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Abstract Bladder cancer remains a significant health challenge due to its high recurrence and progression rates. This study aims to evaluate the role of POLR3G in the development and progression of bladder cancer and the potential of POLR3G to serve as a novel therapeutic target. We constructed a bladder cancer model in Wistar rats by administering N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), which successfully induced a transition from normal mucosa to hyperplasia and ultimately to urothelial carcinoma. We observed a progressive upregulation of POLR3G expression during the bladder cancer development and progression. To investigate the functional role of POLR3G, we performed functional experiments in bladder cancer cell lines. The results demonstrated that knocking down POLR3G significantly inhibited cell proliferation, migration, and invasion. We further conducted RNA sequencing on POLR3G-knockdown bladder cancer cells, and Metascape was employed to perform the functional enrichment analysis of the differentially expressed genes (DEGs). Enrichment analysis revealed the enrichment of DEGs in the RNA polymerase and apoptotic cleavage of cellular proteins pathways, as well as their involvement in the Wnt and MAPK signaling pathways. The downregulation of Wnt pathway-related proteins such as Wnt5a/b, DVL2, LRP-6, and phosphorylated LRP-6 upon POLR3G knockdown was further confirmed by Western blotting, indicating that POLR3G might influence bladder cancer behavior through the Wnt signaling pathway. Our findings suggest that POLR3G plays a crucial role in bladder cancer progression and could serve as a potential therapeutic target. Future studies should focus on the detailed mechanisms by which POLR3G regulates these signaling pathways and its potential as a biomarker for early detection and prognosis of bladder cancer.

BackgroundNatural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients’ NK cells respond to different stimulatory factors in terms of proliferation capability.Methods and resultsTwenty-nine CAD patients’ peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients’ NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell’s function.ConclusionAscorbic acid could promote the proliferation of the CAD patients’ NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.

With the maturity of artificial intelligence (AI) technology, applications of AI in edge computing will greatly promote the development of industrial technology. However, the existing studies on the edge computing framework for the Industrial Internet of Things (IIoT) still face several challenges, such as deep hardware and software coupling, diverse protocols, difficult deployment of AI models, insufficient computing capabilities of edge devices, and sensitivity to delay and energy consumption. To solve the above problems, this paper proposes a software-defined AI-oriented three-layer IIoT edge computing framework and presents the design and implementation of an AI-oriented edge computing system, aiming to support device access, enable the acceptance and deployment of AI models from the cloud, and allow the whole process from data acquisition to model training to be completed at the edge. In addition, this paper proposes a time series-based method for device selection and computation offloading in the federated learning process, which selectively offloads the tasks of inefficient nodes to the edge computing center to reduce the training delay and energy consumption. Finally, experiments carried out to verify the feasibility and effectiveness of the proposed method are reported. The model training time with the proposed method is generally 30% to 50% less than that with the random device selection method, and the training energy consumption under the proposed method is generally 35% to 55% less.

Abstract The consequences of sub-lethal levels of ambient air pollution are underestimated for insects, for example, the accumulation of particulate matter on sensory receptors located on their antennae may have detrimental effects to their function. Here we show that the density of particulate matter on the antennae of houseflies (Musca domestica) collected from an urban environment increases with the severity of air pollution. A combination of behavioural assays, electroantennograms and transcriptomic analysis provide consistent evidence that a brief exposure to particulate matter pollution compromises olfactory perception of reproductive and food odours in both male and female houseflies. Since particulate matter can be transported thousands of kilometres from its origin, these effects may represent an additional factor responsible for global declines in insect numbers, even in pristine and remote areas.

The acquired immunodeficiency syndrome (AIDS) epidemic, resulting from human immunodeficiency virus (HIV) infection, exhibits distinct regional characteristics. This study undertakes a retrospective analysis of the epidemiological and clinical features of 195 HIV-positive cases in Meizhou, China, from May 1, 2018 to December 31, 2019. Western blotting (WB) confirmed and assessed these cases. Notably, the majority of cases emanated from socio-economic groups with comparatively lower levels of education, with 80% being male. Strikingly, 90% of the cases were found to be in the middle to late stages of infection based on CD4+ T cell counts. Among the 30 different serum antibody profiles examined, reactivity with seven bands (p24, p31, gp41, p51, p66, gp120, and gp160) emerged as the most commonly observed WB pattern. The absence of specific bands, specifically p55 (17.44%), p39 (32.31%), and p17 (25.64%) were most frequent, with the detection frequency of p17 bands significantly reduced among cases in the AIDS and middle stages. An analysis of drug resistance genotypes indicated that, despite viral mutations conferring resistance to certain reverse transcriptase inhibitors, the first-line treatment regimen remained effective for patients in Meizhou. Notably, mutations resistant to protease inhibitors were infrequent (2.7%), suggesting that incorporating protease inhibitors into the treatment regimen may enhance therapeutic outcomes for local patients. These findings provide essential insights into the specific epidemiological patterns, serum antibody profiles, and drug resistance genotypes of HIV-infected patients in Meizhou. Significantly, this research contributes to the formulation of future treatment strategies tailored to the local context.

The flexural performance of RC beams strengthened with a novel high-strength and high-toughness epoxy mortar thin layer was investigated through four-point flexural tests on two contrast beams and two strengthened beams. The effects of this strengthening method on the failure modes, crack distribution, load–deflection curves, and bearing capacity of the RC beams with two reinforcement ratios were studied. The experimental results revealed that the contrast beams exhibited the typical bending failure modes where the failure mode of the reinforced beam is the yielding of the tensile reinforcement of the original beam and then fracture damage of the new epoxy mortar-reinforced thin layer. No debonding phenomenon was observed between the reinforced thin layer and the original concrete, and no visible cracks appeared before the tensile failure occurred in the thin layer. The cracks in the reinforced beams developed slowly, increased in number, and decreased significantly in width and spacing. The stiffness of the strengthened beam increased significantly, while its deformation ductility coefficient noticeably decreased. Compared to the corresponding contrast beams, the cracking load for strengthened beams A1 and B1 increased by 14% and 23%, respectively; the yield load increased by 32% and 40%, respectively; and the peak load increased by 18% and 17%, respectively. Finally, a calculation method for the flexural bearing capacity of RC beams strengthened with the novel epoxy mortar thin layer based on the flat section assumption was proposed. The calculated values showed a good agreement with the experimental values (with errors at −11.73% and 4.14%, respectively), providing a valuable reference for further research and application related to this kind of reinforcement method.

A total of five ultra-high-performance concrete (UHPC)-strengthened reinforced concrete (RC) columns and one RC column were built and subjected to eccentric compression testing to examine the force performance of UHPC-strengthened eccentrically compressed plain RC columns. This experimental study examined the crack progression, the damage morphology, the deformation ability, the maximum load-carrying capacity, and the ductile properties of the eccentrically compressed columns. It also investigated the impacts of eccentricity, the reinforcement thickness, and the addition of steel fibers on the effectiveness of reinforcement. The cracking load, peak load, and ductility coefficient of the UHPC-reinforced specimens were increased by 100.28%, 172.30%, and 56.30%, respectively, compared with the RC column at an initial eccentricity of 50 mm. As the eccentricity distance increased, the bearing capacity of the UHPC eccentrically compressed specimens decreased, and the deformation capacity increased. Increasing the steel fiber dosage within the appropriate range decreased the crack width of the specimen. The addition of 2% steel fiber resulted in a 24.8% increase in cracking load, an 8.96% increase in peak load, and a 2.60% increase in ductility coefficient compared to the addition of 1% steel fiber. However, the reinforcing effect of UHPC was weakened under high eccentric pressures. Based on the theory of concrete structure and mechanical principles, the formula for calculating the compressive bearing capacity of RC columns strengthened with high-performance concrete was proposed. The results of calculating the positive section bearing capacity of eccentrically compressed RC columns reinforced with high-performance concrete are in good agreement with the test values. The results of this paper provide an experimental basis and theoretical foundation for the cross-sectional design of UHPC eccentrically compressed columns.

Abstract Background The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration. Methods RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The “survival” and “survminer” packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis. Results Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT. Conclusions MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.

Abstract Antennae and maxillary palps are the most important chemical reception organs of flies. So far, the morphology of antennae and maxillary palps of flies of most feeding habits have been well described, except for that of relatively rare aquatic predatory species. This study describes sensilla on antennae and maxillary palps of three aquatic predatory Lispe species: Lispe longicollis, L. orientalis and L. pygmaea. Types, distribution, and density of sensilla are characterised via light and scanning electron microscopy. One type of mechanoreceptors is found on antennal scape. Mechanoreceptors (two subtypes) and one single pedicellar button (in L. pygmaea) are located on antennal pedicel. Four types of sensilla are discovered on antennal postpedicel: trichoid sensilla, basiconic sensilla (three subtypes), coeloconic sensilla and clavate sensilla. A unique character of these Lispe species is that the coeloconic sensilla are distributed sparsely on antennal postpedicel. Mechanoreceptors and basiconic sensilla are observed on the surface of maxillary palps in all three species. We demonstrated clear sexual dimorphism of the maxillary palps in some of the Lispe species, unlike most other Muscidae species, are larger in males than females. This, along with their courtship dance behaviour, suggest their function as both chemical signal receiver and visual signal conveyer, which is among the few records of a chemical reception organ act as a signal conveyer in insects.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) is a nutrient-sensitive protein modification that alters the structure and function of a wide range of proteins involved in diverse cellular processes. Similar to phosphorylation, another protein modification that targets serine and threonine residues, O-GlcNAcylation occupancy on cellular proteins exhibits daily rhythmicity and has been shown to play critical roles in regulating daily rhythms in biology by modifying circadian clock proteins and downstream effectors. We recently reported that daily rhythm in global O-GlcNAcylation observed in Drosophila tissues is regulated via the integration of circadian and metabolic signals. Significantly, mistimed feeding, which disrupts coordination of these signals, is sufficient to dampen daily O-GlcNAcylation rhythm and is predicted to negatively impact animal biological rhythms and health span. In this review, we provide an overview of published and potential mechanisms by which metabolic and circadian signals regulate hexosamine biosynthetic pathway metabolites and enzymes, as well as O-GlcNAc processing enzymes to shape daily O-GlcNAcylation rhythms. We also discuss the significance of functional interactions between O-GlcNAcylation and other post-translational modifications in regulating biological rhythms. Finally, we highlight organ/tissue-specific cellular processes and molecular pathways that could be modulated by rhythmic O-GlcNAcylation to regulate time-of-day-specific biology.

In recent years, cloud-native technology has become popular among Internet companies. Microservice architecture solves the complexity problem for multiple service methods by decomposing a single application so that each service can be independently developed, independently deployed, and independently expanded. At the same time, domestic industrial Internet construction is still in its infancy, and small and medium-sized enterprises still face many problems in the process of digital transformation, such as difficult resource integration, complex control equipment workflow, slow development and deployment process, and shortage of operation and maintenance personnel. The existing traditional workflow architecture is mainly aimed at the cloud scenario, which consumes a lot of resources and cannot be used in resource-limited scenarios at the edge. Moreover, traditional workflow is not efficient enough to transfer data and often needs to rely on various storage mechanisms. In this article, a lightweight and efficient workflow architecture is proposed to optimize the defects of these traditional workflows by combining cloud-edge scene. By orchestrating a lightweight workflow engine with a Kubernetes Operator, the architecture can significantly reduce workflow execution time and unify data flow between cloud microservices and edge devices.

Misalignment between lifestyle and the natural day-night cycle, such as mistimed eating, can negatively impact health. Here the authors show that mistimed feeding alters protein O-GlcNAcylation, a nutrient sensitive post-translational modification.

Porcine Circovirus-like (PCL) virus, a new emerging virus, has been widely detected in Guangdong, Guangxi, and Anhui provinces in China, which may be a novel agent causing severe diarrhea in newborn piglets and tending to spread widely. Evidence suggests that the virus is related to hemorrhagic enteritis and diarrhea, and many newborn piglets were emaciated to death after infection. Therefore, a sensitive, quick, and accurate detection system for virus detection and epidemiological investigation is necessary. In this study, we developed a real-time quantitative PCR assay based on SYBR green for the detection of PCL virus. The ORF4 conserved region of PCL virus was found by the alignment of the uploaded genome sequences to design specific primers, and the primers were tested and showed good specificity, sensitivity, and reproducibility. Approximately, 138 fecal samples were obtained from diarrheal pigs in South China from June to December 2021. Approximately, 22.46% (31/138) of the samples and 40% (8/20) of the pig farms were positive for PCL virus, respectively, by using this method. Moreover, it is worth noting that the virus was first detected in Hainan and Jiangxi Provinces of China, which means that the virus may spread widely in China. Through evolutionary tree analysis and partial sequence comparison, there are some differences of virus genes in each province, suggesting that there is a risk of variation, and the four PCL virus strains showed a sequence similarity of 86.7%–87.8% for the rep gene and 92.2%–92.9% for the Rep protein, respectively, with Bo-Circo-like virus that is detected in bovine, which further demonstrates a close relationship between the two viruses that originated from different animals. In conclusion, our study provides a useful diagnostic approach to PCL virus detection and epidemiological inquiry. Meanwhile, the epidemic data using this real-time qPCR assay provide evidence for the widespread variations and epidemic of the virus in South China, and warn the appropriate measures for prevention, and control of porcine circovirus-like virus infection should be under consideration in pig production.

BackgroundPrevious reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported.MethodsThe TIMER and UALCAN databases were used for pan-cancer analysis. RNA sequencing and microarray data of patients with ccRCC were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus database. The differential expression of ACADSB in ccRCC and normal kidney tissues was tested. Correlations between ACADSB expression and clinicopathological parameters were assessed using the Wilcoxon test. The influences of ACADSB expression and clinicopathological parameters on overall survival were assessed using Cox proportional hazards models. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different ACADSB expression phenotypes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on genes with similar expression patterns to ACADSB. Correlations between ACADSB and ferroptosis-related genes were assessed using Spearman’s correlation analysis.ResultsPan-cancer analysis revealed that ACADSB is down-regulated in multiple cancers, and decreased expression of ACADSB correlates with poor prognosis in certain types of cancer. Differential expression analyses revealed that ACADSB was down-regulated in ccRCC, indicating that ACADSB expression could be a single significant parameter to discriminate between normal and tumor tissues. Clinical association analysis indicated that decreased ACADSB expression was associated with high tumor stage and grade. The Cox regression model indicated that low ACADSB expression was an independent risk factor for the overall survival of patients with ccRCC. GSEA showed that 10 gene sets, including fatty acid (FA) metabolism, were differentially enriched in the ACADSB high expression phenotype. GO and KEGG pathway enrichment analysis revealed that ACADSB-related genes were significantly enriched in categories related to FA metabolism, branched-chain amino acid (BCAA) metabolism, and iron regulation. Spearman’s correlation analysis suggested that the expression of ACADSB was positively correlated with the expression of ferroptosis driver genes.ConclusionsACADSB showed good diagnostic and prognostic abilities for ccRCC. The downregulation of ACADSB might promote tumorigenesis and tumor progression by inhibiting FA catabolism, BCAA catabolism, and ferroptosis in ccRCC.

Porcine epidemic diarrhea (PED) is an acute and severe atrophic enteritis caused by porcine epidemic diarrhea virus (PEDV) that infects pigs and makes huge economic losses to the global swine industry. Previously, researchers have believed that porcine aminopeptidase-N (pAPN) was the primary receptor for PEDV, but it has been found that PEDV can infect pAPN knockout pigs. Currently, the functional receptor for PEDV remains unspecified. In the present study, we performed virus overlay protein binding assay (VOPBA), found that ATP1A1 was the highest scoring protein in the mass spectrometry results, and confirmed that the CT structural domain of ATP1A1 interacts with PEDV S1. First, we investigated the effect of ATP1A1 on PEDV replication. Inhibition of hosts ATP1A1 protein expression using small interfering RNA (siRNAs) significantly reduced the cells susceptibility to PEDV. The ATP1A1-specific inhibitors Ouabain (a cardiac steroid) and PST2238 (a digitalis toxin derivative), which specifically bind ATP1A1, could block the ATP1A1 protein internalization and degradation, and consequently reduce the infection rate of host cells by PEDV significantly. Additionally, as expected, overexpression of ATP1A1 notably enhanced PEDV infection. Next, we observed that PEDV infection of target cells resulted in upregulation of ATP1A1 at the mRNA and protein levels. Furthermore, we found that the host protein ATP1A1 was involved in PEDV attachment and co-localized with PEDV S1 protein in the early stage of infection. In addition, pretreatment of IPEC-J2 and Vero-E6 cells with ATP1A1 mAb significantly reduced PEDV attachment. Our observations provided a perspective on identifying key factors in PEDV infection, and may provide valuable targets for PEDV infection, PEDV functional receptor, related pathogenesis, and the development of new antiviral drugs.

Porcine reproductive and respiratory syndrome (PRRS) is a vertically transmitted reproductive disorder that is typically characterized by miscarriage, premature birth, and stillbirth in pregnant sows after infection. Such characteristics indicate that PRRSV can infect and penetrate the porcine placental barrier to infect fetus piglets. The porcine trophoblast is an important component of the placental barrier, and secretes various hormones, including estrogen and progesterone, to maintain normal pregnancy and embryonic development during pregnancy. It is conceivable that the pathogenic effects of PRRSV infection on porcine trophoblast cells may lead to reproductive failure; however, the underlying detailed mechanism of the interaction between porcine trophoblast (PTR2) cells and PRRSV is unknown. Therefore, we conducted genome-wide mRNA and long non-coding RNA (lncRNA) analysis profiling in PRRSV-infected PTR2. The results showed that 672 mRNAs and 476 lncRNAs were significantly different from the control group after viral infection. Target genes of the co-expression and co-location of differential mRNAs and lncRNAs were enriched by GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that most of the pathways were involved in cell nutrient metabolism, cell proliferation, and differentiation. Specifically, the estrogen signaling pathway, the PI3K (PhosphoInositide-3 Kinase)-Akt (serine/threonine kinase) signaling pathway, and the insulin secretion related to embryonic development were selected for analysis. Further research found that PRRSV inhibits the expression of G-protein-coupled estrogen receptor 1 (GPER1), thereby reducing estrogen-induced phosphorylation of AKT and the mammalian target of rapamycin (mTOR). The reduction in the phosphorylation of AKT and mTOR blocks the activation of the GPER1- PI3K-AKT-mTOR signaling pathway, consequently restraining insulin secretion, impacting PTR2 cell proliferation, differentiation, and nutrient metabolism. We also found that PRRSV triggered trophoblast cell apoptosis, interrupting the integrity of the placental villus barrier. Furthermore, the interaction network diagram of lncRNA, regulating GPER1 and apoptosis-related genes, was constructed, providing a reference for enriching the functions of these lncRNA in the future. In summary, this article elucidated the differential expression of mRNA and lncRNA in trophoblast cells infected with PRRSV. This infection could inhibit the PI3K-AKT-mTOR pathway and trigger apoptosis, providing insight into the mechanism of the vertical transmission of PRRSV and the manifestation of reproductive failure.

The rubber ring is an essential component of high-pressure hydrogen storage systems. However, the fretting damage can lead to the seal failure of the rubber ring, which may cause hydrogen leakage. Rubber X-ring has been proven to own excellent static sealing performance, while its fretting characteristics under high-pressure hydrogen remain unclear. In this study, a numerical model is developed to explore the fretting characteristics of the X-ring combined seal, in which the effect of hydrogen swelling is well considered. The stress distribution of the fretting seal and the effects of fretting amplitude, friction coefficient, hydrogen pressure, and pre-compression ratio on the fretting behavior of the X-ring are investigated. Moreover, the similarities and differences in the fretting performance of X-ring and O-ring under high-pressure hydrogen are discussed. It is shown that the evolution of the stress concentration zone inside the X-ring is closely linked to the cover’s drag direction and the wedge-ring’s blocking action. The X-ring enters the fretting cycle earlier with increased fretting amplitude, whereas the fretting period remains unchanged. Furthermore, increasing the hydrogen pressure and pre-compression ratio could enhance the fretting sealing performance. The friction coefficient and hydrogen pressure increase the possibility of failure due to cracks or elasticity. The fretting characteristics of the X-ring are superior to those of the O-ring, denoting that X-ring may be an alternative to the O-ring in the fretting seal structure. This work is of theoretical importance for the quantitative evaluation and reliable prevention of fretting damage to rubber rings and improving the safety of high-pressure hydrogen storage systems.

The antennae are the main olfactory organ of flies, playing key roles in their survival and the success of all life stages. Antennal ultrastructural morphology has been well described in the representative species of most calyptrate families, yet only a few studies have focused on Sarcophagidae species, those with ecological and medical relevance. Antennal morphology and the types, shapes, distribution, and density of the antennal sensilla of nine Sarcophagidae species are studied in detail with scanning electron microscopy, including Miltogramminae: Metopia campestris (Fallén) and Mesomelena mesomelaena (Loew), Paramacronychiinae: Agria mihalyii (Rohdendorf & Verves), Wohlfahrtia bella (Macquart), and W. magnifica (Schiner); Sarcophaginae: Sarcophaga (Parasarcophaga) albiceps Meigen, S. (Bercaea) africa (Wiedemann), S. (Boettcherisca) peregrina (Robineau-Desvoidy), and S. (Liosarcophaga) portschinskyi (Rohdendorf), covering all three subfamilies of this family. The morphology of the three segments of the antennae has been described. The scape has only one type of chaetic sensilla, while three subtypes of chaetic sensilla were detected on the pedicel. The postpedicel has four types of sensilla: trichoid sensilla, coeloconic sensilla, clavate sensilla, and three subtypes of basiconic sensilla. Bottle-shaped sensilla were observed in sensory pits on the postpedicel in all nine species. These sensilla have not been discovered in other calyptrate species, suggesting that they are a potential sarcophagid synapomorphy.

Porcine circovirus 3 (PCV3) infections cause clinical diseases similar to those seen in porcine circovirus 2 (PCV2) infections. It is unclear whether PCV3 infections can also cause immunosuppression like that seen with PCV2. Here, we report that Cap inhibits DNA-induced IFN-β mRNA transcription and IFN promoter activation. Cap was also found to inhibit cyclic GMP-AMP (cGAMP) synthase (cGAS) binding to interferon-stimulating DNA (ISD). Immunoprecipitation and mass spectrometry were used to identify cellular interaction partners of Cap. Cap interacted with G3BP1 and inhibited the interaction between GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) and cGAS. Furthermore, the destruction of endogenously expressed G3BP1 by siRNA significantly reduced IFN promoter activation, and phosphorylation of tank-binding kinase 1 (TBK1) was induced by ISD. Overexpression of G3BP1 attenuated the inhibition of ISD binding of cGAS by Cap and promoted phosphorylation of TBK1 and IRF3 induced by ISD. Collectively, our results show that the interaction between Cap and G3BP1 prevents cGAS from recognizing DNA, thereby inhibiting the IFN production.

Background Previous studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC. Methods The RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC. Results Transcriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT. Conclusions POLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

Circadian clocks coordinate time-of-day-specific metabolic and physiological processes to maximize organismal performance and fitness. In addition to light and temperature, which are regarded as strong zeitgebers for circadian clock entrainment, metabolic input has now emerged as an important signal for clock entrainment and modulation. Circadian clock proteins have been identified to be substrates of O-GlcNAcylation, a nutrient sensitive post-translational modification (PTM), and the interplay between clock protein O-GlcNAcylation and other PTMs is now recognized as an important mechanism by which metabolic input regulates circadian physiology. To better understand the role of O-GlcNAcylation in modulating clock protein function within the molecular oscillator, we used mass spectrometry proteomics to identify O-GlcNAcylation sites of PERIOD (PER), a repressor of the circadian transcriptome and a critical biochemical timer of the Drosophila clock. In vivo functional characterization of PER O-GlcNAcylation sites indicates that O-GlcNAcylation at PER(S942) reduces interactions between PER and CLOCK (CLK), the key transcriptional activator of clock-controlled genes. Since we observe a correlation between clock-controlled daytime feeding activity and higher level of PER O-GlcNAcylation, we propose that PER(S942) O-GlcNAcylation during the day functions to prevent premature initiation of circadian repression phase. This is consistent with the period-shortening behavioral phenotype of per(S942A) flies. Taken together, our results support that clock-controlled feeding activity provides metabolic signals to reinforce light entrainment to regulate circadian physiology at the post-translational level. The interplay between O-GlcNAcylation and other PTMs to regulate circadian physiology is expected to be complex and extensive, and reach far beyond the molecular oscillator.

In a health management system, prognostics, which is an engineering discipline that predicts a system’s future health, is an important aspect yet there is currently limited research in this field. In this paper, a hybrid approach for prognostics is proposed. The approach combines the least squares support vector regression (LSSVR) with the hidden Markov model (HMM). Features extracted from sensor signals are used to train HMMs, which represent different health levels. A LSSVR algorithm is used to predict the feature trends. The LSSVR training and prediction algorithms are modified by adding new data and deleting old data and the probabilities of the predicted features for each HMM are calculated based on forward or backward algorithms. Based on these probabilities, one can determine a system’s future health state and estimate the remaining useful life (RUL). To evaluate the proposed approach, a test was carried out using bearing vibration signals. Simulation results show that the LSSVR/HMM approach can forecast faults long before they occur and can predict the RUL. Therefore, the LSSVR/HMM approach is very promising in the field of prognostics.

O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a dynamic post-translational modification that regulates thousands of proteins and almost all cellular processes. Aberrant O-GlcNAcylation has been associated with numerous diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and type 2 diabetes. O-GlcNAcylation is highly nutrient-sensitive since it is dependent on UDP-GlcNAc, the end product of the hexosamine biosynthetic pathway (HBP). We previously observed daily rhythmicity of protein O-GlcNAcylation in a Drosophila model that is sensitive to the timing of food consumption. We showed that the circadian clock is pivotal in regulating daily O-GlcNAcylation rhythms given its control of the feeding-fasting cycle and hence nutrient availability. Interestingly, we reported that the circadian clock also modulates daily O-GlcNAcylation rhythm by regulating molecular mechanisms beyond the regulation of food consumption time. A large body of work now indicates that O-GlcNAcylation is likely a generalized cellular status effector as it responds to various cellular signals and conditions, such as ER stress, apoptosis, and infection. In this review, we summarize the metabolic regulation of protein O-GlcNAcylation through nutrient availability, HBP enzymes, and O-GlcNAc processing enzymes. We discuss the emerging roles of circadian clocks in regulating daily O-GlcNAcylation rhythm. Finally, we provide an overview of other cellular signals or conditions that impact O-GlcNAcylation. Many of these cellular pathways are themselves regulated by the clock and/or metabolism. Our review highlights the importance of maintaining optimal O-GlcNAc rhythm by restricting eating activity to the active period under physiological conditions and provides insights into potential therapeutic targets of O-GlcNAc homeostasis under pathological conditions. [ABSTRACT FROM AUTHOR]