FTO Positively Regulates Odontoblastic Differentiation via SMOC2 in Human Stem Cells from the Apical Papilla under Inflammatory Microenvironment.

Odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs) is crucial for continued root development and dentin formation in immature teeth with apical periodontitis (AP). Fat mass and obesity-associated protein (FTO) has been reported to regulate bone regeneration and osteogenic differentiation profoundly. However, the effect of FTO on hSCAPs remains unknown. This study aimed to identify the potential function of FTO in hSCAPs' odontoblastic differentiation under normal and inflammatory conditions and to investigate its underlying mechanism preliminarily. Histological staining and micro-computed tomography were used to evaluate root development and FTO expression in SD rats with induced AP. The odontoblastic differentiation ability of hSCAPs was assessed via alkaline phosphatase and alizarin red S staining, qRT-PCR, and Western blotting. Gain- and loss-of-function assays and online bioinformatics tools were conducted to explore the function of FTO and its potential mechanism in modulating hSCAPs differentiation. Significantly downregulated FTO expression and root developmental defects were observed in rats with AP. FTO expression notably increased during in vitro odontoblastic differentiation of hSCAPs, while lipopolysaccharide (LPS) inhibited FTO expression and odontoblastic differentiation. Knockdown of FTO impaired odontoblastic differentiation, whereas FTO overexpression alleviated the inhibitory effects of LPS on differentiation. Furthermore, FTO promoted the expression of secreted modular calcium-binding protein 2 (SMOC2), and the knockdown of SMOC2 in hSCAPs partially attenuated the promotion of odontoblastic differentiation mediated by FTO overexpression under LPS-induced inflammation. This study revealed that FTO positively regulates the odontoblastic differentiation ability of hSCAPs by promoting SMOC2 expression. Furthermore, LPS-induced inflammation compromises the odontoblastic differentiation of hSCAPs by downregulating FTO, highlighting the promising role of FTO in regulating hSCAPs differentiation under the inflammatory microenvironment.

ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs.

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis, plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY.

Association between chronic pain classes and cognitive function in older adults: A cross-sectional study based on latent class analysis.

The purpose of this study was to identify latent classes of chronic pain in older adults based on perceptual, cognitive, behavioral, emotional and social factors, and to explore the associations between each class of chronic pain and different cognitive domains. A total of 629 participants were included. Three classes of chronic pain were identified: "episodic recurrent mild pain with good psychosocial state" (class 1), "episodic recurrent moderate pain with general psychosocial state" (class 2) and "continuous multilocational severe pain with attacks accompanied by poor psychosocial state and avoidance of activity" (class 3). After adjusting for relevant confounders, chronic pain presenting as class 1 was associated with worse memory; class 2 was associated with worse global cognitive function, memory, information processing speed, and executive function; and class 3 was additionally associated with worse attention compared to class 2. The findings contribute to the development of targeted programs for treating pain and improving cognitive functioning.

A longitudinal study of factors associated with cognitive frailty in middle-aged and elderly population based on the health ecology model.

BACKGROUND: Cognitive frailty (CF) is an important geriatric syndrome and is reversible. It is crucial to develop preventive interventions for CF. We aimed to explore the associations between CF and its associated factors in Chinese aged 45 years and above. METHODS: Based on the available data of 3 waves in China Health and Retirement Longitudinal Study from 2011 to 2015, 16,071 individuals aged 45 years and above from 3 waves were included. Based on the health ecology model, the associated factors were classified as downstream, midstream and upstream factors. Generalized hierarchical linear model including time level, individual level, and province level was applied to analyze the associations between factors and CF. RESULTS: Multilevel factors have different effects on physical and cognitive function. In the downstream, old age, female, underweight, chronic diseases, and depression were risk factors of reversible CF and potentially reversible CF, and overweight was their protective factor. In the midstream, short or long night sleep duration was their risk factor, and > 30 and ≤ 60 min afternoon naps, alcohol drinking, and participation in social activities were their protective factors. In the upstream, living in rural areas was their risk factor, and high educational level, household consumption and GDP per capita were their protective factors. CONCLUSIONS: Physical function and cognitive function are affected differently by multiple factors. The occurrence and development of physical frailty and cognitive impairment may have some common mechanisms. CF can be influenced by multilevel factors, and multilevel and comprehensive management of CF should be achieved. KEY POINTS: Cognitive frailty was correlated with multilevel factors, including downstream, midstream, and upstream factors. It is crucial to focus on individual interventions such as physiological factors, psychological factors and health behaviors, especially the elderly, women and those with depression. Socioeconomic status was associated with the lower prevalence of cognitive frailty.

Inhibition of porcine deltacoronavirus entry and replication by Cepharanthine.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1ß and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.

Association between ambient air pollution exposure in pregnant women with antiphospholipid syndrome in Nanjing, China.

Antenatal exposure to air pollutants is thought to be associated with a variety of maternal blood markers as well as adverse birth outcomes. However, the dysgenic influence of air pollutants on the antiphospholipid syndrome (APS) in mothers and their pregnancy outcomes remains unclear. In the current study, 371 mother-infant pairs (189 healthy: 182 APS) from Nanjing Maternal and Child Health Hospital as well as air pollutants concentration from their living environment were used to investigate correlations between air pollution with maternal blood indicators and fetal birth weight in the groups of APS and healthy mothers. Generalized linear model was used to evaluate the contributions of air pollutant exposure during pregnancy to the blood indicators variation. The relationships between birth weight with specific air pollutant and blood index were analyzed using ridge regression. Results showed that APS fetal birth weight was significantly impacted by air pollutant exposure during pregnancy, in particular, the birth weight decreased significantly along with increasing fine particulate matter 2.5 (PM2.5) and fine particulate matter 10 (PM10) exposure concentrations throughout pregnancy. In contrast, birth weight increased significantly with sulfur dioxide (SO2) exposure. In addition, APS-related blood indicators comprised of platelet distribution width (PDW), total bilirubin (TBIL), mean platelet volume (MPV), platelet-larger cell ratio (P_LCR), homocysteine (HCY), alkaline phosphatase (ALP), direct bilirubin (DBIL), basophilic granulocyte (BAS), platelet thrombocytocrit (PCT), preprandial glucose levels (OGTT0), monocytes (MON), and monocytes ratio (MON_ratio) were also strongly related with prenatal exposure to PM2.5 and PM10, in which PDW levels showed most strongly negative impaction on fetal birth weight. Together, we showed that prenatal exposure to air pollutant (PM2.5 and PM10) may exacerbate the poor birth outcomes of low birth weight by impacting APS maternal blood indicators especially for PDW.

Relationship between daytime napping with the occurrence and development of diabetes: a systematic review and meta-analysis.

OBJECTIVE: To determine the relationship of napping with incident diabetes risk and glycaemic control in people with diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (PubMed), EMBASE, Web of Science and the Cochrane Library were searched for studies published from database inception to 9 May 2023. ELIGIBILITY CRITERIA: Observational studies reporting the relationship of napping with diabetes or glycaemic control in patients with diabetes in adult populations were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the literature, extracted data and assessed the quality of the included studies. The results were reported as ORs and 95% CIs, which were pooled by using fixed and random effects models, and subgroup analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation method was used to assess the quality of the evidence. RESULTS: Forty studies were included in our review. Habitual napping was associated with an increased diabetes risk (OR 1.20, 95% CI 1.14 to 1.27) and poor glycaemic control in patients with diabetes (OR 2.05, 95% CI 1.55 to 2.73). Nap durations less than 30 min were unrelated to diabetes (OR 1.05, 95% CI 0.97 to 1.14). Nap durations of 30-60 min were associated with diabetes risk (OR 1.09, 95% CI 1.02 to 1.17), but there were differences in the subgroup analysis results. Nap durations of more than 60 min significantly increased the risk of diabetes (OR 1.31, 95% CI 1.20 to 1.44). CONCLUSIONS: Napping is associated with increased diabetes risk and poor glycaemic control, and future research will need to confirm whether there are sex and regional differences. Nap durations of more than 60 min significantly increases the risk of diabetes, and the relationship between nap duration and glycaemic control in patients with diabetes needs to be further explored in the future. PROSPERO REGISTRATION NUMBER: CRD42021292103.

Percutaneous Kyphoplasty Enhanced with Calcium and Zoledronic Acid for Managing Thoracolumbar Compression Fractures in Athletes with Osteoporosis and Fitness Concerns

Background: Athletes and fitness enthusiasts often encounter thoracolumbar compression fractures due to rigorous physical activities. Combining calcium (Ca) and zoledronic acid (ZOL) with percutaneous kyphoplasty (PKP) has shown promising clinical efficacy in elderly patients with osteoporotic thoracolumbar compression fractures (OTCF). However, the potential benefits of this approach in athletes and fitness enthusiasts require further investigation. Methods: We conducted a retrospective analysis of 295 athletes and fitness enthusiasts (mean age 75.91±3.74 years) with OTCF who underwent PKP. Patients were divided into three groups: PKP+Ca (n=92), receiving 1500mg/d Ca carbonate post-surgery; PKP+ZOL (n=98), receiving 5mg ZOL intravenously post-surgery; and PKP+Ca+ZOL (n=105), administered with a combination of Ca and ZOL post-surgery. A two-year follow-up was conducted, and clinical and imaging data were recorded and analyzed before and after treatment. Results: There were no significant differences in general information, lumbar bone mineral density (BMD), visual analog scale (VAS), Oswestry dysfunction index (ODI), and bone marker levels among the three groups before treatment. In the 3rd, 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group exhibited higher vertebral heights compared to the PKP+Ca and PKP+ZOL groups. Additionally, in the 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group demonstrated lower kyphosis than the PKP+Ca and PKP+ZOL groups. Furthermore, in the 12th and 24th months post-treatment, the PKP+Ca+ZOL group had higher BMD values than the PKP+ZOL and PKP+Ca groups. VAS scores in the PKP+Ca+ZOL and PKP+ZOL groups were significantly lower than those in the PKP+Ca group. ODI scores and bone marker concentrations were also lower in the PKP+Ca+ZOL group compared to the other groups. (AU)

Trade-offs in non-native plant herbivore defences enhance performance.

Non-native plants are typically released from specialist enemies but continue to be attacked by generalists, albeit at lower intensities. This reduced herbivory may lead to less investment in constitutive defences and greater investment in induced defences, potentially reducing defence costs. We compared herbivory on 27 non-native and 59 native species in the field and conducted bioassays and chemical analyses on 12 pairs of non-native and native congeners. Non-natives suffered less damage and had weaker constitutive defences, but stronger induced defences than natives. For non-natives, the strength of constitutive defences was correlated with the intensity of herbivory experienced, whereas induced defences showed the reverse. Investment in induced defences correlated positively with growth, suggesting a novel mechanism for the evolution of increased competitive ability. To our knowledge, these are the first linkages reported among trade-offs in plant defences related to the intensity of herbivory, allocation to constitutive versus induced defences, and growth.

The expression of Runx2 in the pathogenesis of periodontitis.

OBJECTIVE: Runt-related transcription factor 2 (Runx2) plays an important role in bone metabolism; however, the relationship between Runx2 and periodontitis remains unclear. We investigated Runx2 expression in the gingiva of patients to explore its role in periodontitis. METHODS: Gingival samples of patients were collected, including healthy samples (control group) and periodontitis samples (P group). Periodontitis samples were divided into three groups based on the periodontitis stage. Samples with stage I and grade B periodontitis were in the P1 group, stage II and grade B in the P2 group, and stage III or IV and grade B in the P3 group. Immunohistochemistry and western blotting were performed to detect Runx2 levels. The probing (PD) and clinical attachment loss (CAL) were recorded. RESULTS: Runx2 expression levels in the P and P3 groups were higher than those in the control group. In addition, Runx2 expression was positively correlated with CAL and PD (r1 = 0.435, r2 = 0.396). CONCLUSION: The high expression level of Runx2 in the gingiva of patients with periodontitis may be correlated with the pathogenesis of periodontitis.

Investigation on risk factors of chronic diseases among community residents: A study based on health management systems supported by Mobile phones.

AIM: To explore the physical and mental health status of community residents and to identify the risk factors of chronic diseases. DESIGN: A cross-sectional, descriptive correlational study was conducted. METHODS: A total of 579 participants were recruited from 15 communities in Tianjin. The demographic information sheet, 7-item Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9) were used. Data collection was undertaken based on the health management system on mobile phones from April to May 2019. RESULTS: Eighty-four participants of the total number of surveyed were with chronic disease. The incidence of depression and anxiety in participants was 44.2% and 41.3%. Logistic regression analysis showed that age (OR = 4.905, 95%CI: 2.619-9.187), religious belief (OR = 0.445, 95%CI: 1.510-11.181) and working condition (OR = 0.161, 95%CI: 0.299-0.664) entered the regression equation. Old age is a risk factor for chronic diseases. No religious belief and working condition are protective factors for chronic diseases.

Apatinib plus drug-eluting bead transarterial chemoembolization as bridging therapy to surgical resection displays an acceptable efficacy and safety profile in hepatocellular carcinoma patients.

BACKGROUND: Apatinib exhibits a synergistic effect with transarterial chemoembolization (TACE) by inhibiting TACE-induced neoangiogenic reaction in hepatocellular carcinoma (HCC) patients. But apatinib plus drug-eluting bead TACE (DEB-TACE) is rarely reported as a bridging therapy to surgery. This study aimed to evaluate the efficacy and safety of apatinib plus DEB-TACE as a bridge to surgical resection in intermediate-stage HCC patients. MATERIALS AND METHODS: Thirty-one intermediate-stage HCC patients who received apatinib plus DEB-TACE as a bridging therapy to surgery were enrolled. After the bridging therapy, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and objective response rate (ORR) were evaluated; meanwhile, relapse-free survival (RFS) and overall survival (OS) were determined. RESULTS: After the bridging therapy, three (9.7%), twenty one (67.7%), seven (22.6%), and twenty four (77.4%) patients achieved CR, PR, SD, and ORR, respectively; besides, PD did not occur. The successful downstaging rate was 18 (58.1%). The median (95% confidence interval [CI]) accumulating RFS was 33.0 (19.6 - 46.6) months. Besides, the median (95% CI) accumulating OS was 37.0 (24.8 - 49.2) months. HCC patients with successful downstaging showed a higher accumulating RFS rate ( P = 0.038) and similar accumulating OS rate ( P = 0.073) compared to those without successful downstaging. The overall incidence of adverse events was relatively low. Besides, all the adverse events were mild and controllable. The most frequent adverse events included pain (14 [45.2%]) and fever (9 [29.0%]). CONCLUSION: Apatinib plus DEB-TACE as a bridging therapy to surgical resection displays good efficacy and safety profile in intermediate-stage HCC patients.

Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

Graphene Oxide Nanoparticles Combined with CRISPR/Cas9 System Enable Efficient Inhibition of Pseudorabies Virus.

We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.

Patterns of Risky Health Behaviors and Associations With Chronic Diseases Among Young Adult Nursing Students: A Latent Class Analysis.

BACKGROUND: Little is known about how health behaviors cluster to form meaningful patterns that influence health outcomes in young adult nursing students. PURPOSE: The purpose of this study was to identify the unique health behavior patterns among young adult nursing students in China and examine the associations between health behaviors and chronic diseases. METHODS: Using an electronic app, the achievements of an exercise target, sedentary behavior, smoking and drinking, and dietary patterns were assessed in 1,480 nursing student participants aged 18-24 years from two medical universities in Eastern China. RESULTS: A four-class model was developed using latent class analysis that included the "failure to achieve exercise target, alcohol-drinking, and insufficient fruit and vegetable group" (Group 1, n = 187, 12.6%), the "alcohol-drinking and sedentary behavior group" (Group 2, n = 290, 19.6%), the "sedentary behavior only group" (Group 3, n = 721, 48.7%), and the "failure to achieve exercise target only group" (Group 4, n = 282, 19.1%). Logistic regressions indicated that nursing students in Group 2 (odds ratio [ OR ] = 0.42), Group 3 ( OR = 0.51), and Group 4 ( OR = 0.30) were less likely to have chronic diseases than those in Group 1 after adjusting for sociodemographic variables. CONCLUSIONS: The health behaviors were clustered in different patterns among young adult nursing students. Tailoring interventions to specific groups is suggested to improve health outcomes.

CTGF Promotes the Osteoblast Differentiation of Human Periodontal Ligament Stem Cells by Positively Regulating BMP2/Smad Signal Transduction.

Objective: This work is aimed at revealing the role and the molecular mechanism of connective tissue growth factor 2 (CTGF) in the osteoblast differentiation of periodontal ligament stem cells (PDLSCs). Methods: The osteogenic differentiation of PDLSCs was induced by osteogenic induction medium (OM), and the expression level of osteogenic related proteins ALP, RUNX2, OCN, and CTGF was estimated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis. We constructed cell lines with CTGF overexpression or knockdown to verify the role of CTGF in the osteoblast differentiation of PDLSCs. Alkaline phosphatase (ALP) staining was introduced to measure the osteoblasts activity, and alizarin red S (ARS) staining was employed to test matrix mineralization. The interaction between CTGF and bone morphogenetic protein-2 (BMP-2) was determined by endogenous coimmunoprecipitation (Co-IP). Results: The expression level of CTGF was increased during the osteogenic induction of PDLSCs. Additionally, CTGF overexpression effectively maintained the stemness and facilitated the osteoblast differentiation in PDLSCs, and CTGF knockdown exerted opposite effects. Moreover, at molecular mechanism, CTGF increased the activity of BMP-2/Smad signaling pathway. Conclusion: This investigation verified that CTGF promotes the osteoblast differentiation in PDLSCs at least partly by activating BMP-2/Smad cascade signal.

Multidecadal, continent-level analysis indicates agricultural practices impact wheat aphid loads more than climate change.

Temperature has a large influence on insect abundances, thus under climate change, identifying major drivers affecting pest insect populations is critical to world food security and agricultural ecosystem health. Here, we conducted a meta-analysis with data obtained from 120 studies across China and Europe from 1970 to 2017 to reveal how climate and agricultural practices affect populations of wheat aphids. Here we showed that aphid loads on wheat had distinct patterns between these two regions, with a significant increase in China but a decrease in Europe over this time period. Although temperature increased over this period in both regions, we found no evidence showing climate warming affected aphid loads. Rather, differences in pesticide use, fertilization, land use, and natural enemies between China and Europe may be key factors accounting for differences in aphid pest populations. These long-term data suggest that agricultural practices impact wheat aphid loads more than climate warming.

Host-virus interactions in PK-15 cells infected with Pseudorabies virus Becker strain based on RNA-seq.

Pseudorabies is a highly contagious viral disease caused by the pseudorabies virus (PRV), and it is one of the most devastating diseases for the swine industry worldwide. However, the host-virus interaction and virus-related host factors at the mRNA level in virus natural host (pig) cells, are not fully understood. Here, we performed time-course RNA sequencing of the PK-15 cells infected with a recombinant strain PRV-Becker-GFP to study the dynamic competition between the host and the virus. At early stage of infection (3 hpi), our results suggested that the activation of cytosolic DNA-sensing pathway and NOD-like receptor signaling pathway might play a role in recognition of PRV, and the activation of NF-kappa B signaling pathway and TNF signaling pathway might be involved in immune response against the virus. However, all these pathways were subsequently inhibited by PRV. Additionally, our data indicated the fatty acid degradation pathway was significantly downregulated during late stage of infection (9 hpi), which was likely to accumulate fatty acids for viral envelope synthesis. Moreover, we verified the expression of 5 representative genes (ALDH1B1, ACAA2, ACSL3, ADH5, and EHHADH) related to fatty acid degradation pathway by RT-qPCR. Overall, our findings provide valuable information to better understand host-virus interactions and the immune escape mechanism of PRV-Becker as a virulent strain, offering novel targets for porcine anti-PRV breeding research and potential clinical treatment.

Softened Microstructure and Properties of 12 µm Thick Rolled Copper Foil.

Up to now, 12 µm thick rolled copper foil is the thinnest rolled copper foil that can be stably produced. The softened microstructure and properties of 12 µm thick rolled copper foil were systematically studied in this paper. The softened process consists of thermal treatment at 180 °C for different times. The results show that the softened annealing texture is mainly cubic texture, and the cubic texture fraction increases with the increase in annealing time. The cubic texture fraction reaches the highest (34.4%) after annealing for 60 min. After annealing for 1-5 min, the tensile strength and the bending times decrease significantly. After annealing for 10-60 min, the tensile strength tends to be stable, and the bending times increase slightly. With the increase in annealing time, the electrical conductivity increases gradually, reaching 92% International Annealed Copper Standard (IACS) after annealing for 60 min. Electrical conductivity can be used as a fast and effective method to analyze the microstructure of metals.

Genome-wide CRISPR/Cas9 screen identifies host factors important for porcine reproductive and respiratory syndrome virus replication.

Porcine reproductive and respiratory syndrome (PRRS), a viral infection caused by PRRS virus (PRRSV) can result in severe reproductive failure, and respiratory disease in the pigs thus causing enormous economic losses to the global swine industry. Although the cellular receptors for PRRSV have been identified, but mechanisms underlying PPRSV replication remain obscure. Here, we have performed a genome-scale CRISPR/Cas9 knockout screen in the pig kidney cells with PRRSV. Several genes were found to be highly enriched post-PRRSV selection, just like KxDL Motif Containing 1(KXD1), Proteasome 26S Subunit, Non-ATPase 3 (PSMD3) and Galectin 2 (LGALS2) and soon on. Importantly, we have identified that loss of KXD1 resulted in the restricted autophagy and inhibited replication of PRRSV. Therefore, our study demonstrates that CRISPR/Cas9 system can be effectively used for the screening of pig factors responsible for PRRSV replication.