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Abstract To investigate the effect of Tetrasphaera’s enrichment on phosphorus removal mechanism, three micro-pressure swirl reactor (MPSR) groups were used to experiment on sewage treatment under different SRT (17.2, 50.8, and 68.2 d). Results showed that Tetrasphaera enrichment in the MPSR system was promoted by extending the SRT. After extending the SRT from 17.2 to 68.2 d, the relative abundance of Tetrasphaera increased from 3.1% to 12.1%, and the TP removal efficiency maintained above 92%. The internal circulation results indicated that after extending the SRT, glycogen and polyhydroxybutyrate were co-synthesized during the anaerobic stage, which enhanced the driving force of nutrient removal. Analysis of the microbial composition and functional gene prediction indicated that efficient phosphorus removal can be attributed to the enrichment of Tetrasphaera at long SRT. Overall, the synergistic mechanisms of Tetrasphaera in the organic matter degradation and phosphorus removal processes were integrated into the MPSR.

Aiming at finding a better way to solve the problem of beer production scheduling, a new collaborative optimization based on the Manhattan Distance and Chameleon Swarm Algorithm is proposed. Firstly, a dynamic relaxation factor is introduced to the constraints at the system level, which combines the changing trend of the inconsistency information and the optimal solution of the discipline level. Additionally, the Manhattan Distance is used to replace the square of the Euclidean Distance at the system level. Thirdly, the Chameleon Swarm Algorithm is used to improve the update rule during the process of iteration. As these improvements are applied to the collaborative optimization, the steps of this new algorithm are given. Through the test case of a multivariate function, it can be found that the algorithm has been improved compared to the original algorithm. Then, a model for beer production scheduling is proposed, and the results of the optimization show that the improved collaborative optimization has better optima effectiveness and fewer iterations and is not sensitive to initial points, which proves that the improved collaborative optimization has a better ability to solve the problem of beer production scheduling than normal collaborative optimization and collaborative optimization with fixed relaxation factors.

Abstract Background Basic resource needs related to transportation, housing, food, and medications are important social determinants of health and modifiable indicators of poverty, but their role in modifying the risk of frailty and health‐related quality of life (HRQoL) remains unknown. The goal of our study was to examine the prevalence of unmet basic needs and their association with frailty and HRQoL in a cohort of older adults with cancer. Methods The CARE registry prospectively enrolls older adults (≥60 years) with cancer. Assessments of transportation, housing, and material hardship were added to the CARE tool in 8/2020. The 44‐item CARE Frailty Index was used to define frailty, and subdomains of physical and mental HRQoL were assessed using the PROMIS® 10‐global. Multivariable analysis examined the association between unmet needs with frailty and HRQoL subdomains, adjusting for covariates. Results The cohort included 494 participants. Median age of 69 years, 63.6% were male and 20.2% were Non‐Hispanic (NH) Black. Unmet basic needs were reported in 17.8% (transportation 11.5%, housing 2.8%, and material hardship 7.5%). Those with unmet needs were more often NH Black (33.0% vs. 17.8%, p = 0.006) and less educated (

Backgroud and aim T lymphocytes are involved in the occurrence and development of essential hypertension, and potassium channels are thought to be critical for lymphocyte activation. This study is to examine the roles of the voltage-gated potassium channels (Kv1.3) and calcium-activated potassium channels (KCa3.1) in peripheral blood T lymphocytes in Kazakh hypertensive patients of Xinjiang, China, mainly focusing on the effects of these channels on nuclear factor of activated T cells (NFAT) and inflammatory cytokines of T lymphocytes. Method Kv1.3 and KCa3.1 gene silencing were performed in cultured T lymphocytes from Kazakh patients with severe hypertension. T cell proliferation after gene silencing was measured using CCK-8. The mRNA and protein expression levels were measured using RT-qPCR and Western blot analysis, respectively. Nuclear translocation of NFAT was observed using laser confocal fluorescence microscopy. Inflammatory cytokine levels were detected with ELISA. Results Compared with control group, gene silencing of Kv1.3 and KCa3.1 respectively inhibited the proliferation of T cells. Moreover, compared with the control group, the mRNA expression levels of NFAT, IL-6 and IFN-γ were significantly decreased after gene silencing. Furthermore, the NFAT protein expression level was significantly down-regulated. In addition, the levels of IFN-γ and IL-6 in the cell culture supernatant were significantly decreased. Conclusion Both Kv1.3 and KCa3.1 potassium channels activated T lymphocytes and enhanced the cytokine secretion possibly through CaN/NFAT signaling pathway, which may in turn induce micro-inflammatory responses and trigger the occurrence and progression of hypertension.

This study aimed to improve the safety and economy of cement production and to investigate the gasification performance and tar properties of wheat straw in a small electrically heated bubbling fluidized bed by varying three factors, namely, gasification reaction conditions, fuel quality and type, and the natural environment, so as to promote the application of the low-temperature gasification of biomass in the cement industry. The gasification experiment was carried out at temperatures of 550–700 °C, air equivalence ratios of 0.1–0.2, moisture contents of 5.25–24%, blended rubber ratios of 0–100%, and furnace vacuums of 0–0.03 within the parameter ranges, and the component analyses of the produced gases and tars were carried out by gas chromatography (GC) and gas chromatography–mass spectrometry (GC-MS). The experimental findings revealed that the optimal operating conditions for gasification were attained at a temperature of 650 °C, an equivalence ratio of 0.15, a moisture content of 5.25%, a rubber blending ratio of 0, and a vacuum degree of 0. Under these conditions, the concentrations of combustible components (H2, CH4, and CO) in the produced gas were 4.01%, 4.60%, and 21.05%, respectively. The carbon conversion rate was 62.40%, with the cold gas efficiency of 39.37%. The lower heating value of the produced gas was 5.915 MJ/Nm3, accompanied by a tar yield of 118.15 g/Nm3 and lower heating value of 3.385 MJ/Nm3.

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

Polymer matrices have limited abilities to dissociate lithium salts and transport ions, thus making most solid-state polymer electrolytes (SPEs) have extremely low ionic conductivities (10−7–10−5 S/cm) at 25 ℃. In this work, a high-energy electron-beam (e-beam) irradiation is applied to a poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] SPE to improve the ionic conductivity. P(VDF-TrFE) easily shows pure all-trans (TTTT) conformation with all fluorine atoms located on one side of the carbon chain to provide an ion transport highway. E-beam irradiation keeps large amounts of TTTT conformation of P(VDF-TrFE) and produces –CF3 side groups, where the latter expands the interchain distance to split the large ferroelectric domains into nanosize to induce a unique relaxor ferroelectric behavior. This enhances the dielectric constant of the irradiated P(VDF-TrFE) from 15 to 20 and thus facilitates lithium salt dissociation. As a consequence, the ionic conductivity of the irradiated P(VDF-TrFE) SPE is increased from 5.8 × 10−5 to 1.6 × 10−4 S cm−1 at 25 ℃. The solid-state Li//Li symmetrical cell cycles for more than 3000 h at 25 ℃ without a short circuit. Furthermore, the solid-state LFP//Li cell cycles stably for more than 350 cycles with a capacity retention of around 91.3% at 1 C and 25 ℃. This study paves a new way to prepare high-performance SPEs by inducing high dielectric constants and abundant TTTT conformations through e-beam irradiation.

IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.

The distribution patterns of the paleo-Changjiang River deltas formed during the MIS 3 period before the last glacial maximum (LGM) contain important information about the deltaic deposits in response to climate and sea-level changes. However, so far, they are still poorly understood. Here, we reconstruct the stratigraphic and chronological framework of the deltaic system based on the analysis of 1835 km of high-resolution seismic profiles obtained from the northern East China Sea, together with a comparison with the research results from four existing boreholes and three groups of published seismic profiles from the study area. Within the strata from MIS 5 to MIS 1 that are preserved on the northern shelf of the East China Sea, we discovered a large-scale paleodeltaic complex formed during the MIS 3 period. During MIS 3, sea level dropped slowly; the paleodelta formed was large in scale and was distributed between water depths of 40 and 150 m. It is now directly exposed at the seabed at a depth of more than 100 m. The paleodelta had extended from the northwest to the southeast, with maximum thickness of the deposits around 55 m. The extensions in the east–west and south–north directions both exceeded 300 km, with a total area around 1.35 × 105 km2. Since the late Pleistocene, the tectonic structure beneath the East China Sea has been relatively stable. As such, sea-level fluctuations, sediment supply, and original topography were the main controlling factors for the development of the delta.

BackgroundCervicogenic headache (CEH) has long been recognized as a referred pain deriving from pathological changes in the upper cervical nerves. However, previous clinical studies found that anterior lower cervical discectomy for the treatment of cervical myelopathy and/or radiculopathy can also help relieve associated headaches. To date, there is still a lack of large sample and prospective study to investigate the effect of anterior cervical decompression and fusion (ACDF) on CEH associated with cervical spondylosis.MethodsA total of 656 patients with cervical radiculopathy and/or myelopathy were enrolled in three spinal centers. Among them, 221 patients who were diagnosed with CEH were collected in this study, and 204 completed a 1-year follow-up. The primary endpoint was headache intensity during a 12-month follow-up period measured by the numeric pain rating scale (NPRS). The secondary outcome measures included headache frequency, headache duration, and the neck disability index (NDI).ResultsAmong all 204 patients with CEH who completed a 1-year follow-up, 166 received anterior cervical surgery (surgery group) and 38 received conservative treatment (conservative group). There were statistically significant lower NPRS in the surgical group during follow-up. Between-group differences showed that NPRS in the surgery group was significantly greater improvement at 1 month (2.8, 95% CI: 2.0, 3.6), 3 months (2.6, 95% CI: 1.8, 3.4), 6 months (2.4, 95% CI: 1.6, 3.2), and 12 months (1.5, 95% CI: 0.7, 2.4) (p < 0.05 for all). There were statistically significant lower NDI, less frequent headaches, and lower headache duration in the surgery group during follow-up (p < 0.05 for all).ConclusionThis study indicates that ACDF can effectively relieve CEH associated with cervical myelopathy and/or radiculopathy.

A recyclable bolt is a kind of green supporting component that can save materials and weaken the influence of underground engineering. It has a good application prospect in foundation pit and slope-supporting engineering, as well as a high economic and environmental effect in future engineering construction. The stress and displacement change of the foundation pit with a recoverable bolt was analyzed by performing a laboratory model test. The test results demonstrated that in the process of excavation, the recyclable anchor rod supporting the structure effectively limited the horizontal displacement of the pile top and had a significant constraint effect on the surface settlement. With the increase in the excavation depth, both the axial force value of the recyclable anchor rod and the maximum bending moment value of the supporting pile increased gradually, and the maximum bending moment value of the supporting pile appeared at 1/3 H. After the excavation, the maximum horizontal displacement of the pile top was 0.04% of the excavation depth. The failure recovery of the anchor was the primary factor contributing to the increased deformation of the foundation pit during the backfilling stage. Upon completion of the backfilling process, the final deformation of the foundation pit reached 0.1% of the excavation depth; this can meet safety requirements, reduce the waste of building materials, and conform to the concept of green sustainable development.

Glycyrrhiza polysaccharide extract 1 (GPS-1) is a bioactive component isolated from Glycyrrhiza uralensis, also known as Chinese licorice. It appears to be pharmacologically active as an antibacterial, antiviral, and anti-tumor agent. GPS-1 has also been shown to buffer liver health and regulate the immune system. Moreover, GPS-1 is low cost and easy to extract. More study was needed to elucidate the biochemical pathways underlying the immunomodulatory and antioxidant benefits observed in Glycyrrhiza polysaccharide extract 1 (GPS-1). in vitro experiments on chicken lymphocytes and dendritic cells (DCs) show that GPS-1 significantly promotes the proliferation of immune cells and is linked to lymphocytes' secretion of IL-12, IFN-γ, and TNF-α by. DC secretion of NO, IL-2, IL-1β, IFN-γ, TNF-α, and IL-12p70 was also increased significantly. Additionally, GPS-1 also displayed a significant antioxidant effect in vitro, able to scavenge DPPH, hydrogen peroxide, ABTS, and other free radicals like superoxide anions. Separately, GPS-1 was tested in vivo in combination with the Newcastle disease virus (NDV) – attenuated vaccine. 120 Lohmann Brown chickens were vaccinated, while another 30 became the unvaccinated blank control (BC) group. For three consecutive days 1 mL of GPS-1 was administered at doses of 19.53 μg/mL, 9.77 μg/mL, or 4.88 μg/mL to the ND-vaccinated birds, except for the vaccine control (VC), where n = 30 per group. In vivo results show that GPS-1 combined with Newcastle disease (ND) vaccine had the best efficacy at significantly increasing chickens' body weight and ND serum antibody titer, enhancing their secretion of IL-2 and IFN- γ, and promoting the development of immune organs. The results also indicate that GPS-1 was able increase the proliferation of in vitro immune cells and elevate their cytokine secretion, which enhances the body's immune response. GPS-1 also clearly has the potential to be used as an immune adjuvant alongside ND vaccination.

Underwater pressure-bearing structures are produced in practice by means of pressure self-enhancement methods in order to improve the stress distribution and enhance the pressure-bearing performance. On the other hand, the pairs equation shows that stress is an important factor influencing the degradation of the structure. In fact, improving the stress distribution will not only improve the pressure-bearing performance, but will have an impact on the life degradation trend. Thus, pressure self-enhancement affects the structural life by changing the stress distribution. With this in mind, this paper considers the effect of pressure self-enhancement on the service time of subsea structures, and a Bayesian network (BN)-based method that can be used to predict the remaining useful life (RUL) of underwater self-enhanced structures is proposed. The method also takes into account the influence of multiple sources of structural factors in order to predict the RUL of the structure more accurately. The life degradation process of an all-electric Christmas tree valve actuator is used as a case study. The prediction results are compared with data in the literature to verify the validity of the method. The results have implications for guidance on the O&M assurance of underwater production systems.

Abstract The two‐dimensional (2D) in‐plane (lateral) heterostructures have attracted increasing interest for potential applications in the atomically thin electronics and optoelectronics. While most studies focus on semiconductor‐semiconductor lateral heterostructures with highly similar lattice structures between the constituent components, the synthesis of metal‐semiconductor lateral heterostructures is much less explored and usually more challenging due to more distinct lattice structures or chemical properties. Herein, a vapor phase epitaxy growth method of high‐quality metal‐semiconductor lateral heterostructures between tetragonal CoSe and hexagonal WSe2 is reported. The 2D CoSe can selectively nucleate at the edge of pre‐grown WSe2 nanosheets to form CoSe‐WSe2 metal‐semiconductor lateral heterostructures. Optical microscopy (OM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies reveal distinct contrast across the heterostructure interface. High‐resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) studies further confirm the microstructure modulation across the heterostructure interface. The field‐effect transistors (FETs) of CoSe‐WSe2 lateral heterostructures show satisfactory Ohmic contacts and considerably better FET performance over those with deposited Cr/Au contacts, suggesting the in‐plane metal‐semiconductor junctions may function as improved contacts for the atomically thin electronics.

As a natural refrigerant, CO2 can greatly improve the environmental protection of the heat pump system. Since there is no perfectly suitable heat transfer correlation for supercritical CO2 at present, the water outlet temperature of the transcritical CO2 heat pump system has not been predicted. To study the applications of transcritical CO2 heat pump systems in heating performance and hot water supply, a series of experiments are carried out by an air source transcritical CO2 heat pump test rig. The experimental results show that the main factors affecting outlet water temperature are the system COP, the discharge pressure, the compressor frequency, and the ambient temperature. Based on the experimental results, a dimensionless correlation equation on outlet water temperature is proposed by the Buckingham PI theorem. This equation can be used to calculate the outlet water temperature of the air source transcritical CO2 heat pump systems with different sizes, and the calculation accuracy can be maintained at 13% with experimental results. Finally, the influence factors of the gas cooler water outlet temperature are analyzed based on the novel calculation method. Therefore, this study provides a reference for the prediction of the water outlet temperature of the transcritical CO2 heat pump system.

The overuse of antibiotics in poultry farming causes the accumulation of drug residue in animals' bodies and the occurrence of antibiotic-resistant bacteria, which not only compromise animals' health but ultimately endanger human health. Thus, there is an urgent need for a novel poultry feed additive to substitute for excessive antibiotics. Glycyrrhiza polysaccharides (GPS) derived from Chinese licorice have shown promising immunomodulatory effects in previous studies. The present study investigated the pharmacological effects of GPS on poultry intestines to assess whether it can be used as a feed additive. The results show that GPS can increase production of sIgA, promote the secretion activity of goblet cells, alter the gut microbial composition and lead to changes in short-chain fatty acids. GPS also elevated both Th1 and Th2 immune responses by facilitating the expression of IL-2, IL-4, IL-1β, and IFN-γ while increasing the proportion of both CD4+ and CD8+ cells in the intestine. Moreover, the results of 16S rRNA gene sequencing showed that GPS could significantly change intestinal microbiota composition in the intestine, evidenced by the increased proportion of Bacteroides, Butyricicoccus and Eisenbergiella, as well as a decreased portion of Erysipelatoclostridium, leading to a healthier intestinal microbiota composition for the host. Taken together, it can be concluded that GPS is safe to use as a novel feed additive that can be used as an alternative to prophylactic antibiotics in poultry feeding.

Ischemia-reperfusion injury (IRI) is a common complication associated with liver surgery, and macrophages play an important role in hepatic IRI. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog primarily used to treat type 2 diabetes and obesity, regulates intracellular calcium homeostasis and protects the cardiomyocytes from injury; however, its role in hepatic IRI is not yet fully understood. This study aimed to investigate whether liraglutide can protect the liver from IRI and determine the possible underlying mechanisms. Our results showed that liraglutide pretreatment significantly alleviated the liver damage caused by ischemia-reperfusion (I/R), as evidenced by H&E staining, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and TUNEL staining. Furthermore, the levels of inflammatory cytokines elicited by I/R were distinctly suppressed by liraglutide pretreatment, accompanied by significant reduction in TNF-α, IL-1β, and IL-6 levels. Furthermore, pretreatment with liraglutide markedly inhibited macrophage type I (M1) polarization during hepatic IRI, as revealed by the significant reduction in CD68+ levels in Kupffer cells (KCs) detected via flow cytometry. However, the protective effects of liraglutide on hepatic IRI were partly diminished in GLP-1 receptor-knockout (GLP-1R-/-) mice. Furthermore, in an in vitro study, we assessed the role of liraglutide in macrophage polarization by examining the expression profiles of M1 in bone marrow-derived macrophages (BMDMs) from GLP-1R-/- and C57BL/6J mice. Consistent with the results of the in vivo study, liraglutide treatment attenuated the LPS-induced M1 polarization and reduced the expression of M1 markers. However, the inhibitory effect of liraglutide on LPS-induced M1 polarization was largely abolished in BMDMs from GLP-1R-/- mice. Collectively, our study indicates that liraglutide can ameliorate hepatic IRI by inhibiting macrophage polarization towards an inflammatory phenotype via GLP-1R. Its protective effect against liver IRI suggests that liraglutide may serve as a potential drug for the clinical treatment of liver IRI.

Leopard coral grouper (Plectropomus leopardus) is an indispensable kind of fish in the coral reef ecosystems and marine aquaculture, and the body color of leopard coral grouper is exhibited in black, brown or red. In order to explore the molecular mechanism affecting the body color of the leopard coral grouper, the illumina sequencing technology was used here, the transcriptome of the skin and brain tissues of the red and black leopard coral grouper were sequenced and the differentially expressed genes between the different body colors of the two tissues were further analyzed in this study. Our results showed that the expressional level of multiple genes in the pathways related to pigment synthesis exhibited significant differences. In addition, encoding gene of microphthalmia-associated transcription factor (MITF) were identified related to the pigment synthesis, phylogenetic analysis and three-dimensional structure predictions on the MITF protein were performed as well. In conclusion, a relatively complete transcriptome data set of different body colors and different tissues in leopard coral grouper were established in this study. The analysis of genes related to the melanin synthesis pathway here will provide a further understanding of the internal mechanism of body color transition in vertebrate.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal human malignancy, and previous researches support the contribution of microRNA (miRNA) to cancer progression. MiR-122-5p is reported to participate in the regulation of various cancers, while the function of miR-122-5p in PDAC remains unclear. In this study, we investigated the precise mechanism of miR-122-5p involved in PDAC pathogenesis. Methods The expression levels of miR-122-5p were detected in human PDAC tissues and cell lines by miRNA RT-PCR. The effects of miR-122-5p on cell proliferation were explored by MTT assays, colony formation assays and flow cytometry assays. The ability of migration and invasion was determined by transwell assays. Dual Luciferase reporter assay was performed to validate the direct interaction between miR-122-5p and its target gene. The related molecules of cell cycle, apoptosis and epithelial–mesenchymal transition (EMT) were examined with qRT-PCR and western blot. In addition, xenograft mouse models were applied to explore the effects of miR-122-5p in vivo. Results MiR-122-5p was underexpressed, while CCNG1 was highly expressed in PDAC tissues and cells. MiR-122-5p was negatively correlated with TNM stage, tumor size and lymph node metastasis in PDAC patients. Overexpression of miR-122-5p suppressed the proliferation, migration and invasion in vitro and inhibited tumorigenesis in vivo. Furthermore, CCNG1 was a direct target of miR-122-5p. Upregulated CCNG1 could partially reverse the effects caused by miR-122-5p. Moreover, miR-122-5p inhibited EMT through downregulation of CCNG1. Conclusion Overexpression of miR-122-5p could inhibit cell proliferation, migration, invasion, and EMT by downregulating CCNG1 in PDAC, suggesting a potential therapeutic target for PDAC.

Abstract Background Hydrogen gas (H2) is hypothesised to play a role in plants that are coping with stresses by regulating signal transduction and gene expression. Although the beneficial role of H2 in plant tolerance to cadmium (Cd) has been investigated previously, the corresponding mechanism has not been elucidated. In this report, the transcriptomes of alfalfa seedling roots under Cd and/or hydrogen-rich water (HRW) treatment were first analysed. Then, the sulfur metabolism pathways were focused on and further investigated by pharmacological and genetic approaches. Results A total of 1968 differentially expressed genes (DEGs) in alfalfa seedling roots under Cd and/or HRW treatment were identified by RNA-Seq. The DEGs were classified into many clusters, including glutathione (GSH) metabolism, oxidative stress, and ATP-binding cassette (ABC) transporters. The results validated by RT-qPCR showed that the levels of relevant genes involved in sulfur metabolism were enhanced by HRW under Cd treatment, especially the genes involved in (homo)glutathione metabolism. Additional experiments carried out with a glutathione synthesis inhibitor and Arabidopsis thaliana cad2–1 mutant plants suggested the prominent role of glutathione in HRW-induced Cd tolerance. These results were in accordance with the effects of HRW on the contents of (homo)glutathione and (homo)phytochelatins and in alleviating oxidative stress under Cd stress. In addition, the HRW-induced alleviation of Cd toxicity might also be caused by a decrease in available Cd in seedling roots, achieved through ABC transporter-mediated secretion. Conclusions Taken together, the results of our study indicate that H2 regulated the expression of genes relevant to sulfur and glutathione metabolism and enhanced glutathione metabolism which resulted in Cd tolerance by activating antioxidation and Cd chelation. These results may help to elucidate the mechanism governing H2-induced Cd tolerance in alfalfa.

Abstract Background Swep is an excellent carbamate herbicide that kills weeds by interfering with metabolic processes and inhibiting cell division at the growth point. Due to the large amount of use, swep residues in soil and water not only cause environmental pollution but also accumulate through the food chain, ultimately pose a threat to human health. This herbicide is degraded in soil mainly by microbial activity, but no studies on the biotransformation of swep have been reported. Results In this study, a consortium consisting of two bacterial strains, Comamonas sp. SWP-3 and Alicycliphilus sp. PH-34, was enriched from a contaminated soil sample and shown to be capable of mineralizing swep. Swep was first transformed by Comamonas sp. SWP-3 to the intermediate 3,4-dichloroaniline (3,4-DCA), after which 3,4-DCA was mineralized by Alicycliphilus sp. PH-34. An amidase gene, designated as ppa, responsible for the transformation of swep into 3,4-DCA was cloned from strain SWP-3. The expressed Ppa protein efficiently hydrolyzed swep and a number of other structural analogues, such as propanil, chlorpropham and propham. Ppa shared less than 50% identity with previously reported arylamidases and displayed maximal activity at 30 °C and pH 8.6. Gly449 and Val266 were confirmed by sequential error prone PCR to be the key catalytic sites for Ppa in the conversion of swep. Conclusions These results provide additional microbial resources for the potential remediation of swep-contaminated sites and add new insights into the catalytic mechanism of amidase in the hydrolysis of swep.

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord. Indeed, cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration. This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord. This scaffold allows cell growth in vitro and in vivo. To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury. Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed), spinal cord injury (transection injury of T10 spinal cord without any transplantation), 3D-CF (3D scaffold was transplanted into the local injured cavity), and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity. Neuroelectrophysiology, imaging, hematoxylin-eosin staining, argentaffin staining, immunofluorescence staining, and western blot assay were performed. Apart from the sham group, neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups. Moreover, latency of the 3D-CF + NSCs group was significantly reduced, while the amplitude was significantly increased in motor evoked potential tests. The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group. Moreover, regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups. These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord. This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No. 2017-0007.2).

IntroductionChordoma is formed from embryonic residues or ectopic chordae and locally aggressive or malignant tumors. We visually analyzed the research tendency and hotspot of chordoma.MethodsThe bibliometric analysis was conducted from the Web of Science Core Collection database over the past two decades. The term and strategies were as follows: "TS = (chordoma) OR TS = (chordoblastoma) OR TS = (chordocarcinoma) OR TS = (chordoepithelioma) OR TS = (chordosarcoma) OR TS = (notochordoma). AND Language: English. AND Reference Type: Article OR Review". A total of 2,118 references were retrieved and used to make a visual analysis by VOSviewer 1.6.15.ResultsThe chordoma was on a steady rise and chordoma but remained the focus of scholars and organizations over the last two decades. The Chinese institutions and scholars lacked cooperation with their counterparts in other countries. The citations of documents and co-citation analysis of cited references suggested that M.L. McMaster, B.P. Walcott, P. Bergh, and S. Stacchiotti were leading researchers in this field of chordoma and their papers had been widely accepted and inspired recent researches. Keywords associated with recent chemotherapy, PD-1-related immunotherapy, and SMARCB1/integrase interactor 1 (INI1) in chordoma were a shortage of research and there may be more research ideas in the future by scholars. The research of chordoma will continue to be the hotspot.ConclusionsThus, explaining the molecular mechanism and potential role of transcriptional inhibition and immunologic responses to SMARCB1/INI1-negative poorly differentiated chordoma will be available for preclinical experiments and clinical trials and lead to new therapeutic opportunities for chordoma patients.

Ivory shell (Babylonia areolata) is a commercially important aquaculture species mainly found on the southeast coast of China. However, it has been greatly affected by vibriosis in recent years. In this study, FP17 (a potential pathogen) was isolated from a dying ivory shell with “acute death syndrome” and confirmed as a pathogen via infectious experiment. Furthermore, phylogenetic analysis based on the average nucleotide identity (ANI) sequencing of the 16S rRNA gene and housekeeping genes (ftsz, gapA, gyrB, mreB, pyrH, rpoA, and topA) indicated that FP17 was identical to Vibrio tubiashii. Transmission electron microscopy showed that FP17 is curved and has a short rod shape, with a single flagellum. Besides, the calculated LD50 after the intramuscular injection of FP17 was 2.11 × 106 CFU/g at 14 d. The genome of the FP17 strain consists of two chromosomes and one plasmid with 5,261,336 bp and 45.08% GC content, including 4824 open reading frames (ORFs) and 150 non-coding RNAs (ncRNA). Genome mining revealed that 120 candidate gene clusters, including vibrioferrin and flagellum-related proteins, are responsible for virulence. Comparative genomic analysis showed that vibrioferrin genes, such as pvs and type Ⅵ secretion system protein genes (vas), are specific in V. tubiashii FP17 but not in the ATCC19109 strain. Furthermore, 92 antimicrobial resistance (AMR) genes, such as tufA, tet(35), crp, etc., were mapped within the genome as the potential candidate for virulence, consistent with antibiotic susceptibility assay. This is the first study to describe the complete genome sequence of V. tubiashii infecting ivory shell. The genetic characteristics, virulence factors, and antimicrobial resistance of the V. tubiashii strain FP17 were also explored.

AimsObesity is a heterogeneous disease in terms of body mass index (BMI) and metabolic status. The purpose of this study was to investigate the risk of type 2 diabetes mellitus (T2DM) in subjects with metabolically abnormal but normal weight (MANW) in China.Materials and MethodsA prospective cohort with a total of 17,238 participants of the Zhejiang metabolic syndrome cohort was recruited. According to the standard of the Working Group on Obesity in China, general obesity is defined. Metabolic abnormality was defined as two or more abnormal components (elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), elevated systolic blood pressure (SBP) or diastolic blood pressure (DBP) or use of antihypertensive therapy, and elevated fasting plasma glucose or antidiabetic treatment). The hazard ratio (HR) and its 95% CI were calculated using a multiple regression model, adjusted for the potential confounding factors.ResultsCompared with metabolically normal and normal weight (MNNW) subjects, the metabolically abnormal and obesity/overweight (MAO) subjects had the highest risk of T2DM disease, with an HR of 4.67 (95% CI: 3.23–6.76), followed by MANW subjects (HR = 2.61, 95% CI: 1.74–3.92) and metabolically normal but obesity/overweight (MNO) subjects (HR = 2.09, 95% CI: 1.29–3.38) after adjusting for age, sex, smoking, drinking, physical activity, and family history of diabetes. Compared with that in the MNNW subjects, the HR in MANW subjects was significantly higher than that in MNO subjects. In normal-weight subjects, the HR of T2DM was significantly positively correlated with the number of components with metabolic abnormalities.ConclusionsMANW subjects had a higher risk of T2DM. MANW subjects should be given more attention in the prevention and control of common chronic diseases.

Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI.Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage.Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1β and IL-18 levels, and NLRP3 expression.Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.

Background: Metabolic syndrome (MetS) at baseline increases the risks of cardiovascular diseases (CVD) and all-cause mortality. However, MetS status is changeable during follow-up. The associations of dynamic changes of MetS with CVD and all-cause mortality remain unclear.Methods: Thirty-one thousand four hundred eighty-one eligible subjects were included from the Kailuan cohort. Dynamic changes of MetS were divided into four patterns as MetS-free, MetS-developed, MetS-recovery and MetS-stable. The outcomes were CVD, all-cause mortality, and the subtypes of CVD as myocardial infarction (MI), stroke and heart failure. Multiple Cox regression models were used to calculate the adjusted hazard ratios (HRs) and confidence intervals (95% CIs).Results: Altered risks of CVD, the subtypes of CVD, and all-cause mortality were observed among different dynamic patterns of MetS. Compared with the MetS-free group, MetS-developed group increased the risks of CVD (HR = 1.78, 95% CI = 1.51–2.11), MI (HR = 1.54, 95% CI = 1.01–2.34), stroke (HR = 1.78, 95% CI = 1.45–2.18), and heart failure (HR = 1.63, 95% CI = 1.11–2.39). MetS-recovery group decreased these risks with the HRs of 0.59 (95% CI = 0.48–0.72) for CVD, 0.62 (95% CI = 0.41–0.96) for MI, 0.59 (95% CI = 0.46–0.75) for stroke, and 0.56 (95% CI = 0.34–0.91) for heart failure compared with the MetS-stable group. However, the increased risk in the MetS-developed group and the decreased risk in the MetS-recovery group were not significant for all-cause mortality. When stratified by the onset age of MetS status change, early development of MetS (

Objective: The objective of this study was to compare the outcomes and complications of percutaneous image-guided versus laparoscopic peritoneal dialysis (PD) catheter placement techniques in the urgent-start setting. Materials and Methods: The medical records of 273 patients who had their first PD catheter between November 2012 and May 2017 were retrospectively reviewed. Patients were divided into radiologic group (n = 26) and laparoscopic group (n = 16). Descriptive and Kaplan–Meier (KM) analysis were used to compare time to first complication, time to catheter removal, and patient survival between the two groups. Complication-free and catheter removal rates at 1, 3, and 12 months were estimated from KM analysis. Results: A total of 42 patients were included in the study. The baseline demographics were similar between the two groups. In the radiologic group, the estimated 1, 3, and 12 months' complication-free rate were 100%, 94%, and 67%, respectively, which was not significantly different from 93%, 85%, and 45%, respectively, in the laparoscopic group (P = 0.543). The rate of catheter complications was not significantly different between the radiologic group (50%) and the laparoscopic group (31%) (P = 0.3382). The catheter removal rate in the radiologic group was 8, 18%, and 38% at 1, 3, and 12 months, respectively, versus 0%, 8%, and 20%, respectively, in the laparoscopic group (P = 0.298). The overall patient survival between two groups was not significantly different (P = 0.116) with estimated patient mortality of 15.4% at 12 months in the radiologic group and no deaths in the laparoscopic group. Conclusion: Image-guided percutaneously placed PD catheters have a similar complication and removal rates compared to laparoscopically placed catheters in the urgent-start setting.

An accurate and effective neurological evaluation is indispensable in the treatment and rehabilitation of traumatic brain injury. However, most of the existing evaluation methods in basic research and clinical practice are not objective or intuitive for assessing the neurological function of big animals, and are also difficult to use to qualify the extent of damage and recovery. In the present study, we established a big animal model of traumatic brain injury by impacting the cortical motor region of beagles. At 2 weeks after successful modeling, we detected neurological deficiencies in the animal model using a series of techniques, including three-dimensional motion capture, electromyogram and ground reaction force. These novel technologies may play an increasingly important role in the field of traumatic brain injury diagnosis and rehabilitation in the future. The experimental protocol was approved by the Animal Care and Use Committee of Logistics University of People’s Armed Police Force (approval No. 2017-0006.2).

Heterosis is most frequently manifested as the superior performance of a hybrid than either of the parents, especially under stress conditions. Nitric oxide (NO) is a well-known gaseous signaling molecule that acts as a functional component during plant growth, development, and defense responses. In this study, the Brassica napus L. hybrid (F1, NJ4375 × MB1942) showed significant heterosis under salt stress, during both germination and post-germination periods. These phenotypes in the hybrid were in parallel with the better performance in redox homeostasis, including alleviation of reactive oxygen species accumulation and lipid peroxidation, and ion homeostasis, evaluated as a lower Na/K ratio in the leaves than parental lines. Meanwhile, stimulation of endogenous NO was more pronounced in hybrid plants, compared with parental lines, which might be mediated by nitrate reductase. Proteomic and biochemical analyses further revealed that protein abundance related to several metabolic processes, including chlorophyll biosynthesis, proline metabolism, and tricarboxylic acid cycle metabolism pathway, was greatly suppressed by salt stress in the two parental lines than in the hybrid. The above responses in hybrid plants were intensified by a NO-releasing compound, but abolished by a NO scavenger, both of which were matched with the changes in chlorophyll and proline contents. It was deduced that the above metabolic processes might play important roles in heterosis upon salt stress. Taken together, we proposed that heterosis derived from F1 hybridization in salt stress tolerance might be mediated by NO-dependent activation of defense responses and metabolic processes.

ObjectiveThe frequency and implications of an elevated cardiac troponin (4th or 5th generation TnT) in patients outside of the emergency department or presenting with non-cardiac conditions is unclear.MethodsConsecutive patients aged 18 years or older admitted for a primary non-cardiac condition who had the 4th generation TnT drawn had the 5th generation TnT run on the residual blood sample. Primary and secondary outcomes were all-cause mortality (ACM) and major adverse cardiovascular events (MACE) respectively at 1 year.Results918 patients were included (mean age 59.8 years, 55% male) in the cohort. 69% had elevated 5th generation TnT while 46% had elevated 4th generation TnT. 5th generation TnT was more sensitive and less specific than 4th generation TnT in predicting both ACM and MACE. The sensitivities for the 5th generation TnT assay were 85% for ACM and 90% for MACE rates, compared to 65% and 70% respectively for the 4th generation assay. 5th generation TnT positive patients that were missed by 4th generation TnT had a higher risk of ACM (27.5%) than patients with both assays negative (27.5% vs 11.1%, pConclusionsIn patients admitted for a non-cardiac condition, 5th generation TnT is more sensitive although less specific in predicting MACE and ACM. 5th generation TnT identifies an intermediate risk group for ACM previously missed with the 4th generation assay.

In recent years, the flow characteristics research of the interstage region in counter-rotating axial fans in terms of fluid dynamics has attracted much attention. Especially, the dynamic relationship between interstage pressure pulsation and blade vibration in counter-rotating axial fans has not yet been clarified. This paper performs the signal processing method of wavelet decomposition and reconstruction in time-frequency analysis process. Under different flow conditions, weak-coupling numerical simulation program is employed to analyze the fluid-structure coupling interaction between interstage pressure pulsations and blade vibrations in counter-rotating axial fans. The results indicate that the fluid-structure coupling interaction field in the interstage of counter-rotating axial fans mainly excites the first-order vibration of the second-stage blade. At the same time, the consistency between the pulsation frequency and the vibration frequency of the airflow reflects the good coupling property. Two stage blades cut the airflow to cause field changes and airflow pulsation, and then, airflow pulsation causes blades deformation and produces vibrations of the same frequency at the blade. The deformation of the blades, in turn, causes the flow field changes. Rotating stall, vortex movement and breakdown produced low-frequency airflow pulsation and vortex vibration of the blade.

The incidence of ulcerative colitis (UC) is increasing worldwide. Currently, no curative treatment is available. Finding a food-based method for prevention of UC would be significant. In this study, the hydrolysate of crucian carp swim bladder (HCSB) was prepared using a simulated gastrointestinal digestion. 178 peptides in HCSB were identified by nano liquid chromatography coupled with hybrid linear ion trap Orbitrap mass spectrometry. In a model of hydrogen peroxide-induced oxidative stress in an intestinal epithelial cell line (IEC-6), HCSB protects IEC-6 cells by increasing antioxidant enzyme activity and reducing the intracellular ROS content. HCSB also represses lipopolysaccharide-induced inflammation of IEC-6 cells. In vivo studies showed that prophylactic administration of HCSB reduces the severity of dextran sodium sulfate-induced UC in mice by reducing myeloperoxidase activity, production of proinflammatory cytokines, and by inhibiting activation of the NF-κB pathway. These results indicate that HCSB has the potential to prevent ulcerative colitis.

This study applied peptidomics to investigate potential biomarkers for evaluating pork-meat freshness. The spoilage time points of pork meat stored at −2, 4, 10, and 25 °C were defined by evaluating meat freshness indicators (color, total viable count, pH, and total volatile basic nitrogen). Peptide MVHMASKE was identified as a potential peptide marker via multivariate analysis. Pearson correlation revealed a negative correlation between intensity of MVHMASKE and total viable count/total volatile basic nitrogen. In addition, the correlation between peptide content and the change in pork-meat freshness was verified using real-life samples, and the content of MVHMASKE showed a significant decline during storage under 4 and 25 °C, correspondingly reflecting the change of pork meat from fresh to spoiled. This study provides favorable evidence to evaluate pork-meat freshness by monitoring the change of peptide MVHMASKE in content based on mass spectrometry-based peptidomics.

In this work, we investigated changes in protein structures in vacuum-packed pork during chill storage and its impact on the in vitro protein digestion. Longissimus dorsi muscles were vacuum packed and stored at 4°C for 3 days. Samples were subjected to Raman spectroscopy, in vitro digestion and nano LC-MS/MS. The 3 d samples had lower α-helix content, but higher β-sheet, β-turn, and random coil contents than the 0 d samples (P < 0.05). SDS-PAGE revealed significant protein degradation in the 3 d samples and the differences in digested products across the storage time. Proteome analysis indicated that the 3 d samples had the higher susceptibility to digestion. Increasing protein digestibility was mainly attributed to the degradation of myofibrillar proteins. Thus, exposure of more enzymatic sites in loose protein structure during chill storage could increase protein degradation in meat.

Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that nigericin could inhibit the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the nigericin anti-cancer process.Conclusions: These findings provided new insight into the molecular mechanism of nigericin toward cancer cells, and suggested a possible clinical application in PC.

Abstract Hepatocellular carcinoma (HCC) is the malignancy derived from normal hepatocytes with increasing incidence and extremely poor prognosis worldwide. The only approved first‐line systematic treatment agent for HCC, sorafenib, is capable to effectively improve advanced HCC patients’ survival. However, it is gradually recognized that the therapeutic response to sorafenib could be drastically diminished after short‐term treatment, defined as primary resistance. The present study is aimed to explore the role of stress‐inducible protein Sestrin2 (SESN2), one of the most important sestrins family members, in sorafenib primary resistance. Herein, we initially found that SESN2 expression was significantly up‐regulated in both HCC cell lines and tissues compared to normal human hepatocytes and corresponding adjacent liver tissues, respectively. In addition, SESN2 expression was highly correlated with sorafenib IC50 of HCC cell lines. Thereafter, we showed that sorafenib treatment resulted in an increase of SESN2 expression and the knockdown of SESN2 exacerbated sorafenib‐induced proliferation inhibition and cell apoptosis. Further mechanistic study uncovered that SESN2 deficiency impaired both AKT and AMPK phosphorylation and activation after sorafenib treatment. Moreover, the correlations between SESN2 expression and both phosphor‐AKT and phosphor‐AMPK expression were illustrated in HCC tissues. Taken together, our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC.

The current study aimed to identify the differences in technical performance between players from clubs of Bundesliga (Germany), La Liga (Spain), Ligue 1 (France), Premier League (England) and Serie A (Italy) when competing in the matches of the UEFA Champions League. Technical performance-related match data of 1,291 players from 1,125 matches (9,799 observations) of the UEFA Champions League (seasons 2009/2010–2017/2018) were collected and analysed. The generalised mixed linear modelling was employed taking the names of the league as the independent variable to predict the count number of 20 technical performance-related match actions and events performed by players belonging to different leagues. The non-clinical magnitude-based inference was used to evaluate the uncertainty in the true effects of the predictor. Results showed that differences in the technical performances between players from La Liga, Premier League and Ligue 1 were all trivial. Bundesliga players made higher numbers of shots than players from La Liga, Premier League and Serie A and achieved more long balls than players from Ligue 1. Serie A players achieved lower numbers of ball touches, passes and lower pass accuracy per match than players from any of the other four leagues. In addition, players from Serie A performed a higher number of long balls per match than Ligue 1 players and lower number of dribbles per match than Premier League players. Non-significant differences in other variables related to passing and organising and all variables related to defending were identified in players between the five leagues. The identified differences in technical performance among leagues could provide a more thorough understanding for practitioners working within the fields of talent identification, player development, player recruitment, coaching and match preparation.

Abstract Background The complex yet interrelated connections between cancer metabolism and oncogenic driver genes are relatively unexplored but have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. The goal of this study was to identify global metabolic profiles of breast tumors isolated from multiple transgenic mouse models and to identify unique metabolic signatures driven by these oncogenes. Methods Using mass spectrometry (GC-MS, LC-MS/MS, and capillary zone electrophoresis (CZE)-MS platforms), we quantified and compared the levels of 374 metabolites in breast tissue from normal and transgenic mouse breast cancer models overexpressing a panel of oncogenes (PyMT, PyMT-DB, Wnt1, Neu, and C3-TAg). We also compared the mouse metabolomics data to published human metabolomics data already linked to clinical data. Results Through analysis of our metabolomics data, we identified metabolic differences between normal and tumor breast tissues as well as metabolic differences unique to each initiating oncogene. We also quantified the metabolic profiles of the mammary fat pad versus mammary epithelium by CZE-MS/MS. However, the differences between the tissues did not account for the majority of the metabolic differences between the normal mammary gland and breast tumor tissues. Therefore, the differences between the cohorts were unlikely due to cellular heterogeneity. Of the mouse models used in this study, C3-TAg was the only cohort with a tumor metabolic signature composed of ten metabolites that had significant prognostic value in breast cancer patients. Gene expression analysis identified candidate genes that may contribute to the metabolic reprogramming. Conclusions This study identifies oncogene-induced metabolic reprogramming within mouse breast tumors and compares the results to that of human breast tumors, providing a unique look at the relationship between and clinical value of oncogene initiation and metabolism during breast cancer.

Abstract Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.

Alopecurus japonicus is a weed in summer crop field, which is harmful to wheat crops. The complete plastome of A. japonicus was reported in this study. The genome was 136,408 bp in length, consisting of an 80,512 bp large single-copy region, a 12,836 bp small single-copy region, and two 21,530 bp inverted repeat regions. The GC content of this plastome was 38.3%. A total of 112 genes were annotated for the plastome of A. japonicus, containing 78 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. Phylogenetic analysis showed that A. japonicus was sister to Alopecurus aequalis.

The rail pressure control in diesel high-pressure common rail (HPCR) system is considered as one of the key issues for precise control of fuel injection. This study investigates the application of generalised proportional integral observer (GPIO)-based control in diesel HPCR system. Firstly, a non-linear mathematical model of HPCR system which uses the metering unit as the actuator is established based on hydromechanics under some proper simplifications. Secondly, a GPIO is developed to estimate the mismatched disturbance caused by the injection process. Then a composite controller combining GPIO and backstepping control method is designed. By introducing the disturbance estimations into the control design process, the disturbance rejection capability of the system is promisingly enhanced. The effectiveness of the proposed control method is validated by the simulation results.

Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.

Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine based on a combination of Yu-Ping-Feng-San and Erchen decoctions. GBFXD has been widely used for decades in treating asthma at the Affiliated Hospital of Nanjing University of Chinese Medicine. Previously, GBFXD was found to reduce lung inflammation and airway remodeling; however, the underlying mechanism remains unknown. In this study, the effects of GBFXD on asthmatic mice were evaluated based on pathology and lung function; airway hyperresponsiveness (AHR) and pathology were compared among the two different mouse models utilized. Furthermore, the mechanism of action of GBFXD on asthmatic mice was analyzed using iTRAQ labeling technology combined with ingenuity pathway analysis (IPA). Modeling analysis of pre- and post-treatment proteins identified 75 differentially expressed proteins. These proteins were related to B-cell development, calcium-induced lymphocyte apoptosis, antigen presentation, and Th1 and Th2 activation pathways. Moreover, 68 differentially expressed proteins were identified in the GBFXD treatment group compared with the model group. Upstream regulatory factors predicted that interleukin (IL)-4 (necessary for inducing polarization of type 2 [M2] macrophages), cyclooxygenase, and prostaglandin E2 are significantly elevated in the model group. Based on IPA analysis, it was concluded that several pathways, including mitochondrial dysfunction and oxidative phosphorylation, are closely associated with the therapeutic effects of GBFXD in asthma. Moreover, the differential expression of several proteins, including the M2 markers, MRC1, ARG1, Retnla, Chil3, and CHIA, were validated by western blotting, confirming that GBFXD can reduce airway inflammation, which fits the pattern of an alternative M2 activation state, and attenuate AHR. Overall, our findings indicate that GBFXD significantly suppresses M2 macrophage polarization, providing further insights into the mechanism underlying the protective effects of GBFXD.

Background Blacks have higher blood pressure levels compared with whites beginning in childhood. Few data are available on racial differences in the incidence of hypertension from young adulthood through middle age. Methods and Results We calculated the cumulative incidence of hypertension from age 18 to 55 years among participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Incident hypertension was defined by the first visit with mean systolic blood pressure ≥130 mm Hg, mean diastolic blood pressure ≥80 mm Hg, or self‐reported use of antihypertensive medication. Among 3890 participants without hypertension at baseline (aged 18–30 years), cumulative incidence of hypertension by age 55 years was 75.5%, 75.7%, 54.5%, and 40.0% in black men, black women, white men, and white women, respectively. Among participants with systolic blood pressure/diastolic blood pressure

High-salt diet has been considered to cause health problems, but it is still less known how high-salt diet affects gut microbiota, protein digestion, and passage in the digestive tract. In this study, C57BL/6J mice were fed low- or high-salt diets (0.25 vs. 3.15% NaCl) for 8 weeks, and then gut contents and feces were collected. Fecal microbiota was identified by sequencing the V4 region of 16S ribosomal RNA gene. Proteins and digested products of duodenal, jejunal, cecal, and colonic contents were identified by LC-MS-MS. The results indicated that the high-salt diet increased Firmicutes/Bacteroidetes ratio, the abundances of genera Lachnospiraceae and Ruminococcus (P < 0.05), but decreased the abundance of Lactobacillus (P < 0.05). LC-MS-MS revealed a dynamic change of proteins from the diet, host, and gut microbiota alongside the digestive tract. For dietary proteins, high-salt diet seemed not influence its protein digestion and absorption. For host proteins, 20 proteins of lower abundance were identified in the high-salt diet group in duodenal contents, which were involved in digestive enzymes and pancreatic secretion. However, no significant differentially expressed proteins were detected in jejunal, cecal, and colonic contents. For bacterial proteins, proteins secreted by gut microbiota were involved in energy metabolism, sodium transport, and protein folding. Five proteins (cytidylate kinase, trigger factor, 6-phosphogluconate dehydrogenase, transporter, and undecaprenyl-diphosphatase) had a higher abundance in the high-salt diet group than those in the low-salt group, while two proteins (acetylglutamate kinase and PBSX phage manganese-containing catalase) were over-expressed in the low-salt diet group than in the high-salt group. Consequently, high-salt diet may alter the composition of gut microbiota and has a certain impact on protein digestion.