylfuran showed the highest relative odor activity value (ROAV). A total of 26 key aroma-active compounds were identified in FMT, and the newly formed compound 1-octen-3-one showed the highest ROAV, which contributed to FMT’s unique mushroom, herbal, and earthy flavor attributes. 1-octen-3-one, (E)-2-nonenal, trimethyl-pyrazine, 2-pentylfuran, and heptanal were screened as the potential markers that contributed to flavor differences between MT and FMT. E. cristatum fermentation significantly altered the sensory properties and flavor compounds of MT. This study provides valuable insights into the sensory qualities of MT and FMT, offering a theoretical basis for the development of FMT products.

Neural radiance fields (NeRFs) and 3D Gaussian splatting have emerged as promising 3D reconstruction techniques recently. However, their application in virtual reality (VR), particularly in firefighting training, remains underexplored. We present an innovative VR firefighting simulation system based on 3D Gaussian Splatting technology. Leveraging these techniques, we successfully reconstruct realistic physical environments. By integrating the Unity3D game engine with head-mounted displays (HMDs), we created and presented immersive virtual fire scenes. Our system incorporates NeRF technology to generate highly realistic models of firefighting equipment. Users can freely navigate and interact with fire within the virtual fire scenarios, enhancing immersion and engagement. Moreover, by utilizing the Photon PUN2 networking framework, our system enables multi-user collaboration on firefighting tasks, improving training effectiveness and fostering teamwork and communication skills. Through experiments and surveys, it is demonstrated that the proposed VR framework enhances user experience and holds promises for improving the effectiveness of firefighting training.

Basalt fiber-reinforced asphalt mixture has shown promising mechanical characteristics but is susceptible to bleeding, which can compromise driving comfort and safety. This paper investigates the bleeding mechanism of basalt fiber-modified asphalt mixtures and proposes mitigation techniques. Scanning Electron Microscopy (SEM) is used to observe the microstructure and spatial structure of the asphalt mixture with fibers, while microstructure, interface properties, and spatial structure are analyzed to determine the mechanism of bleeding. Mixed fibers composed of basalt and lignin fibers are proposed as a solution to alleviate bleeding, and comprehensive pavement performance is evaluated using the Efficiency Coefficient Method (ECF). The results show that the smooth surface, low surface energy, poor surface bonding ability, small specific surface area, and large void network structure of basalt fibers make the pavement susceptible to bleeding. Besides, the mixed fiber reinforced asphalt mixture exhibits a 16.7% increase in resistance to bleeding compared to the basalt fiber asphalt mixture. Furthermore, the comprehensive pavement performance has been enhanced by 9.09% according to ECF result.

Abstract Targetable drivers governing 5-fluorouracil and cisplatin (5FU + CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Here, we establish 5FU + CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines. ADAR1 confers chemoresistance and self-renewal in an RNA editing-dependent manner. WES coupled with RNA-seq identify enrichment of hyper-edited lipid metabolism genes in the resistant lines. Mechanistically, ADAR1-mediated A-to-I editing on 3’UTR of stearoyl-CoA desaturase (SCD1) increases binding of KH domain-containing, RNA-binding, signal transduction-associated 1 (KHDRBS1), thereby augmenting SCD1 mRNA stability. Consequently, SCD1 facilitates lipid droplet formation to alleviate chemotherapy-induced ER stress and enhances self-renewal through increasing β-catenin expression. Pharmacological inhibition of SCD1 abrogates chemoresistance and tumor-initiating cell frequency. Clinically, high proteomic level of ADAR1 and SCD1, or high SCD1 editing/ADAR1 mRNA signature score predicts a worse prognosis. Together, we unveil a potential target to circumvent chemoresistance.

The advanced treatment of secondary effluents was investigated by employing heterogeneous catalytic ozonation integrated with a biological aerated filter (BAF) process. The results indicated that catalytic ozonation with the prepared catalyst (MnxCuyOz/γ-Fe2O3) significantly enhanced the performance of pollutant removal and broke up macromolecules into molecular substances by the generated hydroxyl radicals. These molecular substances were easily absorbed by microorganisms in the microbial membrane reactor. In the BAF process, chemical oxygen demand (COD) (chemical oxygen demand) decreased from 54.26 to 32.56 mg/L, while in catalytic ozonation coupled with the BAF, COD could be reduced to 14.65 mg/L (removal ratio 73%). Under the same condition, NH4+-N decreased from 77.43 to 22.69 mg/L and 15.73 mg/L (removal ratio 70%) in the BAF and the catalytic ozonation coupled with BAF, respectively. In addition, the model that highly correlated influent COD to effluent COD and reactor height for filler could predict the removal ratio of COD of the BAF system. Based on the microbial community analysis, ozone in the solution had a certain screening effect on microorganisms, which helped to better adapt to the ozone-containing environment. Therefore, the integrated process with its efficient, economic, and sustainable advantages was suitable for the advanced treatment of secondary effluents. HIGHLIGHTS The biodegradability of municipal wastewater was improved after ozonation.; The COD at different BAF heights as a function of influent COD was established.; Catalytic ozonation coupled with BAF for advanced treatment of wastewater was feasible.;

As an important part of steel bridge deck, the engineering quality and service condition of steel bridge deck pavement (SBDP) directly affects the capacity and operational efficiency of the bridge. This paper reviews the history of the development of SBDP in China over the past 20 years from the exploration stage, rapid development stage and prosperity stage. The development and application of SBDP at different stages are discussed in terms of materials, structure, design, performance evaluation, maintenance and rehabilitation, respectively. The advantages and disadvantages of different pavement materials and structures, and the application of different research methods are summarized. The review shows that the improvement of pavement materials and structures and the development of new materials should be further studied on the multi-scale to enhance the durability of pavement materials, so as to extend the service life of pavements. The design method of SBDP related to the synergistic effect of vehicle, pavement and bridge should be established, and the design concept and method standard of rigid base pavement structure should be improved and formulate a complete design standard. In addition, multi-disease intelligent identification system and equipment should be studied to track the entire course of disease development in real time. And it is necessary to develop appropriate algorithms to select and classify the complex data of disease and maintenance history.

Anorexia nervosa (AN) has a high mortality rate due to the widespread organ dysfunction caused by the underlying severe malnutrition. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases, while acute liver failure and aplastic crisis related to coagulation disease and encephalopathy rarely occur in AN patients. The supervised increase of caloric intake can quickly improve the elevated aminotransferases caused by starvation and aplastic crisis. This current case report describes a 12-year-old adolescent girl who was admitted with a 3-month history of weight loss. Within 3 months, she had lost 10 kg of weight. The girl was diagnosed with AN, acute liver failure, severe malnutrition with emaciation, electrolyte disorder, bradycardia and aplastic crisis. She was gradually supplemented with vitamins and enteral nutrition to avoid refeeding syndrome. After treatment, her liver function and haematopoietic function returned to normal. In conclusion, acute liver failure and aplastic crisis are rare but potentially life-threatening complications of AN, which could be improved by supervised feeding and timely rehydration. AN should be considered as the potential aetiology of acute liver failure and aplastic crisis.

WC is an indispensable constituent when producing Ti(C, N)-based cermets, yet its role on microstructure and the mechanism remain blurred. Herein, based on the CALPHAD approach, we designed and synthesized the cermets containing unsaturated and supersaturated WC. Formation of a macro-gradient structure was observed, encompassing an undissolved WC area, a WC dissolution area, and a (Ti, W)(C, N) solid-solution area. Such a unique structure has not been reported in cermet systems, which originates from the denitrification-induced W solubility change in Ti(C, N), as clarified computationally. Thus, this work shows the usefulness of thermodynamic calculations in establishing composition-microstructure relationships in cermets.

Neural radiance fields and neural reflectance fields are novel deep learning methods for generating novel views of 3D scenes from 2D images. To extend the neural scene representation techniques to complex underwater environments, beyond neural reflectance fields underwater (BNU) was proposed, which considers the relighting conditions of on-aboard light sources by using neural reflectance fields, and approximates the attenuation and backscatter effects of water with an additional constant. Because the quality of the neural representation of underwater scenes is critical to downstream tasks such as marine surveying and mapping, the model reliability should be considered and evaluated. However, current neural reflectance models lack the ability of quantifying the uncertainty of underwater scenes that are not directly observed during training, which hinders their widespread use in the field of underwater unmanned autonomous navigation. To address this issue, we introduce an ensemble strategy to BNU that quantifies cognitive uncertainty in color space and unobserved regions with the expectation and variance of RGB values and termination probabilities along the ray. We also employ a regularization method to smooth the density of the underwater neural reflectance model. The effectiveness of the present method is demonstrated in numerical experiments.

BackgroundMorus alba L. (Sangzhi) alkaloid (SZ-A) is a new antidiabetic drug approved by the China National Medical Products Administration in 2020. Diabetic nephropathy (DN) is a common diabetic complication and an important cause of morbidity and mortality in patients with diabetes. The effects of SZ-A on DN remain unknown.PurposeThis study evaluated the effects of SZ-A on DN in Zucker diabetic fatty (ZDF) rats and explored the underlying mechanisms based on nitrosative stress, inflammation, and fibrosis.MethodsDiabetic ZDF rats were orally administered 100 and 200 mg/kg of SZ-A once daily for 9 weeks. The glucose metabolism and kidney function were assayed. The pathological injury and fibrosis of the kidneys were separately evaluated using hematoxylin and eosin staining and Masson’s staining. The oxidative and nitrosative stress and inflammation were assayed by determining the levels of related indices in the blood and kidneys and quantifying the related gene and protein expression. The expression of transforming growth factor β1 (TGFβ1) gene and protein were assayed by quantitative real-time PCR and immunohistochemistry, respectively. The renal transcriptomics was analyzed using RNA sequencing.ResultsRepeated treatment with SZ-A significantly improved glucose metabolism, dose-dependently decreased the levels of blood urea nitrogen, urinary albumin, and β2-microglobulin, and evidently relieved the renal injury in diabetic ZDF rats. As for the mechanisms, SZ-A remarkably ameliorated systemic nitrosative stress through lowering the levels of blood inducible nitric oxide synthase and nitric oxide, and significantly relieved systemic and renal inflammation by reducing the levels of blood interleukin-1β and monocyte chemoattractant protein-1 (MCP-1) and decreasing the levels of renal C-reactive protein content and expression of tumor necrosis factor-α in the kidneys. SZ-A also improved renal fibrosis by lowering the expression of TGFβ1 in the kidneys. Additionally, SZ-A significantly lowered the expression of stimulator of chondrogenesis 1 in the kidneys.ConclusionRepeated treatments with SZ-A significantly ameliorates DN by regulating systemic nitrosative stress, renal inflammation, and renal fibrosis partially through inhibition of the cytokine-NO and TGF-β1 signaling in ZDF rats, providing evidence for the additional application of SZ-A in clinical use for the treatment of DN.

RNA binding proteins (RBPs) can participate in regulatory networks to control alternative splicing. Here the authors show that DAP3 functions as an RBP splicing modulator via two mechanisms, and that its overexpression leads to mis-splicing events in cancers.

RNA editing and circRNAs are involved in tumorigenesis. Here the authors report that ADARs regulate the circular transcriptome in a bidirectional manner through and beyond their editing function in multiple cancer cells.

It remains unclear whether low-dose ticagrelor offers better safety and similar efficacy for Asian patients with acute coronary syndromes (ACS). We aimed to compare the safety and effectiveness of low-dose ticagrelor vs standard-dose ticagrelor in Chinese patients with ACS undergoing percutaneous coronary intervention (PCI). In this observational cohort study, a total of 2110 ACS patients who were event-free at 3 months after the index PCI were divided into standard-dose ticagrelor (90 mg twice daily) (n = 1830) or low-dose ticagrelor (45 mg twice daily) (n = 280) on a background of aspirin 100 mg once daily for at least another 9 months. The primary end point was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria over a 1-year follow-up period post-PCI. Predictors of the primary end point were identified. Both Cox regression and propensity score matching analyses were used. The cumulative incidence of BARC type 2, 3, or 5 bleeding was lower in the low-dose ticagrelor group vs the standard-dose group either before (adjusted HR 0.24; 95% CI 0.07–0.77; p = .016) or after matching (HR 0.25; 95% CI 0.08–0.85; p = .026). A composite of cardiac death, myocardial infarction, or stroke was not significantly different between the two groups (0.4% vs 0.9%, respectively). By multivariate analysis, only low-dose ticagrelor was a protected predictor of BARC type 2, 3, or 5 bleeding either before (HR 0.28, 95% CI 0.09–0.89) or after matching (HR 0.24, 95% CI 0.07–0.82). A low-dose regimen of ticagrelor might provide better safety than standard-dose ticagrelor in Chinese patients with ACS undergoing PCI.

The automatic generation of tolerance specifications is an important aspect of achieving digital product design. An obvious feature of the current automatic generation of tolerance based on rule reasoning is that all tolerance types will be inferred for the same assembly feature. However, when labelling part tolerance information, designers need to further screen based on the geometric function of the assembly, which may result in prioritizing tolerance types that do not meet the geometric requirements of the assembly. This paper presents an assembly tolerance type optimization method based on the degree of freedom (DOF) of tolerance zone for the optimization and screening problem after reasoning all possible tolerance types. Firstly, we define the DOF of tolerance zones and their representations, while also define the control parameter degrees of freedom (CPDF) of assemblies, and analyze the CPDF of typical geometric functional tolerances of assemblies; Secondly, the Boolean operation relationship between sets is used to construct a Boolean operation preference method for the CPDF. Then, an algorithm for the optimal selection of the shape and position tolerance items of the assembly is established based on the DOFs of tolerance zone. Finally, the proposed method is verified by an engineering example, and the result shows that the method can optimize and screen the geometric tolerance types of assemblies.

To study the cell proliferation and wound healing activity of polysaccharides from Ganoderma amboinense (GAMPS), the polysaccharide was extracted by water extraction and alcohol precipitation method, and its monosaccharide composition and molecular weight were analyzed. The effects of different concentrations of GAMPS on the cell proliferation were determined by cell survival rate test, and the wound healing ability of GAMPS to NIH/3T3 cells was detected. The preliminary evaluation of the antioxidant ability of GAMPS was conducted by the oxygen radical absorbance capacity (ORAC). The results showed that the GAMPS was composed of glucose, mannose, and galactose at a molar ratio of 67.62:14.07:7.50, and the weight-average molecular weights were 5.439 × 106 and 1.704 × 105 g/mol by using high-performance gel-permeation chromatography-multiple angle laser scatter (HPGPC-MALS) analysis. GAMPS (0.2 μg/μL) showed the strongest proliferation ability to THP-1 cells, with cell survival rate of 178.7%. The wound healing effect of GAMPS (0.1 μg/μL) was obvious on NIH/3T3 and 3.75 μg/μL of GAMPS showed the strongest total antioxidant ability. All the results indicate that GAMPS promotes cell proliferation, and has cell wound healing effect and strong antioxidant activity. The results provide theoretical foundation for the development and utilization of GAMPS.

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.

Osteoporosis, which typically affects postmenopausal women, is an osteolytic disease due to over-activation of osteoclasts. However, current drugs targeting osteoclast inhibition face various side effects, making natural compounds with great interest as alternative treatment options. Cycloastragenol (CAG) is a triterpenoid with multiple biological activities. Previously, CAG’s activity against aging-related osteoporosis was reported, but the mechanisms of actions for the activities were not understood. This study demonstrated that CAG dose-dependently inhibited osteoclast formation in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated bone marrow macrophage (BMMs). Mechanism studies showed that CAG inhibited NF-κB, calcium, and nuclear factor of activated T cells 1 (NFATc1) pathways. Additionally, CAG also promoted the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/anti-oxidative response element (ARE) pathway that scavenges reactive oxygen species (ROS). Furthermore, CAG was also found to prevent bone loss of postmenopausal osteoporosis (PMO) in a preclinical model of ovariectomized (OVX) mice. Collectively, our research confirms that CAG inhibits the formation and function of osteoclasts by regulating RANKL-induced intracellular signaling pathways, which may represent a promising alternative for the therapy of osteoclast-related disease.

Myocardial ischemia/reperfusion (I/R) injury is a major complication of reperfusion therapy in myocardial infarction. Ischemic myocardium produces a variety of peptides. We recently identified PDRPS7 as a novel peptide in cardiomyocytes that can be induced by hypoxia. However, the role of PDRPS7 is unknown. Here, we investigated the effects of PDRPS7 on hypoxia/reoxygenation (H/R)‐induced injury in rat cardiomyoblast H9c2 cells and NRCMs. We found that PDRPS7 improved cell survival and attenuated lactate dehydrogenase leakage following H/R in H9c2 cells and NRCMs. PDRPS7 also alleviated H/R‐induced pulsation reduction in NRCMs. Moreover, H/R‐induced cell apoptosis was decreased in the presence of PDRPS7. H/R‐induced reactive oxygen species generation was reduced by PDRPS7; in addition, PDRPS7 did not impact H2O2‐induced cell injury. Signaling analysis demonstrated that H/R increased the phosphorylation levels of JNKs, ERKs, and p38 mitogen‐activated protein kinases. However, PDRPS7 only attenuated H/R‐induced JNK phosphorylation, but not phosphorylation of ERKs and p38. PDRPS7 protected cardiomyocytes from apoptosis by inhibiting JNK phosphorylation and c‐Jun phosphorylation pathways, markedly upregulating anti‐apoptotic Bcl‐2 expression and inhibiting that of pro‐apoptotic Bax and cleaved caspase‐3. Importantly, pharmacological activation of JNKs diminished the protective effect of PDRPS7 in terms of cell survival against H/R stimulation. In summary, our study identified PDRPS7 as a novel cardioprotective peptide against H/R challenge and this action was mediated, at least in part, through inactivation of JNKs.

Abstract We investigated the effects and possible mechanisms of Bacillus amyloliquefaciens NCPSJ7 against the gray mold caused by Botrytis cinerea in the postharvest Red Globe grapes. The disease incidence, lesion diameter, decay index, and some resistance‐related enzymes were evaluated. The antioxidant capacity of grape treated with 1 × 104 CFU/ml B. cinerea alone and combined with 1 × 107 CFU/ml NCPSJ7 was also determined. The results showed that NCPSJ7 + B. cinerea reduced the disease incidence, lesion diameter, and decay index of postharvest grapes and enhanced the activities of polyphenol oxidase, peroxidase, chitinase, and β‐1,3‐glucanase during different storage periods. Furthermore, the oxidative resistance, demonstrated by an escalating trend in the total phenolic content, DPPH free radical clearance rate, reducing power, and superoxide anion clearance rate after lesion presence, was improved. However, NCPSJ7 showed an inhibitory effect on gray mold, but resulted in the reduced antioxidant capacity in the grapes.

RNA editing and RNA splicing are involved in tumorigenesis. Here the authors report crosstalk between RNA editing and splicing by identifying ADAR1/2-dependent splicing events in esophageal squamous carcinoma cells.

Being one of the hardest materials known in nature, boron carbide (B4C) suffers from severe degradation of mechanical properties when subjected to external pressure or shear stress, which hinders its application in metal forming and machining industries. Herein, based on the phase diagrams, a new strengthening strategy consisting of constructing three-dimensional hafnium diboride (HfB2) networks was proposed to reinforce B4C using the molten-salts method followed by spark plasma sintering (SPS). It was found that the surface amorphization and subsequent decarburization were the main wear regime of pure B4C. Incorporating hard HfB2 networks in B4C resulted in enhanced mechanical properties and reduced wear rates, as the deformation and decarburization of B4C grains were effectively restrained. The excessively high Hf contents, however, made the composites prone to severe adhesive wear following the material transfer from mating materials during the inception of sliding contact, which led to deteriorated wear performances. Thus, the optimal molar ratio of Hf to B4C was determined with the underlying wear mechanisms delineated. The presented results not only show the feasibility of B4C-HfB2 composites as tool materials but also provide a novel designing strategy employing hard networks rather than conventional compliant binders to fabricate wear-resistant composite materials.

Background Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. Methods Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. Results Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.

Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.

Salmonella enterica (S. enterica) is an important foodborne pathogen, causing food poisoning and human infection, and critically threatening food safety and public health. Salmonella typing is essential for bacterial identification, tracing, epidemiological investigation, and monitoring. Serotyping and multilocus sequence typing (MLST) analysis are standard bacterial typing methods despite the low resolution. Core genome MLST (cgMLST) is a high-resolution molecular typing method based on whole genomic sequencing for accurate bacterial tracing. We investigated 250 S. enterica isolates from poultry, livestock, food, and human sources in nine provinces of China from 2004 to 2019 using serotyping, MLST, and cgMLST analysis. All S. enterica isolates were divided into 36 serovars using slide agglutination. The major serovars in order were Enteritidis (31 isolates), Typhimurium (29 isolates), Mbandaka (23 isolates), and Indiana (22 isolates). All strains were assigned into 43 sequence types (STs) by MLST. Among them, ST11 (31 isolates) was the primary ST. Besides this, a novel ST, ST8016, was identified, and it was different from ST40 by position 317 C → T in dnaN. Furthermore, these 250 isolates were grouped into 185 cgMLST sequence types (cgSTs) by cgMLST. The major cgST was cgST235530 (11 isolates), and only three cgSTs contained isolates from human and other sources, indicating a possibility of cross-species infection. Phylogenetic analysis indicated that most of the same serovar strains were putatively homologous except Saintpaul and Derby due to their multilineage characteristics. In addition, serovar I 4,[5],12:i:- and Typhimurium isolates have similar genomic relatedness on the phylogenetic tree. In conclusion, we sorted out the phenotyping and genotyping diversity of S. enterica isolates in China during 2004–2019 and clarified the temporal and spatial distribution characteristics of Salmonella from different hosts in China in the recent 16 years. These results greatly supplement Salmonella strain resources, genetic information, and traceability typing data; facilitate the typing, traceability, identification, and genetic evolution analysis of Salmonella; and therefore, improve the level of analysis, monitoring, and controlling of foodborne microorganisms in China.

Bacillus amyloliquefaciens NCPSJ7 showed potential fungicidal activities for the effective control of fungal infection. From the PCR test, the key genes (srfAA, sfp, fenD, bmyB, ituD, and ituC) were detected in B. amyloliquefaciens NCPSJ7. These genes were closely related to the lipopeptides (LPs) synthesis. Next, three LPs families were identified with liquid chromatography–mass spectrometry (LC/MS), including iturin A, fengycin A, and surfactin. After purification with C18, the main active antifungal compound was proven to be C14-iturin A by ESI-HRMS, which has significant activities against fungi. These results proved that C14-iturin A played an important role in inhibiting the growth of fungi for B. amyloliquefaciens NCPSJ7. Furthermore, the isolated LP could inhibit mycelial growth and conidia germination at 30 μg/mL. SEM allowed us to observe that mycelial morphology and conidia germination were also affected. The mycelial ultrastructure TEM observations showed that the external electron-dense outer layer cell wall, which mainly consisted of glycoproteins, was affected. Furthermore, swollen mitochondria, enriched glycogen, and increased vacuoles were also found. LP also affected the intact wall and membranes, leading to their increased permeability, which was proved by propidium iodide (PI) staining and conductivity measurements. Meanwhile, the ergosterol, which has an affinity for iturin A, also increased. These results indicated that LP caused fungal dysfunction and membrane permeability increase, leading to fungal inhibition. Identifying and studying LPs is important in exploring the fungicidal activities of B. amyloliquefaciens, which promotes the use of B. amyloliquefaciens NCPSJ7 as a potential candidate for biocontrol.

High spliceosome activity is a dependency for cancer cells, making them more vulnerable to perturbation of the splicing machinery compared to normal cells. To identify splicing factors important for prostate cancer (PCa) fitness, we performed pooled shRNA screens in vitro and in vivo. Our screens identified heterogeneous nuclear ribonucleoprotein M (HNRNPM) as a regulator of PCa cell growth. RNA- and eCLIP-sequencing identified HNRNPM binding to transcripts of key homeostatic genes. HNRNPM binding to its targets prevents aberrant exon inclusion and backsplicing events. In both linear and circular mis-spliced transcripts, HNRNPM preferentially binds to GU-rich elements in long flanking proximal introns. Mimicry of HNRNPM-dependent linear-splicing events using splice-switching-antisense-oligonucleotides was sufficient to inhibit PCa cell growth. This suggests that PCa dependence on HNRNPM is likely a result of mis-splicing of key homeostatic coding and non-coding genes. Our results have further been confirmed in other solid tumors. Taken together, our data reveal a role for HNRNPM in supporting cancer cell fitness. Inhibition of HNRNPM activity is therefore a potential therapeutic strategy in suppressing growth of PCa and other solid tumors.

Total flavonoids of Rhizoma drynariae (TFRD), a Chinese medicine, is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good effects. Purpose of this trial was to explore efficacy of TFRD on bone graft’s mineralization and osteoblasts’ differentiation in Masquelet induced membrane technique in rats. Forty male Sprague-Dawley rats were randomly divided into high dose group (H-TFRD), middle dose group (M-TFRD), low dose group (L-TFRD) and control group (control). The critical size bone defect model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) spacer was implanted into the defect of right femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 12 weeks of bone graft, bone tissues in the area of bone graft were examined by X-ray, Micro-CT, hematoxylin-eosin (HE) and Masson trichrome staining to evaluate the growth of the bone graft. The β-catenin, c-myc, COL1A1, BMP-2 and OPN in bone graft were quantitatively analyzed by Western blot and Immunohistostaining. Osteoblasts were cultured in the medium containing TFRD. Cell Counting Kit-8 (CCK-8) method, Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, Western blot, RT-PCR and other methods were used to detect the effects of TFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signaling pathway. In vivo experiments showed that the growth and mineralization of bone graft in TFRD group was better. Moreover, the expression of Wnt/β-catenin and osteogenesis-related proteins in bone tissue of TFRD group was more than that in other groups. In vitro experiments indicated that osteoblasts proliferated faster, activity of ALP was higher, number of mineralized nodules and proteins related to osteogenesis were more in TFRD group. But blocking Wnt/β-catenin signaling pathway could limit these effects. Therefore, TFRD could promote mineralization of bone graft and differentiation of osteoblasts in a dose-dependent manner during growing period of the bone graft of induced membrane technique, which is partly related to the activation of Wnt/β-catenin signaling pathway.

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson’s disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

To explore the effect and mechanism of bivalent ion doping on yttrium iron garnet (YIG), Zn-YIG (Zn-doped YIG) nanoparticles with a size of 60~70 nm were prepared by the sol-gel method. It was proven that Zn ion doping resulted in lattice expansion and internal stress due to crystallite size shrinkage. A Raman spectroscopic analysis proved the influence of Zn doping on the crystal structure and peak intensity by analyzing Raman vibration modes. The characteristics and chemical mechanism of mass loss and phase evolution in each temperature region were explored through TG-DSC measurements. Moreover, it was revealed that the antiferromagnetic coupling, pinning mechanisms and particle aggregation lead to coercivity, exhibiting different variation trends. A saturation magnetization (Ms) curve variation mechanism was further revealed, which was due to the thermal effects, super-exchange effect, and coupling effect between sub-lattices. Meanwhile, the influence of the thermal effect on Ms and its mechanism were explored by spin theory, and it was proven that it was mainly caused by the random arrangement of magnetic moments and thermal vibration. These results provide theoretical support for the wider application of YIG devices in microwave and high-temperature fields.

In this study, a Monte Carlo simulation (MCs)-based isogeometric stochastic Finite Element Method (FEM) is proposed for uncertainty quantification in the vibration analysis of piezoelectric materials. In this method, deterministic solutions (natural frequencies) of the coupled eigenvalue problem are obtained via isogeometric analysis (IGA). Moreover, MCs is employed to solve various uncertainty parameters, including separate elastic and piezoelectric constants and their combined cases.

In order to solve the problem of low accuracy of traditional construction project risk prediction, a project risk prediction model based on EW-FAHP and 1D-CNN(One Dimensional Convolution Neural Network) is proposed. Firstly, the risk evaluation index value of construction project is selected by literature analysis method, and the comprehensive weight of risk index is obtained by combining entropy weight method (EW) and fuzzy analytic hierarchy process (FAHP). The risk weight is input into the 1D-CNN model for training and learning, and the prediction values of construction period risk and cost risk are output to realize the risk prediction. The experimental results show that the average absolute error of the construction period risk and cost risk of the risk prediction model proposed in this paper is below 0.1%, which can meet the risk prediction of construction projects with high accuracy.

Recently, the multitower suspension bridge has been widely used in long-span bridge construction. However, the dynamic response of the deck and pavement system of the multitower suspension bridge under random vehicle load is still not clear, which is of great significance to steel-bridge deck pavement (SBDP) design and construction. To reveal the mechanical mechanism of the steel-bridge deck pavement of the multitower suspension bridge under traffic load, this paper analyzed the mechanical response of the pavement based on case study through the multiscale numerical approach and experimental program. Firstly, considering the full-bridge effect of the multitower suspension bridge, the finite element model (FEM) of the SBDP composite structure was established to obtain key girder segments. Secondly, the influences of pavement layer, bending moment and torque, random traffic flow, and bridge structure on the stress of the girder segment were analyzed. Thirdly, the mechanical response of the pavement layer to the orthotropic plate under random vehicle load was studied. Finally, a full-scale model of the experimental program was established to verify the numerical results. Results show that (1) the pavement layer reduced the stress of the steel-box girder roof by about 10%. In the case of adverse bending moment and torque, the longitudinal and transverse stresses of the pavement layer were mainly concentrated in the stress concentration area near the suspender. Under the action of the random vehicle flow, the stress response of the pavement layer was increased by 40% compared with that under standard load. (2) Three-tower and two-span bridge structures have a great influence on the vertical deformation of the pavement layer under the action of vehicle load. Thus, the pavement material needs to have great deformation capacity. (3) The full-bridge effect has a significant influence on the longitudinal stress of the local orthotropic plate, but a small influence on the transverse stress. (4) There is a good correlation between the experimental measurement results of the full-size model and that of the numerical model. The research results can provide guidance for SBDP design and construction of the multitower suspension bridge.

The maintenance management decisions of network-level asphalt pavements have long been a challenge to highway agencies, and a great amount of factors have been involved. In this study, a network-level optimization method was established by integrating the maintenance benefits into the zero-one programming optimization model. An optimized performance evaluation method of asphalt pavement was proposed which contains 11 different kinds of combinations. The benefit model quantifies the cost savings of user travel time and vehicle fuel consumption to the pavement condition index (PCI) and ride quality index (RQI), respectively. Based on the simplified evaluation method as well as the quantified maintenance benefit model, an optimization model was established by employing the zero-one programming. This optimization model aimed to maximize the improvements/price ratio of pavement maintenance for the whole pavement network. The calculation results present the optimal strategies of maintenance for every road section in the network. The applicability of the newly proposed model was validated by a case study. The methodology developed in this study helps to offer guidelines to highway agencies in managing and making decisions about network-level pavement maintenance.

Translations

Asiatic acid is a triterpenoid compound extracted from a medicinal plant Centella asiatica. It has been used as a highly efficient compound for the treatment of cancer and hyperlipidemia, as well as possessing potential antiinflammatory properties. However, its effects on bone metabolism and osteoporosis haven’t been reported. The purpose of our research were to reveal the biomolecular effects of asiatic acid on osteoclasts, and its underlying molecular mechanisms regulating its effects on receptor activator of NF-κB ligand (RANKL)-induced signaling pathways. We found that asiatic acid inhibited multinucleated tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast differentiation and osteoclast induced bone loss. Real time PCR showed that asiatic acid reduced the expression of down-cascade target genes including Ctsk, Nfatc1, Calcr, and Atp6v0d2. Western blot and luciferase reporter gene assays revealed that asiatic acid inhibits RANKL mediated NF-κB and NFATc1 signalings. Further, in vivo study demonstrated asiatic acid attenuates estrogen deficiency-induced bone loss in ovariectomized mice. MicroCT and histology analyses revealed that osteoclast numbers were significantly suppressed in asiatic acid treated groups. Furthermore, serum levels of TRAcP and CTX-1 were downregulated in treated groups. Taken together, our data show that asiatic acid can inhibit osteoclastic formation and reduce OVX-induced bone resorption through RANKL-activated NF-κB or NFATc1 signaling, suggesting that asiatic acid may be a potential and effective natural compound for the therapy of excessive RANKL-related osteolytic diseases.

Abstract Friction and wear remain the primary modes for energy dissipation in moving mechanical components. Superlubricity is highly desirable for energy saving and environmental benefits. Macroscale superlubricity was previously performed under special environments or on curved nanoscale surfaces. Nevertheless, macroscale superlubricity has not yet been demonstrated under ambient conditions on macroscale surfaces, except in humid air produced by purging water vapor into a tribometer chamber. In this study, a tribological system is fabricated using a graphene‐coated plate (GCP), graphene‐coated microsphere (GCS), and graphene‐coated ball (GCB). The friction coefficient of 0.006 is achieved in air under 35 mN at a sliding speed of 0.2 mm s−1 for 1200 s in the developed GCB/GCS/GCP system. To the best of the knowledge, for the first time, macroscale superlubricity on macroscale surfaces under ambient conditions is reported. The mechanism of macroscale superlubricity is due to the combination of exfoliated graphene flakes and the swinging and sliding of the GCS, which is demonstrated by the experimental measurements, ab initio, and molecular dynamics simulations. These findings help to bridge macroscale superlubricity to real world applications, potentially dramatically contributing to energy savings and reducing the emission of carbon dioxide to the environment.

In order to extend the service life of the steel bridge deck pavement, a long-life steel bridge deck pavement (LLSBDP) was put forward referring to the concept of long-life asphalt pavement. First, the requirements of the LLSBDP were given, based on which, an LLSBDP structure “EAC + SMA” was proposed. Second, a numerical analysis was performed to evaluate the stress status of the “EAC + SMA” structure. Third, an experimental study was conducted to assess the performance of the pavement material and the pavement structure. Meanwhile, for comparison, the performances of traditional steel bridge deck pavement structure “EAC + EAC” were also studied in the numerical and experimental program. The results showed that, with periodical rehabilitation or reconstruction of the SMA surface layer, the EAC base layer can last for a long life without structural distresses. The proposed structure can meet the requirements of LLSBDP and can be used to extend the service life of the steel bridge deck pavement.

Cronobacter sakazakii (C. sakazakii) widely exists in the environment and is a common foodborne pathogenic microorganism. It can cause meningitis, bacteremia, and necrotizing enterocolitis in infants and elderly people with low immunity. Therefore, the development of the rapid detection method for foodborne pathogen C. sakazakii is very important for food safety control. This study has developed a kind of genomic nucleic acid reference material as a positive reference for the rapid detection of C. sakazakii in the edible fungus Flammulina velutipes. First, the genomic nucleic acids were extracted from the standard strain of C. sakazakii, and the nucleic acids were lyophilized. The uniformity test result of the lyophilized powder showed that there were no significant differences between samples. In short-term stability tests at 4°C and 37°C for 14 days, the properties of the nucleic acid reference material were good, and in long-term stability tests at 4°C and −20°C for 8 months, the samples are still stable. To verify the application of this nucleic acid reference material, it was used as a positive control template for PCR detection and applied to the rapid detection of C. sakazakii in F. velutipes. It was found that 13 of the 15 F. velutipes samples were positive for C. sakazakii. As far as we know, this is the first attempt to detect C. sakazakii in F. velutipes using the PCR method with nucleic acid reference material as the positive reference. This study is helpful in promoting the extensive and in-depth application of nucleic acid reference materials in foodborne pathogens detection.