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BackgroundPorcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a single-stranded positive-sense RNA virus that severely impacts the global swine industry. Recently, variation and recombination of this pathogen have led to more recombinant strains. However, commercial PRRSV vaccines provide limited protection, and no effective therapeutic drugs are available in clinical settings. Astragalus membranaceus (AM) has anti-inflammatory and immune-enhancing properties, while Curcuma zedoaria (CZ) possesses anti-inflammatory, antibacterial, and antitumor effects. The combination of AM and CZ, originating from the “Lichong Tang” recorded in the “Intergrating Chinese and Western Medicine” offers complementary and synergistic benefits.MethodsIn this study, the AM extract, CZ extract, and various ratios of CZ-AM extracts were prepared using the decoction method. The NADC30-like PRRSV strain SCCD22 was used for viral challenge. The optimal ratio and mode of action of the CZ-AM extract on Pams-163 were assessed by measuring viral copies and mRNA expression of cytokines. Subsequently, the optimal ratio of combined extracts identified in vitro was used as an adjuvant for the PRRSV inactivated vaccine in 28-day-old piglets. Clinical symptom observations, peripheral blood lymphocyte proliferation assays, levels of PRRSV antibody, cytokine secretion, and NLRP3 inflammasome mRNA were conducted to evaluate the potential of the CZ-AM extract as an adjuvant for the PRRSV inactivated vaccine.ResultsResults showed that the CZ-AM extract inhibited PRRSV in vitro, with the best ratio of CZ to AM being 1:4. Animal experiments demonstrated that using the CZ-AM extract as an adjuvant for the PRRSV inactivated vaccine significantly increased the body weight of piglets, elevated serum PRRSV antibody levels, and enhanced the piglets’ inflammatory response. mRNA analysis indicated that the CZ-AM extract inhibited key inflammatory pathways (TLR4/NLRP3/IL-1β), reducing the expression of inflammatory factors. Lymphocyte proliferation assays indicated that the CZ-AM extract significantly stimulated T and B lymphocyte proliferation.ConclusionThis study not only deepens the understanding of the pharmacological effects of AM and CZ but also expands the application of traditional Chinese medicine in the prevention and control of animal diseases. Furthermore, it provides new insights and methods for optimizing PRRSV vaccines, offering significant scientific value and broad application prospects.

Abstract Background Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI. Methods Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd’s ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance. Results A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I 2 = 66.77%, p

Abstract Due to the increasing interdependencies of power networks (PNs) and communication networks (CNs) in cyber‐physical power systems (CPPSs), the interdependent networks tend to be more vulnerable since failures could propagate recursively between the two networks. However, there is little study on the vulnerability analysis of CPPSs considering unexpected disruptive events or adversarial attacks. Despite being a useful tool for evaluating cascading failures in interdependent networks, the topology‐based percolation theory does not apply to CPPSs as neglecting the propagation dynamics and power flow characteristics. To this end, this paper improves the percolation theory by modelling the failure propagation mechanism to assess the vulnerability of CPPSs. Firstly, a percolation‐based failure propagation simulator (PFPS) is developed, wherein the virus‐caused propagation dynamics of the cyber layer, flow‐based failure propagation mode of the physical layer, and multi‐state interdependences between the cyber layer and physical layer are incorporated. By considering the nodal states and flow‐related operating states, percolation equations and termination conditions of PFPS are formulated. Based on the calculation results of PFPS, metrics in terms of topological integrity, power supply reliability, and failure probability are constructed to quantify both system and component vulnerability. The effectiveness of the proposed method is validated by the test CPPSs.

Streptococcus suis serotype 2 (SS2) is a Gram-positive bacterium. It is a common and significant pathogen in pigs and a common cause of zoonotic meningitis in humans. It can lead to sepsis, endocarditis, arthritis, and pneumonia. If not diagnosed and treated promptly, it has a high mortality rate. The pan-genome of SS2 is open, and with an increasing number of genes, the core genome and accessory genome may exhibit more pronounced differences. Due to the diversity of SS2, the genes related to its virulence and resistance are still unclear. In this study, a strain of SS2 was isolated from a pig farm in Sichuan Province, China, and subjected to whole-genome sequencing and characterization. Subsequently, we conducted a Pan-Genome-Wide Association Study (Pan-GWAS) on 230 strains of SS2. Our analysis indicates that the core genome is composed of 1,458 genes related to the basic life processes of the bacterium. The accessory genome, consisting of 4,337 genes, is highly variable and a major contributor to the genetic diversity of SS2. Furthermore, we identified important virulence and resistance genes in SS2 through pan-GWAS. The virulence genes of SS2 are mainly associated with bacterial adhesion. In addition, resistance genes in the core genome may confer natural resistance of SS2 to fluoroquinolone and glycopeptide antibiotics. This study lays the foundation for further research on the virulence and resistance of SS2, providing potential new drug and vaccine targets against SS2.

Since 2013, the porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), lineage 1.8 (NADC30-like PRRSV) has emerged and become widely prevalent in China. The NADC30-like PRRSV poses significant challenges for disease control, primarily because of its propensity for frequent mutations and recombinations. We successfully isolated and identified a NADC30-like strain, designated SCCD22, in Chengdu, Sichuan Province, China. We meticulously examined the genetic recombination properties and evaluated its pathogenicity in 28-day-old piglets. SCCD22 showed 93.02% nucleotide homology with the NADC30 PRRSV strain, and its non-structural protein 2 coding region showed the same 131 amino acid deletion pattern as that seen in NADC30. Furthermore, we identified two recombination events in SCCD22: one in the NSP2 region (1,028–3,290 nt), where it was highly similar to the JXA1-like strain GZ106; and another in the NSP10 ~ 12 region (9,985–12,279 nt), closely resembling the NADC30-like strain CY2-1604. Piglets infected with SCCD22 exhibited clinical symptoms such as elevated body temperature, prolonged fever, reduced appetite, and roughened fur. Postmortem examinations underscored the typical lung pathology associated with PRRSV, indicating that the lungs were the primary affected organs. Furthermore, extended viral shedding accompanied by progressive viremia was observed in the serum and nasal excretions of infected piglets. In summary, this study reports a domestic PRRSV recombination strain in the Sichuan Province that can provide critical insights into preventing and controlling PRRSV in this region.

Abstract Lagovirus europaeus GI.1 belongs to Lagovirus in the Caliciviridae family. GI.1 causes an acute, septic, and highly lethal disease in rabbits. Lagovirus europaeus GI.2, a new variant of GI.1, has caused explosive mortality in rabbits of all ages in Sichuan Province, China. To explore the differences in pathogenicity of rabbits infected with GI.1/GI.2, we investigated the virulence and disease progression of a naturally occurring GI.1/GI.2 in 4-week-old, 13-week-old, and 25-week-old New Zealand White laboratory rabbits after GI.1/GI.2 infection. Objective measures of disease progression were recorded using continuous body-temperature monitoring. We observed the kittens were infected with GI.2 during the most urgent course of the disease, and GI.1 was not lethal to kittens. We found that the target organ of both GI.1 and GI.2 was the liver, but the disease course of the two viruses was differed. Our study enriches the research on the pathogenicity of GI.1 and GI.2 under the same conditions.

The Schlafen5(SLFN5)gene belongs to the third group of the Schlafen protein family. As a tumor suppressor gene, SLFN5 plays a pivotal role in inhibiting tumor growth, orchestrating cell cycle regulation, and modulating the extent of cancer cell infiltration and metastasis in various malignancies. However, the high expression of SLFN 5 in some tumors was positively correlated with lymph node metastasis, tumor stage, and tumor grade. This article endeavors to elucidate the reciprocal relationship between the SLFN5 gene and malignant tumors, thereby enhancing our comprehension of the intricate mechanisms underlying the SLFN5 gene and its implications for the progression, invasive potential, and metastatic behavior of malignant tumors. At the same time, this paper summarizes the basis of SLFN 5 as a new biomarker of tumor diagnosis and prognosis, and provides new ideas for the target treatment of tumor.

Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) lineage 8 was first detected in mainland China in 2006 and has since rapidly spread to become the primary epidemic strain in the country. In this study, samples such as lung tissue, hilar lymph nodes, abortion fetuses, and blood were collected from large-scale pig farms across 11 prefecture-level cities in Sichuan province between 2019 and 2020 for antigen detection and PRRS virus isolation. The antigen detection results indicated that the positive rate of HP-PRRSV (JXA1-Like strain) was 44.74% (51/114), NADC30-Like PRRSV was 17.54% (20/114), and classical PRRSV (VR2332-Like strain) was 37.72% (43/114). The predominant strain was HP-PRRSV. Positive samples were further inoculated into Marc-145 cells for virus isolation and identification, leading to the isolation of a new JXA1-Like PRRSV strain named SCSN2020. The strain was characterized by RT-qPCR, indirect immunofluorescence assay (IFA), plaque purification, electron microscopy, and whole genome sequencing. The total length of the viral genome was determined to be approximately 15,374 bp. A comparison of the SCSN2020 genome with VR2332 revealed that both strains had the same discontinuous 30-amino acid deletion on the Nsp2 gene. ORF5 genotyping classified the SCSN2020 strain as sublineage 8.7, with a whole genome sequence identity of 99.34% with JXA1. Furthermore, we evaluated the pathogenicity of the SCSN2020 strain in 28-day-old piglets and observed persistent fever from day 4 to day 10, weight loss started on day 7, dyspnea and severe lung lesions began started on day 14. The results of this study highlight the current PRRSV epidemic situation in Sichuan province and provide a scientific reference for subsequent prevention and control measures.

Already a multibillion-dollar global industry, shrimp aquaculture, is growing all the time. The intensive method, which is the most common method in shrimp aquaculture, remains commercially challenged due to the expenditures associated with environmental pollution abatement. Although the comprehensive understanding of this intricate aquaculture environment has been advanced using mathematical modeling, recent attempts to improve the model’s structure have not yielded enough results. This work upgraded the previous method to a three-dimensional hydrodynamic ecosystem model with the effects of shrimps being replaced by approximation equations for the environmental assessment of a shrimp aquaculture pond in Kyushu District, Japan. Our approach was successful, as demonstrated by the high consistency of the simulation results when compared to observation data and the previous results. Additionally, we first revealed the impacts of stratification and confirmed the notable daily variation in the water quality. Our case study offers significant practical information on the characteristics of intensive shrimp aquaculture, implications for long-term sustainable operations, and future research priorities on local-scale ecosystem modeling.

Cholesterol esterification is often dysregulated in cancer. Sterol O-acyl-transferase 1 (SOAT1) plays an important role in maintaining cellular cholesterol homeostasis by catalyzing the formation of cholesterol esters from cholesterol and long-chain fatty acids in cells. Many studies have implicated that SOAT1 plays a vital role in cancer initiation and progression and is an attractive target for novel anticancer therapy. In this review, we provide an overview of the mechanism and regulation of SOAT1 in cancer and summarize the updates of anticancer therapy targeting SOAT1.

BackgroundGlässer's disease, caused by Haemophilus parasuis (HPS), is responsible for economic losses in the pig industry worldwide. However, the existing commercial vaccines offer poor protection and there are significant barriers to the development of effective vaccines.MethodsIn the current study, we aimed to identify potential vaccine candidates and design a multi-epitope vaccine against HPS by performing pan-genomic analysis of 121 strains and using a reverse vaccinology approach.ResultsThe designed vaccine constructs consist of predicted epitopes of B and T cells derived from the outer membrane proteins of the HPS core genome. The vaccine was found to be highly immunogenic, non-toxic, and non-allergenic as well as have stable physicochemical properties. It has a high binding affinity to Toll-like receptor 2. In addition, in silico immune simulation results showed that the vaccine elicited an effective immune response. Moreover, the mouse polyclonal antibody obtained by immunizing the vaccine protein can be combined with different serotypes and non-typable Haemophilus parasuis in vitro.ConclusionThe overall results of the study suggest that the designed multi-epitope vaccine is a promising candidate for pan-prophylaxis against different strains of HPS.

In this study, lung tissue was collected from nursery piglets suspected of being infected with porcine reproductive and respiratory syndrome virus (PRRSV) in a large‑scale pig farm in Sichuan, China. Polymerase chain reaction (PCR) and reverse transcription quantitative‑polymerase chain reaction (RT‑qPCR) methods were used to ensure that no other pathogens were present. Virus isolation was also carried out where the presence of PRRSV was determined by indirect immunoinfluscent assay (IFA). Compared with the common PRRSV strain, the isolate did not produce evident Cytopathic effect (CPE) in the early stage of isolation. CPE was found in the late stage, and the titer was 104.17 TCID50/0.1 mL. The strain was named CJS01. Bioinformatics analysis showed that it was a NADC30‑Like strain. The virus load was determined by measuring the nucleic acid load during the proliferation of the strain on Marc‑145 cells. The strain showed good adaptability on cells, and the virus proliferated on cells for 84 hr when the highest nucleic acid load was achieved. By recombinant analysis of ORF3~7 genes and prediction of its epitope, it was found that CJS01 strain might interfere with the immunesystem of the infected animals.

Abstract The phase offset of quantum oscillations is commonly used to experimentally diagnose topologically nontrivial Fermi surfaces. This methodology, however, is inconclusive for spin-orbit-coupled metals where π-phase-shifts can also arise from non-topological origins. Here, we show that the linear dispersion in topological metals leads to a T 2-temperature correction to the oscillation frequency that is absent for parabolic dispersions. We confirm this effect experimentally in the Dirac semi-metal Cd3As2 and the multiband Dirac metal LaRhIn5. Both materials match a tuning-parameter-free theoretical prediction, emphasizing their unified origin. For topologically trivial Bi2O2Se, no frequency shift associated to linear bands is observed as expected. However, the π-phase shift in Bi2O2Se would lead to a false positive in a Landau-fan plot analysis. Our frequency-focused methodology does not require any input from ab-initio calculations, and hence is promising for identifying correlated topological materials.

Psychological stress is commonly accepted to be closely associated with masticatory muscle disorder, which is the main symptom of temporomandibular disorder (TMD). Previous studies have confirmed that exposure to stress may cause masticatory muscle hyperactivity. However, the central mechanism underlying this process remains unclear. The mesencephalic trigeminal nucleus (Vme), which resides in the brainstem, is the primary afferent center for masticatory proprioception and plays a key role in oral–motor movements by projecting to the trigeminal motor nucleus (Vmo). Therefore, the present study was designed to examine the role of Vme neurons in masseter overactivity induced by chronic stress. We found that subjecting mice to restraint stress (6 h/day) for 14 days caused significant anxiety-like behavior, obvious masseter overactivity, and markedly enhanced electrophysiological excitability of Vme neurons. By using anterograde tract tracing combined with immunofluorescence staining methods, we observed vesicular glutamate transporter 1 (VGLUT1)-positive glutamatergic projections from the Vme to the Vmo. Moreover, chronic restraint stress (CRS) elevated the expression of VGLUT1 and choline acetyltransferase (ChAT) in Vmo. Furthermore, administration of VGLUT1-targeted short hairpin RNA (shRNA) into the bilateral Vme significantly suppressed the enhanced overexcitability of Vme neurons, downregulated the overexpression of VGLUT1 and ChAT in the Vmo, and attenuated the elevated overactivity of the masseter caused by CRS. Taken together, we showed that CRS can excite neurons in the Vme, enhancing glutamatergic excitatory projections from the Vme to the Vmo and resulting in masseter muscle overactivity. These findings provide us with a novel central mechanism underlying the correlation between psychological factors and TMD.

NADC34-like porcine reproductive and respiratory syndrome virus first appeared in 2017 in a herd of pigs in Liaoning Province, China. The virus was subsequently found in other provinces. Given the potential for this virus to cause an epidemic, rapid, sensitive, and specific detection of NADC34-like PRRSV is required. The virus’ ORF5 gene was artificially synthesized based on a Chinese reference strain, and specific primers/probes for the ORF5 gene were designed. Then, the amplified target fragment was cloned into the pMD19-T vector, and a series of diluted recombinant plasmids were used to generate a standard curve. An optimized real-time TaqMan RT-PCR method was established. The method was highly specific for NADC34-like PRRSV, without cross-reactions with other non-targeted pig viruses. The detection limit of this assay was 101 copies/μL. The method had an efficiency of 98.8%, a squared regression value (R2) of 0.999, and showed a linear range of 103–108 copies/μL of DNA per reaction. This method was shown to be analytically specific and sensitive with a low intra- and inter-assay coefficient of variation (

The strain hardening is an effective mode of enhancing mechanical properties in alloys. In this work, the strain hardening behaviors of Mg-xY (x = 1, 2, and 3 wt%) after extrusion process was investigated using uniaxial tensile tests. Results suggest that the Mg–xY alloys are composed of α-Mg with a little amount of Mg24Y5 phase. The average grain size reduces from 19.8 µm to 12.2 µm as the Y content adds from 1 wt% to 2 wt%. Nevertheless, when Y content reaches 3 wt%, the grain size reaches to 12.9 µm, which is close to that of Mg–2Y. The strain hardening rate decreases from 883 MPa to 798 MPa at (σ–σ0.2) = 40 MPa, and Mg–2Y and Mg–3Y have the similar strain hardening response. Moreover, Mg–1Y shows an obvious ascending stage after the steep decreasing stage, which is mainly caused by the activation of twinning. The strain hardening behavior of Mg–xY is explained based on understanding the roles of the deformation mechanisms via deformation microstructure analysis and Visco-Plastic Self Consistent (VPSC) model. The variation of strain hardening characteristics with increasing Y content is related to the effects of grain size and texture. Keywords: Mg‒Y alloy, Strain hardening, Texture, Twinning, VPSC

Abstract Background Although tissue-engineered cartilage has been broadly studied, complete integration of regenerated cartilage with residual cartilage is still difficult for the inferior mechanical and biochemical feature of neocartilage. Chondrogenesis of mesenchymal stem cells can be induced by biophysical and biochemical factors. Methods In this study, autologous platelet-rich fibrin (PRF) membrane was used as a growth factor-rich scaffold that may facilitate differentiation of the transplanted bone marrow mesenchymal stem cells (BMSCs). At the same time, hydrostatic pressure was adopted for pre-adjustment of the seed cells before transplantation that may promote the mechanical flexibility of neocartilage. Results An in vitro study showed that the feasible hydrostatic pressure stimulation substantially promoted the chondrogenic potential of in vitro-cultured BMSC/PRF construct. In vivo results revealed that at every time point, the newborn tissues were the most favorable in the pressure-pretreated BMSC/PRF transplant group. Besides, the transplantation of feasible hydrostatic pressure-pretreated construct by BMSC sheet fragments and PRF granules could obviously improve the integration between the regenerated cartilage and host cartilage milieu, and thereby achieve boundaryless repair between the neocartilage and residual host cartilage tissue in rabbit temporomandibular joints. It could be concluded that feasible hydrostatic pressure may effectively promote the proliferation and chondrogenic differentiation of BMSCs in a BMSC/PRF construct. Conclusion This newly formed construct with biomechanical flexibility showed a superior capacity for cartilage regeneration by promoting the mechanical properties and integration of neocartilage.

At present, due to some elevator cars (EC) has no air conditioning system, resulting in a hot internal environment in the EC in summer. Thermoelectric cooling technology is a lightweight, low cost and fast cooling technology, which has a potential of solving this problem. Thus, a thermoelectric elevator car air conditioner (TE-ECAC) is designed for these EC in this paper. Based on the actual application, the TE-ECAC's cooling characteristic and performance are experimentally investigated in an Enthalpy Lab, and its performance is optimized after the analysis. According to the results, it's found that a stable working state of the TE-ECAC can be achieved at about 200s. Moreover, an optimal cooling coefficient of 1.24 and a maximum air-cooling capacity of 324W are achieved under an operation condition at the cold side flow rate of 1.75 m3/min and the ambient temperature of 28 °C. In addition, since TE-ECAC has greater advantages in economy and weight than conventional elevator air conditioner, it's particularly suitable for EC. Especially suitable for some old EC with a broken air conditioner and must to be replaced with a new air conditioner. All in all, it's a good application prospects for TE-ECAC applying to EC. Keywords: Thermoelectric cooling, Cooling coefficient, Air-cooling capacity, Elevator car, Optimization

To improve the resilience of a distribution system against extreme weather, a fuel-based distributed generator (DG) allocation model is proposed in this study. In this model, the DGs are placed at the planning stage. When an extreme event occurs, the controllable generators form temporary microgrids (MGs) to restore the load maximally. Simultaneously, a demand response program (DRP) mitigates the imbalance between the power supply and demand during extreme events. To cope with the fault uncertainty, a robust optimization (RO) method is applied to reduce the long-term investment and short-term operation costs. The optimization is formulated as a tri-level defender-attacker-defender (DAD) framework. At the first level, decision-makers work out the DG allocation scheme; at the second level, the attacker finds the optimal attack strategy with maximum damage; and at the third level, restoration measures, namely distribution network reconfiguration (DNR) and demand response are performed. The problem is solved by the nested column and constraint generation (NC&CG) method and the model is validated using an IEEE 33-node system. Case studies validate the effectiveness and superiority of the proposed model according to the enhanced resilience and reduced cost. [ABSTRACT FROM AUTHOR]