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Abstract Long-term non-progressors (LTNPs) of HIV-1 infection may provide important insights into mechanisms involved in viral control and pathogenesis. Here, our results suggest that the ribosomal protein lateral stalk subunit P1 (RPLP1) is expressed at higher levels in LTNPs compared to regular progressors (RPs). Functionally, RPLP1 inhibits transcription of clade B HIV-1 strains by occupying the C/EBPβ binding sites in the viral long terminal repeat (LTR). This interaction requires the α-helixes 2 and 4 domains of RPLP1 and is evaded by HIV-1 group M subtype C and group N, O and P strains that do not require C/EBPβ for transcription. We further demonstrate that HIV-1-induced translocation of RPLP1 from the cytoplasm to the nucleus is essential for antiviral activity. Finally, knock-down of RPLP1 promotes reactivation of latent HIV-1 proviruses. Thus, RPLP1 may play a role in the maintenance of HIV-1 latency and resistance to RPLP1 restriction may contribute to the effective spread of clade C HIV-1 strains.

Abstract To improve the extraction of coal resources, gob‐side entry driving is gradually being promoted and applied. However, as the thickness of the coal seam increases, the deformation control of the roadway becomes more difficult. Aiming at this problem, a combination of theoretical calculation, numerical simulation, and field test was used to analyze the aspects of the stress environment, surrounding rock properties, and support forms. The phenomenon and mechanization of intensified deformation and failure of roadway with increasing coal seam thickness were revealed. The specific results include: (1) The ratio of principal stress at the excavation position controls the maximum failure depth of roadway, and the direction of principal stress determines the location of the maximum failure depth; (2) As the thickness of the coal seam increases, the properties of the surrounding rock at the excavation position decrease, the principal stress ratio increases, and the deflection angle of the principal stress increases, which lead to an intensification of the deformation and failure of the roadway. Based on the deformation and failure characteristics of the roadway and the shortcomings of the original support form, a control strategy and support scheme based on a new support structure called “Anchor Cable with C‐shaped Tube” is proposed, which has achieved better deformation control effect in on‐site application.

Abstract Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD+, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

Abstract Background To date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method. Methods Fourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up. Results Segment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P

ABSTRACT: Dietary absorption and digestion are influenced by the microbiota, morphology, and digestive enzymes of intestines, and fermentation is a popular and effective technique to enhance animal rearing growth performance. This study aims to explore the pivotal role of Muscovy duck probiotics fermented feedstuff (FF) in altering the growth performance by reshaping gut morphology, microorganisms and metabolism. The findings showed that FF considerably raised the levels of fatty acids (FA) and small peptides (7-19AA) in the diet. Further feeding trial data reveals that FF greatly increased the Muscovy duck average daily gain (ADG) but had no effect on their daily feed intake (DFI), and the FCR significantly dropped (P < 0.05). Additionally, it was evident that FF improved the integrity of the intestinal mucosa in Muscovy duck by increasing villus height, villus height-to-crypt depth ratio, and lowering crypt depth. Then, in comparison to the control group (NC), there was a significant increase in the gene expression of the mucosal tight junction proteins Occludin, Claudin-1, and Zo-1 in the intestine of Muscovy duck. Additionally, there was higher expression of the mucosal transport channels SGLT-1, PepT1, AQP2, AQP3, and AQP10 in the similarly colon site, jejunum, and duodenum. Furthermore, in AB-PAS/PAS-stained duodenum, jejunum, ileum, and similarly colon site, FF markedly increased relative mucus output and goblet cells while decreasing epithelial cell apoptosis. Following 16S sequencing data indicated that the intestinal microbiota was altered and the diversity and richness of gut microbes was greatly enhanced by FF. Particularly, the boost of core probiotics, such as Rothia of duodenum, Limosilactobacillus and Lentilactobacillus of jejunum, Lactococcus and Rothia of ileum, Ligilactobacillus and Entocuccus of similarly colon site, Gallibacterium of caecum. And reduced potentially pathogenic bacteria (Campylobacter, Prevotellaceae, Clostridia-vadinBB60, and Oscillospira). Nontargeted metabolomics assay for intestinal content confirmed an increased organic acids (oxidanesulfonic acid, cholic acid, gallic acid, coumaric acid, pipecollc acid, 13s-hydroxyoctadecadienoic acid) and glycosides metabolites (5-hydroxydantrolene, 3-hydroxyguanfacine glucuronide, acetylleucine, astragalin, xanthosine, taxiphylin, sinapine, denudatine, penylalanyl-tyrosine and phenylalanyl-valine). These findings demonstrated that FF, a viable option to improve Muscovy duck growth performance through reconstructed intestinal morphology, microorganisms, and metabolism, subsequently promoted the gut health and increased diet digestion and absorption. The study that is being presented offers scientific proof that FF might be a useful strategy for improving Muscovy duck growth performance.

Sebastes schlegelii is a cold temperate ovoviviparous fish found near the seabed layer and is widely distributed in the Yellow Sea and Bohai Sea of China, as well as in the coasts of South Korea and Japan. It is characterized by its tender meat, delicious taste, rich nutrition, and high medicinal value, thus it is an economically important marine fish species in the northern coastal areas of China. In recent years, deep-water cage cultures have rapidly developed in China. Among the economically important fish species suitable for cage culture in northern China, S. schlegelii is the most important local breed with excellent quality and characteristics. However, with the expansion of the scale of the aquaculture industry, aquaculture diseases including those caused by Vibrio harveyi, Vibrio anguillarum, and Photobacterium damselae subsp. damselae, occur frequently. The authors isolated and identified a dominant pathogenic bacterium, the P5W of V. harveyi, from the lesions of diseased S. schlegelii and studied the response of S. schlegelii to V. harveyi infection. Multitissue transcriptome analysis screened the immune differential gene protein kinase B. Protein kinase B, also known as Akt protein, is a serine or threonine protein kinase, which mainly conducts signal transduction by phosphorylating other proteins. It plays an important role in various biological processes such as cell metabolism, transcriptional regulation, cell cycle regulation, immune defense, and embryonic development. Many studies have shown that during viral infection of cells, the Akt pathway is activated, thereby inhibiting viral proliferation. To clarify the sequence information, evolutionary characteristics, and biological functions of the Akt gene in S. schlegelii and to understand the immune response mechanism of S. schlegelii to bacterial invasion, the full-length cDNA of the SsAkt gene was obtained using molecular biology, and the sequence characteristics, tissue expression rules of the gene, and the response rules to Micrococcus luteus and V. anguillarum were studied. The results showed that the length of the open reading frame was 1 440 bp. The predicted relative molecular mass of the SsAkt protein was 55.80 kDa and the isoelectric point was 5.64. Sequence analysis revealed that the SsAkt protein contains three conserved domains: the PH domain (residues 6–109), serine/threonine protein kinase catalytic (S_TKc) domain (residues 148–405), and serine/threonine protein kinase (S_TK_X) domain (residues 406–475). The conserved amino acid site appears in the center of the S_TKc domain and at the end of the S_TK_ X domain: Thr305 and Ser472. Homologous alignment showed that the amino acid sequence of this gene was highly conserved among different species. Phylogenetic tree analysis showed that SsAkt is closely related to Akt in vertebrates, such as Sebastes umbrosus, Lates calcarifer, Larimichthys crocea, and Cyprinus carpio. The relative expression of SsAkt in different tissues of S. schlegelii was detected by real-time fluorescence quantitative PCR. The results showed that SsAkt was expressed in all tested healthy tissues of S. schlegelii, which indicated the relative expression of the SsAkt gene in S. schlegelii. This expression has distinct tissue specificity. The expression of SsAkt in the kidney is the highest, and in the blood and brain, it is also higher than that in other tissues. Therefore, it is speculated that higher expression of SsAkt in the kidney and brain is closely related to immune defense, neurodevelopment, and other processes. To study the role of SsAkt in the immune response of S. schlegelii, we designed a bacterial challenge experiment. The results showed that the transcription level of SsAkt changed significantly, and the relative expression of SsAkt in the three tissues increased after stimulation with M. luteus and V. anguillarum compared with the control group (PBS). After infection with M. luteus, its expression only increased sharply in the kidney, whereas its expression increased slowly in the blood and liver. In the experimental group infected with V. anguillarum, the expression increased significantly in the liver and kidney, and the two relative expression peaks in the kidney occurred at 12 h and 72 h after infection, respectively. The results revealed that the SsAkt gene may play an important role in the immune defense of S. schlegelii, which can further enrich the sequence information and evolutionary data of the Akt gene in marine fish and provide reference materials for an in-depth study of the biological function of this gene. In follow-up experiments, we will explore the specific mechanism of SsAkt in the innate immune defense of S. schlegelii to provide theoretical guidance for the study of the immune signaling pathway of S. schlegelii and to lay a theoretical foundation for revealing the role of SsAkt in other important biological functions in growth and development.

The thermal error of machine tool has always been an important reason affecting the accuracy of machine tool. In modern methods to reduce thermal error, thermal error compensation method and thermal error isolation method are two methods with high operability. Thermal error compensation method emphasizes predicting deformation in advance and then compensating in advance. Thermal error isolation method emphasizes the reduction of numerical value in thermal error propagation path. In this paper, the machine tool swing head is taken as the research object, and the above two methods are innovatively combined; Build an experimental platform and a simulation model to ensure the accuracy of the experiment through mutual verification; The POA-LSTM prediction model is established to predict the expansion of the swing head shell structure caused by thermal load accumulation, and compared with the LSTM prediction model. The results show that the prediction accuracy of the POA-LSTM prediction model in Z direction and X direction is 98.89 % and 98.38 %, respectively, which is higher than that of LSTM's 89.33 % and 89.47 %. The experiment for shell structure optimization is designed to reduce the thermal expansion of the pendulum and improve the machining accuracy. As a result, the thermal expansion inhibition effect on the whole pendulum is 26.14 %, and the thermal expansion inhibition effects on the X-direction, Y-direction and Z-direction are 34.93 %, 33.35 % and 30.24 % respectively.

Vacuum brazing of GH3535 alloy was conducted using Au–18Ni (wt%) filler metal. The effect of brazing temperature on the microstructure and mechanical properties was investigated. Furthermore, the microstructural evolution and fracture mechanisms of brazed joints were discussed. The cross section of brazed joint could be divided into two distinctive reaction zones. The typical microstructure of the joint brazed at 1030 °C/10min was GH3535 substrate/Ni (s.s) + Mo-rich Ni (s.s) + Au-rich phase/Au (s.s) + FeNi3/Au-rich phase + Mo-rich Ni (s.s) + Ni (s.s) + GH3535 substrate. Raising the brazing temperature promoted the diffusion of elements, Ni (s.s) and Au (s.s) gradually increased, and the second phase particles consisting of FeNi3 gradually decreased. With the increase in brazing temperature, the shear strength of brazed joints first increased and then decreased. The maximum room shear strength of 420 MPa was obtained at 960 °C/25min and the high temperature shear strength of 153 MPa was obtained at 600 °C. Fracture analysis indicated that cracks initiated at the interface of Au (s.s) and then propagated along the zone of FeNi3 with dimple and tearing ridges patterns.

An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of smooth muscle cells (SMCs), extracellular matrix degradation, and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. Diagnosis is mostly accidental and the only currently available treatment option remains surgical intervention. Circular RNAs (circRNAs) represent a novel class of regulatory non-coding RNAs that originate from backsplicing. Their highly stable loop structure, combined with a remarkable enrichment in body fluids, make circRNAs promising disease biomarkers. We investigated the contribution of circRNAs to AAA pathogenesis and their potential application to improve AAA diagnostics. Gene expression analysis revealed the presence of deregulated circular transcripts stemming from AAA-relevant gene loci. Among these, the circRNA to the Ataxia Telangiectasia Mutated gene (cATM) was upregulated in human AAA specimens, in AAA-derived SMCs, and serum samples collected from aneurysm patients. In primary aortic SMCs, cATM increased upon angiotensin II and doxorubicin stimulation, while its silencing triggered apoptosis. Higher cATM levels made AAA-derived SMCs less vulnerable to oxidative stress, compared with control SMCs. These data suggest that cATM contributes to elicit an adaptive oxidative-stress response in SMCs and provides a reliable AAA disease signature.

BackgroundOur study aimed to develop machine learning algorithms capable of predicting red blood cell (RBC) transfusion during valve replacement surgery based on a preoperative dataset of the non-anemic cohort.MethodsA total of 423 patients who underwent valvular replacement surgery from January 2015 to December 2020 were enrolled. A comprehensive database that incorporated demographic characteristics, clinical conditions, and results of preoperative biochemistry tests was used for establishing the models. A range of machine learning algorithms were employed, including decision tree, random forest, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), support vector classifier and logistic regression (LR). Subsequently, the area under the receiver operating characteristic curve (AUC), accuracy, recall, precision, and F1 score were used to determine the predictive capability of the algorithms. Furthermore, we utilized SHapley Additive exPlanation (SHAP) values to explain the optimal prediction model.ResultsThe enrolled patients were randomly divided into training set and testing set according to the 8:2 ratio. There were 16 important features identified by Sequential Backward Selection for model establishment. The top 5 most influential features in the RF importance matrix plot were hematocrit, hemoglobin, ALT, fibrinogen, and ferritin. The optimal prediction model was CatBoost algorithm, exhibiting the highest AUC (0.752, 95% CI: 0.662–0.780), which also got relatively high F1 score (0.695). The CatBoost algorithm also showed superior performance over the LR model with the AUC (0.666, 95% CI: 0.534–0.697). The SHAP summary plot and the SHAP dependence plot were used to visually illustrate the positive or negative effects of the selected features attributed to the CatBoost model.ConclusionsThis study established a series of prediction models to enhance risk assessment of intraoperative RBC transfusion during valve replacement in no-anemic patients. The identified important predictors may provide effective preoperative interventions.

ABSTRACT The accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the substrate recognition receptor PRPF19 interacts with CUL4B, DDB1, and RBX1 to form a CRL4B-based E3 ligase, which catalyzes ORF6 ubiquitination and subsequent degradation. Overexpression of PRPF19 promotes ORF6 degradation, releasing ORF6-mediated IFN inhibition, which inhibits SARS-CoV-2 replication. Moreover, we found that activation of CUL4B by the neddylation inducer etoposide alleviates lung lesions in a SARS-CoV-2 mouse infection model. Therefore, targeting ORF6 for degradation may be an effective therapeutic strategy against SARS-CoV-2 infection.IMPORTANCEThe cellular biological function of the ubiquitin-proteasome pathway as an important modulator for the regulation of many fundamental cellular processes has been greatly appreciated. The critical role of the ubiquitin-proteasome pathway in viral pathogenesis has become increasingly apparent. It is a powerful tool that host cells use to defend against viral infection. Some cellular proteins can function as restriction factors to limit viral infection by ubiquitin-dependent degradation. In this research, we identificated of CUL4B-DDB1-PRPF19 E3 Ubiquitin Ligase Complex can mediate proteasomal degradation of ORF6, leading to inhibition of viral replication. Moreover, the CUL4B activator etoposide alleviates disease development in a mouse infection model, suggesting that this agent or its derivatives may be used to treat infections caused by SARS-CoV-2. We believe that these results will be extremely useful for the scientific and clinic communities in their search for cues and preventive measures to combat the COVID-19 pandemic.

ABSTRACT: Riemerella anatipestifer (RA) is an important pathogen of waterfowl, with multiple serotypes and a lack of cross-protection between each serotype, which leads to the continued widespread in the world and causing significant economic losses to the duck industry. Thus, prevention and inhibition of RA infection are of great concern. Previous research has established that Lactobacillus plantarum supernatant (LPS) can prevents the pathogenic bacteria infection. However, LPS whether inhibits RA and underlying mechanisms have not yet been clarified. In this study, we investigated the direct and indirect effects of LPS-ZG7 against RA infection in Muscovy ducks. The results demonstrated that LPS-ZG7 prevented RA growth in the presence of pH-neutralized, and the inhibition was relatively stable and unaffected by heat, acid-base and ultraviolet light (UV). Following flow cytometry data found that LPS-ZG7 increased RA membrane permeability and leakage of intracellular molecules. And scanning electron microscopy revealed LPS-ZG7 damaged the RA membrane integrity and leading to RA death. Furthermore, quantitative real time polymerase chain reaction (qPCR) analysis represented that LPS-ZG7 upregulated mucosal tight junction proteins occludin, claudin-1, and Zo-1 in Muscovy ducks, and increasing mucosal transport channels SGLT-1, PepT1, AQP2, AQP3, and AQP10 in duodenum, jejunum, and colon, then decreased the intestinal permeability and intestinal barrier disruption which were caused from RA. From the data, it is apparent that LPS-ZG7 enhanced intestinal mucosal integrity by rising villus height, villus height-to-crypt depth ratio and lower crypt depth. LPS-ZG7 significantly decreased intestinal epithelia cells apoptosis caused by RA invasion, and enhanced intestinal permeability and contribute to barrier dysfunction, ultimately improving intestinal health of host, indirectly leading to reduce diarrhea rate and mortality caused by RA. Overall, this study strengthens the idea that LPS-ZG7 directly inhibited the RA growth by increased RA membrane permeability and damaged the RA membrane integrity, and then indirectly enhanced intestinal mucosal integrity, improved intestinal health of host and mediated intestinal antimicrobial defense.

With the increasing importance of motorized spindles in high-end machining, the accuracy requirements for motorized spindles have been increasing. Therefore, the accuracy problem caused by thermal deformation of the motor spindle during machining has become a prominent and current topic of interest. The problem of thermal deformation of the spindle is due to the fact that a large amount of heat is accumulated inside the spindle during the high-speed rotation of the electric spindle, which has no timely temperature compensation measures and can only rely on the conditions of heat conduction, heat convection and heat radiation to transfer the heat to the outside world, which leads to the thermal expansion of the spindle. Aiming at this problem, this paper takes the A02 electric spindle as the research object, and collects and analyzes the temperature information of the current temperature rise of the key parts of the electric spindle and the thermal elongation of the spindle by constructing the experimental platform for thermal simulation and analysis; and then through the COMSOL steady-state simulation cloud diagram combined with the K-means clustering and gray correlation analysis, it filters out the four temperature points with the highest correlation degree of the temperature data, and constructs the POA-LSTM thermal error model to predict the thermal elongation of the spindle at different rotational speeds, and compared the accuracy of SSA-LSTM and LSTM thermal error models, at a high rotational speed of 10,000 r/min, the accuracies of Early LSTM, SSA-LSTM, and LSTM were 97.44 %, 90.27 %, and 86.66 %, respectively, and the model accuracy of POA-LSTM was about 98.257 %; thus the POA-LSTM thermal error model has high prediction accuracy and robustness.

Rougui Tea (RGT) is a typical Wuyi Rock Tea (WRT) that is favored by consumers for its rich taste and varied aroma. The aroma of RGT is greatly affected by the process of green-making, but its mechanism is not clear. Therefore, in this study, fresh leaves of RGT in spring were picked, and green-making (including shaking and spreading) and spreading (unshaken) were, respectively, applied after sun withering. Then, they were analyzed by GC-TOF-MS, which showed that the abundance of volatile compounds with flowery and fruity aromas, such as nerolidol, jasmine lactone, jasmone, indole, hexyl hexanoate, (E)-3-hexenyl butyrate and 1-hexyl acetate, in green-making leaves, was significantly higher than that in spreading leaves. Transcriptomic and proteomic studies showed that long-term mechanical injury and dehydration could activate the upregulated expression of genes related to the formation pathways of the aroma, but the regulation of protein expression was not completely consistent. Mechanical injury in the process of green-making was more conducive to the positive regulation of the allene oxide synthase (AOS) branch of the α-linolenic acid metabolism pathway, followed by the mevalonate (MVA) pathway of terpenoid backbone biosynthesis, thus promoting the synthesis of jasmonic acid derivatives and sesquiterpene products. Protein interaction analysis revealed that the key proteins of the synthesis pathway of jasmonic acid derivatives were acyl-CoA oxidase (ACX), enoyl-CoA hydratase (MFP2), OPC-8:0 CoA ligase 1 (OPCL1) and so on. This study provides a theoretical basis for the further explanation of the formation mechanism of the aroma substances in WRT during the manufacturing process.

The miniature heat sink is an essential component in integrated circuit packaging, playing a vital role in ensuring the stable and reliable performance of integrated circuits. In this paper, we establish a simulation model of the heat transfer performance of a miniature heat sink with a square columnar array microstructure and study the effect of the dimensional parameters of the miniature heat sink on the heat transfer performance. Then, the mathematical equations between the heat source temperature and the dimensional parameters of the miniature heat sink are obtained based on the response surface method, and the dimensional parameters are optimized. Finally, wire electrical discharge machining (WEDM) was used to prepare miniature heat sinks and to test the heat transfer performance. The experimental results show that both the simulation model and the mathematical equations have high accuracy, and the heat source temperature of the miniature heat sink with column width, column distance, and column height of 364 μm, 331 μm, and 1500 μm, respectively, can be reduced to 101.8 °C, which is 93.5 °C lower than the heat source temperature of 195.3 °C without heat sink, and the temperature reduction reaches 47.9%. The miniature heat sink has a simple manufacturing process, low manufacturing cost, small overall size, and good heat transfer performance, which has a broad application prospect in the field of integrated circuit packaging.

Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by the ubiquitin-proteasome system (UPS). Importantly, RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity, which may be exploited as a prognostic marker for COVID-19. Furthermore, RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV, suggesting that targeting RNF5 is a broad-spectrum antiviral strategy. Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication, which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.

Numerous viruses manipulate host factors for viral production. We demonstrated that human enterovirus A71 (EVA71), a primary causative agent for hand, foot, and mouth disease (HFMD), increased the level of the DNA damage response (DDR) marker γ-H2AX. DDR is primarily mediated by the ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), or DNA-dependent protein kinase (DNA-PK) pathways. Upregulation of γ-H2AX by EVA71 was dependent on the ATR but not the ATM or DNA-PK pathway. As a nuclear factor, there is no previous evidence of cytoplasmic distribution of γ-H2AX. However, the present findings demonstrated that EVA71 encouraged the localization of γ-H2AX to the cytoplasm. Of note, γ-H2AX formed a complex with structural protein VP3, non-structural protein 3D, and the viral genome. Treatment with an inhibitor or CRISPR/Cas9 technology to decrease or silence the expression of γ-H2AX decreased viral genome replication in host cells; this effect was accompanied by decreased viral protein expression and virions. In animal experiments, caffeine was used to inhibit DDR; the results revealed that caffeine protected neonatal mice from death after infection with EVA71, laying the foundation for new therapeutic applications of caffeine. More importantly, in children with HFMD, γ-H2AX was upregulated in peripheral blood lymphocytes. The consistent in vitro and in vivo data on γ-H2AX from this study suggested that caffeine or other inhibitors of DDR might be novel therapeutic agents for HFMD.

To study the phenomenon of large deformation and the failure of roadways under dynamic pressure, this paper takes the 10607 gas drainage roadway as the research object and presents the results of a theoretical derivation of equations for the boundary of the plastic zone of a dynamic pressure roadway with and without supporting force. The impacts of the mining influence coefficient and supporting force on the plastic zone boundary were explored for various lateral pressure coefficients. As the supporting force was increased, it was observed that there was a slight reduction in the radius of the plastic zone of the dynamic pressure roadway, while its scope and shape barely changed. Based on the failure mechanism of the dynamic pressure roadway, active and passive support technology was proposed, and the support effect was analyzed using FLAC3D 5.0 numerical simulation software for the case of the 10607 gas drainage roadway.

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections.

In high-precision machining machine tools, the high-speed electric spindle is the fundamental transmission component. Nonetheless, the electric spindle's small and tightly sealed internal structure may result in insufficient heat dissipation, resulting in significant heat accumulation during continuous operation. This might induce thermal displacement of the spindle and reduce machine tool machining precision. A response surface was established by a 2-factor 3-level interaction experiment utilizing Design-expert software to reduce the heat displacement of the electric spindle. The electric spindle cooling water jacket was optimized and front and rear bearing cooling water channels were added based on the response surface results. The thermal-solid coupling simulation was carried out using ANSYS, and the optimized data for the front and rear bearing temperature, as well as spindle thermal displacement, were obtained through simulation analysis. Comparing the simulation with the experimental data, it was found that the front and rear bearing temperature decreased by 4.34 °C and 8.97 °C, respectively, and the spindle thermal displacement was reduced by 16.57 μm, resulting in improved machining accuracy. The service life of the bearings was further prolonged by the decreased thermal stress between the inner and outer rings and the balls of the front and rear bearings.

The thermal error generated by the high-speed motorized spindle during machining is the main reason for the exactness of the machine tool, so accurate thermal characteristics analysis is essential. In this paper, the experimental platform of motorized spindle was set up to measure the temperature and thermal displacement data at 10000r/min. Secondly, the simulation parameters of A02 high-speed motorized spindle are obtained through theoretical calculation, and the multiphysics simulation model is established. After calculation, the exactness of the temperature field model can reach about 95%, and the exactness of the displacement field can reach 85%, it shows that the simulation model can accurately predict the state of motorized spindle. Finally, a new cooling jacket structure is proposed, and it is found that the optimized temperature is reduced by 32.11% and the thermal displacement of the front surface is reduced by 32.63%. indicating that the improved cooling water jacket has better cooling performance than the traditional cooling water jacket.

Abstract To analyze the plastic failure process and mechanism of gob floor in the process of close‐distance coal seams mining, a simplified mechanical model of the lateral abutment pressure of the gob was proposed to derive the stress of surrounding rock. The distribution characteristics of gob floor stress deviator were obtained, and the effect of geological parameters (coal depth H and horizontal lateral pressure coefficient λ) were studied. By combining Mohr–Coulomb theory, the influence of surrounding rock cohesion c, internal friction angle φ, different coal seam depths H and different horizontal lateral pressure coefficients λ on the distribution of plastic zone of gob floor was obtained. The results showed that the distribution of the plastic zone under different geological factors is roughly the same as that of the stress deviator. This also proves that the excavation of the rock layer causes the redistribution of stress, which leads to the plastic failure of the surrounding rock. To verify the rationality of the proposed model, industrial experiments and simulation experiments were carried out. The results of on‐site investigation showed that the stability and integrity of surrounding rock in the concentration area of stress deviator is far less than that in the low concentration area. In addition, the acoustic wave test and the displacement field monitoring result of surrounding rock in the simulation experiments of a similar model are basically consistent with the distribution of the stress deviator field. These results agree well with the distribution of stress deviator obtained by theoretical calculation.

Nuclear factor (NF)-κB plays an important role in the innate immune response by inducing antiviral genes’ expression. However, the herpes simplex virus 1 (HSV-1) virus has developed multiple ways to interfere with NF-κB activity to escape the host antiviral response. Here, we found that HSV-1 envelope glycoprotein L(gL) markedly inhibits interferon (IFN) production and its downstream antiviral genes. Our results showed that ectopic expression of gL inhibited IFN-β promoter activation, and decreased IFN-β production, the expression of IFN-stimulated genes (ISGs), and inhibited immunologic stimulant (poly I:C) induced activation of IFN signaling pathway. Depletion of gL by short interfering RNA (siRNA) significantly upregulated IFN-β and ISG production. Further study showed that the N-terminus of the gL bound to the Rel homology domain (RHD) of the p65 and concealed the nuclear localization signal of p65, thereby impeding the translocation of phosphorylated p65 to the nucleus. In summary, our findings indicated that the N-terminal of HSV-1 gL contributes to immune invasion by inhibiting the nuclear translocation of p65.

Optical clocks can be used as the absolute frequency reference due to their high accuracy and stability. In a precise optical clock transmission system, the instability loss of the link is usually evaluated by beating the remote optical signal with the reference clock, which is not suitable for real frequency distribution applications. Therefore, it is necessary to assess the performance directly at the remote site for the optical frequency transfer, because the two sites of the link are usually not co-located. In this paper, we proposed a comb-based remote residual instability evaluation scheme. Two coherent optical combs with different wavelengths were extracted from a frequency stable comb and transmitted after multiplexing. The residual instability was evaluated directly at the remote site by measuring the phase fluctuation difference between the two combs. We achieved 8.61 × 10−19 at 40,000 s over a 10 km fiber link, reaching the instability of optical clocks. These results revealed that our scheme can evaluate optical clock frequency transmission directly at the remote site, which made the method truly practical.

Abstract Discrete element calculations of the top-coal drawing process for different gangue-coal density ratios were conducted to investigate the effect of the gangue-coal density ratio on the drawing mechanism in longwall top-coal caving. The effects were analyzed for the drawing body, the top-coal boundary, and the recovery of top coal. The results show that for increasing density ratio, the initial drawing body on the goaf side is farther away from the drawing support and its width and volume gradually increase. The upper part of the sickle-shaped drawing body extends near the initial drawing body with increasing density ratio in the normal cycling stage, and the distance from the drawing body to the initial drawing body is its maximum width. The larger the density ratio, the smaller the height of the top coal above the goaf at the end of the initial drawing process. The height of the top-coal boundary decreases with increasing density ratio, until it reaches a limit. In a normal cycle, due to hysteretic development, the top-coal boundary moves toward the goaf until the density ratio is approximately 2.0, which is consistent with the physical experiment results. Finally, increasing the advance length of the working face is beneficial for increasing the overall recovery of top coal.

The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.

Background and Aims. Intestinal ultrasound (IUS) is considered a nonirradiating, noninvasive, well-tolerated, and valuable tool for objectively assessing Crohn’s disease (CD) activity. However, there is no widely accepted intestinal ultrasound scoring system. This study is aimed at evaluating the efficacy of IUS key parameters, the International Bowel Ultrasound Activity Score (IBUS-SAS), and IBUS-SAS combined with blood inflammatory markers in assessing CD activity. Methods. 40 CD patients were reviewed in this retrospective study and were divided into the moderate-severe group (n=25) and nonmoderate-severe group (n=15) based on a simplified endoscopic score of Crohn’s disease (SES-CD). Double-balloon enteroscopy/colonoscopy were reviewed by three gastroenterologists. A transabdominal ultrasound was performed by two ultrasound specialists. Blood inflammatory markers were measured from morning samples. Results. In evaluating moderate to severe CD patients, (1) IBUS-SAS had a good predictive effect with an area-under-the-curve (AUC) of 0.855 (P

In the practical processes of coal mines and tunnel, rectangular roadways are widely used in the underground environment. However, the stress distribution law of the rock mass around the rectangular roadways is relatively complicated that is influenced by different parameters, such as the in situ stress, geological structure, and properties of the surrounding rock mass. It is extremely significant to conduct systematic and in-depth research regarding the stress distribution and deformation failure mechanism of the rock mass around the rectangular roadways. Based on theoretical analysis, the stress distribution law of the surrounding rock of rectangular roadway under different rock mass strength grades is studied directly through rectangular roadway in this paper. This further reveals the distribution law of secondary stress field after excavation of rectangular roadway. A coal mine intends to excavate a roadway in rock mass, and then, the rectangular roadway is simulated by FLAC3D software. Then, the strain distribution and failure types of roadway surrounding rock under different rock mass properties are obtained. The results show that the failure of rectangular roadway is mainly shear failure and tensile failure. The roof and floor of roadway are mainly tensile failure, and the side of roadway is mainly shear failure. Moreover, the stress shifting and distribution of the rock mass around rectangular roadways is a complicated dynamic variation process. The damage degree of the floor and roof of the rectangular roadway is greater than that of the two sides of the roadway. Its variation is mainly related to the strength of surrounding rock mass.

In this article, to heighten the accuracy of thermal error forecast model of motorized spindle, a thermal error modeling method of kernel extreme learning machine based on snake optimization is advanced. ANSYS simulation software is used to simulate the thermal characteristics of the electric spindle, and the temperature field distribution is acquired. Then, according to the experimental requirements, a platform is built to obtain the axial temperature and thermal displacement data of the spindle. The FCM algorithm and grey relation analysis are utilized to optimize the survey points, and ten measuring points are reduced to four. The SO-KELM model is established based on the snake-optimized kernel extreme learning machine. Comparing the established model with the KELM model and PSO-KELM model, it is proved that SO-KELM model has good prediction accuracy and stability.

We apply the Empirical Mode Decomposition (EMD) algorithm and the Time Convolutional Network (TCN) structure, predicated on Convolutional Neural Networks, to successfully enable feature extraction within high-precision optical time-frequency signals, and provide effective identification and alerts for abnormal link states. Experimental validation confirms that the proposed method not only delivers an efficacy on par with traditional manual techniques, but also excels in swiftly identifying anomalies that typically elude conventional approaches. This investigation furnishes novel theoretical backing and forecasting tools for high-precision optical transmission.

Abstract A traditional Chinese medicine formula based on the Coix seed and Lotus seed has been used as a general treatment of malnutrition, excessive fatigue, dysfunction of the spleen and stomach, and disorders of water transport in humans in China. However, there is limited information on its effects on the gut microbiota of piglets in vivo. In this study, the mix of Coix seed and Lotus were added the diet of forty weaned piglets (local piglets), and then evaluated it’s affected on the gut microbiota of piglets and on the relations within the gut bacterial community. The results indicated that this traditional Chinese medicine formula (LM) and the extract of the traditional Chinese medicine formula (LMT) downregulated pH of succus gastricus and raised pH of the ileum, and LMT obviously decreased the feed conversion ratio. Further study showed LMT and LM also significantly increased the thick and long of gastrointestinal villi. And then, 16S ribosomal DNA sequencing revealed that groups LMT and LM have higher relative abundance of the genus Lactobacillus in the colon, succus gastricus, and jejunum, which are beneficial bacteria sold as dietary supplements to aid digestion or to augment health. Meanwhile, the relative abundance levels of Prevotellaceae, Alloprevotella, and Prevotella in the colon and Clostridium in succus gastricus and jejunum were lower. These experiments highlight the usefulness of the traditional Chinese medicine formula based on the Coix seed and Lotus seed for decreasing pH in succus gastricus, for improving the structure of intestinal villi and gut microflora, and then for achieving improvements in pig production performance.

The thermal error of electric spindle is an important factor affecting the machining accuracy of machine tools. To establish the thermal error prediction model, the thermal characteristics of A02 electric spindle were simulated and analyzed by ANSYS, to determine the best temperature measuring point. The temperature and thermal error of A02 electric spindle at different rotational speeds were obtained by thermal characteristics experiment. Through the combination of systematic clustering and grey relational analysis, four best temperature measuring points were selected from ten temperature measuring points. A prediction model of least squares support vector machine (LSSVM) optimized by Aquila Optimizer (AO) is established and compared with the model optimized by Particle Swarm Optimization (PSO), it is superior to the latter in prediction accuracy (η), goodness of fit (R2), root mean square error (RMSE) and mean absolute error (MAE). The AO-LSSVM prediction model based on experimental data has a prediction accuracy of more than 94% for the thermal error of motorized spindle and has good stability and generalization ability.

The gradual development of coal mining in deep areas has brought new challenges to the surrounding rock support system. It is imperative to design surrounding rock support elements that exhibit strong tensile and shear resistance and are suitable for pretension load. In this paper, an anchor cable bolt with a c-shaped tube (ACC) is proposed, and in order to study the shear performance of the ACC, the mechanical properties of the ACC and ordinary cable bolts with various diameters and pretension loads are tested. In addition, a comparative analysis is performed to investigate the effect of diameter and pretension load on the shear strength of the ACC and cable bolts. The results show that compared with ordinary cable bolts, the ACC exhibits better shear resistance, where its ability to withstand transverse shear load and shear deformation increased by more than 26.8% and 7.0%, respectively. The diameter and pretension load of the bolt significantly affect its shear performance. The larger the diameter of the bolt, the greater the peak shear load. By increasing the pretension load, the shear load and shear displacement at the peak shear load decrease. The failure of the ACC and ordinary cable bolt is mainly due to a combination of shear and tensile failures. In addition, the action mechanism of the ACC is preliminarily explored, and it provides some references for clarifying the mechanical properties of the ACC.

High-speed electric spindle is an important part of computer numerical control (CNC) machining equipment, and the thermal displacement generated by the electric spindle during operation affects the electric spindle machining stability and machining accuracy. Error compensation for the high-speed motorized spindle can well compensate for the influence of thermal displacement on machine tool processing. Therefore, the prediction of thermal displacement of electric spindle is particularly important. In this paper, firstly, the temperature field information is obtained by simulating and analyzing the calculation of the heat generation and heat exchange inside the electric spindle. Set up the experimental platform with reasonable temperature measurement points according to the simulation results; secondly, the temperature sensitive points are screened by fuzzy C-mean clustering algorithm and Pearson correlation coefficient, which can effectively improve the covariance and correlation between temperature variables; finally, based on the screened data for thermal error modeling, an optimized extreme learning machine based on marine predator algorithm (MPA-ELM) is provided to predict the thermal displacement of electric spindles model. And comparing the model accuracy of extreme learning machine (ELM), MPA-ELM and extreme learning machine optimized by genetic algorithm (GA-ELM), the experimental data show that MPA-ELM has better prediction accuracy.

Shahejie marl in the Shulu Sag is a crucial resource for unconventional hydrocarbon exploration in China. Although breakthroughs have been made in tight oil exploration in this area, the mechanisms underlying the formation of this marl reservoir and factors controlling its ‘sweet spots’ have not been thoroughly studied. To understand the pore structure characteristics and factors influencing the marl reservoir, we analyzed core samples from Wells ST1 and ST3. A series of experiments was conducted on the samples, such as X-ray diffraction, focused ion beam scanning electron microscopy, micro-CT, and total organic carbon test. Additionally, the physical properties of different marl rock fabrics were studied with auxiliary tests, such as mercury intrusion capillary pressure analyses, nuclear magnetic resonance, porosity and permeability tests, and thin-section observation. The results revealed that the marl reservoir is characterized by low porosity (1.61%) and low permeability (2.56mD). The porosity and permeability (1.61% and 3.26mD) of laminated marl were better than those (0.92% and 1.68mD) of massive marl. Clay minerals and quartz content in laminated (11.8 and 8.2%) was less than in massive marl (16.2 and 13.3%). The marl pores include intercrystalline pores, dissolution pores, and microfractures. Additionally, the laminated marl pores were primarily distributed along the dark lamina, with good connectivity. A few isolated and uniform holes were observed in the massive marl. Influenced by rock fabric and mineral composition, layered fractures were mainly developed in the laminated marl, while structural fractures were the main type of microfractures in the massive marl. The primary sedimentary mechanism was the main geological action underlying the differences in marl rock fabric; this mechanism affects the physical properties of the marl reservoir, which are key factors to be considered when searching for the marl reservoir ‘sweet spots’. Particular attention should be paid to these factors during tight oil exploration and development in similar sedimentary basins.

Electrochemical machining (ECM) is an essential method for machining gas film cooling holes in high-temperature resistant nickel-based alloys. However it is difficult to directly measure the temperature of the machining area of the cooling hole during ECM, which leads to a significant error between the simulation and the experimental data on the machining accuracy of the cooling hole. Based on the convective heat transfer model and the k-ε turbulence model, this paper establishes a simulation model of the machining accuracy of the ECM cooling hole considering the influence of the temperature field. The influences of machining voltage, electrolyte concentration, electrolyte inlet flow rate, and tool cathode feed rate on the electrolyte temperature distribution in the machining area and on the machining accuracy of the cooling holes were simulated and analyzed by COMSOL Multiphysics software. Experimental research was done to investigate the influence of craftsmanship parameters on the machining accuracy of cooling holes. The simulation and experimental results show that there is a significant error between the simulation data and the experimental data for the machining accuracy of cooling holes without considering the influence of the temperature field, and the simulation data of the machining accuracy of the cooling hole considering the influence of temperature field is consistent with the experimental data. The simulation model considering the influence of the temperature field, has high prediction accuracy for the machining accuracy of ECM cooling holes, which is of great significance to improve the machining accuracy of cooling holes.

ABSTRACT Ubiquitin signaling is essential for immunity to restrict pathogen proliferation. Due to its enormous impact on human health and the global economy, intensive efforts have been invested in studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its interactions with hosts. However, the role of the ubiquitin network in pathogenicity has not yet been explored. Here, we found that ORF9b of SARS-CoV-2 is ubiquitinated on Lys-4 and Lys-40 by unknown E3 ubiquitin ligases and is degraded by the ubiquitin proteasomal system. Importantly, we identified USP29 as a host factor that prevents ORF9b ubiquitination and subsequent degradation. USP29 interacts with the carboxyl end of ORF9b and removes ubiquitin chains from the protein, thereby inhibiting type I interferon (IFN) induction and NF-κB activation. We also found that ORF9b stabilization by USP29 enhanced the virulence of VSV-eGFP and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). Moreover, we observed that the mRNA level of USP29 in SARS-CoV-2 patients was higher than that in healthy people. Our findings provide important evidence indicating that targeting USP29 may effectively combat SARS-CoV-2 infection. IMPORTANCE Coronavirus disease 2019 (COVID-19) is a current global health threat caused by SARS-CoV-2. The innate immune response such as type I IFN (IFN-I) is the first line of host defense against viral infections, whereas SARS-CoV-2 proteins antagonize IFN-I production through distinct mechanisms. Among them, ORF9b inhibits the canonical IκB kinase alpha (IKKɑ)/β/γ-NF-κB signaling and subsequent IFN production; therefore, discovering the regulation of ORF9b by the host might help develop a novel antiviral strategy. Posttranslational modification of proteins by ubiquitination regulates many biological processes, including viral infections. Here, we report that ORF9b is ubiquitinated and degraded through the proteasome pathway, whereas deubiquitinase USP29 deubiquitinates ORF9b and prevents its degradation, resulting in the enhancement of ORF9b-mediated inhibition of IFN-I and NF-κB activation and the enhancement of virulence of VSV-eGFP and SARS-CoV-2 trVLP.

Enterovirus infection continues to be a global health problem. The lack of specific drugs and broad-spectrum vaccines means an urgent need to develop effective strategies against enteroviruses. Host restrictive factors are a class of intrinsic host antiviral factors that have been broadly defined and investigated during HIV infections and have great significance for drug development and treatment design. In recent years, the essential role of host restrictive factors in regulating enteroviral infections has been gradually recognized and investigated. An increasing number of studies have shown that host-restrictive factors regulate multiple steps in the life cycle of enteroviruses. This mini-review discusses the restrictive factors against enteroviruses, their antiviral mechanism, and the arms race between them and enteroviruses. We also summarise the pathways that enteroviruses use to impair host antiviral signals. This mini-review characterizes the essential role of host restriction factors in enterovirus infections, which provides ideas and potential targets for antiviral drug design by regulating host restrictive factors. It also reveals potential future research on the interplay between host restrictive factors and enteroviruses.

Abstract Background African swine fever (ASF) leads to high mortality in domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). Currently, no vaccine is commercially available for prevention, and the epidemic is still spreading. Here, we constructed a recombinant pseudorabies virus (PRV) (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) that expresses the CD2v protein of ASFV and evaluated its effectiveness and safety as a vaccine candidate in mice. Methods A homologous recombination fragment containing ASFV CD2v was synthesized and co-transfected into HEK 293 T cells, a knockout vector targeting the PRV TK gene. The transfected cells were infected with PRV-ΔgE/ΔgI, and the recombinant strain (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) was obtained by plaque purification in Vero cells. The expression of ASFV CD2v in the recombinant virus was confirmed by sequencing, Western blotting, and immunofluorescence analysis, and the genetic stability was tested in Vero cells over 20 passages. The virulence, immunogenicity and protective ability of the recombinant virus were further tested in a mouse model. Results The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain is stable in Vero cells, and the processing of CD2v does not depend on ASFV infection. The vaccination of PRV-ΔgE/ΔgI/ΔTK-(CD2v) causes neither pruritus, not a systemic infection and inflammation (with the high expression of interleukin-6 (IL6)). Besides, the virus vaccination can produce anti-CD2v specific antibody and activate a specific cellular immune response, and 100% protect mice from the challenge of the virulent strain (PRV-Fa). The detoxification occurs much earlier upon the recombinant virus vaccination and the amount of detoxification is much lower as well. Conclusions The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain has strong immunogenicity, is safe and effective, and maybe a potential vaccine candidate for the prevention of ASF and Pseudorabies.

Pore structure is one of the important parameters for evaluating reservoirs, critical in controlling the storage capacity and transportation properties of hydrocarbons. The conventional pore characterization method cannot fully reflect the pore network morphology. The edge-threshold automatic processing method is applied to extract and quantify pore structures in shale scanning electron microscope (SEM) images. In this manuscript, a natural lacustrine oil-prone shale in the Qingshankou Formation of Songliao Basin is used as the research object. Based on FE-SEM, a high-resolution cross-section of shale was obtained to analyze the microstructure of pores and characterize the heterogeneity of pores by multifractal theory. The stringent representative elementary area (REA) of the SEM cross-section was determined to be 35 × 35. Four pore types were found and analyzed in the stringent REA: organic pores, organic cracks, inorganic pores, inorganic cracks. The results showed that inorganic pores and cracks were the main pore types and accounted for 87.8% of the total pore area, and organic cracks were of the least importance in the Qingshankou shale. Inorganic pores were characterized as the simplest pore morphologies, with the largest average MinFeret diameter, and the least heterogeneity. Moreover, the inorganic cracks had a long extension distance and stronger homogeneity, which could effectively connect the inorganic pores. Organic pores were found to be the most complex for pore structure, with the least average MinFeret diameter, but the largest heterogeneity. In addition, the extension distance of the organic cracks was short and could not effectively connect the organic pore. We concluded that inorganic pores and cracks are a key factor in the storage and seepage capacity of the Qingshankou shale. Organic pores and cracks provide limited storage space.

The high-speed motorized spindle is the core component of high-speed and high-precision machining, and its compact structure leads to internal heat accumulation and thermal deformation. Therefore, it is of great significance to control the temperature rise of the motorized spindle. In order to effectively control the temperature rise of the motorized spindle, a new spiral cooling system is used to analyze the internal heat transfer mechanism of the high-speed motorized spindle, and the heat transfer coefficients of the spiral cooling system and the motorized spindle system are optimized based on the gradient descent method combined with experimental data. The optimized heat transfer coefficient is taken as the boundary condition of the finite element model, and the temperature field prediction model is established to analyze the influence of the spiral cooling system on the temperature field of the motorized spindle. Through experiments, the cooling capacity of the spiral cooling system is verified, and the optimized temperature field simulation data are compared with the experimental data to verify the feasibility of the gradient descent method in constructing the temperature field prediction model of the motorized spindle. It provides a basis for the intelligent control of the thermal performance of the motorized spindle.

Higher sensitivity in timing jitter measurement has great importance in studies related to precise measurements. Timing jitter noise floors contribute one of the main parts in existing measurements. In this article, a phase error signal is obtained by superposition of outputs of two optical heterodyne discrimination apparatus to suppress the noise floor. Excess phase noise of the electrical amplifier is avoided. We demonstrate 2.6 × 10−14 fs2/Hz (~160 ys/√Hz) timing jitter noise floor between two identical 99 MHz repetition-rate mode-locked Ti:sapphire lasers after their repetition rates are tightly synchronized. The performance is extensible to reach an integrated timing jitter resolution of one attosecond.

Electrochemical machining (ECM) is an essential method for machining miniature bearing outer rings on the high-temperature-resistant nickel-based alloy GH4169. However, the influence of electrolyte temperature distribution and bubble rate distribution on electrolyte conductivity in the ECM area could not be fully considered, resulting in the simulation model not being able to accurately predict the machining accuracy of the outer ring of the miniature bearing, making it challenging to model and predict the optimal process parameters. In this paper, a multiphysics field coupled simulation model of electric, flow, and temperature fields during the ECM of the miniature bearing outer ring is established based on the gas–liquid two-phase turbulent flow model. The simulation analyzed the distribution of electrolyte temperature, bubble rate, flow rate, and current density in the machining area, and the profile change of the outer ring of the miniature bearing during the machining process. The analysis of variance and significance of machining voltage, electrolyte concentration, electrolyte inlet flow rate, and interaction on the mean error of the ECM miniature bearing outer rings was derived from the central composite design. The regression equation between the average error and the process parameters was established, and the optimal combination of process parameters for the average error was predicted, i.e., the minimum value of 0.014 mm could be achieved under the conditions of a machining voltage of 16.20 V, an electrolyte concentration of 9.29%, and an electrolyte inlet flow rate of 11.84 m/s. This is important to improve the machining accuracy of the outer ring of the ECM miniature bearing.

Abstract Coix seed has traditionally been used in traditional Chinese medicine to fortify the spleen and inhibit dampness, and has shown anticancer effects in humans. However, it is not known whether coix seed improves post-weaning growth performance and productivity, and the mechanism of interaction between coix seed and gut microbiota remains unknown. In this study, we established four groups: (i) control, (ii) antibiotic-fed, (iii) coix seed powder-fed, and (iv) coix seed extract-fed. The feeding experiment was conducted for 4 weeks. Coix seed extract significantly increased average weight gain and reduced the feed/meat ratio in weaned pigs, in addition to reducing the pH of their gastric juice. Further assays demonstrated that coix seed promotes an increase in the density and length of the gastrointestinal villi. Next, 16s sequencing of gut microbiota showed that coix seed significantly increased the abundance of phylum Bacteroidetes and genus Lactobacillus (p

Traditional high-precision long-distance time-frequency transmission requires a complex compensation structure and a continuous optical link, which make high-precision transmission difficult. In this study, we use two counter-propagating optical frequency combs to realize high-precision two-way time-frequency transfer over a 20-km fiber link. The transmission distance transmitted in this experiment is also farther greater than the current free-space transmission distances transmitted over free space. The two optical frequency combs are locked to the same radio frequency reference source. The method makes measurements more flexible and reduces interference. To suppress the effect of dispersion, we use an optical filter to narrow the bandwidth of the optical comb. Meanwhile, the bandwidth of the optical filter is chosen to ensure that the optical comb has the best signal-to-noise ratio at a remote site. We measure the timing difference over 24 h between the local site and remote site.

3D printing, that is, additive manufacturing, has solved many major problems in general manufacturing, such as three-dimensional tissue structure, microenvironment control difficulty, product production efficiency and repeatability, etc., improved the manufacturing speed and precision of personalized bone implants, and provided a lot of support for curing patients with bone injuries. The application of 3D printing technology in the medical field is gradually extensive, especially in orthopedics. The purpose of this review is to provide a report on the related achievements of bone implants based on 3D printing technology in recent years, including materials, molding methods, optimization of implant structure and performance, etc., in order to point out the existing shortcomings of 3D printing bone implants, promote the development of all aspects of bone implants, and make a prospect of 4D printing, hoping to provide some reference for the subsequent research of 3D printing bone implants.

Good heat dissipation performance of aero-engine an effectively improve the service performance and service life of aero-engine. Therefore, this paper studies the machining method of cooling holes of high-temperature existent material GH 4169 for aero-engine innovatively puts forward the mask electrochemical machining method of cooling holes and explores the entrance morphology and taper formation law of the hole structure of high-temperature resistant material GH 4169. The mathematical model of anode dissolution of cooling holes in ECM is established, and the influence of voltage and electrolyte flow rate on cooling holes in ECM is analyzed. Compared with the mask-less electrochemical machining, the inlet radius of cooling holes in mask electrochemical machining is reduced by about 16.0% and the taper is reduced by 52.8% under the same machining parameters, which indicates that the electrochemical machining efficiency of mask is higher and the machining accuracy is better. Experiments show that the diameter of the mask structure improves the accuracy of the inlet profile of the cooling hole in the ECM. The diameter of the mask increases from 2 mm to 2.8 mm, and the inlet radius of the cooling hole increased from 1.257 mm to 1.451 mm When the diameter of the mask is 2.2 mm, the taper of the cooling hole decreased by 53.4%. The improvement effect is best, and the thickness of the mask has little influence on the forming accuracy of the cooling hole.

Water injection-induced rock softening and the associated water seepage characteristics are the common and basic problems in underground reservoir construction and the prevention of mine water disaster. In this paper, a series of experimental studies was carried out to investigate these characteristics with the weakly cemented sandy mudstone collected from Shendong Buertai coal mine, China. The characteristics of water softening and the stress-seepage interactions in water-saturated weakly cemented sandy mudstone were directly obtained. Then, a modification method of the constitutive model for rock mass considering the softening effect and a stress-damage-driven model for permeability evolution were established. Research results show that water saturation reduces the tensile strength, compressive strength, and cohesion by 56% and reduces the elastic modulus by 28%. The hydraulic effects on Poisson’s ratio and internal friction angle are negligible. The relationship between the permeability of weakly cemented sandy mudstone with complete compaction deformation is to be divided into three stages of seepage shielding, seepage surge, and seepage recovery. Rock permeability in each stage has a negative exponential relationship with the effective stress. This research provides a theoretical basis for the researches of hydromechanical couplings on weakly cemented sandy mudstone, which is insightful for rock engineering practice.

The high-speed and high-precision motorized spindle is the future development trend of the CNC machine tool field, and has become the focus of research in the world. High-speed motorized spindles tend to develop in the direction of high precision, high speed, low energy consumption, high efficiency, and high reliability. We undertake a through, systematic review of the development history perspective of the research on precision bearing technology, dynamic balancing technology, thermal error measurement and compensation technology with regard to the key technologies of high-speed motorized spindles. On this basis, the current level of development of key technologies for high-speed motorized spindles is analyzed, and the objective advantages and disadvantages of existing technologies are summarized. Finally, the development tendency of high-speed motorized spindle technology is predicted and foreseen.