Search Results (76)

As a critical precision transmission element in numerical control (NC) machines, the linear rolling guide (LRG) suffers from surface wear degradation, which significantly impairs machining accuracy and operational reliability. Despite its importance, effective identification methods for LRG degradation remain limited. In this study, a hybrid approach combining multi-scale fuzzy entropy (MFE) with a gray wolf-optimized random forest (GWO-RF) algorithm was proposed to identify the surface wear state of the LRG. Preload degradation and vibration signals were collected at three surface wear stages throughout the LGR’s service life. The vibration signals were decomposed and reconstructed using complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), followed by multi-scale fuzzy entropy analysis of the reconstructed signals. After dimensionality reduction via kernel principal component analysis (KPCA), the processed features were fed into the GWO-RF model for classification. Experimental results demonstrated a recognition accuracy of 97.9%. Full article

This study elucidates potential genetic determinants and mechanisms involved in the synergistic effects of daptomycin (DAP) + fosfomycin (FOF) combination therapy. Among 33 clinically derived DAP-susceptible (S)/DAP-resistant (R) isogenic strain pairs, mutations in the mprF gene occurred in 30/33 DAP-R strains, including polymorphisms of L826F (33%) or T345A/L/I (15%). Strain variants of DAP-S CB1483 serially passaged in vitro for 10 days in DAP +/− FOF identified a key non-synonymous mutation in mprF (L826F) only in the DAP monotherapy arm. Interestingly, passage in FOF alone or DAP + FOF prevented the emergence of this mprF mutation following 10-day passage. This L826F mprF polymorphism, associated with a “gain-in-function” phenotype, exhibited increased amounts of lysyl-phosphatidylglycerol (L-PG) in the cell membrane (CM). Transcriptomics revealed a relatively modest number (~10) of distinct genes that were significantly up- or downregulated (≥2 log fold) in both the DAP-S and DAP-R strain pairs upon DAP + FOF exposures (vs. DAP or FOF alone). Of note, DAP + FOF decreased expression of lrgAB and sdrE and increased the expression level of fosB. In a rabbit infective endocarditis (IE) model, the DAP-R CB185 strain treated with DAP +/− FOF showed significantly reduced lrgB expression in vegetations compared with DAP treatment alone. Overall, these findings indicate that DAP + FOF therapy impacts MRSA through multiple specific mechanisms, enhancing bacterial clearance. Full article

Climate change presents serious threats to the sustainability of coupled Water–Agriculture–Community Systems (WACSs) in New Mexico’s Lower Rio Grande (LRG) region. Enhancing the resilience of WACSs is essential for ensuring the system’s long-term adaptability and sustainability. Although the importance of system feedback and dynamic behavior is increasingly acknowledged in resilience studies, many existing assessments fail to account for the complex interconnections and self-organizing nature of these systems. This study utilizes a System Dynamics (SD) simulation modeling and a function-based resilience framework to assess WACSs’ responses to climate change, specifically investigating whether improvements in Water Conveyance Efficiency (WCE) can enhance system resilience in the LRG. The analysis centers on the interaction of socioeconomic and hydrological dynamics, incorporating future climate projections derived from three models: UKMO, GFDL, and NCAR. Findings reveal that under the UKMO scenario, enhanced WCE leads to improved resilience in the groundwater system; however, agricultural-community resilience declines under both the UKMO and GFDL scenarios. While hydrological resilience shows improvement—particularly with increased WCE—the agriculture–community system consistently exhibits limited capacity to adapt or reorganize. The differing outcomes across climate models underscore the sensitivity of WACS resilience to varying climatic conditions. Full article

Background: Leucine rich α-2 glycoprotein (LRG) is a glycoprotein that is an acute-phase protein produced by neutrophils, macrophages, hepatocytes, and intestinal epithelial cells. This study aimed to determine the serum LRG (s-LRG) and urine LRG (u-LRG) expression levels in children with inflammatory bowel disease (IBD) and evaluated their correlation with clinical disease activity, other inflammatory markers, laboratory results, and endoscopic activity scoring. Methods: This prospective observational study was conducted at a tertiary centre and included children aged 2–18 years with IBD. Clinic activity scoring was used to assess clinical disease activity. Haemoglobin levels, platelet counts, albumin, C-reactive protein, and erythrocyte sedimentation rate were analysed in the blood sample. LRG levels were measured in both blood and urine samples. The endoscopic assessment was scored according to the simple endoscopic score and Mayo endoscopic score. Serum and urine LRG levels were measured using commercial enzyme-linked immunosorbent assay kits. Disease activation was defined based on clinical activity scoring, laboratory results, and endoscopic evaluation. The results were compared between the active IBD and remission groups. Results: Forty-two (50%) patients with active IBD and forty-two (50%) patients in remission were included in this study. The serum levels of LRG were elevated in the patients with active IBD compared with the levels in the patients with IBD in remission (p = 0.020). However, there was no difference in the u-LRG level between the two groups (p = 0.407). In patients with IBD, positive correlations were observed between s-LRG, platelet count, C-reactive protein (CRP), and the erythrocyte sedimentation rate. The serum LRG was negatively correlated with albumin and haemoglobin levels. Urine LRG was not correlated with s-LRG in any patients with IBD included or in patients with active IBD. The cutoff value for s- LRG (77.03 μg/mL) had a sensitivity and specificity of 40.4% (95% CI 25.6–56.7%) and 88.1% (95% CI 74.3–96.0%), respectively. It was found that s-LRG was a more significant parameter than CRP in predicting disease activation. Conclusions: This prospective study demonstrated that the s-LRG level is a useful biomarker for predicting disease activation in children with IBD and appears to be a more significant parameter than the CRP level. However, the u-LRG level is not effective in predicting disease activation in children with IBD. Full article

Flooding is one of the most frequent natural disasters at present, and can pose a serious threat to transmission towers. In response to the accuracy and timeliness requirements of flood emergency monitoring, a local region growth algorithm combining polarization and texture information is proposed for Synthetic Aperture Radar (SAR) image water recognition. Morphological methods and external geographic information are used to optimize the results, allowing for rapid extraction of the flood range. The method is validated using Gaofen-3 (GF-3) Fine Strip Imaging Mode II (FSII) SAR images covering Fangshan District in Beijing, China. The experimental results indicate that this method can obtain more effective water information compared to traditional threshold segmentation methods, and can also reduce the effects of noise and mountain shadows. It has good applicability and timeliness with respect to large-scale flood emergency disaster monitoring, and can help to rapidly and accurately obtain detailed information of flood-affected areas, thus providing reference for emergency rescue and disaster relief services. Full article

Upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into the mouse retina during vascular development, we showed that exogenous LRG1 reduces pericyte coverage and NG2 expression. It leads to diminished collagen IV sheathing, fewer adhesion and gap junctions, and reduced vessel calibre and vascular density. Moreover, in mouse retinae containing exogenous LRG1, the developing blood–retinal barrier remains more permeable with significantly higher numbers of transcytotic vesicles present in microvascular endothelial cells. These results reveal that exogeneous LRG1 is sufficient to interfere with the maturation of developing retinal vessels and drive vessel development towards a dysfunctional phenotype. These observations deliver further evidence that LRG1 is an angiopathic factor and highlight the therapeutic potential of blocking LRG1 in diseases characterized by pathogenic angiogenesis or vascular remodelling. Full article

The larvae of Hyphantria cunea feed on plant leaves, causing significant losses to forestry and agricultural production. At present, cry1 genes such as cry1Ac and cry1Ah are mainly used to control H. cunea. To delay the problem of pest resistance induced by a single insecticidal gene, it is crucial to discover and develop new insecticidal genes or gene combinations. This study found cry9Aa3 and cry9Aa4 showed insecticidal activity against H. cunea. The toxicity of 14 mutants of Cry9Aa3 was analyzed and the LC₅₀ of the triple-amino-acid substitution mutant 316LRG318AAA was 3.69 μg/g, which represents a 1.49-fold increase in insecticidal activity compared to Cry9Aa3. Additionally, enhanced stability of this mutant was detected in the midgut juice of H. cunea. Cry9Aa3 and 316LRG318AAA, in combination with Cry1Ah, demonstrated synergistic effects against H. cunea, with synergistic factors of 4.76 and 8.33, respectively. This study has identified the mutant 316LRG318AAA and its combination with Cry1Ah as exhibiting high toxicity against H. cunea, providing valuable genetic resources for the development of transgenic poplars and holding significant importance for delaying resistance in this pest. Full article

Preclinical evidence suggests that short chain fatty acids (SCFAs) produced by gut microbiota may impact body composition and muscle growth. While aging is implicated in negative alterations to the gut microbiome, exercise may mitigate these changes. Limited human evidence indicates that resistance training (RT) does not appreciably alter the gut microbiome in older adults, and no human study has examined whether resistance training differentially alters the gut microbiome and associated SCFAs between younger and older individuals. Therefore, we examined whether 10 weeks of RT differentially altered fecal microbiota composition, fecal and circulating SCFAs, and serum markers associated with gastrointestinal integrity in two cohorts of adults. Fecal and serum samples were obtained from untrained younger (22 ± 2 years, n = 12) and older (58 ± 8 years, n = 12) participants prior to and following 10 weeks of supervised twice-weekly full-body RT. Outcome measures immediately before (PRE) and after the intervention (POST) included dual X-ray absorptiometry for body composition, ultrasound for vastus lateralis (VL) thickness, 16S rRNA gene sequencing fecal microbiome data, serum and fecal SCFAs measured by gas chromatography, and serum intestinal fatty acid-binding protein 2 (FABP2), lipopolysaccharide-binding protein (LBP), and leucine-rich alpha-2 glycoprotein (LRG-1) quantified by enzyme-linked immunosorbent assays. Main effects and interactions were measured by repeated measures analysis of variance (group × time; G × T) for all dependent variables, and Spearman correlations were used to explore relationships among changes in relevant outcomes. The intervention significantly increased VL thickness and lean body mass (p < 0.05) equally in both groups. Although group differences in microbiome beta diversity were identified, no effects of age, time, or their interaction were observed for the alpha diversity measures. Seven SCFAs were detected in the fecal samples, albeit no significant age, time, or interaction effects were evident. In serum, acetic acid was the only SCFA detected, with no significant age, time, or interaction effects. Serum LRG1 decreased for all participants (p = 0.007) with higher levels in younger adults (p = 0.015), but no G × T interactions were observed for this marker, serum FABP2, or LBP. No significant correlations were observed among RT-induced changes in muscle mass-related outcomes and changes in fecal microbiome diversity, total or individual SCFAs, or serum FABP2/LBP/LRG-1. These results highlight that 10 weeks of RT largely does not affect fecal microbiota, associated SCFAs, or select markers of gastrointestinal integrity in untrained younger or older adults. Full article

Background/Objectives: This study aimed to construct a risk score (RS) based on necroptosis-associated genes to predict the prognosis of patients with advanced epithelial ovarian cancer (EOC). Methods: EOC data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) series 140082 (GSE140082) were used. Based on known necroptosis-associated genes, clustering was performed to identify molecular subtypes of EOC. A least absolute shrinkage and selection operator (LASSO)–Cox regression analysis identified key genes related to prognosis. The expression of one of them, RIPK3, was analyzed via immunohistochemistry in an EOC cohort. Results: An RS made from ten genes (IDH2, RIPK3, FASLG, BRAF, ITPK1, TNFSF10, ID1, PLK1, MLKL and HSPA4) was developed. Tumor samples were divided into a high-risk group (HRG) and low-risk group (LRG) using the RS. The model is able to predict the overall survival (OS) of EOC and distinguish the prognosis of different clinical subgroups. Immunohistochemical verification of the receptor-interacting serine/threonine-protein kinase (RIPK) 3 confirmed that high nuclear expression is correlated with a longer OS. In addition, the score can predict the response to a programmed death ligand 1 (PD-L1) blockade treatment in selected solid malignancies. Patients from the LRG seem to benefit more from it than patients from the HRG. Conclusions: Our RS based on necroptosis-associated genes might help to predict the prognosis of patients with advanced EOC and gives an idea on how the use of immunotherapy can potentially be guided. Full article

Serum concentrations of leucine-rich alpha-2 glycoprotein 1 (LRG1) are elevated in several cardio-metabolic and inflammatory diseases. LRG1 also plays an important role in the development of hepatic steatosis and insulin resistance. In lipodystrophies (LDs), severe cardio-metabolic complications can be observed. The dysregulation of several adipokines plays a significant role in the clinical manifestation of this syndrome. To date, there have been no studies of LRG1 levels in non-HIV-LD patients. We performed a cross-sectional analysis of LRG1 serum levels in 60 patients with non-HIV-associated LD and in 60 age-, sex-, and BMI-matched healthy controls. Furthermore, we investigated the gene expression of Lrg1 in a mouse model of generalised LD. No significant difference was found in the median concentration of LRG1 serum levels between LD patients (18.2 ng/L; interquartile range 8.3 ng/L) and healthy controls (17.8 ng/L; interquartile range 11.0 ng/L). LRG1 serum concentrations correlated positively with CRP serum levels (p < 0.001). Lrg1 mRNA expression was downregulated in the adipose tissue, whereas in the liver, no difference in Lrg1 expression between LD and wild-type mice was detected. In summary, circulating levels of LRG1 are associated with low-grade inflammation but cannot distinguish between patients with LD and controls. Full article

Purpose: Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis and immunotherapy response. Methods: TLS-associated gene data were obtained from TCGA-CRC and GEO cohorts. A comprehensive analysis using univariate Cox regression identified TLS-associated genes with significant prognostic implications. Subsequently, multiple algorithms were employed to select the most influential genes, and a stepwise Cox regression model was constructed. The model’s predictive performance was validated using independent datasets (GSE39582, GSE17536, and GSE38832). To further investigate the immune microenvironment, immune cell infiltration in high-risk (HRG) and low-risk (LRG) groups was assessed using the CIBERSORT and ssGSEA algorithms. Additionally, we evaluated the model’s potential to predict immune checkpoint blockade therapy response using data from The Cancer Imaging Archive, the TIDE algorithm, and external immunotherapy cohorts (GSE35640, GSE78200, and PRJEB23709). Immunohistochemistry (IHC) was employed to characterize TLS presence and CCL2 gene expression. Results: A three-gene (CCL2, PDCD1, and ICOS) TLS-associated model was identified as strongly associated with prognosis and demonstrated predictive power for CRC patient outcomes and immunotherapy efficacy. Notably, patients in the low-risk group (LRG) had a higher overall survival rate as well as a higher re-response rate to immunotherapy compared to the high-risk group (HRG). Finally, IHC results confirmed significantly elevated CCL2 expression in the TLS regions. Conclusions: The multi-algorithm-integrated model demonstrated robust performance in predicting patient prognosis and immunotherapy response, offering a novel perspective for assessing immunotherapy efficacy. CCL2 may function as a TLS modulator and holds potential as a therapeutic target in CRC. Full article

Pb-contaminated soil poses inherent risks for the spread of antibiotic resistance genes (ARGs). However, few reports have investigated the distribution of lead resistance genes (LRGs), particularly their role in ARGs dynamics during Pb-contaminated soil remediation. This study explored the mechanisms driving ARGs variation under different remediation strategies. The results indicated that an increase in the total abundance of ARGs after applying montmorillonite (Imvite), the composite remediation agents of MgO and Ca(H₂PO₄)₂ (MgO-Ca(H₂PO₄)₂), and the composite remediation agents of montmorillonite, MgO, and Ca(H₂PO₄)₂ (Imvite-MgO-Ca(H₂PO₄)₂). Bioelectrochemical systems (BES) effectively reduced ARGs abundance, and when combined with Imvite-MgO-Ca(H₂PO₄)₂, lowered the risk of ARGs proliferation linked to antibiotic deactivation. Changes in Pb concentration and pH reshaped microbial communities, impacting both LRGs and ARGs. To reduce the risk of ARGs proliferation and transmission during, various control strategies, such as modifying Pb stress, adjusting pH, and manipulating microbial community structure, have been proposed. The study provided theoretical foundation and practical strategies for controlling ARGs dissemination during the remediation of heavy metal-contaminated soil. Full article

Introduction: Leucine-rich alpha-2-glycoprotein 1(LRG-1) is a human protein that has shown potential usefulness as a biomarker for diagnosing pediatric acute appendicitis (PAA). This study aims to validate the diagnostic performance of serum LRG-1 in PAA. Material and Methods: This work is a subgroup analysis from BIDIAP (BIomarkers for DIagnosing Appendicitis in Pediatrics), a prospective single-center observational cohort, to validate serum LRG-1 as a diagnostic tool in PAA. This analysis included 200 patients, divided into three groups: (1) healthy patients undergoing major outpatient surgery (n = 56), (2) patients with non-surgical abdominal pain (n = 52), and (3) patients with a confirmed diagnosis of PAA (n = 92). Patients in group 3 were divided into complicated and uncomplicated PAA. In all patients, a serum sample was obtained during recruitment, and LRG-1 concentration was determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Comparative statistical analyses were performed using the Mann–Whitney U, Kruskal–Wallis, and Fisher’s exact tests. The area under the receiver operating characteristic curves (AUC) was calculated for all pertinent analyses. Results: Serum LRG-1 values, expressed as median (interquartile range) were 23,145 (18,246–27,453) ng/mL in group 1, 27,655 (21,151–38,795) ng/mL in group 2 and 40,409 (32,631–53,655) ng/mL in group 3 (p < 0.0001). Concerning the type of appendicitis, the serum LRG-1 values obtained were 38,686 (31,804–48,816) ng/mL in the uncomplicated PAA group and 51,857 (34,013–64,202) ng/mL in the complicated PAA group (p = 0.02). The area under the curve (AUC) obtained (group 2 vs. 3) was 0.75 (95% CI 0.67–0.84). For the discrimination between complicated and uncomplicated PAA, the AUC obtained was 0.66 (95% CI 0.52–0.79). Conclusions: This work establishes normative health ranges for serum LRG-1 values in the pediatric population and shows that serum LRG-1 could be a potentially helpful tool for diagnosing PAA in the future. Future prospective multicenter studies, with the parallel evaluation of urinary and salivary LRG-1, are necessary to assess the implementability of this molecule in actual clinical practice. Full article

(1) Background: Serum leucine-rich α2 glycoprotein (LRG) has been reported as a useful biomarker for monitoring disease activity in patients with inflammatory bowel disease (IBD). We investigated whether serum LRG can differentiate patients with normal colonic mucosa from those with IBD or other forms of colitis. (2) Methods: Patients with diarrhea, abdominal pain, or bloody stools were consecutively enrolled at their initial visit to our hospital. Serum LRG and C-reactive protein were measured, and a colonoscopy and histology were performed. (3) Results: We enrolled 317 patients (181 men, 136 women; median age: 51 years). Based on the endoscopic and histological criteria, 260 patients were diagnosed with ulcerative colitis (n = 134), Crohn’s disease (n = 10), infectious colitis (n = 43), diverticular colitis (n = 17), or nonspecific colitis (n = 56). The remaining 57 patients were diagnosed with normal colonic mucosa including histology. The latter group’s median LRG value (9.5 µg/mL, range: 5.8–13.5) was significantly lower than that of the other 260 patients (13.6 µg/mL, range: 6.8–62.7, p < 0.0001). The optimal LRG cut-off value of <10.4 µg/mL was derived from the receiver operating characteristic (ROC) curve, showing a 91% sensitivity and 77% specificity for identifying patients with normal colonic mucosa. (4) Conclusions: serum LRG values < 10.4 µg/mL could be a useful biomarker for predicting patients with normal colonic mucosa. Full article

Background: Joint pain has been recognized as one of the major causes of limitations in mobility, functional decline, and consequently declined quality of life in older adults. Hence, this study aimed to identify the predictors, protective factors, and adverse outcomes of joint pain in community-dwelling older adults. Methods: In this Long-term Research Grant Scheme—Towards Useful Ageing (LRGS-TUA) longitudinal study, a total of 1005 older participants aged 60 years and above who were successfully followed up after five years were included in the analysis. The participants self-reported their joint pain status at baseline and during the fifth year. Subsequently, the baseline characteristics were used to predict changes in joint pain status. Adverse outcomes related to joint pain were evaluated based on the participants’ joint pain statuses. Results: Results showed that being female, having diabetes mellitus, and higher body mass index were associated with the incidence of joint pain. Meanwhile, increased intake of pantothenic acid and higher levels of blood albumin levels were associated with recovery from joint pain. Participants with persistent joint pain at baseline and follow-up showed higher levels of depression and disability compared to individuals who never experience any joint pain. However, participants who had recovered from joint pain did not differ significantly from those without joint pain at baseline and follow-up in these measures. Conclusions: By identifying the modifiable risk factors, factors associated with recovery, and adverse outcomes related to joint pain, this study adds to current evidence that may contribute to further management strategies for joint pain in older adults. Full article