An online monitoring method of milling cutter wear condition driven by digital twin.

Real-time online tracking of tool wear is an indispensable element in automated machining, and tool wear directly impacts the processing quality of workpieces and overall productivity. For the milling tool wear state is difficult to real-time visualization monitoring and individual tool wear prediction model deviation is large and is not stable and so on, a digital twin-driven ensemble learning milling tool wear online monitoring novel method is proposed in this paper. Firstly, a digital twin-based milling tool wear monitoring system is built and the system model structure is clarified. Secondly, through the digital twin (DT) data multi-level processing system to optimize the signal characteristic data, combined with the ensemble learning model to predict the milling cutter wear status and wear values in real-time, the two will be verified with each other to enhance the prediction accuracy of the system. Finally, taking the milling wear experiment as an application case, the outcomes display that the predictive precision of the monitoring method is more than 96% and the prediction time is below 0.1 s, which verifies the effectiveness of the presented method, and provides a novel idea and a new approach for real-time on-line tracking of milling cutter wear in intelligent manufacturing process.

Human leukocyte antigen-G 14 bp insertion/deletion polymorphism contributes to preeclampsia risk in Asian population: A systematic review and meta­analysis.

Preeclampsia remains enigmatic and responsible for vast maternal and fetal morbidity and mortality worldwide. Our objective was to assess the strength of the effect of the 14 bp deletion/insertion polymorphism in exon 8 of the 3'UTR region of the human leukocyte antigen-G (HLA-G) gene on preeclampsia risk across different populations. A systematic review by a meta-analysis was performed to summarize the scattered epidemiologic evidence, which remains inconclusive and controversial. A systematic literature search according to the PRISMA guidelines was conducted to screen relevant publications. Odds ratio and corresponding 95% confidence interval were estimated to measure the magnitude of the association between this polymorphism and preeclampsia onset. Thirty studies comprising 9402 subjects were eligible. Pooled estimates suggested that both fetal and paternal insertion variants were significantly associated with increased odds of this disease. Nevertheless, the presence of the 14 bp insertion sequence in mothers does not seem to increase the risk of preeclampsia. Moreover, the results of subgroup analysis suggested that the fetal, maternal, and paternal polymorphism has a significant deleterious impact on the preeclampsia risk in the Asian population. In addition, the significant association between the paternal polymorphism and preeclampsia in primigravida was observed in the pooled estimation with a small sample size. By summarizing the amount of significant evidence, our study nominated this polymorphism as a potential biomarker for early risk stratification for Asians. Further large-scale validation is needed to establish fully solid and conclusive evidence for the impact of the insertion polymorphism on preeclampsia risk.

The forkhead box protein P3 gene rs3761548 promoter polymorphism confers a genetic contribution to the risk of preeclampsia: A systematic review and meta-analysis.

Various studies have investigated the risk of preeclampsia with the forkhead box protein P3 (FOXP3) gene rs2232365 and rs3761548 polymorphisms. However, the results remained contradictory. A comprehensive literature search was conducted using the Cochrane Library, PubMed, and Web of Science (up to Oct 11, 2021). Meta-analysis was carried out in the R language environment for statistical computing and graphics. A fixed-effect or random-effects model was used according to the statistical significance of heterogeneity among included studies. The pooled odds ratios and corresponding 95% confidence intervals were calculated to estimate the strength of the effect. For the rs2232365 polymorphism, statistical significance was detected neither in the overall population nor among the East Asian and West Asian subgroups. However, for rs3761548, the summarized statistics revealed a significant association between the C allele carriage and preeclampsia risk in the homozygote, heterozygote, and dominant models. The further stratified analysis found this effect might be specific to West-South Asian ethnic subgroups. To sum up, this meta-analysis showed that the FOXP3 rs3761548 polymorphism was significantly associated with preeclampsia susceptibility, and it had a deleterious effect especially in the West-South Asian population. In contrast, rs2232365 may serve as neither a protective nor a risk factor for preeclampsia onset.

Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity.

Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons. However, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behaviour tests, we studied the effects of Nmb on the sensory neuronal excitability and peripheral pain sensitivity mediated by Cav3.2 T-type channels. Results: Nmb reversibly and concentration-dependently increased T-type channel currents (IT) in small-sized trigeminal ganglion (TG) neurons through the activation of neuromedin B receptor (NmbR). This NmbR-mediated IT response was Gq protein-coupled, but independent of protein kinase C activity. Either intracellular application of the QEHA peptide or shRNA-mediated knockdown of Gß abolished the NmbR-induced IT response. Inhibition of protein kinase A (PKA) or AMP-activated protein kinase (AMPK) completely abolished the Nmb-induced IT response. Analysis of phospho-AMPK (p-AMPK) revealed that Nmb significantly activated AMPK, while AMPK inhibition prevented the Nmb-induced increase in PKA activity. In a heterologous expression system, activation of NmbR significantly enhanced the Cav3.2 channel currents, while the Cav3.1 and Cav3.3 channel currents remained unaffected. Nmb induced TG neuronal hyperexcitability and concomitantly induced mechanical and thermal hypersensitivity, both of which were attenuated by T-type channel blockade. Moreover, blockade of NmbR signalling prevented mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain, and this effect was attenuated by siRNA knockdown of Cav3.2. Conclusions: Our study reveals a novel mechanism by which NmbR stimulates Cav3.2 channels through a Gßγ-dependent AMPK/PKA pathway. In mouse models, this mechanism appears to drive the hyperexcitability of TG neurons and induce pain hypersensitivity.

Dual role of B7-H6 as a novel prognostic marker in hepatocellular carcinoma.

B7 homolog 6 (B7-H6), a new member of the B7 family, is identified as an activating ligand for cytotoxicity triggering receptor 3 (NKp30) expressing on natural killer cells. The purpose of this study was to investigate the clinical significance of B7-H6 in hepatocellular carcinoma (HCC). We evaluated B7-H6 expression by immunohistochemistry in a cohort of 90 HCC tumors with clinical follow-up, the potential relationship between the B7-H6 expression and the clinicopathological characteristics of HCC patients was also analyzed. Stable B7-H6 knockdown in hepatoma cell line was established to explore the function and mechanism of B7-H6 in HCC. This study showed that high expression of B7-H6 was significantly associated with smaller tumor size, single tumor number in HCC, but no significant association was found between B7-H6 overexpression and other clinicopathological parameters. Moreover, Kaplan-Meier survival analysis showed that high expression of B7-H6 was significantly correlated with better survival of HCC patients. Knockdown of B7-H6 inhibited tumor cell proliferation and induced cell apoptosis. However, it also impaired the sensitivity of tumor cells to NK-mediated lysis together with significantly decreased degranulation and IFN-γ release of NK cells. These results indicated that B7-H6 has a dual role in HCC. It could be an independent indicator for better survival of HCC and maybe a potential target for future cancer treatment.

Cross-Cultural Adaptation and Psychometric Evaluation of the Community Healthy Activities Model Program for Seniors Physical Activity Questionnaire in Chinese Older Adults.

The study's aims were to translate the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire to Chinese and examine its psychometric properties. Adapting it for use in China involved forward translation, synthesis, back translation, expert review, and pretesting. A convenience sample of 201 Chinese older adults completed the Chinese version (CHAMPS-C) to evaluate its construct validity index and associations with physiological, psychosocial, and energy expenditure measures. The construct validity index of the CHAMPS-C was 0.95, and it had fair to moderate associations with physiological and psychosocial measures, other scales of physical activity, and accelerometer measurements. Our structured, stepwise process of cross-cultural adaptation produced a scale (i.e., CHAMPS-C), with items equivalent in meaning to the English version, for use with Chinese older adults. The findings of this study indicate that the CHAMPS-C has acceptable reliability and validity to assess the physical activity of older Chinese adults.

Implications of soluble E-cadherin level of antiviral treatment in patients with chronic hepatitis C virus infection.

BACKGROUND AND AIMS: Soluble E-cadherin (sE-cadherin) has been observed elevated in patients with various diseases, and implicated in the occurrence and development of those diseases. The implications of sE-cadherin in chronic hepatitis C virus (HCV) infection are still unclear. The purpose of this study is to explore the significance of sE-cadherin in chronic hepatitis C infection and the correlation with treatment response. METHODS: 87 chronic HCV infected patients and 60 healthy subjects were enrolled in this study. Blood samples from patients receiving the combined treatment of pegylated interferon-a (Peg-IFN-α) with ribavirin (RBV) were collected before treatment, during 4th, 12th therapy weeks, end of the treatment, and 24 weeks post-therapy. Plasma sE-cadherin level was detected by enzyme-linked immunosorbent assay (ELISA) and the relationship between sE-cadherin and antiviral treatment outcome was analyzed. RESULTS: Plasma sE-cadherin concentrations of Chronic HCV infected patients were significantly higher than that of healthy controls. A strong correlation between sE-cadherin level and the HCV viral load, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and also glutamyl transpeptidase (GGT) level was detected. Chronic HCV infected patients achieving rapid virological response (RVR) and sustained virological response (SVR) had lower baseline sE-cadherin concentrations compared with the non-RVR and non-SVR groups respectively. Univariate and multivariate regression analyses suggested that baseline plasma sE-cadherin level was predictive of therapeutic effect in patients with chronic HCV infection. CONCLUSION: Baseline sE-cadherin level could be considered as an independent predictor of SVR with Peg-IFN-α plus ribavirin therapy in the Chinese Han population chronic HCV infection patients. Effective antiviral therapy might restore sE-cadherin at physiological levels.

Specific matrix metalloproteinases and calcification factors are associated with the vulnerability of human carotid plaque.

The rupture of atherosclerotic plaque provokes the majority of acute cerebrovascular events. Studies have demonstrated that various matrix metalloproteinases (MMPs) may promote atherosclerotic plaque progression and rupture. However, results have been incongruous and the mechanisms of this remain obscured. Therefore, in the current study, carotid plaques were characterized by assessing the levels of MMPs and calcification factors, and evaluating their association with plaque vulnerability. Human carotid plaques were obtained from carotid endarterectomies, and classified into stable and vulnerable groups by ultrasonography and histological analyses. The mRNA and protein levels of MMPs, vascular endothelial growth factor (VEGF), bone sialoprotein 2 (BSP) and osteopontin were investigated by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Immunohistochemistry was used to localize MMP-2 and MMP-14 in stable and vulnerable plaques. The activation of various associated signaling pathways was also investigated using western blotting. The mRNA levels of MMP-2, -7, -9 and -14 were elevated in vulnerable plaques, among which expression of MMP-2 and -14 were the highest. Consistent with the mRNA levels, the protein levels of MMP-2 and -14 were also elevated. Immunohistochemistry also demonstrated positive staining of MMP-2 and MMP-14 in vulnerable plaques. Factors that indicate neovascularization and calcification, including VEGF and BSP, were concurrently elevated in vulnerable plaques. In addition, the protein levels of extracellular regulated kinase (ERK) and protein kinase C (PKC) were upregulated in vulnerable plaques. The current study provides novel insights into the MMP profiles of vulnerability plaques, and may assist in the development of novel methods for the diagnosis of plaque vulnerability and the prevention of plaque rupture.

Correction: Nur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFα secretion and lowering CSF-1R expression.

[This corrects the article DOI: 10.1371/journal.pone.0171347.].

Nur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFα secretion and lowering CSF-1R expression.

Nur77, an orphan member of the nuclear receptor superfamily, plays critical roles in inflammation and immunity. However, the role of Nur77 in tumor microenvironment remains elusive. Results showed that deletion of Nur77 strikingly enhanced tumor metastasis compared to WT mice. Additionally, compared to the conditioned media derived from Nur77+/+ peritoneal macrophages (CM1), the conditioned media derived from Nur77-/- peritoneal macrophages (CM2) significantly promoted the EMT of cancer cells, and greatly enhanced the migratory and invasive abilities of cancer cells. Moreover, studies using TNF-α blocking antibody demonstrated that pro-inflammatory cytokine TNF-α was indispensable in supporting CM2-induced EMT to drive cancer cells migration and invasion. Furthermore, we found that Nur77 promoted the expression of CSF-1R, a novel downstream target gene of Nur77, and subsequently enhanced the migration of inflammatory cells. Notably, infiltration of inflammatory cells in the tumors of Nur77-/- mice was markedly abrogated compared to Nur77+/+ mice. Collectively, these results revealed that host Nur77 expression was pivotal in antitumor immune response, and in inhibiting tumor metastasis.

Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4.

The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-ß (TGF-ß). Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro.