Phosphoproteomic Analysis Indicates Phosphorylated Proteins in Response to Postharvest Blueberries Fruit Softening during Shelf Life.

Postharvest blueberry fruit is prone to softening. Protein phosphorylation is an important post-translational modification that was involved in fruit softening. However, little is known about protein phosphorylation in postharvest blueberry fruit softening. The firmness, the apparent morphology, and cell structures of blueberry fruit were changed. As the decay rate of postharvest blueberry fruit increased, the soluble solid and titrable acid contents decreased significantly. Phosphoproteomic sequencing results showed that there were 4100 phosphorylated peptides, 5635 phosphorylated sites, and 1437 phosphorylated proteins and showed significant differences on 0 and 8 d. The GO database and KEGG pathway results indicated that these phosphorylated proteins were mainly involved in "biological process", "molecular function", "plant hormone signal transduction", and "metabolic pathways". Besides, a number of phosphorylated proteins were found in cell wall metabolism, plant hormone signaling, primary metabolism, energy metabolism, membrane and transport, ubiquitination-based proteins, and other metabolisms.

VirB11, a traffic ATPase, mediated flagella assembly and type IV pilus morphogenesis to control the motility and virulence of Xanthomonas albilineans.

Xanthomonas albilineans (Xal) is a gram-negative bacterial pathogen responsible for developing sugarcane leaf scald disease, which engenders significant economic losses within the sugarcane industry. In the current study, homologous recombination exchange was carried out to induce mutations within the virB/D4-like type IV secretion system (T4SS) genes of Xal. The results revealed that the virB11-deletion mutant (ΔvirB11) exhibited a loss in swimming and twitching motility. Application of transmission electron microscopy analysis further demonstrated that the ΔvirB11 failed to develop flagella formation and type IV pilus morphology and exhibited reduced swarming behaviour and virulence. However, these alterations had no discernible impact on bacterial growth. Comparative transcriptome analysis between the wild-type Xal JG43 and the deletion-mutant ΔvirB11 revealed 123 differentially expressed genes (DEGs), of which 28 and 10 DEGs were notably associated with flagellar assembly and chemotaxis, respectively. In light of these findings, we postulate that virB11 plays an indispensable role in regulating the processes related to motility and chemotaxis in Xal.

Causal relationships between inflammatory cytokines and myopia: an analysis of genetic and observational studies.

Objective: This study aims to explore the causal relationship between inflammatory markers and myopia through the use of bidirectional Mendelian randomization (MR) and myopia animal models. Methods: The authors utilized data from a comprehensive and publicly accessible genome-wide association study (GWAS) for our analysis, which includes 460 536 European ancestry control subjects and 37 362 myopia patients. Utilizing a two-sample Mendelian randomization analysis framework, 27 inflammatory markers were investigated as exposure variables with myopia serving as the outcome variable. Nine MR analysis techniques were employed, with inverse-variance weighting (IVW) as the principal MR analysis method. Heterogeneity was assessed using Cochrane's Q test. The identification of single-nucleotide polymorphisms (SNPs) and outliers linked to myopia was achieved via MR-PRESSO. The expression of interleukin-2 (IL-2) in the vitreous of guinea pigs subjected to experimentally induced form-deprivation myopia (FDM) was examined. Results: Elevated concentrations of IL-2 and IL-2ra were found to be associated [IVW estimate odds ratio (OR): 1.003, 95% CI: 1.001-1.005, P=0.001] and strongly associated (IVW estimate OR: 1.002, 95% CI: 1.000-1.003, P=0.049) with an increased risk of myopia, respectively. Conversely, lower levels of C-reactive protein (CRP) (IVW estimate OR: 0.996, 95% CI: 0.994-0.999, P=0.002) and tumour necrosis factor alpha (IVW estimate OR: 0.995, 95% CI: 0.994-0.996, P<0.001) were robustly linked to a heightened risk of myopia. IL-2 expression was notably upregulated in the vitreous of guinea pigs with experimentally induced FDM. Conclusions: Elevated levels of inflammatory factors, especially IL-2 and IL-2ra, have a potential causal relationship with myopia susceptibility, providing new insights into the pathogenesis of myopia.

African Swine Fever Virus Modulates the Endoplasmic Reticulum Stress-ATF6-Calcium Axis to Facilitate Viral Replication.

ABSTRACTAfrican swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boar, which threatens the global pig industry. The endoplasmic reticulum (ER) is a multifunctional signaling organelle in eukaryotic cells that is involved in protein synthesis, processing, posttranslational modification and quality control. As intracellular parasitic organisms, viruses have evolved several strategies to modulate ER functions to favor their life cycles. We have previously demonstrated that the differentially expressed genes associated with the unfolded protein response (UPR) (downstream the ER stress) are significantly enriched upon ASFV infection. However, the correlation between the ER stress or UPR and ASFV replication has not been illuminated yet. Here, we demonstrated that ASFV infection induces ER stress both in target cells and in vivo, and subsequently activates the activating transcription factor 6 (ATF6) branch of the UPR to facilitate viral replication. Mechanistically, ASFV infection disrupts intracellular calcium (Ca2+) homeostasis, while the ATF6 pathway facilitates ASFV replication by increasing the cytoplasmic Ca2+ level. More specifically, we demonstrated that ASFV infection triggers ER-dependent Ca2+ release via the inositol triphosphate receptor (IP3R) channel. Notably, we showed that the ASFV B117L protein plays crucial roles in ER stress and the downstream activation of the ATF6 branch, as well as the disruption of Ca2+ homeostasis. Taken together, our findings reveal for the first time that ASFV modulates the ER stress-ATF6-Ca2+ axis to facilitate viral replication, which provides novel insights into the development of antiviral strategies for ASFV.

Structural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R.

The African swine fever virus (ASFV) type II topoisomerase (Topo II), pP1192R, is the only known Topo II expressed by mammalian viruses and is essential for ASFV replication in the host cytoplasm. Herein, we report the structures of pP1192R in various enzymatic stages using both X-ray crystallography and single-particle cryo-electron microscopy. Our data structurally define the pP1192R-modulated DNA topology changes. By presenting the A2+-like metal ion at the pre-cleavage site, the pP1192R-DNA-m-AMSA complex structure provides support for the classical two-metal mechanism in Topo II-mediated DNA cleavage and a better explanation for nucleophile formation. The unique inhibitor selectivity of pP1192R and the difunctional mechanism of pP1192R inhibition by m-AMSA highlight the specificity of viral Topo II in the poison binding site. Altogether, this study provides the information applicable to the development of a pP1192R-targeting anti-ASFV strategy.

Diffusible signal factor (DSF)-mediated quorum sensing modulates swarming in Xanthomonas albilineans.

Xanthomonas spp. are plant pathogens known for significantly impacting crop yields. Among them, Xanthomonas albilineans (Xal) is notable for colonizing the xylem and causing sugarcane leaf scald disease. This study employed homologous recombination to mutate quorum sensing (QS) regulatory genes (rpf) to investigate their role in Xal pathogenicity. Deletions of rpfF (ΔrpfF), rpfC (ΔrpfC), and rpfG (ΔrpfG) led to reduced swarming, growth, and virulence. However, DSF supplementation restored swarming and growth in the ΔrpfF mutant. Deleting rpfC, rpfG, and rpfF also reduced twitching motility and affected Type IV Pilus (T4P) expression. Transcriptomic analysis revealed that ΔrpfF positively regulates flagellar genes. DSF supplementation in ΔrpfF (ΔrpfF-DSF) modulated the expression of flagellar, chemotaxis, and T4P genes. These findings elucidate the DSF-mediated swarming pathway in Xal and provide valuable insights into its regulatory mechanisms.

Multi-parameter MRI-Based Machine Learning Model to Evaluate the Efficacy of STA-MCA Bypass Surgery for Moyamoya Disease: A Pilot Study.

Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery represents the primary treatment for Moyamoya disease (MMD), with its efficacy contingent upon collateral vessel development. This study aimed to develop and validate a machine learning (ML) model for the non-invasive assessment of STA-MCA bypass surgery efficacy in MMD. This study enrolled 118 MMD patients undergoing STA-MCA bypass surgery. Clinical features were screened to construct a clinical model. MRI features were extracted from the middle cerebral artery supply area using 3D Slicer and employed to build five ML models using logistic regression algorithm. The combined model was developed by integrating the radiomics score (Rad-score) with the clinical features. Model performance validation was conducted using ROC curves. Platelet count (PLT) was identified as a significant clinical feature for constructing the clinical model. A total of 3404 features (851 × 4) were extracted, and 15 optimal features were selected from each MRI sequence as predictive factors. Multivariable logistic regression identified PLT and Rad-score as independent parameters used for constructing the combined model. In the testing set, the AUC of the T1WI ML model [0.84 (95% CI, 0.70-0.97)] was higher than that of the clinical model [0.66 (95% CI, 0.46-0.86)] and the combined model [0.80 (95% CI, 0.66-0.95)]. The T1WI ML model can be used to assess the postoperative efficacy of STA-MCA bypass surgery for MMD.

FADD regulates adipose inflammation, adipogenesis, and adipocyte survival.

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/-) mice did not show any significant changes in body weight or composition. However, Fadd+/- mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/- mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

The Distal Promoter of the B438L Gene of African Swine Fever Virus Is Responsible for the Transcription of the Alternatively Spliced B169L.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSSs) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92-169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

Differentiation of tuberculous and brucellar spondylitis using conventional MRI-based deep learning algorithms.

PURPOSE: To investigate the feasibility of deep learning (DL) based on conventional MRI to differentiate tuberculous spondylitis (TS) from brucellar spondylitis (BS). METHODS: A total of 383 patients with TS (n = 182) or BS (n = 201) were enrolled from April 2013 to May 2023 and randomly divided into training (n = 307) and validation (n = 76) sets. Sagittal T1WI, T2WI, and fat-suppressed (FS) T2WI images were used to construct single-sequence DL models and combined models based on VGG19, VGG16, ResNet18, and DenseNet121 network. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. The AUC of DL models was compared with that of two radiologists with different levels of experience. RESULTS: The AUCs based on VGG19, ResNet18, VGG16, and DenseNet121 ranged from 0.885 to 0.973, 0.873 to 0.944, 0.882 to 0.929, and 0.801 to 0.933, respectively, and VGG19 models performed better. The diagnostic efficiency of combined models outperformed single-sequence DL models. The combined model of T1WI, T2WI, and FS T2WI based on VGG19 achieved optimal performance, with an AUC of 0.973. In addition, the performance of all combined models based on T1WI, T2WI, and FS T2WI was better than that of two radiologists (P<0.05). CONCLUSION: The DL models have potential guiding value in the diagnosis of TS and BS based on conventional MRI and provide a certain reference for clinical work.

New species and records of Hybos Meigen (Diptera, Empidoidea) from Huaping National Nature Reserve, China.

In this study, 21 species of Hybos Meigen, 1803 are reviewed in Huaping National Nature Reserve, China. Among these, three species, i.e., Hybosdenticulatussp. nov., Hybosforcipatasp. nov. and H.paraterminalissp. nov., are described as new to science. In addition, nine known species of this genus are reported for the first time in Guangxi. All the known species were enumerated, and an identification key to the species of Hybos from Huaping National Nature Reserve based on morphological characteristics is provided.

A simple chemiluminescent method for the quantification of exosomes based on horseradish peroxidase adsorbed on two-dimensional nanomaterials.

The development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H2O2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 102 particles µL-1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS2 for exosomes were also tested. MoS2-HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 102 particles µL-1. The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process.

DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

Abnormal Thickness-Dependent Thermal Transport in Suspended 2D PdSe2.

Research on 2D materials originally focused on the highly symmetrical materials like graphene, h-BN. Recently, 2D materials with low-symmetry lattice such as PdSe2 have drawn extensive attention, due to the interesting layer-dependent bandgap, promising mechanical properties and excellent thermoelectric performance, etc. In this work, the phonon thermal transport is studied in PdSe2 with a pentagonal fold structure. The thermal conductivity of PdSe2 flakes with different thicknesses ranging from few nanometers to several tens of nanometers is measured through the thermal bridge method, where the thermal conductivity increases from 5.04 W mk-1 for 60 nm PdSe2 to 34.51 W mk-1 for the few-layer one. The atomistic modelings uncover that with the thickness thinning down, the lattice of PdSe2 becomes contracted and the phonon group velocity is enhanced, leading to the abnormal increase in the thermal conductivity. And the upshift of the optical phonon modes contributes to the increase of the thermal conductivity as well by creating less acoustic phonon scattering as the thickness reduces. This study probes the interesting abnormal thickness-dependent thermal transport in 2D materials, which promotes the potential thermal management at nanoscale.

Combined effects of pre-pregnancy BMI and gestational weight gain on preterm birth: comparison between spontaneous and ART conception.

BACKGROUND: Inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are both linked to preterm birth (PTB); however, which one plays a dominant role in PTB risk is not yet sure. We aimed to evaluate the combined effect of pre-pregnancy BMI and GWG on the risk of PTB in singleton pregnancies conceived both spontaneously and through assisted reproductive technology (ART). METHODS: The data included all mothers (n = 17,540,977) who had a live singleton birth from the US National Vital Statistics System (NVSS) 2015-2019. Logistic regression models, quantile-g-computation, and generalized additive model were used to analyze the combined association of pre-pregnancy BMI and GWG with PTB. RESULTS: The singleton PTB rate was significantly higher in ART pregnancies (11.5%) than in non-ART pregnancies (7.9%). When compared to those women with pre-pregnancy normal weight and GWG within Institute of Medicine (IOM) guidelines, the highest PTB risk was observed in non-ART women with pre-pregnancy underweight and GWG below IOM guidelines (aOR 2.56; 95% CI 2.53-2.60) and in ART women with pre-pregnancy obese and GWG below IOM guidelines (aOR 2.56; 95%CI 2.36-2.78). GWG dominated the combined effect with its joint effect coefficient of - 0.281 (P < 0.05) in non-ART women and - 0.108 (P < 0.05) in ART women. CONCLUSIONS: Inappropriate GWG played a dominant role in increasing the risk of PTB in both non-ART and ART populations. Counseling regarding pre-pregnancy BMI and especially GWG appears to be even more crucial for pregnancies conceived via ART, given their impact on PTB.

Factors affecting the social alienation among the elderly patients with type 2 diabetes mellitus / 预防医学

Objective@#To investigate the influencing factors for social alienation among the elderly patients with type 2 diabetes mellitus (T2DM), so as to provide insights into formulating targeted intervention measures.@*Methods@#T2DM patients aged 60 years and older were selected from Hangzhou First People's Hospital from January to October 2023. Their demographics, diabetes complications were collected using questionnaire surveys, social support level was evaluated using the Social Support Scale, and the stigma was evaluated using the Chinese version of the Type 2 Diabetes Stigma Assessment Scale, and the social alienation was assessed using General Alienation Scale. Factors affecting the social alienation were identified among the elderly patients with T2DM using a multiple linear regression model.@*Results@#A total of 316 elderly patients with T2DM were investigated, including 171 males (54.11%) and 145 females (45.89%), and had a mean age of (69.75±8.12) years. The level of social support was mainly medium, with 162 cases accounted for 51.27%. The average stigma scores were (61.87±12.50) points, and average social alienation scores were (42.09±6.33) points. Multiple linear regression analysis identified educational level (high school/junior college, β'=-0.159; college and above, β'=-0.301), marital status (married persons, β'=-0.236), monthly household income (3 000 Yuan and more, β'=-0.175), diabetes complications (β'=0.192), social support level (medium, β'=-0.210; high, β'=-0.352) and stigma score (β'=0.283) as factors affecting the social alienation among the elderly patients with T2DM.@*Conclusion@#The social alienation among the elderly patients with T2DM are associated with educational level, marital status, family income, diabetes complications, social support level and stigma.

Variation of carbon source and sink along the environmental gradient from lakeside to highlands in Yuanchi swamp wetlands, Changbai Mountains, China.

Lacustrine wetlands have long-term carbon storage capacity and contribute significantly to regional carbon cycle, but it is unclear how its carbon sinks respond to climate change. We measured soil heterotrophic respiration carbon emissions (CO2 and CH4), vegetation carbon sequestration, and related environmental factors (temperature, water level, etc.) of five kinds of natural swamps (Phragmites marsh-L, Carex schmidtii marsh-C, Rhododendron capitatum swamp-D, Betula fruticose swamp-H, Larix olgensis swamp-LT)by using static chamber gas chromatography and relative growth equation methods, along the water environmental gradients from lakeside to highlands in Yuanchi of Changbai Mountains. We quantified the carbon source/sink function (CSS) and global warming potential (GWP) of various swamp types by estimating ecosystem net carbon balance, and revealed the variation patterns and formation mechanisms of CSS and GWP along the environmental gradients, aiming to explore the response of carbon source/sink of lakeside wetland in high altitude area to climate change. The results showed that marshes (L and C) were weak sources (-1.018 and -0.090 t C·hm-1·a-1) at the lower habitats of the water environment gradient, shrub swamps (D and H) were strong or weak sinks (1.956 and 0.239 t C·hm-1·a-1) at the middle habitats, forest swamp (LT) was strong source (-3.214 t C·hm-1·a-1) at the upper habitat. The spatial changes were promoted by water level and suppressed by soil temperature. For GWP, strong thermal radiation for marshes (from 44.682 to 59.282 t CO2·hm-1·a-1), cold radiation for shrub swamps (from -0.920 to -7.008 t CO2·hm-1·a-1), and weak thermal radiation for forest swamp (11.668 t CO2·hm-1·a-1), and their GWP was only promoted by soil temperature. Under current climate change background, marshes and forest swamp at both ends of the water environment gradient from lakeside to highlands played a positive feedback effect due to the increases of CH4 or CO2 emissions, while the middle shrub swamp still maintained a negative feedback effect in Yuanchi located the high-altitude area of the temperate Changbai Mountains.

Prognostic value of cell division cycle-associated protein-3 in prostate cancer.

BACKGROUND: The study was aimed to explore cell division cycle-associated protein-3 (CDCA3) expression and its correlation with clinicopathological characteristics, and identification of co-expressed genes of CDCA3 in prostate cancer (PCa). METHODS: Data for CDCA3 mRNA expression in PCa were obtained from The Cancer Genome Atlas database. Furtherly, CDCA3 protein expression was examined by immunohistochemistry in 80 cases, including 20 normal prostate samples and 60 PCa samples. Then we used "survival" package to obtain the differentially expressed CDCA3 mRNA associated with prognosis of PCa patients. "pROC" package was used to analyze receiver operating characteristic of CDCA3. We used chi-square test, Kruskal-Wallis test and Wilcoxon rank sum test to identify clinicopathological parameters that correlated with CDCA3 expression. In order to determine the effects of CDCA3 expression and clinicopathological parameters on survival, univariate cox regression analysis was performed. Finally, the co-expressed genes of CDCA3 in PCa were explored by search tool for the retrieval of interacting genes, Kyoto encyclopedia of genes and genomes enrichment analysis and Spearman correlation analysis. RESULTS: In this study, we found that CDCA3 expression was increased in PCa. PCa patients with higher CDCA3 expression had poor outcomes. In terms of receiver operating characteristic, CDCA3 had an area under the curve of 0.857. High CDCA3 expression was positively correlated with advanced T stage, N stage, Gleason score, and served as an independent predictor of progress free interval in PCa patients. Then 20 proteins closely related to CDCA3 were screened through STRING website. Functional enrichment analysis revealed that, Kyoto encyclopedia of genes and genomes pathway was mainly enriched in cell cycle, including 6 genes, BUB1, CCNA2, CDK1, CDC20, TTK, and CCNB2. CONCLUSION: CDCA3 is significantly associated with the prognosis of PCa, which may be an indicator of the diagnosis and prognosis of PCa and a new therapeutic target.

New species and records of the genus Hybos Meigen (Diptera, Empidoidea, Hybotinae) from Wuyishan National Park, China.

Wuyishan National Park is well known for its rich biodiversity. Previously, only five species of Hybos Meigen, 1803 were known to occur in this region. In this study, 27 species of the genus Hybos from Wuyishan National Park are reviewed based on comparative morphological characteristics. Among these, nine species are described as new to science: Hybosbrevidigitatussp. nov., Hybosconstractussp. nov., Hyboscurvitibiasp. nov., Hybosdazhulanussp. nov., Hybosfujianensissp. nov., Hybosleucopogussp. nov., Hyboslongidigitatussp. nov., Hybosmodificatussp. nov., and Hyboswuyishanussp. nov. Diagnoses, detailed descriptions, remarks, colored illustrations, distributions, and some of the female terminalia characteristics are provided for nine new species. In addition, 13 species of this genus are reported for the first time in Wuyishan National Park. A key to Hybos species from Wuyishan National Park is also given.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.