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Abstract Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

In the study, a hybrid lubricant was prepared by introducing graphene into a polyphosphate lubricant. In the tribological test of a steel/steel friction pair at the high temperature of 800 °C, the addition of a small proportion of graphene significantly enhances the lubrication performance of polyphosphate at elevated temperatures. The coefficient of friction and the wear were obviously held down while the surface quality of the high-temperature friction pair was enhanced effectively with the graphene-strengthened polyphosphate lubricant, compared with the dry sliding condition. Through scanning electron microscopy and Raman spectroscopy analysis, the formation mechanism of tribofilm and the antiwear performance of the hybrid lubricant are further explained. This lubricant effectively combines the advantages of both; the combination of polyphosphate melted at elevated temperature with graphene and metal surfaces ensures the self-sealing of the friction contact area and brings better high-temperature oxidation resistance. At the same time, the presence of graphene provides excellent strength to the friction film and ensures the anti-wear and wear-resistant performance of the lubricant at high temperatures.

Abstract This study compared the radiologic and clinical outcomes of a new seven-axis robotic-assisted total hip arthroplasty (THA) and conventional THA. Hundred and four patients were randomly assigned to two groups—the robotic-assisted THA group (RAS group) and the conventional THA group (CON group). The preoperative and postoperative Harris Hip score (HHS), acetabular inclination, anteversion, femoral offset, and leg length discrepancy (LLD) were compared. During the follow-up, no patients had any complications that could be associated with the use of the robot. The proportion of acetabular cups in the safety zone was significantly higher in the RAS group than that in the CON group. The two groups had significantly different mean absolute difference of inclination and anteversion. There was no significant difference in the postoperative HHSs, changes in HHSs, femoral offset, and lower limb length between the two groups. The seven-axis robotic-assisted THA system is safe and effective, and leads to better acetabulum cup positioning compared to conventional THA. The improvements observed in the HHS, LLD, and femoral offset in the RAS group were similar to those in the CON group. Clinical trial registration time: 19/05/2022. Clinical trial registration number: ChiCTR2200060115.

To improve the wear resistance of CoCrFeNi high-entropy alloys (HEAs) for a wider range of industrial applications, the alloying strategy was applied to CoCrFeNi HEA by doping Mo element in various ratios, and CoCrFeNiMox (x = 0, 0.2, 0.5, and 1.0) HEA deposits were fabricated by cold spray. The microstructure evolution, mechanical properties, and tribological properties of cold-sprayed CoCrFeNiMox HEA deposits were systematically investigated. The results showed that Mo0, Mo0.2, and Mo0.5 deposits have a face-centered-cubic (FCC) single structure, while Mo1.0 deposit was composed of FCC matrix and hard brittle phases. The doping of Mo element into CoCrFeNi HEA deposits significantly increased the hardness due to the enhanced solid solution strengthening and precipitation strengthening. As a result, the anti-wear properties of Mo-doped CoCrFeNi HEA deposits were gradually improved with the increase in Mo ratios. To be specific, the Mo1.0 deposit exhibited the lowest specific wear rate of 5.1 × 10−5 mm3/N·m, which was reduced by 94.9% in comparison to the Mo0 deposit. Overall, the current study proposes a new strategy to manipulate the mechanical properties of cold-sprayed HEA deposits by alloying.

Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

Abstract Cervicogenic headache is an often observed secondary headache in clinical settings, with patients who endure prolonged and persistent pain being particularly susceptible to mood changes. Currently, the Mulligan is one of the effective methods for CEH. However, there is a lack of evaluation about the strength and frequency of headaches, as well as the assessment of pain-induced emotions, in individuals with CEH using this particular procedure. Herein, we aimed to evaluate the effectiveness of the Mulligan maneuver from a multidimensional perspective of pain intensity and mood. A total of forty patients diagnosed with CEH who satisfied the specified inclusion criteria were recruited and allocated randomly into two groups: the control group and the treatment group, with each group consisting of twenty cases. The control group received health education, while the treatment group received the Mulligan maneuver once daily over a course of 10 treatment sessions.The clinical outcome of patients with CEH in two groups was assessed using the Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Resting-state functional magnetic resonance imaging was employed to examine variations in brain function activities between the two CEH groups. Brain regions showing differences were identified as regions of interest and subsequently correlated with clinical behavioral measures using Pearson’s correlation analysis. The differences in VAS, HAMA and HAMD between the two groups of CEH patients were also statistically significant. The brain regions that showed differences in the ReHo scores between the two groups of CEH patients included the left cerebellum, the frontal gyrus, and the middle temporal gyrus. There was a positive correlation between the left frontal gyrus and VAS, HAMA and HAMD. The left middle temporal gyrus had a negative correlation with VAS, HAMA, and HAMD and the left cerebellum had a positive correlation with VAS correlation. The Mulligan maneuver may improve pain levels and have a moderating effect on pain-related negative emotions by regulating the function of relevant brain regions in CEH patients.

Abstract Objective The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted (RA) total knee arthroplasty (TKA) system and to explore whether it could provide superior short-term clinical and radiological outcomes compared with conventional surgery. Methods In the present retrospective study, 90 patients who underwent RA-TKA were included in robot-assisted system (RAS) group and 90 patients who underwent conventional TKA were included in the conventional group. The duration of surgery and robot-related complications were recorded to evaluate the learning curve through cumulative sum and risk-adjusted cumulative sum methods. The demographic data, preoperative clinical data, preoperative imaging data, duration of surgery, alignment of the prosthesis, lower limb force line alignment, Knee Society score, 10-cm visual analog scale pain score and range of motion were compared between the RAS and conventional groups. In addition, the proficiency group was compared with the conventional group using propensity score matching. Results RA-TKA was associated with a learning curve of 20 cases for the duration of surgery. There was no significant difference in indicators representing the accuracy of the prosthetic installation between the learning and proficiency phases in RA-TKA group patients. A total of 49 patients in the proficiency group were matched with 49 patients from the conventional group. The number of postoperative hip–knee–ankle (HKA) angle, component femoral coronal angle (CFCA), component tibial coronal angle (CTCA), and sagittal tibial component angle (STCA) outliers in the proficiency phase was lower than that in the conventional group, while deviations of the HKA angle, CFCA, CTCA, and STCA in the proficiency phase were significantly lower than those in the conventional group (P

ObjectiveOsteonecrosis of the femoral head (ONFH) is a common orthopedic condition that will prompt joint dysfunction, significantly impacting patients’ quality of life. However, the specific pathogenic mechanisms underlying this disease remain elusive. The objective of this study is to examine the differentially expressed messenger RNAs (DE mRNAs) and key genes linked to ONFH, concurrently investigating the immune cell infiltration features in ONFH patients through the application of the CIBERSORT algorithm.MethodsMicroarray was applied to scrutinize mRNA expression profiles in both ONFH patients and healthy controls, with data integration sourced from the GEO database. DE mRNAs were screened using the Limma method. The biological functions of DE mRNAs were explored through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) functional analysis, and Gene Set Enrichment Analysis (GSEA). Additionally, support vector machine–recursive feature elimination (SVM-RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to discern diagnostic biomarkers associated with the disease. Receiver operating characteristic (ROC) analysis was utilized to assess the statistical performance of the feature genes. The validation of key genes was performed using qRT-PCR in bone tissues obtained from ONFH patients and healthy controls. Osteogenic differentiation of BMSC was then performed and detected by alkaline phosphatase staining (ALP) and qRT-PCR to verify the correlation between key genes and osteogenic differentiation. Finally, immune cell infiltration analysis was executed to evaluate immune cell dysregulation in ONFH, concurrently exploring the correlation between the infiltration of immune cells and key genes.ResultsAfter consolidating the datasets, the Limma method revealed 107 DEGs, comprising 76 downregulated and 31 upregulated genes. Enrichment analysis revealed close associations of these DE mRNAs with functions such as cell migration, osteoblast differentiation, cartilage development and extracellular region. Machine learning algorithms further identified APOD, FBXO43 and LRP12 as key genes. ROC curves demonstrated the high diagnostic efficacy of these genes. The results of qRT-PCR showed that the expression levels of key genes were consistent with those of microarray analysis. In addition, the results of in vitro experiments showed that APOD was closely related to osteogenic differentiation of BMSC. Immune infiltration analysis suggested a close correlation between ONFH and imbalances in levels of Neutrophils, Monocytes, Macrophages M2, Dendritic cells activated and Dendritic cells resting.ConclusionAPOD is closely related to osteogenic differentiation of BMSCs and can be used as a diagnostic marker of ONFH. Immune cell infiltration significantly differs between controls and ONFH patients.

This paper focuses on studying the influences of thickener (hydroxypropyl methyl cellulose, HPMC) on ECC performance, with the adding dosages of 0%−0.1% by mass of the reference mix. The tensile properties (including the tensile strength, the tensile strain capacity, and the cracking characteristics) and the compressive strength were thoroughly evaluated. Particularly, the matrix toughness and the fiber-matrix bridging behaviors were further studied by a varies of so-called meso-scale experiments. Meanwhile, the fibers dispersions in the mixes with HPMC were analyzed. The results showed that, both the tensile strength and the tensile strain first increased and then decreased, with the largest values at the 0.05% HPMC (the strain value was up to 8%); while the compressive strength gradually declined according to the HPMC contents. After adding 0.05% HPMC, the crack numbers reached a stable level of around 100 with the average crack width of approximately 60 µm, and the dispersion coefficient of fibers tended to a higher level of around 0.35. The variation trends of the matrix fracture toughness and the maximum fiber bridging stress were almost agreement with that of the compressive strength and the tensile properties, respectively. Therefore, no more than 0.05% HPMC was recommended to be used into ECC (or 3D printing ECC).

Abstract Objective The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted total hip arthroplasty (RA-THA) system, and to explore whether it was able to provide greater accuracy in acetabular cup positioning, superior leg length discrepancy (LLD), and hip offset than conventional methods. Methods A total of 160 patients in which unilateral THA was performed in the second affiliated Hospital of Xi'an Jiaotong University from July 2021 to September 2022 were studied. The first 80 patients underwent robot-assisted THA, while conventional THA was performed on the subsequent 80 by the same team of experienced surgeons. The learning curve for the RA-THA system was evaluated using cumulative sum (CUSUM) analysis. The demographic data, preoperative clinical data, duration of surgery, postoperative Harris hip score (HHS) and postoperative radiographic data from patients that had conventional THA were compared. Results The 80 patients who underwent primary unilateral RA-THA comprised 42 males and 38 females and were followed up for 12 weeks. Using analysis by CUSUM, the learning curve of the RA-THA system could be divided into learning and proficiency phases, the former of which consisted of the first 17 cases. There was no significant difference between the learning and proficiency phases in terms of LLD, hip offset, or accuracy of acetabular prosthesis position in the RA-THA groups. The proportion of acetabular prostheses located in the Lewinnek safe zone was 90.5% in the proficiency group and 77.5% in the conventional group, respectively, a difference that was statistically significant (P

Rolling mill bearings are prone to wear, erosion, and other damage characteristics due to prolonged exposure to rolling forces. Therefore, regular inspection of rolling mill bearings is necessary. Ultrasonic technology, due to its non-destructive nature, allows for measuring the oil film thickness distribution within the bearing during disassembly. However, during the process of using ultrasonic reflection coefficients to determine the oil film thickness and distribution state of rolling mill bearings, changes in bearing temperature due to prolonged operation can occur. Ultrasonic waves are susceptible to temperature variations, and different temperatures of the measured structure can lead to changes in measurement results, ultimately distorting the results. This paper proposes using density and sound speed compensation methods to address this issue. It simulates and analyzes the oil film reflection coefficients at different temperatures, ultimately confirming the feasibility and effectiveness of this approach. The paper establishes a functional relationship between bearing pressure and reflection coefficients, oil film thickness, and reflection coefficients. This allows for the compensation of reflection coefficients under any pressure conditions, enhancing the accuracy of oil film thickness detection. The proposed method provides technical support for the maintenance of plate rolling processes in the steel industry.

Porcine reproductive and respiratory syndrome virus (PRRSV) has seriously affected the viability of swine industries worldwide, and effective measures to control PRRSV are urgently required. Understanding the mechanisms of action of antiviral proteins is crucial for developing antiviral strategies. Interferon-induced bone marrow stromal cell antigen 2 (BST2) can inhibit the replication of various viruses via different pathways. However, little is known about the effects of BST2 on PRRSV. Therefore, this study aimed to evaluate whether the interferon-induced BST2 can inhibit PRRSV replication. We used western blotting and RT-qPCR techniques to analyze the effect of BST2 overexpression and knockdown on PRRSV replication. Overexpression of BST2 inhibited the replication of PRRSV, whereas knockdown of BST2 by small interfering RNA promoted PRRSV replication. Additionally, the expression of BST2 was upregulated during the early phase of PRRSV infection in porcine alveolar macrophages. Analysis of PRRSV proteins showed that BST2 restricted the expression of several non-structural viral proteins. BST2 downregulated the expression of Nsp12 through a proteasome-dependent pathway and downregulated the expression and transcription of E protein. These findings demonstrate the potential of BST2 as a critical regulator of PRRSV replication.

Objectives To explore the basic occupational information and the preferences of surgical techniques in Chinese joint surgeons. Methods A survey study was conducted during the Chinese Hip Society (CHS) conference of 2020. Participants from hospitals all over the country were included as the potential respondents. The questions were asked for respondents' basic information, overviews of total hip arthroplasty (THA), surgical techniques, and prosthesis selection. After data collection and filtration, analysis was conducted using chi‐square test or Fisher's exact test. Results Only 8.31% of joint surgeons used robotics or navigation systems to assisted their total hip arthroplasty. For the approach preference, posterolateral approaches were generally favored, being used commonly by 75.36% of respondents while the direct anterior approach was considered the preferred choice by 8.31% of Chinese joint surgeons. 24.36% of the respondents choose to use domestic prosthesis in over 80% of their patients. Conclusions The intelligent THA is in the early stage at present but developing rapidly in China. The composition of surgical approach is simple at present and the continuing education should aim at increasing the diversity of approach selection in the following years. Domestic prosthesis is playing significant role in the prosthesis market. Joint registration system is urgently needed for Chinese joint surgery.

Abstract Background The treatment and prognosis of lung adenocarcinoma (LUAD) remains a challenge. The study aimed to conduct a systematic analysis of the predictive capacity of N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) in the prognosis of LUAD. Methods 594 samples were totally selected from a dataset from The Cancer Genome Atlas. The identification of prognostic m6A-related lncRNAs were performed by Pearson correlation analysis and Cox regression analysis. Systematic analyses, including cluster analysis, survival analysis, and immuno-correlated analysis, were conducted. A prognosis model was built from the optimized subset of m6A-related lncRNAs. The assessment of model was performed by survival analysis, and receiver operating characteristic (ROC) curve. Finally, the risk score of patients with LUAD calculated by the prognosis model was implemented by the analysis of Cox regression. Differential analysis was for further evaluation of the cuproptosis-related genes in two risk sets. Results These patients were grouped into two clusters according to the expression levels of 22 prognostic m6A-related lncRNAs. The patients with LUAD in cluster 2 was significantly worse in the overall survival (OS) (P = 0.006). Three scores calculated by the ESTIMATE methods in cluster 2 were significantly lower. After the least absolute shrinkage and selection operator algorithm, 10 prognostic m6A-related lncRNAs were totally selected to construct the final model to obtain the risk score. Then the area under the ROC curve of the prognosis model for 1, 3, and 5-year OS was 0.767, 0.709, and 0.736 in the training set, and 0.707, 0.691, and 0.675 in the test set. The OS of the low-risk cohort was significantly higher than that of the high-risk cohort in both the training set (P

During 2018–2020, we isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection.

African swine fever is a highly lethal contagious disease of pigs for which there is no vaccine. Its causative agent African swine fever virus (ASFV) is a highly complex enveloped DNA virus encoding more than 150 open reading frames. The antigenicity of ASFV is still unclear at present. In this study, 35 proteins of ASFV were expressed by Escherichia coli, and ELISA was developed for the detection of antibodies against these proteins. p30, p54, and p22 were presented as the major antigens of ASFV, positively reacting with all five clinical ASFV-positive pig sera, and 10 pig sera experimentally infected by ASFV. Five proteins (pB475L, pC129R, pE199L, pE184L, and pK145R) reacted well with ASFV-positive sera. The p30 induced a rapid and strong antibody immune response during ASFV infection. These results will promote the development of subunit vaccines and serum diagnostic methods against ASFV.

PurposeInvestigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes.MethodsPatients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs.ResultsIn comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs.ConclusionThe present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

Abstract Background Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. Results Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). Conclusions The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract

Abstract Background As the major suppliers of food for higher consumers, phytoplankton are closely related to the yield, nutritional ingredients and even toxin contents of mariculture animals, potentially influencing the human health when they are consumed. With the increase of shellfish culture density, phytoplankton in the coastal waters have been excessively consumed in recent years, and the nutrients they depend on are becoming more and more limited, which severely restrict the shellfish mariculture and threaten the coastal ecosystems. Results In the present study, nutrient concentrations, phytoplankton assemblages and scallop growth status were investigated in the main bay scallop farming waters of the Bohai Sea (Qinhuangdao site) and North Yellow Sea (Zhuanghe site) in 2018. Both phosphate and silicate limitations were observed at the two sites, with the major determinant of phytoplankton assemblages being silicate in Qinhuangdao and phosphate in Zhuanghe, respectively. The phytoplankton assemblages at the two sites displayed different community structures and succession patterns. The phytoplankton community was dominated by dinoflagellates and diatoms in Qinhuangdao, while dinoflagellates were the most abundant group in Zhuanghe, which accounted for 41.9% of the total phytoplankton abundance. The dominant genera of diatoms in Qinhuangdao were Skeletonema, Thalassiosira and Leptocylindrus, while those in Zhuanghe were Thalassiosira and Cyclotella. Greater biomass and more appropriate structure of phytoplankton contributed to higher growth rate and glycogen content of cultured bay scallops. Conclusions Our study characterized the relationship between nutrient concentration, phytoplankton community and scallop mariculture in the main bay scallop farming waters in northern China. The results suggest that, as nutrient limitation intensified, dinoflagellates are becoming the dominant phytoplankton species in the scallop farming waters of the Bohai Sea and the North Yellow Sea, which is harmful to the coastal mariculture.

Abstract Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.

Abstract Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.

African swine fever, which is induced by the African swine fever virus (ASFV), poses a significant threat to the global pig industry due to its high lethality in domestic pigs and wild boars. Despite the severity of the disease, there is a lack of effective vaccines and drugs against the ASFV. The p72 protein, constituting 31 to 33% of the total virus particle mass, serves as the primary capsid protein of ASFV. It is a crucial antigen for the development of ASF subunit vaccines and serological diagnostic methods. In this investigation, 27 monoclonal antibodies (mAbs) were generated through mouse immunization with the truncated C-terminal p72 protein expressed by Escherichia coli. Among these, six mAbs exhibited binding to the p72 trimer, with their respective recognized epitopes identified as 542VTAHGINLIDKF553, 568GNAIKTP574, and 584FALKPREEY592. All three epitopes were situated within the interval sequences of functional units of the C-terminal jelly-roll barrel of p72. Notably, two epitopes, 568GNAIKTP574 and 584FALKPREEY592, were internal to the p72 trimer, while the epitope 542VTAHGINLIDKF553 was exposed on the surface of the trimer and consistently conserved across all ASFV genotypes. These findings enhance our comprehension of the antigenic function and structure of the p72 protein, facilitating the utilization of p72 in the development of diagnostic techniques for ASFV.

Abstract Background Determining the prognosis of lung adenocarcinoma (LUAD) is challenging. The present study aimed to identify prognostic ferroptosis-related long noncoding RNAs (FRLs) and construct a prognostic model. Moreover, differential analysis of immune and N6-methyladenosine (m6A)-related genes was systematically conducted. Methods A total of 504 patients selected from a dataset from The Cancer Genome Atlas were included. The patients with LUAD were randomly divided into a training group and a test group at a ratio of 1:1. Pearson correlation analysis and univariate Cox regression analysis were used to identify the prognostic FRLs. Then, a prognostic model was constructed from the optimized subset of prognostic FRLs based on the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, the receiver operating characteristic (ROC) curve and survival analysis were used to evaluate the performance of the model. The risk score based on the prognostic model was analyzed using Cox regression analysis. Moreover, gene set enrichment analysis and differential analysis of immune- and m6A-related genes were conducted. Results After univariate Cox regression analysis and LASSO algorithm analysis, a total of 19 prognostic FRLs were selected to construct the final model to obtain the risk score. The area under the ROC curve of the prognostic model for 1-year, 3-year, and 5-year overall survival (OS) was 0.763, 0.745, and 0.778 in the training set and 0.716, 0.724, and 0.736 in the validation set, respectively. Moreover, the OS of the high-risk group was significantly worse than that of the low-risk group in the training group (P

Intestinal autochthonous bacteria play important roles in the maintenance of the physiological homeostasis of animals, especially contributing to the host immune system. In the present study, the variation of autochthonous bacterial community in the intestinal tract of 2-7 months-old tiger pufferfish Takifugu rubripes and bacterial communities in the seawater of recirculating aquaculture system (RAS) and the following offshore sea cage aquaculture system (OSCS) were analyzed during the aquaculture period from May to October 2021. Proteobacteria was found to be the most dominant phyla in both intestinal and seawater bacterial communities, which accounted for 68.82% and 65.65% of the total bacterial abundance, respectively. Arcobacter was the most core bacterial taxon in the intestinal bacterial community, with the most dominant abundance (42.89%) at the genus level and dominant positions in co-occurrence relationships with other bacterial taxa (node-betweenness value of 150). Enterococcaceae was specifically enriched in the intestinal bacterial community of pufferfishes from RAS, while Vibrionaceae was enriched in the intestinal bacterial community from OSCS. The F-values of beta diversity analysis between intestinal and seawater bacterial communities generally increased from May (6.69) to October (32.32), indicating the increasing differences between the intestinal and seawater bacterial communities along with the aquaculture process. Four bacterial taxa of Weissella sp., Akkermansia muciniphila, Dietzia sp. and Psychrobacter pacificensis had significant correlations with immune response parameters, and they were suggested to be the indicators for immune status and pathological process of pufferfish. The knowledge about the specific core bacteria, potentially pathogenic bacteria and the change of bacterial community in the intestinal tract of cultured pufferfish is of great scientific significance and will contribute to the understanding of intestinal bacterial homeostasis and biosecurity practice in pufferfish aquaculture.

PurposeLumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization.MethodsA total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01–0.08 Hz), the slow-4 band (0.027–0.073 Hz), and the slow-5 band (0.01–0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect.ResultsCompared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band.ConclusionThe present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.

Abstract Background Our objective was to obtain normal patellofemoral measurements to analyse sex and individual differences. In addition, the absolute values and indices of tibial tuberosity-trochlear groove (TT-TG) distances are still controversial in clinical application. A better method to enable precise prediction is still needed. Methods Seventy-eight knees of 78 participants without knee pathologies were included in this cross-sectional study. A CT scan was conducted for all participants and three-dimensional knee models were constructed using Mimics and SolidWorks software. We measured and analysed 19 parameters including the TT-TG distance and dimensions and shapes of the patella, femur, tibia, and trochlea. LASSO regression was used to predict the normal TT-TG distances. Results The dimensional parameters, TT-TG distance, and femoral aspect ratio of the men were significantly larger than those of women (all p values 0.05). The Pearson correlation coefficients between the anterior femoral offset and other indexes were consistently below 0.3, indicating no relationship or a weak relationship. Similar results were observed for the sulcus angle and the Wiberg index. Using LASSO regression, we obtained four parameters to predict the TT-TG distance (R2 = 0.5612, p

Bacteria in coastal waters drive global biogeochemical cycling and are strongly related to coastal environmental safety. The bacterial community in offshore shellfish farming waters of North China has its own characteristics and particularities, while the knowledge is limited. In this study, the bacterial community characteristics, the particularities of bacterial community in the waters with surface cold patches (SCPs) and the variation of pathogenic bacteria were investigated in the offshore shellfish farming waters in the North Yellow Sea (NYS) from 2017 to 2019. For all studied samples, Desulfobacterales acted as the keystone species taxon in microbial co-occurrence networks, and the proportional abundance of Actinobacteriota was found to be as low as 1.3%. The abundance of Marinobacter and Synechococcus was remarkably prominent in 13 genera with nitrogen-transforming function. The top two different bacterial functions in the spatial analysis (between the waters with SCPs and the ambient waters) were xenobiotics biodegradation and metabolism and metabolism of cofactors and vitamins, which were same with that in the seasonal analysis (between spring and summer). The abundance differences of most pathogenic bacteria analyzed in this study (11 out of 12 genera) also had the same variation dynamics between the spatial analysis and the seasonal analysis. An ANN predictive model for Vibrio abundance was constructed for Vibrio forecasting, with acceptable predictive accuracy. According to the above results, the bacterial community in the shellfish aquaculture waters in this study was characterized by the enhancing ability of nitrogen removal. Temperature was concluded as the predominant environmental factor to drive the variation of bacterial community function and pathogenic bacteria patterns in the offshore shellfish farming waters with SCPs. The results of this study will further our understanding of the bacterial community characteristics in offshore shellfish farming waters, and help for Vibrio forecasting and coastal environmental safety in aquaculture seawater.

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

On-orbit service for spacecraft relies heavily on on-orbit docking with the orbital replacement unit docking interface. Foreign research on the docking interface of the orbit replaceable unit has been in-depth, while the domestic work is still limited. Currently, most design on the docking interface relies on the axial feed of the manipulator, which may result in insufficient docking interface mating force under specific conditions. In view of the above problems, it requires a linear plug-in locking interface for the docking of the orbital replaceable unit, and the design scheme of the tapered rod guide and linkage locking parts needs to be determined. Optimization of the linkage locking mechanism is completed by a finite element simulation. The effect of clearance of the taper rod, effective locking points and friction coefficient have been analyzed by means of dynamics modelling during the docking and locking processes. The research also verified the design rationality for the orbital replaceable unit linkage. A processing path and verification for the prototype have been made as well. This work introduces the idea of self-plugging during the orbital docking process. It lays a foundation for the prototype development and control strategy of the orbital replaceable unit.

BackgroundCrohn’s disease (CD) is characterized by repetitive phases of remission and exacerbation, the quality of life of patients with CD is strongly influenced by disease activity, as patients in the active phase experience significantly worse symptoms. To investigate the underlying mechanism of how the course of CD is exacerbated based on the bi-directionality of the brain-gut axis (BGA), we conducted a multi-modality neuroimaging study that combined resting-state functional magnetic resonance imaging (rs-fMRI) with proton magnetic resonance spectroscopy (MRS) to detect abnormalities in the anterior cingulate cortex (ACC).Materials and MethodsClinical scales including Visual Analog Scale (VAS) and Hospital Anxiety and Depression Scale (HADS) were used to evaluate the degree of abdominal pain and mood state of participants. We made a comparison between CD patients in the active phase, the remission phase and healthy controls (HCs), not only employed the innovative wavelet-transform to analyze the amplitude of low frequency fluctuation (ALFF) but also compared the sensitivity of wavelet-transform and the traditional fast Fourier transform (FFT). Brain metabolites such as glutamate (Glu), myo-inositol (mIns) and gamma-aminobutyric acid (GABA) were also detected. Then correlation analysis was made to see whether changes in the ACC correlated with CD’s clinical symptoms.ResultsCD patients in the active phase showed higher VAS scores (p = 0.025), the scores of anxiety and depression were also higher (all p < 0.05). Wavelet-transform is slightly more sensitive in the current research. Patients in the active phase exhibited higher ALFF in the left ACC and the left superior frontal gyrus, medial (SFGmed). Patients in the active phase showed increased Glu levels in the ACC than patients in the remission phase or HCs (p = 0.039 and 0.034 respectively) and lower levels of mIns than HCs (p = 0.036). There was a positive correlation between mWavelet-ALFF values of the ACC and HADS-depression scores in CD patients (r = 0.462, p = 0.006). Besides, concentrations of Glu positively correlated with mWavelet-ALFF in the ACC in all participants (r = 0.367, p = 0.006).ConclusionAbnormal spontaneous activity and metabolic levels in the ACC were detected in CD patients in the active phase along with severer abdominal pain and worse mood state, these may contribute to the exacerbation of CD. Therefore, the ACC might be a potential neural alternative for managing the exacerbation of CD.

Abstracts Background Ultrasound is a useful tool to evaluate and quantify skin lesions. Few studies have assessed the criterion validity of skin ultrasound in systemic sclerosis (SSc). The aims of the study were to investigate skin thickness and stiffness using ultrasound and shear wave elastography (SWE) in SSc and to validate skin ultrasound measurements against histological skin thickness. Methods A total of 22 patients with diffuse cutaneous SSc (dcSSc), 22 with limited cutaneous SSc (lcSSc), and 22 age- and gender-matched healthy controls were enrolled. Skin thickness and stiffness were measured by B-mode ultrasound with SWE imaging on the bilateral fingers and hands. Additional ultrasound evaluation was carried out in 13 patients (9 dcSSc and 4 lcSSc) on their dorsal forearms, followed by skin biopsy conducted in the same skin areas. Correlations between ultrasound measurements and histological skin thickness and modified Rodnan skin score (mRSS) were investigated using Spearman’s correlation. Results Compared with controls, ultrasound-measured skin thickness and skin stiffness were significantly higher in patients with SSc (p

Abstract Background Porcine epidemic diarrhea virus (PEDV) infection causes an acute enteric tract infectious disease characterized by vomiting, anorexia, dehydration, weight loss and high mortality in neonatal piglets. During PEDV infection, the spike protein (S) is a major virion structural protein interacting with receptors and inducing neutralizing antibodies. However, the neutralizing B-cell epitopes within PEDV S protein have not been well studied. Methods To accurately identify the important immunodominant region of S1, the purified truncated S1 proteins (SA, SB, SC, SD and SE) were used to immunize BALB/c mice to prepare polyclonal antibodies. The antisera titers were determined by indirect ELISA, western blot and IFA after four immunizations to find the important immunodominant region of S1, and then purified the immunodominant region of S1 protein and immunized mice to generate the special antibodies, and then used recombinant peptides to determine the B-cell epitopes of monoclonal antibodies. Results Five antisera of recombinant proteins of the spike protein region of PEDV were generated and we found that only the polyclonal antibody against part of the S1 region (signed as SE protein, residues 666–789) could recognize the native PEDV. Purified SE protein was used to immunize BALB/c mice and generate mAb 2E10. Pepscan of the SE protein demonstrated that SE16 ( 722 SSTFNSTREL 731 ) is the minimal linear epitope required for reactivity with the mAb 2E10. Further investigation indicated that the epitope SE16 was localized on the surface of PEDV S protein in the 3D structure. Conclusions A mAb 2E10 that is specifically bound to PEDV was generated and identified a specific linear B-cell epitope (SE16, 722 SSTFNSTREL 731 ) of the mAb. The epitope region of PEDV S1 localized in the different regions in comparison with the earlier identified epitopes. These findings enhance the understanding of the PEDV spike protein structure for vaccine design and provide a potential use for developing diagnostic methods to detect PEDV.

Aiming at the problem that fixed mobile edge computing (MEC) server is difficult to meet the needs of mobile users and temporary computing services, this study proposes a network resource allocation strategy based on unmanned aerial vehicle (UAV) cooperative edge computing. First, a UAV-aided MEC scene is designed, and a single UAV with an MEC server is used to provide auxiliary computing services for ground multiusers. Then, an optimization model aiming at total system delay is constructed by considering the system communication model and calculation model. Finally, Deep Q-Network is used to solve the optimization problem to obtain the best resource allocation scheme. Based on the experimental platform, the proposed strategy is demonstrated and analyzed. The results show that when the number of user equipment is 40, the total delay is about 33s, which is 35.29%, 31.25%, and 15.38% lower than other comparison strategies and effectively reduces the computing delay of users.

Electromagnetic docking technology can realize the flexible docking and safe separation of spacecraft, and presents broad application prospects. However, an electromagnetic force with nonlinearity and uncertainty properties increases the difficulties of the electromagnetic docking control. In this work, the magnetic dipole far-field model of a single coil has been established by simplifying the electromagnetic docking device. Afterward, the electromagnetic force and electromagnetic torque models were obtained during space electromagnetic docking. The space electromagnetic docking dynamics model was established by analyzing the influences of disturbance force and disturbance torque caused by a geomagnetic field. According to the one-dimensional docking reference trajectory, the sliding mode variable structure controllers based on exponential reaching law were proposed and verified. The quasi-sliding mode control method has been adopted to solve the chattering problem in sliding mode variable structure control. The simulation results show that it is necessary to design and add an electromagnetic controller to achieve flexible docking. The sliding mode variable structure controller based on quasi sliding mode can realize one-dimensional electromagnetic flexible docking, and have made good tracking effect on the reference trajectory. Compared with the control method based on exponential reaching law, it can reduce the chattering phenomenon in the control process. The sliding mode variable structure control strategy based on quasi sliding mode presented good robustness. Therefore, it can provide theoretical guidance and control reference for the flexible docking process between electromagnetic satellites.

Silver products with high relief have become popular in the silver decoration industry. However, it is difficult to obtain these products through conventional processing at ambient temperature. The aim of this work is to solve this problem by increasing the deformation temperature. Detailed studies were conducted on the evolution of microstructure characteristics in bulk high-purity silver by electron backscatter diffraction (EBSD) to achieve high-relief applications at elevated temperatures. The high temperature sample is mainly composed of recrystallized and substructured grains, exhibiting a more stable state than the ambient temperature sample. More than 70% annealing twins are observed in the hot-working sample. They are characterized by the amount of Σ3n-type triple grain boundary junctions within large grain clusters formed by multiple twinning. These particular boundaries improve the intergranular corrosion resistance and degradation, which is significantly essential for high-purity silver jewelry exposed to sweat and air. The closed multi-coining processes at different temperatures were conducted subsequently. The performance of workpieces demonstrates that increasing the deformation temperature is a viable alternative for producing durable high-relief silver products.

Compared with cubic Continuously Variable Crown (CVC), quintic CVC presents integrated control capability of quadratic and quartic crown. In order to take full advantage of quintic CVC and have better comprehensive control of the edge wave, center wave, high order wave and complex wave in practical application, it is necessary to further clarify the complicated profile control characteristics of quintic CVC. In this paper, quintic CVC technology in a 1500 mm continuous hot rolling mill production line has been taken as the research object and use finite element method to study its profile control characteristics. Through finite element simulation, an integrated model of rolls and strip was established to analyze the influence of the shifting, bending force and rolling force on strip profile with different strip widths. Both crown adjustment area and transverse stiffness are gained to study the control capability of quintic CVC. The simulation results show that the positive shifting and positive bending of CVC work roll reduce the quadratic crown and increase the quartic crown, and the controlling effect of shifting on both quadratic and quartic crown is more remarkable than that of bending. The control capability of the crown increases with the increase of strip width. That is, wider strip has a larger crown adjustment area. Meanwhile, there is a strong coupling relationship that the increase of quadratic crown can lead to the decrease of the quartic crown, which is not good for the flexible control of strip profile. With the increase of rolling force, the quadratic crown of strip increases significantly, while the quartic crown does not change obviously. Additionally, the increase of strip width significantly increases the transverse stiffness of mill.

The back-up rolls of hot strip mills wear considerably under the conditions of high temperature and heavy load, which affects the roll service period and the stability of strip profile control. Serious uneven wear, short service periods, and spalling problems occurred on conventional back-up rolls of upstream stand CVC mills in 1500 mm continuous hot rolling production lines. Through finite element simulations, the problems are determined to be caused by the configuration of a flat roll contour of the back-up roll and the CVC roll contour of the work roll, which leads to uneven contact pressure between the rolls. The wear distribution form is ‘anti-CVC’ shape, and there is peak contact pressure between the rolls on both sides of the roll body. In particular, the long-term negative shifting of CVC on site further increases the peak contact pressure between the rolls, resulting in uneven wear and spalling accident. Based on the design technology of VCR back-up roll contours with variable contact lengths, and considering the cooperation between the middle of the back-up roll and the CVC work roll contour, the roll contour of the back-up roll has been improved. The designed VCRplus roll contour was analyzed and evaluated by finite element simulation, including the distribution of contact pressure between rolls, the control effect of bending force, and the transverse stiffness of the roll gap. The simulation results show that the VCRplus roll contour can effectively improve the uneven distribution of contact pressure between the rolls, and effectively improve the control effect of bending force and the transverse stiffness of the roll gap. Industrial tests demonstrate that VCRplus back-up roll contours have the advantages of uniform back-up roll wear, enhanced self-sustaining of the roll contour, and further extension of the back-up roll service life. The roll contour has now stably been put into industrial production, and the rolling capacity during the back-up roll service period has been extended from 150,000,000 kg to 250,000,000 kg.

Constitutive models play a significant role in understanding the deformation behavior of materials and in optimizing the manufacturing process. In order to improve the reliability of calculation results, the high temperature flow behavior of TA31 titanium alloy obtained from an annealed hot-rolled plate has been investigated by a Gleeble-3500 thermo-mechanical simulator. The isothermal hot compression tests are conducted in the temperature range of 850 to 1050 °C and the strain rate range from 0.001 to 10 s−1 with a height reduction of 60%. The annealed TA31 shows a dynamic recovery characteristic during thermo-mechanical processing. The experimental data have been used to develop an Arrhenius-type constitutive model and a modified Johnson–Cook model under the consideration of coupling effect on strain, temperature, and strain rate, as well as the strain-softening phenomenon. The material parameters are determined by a global optimization method based on the initial values by means of a regression method. A comparation of the predicted results has been performed based on the modified Johnson–Cook model and those acquired from the Arrhenius-type model. The correlation coefficient and average absolute relative error of the modified Johnson–Cook model are 4.57% and 0.9945, respectively. However, when the optimization method has been applied, they are 15.77% and 0.9620 for the Arrhenius-type model, respectively. These results indicate that the modified Johnson–Cook model is more accurate and efficient in predicting the flow stress of annealed TA31 titanium alloy under a set of model material parameters. Furthermore, the simple mathematical expression of this model is helpful to incorporate it into the finite element software to obtain detailed and valuable information during the thermo-mechanical processing simulation for TA31 in further work.

ABSTRACT Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, and, as of yet, none of the currently available broad-spectrum drugs or vaccines can effectively control these diseases. Host antiviral proteins play an important role in inhibiting viral proliferation. One of the isoforms of cytoplasmic poly(A)-binding protein (PABP), PABPC4, is an RNA-processing protein, which plays an important role in promoting gene expression by enhancing translation and mRNA stability. However, its function in viruses remains poorly understood. Here, we report that the host protein, PABPC4, could be regulated by transcription factor SP1 and broadly inhibits the replication of CoVs, covering four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus) of the Coronaviridae family by targeting the nucleocapsid (N) protein through the autophagosomes for degradation. PABPC4 recruited the E3 ubiquitin ligase MARCH8/MARCHF8 to the N protein for ubiquitination. Ubiquitinated N protein was recognized by the cargo receptor NDP52/CALCOCO2, which delivered it to the autolysosomes for degradation, resulting in impaired viral proliferation. In addition to regulating gene expression, these data demonstrate a novel antiviral function of PABPC4, which broadly suppresses CoVs by degrading the N protein via the selective autophagy pathway. This study will shed light on the development of broad anticoronaviral therapies. IMPORTANCE Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, but none of the currently available drugs or vaccines can effectively control these diseases. During viral infection, the host will activate the interferon (IFN) signaling pathways and host restriction factors in maintaining the innate antiviral responses and suppressing viral replication. This study demonstrated that the host protein, PABPC4, interacts with the nucleocapsid (N) proteins from eight CoVs covering four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus) of the Coronaviridae family. PABPC4 could be regulated by SP1 and broadly inhibits the replication of CoVs by targeting the nucleocapsid (N) protein through the autophagosomes for degradation. This study significantly increases our understanding of the novel host restriction factor PABPC4 against CoV replication and will help develop novel antiviral strategies.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world which affects the quality of life for millions of elderly individuals worldwide. Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to AMD. To better understand the disease pathogenesis and identify causal genes for AMD, we applied random walk (RW) and support vector machine (SVM) to identify AMD-related genes based on gene interaction relationship and significance of genes. Our model achieved 0.927 of area under the curve (AUC), and 65 novel genes have been identified as AMD-related genes. To verify our results, a statistics method called summary data-based Mendelian randomization (SMR) has been implemented to integrate GWAS data and transcriptome data to verify AMD susceptibility-related genes. We found 45 genes are related to AMD by SMR. Among these genes, 37 genes overlap with those found by SVM-RW. Finally, we revealed the biological process of genetic mutations leading to changes in gene expression leading to AMD. Our results reveal the genetic pathogenic factors and related mechanisms of AMD.

Abstract Introduction Evidence suggests that Crohn's disease (CD) pathophysiology goes beyond the gastrointestinal tract and is also strongly associated with the brain. In particular, the anterior cingulate cortex (ACC), which plays an integral role in the first brain as part of the default mode network (DMN) and pain matrix, shows abnormalities using multiple neuroimaging modalities. This review summarizes nine related studies that investigated changes in the ACC using structural magnetic resonance imaging, resting‐state functional magnetic resonance imaging, and magnetic resonance spectroscopy. Methods An extensive PubMed literature search was conducted from 1980 to August 2020. In a review of the articles identified, particular attention was paid to analysis methods, technical protocol characteristics, and specific changes in the ACC. Results In terms of morphology, a decrease in gray matter volume and cortical thickness was observed along with an increase in local gyrification index. In terms of function, functional connectivity (FC) within the DMN was increased. FC between the ACC and the amygdala was decreased. Higher amplitudes of low‐frequency fluctuation and graph theory results, including connectivity strength, clustering coefficient, and local efficiency, were detected. In terms of neurotransmitter changes, the concentrations of glutamate increased along with a decrease in gamma‐aminobutyric acid, providing a rational explanation for abdominal pain. These changes may be attributed to stress, pain, and negative emotions, as well as changes in gut microbiota. Conclusions For patients with CD, the ACC demonstrates structural, functional, and metabolic changes. In terms of clinical findings, the ACC plays an important role in the onset of depression/anxiety and abdominal pain. Therefore, successful modulation of this pathway may guide treatment.

Novel porcine circovirus type 3 (PCV3), first identified in the United States, has been detected in many other countries. Porcine circovirus is associated with postweaning multisystemic wasting syndrome, reproductive failure, congenital tremors, and other clinical symptoms. In this study, we established a double polymerase chain reaction assay for detecting both porcine circovirus type 2 (PCV2) and PCV3. This is the first study to detect and characterize the PCV3 genome in the Tianjin region of North China. We collected a total of 169 tissue samples from seven farms between 2016 and 2018. The PCV3-positive rate of all tissue samples was 37.3% (63/169) and the rate of PCV2 and PCV3 coinfection was 14.8% (25/169). PCV2 and PCV3 coinfections with more serious clinical symptoms were found in only three farms. We sequenced three PCV3 strains selected from tissue samples that were positively identified. The complete genome sequences of the three strains shared 97.6–99.4% nucleotide identities with the PCV3 strains in GenBank. Our results showed the extent of PCV3’s spread in Tianjin, and the need to further study PCV3’s pathobiology, epidemiology, isolation, and coinfection.

Pseudorabies virus (PRV) is the etiological agent of Aujeszky's disease, which has caused severe economic loss in China since its re-emergence in 2011. UL46, a late gene of herpesvirus, codes for the abundant but non-essential viral phosphoproteins 11 and 12 (VP11/12). In this study, VP11/12 was found to localize inside both the nucleus and cytoplasm. The nuclear localization signal (NLS) of VP11/12 was identified as 3RRARGTRRASWKDASR18. Further research identified α5 and α7 to be the receptors for NLS and the chromosome region maintenance 1 (CRM1) to be the receptor for the nuclear export signal. Moreover, we found that PRV VP11/12 interacts with EP0 and the stimulator of interferon genes protein (STING), whereas the NLS of VP11/12 is the important part for VP11/12 to interact with UL48. To our knowledge, this is the first study to provide reliable evidence verifying the nuclear localization of VP11/12 and its role as an additional shuttling tegument protein for PRV. In addition, this is also the first study to elucidate the interactions between PRV VP11/12 and EP0 as well as between PRV VP11/12 and STING, while identifying the precise interaction sites of PRV VP11/12 and VP16.

Abstract As an analogue to the vapor–liquid–solid process, the solution–liquid–solid (SLS) method offers a mild solution‐phase route to colloidal 1D nanostructures with controlled sizes, compositions, and properties. However, direct growth of 1D nanostructure arrays through SLS processes remains in its infancy. Herein, this study shows that SLS processes are also suitable for the growth of nanorod arrays on the substrate. As a proof of concept, seedless growth of silica nanorod arrays on a variety of hydrophilic substrates such as pristine and oxide‐modified glass, metal sheets, Si wafers, and biaxially oriented polypropylene film are demonstrated. Also, the silica nanorod arrays can be used as a new platform for the fabrication of catalysts for photothermal CO2 hydrogenation and the reduction of 4‐nitrophenol reactions. This work offers some fundamental insight into the SLS growth process and opens a new avenue for the mild preparation of functional 1D nanostructure arrays for various applications.

Abstract Background Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. Methods The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. Results The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine. Conclusion Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.

The purpose of this article is to solve the uneven deformation problem of electrical steel strip caused by high-temperature phase transition during hot rolling process. The hot rolling process of electrical steel strip is built by ABAQUS software, importing the constitutive model of electrical steel. The effect of temperature drop in the edge of electrical steel strip on the profile and flatness of strip is studied. Simulation results show that the strip edge temperature drop has great effect on hot rolling process of electrical steel strip. When electrical steel strip is in single-phase state, the strip edge temperature drop can reduce the strip crown, but also lead to larger rolling pressure and local high point height in the strip edge. When electrical steel strip is in two-phase state, the local high point height in the strip edge does not exist, but the strip edge temperature drop can lead to larger strip crown.

Hot rolling of titanium alloy currently is carried out without lubrication because of the surface defects. In order to explore an effective lubrication scheme to reduce friction and wear during hot rolling of titanium alloy, a mixed graphene-incorporating lubricant has been proposed to study its lubrication performance and mechanism. The tribological experiments were carried out by ball-disk friction and wear tester under hot-rolling parameters. Scanning electron microscopy (SEM), X-ray energy spectrum analyzer (EDS), X-ray powder diffractometer (XRD) and Raman analysis were used to analyse the surface and cross-section of the wear marks on the samples after the tribological experiments. The results show that the friction coefficient decreases up to about 35% compared with tests under dry and lubricated conditions. The surface quality of the wear marks is improved significantly after applying the proposed lubricant. The graphene which is embedded in the phosphate film can be effectively applied as a lubricating material to strengthen the lubricating film with less combustion loss at high temperatures. A chemical- and mechanical-induced lubrication mechanism for the hot rolling of titanium sheets has been proposed due to the synergistic lubrication effect of the graphene, ZrO2 nano particles and phosphate. It is of great significance and potential value to apply this proposed lubricant as an effective way to reduce the wear, friction and oxidation during the hot-rolling process of titanium alloy.