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The depth-dependent dynamics of dissolved organic matter (DOM) structure and humification in an artificial lake limits the understanding of lake eutrophication and carbon cycling. Using fluorescence regional integration (FRI) and parallel factor analysis (PARAFAC) models to analyze the 3D fluorescence spectroscopy dataset, we revealed the depth-dependent structure and vertical distribution of DOM in the estuarine and center regions of Lake Hongfeng. The percentage fluorescence response (Pi,n) showed humic acid is an important part of DOM in Lake Hongfeng. Fluorescence results show that the fulvic-like and protein-like materials in HF1-DOM located at the estuarine position showed greater variation in the middle stage, probably due to human influence and sediment suspension. Fluorescence index (PI+II+IV,n/PIII+V,n and FIC4/FIC3) can be used to indicate the degree of humification of DOM in artificial lakes. Results of each index show that the estuary is more affected by human activities, and the humification degree is significantly lower than that of the center of the lake. The evaluation index system of the humification degree of artificial lake established in this study can effectively predict the eutrophication state of the typical area of artificial lake and deeply understand the possible important influence of human activities on the carbon cycle of lake. HIGHLIGHTS Complex factors in the estuary of the lake lead to significant changes in DOM structure.; Depth-dependent change sensitivity was for humic > fulvic> protein-like components.; Higher DOM humification in the middle of the lake is attributed to microbial action.; Spectral indices were confirmed to evaluate the DOM humification degree.;

Abstract High areal capacity and low-temperature ability are critical for lithium-ion batteries (LIBs). However, the practical operation is seriously impeded by the sluggish rates of mass and charge transfer. Herein, the active electronic states of TiNb2O7 material is modulated by dopant and O-vacancies for enhanced low-temperature dynamics. Femtosecond laser-based transient absorption spectroscopy is employed to depict carrier dynamics of TiNb2O7, which verifies the localized structure polarization accounting for reduced transport overpotential, facilitated electron/ion transport, and improved Li+ adsorption. At high-mass loading of 10 mg cm−2 and −30 °C, TNO-x @N microflowers exhibit stable cycling performance with 92.9% capacity retention over 250 cycles at 1 C (1.0-3.0 V, 1 C = 250 mA g−1). Even at −40 °C, a competitive areal capacity of 1.32 mAh cm−2 can be achieved. Such a fundamental understanding of the intrinsic structure-function put forward a rational viewpoint for designing high-areal-capacity batteries in cold regions.

Abstract Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.

Abstract Imperceptible examination and unideal treatment effect are still intractable difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). At present, despite 5-fluorouracil (5-FU), as a clinical first-line FOLFIRINOX chemo-drug, has achieved significant therapeutic effects. Nevertheless, these unavoidable factors such as low solubility, lack of biological specificity and easy to induce immunosuppressive surroundings formation, severely limit their treatment in PDAC. As an important source of energy for many tumor cells, tryptophan (Trp), is easily degraded to kynurenine (Kyn) by indolamine 2,3- dioxygenase 1 (IDO1), which activates the axis of Kyn-AHR to form special suppressive immune microenvironment that promotes tumor growth and metastasis. However, our research findings that 5-FU can induce effectively immunogenic cell death (ICD) to further treat tumor by activating immune systems, while the secretion of interferon-γ (IFN-γ) re-induce the Kyn-AHR axis activation, leading to poor treatment efficiency. Therefore, a metal matrix protease-2 (MMP-2) and endogenous GSH dual-responsive liposomal-based nanovesicle, co-loading with 5-FU (anti-cancer drug) and NLG919 (IDO1 inhibitor), was constructed (named as ENP919@5-FU). The multifunctional ENP919@5-FU can effectively reshape the tumor immunosuppression microenvironment to enhance the effect of chemoimmunotherapy, thereby effectively inhibiting cancer growth. Mechanistically, PDAC with high expression of MMP-2 will propel the as-prepared nanovesicle to dwell in tumor region via shedding PEG on the nanovesicle surface, effectively enhancing tumor uptake. Subsequently, the S-S bond containing nanovesicle was cut via high endogenous GSH, leading to the continued release of 5-FU and NLG919, thereby enabling circulating chemoimmunotherapy to effectively cause tumor ablation. Moreover, the combination of ENP919@5-FU and PD-L1 antibody (αPD-L1) showed a synergistic anti-tumor effect on the PDAC model with abdominal cavity metastasis. Collectively, ENP919@5-FU nanovesicle, as a PDAC treatment strategy, showed excellent antitumor efficacy by remodeling tumor microenvironment to circulate tumor chemoimmunotherapy amplification, which has promising potential in a precision medicine approach.

Allosteric cooperativity between ATP and substrates is a prominent characteristic of the cAMP-dependent catalytic subunit of protein kinase A (PKA-C). This long-range synergistic action is involved in substrate recognition and fidelity, and it may also regulate PKA’s association with regulatory subunits and other binding partners. To date, a complete understanding of this intramolecular mechanism is still lacking. Here, we integrated NMR(Nuclear Magnetic Resonance)-restrained molecular dynamics simulations and a Markov State Model to characterize the free energy landscape and conformational transitions of PKA-C. We found that the apoenzyme populates a broad free energy basin featuring a conformational ensemble of the active state of PKA-C (ground state) and other basins with lower populations (excited states). The first excited state corresponds to a previously characterized inactive state of PKA-C with the αC helix swinging outward. The second excited state displays a disrupted hydrophobic packing around the regulatory (R) spine, with a flipped configuration of the F100 and F102 residues at the αC-β4 loop. We validated the second excited state by analyzing the F100A mutant of PKA-C, assessing its structural response to ATP and substrate binding. While PKA-CF100A preserves its catalytic efficiency with Kemptide, this mutation rearranges the αC-β4 loop conformation, interrupting the coupling of the two lobes and abolishing the allosteric binding cooperativity. The highly conserved αC-β4 loop emerges as a pivotal element to control the synergistic binding of nucleotide and substrate, explaining how mutations or insertions near or within this motif affect the function and drug sensitivity in homologous kinases.

Abstract In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.

The hot corrosion behaviors of Co–Al–W superalloys with Re additions were investigated at 900 °C. The results showed that the addition of Re improved the hot corrosion resistance significantly. The alloys developed multi-layer oxidation and corrosion products, which located from surface to substrate were: the CoO and Co3O4 layer, the CoWO4 and CoAl2O4 layer, the Al2O3 layer, and the Co3W layer. The addition of Re promotes the formation of the α-Al2O3 scale, which is stable and dense. The thickness the α-Al2O3 scale in 1Re alloy is 1.9 μm, which is much thicker than that of the base alloy. The well-developed α-Al2O3 scale leads to the improvements in hot corrosion resistance.

Mining activities may cause severe ground subsidence, endangering surface structures, and farmlands. Therefore, the acquisition of spatial-temporal evolution of the mining goaf is of great significance. Hotspot analysis (HSA) based on the Getis-Ord G$_{i}^*$ statistics has been utilized to identify the areas with a rapid deformation rate. In this article, we propose an improved HSA (IHSA) method for automatic extraction of the surface subsidence caused by the mining goaf. In addition, we design a comprehensive workflow for the automatic spatial-temporal evolution inversion of surface deformation induced by the mining goaf. First, time series interferometric synthetic aperture radar (InSAR) is utilized to generate the surface deformation of the mining area. Then, the IHSA method is used for the automatic identification of the mining goaf. Finally, the total least-squares probability integral method (TLS-PIM) is applied for goaf inversion based on the extracted deformation information. For this study, the Wuxiang is selected as the study area. We have compared the IHSA method with four methods using five indicators, and likewise, we have compared the TLS-PIM method with four methods in terms of their correlation with the InSAR results in the strike and dip directions. The experimental results demonstrate the superiority of our method as a support for the geological hazard investigation and mine safety supervision department.

Abstract Purpose Patellofemoral arthroplasty (PFA) was shown to be a potentially effective surgical technique for isolated patellofemoral osteoarthritis but varying reports on PFA-related implant failure and complications have rendered the procedure controversial. This study aimed to identify impactful publications, research interests/efforts, and collaborative networks in the field of PFA research. Methods The study used the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed to retrieve relevant publications on PFA research published between 1950–2022. Statistical tests in R software were used for analysis while VOSviewer, Bibliometrix, and CiteSpace were employed for data visualization. Results Two hundred forty-one articles were analyzed with the number of published papers increasing over time. Knee was the most frequent journal and Clinical Orthopaedics and Related Research was the most cited journal. Clinical outcomes, such as prosthesis survival, revision, and complications, were researched most frequently as demonstrated by keyword analysis. The United States was the top contributor to cooperative networks, followed by the United Kingdom while Technical University Munich formed close ties among authors. Conclusion Publications on PFA research have witnessed a notable surge. They primarily came from a limited number of centers and were characterized by low-level evidence. The majority of studies primarily focused on the clinical outcomes of PFA, while revision of PFA and patient satisfaction have emerged as new research areas.

Abstract Cultured meat production has emerged as a breakthrough technology for the global food industry with the potential to reduce challenges associated with environmental sustainability, global public health, animal welfare, and competition for food between humans and animals. The muscle stem cell lines currently used for cultured meat cannot be passaged in vitro for extended periods of time. Here, we develop a directional differentiation system of porcine pre-gastrulation epiblast stem cells (pgEpiSCs) with stable cellular features and achieve serum-free myogenic differentiation of the pgEpiSCs. We show that the pgEpiSCs-derived skeletal muscle progenitor cells and skeletal muscle fibers have typical muscle cell characteristics and display skeletal muscle transcriptional features during myogenic differentiation. Importantly, we establish a three-dimensional differentiation system for shaping cultured tissue by screening plant-based edible scaffolds of non-animal origin, followed by the generation of pgEpiSCs-derived cultured meat. These advances provide a technical approach for the development of cultured meat.

ObjectiveThe aim of this study is to examine the predictive factors for cancer-specific survival (CSS) in patients diagnosed with Small-Cell Carcinoma of the Prostate (SCCP) and to construct a prognostic model.MethodsCases were selected using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was utilized to calculate survival rates, while Lasso and Cox regression were employed to analyze prognostic factors. An independent prognostic factor-based nomogram was created to forecast CSS at 12 and 24 months. The model’s predictive efficacy was assessed using the consistency index (C-index), calibration curve, and decision curve analysis (DCA) in separate tests.ResultsFollowing the analysis of Cox and Lasso regression, age, race, Summary stage, and chemotherapy were determined to be significant risk factors (P < 0.05). In the group of participants who received training, the rate of 12-month CSS was 44.6%, the rate of 24-month CSS was 25.5%, and the median time for CSS was 10.5 months. The C-index for the training cohort was 0.7688 ± 0.024. As for the validation cohort, it was 0.661 ± 0.041. According to the nomogram, CSS was accurately predicted and demonstrated consistent and satisfactory predictive performance at both 12 months (87.3% compared to 71.2%) and 24 months (80.4% compared to 71.7%). As shown in the external validation calibration plot, the AUC for 12- and 24-month is 64.6% vs. 56.9% and 87.0% vs. 70.7%, respectively. Based on the calibration plot of the CSS nomogram at both the 12-month and 24-month marks, it can be observed that both the actual values and the nomogram predictions indicate a predominantly stable CSS. When compared to the AJCC staging system, DCA demonstrated a higher level of accuracy in predicting CSS through the use of a nomogram.ConclusionClinical prognostic factors can be utilized with nomograms to forecast CSS in Small-Cell Carcinoma of the Prostate (SCCP).

Soft tissue injuries (STIs) are the most common cause of extremity pain and motion dysfunction. Persistent inflammatory activation of immune cells characterized by senescence‐associated secretory phenotype (SASP) and mitochondrial stress are considered the primary causes of STIs, a pathological process also termed inflammaging. Meanwhile, scavenging excessive “cellular waste” in the inflammaging microenvironment and further activating tissue repair processes remain elusive. Herein, an anti‐inflammaging photothermal hydrogel microneedle patch for treating STIs is developed. Taurine‐loaded Prussian blue nanoparticles (Taurine@PB) are encapsulated in a methacrylate‐based hyaluronic acid hydrogel (HAMA) and further fabricated into taurine@PB@HAMA@microneedles (TPH@MN) patches. The acidic microenvironment of chronic inflammation and mild photothermal effects promote taurine release and anti‐inflammaging immunomodulation, inhibiting mitochondrial stress via the SIRT3‐NF‐κB axis to promote glycolytic metabolic microenvironment of neutrophils reprogramming toward oxidative phosphorylation metabolism. Furthermore, TPH@MN activates macrophage efferocytosis and initiates the process of tissue repair. In mouse models of chronic diabetic wounds and tibialis anterior (TA) muscle injury, TPH@MN inhibits SASP expression and promotes STIs healing through thermosensitized anti‐inflammaging immunomodulation. In summary, TPH@MN circumvents the side effects of systemic administration, providing new translatable options in the treatment modalities for patients suffering from STIs worldwide.

ABSTRACT: Mycoplasma gallisepticum (MG) is a highly contagious avian respiratory pathogen characterized by rapid spread, widespread distribution, and long-term persistence of infection. Previous studies have shown that chicken macrophage HD11 cells play a critical role in the replication and immunomodulation of MG. Macrophages are multifunctional immunomodulatory cells that polarize into different functions and morphologies in response to exogenous stimuli. However, the effect of MG infection on HD11 polarization is not well understood. In this study, we observed a time-dependent increase in both the expression of the MG-related virulence protein pMGA1.2 and the copy number of MG upon MG infection. Polarization studies revealed an upregulation of M1-type marker genes in MG-infected HD11 cells, suggesting that MG mainly induces HD11 macrophages towards M1-type polarization. Furthermore, MG activated the inflammatory vesicle NLRP3 signaling pathway, and NLRP3 inhibitors affected the expression of M1 and M2 marker genes, indicating the crucial regulatory role of the NLRP3 signaling pathway in MG-induced polarization of HD11 macrophages. Our findings reveal a novel mechanism of MG infection, namely the polarization of MG-infected HD11 macrophages. This discovery suggests that altering the macrophage phenotype to inhibit MG infection may be an effective control strategy. These findings provide new perspectives on the pathogenic mechanism and control measures of MG.

Background and objectiveSurgery is the primary therapy that crucially affects the survival of patients with kidney cancer (KC). However, pertinent surgical decision criteria for individuals with stage T2-3 KC are lacking. This study aimed to display the practical choices and evolving trends of surgical procedures and elucidate their implied value.MethodsThrough the Surveillance, Epidemiology, and End Results (SEER) dataset, the levels and evolving trends of different surgical methods were examined to determine cancer-specific risk of death (CSRD). Additionally, stratification analysis and survival rate analysis were performed to explore the effectiveness of partial nephrectomy (PN).ResultsIn this study, 9.27% of patients opted for PN. Interestingly, an upward trend was observed in its decision, with an average annual percentage change (AAPC) of 7.0 (95% CI: 4.8–9.3, P

IntroductionHypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE.MethodsThis case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used to examine the association between initial glycans and HIE, by which the significant parameters were used to develop a diagnostic model. Though receiver operating characteristic (ROC) curves, area under the curve (AUC) and 95% confidence interval (CI) were calculated to assess the performance of the diagnostic model.ResultsThere were significant differences in 11 initial glycans between the patient and control groups. The levels of fucosylated and galactosylated glycans were significantly lower in HIE patients than in control individuals, while sialylated glycans were higher in HIE patients (p < 0.05). A prediction model was developed using three initial IgG N-glycans and fetal distress, low birth weight, and globulin. The ROC analysis showed that this model was able to discriminate between HIE patients and healthy individuals [AUC = 0.798, 95% CI: (0.716–0.880)].DiscussionIgG N-glycosylation may play a role in the pathogenesis of HIE. Plasma IgG N-glycans are potential noninvasive biomarkers for screening individuals at high risk of HIE.

The loss of rural kindergarten teachers has become a common social concern in China, which is of great importance to the development of preschool education. This study conducted a survey of 2944 kindergarten teachers in mainland China, to explore the relationship between work–family conflict and turnover intention, the mediating effect of emotional exhaustion, and the moderating effect of professional identity. The study used the work–family conflict questionnaire, the emotional exhaustion scale, the turnover intention questionnaire, and the professional identity questionnaire. The results showed that (1) work–family conflict significantly predicted turnover intention; (2) emotional exhaustion played a mediating role between work–family conflict and turnover intention; and (3) professional identity moderated the latter half path of the mediation model, that is, strong professional identity alleviated the indirect predicting effect of work–family conflict on turnover intention through emotional exhaustion. The results clarified the influencing mechanism of work–family conflict on turnover intention, which could help improve rural preschool teachers’ positive emotions and reducing turnover.

Under the influence of mountainous terrain, the spatial synergy between tourism resources and tourism service facilities has emerged as a pivotal factor affecting the overall efficiency enhancement of regional tourism destinations. In order to explore the synergistic effect of the two, taking Qimen County as the study site, this study utilizes Point of Interest (POI) data of tourism resources and tourism service facilities. It constructs a fine-scale multidimensional spatial synergy methodology based on grid vectorization to conduct scenario-based comparative analyses of altitude and population density. The objective is to elucidate the effects of fine-scale tourism development synergy and propose enhancement strategies. The findings are as follows: (1) The vertical zonation of mountains has led to a widespread, decentralized distribution of natural tourism resources in mid-to-high-altitude areas, while humanistic tourism resources in low-altitude urbanized areas exhibit a granular, clustered distribution. These contrasting scenarios manifest a polarization, making it difficult to achieve supply–demand matching of the layout pattern of tourism service facilities along transportation routes. (2) The spatial gradient effect of the synergy between the two in mountainous counties is significant, with a higher synergy level in core towns and obvious misalignment in peripheral areas. (3) Altitude and population density are critical factors influencing the supply of tourism service facilities. Through scale aggregation guidance and cost–benefit mechanisms, the spatial distribution can be classified, stratified, and optimized to better serve resource development. This study provides valuable insights into understanding laws governing development and utilization within mountainous county areas for academic research purposes.

This experiment was carried out to investigate the effect of pterostilbene (PTE) supplementation in feed on Arbor Acres broilers in terms of serum biochemical parameters, immune and inflammatory responses, antioxidant status, and intestinal morphological structure. For a duration of 42 days, a total of 480 1-day-old Arbor Acres broilers were randomly divided into four groups. Each group was assigned to receive either the basal diet or the basal diet supplemented with 200, 400, or 600 mg/kg of PTE. Each treatment consisted of eight replicates, with 15 chicks per replicate. In comparison with the control group, three PTE treatments significantly increased the lymphocyte transformation rate in the spleen of broilers. The automated biochemical analysis, enzyme-linked immunosorbent assay, and RT-qPCR analysis kits found that 400 mg/kg of PTE significantly increased the serum levels of complement C3, IL-4, and iNOS; reduced the serum levels of IL-6, TNF-α, and mRNA levels of the genes IL-6, IL-8, TNF-α, NLRP3, and IFN-γ; significantly improved the activities of antioxidant enzymes including CAT, GSH-Px, and T-SOD in the jejunum; and significantly reduced the MDA contents in the serum and jejunum of broilers. Nikon microscope observations and ImagePro Plus 6.0 measure results found that 400 mg/kg of PTE supplementation significantly reduced the relative length and weight of the jejunum and improved the jejunal villi structure, resulting in increased intestinal villi, deepened crypt, and an enhanced ratio of villi height to crypt depth (VH/CD). RT-qPCR and Western blot found that dietary PTE also resulted in increased mRNA levels of the genes Claudin-2, Occludin, ZO-1, and Sirt1, and decreased NF-κB protein levels in the jejunum. The results of this study demonstrated that dietary PTE improved the immune function and intestinal health of broilers by reducing inflammation and increasing the antioxidant capacity of the animals.

Direct contact condensation (DCC) is a phenomenon observed when steam interacts with subcooled water, exhibiting higher heat and mass transfer rates compared to wall condensation. It has garnered significant interest across industries such as nuclear, chemical, and power due to its advantageous characteristics. In the context of pressure-relief tanks, understanding and optimizing the DCC process are critical for safety and efficiency. The efficiency of pressure-relief tanks depends on the amount of steam condensed per unit of time, which directly affects their operational parameters and design. This study focuses on investigating the direct gas–liquid contact condensation process in pressure-relief tanks using computational fluid dynamics (CFD). Through experimental validation and a sensitivity analysis, the study provides insights into the influence of inlet steam parameters and basin temperature on the steam plume characteristics. Furthermore, steady-state and transient calculation models are developed to simulate the behaviour of the pressure-relief tank, providing valuable data for safety analysis and design optimization. There is a relatively high-pressure area in the upper part of the bubble hole of the pressure-relief tube, and the value increases as it is closer to the holes. The steam velocity in the bubbling hole near the 90° elbow position is higher. This study contributes to the understanding of steam condensation dynamics in pressure-relief tanks. When the steam emission and pressure are fixed, the equilibrium temperature increases linearly as the initial temperature increases (where a = 1, b = 20 in y = a x+ b correlation), the equilibrium pressure increases nearly exponentially, and the equilibrium gas volume decreases. When the steam emission and initial temperature are fixed, the equilibrium temperature does not change as the steam discharge pressure increases. The correlations between the predicted equilibrium parameters and the inlet steam parameters and tank temperature provide valuable insights for optimizing a pressure-relief tank design and improving the operational safety in diverse industrial contexts.

How soil sulfur (S) transformation processes and S availability respond to nitrogen (N) addition and precipitation increment are still not clearly understood in grassland ecosystems. Thus, we examined the inorganic S fractions, organic S and available S in the soil. We also measured the S concentrations in the above-ground tissues of six plant species under N and water addition in a semi-arid steppe. Nitrogen addition promoted soil acidification and the transformation of inorganic S fractions as demonstrated by the dissolution of insoluble S into soluble S and adsorbed S, therefore increasing soil S availability. This resulted in significant increases in plant S concentrations, except Leymus chinensis, under N addition. Water addition accelerated the transformation of soil S fractions through increasing the abundances of S cycling genes and enzyme-encoding sulfate reduction genes. Specifically, water addition increased the ratio of soluble S to adsorbed S. Additionally, higher soil organic S and soil total S concentrations under water addition treatment could also be due to increased S return from above-ground plant biomass, sulfate input from irrigation water, and S transported from deep soil layers by plant roots. However, water addition decreased the tissue S concentrations of Stipa krylovii and Leymus chinensis, possibly due to the dilution effect caused by enhanced biomass production. Nitrogen and water addition synergistically accelerated soil S cycling and transformations, which could mitigate ecosystem S deficiency and enlarge soil S pools in semi-arid grasslands.

Aluminum (Al) exposure significantly interferes with the energy supply in astrocytes, which may be a potential mechanism of Al-induced neurotoxicity. This study was designed to explore the mechanisms of Al-induced energy supply impairment in rat C6 astroglioma cell line. Aluminum-maltolate (Al(mal)3) (0.1 mM, 24 h) exposure significantly decreased brain-type creatine kinase (BCK) co-localization with the endoplasmic reticulum (ER) and resulted in mitochondrial dysfunctions, accompanied by a decrease in AMPK phosphorylation. The results of molecular docking showed that Al(mal)3 increased BCK’s hydrophobicity and hindered the localization movement of BCK between subcells·H2O2 co-administration was found to exacerbate mitochondrial dysfunction, Ca2+ dyshomeostasis, and apoptosis. After treated with Al(mal)3, additional oxidative stress contributed to BCK activity inhibition but did not promote a further decrease in AMPK phosphorylation. The activation of p-AMPK by its agonist can partially restore mitochondrial function, BCK activity, and ER-localized-BCK levels in Al(mal)3-treated astrocytes. In summary, Al exposure resulted in a sustained depletion of the mitochondrial and antioxidant systems, which was associated with reduced p-AMPK activity and decreased ER-localized-BCK levels in astrocytes. This study provides a theoretical basis for exploring the mechanisms of neurotoxicity induced by Al exposure.

ABSTRACT Spike-receptor interaction is a critical determinant for the host range of coronaviruses. Here, we investigated all the five World Health Organization-designated variants of concern (VOC), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), for their Spike receptor-binding domain (RBD)’s interactions with ACE2 orthologs of 18 animal species. We found that, compared to the RBD of an early isolate WHU01, the Alpha RBD has markedly increased affinity to cattle and pig ACE2 proteins and decreased affinity to horse and donkey ACE2 proteins. The RBDs of Beta and Gamma variants have almost completely lost affinity to bat, horse, and donkey ACE2 orthologs. Mainly due to the Q493R and N501Y mutations, the Omicron RBD showed markedly enhanced affinity to mouse ACE2. Molecular dynamic simulations further suggest that Omicron RBDs are optimal for electrostatic interactions with mouse ACE2. Interestingly, the Omicron RBD also showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of horse, donkey, pig, dog, cat, pangolin, American pika, and bat. The K417N, G496S, and Y505H substitutions were identified as three major contributors that commonly have negative impact on RBD binding to these eight ACE2 orthologs. These findings show that Spike mutations have been continuously shaping SARS-CoV-2’s binding affinities to animal ACE2 orthologs and suggest the importance of surveillance of animal infection by circulating SARS-CoV-2 variants. IMPORTANCE Spike-receptor interaction is a critical determinant for the host range of coronaviruses. In this study, we investigated the SARS-CoV-2 WHU01 strain and five WHO-designated SARS-CoV-2 variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and the early Omicron variant, for their Spike interactions with ACE2 proteins of 18 animal species. First, the receptor-binding domains (RBDs) of Alpha, Beta, Gamma, and Omicron were found to display progressive gain of affinity to mouse ACE2. More interestingly, these RBDs were also found with progressive loss of affinities to multiple ACE2 orthologs. The Omicron RBD showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of some livestock animals (horse, donkey, and pig), pet animals (dog and cat), and wild animals (pangolin, American pika, and Rhinolophus sinicus bat). These findings shed light on potential host range shift of SARS-CoV-2 VOCs, especially that of the Omicron variant.

BackgroundJob satisfaction for preschool teachers in rural areas has an important impact on their professional development, physical and mental health, and the development of preschool education. However, few studies have explored the factors that influence rural preschool teachers’ job satisfaction.PurposeThis study aims to examine the influence of rural preschool teachers’ work–family conflict on their job satisfaction, and the mediating effect of occupational identity, the moderating effect of social support.MethodParticipants included 3,065 rural preschool teachers from Zhejiang Province in mainland China. Teachers completed questionnaires on work–family conflict, occupational identity, job satisfaction, and social support. The correlation and moderated mediation analyses were conducted using SPSS PROCESS.Results(1) work–family conflict is associated with poorer job satisfaction in preschool teachers; (2) occupational identity mediates the relationship between work–family conflict and job satisfaction; and (3) a high level of social support alleviates the negative influence of work–family conflict on job satisfaction and promotes the positive effect of occupational identity on job satisfaction.ConclusionThe study revealed the negative impact of work–family conflict on preschool teachers’ job satisfaction, and the protecting effect of social support, which has important implications for improving teachers’ future job satisfaction.

The composite modification method helped improve the viscoelastic properties, aging resistance, and high and low-temperature resistance of asphalt. In this paper, organic modified bentonite (OBT) was successfully prepared by means of liquid phase grinding. The pre-treated OBT was incorporated with styrene-butadiene-styrene (SBS) to prepare modified asphalt (OBTS-MA). It aims at enhancing the properties of composited modified asphalt with new method. After characterizations, the data of three basic indices indicated that the ductility value of OBTS-MA was significantly increased by 210% compared with the asphalt. ATR-FTIR data showed that the carbonyl content of OBTS-MA was markedly lower than that of the asphalt after aging. Nanoindentation and fluorescence microscopy tests revealed that OBT and SBS formed stable structure in OBTS-MA, which significantly optimized the apparent mechanical properties of modified asphalt. This study provided a new idea for optimizing asphalt modification with potential cost-saving and environmentally friendly characteristics. It also performed good prospects and ecological benefits in the future.

Abstract The development of the Internet and big data has led to the emergence of graphs as an important data representation structure in various real-world scenarios. However, as data size increases, computational complexity and memory requirements pose significant challenges for graph embedding. To address this challenge, this paper proposes a multilevel embedding refinement framework (MERIT) based on large-scale graphs, using spectral distance-constrained graph coarsening algorithms and an improved graph convolutional neural network model that addresses the over-smoothing problem by incorporating initial values and identity mapping. Experimental results on large-scale datasets demonstrate the effectiveness of MERIT, with an average AUROC score 8% higher than other baseline methods. Moreover, in a node classification task on a large-scale graph with 126,825 nodes and 22,412,658 edges, the framework improves embedding quality while enhancing the runtime by 25 times. The experimental findings highlight the superior efficiency and accuracy of the proposed approach compared to other graph embedding methods.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Abstract Chick embryos are a valuable model for studying immunity and vaccines. Therefore, it is crucial to investigate the molecular mechanism of the Mycoplasma gallisepticum (MG)-induced immune response in chick embryos for the prevention and control of MG. In this study, we screened for downregulated let-7d microRNA in MG-infected chicken embryonic lungs to explore its involvement in the innate immune mechanism against MG. Here, we demonstrated that low levels of let-7d are a protective mechanism for chicken embryo primary type II pneumocytes (CP-II) in the presence of MG. Specifically, we found that depressed levels of let-7 in CP-II cells reduced the adhesion capacity of MG. This suppressive effect was achieved through the activated mitogen-activated protein kinase phosphatase 1 (MKP1) target gene and the inactivated mitogen-activated protein kinase (MAPK) pathway. Furthermore, MG-induced hyperinflammation and cell death were both alleviated by downregulation of let-7d. In conclusion, chick embryos protect themselves against MG infection through the innate immune molecule let-7d, which may result from its function as an inhibitor of the MAPK pathway to effectively mitigate MG adhesion, the inflammatory response and cell apoptosis. This study may provide new insight into the development of vaccines against MG.

Improper drilling parameters may cause severe vibration of drill string which leads to reduce the rate of penetration and drilling tool premature failure accidents in the drilling process of ultra-deep well. The study on dynamic characteristics of drill string plays an important role in increasing the safety of drilling tool and optimizing the drilling parameters. Considering the influences of real borehole trajectory, interaction between bit and formation, contact between drill string and borehole wall, stiction of drilling fluid and other factors, a comprehensive drill string dynamic model was established to simulate the changes of wellhead hook load, torque, equivalent stress of drill string and BHA (bottom-hole assembly) section acceleration and motion trajectory with time at different WOBs (weights on bit) and rotary speeds. The safety factor and overpull margin of wellhead drill string were calculated and the strength of drilling tool in ultra-deep well was checked using the fourth strength theory. The analysis results show that, in the drilling process of ultra-deep well, the transverse motion amplitude of the drill string near the wellhead is relatively small and vibration of drill string mainly occurs in the lower well section. As the rotary speed increases, the number of collision between lower drilling tool and borehole wall increases, wellhead transverse stress increases, change in torque is not large and change in wellhead equivalent stress is relatively small. As the WOB increases, wellhead torque will increase, axial load and equivalent stress will decrease and vibration acceleration of BHA will increase sharply. Wellhead overpull margin and safety factor will decrease with the increase of rotary speed and increase with the increase of WOB. Wellhead safety factor of S135 drilling tool in an Φ190.5 mm ultra-deep well on the south margins of Junggar basin changes around 1.8. The drilling tool is safe and has relatively sufficient ability to deal with the downhole accidents if a large size high steel grade drill string (Φ139.7 mm S135) is used. However, in view of BHA safety, neither rotary speed shall be too high nor WOB shall be too large.

Abstract. Background:. Total knee arthroplasty (TKA) can reduce severe joint pain and improve functional disability in hemophilia. However, the long-term outcomes have rarely been reported in China. Therefore, this study aimed to evaluate the long-term outcomes and complications of TKA in Chinese patients with hemophilic arthropathy. Methods:. We retrospectively reviewed patients with hemophilia who underwent TKA between 2003 and 2020, with at least 10 years of follow-up. The clinical results, patellar scores, patients' overall satisfaction ratings, and radiological findings were evaluated. Revision surgery for implants during the follow-up period was recorded. Results:. Twenty-six patients with 36 TKAs were successfully followed up for an average of 12.4 years. Their Hospital for Special Surgery Knee Score improved from an average of 45.8 to 85.9. The average flexion contracture statistically significantly decreased from 18.1° to 4.2°. The range of motion (ROM) improved from 60.6° to 84.8°. All the patients accepted patelloplasty, and the patients' patellar score improved from 7.8 preoperatively to 24.9 at the last follow-up. There was no statistically significant difference in clinical outcomes between the unilateral and bilateral procedures, except for a better ROM at follow-up in the unilateral group. Mild and enduring anterior knee pain was reported in seven knees (19%). The annual bleeding event was 2.7 times/year at the last follow-up. A total of 25 patients with 35 TKAs were satisfied with the procedure (97%). Revision surgery was performed in seven knees, with 10- and 15-year prosthesis survival rates of 85.8% and 75.7%, respectively. Conclusions:. TKA is an effective procedure for patients with end-stage hemophilic arthropathy, which relieves pain, improves knee functions, decreases flexion contracture, and provides a high rate of satisfaction after more than ten years of follow-up.

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in colored wheat. Using the entropy method revealed that among the 72 colored wheat varieties, 10 were suitable for cultivation. Variety 70 was the top-performing variety, with a comprehensive index of 87.15%. In the final established structural equation model, each agronomic trait exhibited a positive direct effect on yield. Notably, plant height, spike length, and flag leaf width had significant impacts on yield, with path coefficients of 0.55, 0.40, and 0.27. Transcriptome analysis and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) validation were used to identify three dwarfing genes controlling plant height: Rht1, Rht-D1, and Rht8. Subsequent RT-qPCR validation clustering heatmap results indicated that Rht-D1 gene expression increased with the growth of per-acre yield. Rht8 belongs to the semi-dwarf gene category and has a significant positive effect on grain yield. However, the impact of Rht1, as a dwarfing gene, on agronomic traits varies. These research findings provide crucial references for the breeding of new varieties.

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 μM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 μM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.

In this study, we investigated the feasibility of using electroencephalogram (EEG) signals to differentiate between four distinct subject-driven cognitive states: resting state, narrative memory, music, and subtraction tasks. EEG data were collected from seven healthy male participants while performing these cognitive tasks, and the raw EEG signals were transformed into time–frequency maps using continuous wavelet transform. Based on these time–frequency maps, we developed a convolutional neural network model (TF-CNN-CFA) with a channel and frequency attention mechanism to automatically distinguish between these cognitive states. The experimental results demonstrated that the model achieved an average classification accuracy of 76.14% in identifying these four cognitive states, significantly outperforming traditional EEG signal processing methods and other classical image classification algorithms. Furthermore, we investigated the impact of varying lengths of EEG signals on classification performance and found that TF-CNN-CFA demonstrates consistent performance across different window lengths, indicating its strong generalization capability. This study validates the ability of EEG to differentiate higher cognitive states, which could potentially offer a novel BCI paradigm.

In recent decades, the hydrological processes on the Loess Plateau have undergone significant changes due to the combined effects of climate change and human activities. This study investigates the Qin River basin, the core area of the Loess Plateau. Between 1971 and 2000, the hydrometeorology of the flood season in the Qin basin on the Loess Plateau in China changed abruptly in 1982 and 1992. This study uses distributed hydrologic modeling and statistical analysis to distinguish the spatial and temporal impacts of climate change and human activities. The fastest dynamic changes in land use occurred in grassland and construction land, accounting for 0.36% and −0.1%, respectively, from 1982 to 1991. From 1992 to 2000, it was 0.29% and 0.3%, respectively. The increase in basin area where the Normalized Difference Vegetation Index increased was 95%. However, except for significant changes in runoff from 1981 to 1992, there were no significant changes in precipitation, runoff, and temperature during other flood seasons. During the two studied variation periods, from 1982 to 1991 and from 1992 to 2000, the contribution rate of climate change to flood season runoff (CClimate) decreased from 83.26% to 74.47%, while the contribution rate of human activity disturbance to flood season runoff (Chuman) increased from 16.74% to 25.53%. In terms of spatial distribution, from 1982 to 1991, areas with a Chuman > 50% were primarily concentrated in the upper reaches of the basin, while from 1992–2000, these areas shifted to the lower reaches. This study offers valuable insights for water resource planning and soil conservation measures in the Loess Plateau and similar arid regions worldwide, aiming to ensure water resource safety and sustainability in response to climate change and human interference.

Abstract Background By continually monitoring end-tidal carbon dioxide concentrations, capnography can detect abnormal ventilation or apnoea early. This randomized, controlled study explored the effect of early intervention with capnography on the incidence of hypoxia in mildly obese patients undergoing sedation for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods This is a single-center, randomized, single-blind, parallel-assignment, controlled trial. Mildly obese patients (28 kg/m2 ≤ BMI

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Abstract With the rise of edge computing technology and the development of intelligent mobile devices, task offloading in the edge-cloud environment has become a research hotspot. Task offloading is also a key research issue in Mobile CrowdSourcing (MCS), where crowd workers collect sensed data through smart devices they carry and offload to edge-cloud servers or perform computing tasks locally. Current researches mainly focus on reducing resource consumption in edge-cloud servers, but fails to consider the conflict between resource consumption and service quality. Therefore, this paper considers the learning generation offloading strategy among multiple Deep Neural Network(DNN), proposed a Deep Neural Network-based Task Offloading Optimization (DTOO) algorithm to obtain an approximate optimal task offloading strategy in the edge-cloud servers to solve the conflict between resource consumption and service quality. In addition, a stack-based offloading strategy is researched. The resource sorting method allocates computing resources reasonably, thereby reducing the probability of task failure. Compared with the existing algorithms, the DTOO algorithm could balance the conflict between resource consumption and service quality in traditional edge-cloud applications on the premise of ensuring a higher task completion rate.

BackgroundThe continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC).MethodsPatients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates.ResultsA total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC.ConclusionThe OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.

The Gutong Patch (GTP) is common in clinical practice for bone diseases. This study compared the efficacy and safety of GTP and nonsteroidal anti-inflammatory drugs (NSAIDs) for KOA patients from 35 medical centers assigned to GTP, selective COX-2 inhibitor (SCI), GTP + SCI, non-selective COX-2 inhibitor (NSCI), and GTP + NSCI groups. The visual analog scale (VAS) pain score, EuroQol-VAS, EuroQol 5D-3 L, time to articular pain relief / disappearance, and joint motion recovery were the efficacy assessments. Safety assessments included contact dermatitis, gastrointestinal disorders, etc. The p-value

BackgroundLupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients.MethodsThis case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated.ResultsThere were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858).ConclusionOur findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.

Soil ingestion by livestock is common in grazing ecosystems, but few studies have been conducted to assess its effect on the animal organism. The topic is worthy of attention because these potential effects are likely to be enriched in the food chain and interfere with animal and human health. In this study, we present an indoor feeding trial conducted based on a completely randomized design to comprehensively evaluate the effects of simulated soil ingestion during grazing on nutrient digestibility, rumen fermentation, and microflora, and mineral deposition in the organs and tissues of sheep. Eighteen Mutton Merino crossbred sheep (42.7 ± 2.34 kg) were randomly allotted to three treatments and fed diets containing 0% (Control), 5% (SOIL5), and 10% (SOIL10) for 62 d, including a 7-d metabolism trial. It was found that soil intake altered the rumen fermentation in sheep, as evidenced by a decrease in total volatile fatty acids (VFA) and acetate concentrations in rumen fluid of 50.6% and 51.3%, respectively (p

Protected grape cultivation develops rapidly because of huge economic benefits. However, adverse environmental conditions (insufficient sunlight, high temperature, etc.) in protected cultivation led to low-quality berries. This study aimed to evaluate the effects of berry thinning on the quality attributes of two table grape cultivars (Baoguang and Cuiguang) under linkage greenhouse conditions. Three treatments (L, light berry thinning; M, moderate berry thinning; H, heavy berry thinning) were compared with the control (C, no berry thinning). Berry thinning increased berry weight, total soluble solids (TSS), fructose, glucose, the ratio of TSS to titratable acidity (TA), anthocyanin contents, berry firmness, and mineral contents (Ca, Fe, Na, Mg). Conversely, TA and organic acid profiles were decreased by berry thinning. Cultivars showed significant effects on most of the berry quality parameters. The interaction of cultivars by berry-thinning treatments affected sugar and acid components, anthocyanin contents, and mineral elements.

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level. Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols, which have profound effects on neuropathology. 25-Hydroxycholesterol (25-HC), the main product of the membrane-associated enzyme cholesterol-25-hydroxylase (CH25H), plays important roles in mediating neuroinflammation. However, whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC, as well as the resulting pathological effects, remain unclear. In the present study, spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression. A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo. In cultured primary astrocytes, thrombin interacted with protease-activated receptor 1, mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway. Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration. Finally, injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function. Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.

Abstract Interstitial fluid (ISF) from brain drains along the basement membranes of capillaries and arteries as Intramural Periarterial Drainage (IPAD); failure of IPAD results in cerebral amyloid angiopathy (CAA). In this study, we test the hypothesis that IPAD fails after subarachnoid haemorrhage (SAH). The rat SAH model was established using endovascular perforation method. Fluorescence dyes with various molecular weights were injected into cisterna magna of rats, and the pattern of IPAD after SAH was detected using immunofluorescence staining, two-photon fluorescent microscope, transmission electron microscope and magnetic resonance imaging tracking techniques. Our results showed that fluorescence dyes entered the brain along a periarterial compartment and were cleared from brain along the basement membranes of the capillaries, with different patterns based on individual molecular weights. After SAH, there was significant impairment in the IPAD system: marked expansion of perivascular spaces, and ISF clearance rate was significantly decreased, associated with the apoptosis of endothelial cells, activation of astrocytes, over-expression of matrix metalloproteinase 9 and loss of collagen type IV. In conclusion, experimental SAH leads to a failure of IPAD, clinically significant for long term complications such as CAA, following SAH.