Association between periodontal disease and coronary heart disease: A bibliometric analysis.

Background: Periodontal disease and coronary heart disease are both prevalent diseases worldwide and cause patients physical and mental suffering and a global burden. Recent studies have suggested a link between periodontal disease and coronary heart disease, but there is less research in this field from the perspective of bibliometrics. Objective: This study aimed to quantitatively analyze the literature on periodontal disease and coronary heart disease to summarize intellectual bases, research hotspots, and emerging trends and pave the way for future research. Methods: The Science Citation Index Expanded database was used to retrieve study records on periodontal disease and coronary heart disease from 1993 to 2022. After manual screening, the data were used for cooperative network analysis (including countries/regions, institutions and authors), keyword analysis, and reference co-citation analysis by CiteSpace software. Microsoft Excel 2019 was applied for curve fitting of annual trend in publications and citations. Results: A total of 580 studies were included in the analysis. The number of publications and citations in this field has shown an upward trend over the past 30 years. There was less direct collaboration among authors and institutions in this field but closer collaboration between countries. The United States was the country with the most published articles in this field (169/580, 29.14%). Based on the results of keyword analysis and literature co-citation analysis, C-reactive protein, oral flora, atherosclerosis, infection, and inflammation were previous research hotspots, while global burden and cardiovascular outcomes were considered emerging trends in this field. Conclusion: Studies on periodontal disease and coronary heart disease, which have attracted the attention of an increasing number of researchers, have been successfully analyzed using bibliometrics and visualization techniques. This paper will help scholars better understand the dynamic evolution of periodontal disease and coronary heart disease and point out the direction for future research. Clinical significance: This paper presents an overview between periodontal disease and coronary heart disease. Further exploration of the two diseases themselves and the potential causal relationship between the two is necessary and relevant, which may impact basic research, diagnosis, and treatment related to both diseases. This will aid the work of researchers and specialist doctors, and ultimately benefit patients with both diseases.

Association between life's essential 8 and periodontitis: a study based on NHANES 2009-2014.

Background: This research aims to investigate the relationship between Life's Essentials 8 (LE8), the American Heart Association's latest indicator, and periodontitis. The purpose is to provide guidance on preventative measures. Methods: Data for our investigation were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, with a total of 8,784 participants eligible. LE8 scores were compiled from 8 index scores (the score for each component of diet, physical activity, nicotine exposure, sleep duration, body mass index, blood lipids, blood glucose, and blood pressure). Periodontitis was classified by the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP). The study utilized multivariable logistic analyses to investigate the potential correlation. Results: After controlling for all covariates, LE8 was discovered to have a significant negative correlation with periodontitis prevalence [0.91 (0.88, 0.94)]. This trend continued to hold statistical significance even after converting LE8 into a categorical variable. Furthermore, a noteworthy adverse correlation was discovered across both genders, specifically males [0.35 (0.22, 0.55)] and females [0.39 (0.25, 0.60)], as well as for the majority of categorical classifications, namely ethnicity, age, education level, and marital status. However, only the age subgroups displayed some degree of significant difference from each other. Conclusion: Life's essential 8 was negatively associated with periodontitis, but more prospective trails are needed to confirm our findings.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and prevalence of periodontitis among US adults: a cross-sectional NHANES study.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed lipid parameter, but there is currently a lack of research exploring its relationship with periodontitis. This study aims to identify the potential association between NHHR and periodontitis. The association between NHHR and periodontitis were examined through univariate and multivariate weighted logistic regression utilizing the National Health and Nutrition Examination Survey data from 2009 to 2014. The participants were grouped based on the type of periodontitis. This study included a total of 9023 participants, with 1947 individuals having no periodontitis, and an additional 7076 individuals suffering from periodontitis. Patients in periodontitis group demonstrated a statistically significant elevation in NHHR values 2.82 (2.05-3.80) compared to those in no periodontitis group (p < 0.001). Logistic regression analysis of variables demonstrated a positive association between NHHR and periodontitis [1.07 (1.02, 1.12) p = 0.0067]. The study revealed a positive association between NHHR and an elevated prevalence of periodontitis development. For each unit increase in NHHR, there is a 7% increase in the prevalence of periodontitis. Further investigations into NHHR may enhance our understanding of preventing and treating periodontitis. However, additional studies are required to validate these findings.

Current developments and opportunities of pluripotent stem cells-based therapies for salivary gland hypofunction.

Salivary gland hypofunction (SGH) caused by systemic disease, drugs, aging, and radiotherapy for head and neck cancer can cause dry mouth, which increases the risk of disorders such as periodontitis, taste disorders, pain and burning sensations in the mouth, dental caries, and dramatically reduces the quality of life of patients. To date, the treatment of SGH is still aimed at relieving patients' clinical symptoms and improving their quality of life, and is not able to repair and regenerate the damaged salivary glands. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and extended pluripotent stem cells (EPSCs), are an emerging source of cellular therapies that are capable of unlimited proliferation and differentiation into cells of all three germ layers. In recent years, the immunomodulatory and tissue regenerative effects of PSCs, their derived cells, and paracrine products of these cells have received increasing attention and have demonstrated promising therapeutic effects in some preclinical studies targeting SGH. This review outlined the etiologies and available treatments for SGH. The existing efficacy and potential role of PSCs, their derived cells and paracrine products of these cells for SGH are summarized, with a focus on PSC-derived salivary gland stem/progenitor cells (SGS/PCs) and PSC-derived mesenchymal stem cells (MSCs). In this Review, we provide a conceptual outline of our current understanding of PSCs-based therapy and its importance in SGH treatment, which may inform and serve the design of future studies.

Research hotspots and emerging trends in the treatment of Sjogren's syndrome: A bibliometric analysis from 1900 to 2022.

Objective: Sjogren's syndrome (SS) is an autoimmune disease that mainly affects the salivary and lacrimal glands and further leads to dry mouth and eyes. In recent years, knowledge about the treatment of SS is developing rapidly. This study aims to assess research progress on SS treatment using a bibliometric approach and to identify research hotspots and emerging trends in this area. Methods: The publications related to the treatment of SS were retrieved from the Science Citation Index Expanded (SCI-E) database. The following search terms were used to extract document data: TS=(Sjogren* OR Sicca*) AND TS= (Treat* OR Therap* OR Disease Management). Articles and review articles published in English from 1900 to 2022 were selected. After the manual screening, the publication data were exported to a plain text file and applied for cooperative network analysis, keyword analysis, and reference co-citation analysis by using CiteSpace. Results: A total of 2038 publications were included in the analysis from 571 journals by 9063 authors. The annual number of published studies and times cited showed an overall upward trend since 1992. There was a degree of national/regional collaboration in this area, but direct collaboration between institutions and authors was still lacking. The country with the highest number of publications was in the United States, followed by China and Japan. Five SS-related treatments as the research hotspots were summarized by analyzing keywords and references, including immunosuppressive and anti-inflammatory therapy, regenerative therapy, gene therapy, surgical treatment, and symptomatic treatment. Among them, B cells, T cells, mucosal-associated invariant T (MAIT) cells, mesenchymal stem cells (MSCs), rituximab, belimumab, cell-target therapy, and immunosuppressive and anti-inflammatory therapy were emerging trends in this field. Conclusions: This study conducted a data-based and objective introduction to the treatment of SS from a fresh perspective. An analysis of the intellectual bases, research hotspots, and emerging trends in the field will contribute to future research and treatment decisions, which will ultimately benefit SS patients.

Risk factors for cough after pulmonary resection.

BACKGROUND: To investigate the risk factors for cough after pulmonary resection. METHODS: The PubMed, Embase, Web of Science, ClinicalTrials.gov, and China National Knowledge Network databases were searched from inception to November 2022. The Q tests and I2 statistic were used to evaluate the heterogeneity. Odds ratios (OR) were combined using the inverse variance method. All statistical analyses were performed by RevMan 5.4.1. RESULTS: Nineteen studies with 4755 patients were included, the incidence of postoperative cough was 21.1%-55.8%. The results showed that young age [OR = 0.66, 95% CI (0.46, 0.96), p = 0.03], female sex [OR = 1.69, 95% CI (1.07, 2.66), p = 0.02], preoperative cough [OR = 5.96, 95% CI (2.58, 13.73), p < 0.01], right lobe operation [OR = 2.14, 95% CI (1.44, 3.19), p < 0.01], lobectomy [OR = 3.70, 95% CI (1.73, 7.90), p < 0.01], subcarinal lymph node dissection [OR = 3.45, 95% CI (1.86, 6.39), p < 0.01], mediastinal lymph node removal [OR = 3.49, 95% CI (2.07, 5.89), p < 0.01], closure of bronchial stump with stapler [OR = 5.19, 95% CI (1.79, 15.07), p < 0.01], peritracheal lymph node resection [OR = 3.05, 95%CI (1.40,6.64), p < 0.01], postoperative acid reflux [OR = 11.07, 95%CI (4.38,28.02), p < 0.01] were independent risk factors for cough after pulmonary resection. CONCLUSIONS: Young age, female sex, preoperative cough, right lobe operation, lobectomy, subcarinal lymph node dissection, mediastinal lymph node removal, closure of bronchial stump with stapler, peritracheal lymph node resection, and postoperative acid reflux are independent risk factors for cough after pulmonary resection.

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

Prognostic Value and Genome Signature of m6A/m5C Regulated Genes in Early-Stage Lung Adenocarcinoma.

RNA modifications implicate pathological and prognosis significance in cancer development and progression, of which, m6A and m5C are representative regulators. These RNA modifications could produce effects on the function of other RNA by regulating gene expression. Thus, in this study, we aimed to explore the correlation between m6A/m5C regulators and early-stage lung adenocarcinoma (LUAD). Only the early-stage LUAD samples were included in this investigation, and the RNA-seq dataset of The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate the expression of 37 m6A/m5C regulated genes. Based on the expression level of these 37 genes, early-stage LUAD patients were divided into 2 clusters, which were performed by consensus clustering, and the m6A/m5C subtypes had significantly different prognostic outcomes (p < 0.001). Cluster1, which has a better prognosis, was characterized by the C3 (inflammatory) immune subtype, low immune infiltration, chemokine expression, major histocompatibility complex (MHC) expression, and immune checkpoint molecule expression. Furthermore, compared with cluster1, cluster2 showed a T cell exhaustion state, characterized by a high expression of immune checkpoint genes, and immune cells, such as T cells, CD8+ T cells, cytotoxic lymphocytes, NK cells, and so on. In addition, patients in cluster2 were with high tumor mutational burden (TMB) and numerous significant mutated oncogene and tumor suppressor genes, such as WNT10B, ERBB4, SMARCA4, TP53, and CDKN2A (p < 0.001). A total of 19 genes were mostly related to the prognosis of LUAD and were upregulated in cluster2 (p < 0.05), showing a positive correlation with the mRNA expression of 37 m6A/m5C regulated genes. The predictive risk model was constructed using Cox and LASSO (least absolute shrinkage and selection operator) regression analysis. Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791). The high-risk score was associated with a poorer prognosis. This model was also validated using two additional GEO datasets: GSE72094 (p = 0.011, AUC = 0.736) and GSE50081 (p = 0.012, AUC = 0.628). In summary, it was established that the m6A/m5C-regulated genes performed a crosstalk function in the mRNA expression of early-stage LUAD. By interacting with other mRNA genes, m6A/m5C modification disturbs DNA replication and the tumor immune microenvironment (TIME). The seven-gene risk model may be a critical tool for the prognostic assessment of early-stage LUAD.

Transcriptome analysis highlights the role of ferroptosis in palmitic acid-induced endothelial dysfunction.

Background: Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood. Aim: We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis. Methods: Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe2+), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins. Outcomes: At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe2+, and ROS. Results: PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe2+, MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death. Clinical Translation: This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction. Strengths and Limitations: In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed. Conclusion: Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study.

Clinical trials using dental stem cells: 2022 update.

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

dCas9-BE3 and dCas12a-BE3 Systems Mediated Base Editing in Kiwifruit Canker Causal Agent Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker of kiwifruit with heavy economic losses. However, little is known about the pathogenic genes of Psa. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing technology has dramatically facilitated the characterization of gene function in various organisms. However, CRISPR genome editing could not be efficiently employed in Psa due to lacking homologous recombination repair. The base editor (BE) system, which depends on CRISPR/Cas, directly induces single nucleoside C to T without homology recombination repair. Here, we used dCas9-BE3 and dCas12a-BE3 systems to create substitutions of C to T and to convert CAG/CAA/CGA codons to stop codons (TAG/TAA/TGA) in Psa. The dCas9-BE3 system-induced single C-to-T conversion frequency of 3 to 10 base positions ranged from 0% to 100%, with a mean of 77%. The dCas12a-BE3 system-induced single C-to-T conversion frequency of 8 to 14 base positions in the spacer region ranged from 0% to 100%, with a mean of 76%. In addition, a relatively saturated Psa gene knockout system covering more than 95% of genes was developed based on dCas9-BE3 and dCas12a-BE3, which could knock out two or three genes at the same time in the Psa genome. We also found that hopF2 and hopAO2 were involved in the Psa virulence of kiwifruit. The HopF2 effector can potentially interact with proteins such as RIN, MKK5, and BAK1, while the HopAO2 effector can potentially interact with the EFR protein to reduce the host's immune response. In conclusion, for the first time, we established a PSA.AH.01 gene knockout library that may promote research on elucidating the gene function and pathogenesis of Psa.

Does the presence of a micropapillary component predict worse prognosis in pathological stage IA lung adenocarcinoma?

Considerable evidence has verified that the micropapillary pattern is significantly associated with worse prognosis in pulmonary adenocarcinoma. However, whether the presence of a micropapillary component in pathological stage IA lung adenocarcinoma is also related to worse prognosis remains unclear up to now. The aim of this meta-analysis was to identify the prognostic role of presence of a micropapillary component in pathological stage IA lung adenocarcinoma patients. Relevant studies were searched from the PubMed, EMBASE, Web of Science and CNKI databases and reviewed. The primary and secondary outcomes were the recurrence risk and long-term survival including the overall survival (OS) and disease-free survival (DFS), respectively. All statistical analysis were conducted by STATA 12.0 software. A total of 5257 lung adenocarcinoma patients at the pathological stage IA from ten retrospective studies were enrolled. The recurrence rates in pathological stage IA lung adenocarcinoma patients with and without the a micropapillary component were 32% [95% confidence interval (CI): 20%- 44%] and 7% (95% CI: 4%-10%) separately and pooled results indicated that presence of a micropapillary component was an obvious risk factor for recurrence [odds ratio (OR)= 3.41, 95% CI: 2.80-4.16, P＜0.001]. Besides, the presence of a micropapillary component was significantly related to poorer OS [hazard ratio (HR)= 2.44, 95% CI: 1.28-4.68, P = 0.007] and DFS (HR=2.60, 95% CI: 1.63-4.16, P＜0.001). Subgroup analysis focusing on invasive adenocarcinoma manifested consistent results. In pathological stage IA lung adenocarcinoma, the presence of a micropapillary component predicts obviously higher recurrence risk and worse prognosis even after focusing on invasive adenocarcinoma. However, more prospective high-quality studies are still needed to verify our findings.

Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study.

OBJECTIVE: In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. METHODS: We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. RESULTS: Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. CONCLUSION: This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Evaluation of the apposition in unruptured aneurysms treated with flow diverters by optical coherence tomography: Preliminary clinical experience.

Background: The risk of perioperative stroke and the rate of occlusion of long-term aneurysms in the treatment of unruptured aneurysms with flow diverters (FDs) are affected by stent apposition. Optical coherence tomography (OCT) may be an optional technique in evaluating apposition. Purpose: To explore the feasibility of the OCT imaging technique in evaluating stent apposition in the clinical application of the FD for unruptured aneurysms. Methods: OCT and Vaso CT were used in patients with indications for surgery to treat unruptured aneurysms with the FDs, to evaluate the apposition of the FDs after fully released, and to analyze OCT images for FDs apposition and compare with corresponding Vaso CT images. Results: A total of four patients were enrolled, and OCT found malapposition after FDs placement in all four patients, and the maximum gap between the stent and vascular wall ranged from 0.68 to 1.95 mm and the length of malapposition ranged from 1.80 to 7.40 mm. However, Vaso CT found malapposition only in two of the four patients and missed malapposition near aneurysm in all three patients treated by the FD combined with coiling and could not accurately evaluate the maximum gap and the length of the malapposition. Conclusion: The optical coherence tomography technique is a possible approach to evaluate apposition after the treatment of unruptured aneurysms by the FDs.

First Report of root rot Caused by Fusarium solani and F. breve on kiwifruit in China.

China is considered as the main producer of kiwifruit (Actinidia spp.) in the world. During 2020-2021, root rot (~8000 plants, ~5% disease incidence) of 3-year-old kiwifruit (cv. Xuxiang) was observed in Lujiang County (117°24'E, 31°15'N), Anhui, China. This disease usually occurred in fields with poor drainage in hot and humid summers. Symptoms started on leaves showing dehydration and curling, the last root of diseased plant turned black and died. Dig out the skin on rotten root was cracking and flaking and white mycelium covered on surface. Twenty rotten tissues from ten plants were cut and surface disinfected with 1% NaOCl for 5 min, rinsed in sterile water, and cultured on potato dextrose agar (PDA) at 25 ± 2°C in the dark. Fifteen fungal isolates were obtained. The first type (KWRR1, 3-10) was cotton-like, reverse with white outer margin, and light brown inner region on PDA. The second type (KWRR2, 11-15) was cotton-like on PDA but appeared pale yellow in reverse. On oatmeal agar, the KWRR1 colony was flat with little aerial hyphae and was red, while KWRR2 was hyaline. On carnation leaf agar (CLA), microconidia of the KWRR1 and KWRR2 isolates were reniform, fusiform or oblong, 0-1 septate, and measuring 1.9-4.3×8.4-15.7 µm and 3.0-3.8×8.2-16.7 µm, respectively (n=50). The macroconidia of KWRR1 were straight or moderately curved, 3-5 septa (2.7-4.6×21.5-52.6 µm in size, n=50). For KWRR2, the macroconidia were straight or slightly curved and with 3-4 septate, 4.1-4.8×26.1-30.8 µm (n=50). Chlamydospores of the KWRR1 and KWRR2 isolates were 1-2 celled, irregular globose, measuring 4.5-8.5 µm and 7.6-9.0 µm diam, respectively (n=50). To identify the isolates, four DNA fragments (RPB1, RPB2, ITS and TEF-1α) were amplified and sequenced from all isolates (O'Donnell, et al. 2012; White et al. 1990; O'Donnell et al. 2022). BLAST analysis of the RPB1, RPB2, ITS and TEF-1α sequences of the KWRR1 isolates (OL474057, OL474055, OL468550, OP382187) showed highest identity with F. solani (NRRL66304; MW218134, KT313623, KT313633, KT313611) at 98.2%-99.8%, while KWRR2 (OL505579, OL474056, OL468551, OP382188) showed that their homology with F. breve (NRRL28009; HM347149, EF470136, DQ094351, DQ246869) at 98.2%-99.4%. F. solani and F. breve belong to clade 3 of the F. solani species complex (FSSC) (Geiser et al. 2021). Phylogenetic analysis based on RPB2, ITS and TEF-1α sequences with MEGA7 software (Sisic et al. 2018), placed the KWRR1 sequences with F. solani (FSSC5), while there of KWRR2 nested with F. breve (FSSC15). One-year-old seedlings (n=6) of 'Xu Xiang', growing in a greenhouse (at 28℃, relative humidity 80%), were inoculated by drenching the soil with a conidial suspension with one of the two isolates (30 ml, 106 conidia/ml). Control plants (n=6) were inoculated with sterilized water and the pathogenicity assay was repeated three times. One month post-inoculation, the leaves of inoculated plants became chlorotic, wilted and died, whereas the controls were disease-free. F. solani and F. breve were successfully reisolated from diseased samples (n=6) and verified based on morphology and sequencing as described above, fulfilling Koch's postulates. Members of the FSSC cause root rot on many hosts (Coleman. 2016; Schroers et al. 2016), but this is the first report of F. solani and F. breve causing root rot disease on kiwifruit in China. The result will serve as the foundation for management of root rot of kiwifruit.

Icariside II induces rapid phosphorylation of endothelial nitric oxide synthase via multiple signaling pathways.

Icariside II, as a favonoid compound derived from epimedium, has been proved to involed in a variety of biological and pharmacological effects such as anti-inflammatory, anti-osteoporosis, anti-oxidation, anti-aging, and anti-cancer but its mechanism is unclear, especially in terms of its effect on post-transcriptional modification of endothelial nitric oxide synthase (eNOS). Phosphorylation of eNOS plays an important role in the synthesis of nitric oxide in endothelial cells, which is closely related to erectile dysfunction, atherosclerosis, Alzheimer's disease, and other diseases. Our study aims to investigate the effect and mechanism of Icariside II on the rapid phosphorylation of eNOS. In this study, human umbilical vein endothelial cells (HUVECs) were stimulated with Icariside II in the presence or absence of multiple inhibitors (1 µM), including LY294002 (PI3K-inhibitor), MK-2206 (AKT-inhibitor), Bisindolylmaleimide X (AMPK-inhibitor), H-89 (CaMKII-inhibitor), KN-62 (PKA-inhibitor), Dorsomorphin (PKC-inhibitor). The proliferation of HUVECs was assessed using cell counting kit-8 (CCK-8). The release of nitric oxide (NO) within HUVECs was detected via fluorescence probe (DAF-FM). Western blot was used to examine the effect of Icariside II on the expression of eNOS, phosphorylation of eNOS, and common signaling pathways proteins. In this study, Icariside II was found to promote the cell proliferation and rapid NO release in HUVECs. The phosphorylation of eNOS-Ser1177 was significantly increased after Icariside II stimulation and reached a peak at 10 min (p < 0.05). Meanwhile, the phosphorylation of eNOS-Thr495 was significantly decreased after 45 min of stimulation (p < 0.05). Following the intervention with multiple inhibitors, it was found that MK-2206 (AKT inhibitor), LY294002 (PI3K inhibitor), KN-62 (AMPK inhibitor), and Bisindolylmaleimide X (PKC inhibitor) could significantly inhibit the phosphorylation of eNOS-Ser1177 caused by Icariside II (p < 0.05), while MK-2206, LY294002, and Bisindolylmaleimide X reversed the alleviated phosphorylation of eNOS-Thr495. We concluded that Icariside can regulate rapid phosphorylation of eNOS- Ser1177 and eNOS-Thr495 via multiple signaling pathways, resulting in the up-regulation of eNOS and the increased release of NO.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis.

BACKGROUND: Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial. AIM: To investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer. METHODS: Published literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated by I 2 statistics. RESULTS: Eleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69, I 2 = 68.6%), and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84 (95%CI: 1.12-3.02, I 2 = 67.1%), suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients. In addition, overexpression of Twist was correlated with T stage (T3 + T4 vs T1 + T2, RR = 1.38, 95%CI: 1.14-1.67), lymph node metastasis (yes vs no, RR = 1.34, 95%CI: 1.11-1.60), distant metastasis (yes vs no, RR = 1.18, 95%CI: 1.02-1.35), tumor, node and metastasis (TNM) stage (III + IV vs I + II, RR = 1.35, 95%CI: 1.14-1.60), and clinical stage (III + IV vs I + II, RR = 1.58, 95%CI: 1.34-1.87). However, no correlation between Twist expression and age, gender, tumor location, differentiation, or venous invasion was observed. CONCLUSION: High expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.