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ABSTRACT: Betaine has been shown to enhance growth performance and increase breast muscle yield in ducks and broilers through various mechanisms, including the modification of DNA methylation. However, the impact of in ovo betaine injection on muscle growth in newly hatched goslings remains unclear. In this study, fifty eggs were injected with saline or betaine at 7.5 mg/egg prior to incubation, and the subsequent effects on breast muscle growth in the newly hatched goslings were investigated. Betaine significantly increased (P < 0.05) the hatch weight, breast muscle weight, and breast muscle index, accompanied by an augmentation in muscle bundle cross-sectional area. Concurrently, betaine significantly upregulated (P < 0.05) the expression levels of myogenic regulatory factors, including myogenin (MyoG) and paired box 7 (Pax7) both mRNA and protein, while downregulating (P < 0.05) the mRNA and protein levels of myostatin (MSTN). Histological analysis revealed a higher abundance of proliferating cell nuclear antigen (PCNA) and Pax7 immune-positive cells in the breast muscle of the betaine group, consistent with elevated PCNA and Pax7 mRNA and protein levels. Additionally, significantly increased (P < 0.05) contents of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were observed in the breast muscle of the betaine group, so was mRNA expression of IGF-1, IGF-2, and insulin-like growth factor 1 receptor (IGF-1R). Betaine also significantly in8creased (P < 0.05) global DNA methylation of the breast muscle, accompanied by enhanced mRNA and protein levels of methionine cycle and DNA methylation-related enzymes, Interestingly, the promoter regions of IGF-1, IGF-2, and IGF-1R genes were significantly hypomethylated (P < 0.05). Moreover, in ovo betaine injection significantly upregulated (P < 0.05) the protein level of farnesoid X receptor (FXR) in breast muscle and FXR binding to the promoter of IGF-2 gene. These findings suggest that in ovo betaine injection promotes breast muscle growth during embryonic development in goslings through the FXR-mediated IGF-2 pathway, ultimately improving hatch weight and breast muscle weight.

Abstract Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.

The rising prevalence of diabetes has underscored concerns surrounding diabetic wounds and their potential to induce disability. The intricate healing mechanisms of diabetic wounds are multifaceted, influenced by ambient microenvironment, including prolonged hyperglycemia, severe infection, inflammation, elevated levels of reactive oxygen species (ROS), ischemia, impaired vascularization, and altered wound physicochemical properties. In recent years, hydrogels have emerged as promising candidates for diabetic wound treatment owing to their exceptional biocompatibility and resemblance to the extracellular matrix (ECM) through a three-dimensional (3D) porous network. This review will first summarize the microenvironment alterations occurring in the diabetic wounds, aiming to provide a comprehensive understanding of its pathogenesis, then a comprehensive classification of recently developed hydrogels will be presented, encompassing properties such as hypoglycemic effects, anti-inflammatory capabilities, antibacterial attributes, ROS scavenging abilities, promotion of angiogenesis, pH responsiveness, and more. The primary objective is to offer a valuable reference for repairing diabetic wounds based on their unique microenvironment. Moreover, this paper outlines potential avenues for future advancements in hydrogel dressings to facilitate and expedite the healing process of diabetic wounds.

Both DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m6A) modifications are reported to participate in cellular stress responses including inflammation. Phosphoenolpyruvate carboxykinase 2 (PCK2) is upregulated in Kupffer cells (KCs) to facilitate the proinflammatory phosphorylation signaling cascades upon LPS stimulation, yet the role of 5mC and m6A in PCK2 upregulation remain elusive. Here, we report that the significantly augmented PCK2 mRNA and protein levels are associated with global 5mC demethylation coupled with m6A hypermethylation in LPS-activated KCs. The suppression of 5mC demethylation or m6A hypermethylation significantly alleviates the upregulation of PCK2 and proinflammatory cytokines in LPS-challenged KCs. Further reciprocal tests indicate 5mC demethylation is upstream of m6A hypermethylation. Specifically, CpG islands in the promoters of PCK2 and RNA methyltransferase (METTL3 and METTL14) genes are demethylated, while the 3′UTR of PCK2 mRNA is m6A hypermethylated, in LPS-stimulated KCs. These modifications contribute to the transactivation of the PCK2 gene as well as increased PCK2 mRNA stability and protein production via a m6A-mediated mechanism with IGF2BP1 as the reader protein. These results indicate that DNA 5mC and RNA m6A collaborate to upregulate PCK2 expression, respectively, at the transcriptional and post-transcriptional levels during KC activation.

With the continuous improvement of the performance and capabilities of spacecrafts, the application of active magnetic bearings (AMBs) has become a major focus in current research. The AMBs-flywheel system is not only responsible for attitude control but also provides the required energy during shadow periods. In magnetically suspended single gimbal control moment gyroscope (SGCMG), self-excited vibration caused by high-speed rotor rotation significantly affects the stability of the AMB system. The research focus lies in magnetically supporting the flywheel at high speeds with low power consumption to explore gyroscopic mechanics at ultra-high speeds and assess the corresponding stability. This study presents an assessment of the stability performance of a high-speed flywheel equipped on a single gimbal with an angular momentum of 75 Nm. To achieve ultra-high-speed operation under low driving power, a high-precise dynamic balance was performed followed by a novel unbalance control strategy of a radial and axial automatic balancing algorithm to suppress effectively synchronous vibrations due to nutation and precession. Corresponding experiments including static stable suspension experiments as well as low-speed, high-speed, and series-based stability assessments were conducted. Stable suspension at any speed ranging from 0 to 30,000 r/min was successfully implemented. The stability performance of the high-speed flywheel on a rotating platform at different gimbal speeds was verified, with a maximum speed reaching 31,200 r/min. The entire output torque process within the range of 30,000 r/min was revealed.

Abstract. Background:. Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). Methods:. This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. Results:. MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively (P = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs. 22.6% [85/376], P = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31–1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13–0.95). Conclusion:. As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. Trial Registration:. ChiCTR.org.cn, ChiCTR-TRC-12003513

Maritime transportation plays a critical role in global trade, and studies on maritime transportation safety management are of great significance to the sustainable development of the maritime industry. Consequently, there has been an increasing trend recently in studies on maritime transportation safety management, especially in terms of safety risk analysis and emergency management. Therefore, the general idea of this article is to provide a detailed literature review of maritime transportation safety management based on 186 articles in the Web of Science (WOS) database published from 2011 to 2022. The purposes of this article are as follows: (1) to provide a statistics-based description and conduct a network-based bibliometric analysis on the basis of the collected articles; (2) to summarize the methodologies/technologies employed in maritime transportation safety management spatiotemporally; and (3) to propose four potential research perspectives in terms of maritime transportation safety management. Based on the findings and insights obtained from the bibliometric and systematic review, the development of a resilient maritime transportation system could be facilitated by means of data- or intelligence-driven technologies, such as scenario representation, digital twinning, and data simulation. In addition, the issues facing intelligent maritime shipping greatly challenge the current maritime safety management system due to the co-existence of intelligent and non-intelligent maritime operation.

IntroductionEpidemiological studies have shown that tooth loss may be associated with an increased risk of cognitive decline and dementia. However, some results do not show a significant association. Therefore, we performed a meta-analysis to evaluate this association.MethodsRelevant cohort studies were searched in PubMed, Embase, Web of Science (up to May 2022), and the reference lists of retrieved articles. The pooled relative risk (RR) and 95% confidence intervals were computed using a random-effects model (CI). Heterogeneity was evaluated using the I2 statistic. Publication bias was evaluated using the Begg's and Egger's tests.ResultsEighteen cohort studies met the inclusion criteria. Original studies with 356,297 participants with an average follow-up of 8.6 years (ranging from 2 to 20 years) were included in this study. The pooled RRs of tooth loss on dementia and cognitive decline were 1.15 (95% CI: 1.10–1.20; P < 0.01, I2 = 67.4%) and 1.20 (95% CI: 1.14–1.26; P = 0.04, I2 = 42.3%), respectively. The results of the subgroup analysis showed an increased association between tooth loss and Alzheimer's disease (AD) (RR = 1.12, 95% CI: 1.02–1.23) and vascular dementia (VaD) (RR = 1.25, 95% CI: 1.06–1.47). The results of the subgroup analysis also showed that pooled RRs varied by geographic location, sex, use of dentures, number of teeth or edentulous status, dental assessment, and follow-up duration. None of the Begg's and Egger's tests or funnel plots showed evidence of publication bias.DiscussionTooth loss is associated with a significantly increased risk of cognitive decline and dementia, suggesting that adequate natural teeth are important for cognitive function in older adults. The likely mechanisms mostly suggested include nutrition, inflammation, and neural feedback, especially deficiency of several nutrients like vitamin D.

BackgroundA previous phase IV trial revealed sex as a potential effect modifier of MUSKARDIA efficacy in stable coronary artery disease (CAD).ObjectiveTo assess the clinical effect of MUSKARDIA as a supplemental treatment to optimal medical therapy (OMT) in stable CAD cases.MethodsThis study was a subgroup analysis of a multicenter, randomized, double-blinded, placebo-controlled phase IV clinical study. Eligible individuals underwent randomization to the oral MUSKARDIA and placebo groups and were treated for 24 months. All participants received OMT according to existing guidelines. The primary composite outcome was the major adverse cardiovascular event (MACE), included cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary composite outcome encompassed all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina and/or heart failure, and undergoing coronary procedure/surgery during treatment. Safety signals, especially cardiovascular adverse events (AEs), were analyzed.ResultsThe female subgroup included 776 participants (384 and 392 in the MUSKARDIA and placebo groups, respectively). The occurrence of the primary composite outcome was lower in the MUSKARDIA group compared with placebo-treated individuals (HR = 0.27, 95%CI: 0.09–0.83; P = 0.02), but the secondary composite outcome showed no significant difference (HR = 0.77, 95%CI: 0.47–1.25; P = 0.29). The MUSKARDIA group had reduced incidence of cardiovascular AEs compared with placebo-treated cases (2.9% vs. 5.6%).ConclusionAs a supplemental treatment to OMT, 24-month administration of MUSKARDIA is effective and safe in female stable CAD cases.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT01897805].

In order to seek a more outstanding diagnosis and treatment of diabetic retinopathy (DR), we predicted the miRNA biomarkers of DR and explored the pathological mechanism of DR through bioinformatics analysis.Method: Based on public omics data and databases, we investigated ncRNA (non-coding RNA) functions based on the ceRNA hypothesis.Result: Among differentially expressed miRNAs (DE-miRNAs), hsa-miR-1179, -4797-3p and -665 may be diagnosis biomarkers of DR. Functional enrichment analysis revealed differentially expressed mRNAs (DE-mRNAs) enriched in mitochondrial transport, cellular respiration and energy derivation. 18 tissue/organ-specific expressed genes, 10 hub genes and gene cluster modules were identified. The ceRNA networks lncRNA FBXL19-AS1/miR-378f/MRPL39 and lncRNA UBL7-AS1/miR-378f/MRPL39 might be potential RNA regulatory pathways in DR.Conclusion: Differentially expressed hsa-miR-1179, -4797-3p and -665 can be used as powerful markers for DR diagnosis, and the ceRNA network: lncRNA FBXL19-AS1/UBL7-AS1-miR-378f-MRPL39 may represent an important regulatory role in DR progression.

The complex and variable hydro-meteorological conditions in Arctic waters and scattered and limited port infrastructures pose a great threat and challenge to Arctic emergency search and rescue. It is crucial to determine an available and effective emergency port for rescue in the event of a maritime accident occurring in Arctic waters. In the present study, a directed-weighted emergency port network consisting of maritime accident nodes and port nodes for maritime accident-prone areas in Arctic waters is developed based on complex network theory. For this, the maritime accident nodes are identified by using a K-means clustering algorithm based on historical accident data; the port nodes are determined by screening of the port location and scale; the weights for edges between accident nodes and port nodes are characterized in terms of ERT (emergency rescue time) and PEC (port emergency capacity), and the PECs for different emergency ports along Arctic waters are acquired by entropy-weighted TOPSIS. With the developed emergency port network, the topological properties associated with the accident nodes, port nodes, and the edge weights between accident nodes and port nodes are analyzed. What is more, the emergency ports for each maritime accident point occurring in Arctic waters are obtained and ranked.

This study aims to investigate the effect of heat stress on the physiological metabolism of young laying hens and whether N-acetyl-l-cysteine (NAC) can effectively alleviate heat stress. 120 Hy-Line Brown laying hens aged 12 weeks were randomly divided into four groups: the control group (fed on basal diet under thermal neutral condition), HS group (fed on basal diet under heat stress condition), CN group (fed on the basic meal supplemented with 1,000 mg NAC per kg under thermal neutral condition), and HS+N group (fed on the basic meal was supplemented with 1000 mg NAC per kg under heat stress condition). The HS and HS+N groups were exposed to 36 ± 1°C for 10 h/day. The effects of NAC on the changes of serum concentrations of T3, T4, and CORT and hypothalamic gene and protein expressions induced by heat stress were measured. Results showed that heat stress upregulated the contents of T3, T4, and CORT, while NAC reduced the contents of T3, T4, and CORT. In addition, NAC downregulated AgRP expression, while upregulated the expression of POMC. Moreover, the expressions of AMPKα1, LKB1, and CPT1 were inhibited by NAC, while the expressions of AKT1, ACC, GPAT, and PPARα were increased after NAC treatment, and HMGR did not change significantly. Western blot and comprehensive immunofluorescence section of AMPK in the hypothalamus showed that NAC attenuated the activity of AMPK. In conclusion, NAC can enhance the resistance of laying hens to heat stress by alleviating the metabolic disorders of serum T3, T4, and CORT induced by heat stress, inhibiting the activation of the AMPK pathway and regulating the expression of appetite-related genes in the hypothalamus.

Emerging evidence has revealed the dysbiosis of gut microbiota contributes to development of metabolic diseases in animals. However, the potential interaction between gut microbiota and host metabolism in growing hens under metabolic disorder induced by chronic heat exposure (CHE) remains inconclusive. The aim of our study was to examine the potential association among the cecal microbiota community, physiological indicators, and serum metabolite profiles in CHE hens. One hundred and eighty Hy-Line Brown hens were randomly allocated into three groups: thermoneutral control (TN), heat stress (HS), and pair-fed (PF). The experiment lasted for 5 weeks, with the first 2 weeks serving as the adaptation period. Results showed that the expression level of heat shock protein 70 (HSP70) in both serum and cecal tissues was significantly increased in the HS group. Serum parameters analysis also revealed that CHE caused physiological function damage and metabolic disorders. These results suggest the experiment was successful, inducing chronic heat stress. 16S rRNA sequencing analysis showed that the CHE can clearly induce dysbiosis of the gut microbial community reflected in the increment of the F/B ratio. Besides, serum untargeted metabolomics revealed the relative concentrations of 40 metabolites were significantly altered in the HS group compared with the TN group. Pathway analysis showed that these metabolites were mainly involving the increased proteolysis rather than lipolysis, and this tendency could be a specific metabolic adaptation of the poultry. The pair-feed experiment showed that the above changes induced by CHE were partly independent from the reduction of feed intake. Mantel correlation analysis between gut microorganisms and physiological indicators showed that the phylum Firmicutes and Euryarchaeota have a potential interaction with a serum lipid parameter. Random forest analysis showed that both genus Faecalibacterium and Methanobrevibacter were important predictors of the CHE-induced lipid metabolism disorder. Taken together, our findings may contribute to a better understanding of the metabolic mechanisms underlying the energy metabolism imbalance caused by the CHE and provide novel insights into the host-microbes interactions and its effects on the metabolic adaptation of hens under chronic heat exposure.

Motivation: A protein complex is the combination of proteins which interact with each other. Protein–protein interaction (PPI) networks are composed of multiple protein complexes. It is very difficult to recognize protein complexes from PPI data due to the noise of PPI.Results: We proposed a new method, called Topology and Semantic Similarity Network (TSSN), based on topological structure characteristics and biological characteristics to construct the PPI. Experiments show that the TSSN can filter the noise of PPI data. We proposed a new algorithm, called Neighbor Nodes of Proteins (NNP), for recognizing protein complexes by considering their topology information. Experiments show that the algorithm can identify more protein complexes and more accurately. The recognition of protein complexes is vital in research on evolution analysis.Availability and implementation: https://github.com/bioinformatical-code/NNP.

Tumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs for HCC and analyze the role of immune cell infiltration in this pathology. We used OA datasets from The Cancer Genome Atlas database. First, the “maftools” package was used to screen the highest mutation frequency in all samples. R software was used to identify differentially expressed genes (DEGs) according to mutation frequency and perform functional correlation analysis. Then, the gene ontology (GO) enrichment analysis was performed with “clusterProfiler”, “enrichplot”, and “ggplot2” packages. Finally, the correlations between diagnostic markers and infiltrating immune cells were analyzed, and CIBERSORT was used to evaluate the infiltration of immune cells in HCC tissues. As a result, we identified a total of 359 DEGs in this study. These DEGs may affect HCC prognosis by regulating fatty acid metabolism, hypoxia, and the P53 pathway. The top 15 genes were selected as the hub genes through PPI network analysis. SRSF1, SNRPA1, and SRSF3 showed strong similarities in biological effects, NCBP2 was demonstrated as a diagnostic marker of HCC, and high NCBP2 expression was significantly correlated with poor over survival (OS) in HCC. In addition, NCBP2 expression was correlated with the infiltration of B cells (r = 0.364, p = 3.30 × 10−12), CD8+ T cells (r = 0.295, p = 2.71 × 10−8), CD4+ T cells, (r = 0.484, p = 1.37 × 10−21), macrophages (r = 0.551, p = 1.97 × 10−28), neutrophils (r = 0.457, p = 3.26 × 10−19), and dendritic cells (r = 0.453, p = 1.97 × 10−18). Immune cell infiltration analysis revealed that the degree of central memory T-cell (Tcm) infiltration may be correlated with the HCC process. In conclusion, NCBP2 can be used as diagnostic markers of HCC, and immune cell infiltration plays an important role in the occurrence and progression of HCC.

In order to further improve driving comfort, this paper takes the semi-vehicle active suspension as the research object. Furthermore, combined with a 5-DOF driver-seat model, a new 9-DOF driver seat-active suspension model is proposed. The adaptive Kalman filter combined with L2 feedback control algorithm is used to improve the controller. First, a discrete 9-DOF driver seat-active suspension model is established. Then, the L2 feedback algorithm is used to solve the optimal feedback matrix of the model, and the adaptive Kalman filter algorithm is used to replace the linear Kalman filter. Finally, the improved active suspension model and algorithm are verified through simulation and test. The results show that the new algorithm and model not only significantly improve the driver comfort, but also comprehensively optimize the other performance of the vehicle. Compared with the traditional LQG control algorithm, the RMS value of the acceleration experienced by the driver’s limb are, respectively, decreased by 10.9%, 15.9%, 6.4%, and 7.5%. The RMS value of pitch angle acceleration experienced by the driver decreased by 6.4%, and the RMS value of the dynamic tire deflection of front and rear tire decreased by 32.6% and 12.1%, respectively.

Mammary cancer is the most prevalent canine tumor and frequently results in death. This study was carried out for the diagnosis of three canine breast tumors based on clinical, histopathological, immunohistochemistry, and in situ TUNEL assay. Firstly, the morphology of tumor cells was examined by hematoxylin and eosin staining. We found two cases of ductal carcinoma characterized by ductal dilatation and one case of solid carcinoma characterized by extensive connective tissue proliferation. Immunohistochemical assay in paraffin-embedded sections immediately followed surgical removal. The results demonstrated that the expression level of Estrogen receptor (ER), progesterone receptor (PR), p53, vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) proteins were abnormal. Finally, in situ TUNEL showed a significant decrease in apoptotic cells in canine breast tumors (P<0.01). Taken together, clinical, histopathological, immunohistochemistry, and in situ TUNEL assay will provide a better understanding of the pathogenesis of breast tumors in dogs under field conditions. [ABSTRACT FROM AUTHOR]