Overexpression of miRNA29a gene inhibits proliferation and promotes apoptosis of jejunal epithelial cells in yak.

MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a play a key role in functions of mammal cell differentiation, proliferation, apoptosis, and signal transduction. However, the underlying functions for miR-29a in jejunal epithelial cells biological function still to be investigated. In order to explore the yak jejunal epithelial cells proliferation and barrier dysfunction with over expression of miR-29a gene, three 0-day-old Pamir male yaks were randomly selected and slaughtered in present study, and the jejunal epithelial cells were isolated and cultured to determine yak jejunal epithelial cells proliferation and protein composition on differential expression of miR-29a gene in Pamir plateau. Here, we demonstrated that the overexpression of miR-29a gene could inhibit the proliferation of Pamir yaks jejunum epithelial cells, and contribute to the apoptosis of Pamir yaks jejunal epithelial cells with some extent. A total of 133 differentially expressed proteins were identified in different expression of miR-29a groups by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: cell proliferation and inflammatory response. Interestingly, GPR41, as a bridge protein, was contacted two predominant themes to involved in Pamir Yaks jejunal mechanical barrier PPI network, and the target proteins displayed strong mutual interactions in the complex PPI network. Overall, our study suggested that the over-expression miR-29a inhibited the jejunal epithelial cells proliferation and the expressions of specific proteins, which damaged jejunal barrier function to slow down the intestine structure and function advanced mature development during young livestock period for influence the enhanced performance of production efficiency.

Polyprenylated xanthones with potential anti-inflammatory and anti-HIV effects from the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume.

A phytochemical study on the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume resulted in the isolation and characterisation of a new polyprenylated xanthone, cratocochinone (1), as well as seven known analogues, fuscaxanthone K (2), pruniflorone Q (3), 1,3,5,8-tetrahy-droxy- 2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (4), cochinensoxanthone (5), cratoxylum-xanthone B (6), cochinchinone I (7) and cochinchinone K (8). The chemical structure of 1 was determined by comprehensive spectral analyses. The known compounds 2 - 8 were identified by comparing their experimental spectroscopic data with those reported data in the literature. The anti-inflammatory and anti-HIV effects of all isolates 1-8 were evaluated. As a result, compounds 1-8 showed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values ranging from 0.68 ± 0.06 to 10.27 ± 0.18 µM. Meanwhile, compounds 1-8 displayed notable anti-HIV-1 reverse transcriptase (RT) effects with EC50 values ranging from 0.19 to 10.72 µM.

Glutathione-Conjugated Fluorometric Ratiometric NIR-Silicon Nanoparticles and Its Applications for In Vitro and In Vivo Imaging.

Glutathione (GSH), a tripeptide molecule, is the most abundant nonprotein biothiol in living cells, playing a crucial role in preventing oxidative damage to cellular components and maintaining intracellular redox homeostasis. As a thiol molecule, GSH contains a sulfhydryl (-SH) group that is vital for the body's response to reactive oxygen species (ROS). To confirm whether GSH can be used as a bioindicator or in the early diagnosis of cancers at the cellular level, it is essential to achieve highly selective detection and conjugation of GSH to silicon nanoparticles (SiNPs) under pathological conditions. We are herein excited to report a type of fluorescent ratiometric near-infrared silicon nanoparticle (NIR-SiNP) probe, that is, glutathione peptide conjugated (NIR-SiNPs-GSH), which simultaneously possess small pore sizes at an average of 6.7 nm, an emission of 670 nm, a bioimaging functionality of living cancer cells and animals, and favorable biocompatibility. Taking advantage of these virtues, we further manifest that such resulting NIR-SiNPs, NIR-SiNPs-GSH bioprobes are marvelously worthy for immunofluorescence imaging of cancer cells and living mice. Furthermore, it was shown that DAPI and probes could selectively stain malignant tumor cell nuclei, indicating the possibility for bioimaging and identification of cancer cells and animals. In summary, the suggested NIR-SiNPs-GSH probe has the potential to be a very effective chemical tool for early tumor detection in the future.

Alkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology.

Chelidonium majus L. (C. majus), commonly known as "Bai Qu Cai" in China, belongs to the genus Chelidonium of the Papaveraceae family. It has rich medicinal value, such as alleviating coughs, asthma, spasms and pain. Recent studies have demonstrated that C. majus is abundant in various alkaloids, which are the primary components of C. majus and have a range of pharmacological effects, including anti-microbial, anti-inflammatory, anti-viral, and anti-tumor effects. So far, 94 alkaloids have been isolated from C. majus, including benzophenanthridine, protoberberine, aporphine, protopine and other types of alkaloids. This paper aims to review the research progress in phytochemistry, pharmacology and toxicology of C. majus alkaloids, in order to provide a theoretical basis for the application of C. majus in the field of medicinal chemistry and to afford reference for further research and development efforts.

Janus kinase inhibitors and adverse events of acne in dermatologic indications: a systematic review and network meta-analysis.

Background: The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence.Purpose: To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event.Methods: A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0.Results: A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39-21.88]), vitiligo (4.15 [95% CI, 1.27-13.58]), alopecia areata (3.86 [95% CI, 1.58-9.42]), and atopic dermatitis (2.82 [95% CI, 1.75-4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne.Conclusions: There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.

Sodium Houttuyniae attenuates ferroptosis by regulating TRAF6-c-Myc signaling pathways in lipopolysaccharide-induced acute lung injury (ALI).

The impact of Sodium Houttuyniae (SH) on lipopolysaccharide (LPS)-induced ALI has been investigated extensively. However, it remains ambiguous whether ferroptosis participates in this process. This study aimed to find out the impacts and probable mechanisms of SH on LPS-induced ferroptosis. A rat ALI model and type II alveolar epithelial (ATII) cell injury model were treated with LPS. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and Giemsa staining were executed to ascertain the effects of SH on LPS-induced ALI. Moreover, Transmission electron microscopy, Cell Counting Kit-8 (CCK8), ferrous iron colorimetric assay kit, Immunohistochemistry, Immunofluorescence, Reactive oxygen species assay kit, western blotting (Wb), and qRT-PCR examined the impacts of SH on LPS-induced ferroptosis and ferroptosis-related pathways. Theresults found that by using SH treatment, there was a remarkable attenuation of ALI by suppressing LPS-induced ferroptosis. Ferroptosis was demonstrated by a decline in the levels of glutathione peroxidase 4 (GPX4), FTH1, and glutathione (GSH) and a surge in the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), NOX1, NCOA4, and Fe2+, and disruption of mitochondrial structure, which were reversed by SH treatment. SH suppressed ferroptosis by regulating TRAF6-c-Myc in ALI rats and rat ATII cells. The results suggested that SH treatment attenuated LPS-induced ALI by repressing ferroptosis, and the mode of action can be linked to regulating the TRAF6-c-Myc signaling pathway in vivo and in vitro.

2-Arylbenzofurans from the stems and leaves of Artocarpus tonkinensis and their potential antiproliferative activities.

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone (1), as well as seven known 2-arylbenzofurans (2-8). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 µM.

Experimental Study for the Sorption and Diffusion of Supercritical Carbon Dioxide into Polyetherimide.

Supercritical carbon dioxide (SCCO2) is a non-toxic and environmentally friendly fluid and has been used in polymerization reactions, processing, foaming, and plasticizing of polymers. Exploring the behavior and data of SCCO2 sorption and dissolution in polymers provides essential information for polymer applications. This study investigated the sorption and diffusion of SCCO2 into polyetherimide (PEI). The sorption and desorption processes of SCCO2 in PEI samples were measured in the temperature range from 40 to 60 °C, the pressure range from 20 to 40 MPa, and the sorption time from 0.25 to 52 h. This study used the ex situ gravimetric method under different operating conditions and applied the Fickian diffusion model to determine the mass diffusivity of SCCO2 during sorption and desorption processes into and out of PEI. The equilibrium mass gain fraction of SCCO2 into PEI was reported from 9.0 wt% (at 60 °C and 20 MPa) to 12.8 wt% (at 40 °C and 40 MPa). The sorption amount increased with the increasing SCCO2 pressure and decreased with the increasing SCCO2 temperature. This study showed the crossover phenomenon of equilibrium mass gain fraction isotherms with respect to SCCO2 density. Changes in the sorption mechanism in PEI were observed when the SCCO2 density was at approximately 840 kg/m3. This study qualitatively performed FTIR analysis during the SCCO2 desorption process. A CO2 antisymmetric stretching mode was observed near a wavenumber of 2340 cm-1. A comparison of loss modulus measurements of pure and SCCO2-treated PEI specimens showed the shifting of loss maxima. This result showed that the plasticization of PEI was achieved through the sorption process of SCCO2.

Genetic structure analysis of yak breeds and their response to adaptive evolution.

Yaks are crucial genetic resources in the Tibetan Plateau and surrounding regions. Throughout the long process of domestication, natural and artificial selection pressures have enabled yaks to demonstrate adaptive characteristics to the environment in terms of physiological structure and genetic molecules, but no systematic cell analysis has been carried out on this phenomenon of yaks. Here, the population structure and genetic diversity of yak were studied by WGRS, and the genes related to yak adaptability were excavated. Combined with scRNA-seq method, the transcription map of yak lung tissue and skin tissue was constructed, which provided a new comprehensive insight into yak adaptability. The analysis of yak population structure showed that there was obvious genetic differentiation between TZ _ yak and other seven yak populations, while there was significant genetic exchange between PL _ yak and SB _ yak at high altitude. WGRS and scRNA-seq analysis revealed that the gene HIF1A related to high altitude adaptation was expressed in various cell types, while EPAS1 was predominantly expressed in epithelial and endothelial cells of yak lung tissue. Endothelial cells play a critical role in hypoxia-adapted VEGF signaling, which correlates closely with the high expression of KDR and VEGFA genes in endothelial cells and monocytes. Furthermore, in the selection signal of High _ yak vs Low _ yak, 19.8 % of the genes overlapped with the genes screened by skin scRNA-seq, including genes related to coat color such as RORA, BNC2, and KIT. Notably, BNC2 is a gene associated with melanin deposition and shows high expression levels in HS cells. Additionally, GRN in melanocytes and SORT1 in IRS play an important role in cell communication between melanocytes and IRS. These findings offer new insights into the natural polymorphism of yaks and provide a valuable reference for future research on high-altitude mammals, and potentially even human genetics.

Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy.

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 µg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

Proteomics for early prenatal screening of gestational diabetes mellitus.

In this editorial, we comment on the article by Cao et al. Through applying isobaric tags for relative and absolute quantification technology coupled with liquid chromatography-tandem mass spectrometry, the researchers observed significant differential expression of 47 proteins when comparing serum samples from pregnant women with gestational diabetes mellitus (GDM) to the healthy ones. GDM symptoms may involve abnormalities in inflammatory response, complement system, coagulation cascade activation, and lipid metabolism. Retinol binding protein 4 and angiopoietin like 8 are potential early indicators of GDM. GDM stands out as one of the most prevalent metabolic complications during pregnancy and is linked to severe maternal and fetal outcomes like pre-eclampsia and stillbirth. Nevertheless, none of the biomarkers discovered so far have demonstrated effectiveness in predicting GDM. Our topic was designed to foster insights into advances in the application of proteomics for early prenatal screening of GDM.

CD36-mediated ROS/PI3K/AKT signaling pathway exacerbates cognitive impairment in APP/PS1 mice after noise exposure.

There is an association between noise exposure and cognitive impairment, and noise may have a more severe impact on patients with Alzheimer's disease (AD) and mild cognitive impairment; however, the mechanisms need further investigation. This study used the classic AD animal model APP/PS1 mice to simulate the AD population, and C57BL/6J mice to simulate the normal population. We compared their cognitive abilities after noise exposure, analyzed changes in Cluster of Differentiation (CD) between the two types of mice using transcriptomics, identified the differential CD molecule: CD36 in APP/PS1 after noise exposure, and used its pharmacological inhibitor to intervene to explore the mechanism by which CD36 affects APP/PS1 cognitive abilities. Our study shows that noise exposure has a more severe impact on the cognitive abilities of APP/PS1 mice, and that the expression trends of differentiation cluster molecules differ significantly between C57BL/6J and APP/PS1 mice. Transcriptomic analysis showed that the expression of CD36 in the hippocampus of APP/PS1 mice increased by 2.45-fold after noise exposure (p < 0.001). Meanwhile, Western Blot results from the hippocampus and entorhinal cortex indicated that CD36 protein levels increased by approximately 1.5-fold (p < 0.001) and 1.3-fold (p < 0.05) respectively, after noise exposure in APP/PS1 mice. The changes in CD36 expression elevated oxidative stress levels in the hippocampus and entorhinal cortex, leading to a decrease in PI3K/AKT phosphorylation, which in turn increased M1-type microglia and A1-type astrocytes while reducing the numbers of M2-type microglia and A2-type astrocytes. This increased neuroinflammation in the hippocampus and entorhinal cortex, causing synaptic and neuronal damage in APP/PS1 mice, ultimately exacerbating cognitive impairment. These findings may provide new insights into the relationship between noise exposure and cognitive impairment, especially given the different expression trends of CD molecules in the two types of mice, which warrants further research.

Macrophages regulate plaque progression in diabetic Apoe-/- mice dependent on Pi4p/Nlrp3 signaling pathway.

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease complicated by diabetes mellitus (DM) is the leading cause of death in diabetic patients, and it is strongly associated with macrophages and inflammasomes. It has been found that activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is closely associated with phosphatidylinositol 4-phosphate (PI4P) on the trans-Golgi. However, how PI4P and NLRP3 regulate macrophage function and its role in diabetic atherosclerotic plaques is unclear. METHODS: The expression of Pi4p and Nlrp3-inflammasome-related proteins in atherosclerosis in apolipoprotein E-deficient (Apoe-/-) and Apoe-/- DM mice was investigated. Then, Pi4p levels were affected by shRNA-Pi4kb or cDNA-Sac1 plasmid to investigate the effects of changes in Pi4p-related metabolic enzymes on macrophage function. Finally, genetically modified macrophages were injected into diabetic Apoe-/- mice to explore the effects on atherosclerosis. RESULTS: DM promoted plaque progression in atherosclerotic mice and increased expression of Pi4p and Nlrp3 in plaques. In addition, impaired macrophage function induced by high glucose was reversed by transfected shRNA-Pi4kb or cDNA-Sac1 plasmid. Furthermore, decreased levels of Pi4p reduced plaque area in diabetic Apoe-/- mice. CONCLUSIONS: Our data suggests that Pi4p/Nlrp3 in macrophages play an important role in the exacerbation of atherosclerosis in diabetic mice. Pi4p-related metabolizing enzymes (PI4KB and SAC1) may be a potential therapeutic strategy for diabetic atherosclerosis, and macrophage therapy is also a potential treatment.

The value of SDC2 and Septin9 combined with serum tumor markers in early diagnosis of colorectal cancer.

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.

Development of a cost-effective confocal Raman microscopy with high sensitivity.

Confocal Raman microscopy is a powerful technique for identifying materials and molecular species; however, the signal from Raman scattering is extremely weak. Typically, handheld Raman instruments are cost-effective but less sensitive, while high-end scientific-grade Raman instruments are highly sensitive but extremely expensive. This limits the widespread use of Raman technique in our daily life. To bridge this gap, we explored and developed a cost-effective yet highly sensitive confocal Raman microscopy system. The key components of the system include an excitation laser based on readily available laser diode, a lens-grating-lens type spectrometer with high throughput and image quality, and a sensitive detector based on a linear charge-coupled device (CCD) that can be cooled down to -30 °C. The developed compact Raman instrument can provide high-quality Raman spectra with good spectral resolution. The 3rd order 1450 cm-1 peak of Si (111) wafer shows a signal-to-noise ratio (SNR) better than 10:1, demonstrating high sensitivity comparable to high-end scientific-grade Raman instruments. We also tested a wide range of different samples (organic molecules, minerals and polymers) to demonstrate its universal application capability.

The complete chloroplast genome of Blechnopsis orientalis (Linnaeus) C. Presl 1753 (Blechnaceae).

Blechnopsis orientalis (Linnaeus) C. Presl (1753) is a fern used both as food and medicine. It is found primarily in southern China and Southeast Asia, thriving in warm, humid shrublands or sparse forest. The total length of the chloroplast genome is 155,211 bp, including a large single-copy region (LSC, 81,877 bp), a small single-copy region (SSC, 21,500 bp), and two inverted repeat regions (IRs, 25,917 bp). The GC content is 41.3%. A total of 131 genes were annotated, including 88 protein-coding genes, eight rRNA genes, and 35 tRNA genes. The phylogenetic analysis using the maximum-likelihood method showed that B. orientalis and Oceaniopteris gibba were closely related. This study provides genomic resources for phylogenetic genetics and resource exploitation of B. orientalis.

Association of lifestyle with sleep health in general population in China: a cross-sectional study.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Analysis of the recombination and evolution of the new type mutant pseudorabies virus XJ5 in China.

Pseudorabies have caused enormous economic losses in China's pig industry and have recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Our laboratory isolated a pseudorabies virus in 2015 and named it XJ5. The pathogenic ability of this mutant strain was much stronger than that of the original isolate. After we sequenced its whole genome (GenBank accession number: OP512542), we found that its overall structure was not greatly changed compared with that of the previous strain Ea (KX423960.1). The whole genome alignment showed that XJ5 had a strong genetic relationship with the strains isolated in China after 2012 reported in GenBank. Based on the isolation time of XJ5 and the mutation and recombination analysis of programs, we found that the whole genome homology of XJ5 and other strains with Chinese isolates was greater than 95%, while the homology with strains outside Asia was less than 94%, which indicated that there may be some recombination and mutation patterns. We found that virulent PRV isolates emerged successively in China in 2011 and formed two different evolutionary clades from foreign isolates. At the same time, this may be due to improper immunization and the presence of wild strains in the field, and recent reports have confirmed that Bartha vaccine strains recombine with wild strains to obtain new pathogenic strains. We performed genetic evolution analysis of XJ5 isolated and sequenced in our laboratory to trace its possible mutations and recombination. We found that XJ5 may be the result of natural mutation of a virus in a branch of mutant strains widely existing in China.

Identification of Copper Homeostasis-Related Gene Signature for Predicting Prognosis in Patients with Epithelial Ovarian Cancer.

Objectives: This research aims to establish a copper homeostasis-related gene signature for predicting the prognosis of epithelial ovarian cancer and to investigate its underlying mechanisms. Methods: We mainly constructed the copper homeostasis-related gene signature by LASSO regression analysis. Then multiple methods were used to evaluate the independent predictive ability of the model and explored the mechanisms. Results: The 15-copper homeostasis-related gene (15-CHRG) signature was successfully established. Utilizing an optimal cut-off value of 0.35, we divided the training dataset into high-risk and low-risk subgroups. Kaplan-Meier analysis revealed that survival times for the high-risk subgroup were significantly shorter than those in the low-risk group (P < .05). Additionally, the Area Under the Curve (AUC) of the 15-CHRG signature achieved 0.822 at 1 year, 0.762 at 3 years, and 0.696 at 5 years in the training set. COX regression analysis confirmed the 15-CHRG signature as both accurate and independent. Gene set enrichment (GSEA), Kyoto Encyclopedia of Gene and Genome (KEGG) and Gene Ontology (GO) analysis showed that there were significant differences in apoptosis, p53 pathway, protein synthesis, hydrolase and transport-related pathways between high-risk group and low-risk group. In tumor immune cell (TIC) analysis, the increased expression of resting mast cells was positively correlated with the risk score. Conclusion: Consequently, the 15-CHRG signature shows significant potential as a method for accurately predicting clinical outcomes and treatment responses in patients with epithelial ovarian cancer.