Identification of core gene in chronic rhinosinusitis with nasal polyps and correlations with inflammation-related genes.

OBJECTIVE: Our aim in this study is to identify the core genes of chronic rhinosinusitis with nasal polyps and analyze the correlations between it and inflammation-related genes. METHODS: GSE72713 dataset containing gene expression data of ECRSwNP, nonECRSwNP and healthy samples was obtained from Gene Expression Omnibus (GEO) and filtered by limma to identify DEGs among three groups, then the functions and correlated pathways of DEGs were analyzed using GO and KEGG. The core DEGs were selected by the intersection of DEGs and the PPI network was constructed via STRING. The correlations between the expression levels of CRSwNP core gene and inflammation-related genes were analyzed via the Mann-Whitney U test. RESULTS: The DEGs among ECRSwNP, nonECRSwNP, and CTRL were filtered respectively, and enrichment analysis showed they were associated with olfaction and/or immune responses. The PPI network was constructed by 7 core DEGs obtained via the intersection among three groups, and ALOX15 was confirmed as the core gene in the network. Subsequently, the correlations between the expression levels of ALOX15 and inflammation-related genes were illustrated. CONCLUSION: In this study, the core gene ALOX15 was selected from the DEGs among ECRSwNP, nonECRSwNP, and CTRL. IL5, IL1RL1, and IL1RAP were found to exhibit a significant positive correlation with ALOX15. LEVEL OF EVIDENCE: Level 3.

Super Resolution of Pulmonary Nodules Target Reconstruction Using a Two-Channel GAN Models.

RATIONALE AND OBJECTIVES: To develop a Dual generative-adversarial-network (GAN) Cascaded Network (DGCN) for generating super-resolution computed tomography (SRCT) images from normal-resolution CT (NRCT) images and evaluate the performance of DGCN in multi-center datasets. MATERIALS AND METHODS: This retrospective study included 278 patients with chest CT from two hospitals between January 2020 and June 2023, and each patient had all three NRCT (512×512 matrix CT images with a resolution of 0.70 mm, 0.70 mm,1.0 mm), high-resolution CT (HRCT, 1024×1024 matrix CT images with a resolution of 0.35 mm, 0.35 mm,1.0 mm), and ultra-high-resolution CT (UHRCT, 1024×1024 matrix CT images with a resolution of 0.17 mm, 0.17 mm, 0.5 mm) examinations. Initially, a deep chest CT super-resolution residual network (DCRN) was built to generate HRCT from NRCT. Subsequently, we employed the DCRN as a pre-trained model for the training of DGCN to further enhance resolution along all three axes, ultimately yielding SRCT. PSNR, SSIM, FID, subjective evaluation scores, and objective evaluation parameters related to pulmonary nodule segmentation in the testing set were recorded and analyzed. RESULTS: DCRN obtained a PSNR of 52.16, SSIM of 0.9941, FID of 137.713, and an average diameter difference of 0.0981 mm. DGCN obtained a PSNR of 46.50, SSIM of 0.9990, FID of 166.421, and an average diameter difference of 0.0981 mm on 39 testing cases. There were no significant differences between the SRCT and UHRCT images in subjective evaluation. CONCLUSION: Our model exhibited a significant enhancement in generating HRCT and SRCT images and outperformed established methods regarding image quality and clinical segmentation accuracy across both internal and external testing datasets.

Arming oncolytic viruses with bispecific T cell engagers: The evolution and current status.

Oncolytic viruses (OVs) are emerging as therapeutically relevant anticancer agents as contemporary immunotherapy gains traction. Furthermore, OVs are an ideal platform for genetic modification to express therapeutic transgenes. Bispecific T cell engagers (BiTEs) can redirect T cells to tumor cells, resulting in targeted cytotoxicity. BiTEs have demonstrated success in hematological cancers but are rarely used in solid tumors. The drawbacks of BiTEs, including inadequate delivery and on-target-off-tumor activity have limited their efficacy. Combining OVs with BiTEs is a prospective area to investigate. This combined strategy can benefit from the best qualities of both therapies while overcoming the limitations.

Evaluating the Clinical Application of Automatic Chromosome Harvesting for Prenatal Karyotype Analysis.

Objective: The clinical value of an automatic chromosome harvester was evaluated, which included a comparison between the manual and automatic harvesting for the isolation of amniotic fluid cell chromosomes. Methods: Amniotic fluid samples from 96 high-risk gravida cases identified at 17-25 weeks treated at the Prenatal Diagnostic and Reproductive Center from June to July 2022 were collected. These samples underwent both manual and automatic chromosome collection, and their harvest time and number of amniotic cells were compared. These chromosomes were then used to produce karyotypic data for each sample using an automatic chromosomal karyotype analysis system, scan karyotype. Results: The average automatic harvesting time per sample, 3.92 min, was significantly lower than that of the manual harvesting, 7.89 min (p < 0.001). In addition, the average number of cells from the automatic harvesting (4.16 × 106 pieces) was significantly increased when compared with those of the manual group (2.10 × 106 pieces; p < 0.001). Further karyotyping revealed that both sets of chromosomes produced clear bands and good dispersion data, producing no significant differences in these evaluations (p > 0.05). However, the number of analyzable karyotypes obtained using the automatic harvester was significantly higher than those of the manual harvesting (p < 0.001). Conclusions: The automatic chromosome harvester can effectively save time, manual labor and consumables, harvest more analyzable karyotypes, and improve the efficiency of clinical diagnosis. The automatic chromosome harvester is highly stable and repeatable, which has the potential to help achieve large-scale standardized chromosome harvesting and is worthy of widespread clinical promotion.

Live-attenuated Japanese encephalitis virus inhibits glioblastoma growth and elicits potent antitumor immunity.

Glioblastomas (GBMs) are highly aggressive brain tumors that have developed resistance to currently available conventional therapies, including surgery, radiation, and systemic chemotherapy. In this study, we investigated the safety of a live attenuated Japanese encephalitis vaccine strain (JEV-LAV) virus as an oncolytic virus for intracerebral injection in mice. We infected different GBM cell lines with JEV-LAV to investigate whether it had growth inhibitory effects on GBM cell lines in vitro. We used two models for evaluating the effect of JEV-LAV on GBM growth in mice. We investigated the antitumor immune mechanism of JEV-LAV through flow cytometry and immunohistochemistry. We explored the possibility of combining JEV-LAV with PD-L1 blocking therapy. This work suggested that JEV-LAV had oncolytic activity against GBM tumor cells in vitro and inhibited their growth in vivo. Mechanistically, JEV-LAV increased CD8+ T cell infiltration into tumor tissues and remodeled the immunosuppressive GBM microenvironment that is non-conducive to immunotherapy. Consequently, the results of combining JEV-LAV with immune checkpoint inhibitors indicated that JEV-LAV therapy improved the response of aPD-L1 blockade therapy against GBM. The safety of intracerebrally injected JEV-LAV in animals further supported the clinical use of JEV-LAV for GBM treatment.

Association between thyroid dysfunction and venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Thyroid dysfunction plays an important role in the development of cardiovascular disease. However, its relationship with venous thromboembolism (VTE) remains unclear. We performed a meta-analysis of published cohort and case-control studies to investigate the association between thyroid dysfunction and VTE comprehensively. METHODS: Three reviewers independently searched EMbase, PubMed, China national knowledge infrastructure, and Cochrane Library databases for relevant articles from the time of database establishment to 01 October 2022 and identified all studies on thyroid dysfunction and VTE as studies of interest. Of the 2418 publications retrieved, we identified 10 articles with 15 studies that met our selection criteria. Pooled ORs and 95% confidence intervals were calculated using fixed- or random-effect models. RESULTS: We pooled 8 studies by a fixed-effect model, which suggested an increased risk of VTE in patients with (subclinical) hyperthyroidism (OR 1.33, 95% CI: 1.29-1.38). In the other 7 studies on patients with (subclinical) hypothyroidism, the risk was similarly increased when pooled by a random-effect model (OR 1.52, 95% CI: 1.23-1.89). After sensitivity analysis and risk of bias analysis, the risk of VTE was still increased in both (subclinical) hyperthyroidism (OR 1.322, 95% CI: 1.278-1.368) and (subclinical) hypothyroidism (OR 1.74, 95% CI: 1.41-2.16). CONCLUSION: Patients with thyroid dysfunction have an increased risk of VTE. Therefore, it is recommended to perform thyroid function screening routinely in patients at high risk of VTE.

Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer.

Although productive progress has been made in colorectal cancer (CRC) researchs, CRC is the second most frequent type of malignancy and the major cause of cancer-related death among gastrointestinal cancers. As angiogenesis constitutes an important point in the control of CRC progression and metastasis, understanding the key signaling pathways that regulate CRC angiogenesis is critical in elucidating ways to inhibit CRC. Herein, we comprehensively summarized the angiogenesis-related pathways of CRC, including vascular endothelial growth factor (VEGF), nuclear factor-kappa B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless and int-1 (Wnt), and Notch signaling pathways. We divided the factors influencing the specific pathway into promoters and inhibitors. Among these, some drugs or natural compounds that have antiangiogenic effects were emphasized. Furthermore, the interactions of these pathways in angiogenesis were discussed. The current review provides a comprehensive overview of the key signaling pathways that are involved in the angiogenesis of CRC and contributes to the new anti-angiogenic strategies for CRC.

In Situ Tumor Vaccine Expressing Anti-CD47 Antibody Enhances Antitumor Immunity.

In situ tumor vaccine is a potential cancer therapy due to their advantages in induction of antitumor immune responses. Oncolytic virotherapy utilizes natural or engineered oncolytic viruses to kill tumors selectively, representing a promising in situ tumor vaccine for cancer immunotherapy. In addition to direct oncolysis, oncolytic viruses elicit potent and durable antitumor immune responses by induction of immunogenic cell death of tumors. Membrane protein CD47 overexpressed on tumor cells engages in "don't eat me" signal that prevents macrophages from engulfing tumor cells. CD47-targeting agents have been tested via preclinical and clinical trials. As potential tumor vaccine vectors, oncolytic viruses can be engineered to express anti-CD47 antibodies to induce potentiated tumor killing. Therefore, we developed an adenovirus-based tumor vaccine loaded with a CD47-targeting nanobody fused with the IgG2a Fc protein. B16-F10 melanoma, A20 lymphoma, and 4T1 breast cancer models in immunocompetent mice were established to evaluated in vivo antitumor efficacy of in situ tumor vaccination. The tumor vaccine armed with a nanobody against CD47 induced durable suppression of the tumor and long-term survival of tumor-bearing mice, and also elevated the number of tumor-infiltrating immune cells with an activated immunophenotype, suggesting that it could remodel the tumor immune microenvironment. Systemic antitumor effects and immune memory were also observed in immunocompetent mice following in situ vaccination with the anti-CD47 tumor vaccines; tumorigenesis was completely inhibited in these mice after tumor re-challenge. The recombinant anti-CD47 tumor vaccine has an effectual antitumor activity and may be a promising antitumor agent.

Transnasal Endoscopy and Combined Approach to Infratemporal Fossa Abscess and Parapharyngeal Abscess.

The infratemporal fossa is a very important anatomical space that is relatively closed with an irregular shape and is adjacent to the parapharyngeal space. Infratemporal fossa abscess is rare clinically. It can occur as a complication of maxillary sinusitis, maxillary sinus fracture, or odontogenic infection. If not handled in time, it may endanger the lives of patients. This paper reports the diagnosis and treatment of infratemporal fossa abscess in 2 diabetic patients. Computed tomography and magnetic resonance imaging are the best methods to diagnose suspected cases of this disease. The key treatment is to combine sensitive antibiotic treatment with endoscopic abscess drainage. Different approaches can be selected according to the range of lesions. If necessary, a combined approach to drain the pus is needed. Early diagnosis, timely initiation of antibiotics, and surgical intervention are essential for curing this disease.

Color fading in lotus (Nelumbo nucifera) petals is manipulated both by anthocyanin biosynthesis reduction and active degradation.

Flower color is a key trait that determines the ornamental quality of aquatic lotus (Nelumbo nucifera). Color fading significantly decreases the ornamental value of lotus flowers. However, the molecular mechanism underlying lotus petal discoloration remains largely unknown. Here, the anthocyanin content and global transcriptional profiling of lotus petals of cultivar 'Qiusanse' in four developmental stages were analyzed. Five anthocyanin components were detected, and the total anthocyanin content decreased as the petal color changed from red to nearly white. Moreover, the malondialdehyde (MDA) content and peroxidase (POD) activity increased during color fading. RNA-seq analysis revealed a total of 4,092 differentially expressed genes (DEGs) between petal developmental stages. Notably, oxidoreductase and hydrolase activity related genes were overrepresented in DEGs. The expression pattern of key anthocyanin biosynthesis genes including, CHS, F3H, ANS, UFGT, and transcription factor regulators, including MYBs, WRKYs and bHLHs were correlated with anthocyanin accumulation. Interestingly, DEGs associated with anthocyanin degradation and vacuolar pH regulation, including peroxidase, proton pumps regulators such as WRKY3 and MYB5-like, were significantly upregulated during the late stages of flowering. This study reveals for the first time the transcriptional dynamics during lotus petal discoloration. Our results suggest the involvement of anthocyanin biosynthesis repressors and degrading genes as well as pH regulators in controlling color fading of lotus petals. The study also provides valuable information and candidate genes for improving the lotus flower color.

Time-course analysis and transcriptomic identification of key response strategies to complete submergence in Nelumbo nucifera.

Water submergence is an environmental stress with detrimental effects on plant growth and survival. As a wetland plant species, lotus (Nelumbo nucifera) is widely cultivated in flood-prone lowlands throughout Asian countries, but little is known about its endurance and acclimation mechanisms to complete submergence. Here, we combined a time-course submergence experiment and an RNA-sequencing transcriptome analysis on two lotus varieties of "Qiuxing" and "China Antique". Both varieties showed a low submergence tolerance, with a median lethal time of around 10 days. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) identified a number of key genes putatively involved in lotus submergence responses. Lotus plants under complete submergence developed thinned leaves and elongated petioles containing high density of aerenchyma. All four lotus submergence responsive ERF-VII genes and gene sets corresponding to the low oxygen "escape" strategy (LOES) were elevated. In addition, a number of lotus innate immunity genes were rapidly induced by submergence, likely to confer resistance to possible pathogen infections. Our data also reveals the likely involvement of jasmonic acid in modulating lotus submergence responses, but to a lesser extent than the gaseous ethylene hormone. These results suggest that lotus plants primarily take the LOES strategy in coping with submergence-induced complex stresses, and will be valuable for people understanding the molecular basis underlying the plant submergence acclimations.

Long noncoding RNA RP11-241J12.3 targeting pyruvate carboxylase promotes hepatocellular carcinoma aggressiveness by disrupting pyruvate metabolism and the DNA mismatch repair system.

Accumulating evidence indicates that hepatitis B virus X protein (HBx) plays a key role in HBV-related hepatocellular carcinoma (HCC) aggressiveness; however, the underlying mechanisms are not entirely clear. Long non-coding RNAs (lncRNAs), which participate in the regulation of diverse biological processes, may be critical for the function of HBx. Our research indicated that HBx induced changes in the expression of numerous lncRNAs and implicated the novel lncRNA RP11-241J12.3 in HBx-mediated HCC aggressiveness. Although RP11-241J12.3 expression was downregulated in transient HBx-expressing HCC cells (similar to the early stage of HBV infection), its oncogenic properties remained. The results showed that RP11-241J12.3 not only accelerated DNA synthesis and upregulated the expression of pyruvate carboxylase (PC) and MSH3, which is a key protein in pyruvate metabolism and DNA mismatch repair (MMR), but also promoted tumor growth in vitro and in vivo, thus promoting HCC aggressiveness. More importantly, we revealed that RP11-241J12.3 may interact with PC and identified its location in the cytoplasm close to the nucleus using fluorescence in situ hybridization (FISH). We also observed RP11-241J12.3 expression was upregulated in HCC tissues compared with the paracarcinomatous tissues. Furthermore, RP11-241J12.3 expression levels showed a close relationship with clinical stage and tumor size and that low RP11-241J12.3 expression was significantly correlated with longer HCC patient survival. These results further our understanding of the lncRNAs regulated by HBx in HCC, and provide evidence that dysregulation of RP11-241J12.3 contributes to HCC aggressiveness.

[Analysis of allergen distribution and clinical characteristics of autumn allergic rhinitis in Changchun and surrounding areas].

Objective:To investigate the allergen characteristics, allergen distribution and clinical symptoms of autumn allergic rhinitis in Changchun and surrounding areas. Methods:The allergen test results of 1080 allergic rhinitis（AR） suspected patients from Changchun and surrounding areas were collected, from August to October 2019 and August to October 2020 in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University. The positive rates of major allergens and their differences in gender, age, different years and clinical symptom were compared and analyzed. Results:①Among the 1080 suspected AR patients, 804 patients（74.44%） had positive allergens. ②The top 3 allergens of autumn AR in Changchun and surrounding areas were Artemisia（36.20%）, Dwarf ragweed（33.24%） and Candida/Penicillium notarum/Cladosporium/Alternaria/Aspergillus niger（19.81%）. The positive rates of Artemisia and Dwarf ragweed were higher in men than in women（P<0.05）. ③Artemisia was the major allergen of autumn AR in juvenile group, youth group and middle-aged group. ④The positive rate of two or more allergens was 2.39 times that of single allergen. ⑤Patients with positive autumn pollen allergens had more severe symptoms of nasal congestion, red eye/eye itching and epiphora than those in other groups. Conclusion:Seasonal AR had typical clinical symptom characteristics. Major allergens in autumn AR in Changchun and surrounding areas are autumn pollen allergens（Artemisia, Dwarf ragweed, Humulus）. The distribution of those allergens was different in gender, age, and different years.

Chrysin induces autophagy through the inactivation of the ROS­mediated Akt/mTOR signaling pathway in endometrial cancer.

Endometrial cancer (EC) is widely known as an aggressive malignancy. Due to the limited therapeutic options and poor prognosis of patients with advanced­stage EC, there is a need to identify effective alternative treatments. Chrysin is a naturally active flavonoid (5,7­dihydroxyflavone), which has been demonstrated to exert anticancer effects and may present a novel strategy for EC treatment. However, the role of chrysin in EC remains largely unclear. The aim of the present study was to examine the anticancer effects of chrysin on EC. The results revealed that, in addition to apoptosis, chrysin increased the LC3II expression levels and markedly accelerated the autophagic flux, suggesting that chrysin induced both the autophagy and apoptosis of EC cells. Furthermore, the inhibition of autophagy by chloroquine enhanced the inhibitory effect on cell proliferation and the promotion of the chrysin­induced apoptosis of EC cells, indicating that chrysin­induced autophagy was a cytoprotective mechanism. Additionally, chrysin led to the production of intracellular reactive oxygen species (ROS). N­acetylcysteine (NAC) pretreatment significantly inhibited chrysin­induced autophagy, suggesting that ROS activated autophagy induced by chrysin in EC cells. Furthermore, the phosphorylated (p­)Akt and p­mTOR levels were significantly decreased in a concentration­dependent manner following treatment with chrysin, while NAC blocked these effects. Taken together, these findings demonstrated that chrysin­induced autophagy via the inactivation of the ROS­mediated Akt/mTOR signaling pathway in EC cells.

Comprehensive analysis of AGPase genes uncovers their potential roles in starch biosynthesis in lotus seed.

BACKGROUND: Starch in the lotus seed contains a high proportion of amylose, which endows lotus seed a promising property in the development of hypoglycemic and low-glycemic index functional food. Currently, improving starch content is one of the major goals for seed-lotus breeding. ADP-glucose pyrophosphorylase (AGPase) plays an essential role in regulating starch biosynthesis in plants, but little is known about its characterization in lotus. RESULTS: We describe the nutritional compositions of lotus seed among 30 varieties with starch as a major component. Comparative transcriptome analysis showed that AGPase genes were differentially expressed in two varieties (CA and JX) with significant different starch content. Seven putative AGPase genes were identified in the lotus genome (Nelumbo nucifera Gaertn.), which could be grouped into two subfamilies. Selective pressure analysis indicated that purifying selection acted as a vital force in the evolution of AGPase genes. Expression analysis revealed that lotus AGPase genes have varying expression patterns, with NnAGPL2a and NnAGPS1a as the most predominantly expressed, especially in seed and rhizome. NnAGPL2a and NnAGPS1a were co-expressed with a number of starch and sucrose metabolism pathway related genes, and their expressions were accompanied by increased AGPase activity and starch content in lotus seed. CONCLUSIONS: Seven AGPase genes were characterized in lotus, with NnAGPL2a and NnAGPS1a, as the key genes involved in starch biosynthesis in lotus seed. These results considerably extend our understanding on lotus AGPase genes and provide theoretical basis for breeding new lotus varieties with high-starch content.

The Establishment of an Efficient Callus Induction System for Lotus (Nelumbo nucifera).

The lotus (Nelumbo nucifera) is one of the most popular aquatic plants in Asia, and has emerged as a novel model for studying flower and rhizome development, and primary and secondary metabolite accumulation. Here, we developed a highly efficient callus induction system for the lotus by optimizing a series of key factors that affect callus formation. The highest efficient callus production was induced on immature cotyledon and embryo explants grown on Murashige and Skoog (MS) basal medium containing an optimized combination of 3 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/L 6-benzylaminopurine (6-BA). In addition, lotus callus induction was proven to be influenced by lotus genotypes, light conditions, the developmental stages of explants and the time of explant sampling. Collecting immature cotyledons from seeds of the genotype "Shilihe 1", at 9 days post pollination, and to culture the explants in darkness, are proposed as the optimum conditions for lotus callus induction. Interestingly, highly efficient callus induction was also observed in explants of immature embryo derived aseptic seedlings; and a small amount of lotus benzylisoquinoline alkaloid (BIA) and obvious expression of BIA biosynthetic genes were detected in lotus callus.