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In this research, two distinct designs of protective structures were developed to address structural damage caused by ships impacting the internal structures of floating docks during maintenance operations. The designed protective structures consist of support sections and load-bearing sections, with the load-bearing section comprising three frame sections. For ease of description, the front frame section, middle frame section, and rear frame section are referred to as Frame A, Frame B, and Frame C, respectively. A drop-weight test was conducted with a stern-shaped indenter impacting the structures at 3.89 m/s. This study also assessed varying impact speeds and positions. The results showed that Specimen 2 had localized indentations on Frame B, while Specimen 1 exhibited overall deformation of Frame B and additional deformations in Frame A. The simulations agreed with the experimental results, confirming the model’s accuracy. At speeds from 2.34 m/s to 5.45 m/s, Specimen 2 consistently showed localized deformations, while Specimen 1 showed comprehensive deformation of Frame B at 3.89 m/s due to lower rigidity. When the indenter impacted the specimens at different locations with a speed of 5.45 m/s, the two specimens exhibited varying degrees of damage. As the impact location shifted from the central area to the end, the maximum indentation depth of Specimen 1 decreased from 52.26 mm to 41.71 mm, while that of Specimen 2 decreased from 43.26 mm to 38.50 mm. The reduction in indentation depth and extent as the impact location approached the support frame can be attributed to the increasing involvement of the web plate beneath the frame in resisting the impact. Additionally, compared to Specimen 1, Specimen 2 exhibited a relatively smaller overall indentation depth, and the impact of location variation on indentation depth was also relatively minor.

Within the lifecycle of a ship’s hull structure, damage due to collisions has been a focal point of research for researchers both domestically and internationally. To enhance the predictive accuracy of failure criteria in the simulation of ship hull collisions, this paper focuses on the modified Mohr–Coulomb (MMC) failure criterion for metals, utilizing a hybrid experimental–numerical method for parameter calibration. Consideration of stress-state-dependent mesh size sensitivity has been amended, and the approach is integrated into the comprehensive nonlinear finite element software Abaqus 2020. Finite element tensile simulations were conducted to validate the effectiveness of the MMC criterion. Simulation analyses were conducted based on drop hammer collision experiments with various failure criteria and grid sizes. The comparative validation highlighted the superiority of the mesh size sensitivity-corrected MMC failure criterion. The outcomes of this research provide a foundation for assessing the structural safety of ship hulls.

Abstract Background Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. Materials and methods The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. Results A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aβ-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. Conclusion The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.

In 2021, twenty children exhibiting influenza-like illnesses were reported from a kindergarten in Shandong Province, China. Eleven genomes of Coxsackievirus A4 (CV-A4) were obtained from the pediatric cases, sharing

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1β, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

Abstract Background Metastasis was the major cause of the high mortality in ovarian cancer. Although some mechanisms of metastasis in ovarian cancer were proposed, few have been targeted in the clinical practice. In the study, we aimed to identify novel genes contributing to metastasis and poor clinical outcome in ovarian cancer from bioinformatics databases. Methods Studies collecting matched primary tumors and metastases from ovarian cancer patients were searched in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by software R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the DEGs were implemented by Metascape. Venn diagram was plotted to present overlapping DEGs. The associations between the overlapping DEGs and prognosis were tested by Cox proportional hazard regression model using a cohort of ovarian cancer patients from the TCGA database. Genes affecting patients’ outcomes significantly were served as hub genes. The mechanisms of the hub genes in promoting ovarian cancer metastasis were then predicted by R software. Results Two gene expression profiles (GSE30587 and GSE73168) met the inclusion criteria and were finally analyzed. A total of 259 genes were significantly differentially expressed in GSE30587, whereas 712 genes were in GSE73168. In GSE30587, DEGs were mainly involved in extracellular matrix (ECM) organization; For GSE73168, most of DEGs showed ion trans-membrane transport activity. There were 9 overlapping genes between the two datasets (RUNX2, FABP4, CLDN20, SVEP1, FAM169A, PGM5, ZFHX4, DCN and TAS2R50). ZFHX4 was proved to be an independent adverse prognostic factor for ovarian cancer patients (HR = 1.44, 95%CI: 1.13–1.83, p = 0.003). Mechanistically, ZFHX4 was positively significantly correlated with epithelial-mesenchymal transition (EMT) markers (r = 0.54, p = 2.59 × 10−29) and ECM-related genes (r = 0.52, p = 2.86 × 10−27). Conclusions ZFHX4 might promote metastasis in ovarian cancer by regulating EMT and reprogramming ECM. For clinical applications, ZFHX4 was expected to be a prognostic biomarker for ovarian cancer metastasis.

Abstract Background Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer’s disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. Methods The ameliorating effect of miR-22-3p on apoptosis of the Aβ-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. Results The miR-22-3p played an important role in ameliorating apoptosis in the Aβ-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aβ deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. Conclusion Our study showed that miR-22-3p could improve apoptosis and reduce Aβ deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.

Alzheimer’s disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the “amyloid cascade hypothesis” with the main focus of the pathological accretion of β-amyloid (Aβ) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aβ, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

As the number of offshore wind turbines continues to rise and their proximity to navigational routes decreases, the risk of collisions between passing vessels and wind turbines increases, thereby presenting serious threats to the safety of personnel and equipment. Given that collisions between floating wind turbines and vessels entail a complex interplay of wind, wave, and mooring loads, this study established a bidirectional fluid-structure coupling simulation methodology based on Star-CCM+ and ABAQUS. Under the combined influences of wind, wave, and mooring loads, the study investigated the dynamic response of floating wind turbines following bow and side impacts from vessels. Analyses were conducted on the structural damage and deformation of floating wind turbines, the transformation of energy during collision processes, and the resultant motion response of the turbines. A sensitivity analysis was performed on parameters such as collision speed, collision angle, wind speed, and wave height. The findings indicate that the amplitude of pitching and heaving motions of the turbine exceed those observed under conditions devoid of collision loads, with the amplitude of motion intensifying with an increase in these parameters. The turbine’s floating body absorbed a minimal amount of internal energy, leading to minor damage, with the stress generated predominantly localized in the collision area of the floating body. The impact of a side collision from vessels exerted a larger influence on the structural dynamic response of floating wind turbines. The analysis results indicate that even though the offshore wind turbine structure is not critically damaged by ship impact, the equipment inside may still fail to work due to the high value of acceleration induced by ship impact. The research outcomes can benefit the safety design of offshore wind turbines in engineering practice.

Abstract FKBP4 belongs to the family of immunophilins, which serve as a regulator for steroid receptor activity. Thus, FKBP4 has been recognized to play a critical role in several hormone-dependent cancers, including breast and prostate cancer. However, there is still no research to address the role of FKBP4 on lung adenocarcinoma (LUAD) progression. We found that FKBP4 expression was elevated in LUAD samples and predicted significantly shorter overall survival based on TCGA and our cohort of LUAD patients. Furthermore, FKBP4 robustly increased the proliferation, metastasis, and invasion of LUAD in vitro and vivo. Mechanistic studies revealed the interaction between FKBP4 and IKK kinase complex. We found that FKBP4 potentiated IKK kinase activity by interacting with Hsp90 and IKK subunits and promoting Hsp90/IKK association. Also, FKBP4 promotes the binding of IKKγ to IKKβ, which supported the facilitation role in IKK complex assembly. We further identified that FKBP4 TPR domains are essential for FKBP4/IKK interaction since its association with Hsp90 is required. In addition, FKBP4 PPIase domains are involved in FKBP4/IKKγ interaction. Interestingly, the association between FKBP4 and Hsp70/RelA favors the transport of RelA toward the nucleus. Collectively, FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to potentiate the transcriptional activity and nuclear translocation of NF-κB, thereby promoting LUAD progression. Our findings suggest that FKBP4 may function as a prognostic biomarker of LUAD and provide a newly mechanistic insight into modulating IKK/NF-κB signaling.

Investigating the loss of integrity (E) in cabin walls and decks, as well as the role of insulation capabilities, holds significant implications for preventing serious human, economic and environmental damage caused by the ignition of cabins in ships and ocean platforms due to fires and explosions. In this study, the fire resistance of A-60 class ship bulkheads and decks was evaluated through two groups of standard fire resistance tests. In the first test, the steel structure side of the bulkhead was exposed to the fire, while in the second test, the mineral wool and L-shaped stiffeners side of the deck was exposed to the fire. Numerical material models for steel and mineral wool were established based on standards, and the temperature distribution and structural deformation were simulated using Abaqus. The results showed a good correlation with the experimental data. The maximum and average temperature increases on the unheated surface of the bulkhead during the standard fire resistance test were 158 °C and 136 °C, respectively. The corresponding values for the deck were 176 °C and 138 °C. Upon the conclusion of the experiment, the maximum displacement deformation in the direction towards the furnace from the center of the cabin wall was 54 mm, and from the center of the deck, the maximum displacement deformation towards the furnace was 28 mm. This research can provide guidance for the design of fire-resistant ship compartment structures.

Numerous collision conditions can occur during ship operations, resulting in various consequences that require specific consideration for optimizing crashworthiness design. Existing studies have investigated crashworthiness design in ship structures; however, they often focus on single working conditions and do not comprehensively consider the diverse scenarios encountered during ship operations. To overcome this drawback, this paper proposes a novel method that addresses multi-working conditions and combines orthogonal testing with a backpropagation neural network (BPNN) to establish an efficient surrogate model for collision optimization. The accuracy of the BPNN was improved by introducing the genetic algorithm and Adam algorithm. The technique for order preference by similarity to ideal solution (TOPSIS) is introduced to formulate a multi-working condition optimization function. The crashworthiness of the ship structure is optimized using the sparrow search algorithm (SSA) while considering the constraint of lightweight design. The results demonstrate a substantial reduction in the objective functions for the optimized collision conditions. Moreover, the BPNN predicted values are in good agreement with the finite element simulation results, affirming the effectiveness of the proposed method in improving the crashworthiness of the ship structure and providing valuable guidance for engineering design.

Although the variation in chromatin architecture during adaptive immune responses has been thoroughly investigated, the 3D landscape of innate immunity is still unknown. Herein, chromatin regulation and heterogeneity among human primary monocytes were investigated. Peripheral blood was collected from two healthy persons and two patients with systemic lupus erythematosus (SLE), and CD14+ monocytes were selected to perform Hi-C, RNA-seq, ATAC-seq and ChIP-seq analyses. Raw data from the THP1 cell line Hi-C library were used for comparison. For each sample, we constructed three Hi-C libraries and obtained approximately 3 billion paired-end reads in total. Resolution analysis showed that more than 80% of bins presented depths greater than 1000 at a 5 kb resolution. The constructed high-resolution chromatin interaction maps presented similar landscapes in the four individuals, which showed significant divergence from the THP1 cell line chromatin structure. The variability in chromatin interactions around HLA-D genes in the HLA complex region was notable within individuals. We further found that the CD16-encoding gene (FCGR3A) is located at a variable topologically associating domain (TAD) boundary and that chromatin loop dynamics might modulate CD16 expression. Our results indicate both the stability and variability of high-resolution chromatin interaction maps among human primary monocytes. This work sheds light on the potential mechanisms by which the complex interplay of epigenetics and spatial 3D architecture regulates chromatin in innate immunity.

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Abstract Respirasome, as a vital part of the oxidative phosphorylation system, undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons. Copious research has been carried out on this lynchpin of respiration. From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1, scientists have gradually uncovered the mysterious veil of the electron transport chain (ETC). With the discovery of the mammalian respiratory mega complex I2III2IV2, a new perspective emerges in the research field of the ETC. Behind these advances glitters the light of the revolution in both theory and technology. Here, we give a short review about how scientists ‘see’ the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.

Respiration is one of the most vital and basic features of living organisms. In mammals, respiration is accomplished by respiratory chain complexes located on the mitochondrial inner membrane. In the past century, scientists put tremendous efforts in understanding these complexes, but failed to solve the high resolution structure until recently. In 2016, three research groups reported the structure of respiratory chain supercomplex from different species, and fortunately the structure solved by our group has the highest resolution. In this review, we will compare the recently solved structures of respirasome, probe into the relationship between cristae shape and respiratory chain organization, and discuss the highly disputed issues afterwards. Besides, our group reported the first high resolution structure of respirasome and medium resolution structure of megacomplex from cultured human cells this year. Definitely, these supercomplex structures will provide precious information for conquering the mitochondrial malfunction diseases. Keywords: Structure of respirasome, Cristae organization, Substrate channeling, Electron transfer pathway, Assembly of respirasome

The study was to investigate the ameliorating effects and potential mechanism of an exopolysaccharide (LEP-2a) and its derivatives against CCl4 induced acute liver damage. LEP-2a, one exopolysaccharide from Lachnum YM406, was phosphorylated and selenized to prepare its derivatives. LEP-2a and its derivatives could alleviate liver injury, which were proved by hepatosomatic index, liver histopathological assessment and biochemical indicators of liver damage, antioxidant defense system and inflammatory reaction. The mechanisms of liver protection effect were related to reducing hepatocyte apoptosis by down-regulating expression of Fas, Fas-L and ratio of Bax/Bcl-2 as well as the activation of caspase 3/8 and cleavage of PARP caused by CCl4, which were associated with Fas/Fas-L and mitochondrial pathway. Moreover, liver fibrosis was also markedly relieved by activating HGF/c-Met pathway and down-regulating expression of vimentin and ICAM-1 as well as normalizing PHB expression. In conclusion, LEP-2a and its derivatives exhibited notable liver protection effect in multiple ways.

Pork is perishable due to oxidation and microbial spoilage. Edible coating based on biopolymers and phenolic compounds is an effective way to preserve the quality of pork. In this study, ferulic acid-grafted-CS (ferulic acid-g-CS) with strong antioxidant and antimicrobial activities was synthesized through a carbodiimide-mediated coupling reaction. The obtained ferulic acid-g-CS was used as an edible coating material for fresh pork. The effect of ferulic acid-g-CS coating on the quality of pork during storage was investigated at 4 °C for 8 days. As compared to the uncoated pork, pork coated with CS and ferulic acid-g-CS showed lower total viable counts, total volatile basic nitrogen values, pH values, thiobarbituric acid reactive substances, and drip losses. Besides, pork coated with CS and ferulic acid-g-CS presented more compact microstructures than the uncoated pork at the eighth day. Sensory evaluation assay showed pork coated with CS and ferulic acid-g-CS had better color, odor, and over acceptance in comparison with the uncoated pork. Ferulic acid-g-CS coating, due to its relatively higher antioxidant and antimicrobial activities compared to CS coating, had a better performance in refrigerated pork preservation. Ferulic acid-g-CS coating effectively extended the shelf life of refrigerated pork to 7 days. This study revealed ferulic acid-g-CS coating was a promising technology for refrigerated pork preservation.

Hydroxycinnamic acids are one category of bioactive phenolic acids that are widely distributed in plants. In this study, chitosan (CS) was functionalized with three kinds of hydroxycinnamic acids (p-coumaric acid, caffeic acid and ferulic acid) through the carbodiimide-mediated grafting method. The obtained hydroxycinnamic-acid-grafted CSs (hydroxycinnamic acid-g-CSs) were further fabricated into food packaging films through solvent casting. For the first time, the functionalities of the different hydroxycinnamic acid-g-CS films were compared. Results showed the grafting ratio of p-coumaric acid-g-CS, caffeic acid-g-CS and ferulic acid-g-CS was 73.68, 129.42 and 91.75 mg/g, respectively. Instrumental analyses confirmed hydroxycinnamic acids conjugated with CS through amide and ester bonds. The functionalization of CS film with hydroxycinnamic acids produced a more compact microstructure and higher UV light barrier ability, mechanical strength, water vapor barrier ability, thermal stability and antioxidant and antimicrobial activities. Among the different hydroxycinnamic acid-g-CS films, caffeic acid-g-CS film presented the strongest barrier, mechanical, antioxidant and antimicrobial properties. Moreover, caffeic acid-g-CS film packaging effectively extended the shelf life of pork to 10 days at 4 °C. Our results suggest caffeic acid-g-CS film can be used in the active food packaging field.