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Welding process, as one of the crucial industrial technologies in ship construction, accounts for approximately 70% of the workload and costs account for approximately 40% of the total cost. The existing welding quality prediction methods have hypothetical premises and subjective factors, which cannot meet the dynamic control requirements of intelligent welding for processing quality. Aiming at the low efficiency of quality prediction problems poor timeliness and unpredictability of quality control in ship assembly-welding process, a data and model driven welding quality prediction method is proposed. Firstly, the influence factors of welding quality are analyzed and the correlation mechanism between process parameters and quality is determined. According to the analysis results, a stable and reliable data collection architecture is established. The elements of welding process monitoring are also determined based on the feature dimensionality reduction method. To improve the accuracy of welding quality prediction, the prediction model is constructed by fusing the adaptive simulated annealing, the particle swarm optimization, and the back propagation neural network algorithms. Finally, the effectiveness of the prediction method is verified through 74 sets of plate welding experiments, the prediction accuracy reaches over 90%.

Networked cyber-physical systems are facing serious security threats from malicious attacks. It is noted that the networked cyber-physical system should take defense measures into account at the beginning of its construction. From the conservative defensive perspective, this paper proposes a robust optimal defense resource allocation strategy to reduce the maximum possible losses of the networked cyber-physical system caused by potential attacks. Then, based on the robust optimal allocation strategy, it can be proved that the topology of the networked cyber-physical system has a great influence on the loss function. In order to further improve security, the effects of adding redundant connections are investigated. Furthermore, by taking geographical knowledge into account, a hexagonal construction scheme is proposed for providing a geographically-feasible and economically-viable solution for building networked cyber-physical systems, where the loss function has a cubic decay.

Galectin-3 (Gal-3) has a long, aperiodic, and dynamic proline-rich N-terminal tail (NT). The functional role of the NT with its numerous prolines has remained enigmatic since its discovery. To provide some resolution to this puzzle, we individually mutated all 14 NT prolines over the first 68 residues and assessed their effects on various Gal-3–mediated functions. Our findings show that mutation of any single proline (especially P37A, P55A, P60A, P64A/H, and P67A) dramatically and differentially inhibits Gal-3–mediated cellular activities (i.e., cell migration, activation, endocytosis, and hemagglutination). For mechanistic insight, we investigated the role of prolines in mediating Gal-3 oligomerization, a fundamental process required for these cell activities. We showed that Gal-3 oligomerization triggered by binding to glycoproteins is a dynamic process analogous to liquid–liquid phase separation (LLPS). The composition of these heterooligomers is dependent on the concentration of Gal-3 as well as on the concentration and type of glycoprotein. LLPS-like Gal-3 oligomerization/condensation was also observed on the plasma membrane and disrupted endomembranes. Molecular- and cell-based assays indicate that glycan binding–triggered Gal-3 LLPS (or LLPS-like) is driven mainly by dynamic intermolecular interactions between the Gal-3 NT and the carbohydrate recognition domain (CRD) F-face, although NT–NT interactions appear to contribute to a lesser extent. Mutation of each proline within the NT differentially controls NT–CRD interactions, consequently affecting glycan binding, LLPS, and cellular activities. Our results unveil the role of proline polymorphisms (e.g., at P64) associated with many diseases and suggest that the function of glycosylated cell surface receptors is dynamically regulated by Gal-3.

Lethal encephalitis caused by rabies virus (RABV) in mammals is known to be associated with the production of several pro-inflammatory cytokines, but the mechanism of such induction remains unclear. In this study, we establish that the laboratory strain CVS-11 infects astrocytes which are the most abundant glial cell population and the dominant source of inflammatory factors in the central nervous system (CNS). A screen identifies the E3 ubiquitin ligase FBXL18 as a critical factor responsible for RABV-induced inflammation. Mechanistically, infection by RABV upregulates FBXL18, which induces K11-type ubiquitination of BST2 on Lys 109 and Lys 110 , two residues that are also ubiquitinated for degradation via K33-type ubiquitination by a yet unknown E3 ligase. FBXL18-mediated ubiquitination stabilizes BST2, leading to hyperphosphorylation of IκBα and excessive NF-κB activation. Knockdown of FBXL18 effectively inhibits IL-6 production and RABV replication in astrocytes and neurons, thereby mitigating the virulence of RABV in mice. Our findings suggest that targeting FBXL18 is a potentially effective strategy for rabies treatment. RABV upregulates FBXL18, which stabilizes BST2 via K11-linked ubiquitination at Lys109/110, thereby activating NF-κB. FBXL18 knockdown effectively suppresses inflammation and virulence, highlighting its potential as a therapeutic target for rabies.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. However, acquired resistance of cancer cells to TRAIL is a roadblock. Agents that can either potentiate the effect of TRAIL or overcome resistance to TRAIL are urgently needed. This article reports that ginsenoside compound K (CK) potentiates TRAIL-induced apoptosis in HCT116 colon cancer cells and sensitizes TRAIL-resistant colon cancer HT-29 cells to TRAIL. On a cellular mechanistic level, CK downregulated cell survival proteins including Mcl-1, Bcl-2, surviving, X-linked inhibitor of apoptosis protein and Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein, upregulated cell pro-apoptotic proteins including Bax, tBid and cytochrome c, and induced the cell surface expression of TRAIL death receptor DR5. Reduction of DR5 levels by siRNAs significantly decreases CK- and TRAIL-mediated apoptosis. Importantly, our results indicate, for the first time, that DR5 upregulation is mediated by autophagy, as blockade of CK-induced autophagy by 3-MA, LY294002 or Atg7 siRNAs substantially decreases DR5 upregulation and reduces the synergistic effect. Furthermore, CK-stimulated autophagy is mediated by the reactive oxygen species–c-Jun NH2-terminal kinase pathway. Moreover, we found that p53 and the C/EBP homologous (CHOP) protein is also required for DR5 upregulation but not related with autophagy. Our findings contribute significantly to the understanding of the mechanism accounted for the synergistic anticancer activity of CK and TRAIL, and showed a novel mechanism related with DR5 upregulation.

Polysaccharides from Pleurotus eryngii exhibit a variety of biological activities. Here, we obtained a homogeneous branched β-1,6-glucan (APEP-A-b) from the fruiting bodies of P. eryngii and investigated its effect on immunity and gut microbiota. Our results showed that APEP-A-b significantly increases splenic lymphocyte proliferation, NK cell activity and phagocytic capacity of peritoneal cavity phagocytes. Furthermore, we found that the proportion of CD4 + and CD8 + T cells in lamina propria are significantly increased upon APEP-A-b treatment. Additionally, APEP-A-b supplementation demonstrated pronounced changes in microbiota reflected in promotion of relative abundances of species in the Lachnospiraceae and Rikenellaceae families. Consistently, APEP-A-b significantly increased the concentration of acetic and butyric acid in cecum contents. Overall, our results suggest that β-1,6-glucan from P. eryngii might enhance immunity by modulating microbiota. These results are important for the processing and product development of P. eryngii derived polysaccharides.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. Here, we report that gefitinib and TRAIL in combination produce a potent synergistic effect on TRAIL-sensitive human colon cancer HCT116 cells and an additive effect on TRAIL-resistant HT-29 cells. Interestingly, gefitinib increases the expression of cell surface receptors DR4 and DR5, possibly explaining the synergistic effect. Knockdown of DR4 and DR5 by siRNA significantly decreases gefitinib- and TRAIL-mediated cell apoptosis, supporting this idea. Because the inhibition of gefitinib-induced autophagy by 3-MA significantly decreases DR4 and DR5 upregulation, as well as reduces gefitinib- and TRAIL-induced apoptosis, we conclude that death receptor upregulation is autophagy mediated. Furthermore, our results indicate that death receptor expression may also be regulated by JNK activation, because pre-treatment of cells with JNK inhibitor SP600125 significantly decreases gefitinib-induced death receptor upregulation. Interestingly, SP600125 also inhibits the expression CHOP, yet CHOP has no impact on death receptor expressions. We also find here that phosphorylation of Akt and ERK might also be required for TRAIL sensitization. In summary, our results indicate that gefitinib effectively enhances TRAIL-induced apoptosis, likely via autophagy and JNK- mediated death receptor expression and phosphorylation of Akt and ERK.

An alkali-soluble β-glucan (AHEP-A-b, 20 kDa) purified from Hericium erinaceus fruiting bodies, was structurally characterized and examined for antioxidant activity. Methylation analysis and NMR spectroscopy show that the backbone of AHEP-A-b is composed of (1→6)-linked-D-β-glucopyran residues, branched at O-3 of glucopyranose (Glcp) residues with [→3)-β-D-Glcp-(1→] oligosaccharides or single unit of β-Glcp. Periodate oxidation analysis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) indicate that the degree of polymerization (DP) of [→3)-β-D-Glcp-(1→] side chains is 2 to 8. Functionally, AHEP-A-b is a relatively strong antioxidant as demonstrated by using 2, 2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radical (ABTS·+), 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and hydroxyl radicals scavenging assays. The present study lays the foundation for further studies into structure-activity relationships of polysaccharides from H. erinaceus.

Monosialotetrahexosylganglioside (GM1) has good activity on brain diseases and was developed to be a drug applied in clinics for neurological disorders and nerve injury. It is difficult to isolate GM1 in industry scale from the brains directly. In this work, a simple and highly efficient method with high yield was developed for the isolation, conversion, and purification of GM1 from a pig brain. Gangliosides (GLS) were first extracted by supercritical CO2 (SCE). The optimum extraction time of GLS by SCE was 4 h, and the ratio of entrainer to acetone powder from the pig brain was 3:1 (v/w). GM1 was then prepared from GLS by immobilized sialidase and purified by reverse-phase silica gel. Sodium alginate embedding was used for the immobilization of sialidase. Under the optimized method, the yield of high-purity GM1 was around 0.056%. This method has the potential to be applied in the production of GM1 in the industry.

PurposeIncreased ethanol accumulation during ethanol fermentation generates stress in yeast cells, which finally reduces the fermentation performance and efficiency. Trehalose, a potential stress protectant, has been reported to regulate the response of yeast to diverse environmental stresses. This study aimed to explore how exogenous trehalose application affects the survival, transcriptome and antioxidant enzymes of Wickerhamomyces anomalus grown under ethanol stress conditions.Design/methodology/approachExogenous trehalose was applied to the growth condition of W. anomalus, and optical densitometric method was used to detect contents of intracellular trehalose and MDA and activities of CAT and SOD. The survival was evaluated using spot analysis. Differentially expressed genes (DEGs) were identified through transcriptomics analysis.FindingsThe results showed that ethanol stress induced the accumulation of intracellular trehalose, with further exogenous trehalose application improving the survival and alleviating oxidative stress in ethanol-stressed W. anomalus. Transcriptomic results showed that trehalose has pleiotropic regulating effects on ethanol-stressed W. anomalus since most DEGs annotated to energy metabolism, amino acid metabolism, translation, folding, sorting and transport were affected post trehalose addition. Therefore, it is found that trehalose protected W. anomalus against ethanol stress, and these findings provide interesting insights into the mechanistic role of trehalose in improving ethanol stress tolerance of W. anomalus.Originality/value(1) Protective effect of exogenous trehalose addition on the survival of ethanol-stressed W. anomalus was proved. (2) Exogenous trehalose addition could partly alleviate oxidative stress induced by ethanol stress and affect transcriptome in W. anomalus.