A Multi-Service Composition Model for Tasks in Cloud Manufacturing Based on VS-ABC Algorithm

This study analyzes the impact of Industry 4.0 and SARS-CoV-2 on the manufacturing industry, in which manufacturing entities are faced with insufficient resources and uncertain services; however, the current study does not fit this situation well. A multi-service composition for complex manufacturing tasks in a cloud manufacturing environment is proposed to improve the utilization of manufacturing service resources. Combining execution time, cost, energy consumption, service reliability and availability, a quality of service (QoS) model is constructed as the evaluation standard. A hybrid search algorithm (VS–ABC algorithm) based on the vortex search algorithm (VS) and the artificial bee colony algorithm (ABC) is introduced and combines the advantages of the two algorithms in search range and calculation speed. We take the customization production of automobiles as an example, and the case study shows that the VS–ABC algorithm has better applicability compared with traditional vortex search and artificial bee colony algorithms

Testosterone does not mediate the correlation between dietary inflammation and serum klotho levels among males: insights from NHANES database

IntroductionSerum Klotho (S-Klotho) is a transmembrane protein holds pivotal roles in anti-aging. The Dietary Inflammation Index (DII), a meticulously dietary tool, quantifies the inflammatory potential of an individual's diet. The existing research strongly suggests that a low DII diet plays a significant role in delaying aging and reducing aging-related symptoms in males. Testosterone could potentially act as a mediating intermediary between DII and S-Klotho. However, this aspect remains unexplored. This study aims to investigate the potential causal link of testosterone between DII and S-Klotho in males.MethodsWe utilized data from National Health and Nutrition Examination Survey (NHANES) which focused on male participants from 2013-2016. Mediation analyses were used to investigate the effects of testosterone (TT), free testosterone (FT), and free androgen index (FAI) on the DII-S-Klotho relationship, using three modes adjusting for covariates.ResultsMediation analysis unveiled a significant inverse correlation between DII and S-Klotho levels (model 1: c = -14.78, p = 0.046). The interaction between DII and S-Klotho was modulated by TT in model 1 (ab = -1.36; 95% CI: -5.59, -0.55; p = 0.008), but lost significance after adjustments (model 2: ab = -0.39; 95% CI: -4.15, 1.66; p = 0.378; model 3: ab = -0.59; 95% CI: -4.08, 2.15; p = 0.442). For FT, the mediating impact was not statistically significant (model 1: ab = 0.43; 95% CI: -0.51, 5.44; p = 0.188; model 2: ab = 0.72; 95% CI: -0.26, 5.91; p = 0.136; model 3: ab = 0.84; 95% CI: -0.02, 8.06; p = 0.056). Conversely, FAI consistently influenced the DII-S-Klotho relationship (model 1: ab = 2.39; 95% CI: 0.69, 9.42; p = 0.002), maintaining significance after adjustments (model 2: ab = 3.2; 95% CI: 0.98, 11.72; p = 0.004; model 3: ab = 3.15; 95% CI: 0.89, 14.51; p = 0.026).DiscussionThis study observed no mediating influence of TT or FT on the correlation between DII and S-Klotho after covariate control. Remarkably, FAI continued to significantly mediate the DII-S-Klotho connection even following covariate adjustment, although its significance in males warrants careful consideration

Myeloid DLL4 Does Not Contribute to the Pathogenesis of Non-Alcoholic Steatohepatitis in Ldlr-/- Mice.

Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH) and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4) attenuates atherosclerosis by altering the macrophage-mediated inflammatory response. However, the specific contribution of macrophage DLL4 to hepatic inflammation is currently unknown. We hypothesized that myeloid DLL4 deficiency in low-density lipoprotein receptor knock-out (Ldlr-/-) mice reduces hepatic inflammation. Irradiated Ldlr-/- mice were transplanted (tp) with bone marrow from wild type (Wt) or DLL4f/fLysMCre+/0 (DLL4del) mice and fed either chow or high fat, high cholesterol (HFC) diet for 11 weeks. Additionally, gene expression was assessed in bone marrow-derived macrophages (BMDM) of DLL4f/fLysMCreWT and DLL4f/fLysMCre+/0 mice. In contrast to our hypothesis, inflammation was not decreased in HFC-fed DLL4del-transplanted mice. In line, in vitro, there was no difference in the expression of inflammatory genes between DLL4-deficient and wildtype bone marrow-derived macrophages. These results suggest that myeloid DLL4 deficiency does not contribute to hepatic inflammation in vivo. Since, macrophage-DLL4 expression in our model was not completely suppressed, it can't be totally excluded that complete DLL4 deletion in macrophages might lead to different results. Nevertheless, the contribution of non-myeloid Kupffer cells to notch signaling with regard to the pathogenesis of steatohepatitis is unknown and as such it is possible that, DLL4 on Kupffer cells promote the pathogenesis of steatohepatitis

Association between Geriatric Nutritional Risk Index and Depression after Ischemic Stroke

Background: Malnutrition is associated with poor outcomes after stroke. However, the association between malnutrition and post-stroke depression (PSD) remains unelucidated. We aimed to explore the association between geriatric nutritional risk index (GNRI) and depression after ischemic stroke. Methods: In total, 344 patients with ischemic stroke were included in this analysis. The GNRI was calculated from serum albumin level, weight, and height at admission. Malnutrition was defined using the GNRI cutoff points. A lower GNRI score indicates an elevated nutritional risk. The outcome was depression, measured 14 days after ischemic stroke. Logistic regression models were used to estimate the association between the GNRI and risk of PSD. Results: A total of 22.9% developed PSD 14 days after stroke. The mean GNRI was 99.3 ± 6.0, and 53.8% of the patients had malnutrition. After adjusting for covariates, baseline malnutrition was not associated with risk of PSD (OR, 0.670; 95%CI, 0.370–1.213; p = 0.186). The restricted cubic splines revealed a U-shaped association between the GNRI and PSD. Compared to moderate GNRI, higher GNRI (OR, 2.368; 95%CI, 0.983–5.701; p = 0.085) or lower GNRI (OR, 2.226; 95%CI, 0.890–5.563; p = 0.087) did not significantly increase the risk of PSD. Conclusion: A low GNRI was not associated with an increased risk of depression after ischemic stroke

A Multi-Service Composition Model for Tasks in Cloud Manufacturing Based on VS–ABC Algorithm

This study analyzes the impact of Industry 4.0 and SARS-CoV-2 on the manufacturing industry, in which manufacturing entities are faced with insufficient resources and uncertain services; however, the current study does not fit this situation well. A multi-service composition for complex manufacturing tasks in a cloud manufacturing environment is proposed to improve the utilization of manufacturing service resources. Combining execution time, cost, energy consumption, service reliability and availability, a quality of service (QoS) model is constructed as the evaluation standard. A hybrid search algorithm (VS–ABC algorithm) based on the vortex search algorithm (VS) and the artificial bee colony algorithm (ABC) is introduced and combines the advantages of the two algorithms in search range and calculation speed. We take the customization production of automobiles as an example, and the case study shows that the VS–ABC algorithm has better applicability compared with traditional vortex search and artificial bee colony algorithms

Research advance and clinical implication of circZNF609 in human diseases

AbstractCircular ribonucleic acids (circRNAs) are single-stranded RNAs with covalently closed-loop structures that lack terminal 5′ caps and 3′ poly-(A) tails. Recent evidence confirmed that some circRNAs can be translated into proteins. More importantly, there is a growing body of evidence that dysregulation of circRNAs is closely associated with the development of human diseases, especially malignant tumors. CircZNF609 is a novel circular RNA with an open reading frame and an internal ribosomal entry site that can interact with microRNAs and mRNAs and be translated into proteins. Studies have shown that circZNF609 is abnormally expressed in various human diseases, especially malignant tumors such as hepatocellular carcinoma, nasopharyngeal carcinoma, colorectal cancer and glioma, which lead to the occurrence and development of diseases. This article attempts to provide a comprehensive overview of the structural properties of circZNF609 discovered so far and focuses on the pathogenesis of circZNF609 in human diseases and its potential clinical application value. Finally, we elaborate on the directions of future investigations of this molecule

METTL3-Mediated m6A Methylation Regulates Muscle Stem Cells and Muscle Regeneration by Notch Signaling Pathway

The Pax7+ muscle stem cells (MuSCs) are essential for skeletal muscle homeostasis and muscle regeneration upon injury, while the molecular mechanisms underlying muscle stem cell fate determination and muscle regeneration are still not fully understood. N6-methyladenosine (m6A) RNA modification is catalyzed by METTL3 and plays important functions in posttranscriptional gene expression regulation and various biological processes. Here, we generated muscle stem cell-specific METTL3 conditional knockout mouse model and revealed that METTL3 knockout in muscle stem cells significantly inhibits the proliferation of muscle stem cells and blocks the muscle regeneration after injury. Moreover, knockin of METTL3 in muscle stem cells promotes the muscle stem cell proliferation and muscle regeneration in vivo. Mechanistically, METTL3-m6A-YTHDF1 axis regulates the mRNA translation of Notch signaling pathway. Our data demonstrated the important in vivo physiological function of METTL3-mediated m6A modification in muscle stem cells and muscle regeneration, providing molecular basis for the therapy of stem cell-related muscle diseases

Identification of anti-ErbB2 dual variable domain immunoglobulin (DVD-Ig™) proteins with unique activities.

Inhibiting ErbB2 signaling with monoclonal antibodies (mAbs) or small molecules is an established therapeutic strategy in oncology. We have developed anti-ErbB2 Dual Variable Domain Immunoglobulin (DVD-Ig) proteins that capture the function of a combination of two anti-ErbB2 antibodies. In addition, some of the anti-ErbB2 DVD-Ig proteins gain the new functions of enhancing ErbB2 signaling and cell proliferation in N87 cells. We further found that two DVD-Ig proteins, DVD687 and DVD688, have two distinct mechanisms of actions in Calu-3 and N87 cells. DVD687 enhances cell cycle progression while DVD688 induces apoptosis in N87 cells. Using a half DVD687, we found that avidity may play a key role in the agonist activity of DVD687 in N87 cells

DVD687 and DVD688 show different mechanism of actions (MOAs).

<p>Apoptosis assay was used to analyze (A) N87 or (C) Calu-3 cells after DVD-Ig proteins, mAbs, or combination treatment. BrdU-incorporation assay was used to analyze (B) N87 or (D) Calu-3 cells after DVD-Ig proteins, mAbs, or combination treatment. Three independent experiments with triplicates were performed. One representative experiment is shown here. The error bars indicate standard deviation from the mean. p value was calculated via student T-test.</p

NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer

Summary: Aberrant RNA modifications are frequently associated with cancers, while the underlying mechanisms and clinical significance remain poorly understood. Here, we find that the ac4C RNA acetyltransferase NAT10 is significantly upregulated in esophageal cancers (ESCAs) and associated with poor ESCA prognosis. In addition, using ESCA cell lines and mouse models, we confirm the critical functions of NAT10 in promoting ESCA tumorigenesis and progression in vitro and in vivo. Mechanistically, NAT10 depletion reduces the abundance of ac4C-modified tRNAs and decreases the translation efficiencies of mRNAs enriched for ac4C-modified tRNA-decoded codons. We further identify EGFR as a key downstream target that facilitates NAT10’s oncogenic functions. In terms of clinical significance, we demonstrate that NAT10 depletion and gefitinib treatment synergistically inhibit ESCA progression in vitro and in vivo. Our data indicate the mechanisms underlying ESCA progression at the layer of mRNA translation control and provide molecular insights for the development of effective cancer therapeutic strategies