Quercetin prevented diabetic nephropathy by inhibiting renal tubular epithelial cell apoptosis via the PI3K/AKT pathway.

Diabetic nephropathy (DN) is the most common and serious complication of diabetes, posing a significant threat to human health. Currently, safe and effective preventive strategies for DN are lacking. The study aimed to explore the preventive effect and the underlying mechanism of quercetin against DN. In the in vivo experiments, we established a mouse model of type 2 diabetes mellitus (T2DM) induced by a combination of high-fat diet (HFD) and streptozotocin (STZ) to explore the preventive effect of quercetin on DN and its protective role against renal tubular epithelial cell apoptosis. Subsequently, in vitro experiments using human tubular epithelial cells (HK-2 cells) were conducted to further validate the protective effects of quercetin on renal tubular epithelial cell apoptosis. Additionally, we employed RNA sequencing analysis (RNA-seq) and network pharmacology analysis to comprehensively elucidate the molecular mechanisms involved. In vivo, we observed a significant increase in the ratio of urinary microalbumin to creatinine in diabetic mice compared to control mice, accompanied by the activation of renal tubular epithelial cell apoptosis. Remarkably, all of these changes were reversed after quercetin treatment. In vitro, high-glucose-induced apoptosis in HK-2 cells was significantly attenuated by quercetin. Subsequent RNA sequencing analysis and network pharmacology analysis revealed that quercetin was most likely to inhibit high-glucose-induced HK-2 cell apoptosis through the PI3K/AKT signaling pathway. Western Blotting results further demonstrated that quercetin could inhibit the activation of the PI3K/AKT signaling pathway in HK-2 cells induced by high glucose. Our results supported that quercetin could prevent DN by inhibiting tubular epithelial cell apoptosis via the PI3K/AKT pathway. Quercetin might be a promising candidate for the prevention of DN.

The associations between dietary flavonoids intake and risk of depressive symptom in diabetic patients: Data from NHANES 2007-2008, 2009-2010, and 2017-2018.

BACKGROUND: The increasing incidence of depressive symptoms in diabetic patients contributes to the global burden of disease, but few epidemiological studies have evaluated the relationship between dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. OBJECTIVE: This study intended to evaluate the associations of dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. METHODS: We conducted a cross-sectional analysis of 1993 adults aged ≥20 years old who participated in the 2007-2008, 2009-2010, and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). Chi-square test and independent-sample t-test were used to compare subjects' characteristics. Logistic regression model was further used to analyze the relationship between dietary flavonoid intake and depressive symptoms in diabetic patients. Restricted cubic spline (RCS) analysis was used to investigate the non-linear relationship between dietary flavonoid intake and the prevalence of depressive symptoms in diabetic patients. The weighted quartile sum (WQS) regression was used to analyze the effect of 29 flavonoids monomers. RESULTS: The results showed that the total flavonoid intake in the third quartile (OR, 0.635; 95 % CI,0.419-0.962; P, 0.032) was significantly associated with a reduced risk of depressive symptoms in diabetic patients compared with the lowest quartile. And there was a U-shaped association between dietary flavonoid intake and risk of depressive symptoms in diabetic patients. Top contributors of flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate, accounting for a percentage of 30.83 %, 22.17 %, and 6.92 %, respectively. CONCLUSION: Moderate (56.07-207.12 mg/day) dietary flavonoid intake was associated with a reduced risk of depressive symptoms in diabetic patients. The important flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate.

The immune landscape and prognostic analysis of CXCL8 immune-related genes in cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CESC), one of the most common malignancies in women, imposes a significant burden on women's health worldwide. Despite extensive research, the molecular and pathogenic mechanisms of cervical squamous cell carcinoma and CESC remain unclear. This study aimed to explore the immune-related genes, immune microenvironment infiltration, and prognosis of CESC, providing a theoretical basis for guiding clinical treatment. Initially, by mining four gene sets and immune-related gene sets from public databases, 14 immune-related genes associated with CESC were identified. Through univariate and multivariate COX regression analyses, as well as lasso regression analysis, four CESC-independent prognostic genes were identified, and a prognostic model was constructed, dividing them into high and low-risk groups. The correlation between these genes and immune cells and immune functions were explored through ssGSEA enrichment analysis, revealing a close association between the high-risk group and processes such as angiogenesis and epithelial-mesenchymal transition. Furthermore, using public databases and qRT-PCR experiments, significant differences in CXCL8 expression between normal cervical cells and cervical cancer cells were discovered. Subsequently, a CXCL8 knockdown plasmid was constructed, and the efficiency of CXCL8 knockdown was validated in two CESC cell lines, MEG-01 and HCE-1. Through CCK-8, scratch, and Transwell assays, it was confirmed that CXCL8 knockdown could inhibit the proliferation, invasion, and migration abilities of CESC cells. Targeting CXCL8 holds promise for personalized therapy for CESC, providing a strong theoretical basis for achieving clinical translation.

Factors influencing the accuracy and safety of preoperative computed tomography (CT)-guided soft hook-wire localization for pulmonary nodules: a comprehensive analysis.

Background: The necessity of localization of pulmonary nodules lies in ensuring the ability to locate the nodule quickly and accurately during surgery, thereby improving the success rate of the operation. The accuracy and risk of preoperative localization of pulmonary nodules need further exploration. Therefore, the purpose of this study was to investigate the factors of accuracy and safety of computed tomography (CT)-guided localization of pulmonary nodules using a flexible wire hook positioner. Methods: In this retrospective cross-sectional analysis, 281 patients with a single pulmonary nodule underwent video-assisted thoracoscopic surgery (VATS) following localization with a soft hook-wire guided by CT scan from January 2021 to July 2022 at Nanjing Drum Tower Hospital. The patients underwent VATS to remove pulmonary nodules within 24 hours after localization. The demographic, pulmonary nodule, and technical factors were analyzed retrospectively. Univariate and multivariate analysis were used to analyze the identified factors that influence pulmonary nodule localization accuracy and complications. Results: Localization was successfully performed in 280 patients, with only 1 patient being excluded due to a displaced positioner and the hook wire failing to enter the lung parenchyma as a result of pneumothorax. Out of the total cases, 191 (68.2%) were accurately positioned in group G0, whereas 89 cases (31.7%) were inaccurately positioned in group G1. Hemorrhage and self-limited hemoptysis were observed in 64 patients (22.8%), whereas pneumothorax was observed in 84 patients (29.9%). There were no serious complications such as air embolism or death. The accuracy of localization was found to be influenced by both the depth of pulmonary nodules [odds ratio (OR) =22.610, 95% confidence interval (CI): 10.351-49.391, P=0.001] and the depth of the needle used (OR =0.322, 95% CI: 0.136-0.765, P=0.010). Additionally, postoperative hemorrhage was found to be affected by several important factors, including the diameter (P=0.036) and depth of the nodule (P=0.011), as well as the thickness of the chest wall (P=0.043) and the depth of the needle used (P=0.005). Conclusions: The CT-guided flexible wire hook positioner has been found to be a safe and effective device for locating pulmonary nodules. The depth of pulmonary nodules and needle penetration are key factors affecting the accuracy of lung nodule localization under CT guidance and are important factors affecting postoperative bleeding.

Prevalence of Gastrointestinal Parasites in Zoo Animals and Phylogenetic Characterization of Toxascaris leonina (Linstow, 1902) and Baylisascaris transfuga (Rudolphi, 1819) in Jiangsu Province, Eastern China.

The burden of gastrointestinal parasites in zoo animals has serious implications for their welfare and the health of veterinarians and visitors. Zhuyuwan Zoo is located in the eastern suburb of Yangzhou city in eastern China, in which over 40 species of zoo animals are kept. In order to understand the infection status of GI parasites in Zhuyuwan Zoo, a total of 104 fresh fecal samples collected randomly from birds (n = 19), primates (n = 19), and non-primate mammals (n = 66) were analyzed using the saturated saline flotation technique and nylon sifter elutriation and sieving method for eggs/oocysts, respectively. Two Ascaris species were molecularly characterized. The results showed that the overall prevalence of parasitic infection was 42.3% (44/104). The parasitic infection rate in birds, primates, and non-primate mammals were 26.3% (5/19), 31.6% (6/19), and 50.0% (33/66), respectively. A total of 11 species of parasites were identified, namely, Trichostrongylidae, Capillaria sp., Trichuris spp., Strongyloides spp., Amidostomum sp., Toxascaris leonina, Baylisascaris transfuga, Parascaris equorum, Paramphistomum spp., Fasciola spp., and Eimeria spp. Paramphistomum spp. eggs were first detected from the captive Père David's deer, and Fasciola spp. eggs were first reported from sika deer in zoo in China. A sequence analysis of ITS-2 and cox1 showed that the eggs isolated from the African lion (Panthera leo Linnaeus, 1758) were T. leonina, and the eggs from the brown bear (Ursus arctos Linnaeus, 1758) were B. transfuga. The public health threat posed by these potential zoonotic parasitic agents requires attention. These results lay a theoretical foundation for prevention and control of wild animal parasitic diseases at zoos in China.

A higher non-HDL-C/HDL-C ratio was associated with an increased risk of progression of nonculprit coronary lesion in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The ratio of nonhigh-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) has been shown associated with various metabolic diseases and atherosclerosis in primary prevention. However, there is limited evidence on the relationship between the non-HDL-C/HDL-C ratio and progression of nonculprit coronary lesion (NCCL) after percutaneous coronary intervention (PCI). HYPOTHESIS: Our study aimed to investigate the potential association between the non-HDL-C/HDL-C ratio and NCCL progression in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: We conducted a retrospective analysis of ACS patients who underwent coronary angiography twice at a single center from 2016 to 2022. Lipid measurements, demographic, clinical, and other laboratory data were collected from electronic medical records. NCCLs were evaluated using quantitative coronary angiography. The primary outcome was the progression of NCCL. Patients were categorized based on NCCL progression and tertiles of the non-HDL-C/HDL-C ratio. Associations were analyzed using univariate and multivariate logistic regression analysis. RESULTS: The study included 329 ACS patients who underwent PCI, with a median follow-up angiography of 1.09 years. We found NCCL progression in 95 (28.9%) patients with acceptable low-density lipoprotein cholesterol control (median: 1.81 mmol/L). Patients in the top tertile of the non-HDL-C/HDL-C ratio had a higher risk of NCCL progression. After adjusting for potential confounding factors, the non-HDL-C/HDL-C ratio remained a significant predictor for NCCL progression (adjusted odds ratio: 1.45; 95% confidence interval: 1.14-1.86; p < 0.05). CONCLUSIONS: The non-HDL-C/HDL-C ratio predicts NCCL progression in ACS patients following PCI, providing a valuable tool for risk assessment and enhancing secondary prevention of atherosclerotic cardiovascular disease.

Evaluation of Prognosis in Patients with Lung Adenocarcinoma with Atypical Solid Nodules on Thin-Section CT Images.

Purpose To evaluate the clinicopathologic characteristics and prognosis of patients with clinical stage IA lung adenocarcinoma with atypical solid nodules (ASNs) on thin-section CT images. Materials and Methods Data from patients with clinical stage IA lung adenocarcinoma who underwent resection between January 2005 and December 2012 were retrospectively reviewed. According to their manifestations on thin-section CT images, nodules were classified as ASNs, subsolid nodules (SSNs), and typical solid nodules (TSNs). The clinicopathologic characteristics of the ASNs were investigated, and the differences across the three groups were analyzed. The Kaplan-Meier method and multivariable Cox analysis were used to evaluate survival differences among patients with ASNs, SSNs, and TSNs. Results Of the 254 patients (median age, 58 years [IQR, 53-66]; 152 women) evaluated, 49 had ASNs, 123 had SSNs, and 82 had TSNs. Compared with patients with SSNs, those with ASNs were more likely to have nonsmall adenocarcinoma (P < .001), advanced-stage adenocarcinoma (P = .004), nonlepidic growth adenocarcinoma (P < .001), and middle- or low-grade differentiation tumors (P < .001). Compared with patients with TSNs, those with ASNs were more likely to have no lymph node involvement (P = .009) and epidermal growth factor receptor mutation positivity (P = .018). Average disease-free survival in patients with ASNs was significantly longer than that in patients with TSNs (P < .001) but was not distinguishable from that in patients with SSNs (P = .051). Conclusion ASNs were associated with better clinical outcomes than TSNs in patients with clinical stage IA lung adenocarcinoma. Keywords: Adenocarcinoma, Atypical Solid Nodules, CT, Disease-free Survival, Lung, Prognosis, Pulmonary Supplemental material is available for this article. Published under a CC BY 4.0 license.

An MRI-Based Radiomics Nomogram for Differentiation of Benign and Malignant Vertebral Compression Fracture.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram combining radiomics signatures and clinical factors to differentiate between benign and malignant vertebral compression fractures (VCFs). MATERIALS AND METHODS: A total of 189 patients with benign VCFs (n = 112) or malignant VCFs (n = 77) were divided into training (n = 133) and validation (n = 56) cohorts. Radiomics features were extracted from MRI T1-weighted images and short-TI inversion recovery images to develop the radiomics signature, and the Rad score was constructed using least absolute shrinkage and selection operator regression. Demographic and MRI morphological characteristics were assessed to build a clinical factor model using multivariate logistic regression analysis. A radiomics nomogram was constructed based on the Rad score and independent clinical factors. Finally, the diagnostic performance of the radiomics nomogram, clinical model, and radiomics signature was validated using receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were used to build a combined radiomics model (combined-RS). Pedicle or posterior element involvement, paraspinal mass, and fluid sign were identified as the most important morphological factors for building the clinical factor model. The radiomics signature was superior to the clinical model in terms of the area under the curve (AUC), accuracy, and specificity. The radiomics nomogram integrating the combined-RS, pedicle or posterior element involvement, paraspinal mass, and fluid sign achieved favorable predictive efficacy, generating AUCs of 0.92 and 0.90 in the training and validation cohorts, respectively. The DCA indicated good clinical usefulness of the radiomics nomogram. CONCLUSION: The MRI-based radiomics nomogram, combining the radiomics signature and clinical factors, showed favorable predictive efficacy for differentiating benign from malignant VCFs.

Association between dietary flavonoid intake and depressive symptoms: A cross-sectional research.

OBJECTIVE: To investigate the relationship between dietary flavonoid intake and depression symptoms in American adults. METHODS: Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018 survey cycles. Both males and females aged 18 years and older with complete information about dietary flavonoid intake (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols), depression symptoms, and covariates were included. Logistic regression models were conducted to calculate the odds ratio (OR) of single dietary flavonoid subclass intake on depression, and the restricted cubic spline (RCS) models were utilized to explore the corresponding dose-response relationships. Additionally, we implemented the weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models to estimate the mixed effects of six flavonoid subclasses and identify the predominant types. RESULTS: After multivariable adjustments, people with higher consumption of flavanones (OR: 0.68, 95% CI: 0.52-0.90, p = 0.008), flavones (OR: 0.63, 95% CI: 0.46-0.87, p = 0.007), flavonols (OR: 0.66, 95% CI: 0.49-0.89, p = 0.008), and total flavonoids (OR: 0.69, 95% CI: 0.50-0.95, p = 0.024) had lower odds of depression symptoms. Meanwhile, significant dose-response relationships were supported by the RCS models. However, no obvious associations between isoflavones, anthocyanidins, flavan-3-ols, and the odds of suffering from depression symptoms were found by the logistic regression models and RCS models. As for the mixed effect, the WQS and qgcomp models both demonstrated that the mixture of six flavonoid subclasses was inversely related to the odds ratios of depression symptoms, and flavones, flavanones, and anthocyanidins were the top 3 contributors. CONCLUSION: Our study implied dietary flavonoid intake was associated with the decreased probability of depression symptoms in U.S. adults, among which flavones, flavanones, and anthocyanidins may occupy the predominant roles.

Localization in vivo and in vitro confirms EnApiAP2 protein encoded by ENH_00027130 as a nuclear protein in Eimeria necatrix.

Introduction: Apicomplexan AP2 family of proteins (ApiAP2) are transcription factors (TFs) that regulate parasite growth and development, but little is known about the ApiAP2 TFs in Eimeria spp. ENH_00027130 sequence is predicted to encode a Eimeria necatrix ApiAP2 protein (EnApiAP2). Methods: The cDNAs encoding full-length and truncated EnApiAP2 protein were cloned and sequenced, respectively. Then, the two cDNAs were cloned into the pET28a(+) expression vector and expressed expressed in Escherichia coli BL21. The mouse polyclonal antibody (pAb) and monoclonal antibody (mAb) against recombinant EnApiAP2 (rEnApiAP2) and EnApiAP2tr (rEnApiAP2tr) were prepared and used to localize the native EnApiAP2 protein in E. necatrix, respectively. Finally, the recombinant pEGFP-C1-ΔNLS-EnApiAP2s (knockout of a nuclear localization sequence, NLS) and pEGFP-C1-EnApiAP2 plasmid were constructed and transfected into DF-1 cells, respectively, to further observe subcellular localization of EnApiAP2 protein. Results: The EnApiAP2 gene had a size of 5019 bp and encoded 1672 amino acids, containing a conserved AP2 domain with a secondary structure consisting of an α-helix and three antiparallel ß-strands. The rEnApiAP2 and rEnApiAP2tr were predominantly expressed in the form of inclusion bodies, and could be recognized by the 6×His tag mAb and the serum of convalescent chickens after infection with E. necatrix, respectively. The native EnApiAP2 protein was detected in sporozoites (SZ) and second generation merozoites (MZ-2) extracts, with a size of approximately 210 kDa. A quantitative real-time PCR (qPCR) analysis showed that the transcription level of EnApiAP2 was significantly higher in SZ than in MZ-2, third generation merozoites (MZ-3) and gametocytes (P<0.01). EnApiAP2 protein was localized in the nuclei of SZ, MZ-2 and MZ-3 of E. necatrix. The protein of EnApiAP2 was localized in the nucleus of the DF-1 cells, whereas the ΔNLS-EnApiAP2 was expressed in the cytoplasm, which further confirmed that EnApiAP2 is nucleoprotein. Discussion: EnApiAP2 protein encoded by ENH_00027130 sequence was localized in the nucleus of E. necatrix parasites, and relied on the NLS for migration to DF-1 cell nucleus. The function of EnApiAP2 need further study.

Comparative proteomic analysis of wall-forming bodies and oocyst wall reveals the molecular basis underlying oocyst wall formation in Eimeria necatrix.

BACKGROUND: The durable oocyst wall formed from the contents of wall-forming bodies (WFBs) protects Eimeria parasites from harsh conditions and enhances parasite transmission. Comprehending the contents of WFBs and proteins involved in oocyst wall formation is pivotal to understanding the mechanism of the oocyst wall formation and the search for novel targets to disrupt parasite transmission. METHODS: Total proteins extracted from WFBs and the oocyst wall of Eimeria necatrix were subjected to comparative proteomic analysis using tandem mass tag in conjunction with liquid chromatography tandem-mass spectrometry techniques. After functional clustering analysis of the identified proteins, three proteins, including E. necatrix disulfide isomerase (EnPDI), thioredoxin (EnTrx) and phosphoglycerate kinase (EnPGK), were selected for further study to confirm their potential roles in oocyst wall formation. RESULTS: A total of 3009 and 2973 proteins were identified from WFBs and the oocyst wall of E. necatrix, respectively. Among these proteins, 1102 were identified as differentially expressed proteins, of which 506 were upregulated and 596 downregulated in the oocyst wall compared to the WFBs. A total of 108 proteins, including compositional proteins of the oocyst wall, proteases, oxidoreductases, proteins involved in glycosylation, proteins involved in synthesis of the acid-fast lipid layer and proteins related to transport, were proposed to be involved in oocyst wall formation. The approximate molecular sizes of native EnPDI, EnTrx and EnPGK proteins were 55, 50 and 45 kDa, respectively. EnPDI was present in both type 1 and type 2 WFBs, EnTrx was present only in type 2 WFB2 and EnPGK was present only in type 1 WFBs, whereas all of them were localized to the outer layer of the oocyst wall, indicating that all of them participate in the formation of the oocyst wall. CONCLUSIONS: To the best of our knowledge, this is the first report on the proteomes of WFBs and the oocyst wall of E. necatrix. The data obtained from this study form a basis for deciphering the molecular mechanisms underlying oocyst wall formation of Eimeria parasites. They also provide valuable resources for future studies on the development of novel therapeutic agents and vaccines aimed at combating coccidian transmission.

Prevalence and risk factors associated with gastrointestinal parasites in goats (Capra hircus) and sheep (Ovis aries) from three provinces of China.

Gastrointestinal (GI) parasites in small ruminants, especially goats and sheep, have caused significant socio-economic and public health challenges worldwide. The aim of the present study was to investigate the diversity and prevalence of GI parasites in goats and sheep in Jiangsu, Shaanxi and Hunan provinces of China, and to assess whether the age of animals, sampling season and feeding mode influence the distribution and infection of GI parasites. A total of 1,081 fecal samples collected from goats (n = 835) and sheep (n = 246) were detected by saturated saline flotation technique and nylon sifter elutriation and sieving method for eggs/oocysts, respectively. Based on the morphological observation of eggs and oocysts, one tapeworm, five nematodes, three trematodes and nineteen coccidia were identified, of which seven helminths belong to zoonotic parasites. The infection rate of parasites was 83.4% (902/1081) in total samples, 91.6% (765/835) in goats, and 55.7% (137/246) in sheep. The infection rate of coccidia was 71.0% (767/1081), and that of helminths was 56.2% (607/1081). The dominant species was E. alijeri (67.3%, 562/835) in goats, E. parva (30.1%, 74/246) in sheep. The highest prevalent helminths were Trichostrongylidae spp. in goats (58.3%, 487/835), and Moniezia spp. in sheep (22.76%, 56/246). Of 902 positive samples, 825 (91.5%, 825/902) contained multiple (2-10) parasites. The feeding mode, sampling season and regions were relevant risk factors which have significant influence on the occurrence of GI parasites in goats and sheep. The risk coefficient of parasite infection in autumn was 2.49 times higher than spring (Odds ratio = 2.49, 95% CI = 1.51-4.09, p < 0.001). Compared to raising on the high beds, the goats and sheep raising on the ground had the higher risk of parasite infection (OR = 3.91, 95% CI = 2.07-7.40, p < 0.001). The risk coefficient of parasite infection in Shaanxi and Hunan was 3.78 and 1.25 times higher than that in Jiangsu (OR = 3.78, 95% CI = 2.01-7.12, p < 0.001; OR = 1.25, 95% CI = 1.21-1.29, p < 0.001). These data are significant for the development of prevention strategies to minimise economic losses from small ruminant production and to reduce the risk of water and food infecting humans as vectors of zoonotic parasitic diseases.

Extracellular volume fraction as a potential predictor to differentiate lung cancer from benign lung lesions with dual-layer detector spectral CT.

Background: Extracellular volume (ECV) fraction has been used in cardiovascular diseases, pancreatic fibrosis, and hepatic fibrosis. The diagnostic value of ECV for focal lung lesions remains to be explored. The aim of this study was to evaluate the feasibility of ECV derived from a dual-layer detector computed tomography (DLCT) to differentiate lung cancer (LC) from benign lung lesions (BLLs). Methods: Retrospectively, 128 consecutive patients with pathologically confirmed LC (n=86) or BLLs (n=42) were included. Conventional computed tomography (CT) characteristics and spectral CT parameters were assessed. All patients' hematocrits were measured to correct contrast volume distributions in blood while calculating ECV. After performing logistic regression analysis, a conventional CT-based model (Model A), DLCT-based model (Model B), combined diagnostic models (Model C), and an ECV-based model (Model D) were developed. The diagnostic effectiveness of each model was examined using the receiver operating characteristic (ROC) curve and their corresponding 95% confidence intervals (CIs). The area under the curve (AUC) of each model was compared using the DeLong test. Results: Certain conventional CT features (such as lesion size, lobulation, spiculation, pleural indentation, and enlarged lymph nodes) differed significantly between the LC and BLL groups (all P<0.05). Statistical differences were found in the following DLCT parameters (all P<0.05): effective atomic number (Zeff) (non-enhancement), electron density (ED) (non-enhancement), ECV, iodine concentration (IC), and normalized iodine concentration (NIC). Models A, B, C, and D had AUCs of 0.801 [95% confidence interval (CI): 0.721-0.866], 0.805 (95% CI: 0.726-0.870), 0.925 (95% CI: 0.865-0.964), and 0.754 (95% CI: 0.671-0.826), respectively. The AUC of Model D (ECV) showed no significant difference from that of Models A and B (DeLong test, P>0.05). Conclusions: The ECV derived from DLCT may be a potential new method to differentiate LC from BLLs, broadening the scope of ECV in clinical research.

Expression of a SAG protein with a CAP domain from Eimeria necatrix and its role in invasion and immunoprotection.

Eimeria necatrix is a high pathogenic pathogen, which seriously endangers the poultry industry. The surface antigens (SAGs) of Apicomplexa are a kind of membrane protein anchored on the surface of the parasites through its carboxyl terminal glycosylphosphatidylinositol (GPI) structure. However, little is known about GPI-linked surface proteins in E. necatrix. In the present work, the E. necatrix sag gene (Ensag-CAP) was amplified and cloned for expression of the recombinant protein (rEnSAG-CAP). The full length Ensag-CAP gene was 813 bp, coding 270 amino acids with a predicated molecular weight of 28.86 kDa and contained a CAP domain with four sequence motifs CAP1, CAP2, CAP3 and CAP4. The rEnSAG-CAP was about 32 kDa and mainly expressed in a soluble form. Western blot analysis indicated that the rEnSAG-CAP could be recognized by anti-rEnSAG-CAP monoclonal antibody (anti-rEnSAG-CAP McAb) and the convalescent serum of chicken infected with E. necatrix. Native protein of EnSAG-CAP was detected in second-generation merozoites (MZ-2) using anti-rEnSAG-CAP polyclonal antibody (anti-rEnSAG-CAP pAb). The findings from the indirect immunofluorescence assay and enzyme digestion utilizing Bacillus cereus phosphoinositide-specific phospholipase C (PI-PLC) revealed that EnSAG-CAP predominantly localized at the surfaces of SZ and MZ-2 via a GPI anchor. It was observed that EnSAG-CAP can be cleaved from MZ-2 by PI-PLC. Real-time quantitative PCR (qPCR) analysis showed that transcript levels of Ensag-CAP in MZ-2 was significantly higher than that in SZ (P < 0.05). The anti-rEnSAG-CAP McAb in vitro could significantly inhibit the sporozoite invasion into MDBK cells (P < 0.01), which suggests that the protein might participate in sporozoite invasion into MDBK cells. rEnSAG-CAP afforded an immune protection against E. necatrix. The ACI value was 164.99 in the chickens immunized with 200 µg rEnSAG-CAP. Chickens immunized with rEnSAG-CAP had a significantly higher antigen-specific serum IgY response (P < 0.0001). The data indicates that EnSAG-CAP could serve as a potential candidate antigen for the development of a recombinant coccidiosis vaccine.

Synthesis, biological evaluation and action mechanism of 7H-[1,2,4] triazolo [3,4-b] [1,3,4] thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors.

In our work, several 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors (α-GIs) were synthesized and characterized by 1H NMR, 13C NMR, and HRMS spectrum. Then, their bio-activity against the α-glucosidase (α-Glu) was further evaluated. Among them, almost all compounds displayed better bio-activity with IC50 from 31.23 ± 0.89 to 213.50 ± 4.19 µM than acarbose (IC50 = 700.20 ± 10.55 µM). In particular, compound 5o showed the best potency to inhibit α-Glu in a mixed manner. Moreover, the action mechanisms of 5o were further clarified including fluorescence quenching, circular dichroism spectra, three-dimensional fluorescence spectra, molecular docking, etc. All mechanism studies revealed that 5o could arouse the changed secondary structure of α-Glu to hinder enzyme catalytic activity. It was observed from an in vivo study that 5o of 20 mg/kg could significantly decrease by 24.45 % postprandial blood glucose in mice vs. the control. Meanwhile, 5o had low drug-drug interaction potential and was likely to be an orally active compound. Moreover, 5o was observed to be no obvious cytotoxicity to HEK-293 cells. In summary, compound 5o exhibited one potential to be further applied as an antidiabetic drug.

FEELing (key)Pressed: Implicit Touch Pressure Bests Brain Activity in Modelling Emotion Dynamics in the Space Between Stressed and Relaxed.

In-body lived emotional experiences can be complex, with time-varying and dissonant emotions evolving simultaneously; devices responding in real-time to estimate personal human emotion should evolve accordingly. Models assuming generalized emotions exist as discrete states fail to operationalize valuable information inherent in the dynamic and individualistic nature of human emotions. Our multi-resolution emotion self-reporting procedure allows the construction of emotion labels along the Stressed-Relaxed scale, differentiating not only what the emotions are, but how they are transitioning - e.g., "hopeful but getting stressed" vs. "hopeful and starting to relax". We trained participant-dependent hierarchical models of contextualized individual experience to compare emotion classification by modality (brain activity and keypress force from a physical keyboard), then benchmarked classification performance at F1-scores=[0.44, 0.82] (chance F1=0.22, σ = 0.01) and examined high-performing features. Notably, when classifying emotion evolution in the context of an experience that realistically varies in stress, pressure-based features from keypress force proved to be the more informative modality, and more convenient when considering intrusiveness and ease of collection and processing. Finally, we present our FEEL (Force, EEG and Emotion-Labelled) dataset, a collection of brain activity and keypress force data, labelled with self-reported emotion collected during tense videogame play (N=16) and open-sourced for community exploration.

Utilizing bio-affinity ultrafiltration combined with UHPLC Q-Exactive Plus Orbitrap HRMS to detect potential α-glucosidase inhibitors in Oxalis corniculate L.

Oxalis corniculate L. (O. corniculate) was used to treat diabetes in Chinese folk as a popular tea drink. In this work, 31 compounds from O. corniculate were screened and identified as potential α-Glucosidase inhibitors (α-GIs). Among them, 6 compounds displayed stronger inhibitory activity than acarbose (IC50 = 212.9 ± 5.98 µg/mL). Especially, the most effective compounds quercetin (Qu, IC50 = 4.70 ± 0.40 µg/mL) and luteolin (Lu, IC50 = 15.72 ± 0.75 µg/mL) inhibited α-Glu in competitive and mixed manners, respectively. Moreover, fluorescence quenching, circular dichroism (CD), and molecular docking study revealed that they can arouse the changes in the secondary structure and hydrophobic micro-environment of the enzyme mainly through a hydrophobic binding. Furthermore, it was observed that oral administration of Qu (20 mg/kg) can significantly reduce postprandial blood glucose (PBG) levels in mice vs. the control group. To sum up, the above research confirmed that O. corniculate could prevent and treat postprandial hyperglycemia as a good tea drink, and the plant was an excellent source to obtain natural α-GIs.

FvWRKY50 is an important gene that regulates both vegetative growth and reproductive growth in strawberry.

The WRKY transcription factors play important roles in plant growth and resistance, but only a few members have been identified in strawberry. Here we identified a WRKY transcription factor, FvWRKY50, in diploid strawberry which played essential roles in strawberry vegetative growth, and reproductive growth. Knocking out FvWRKY50 by genome editing accelerated flowering time and leaf senescence but delayed anthocyanin accumulation in fruit. Further analysis showed that FvWRKY50 acted as a transcriptional repressor to negatively regulate the expression of flowering- and leaf senescence-related genes, including FvFT2, FvCO, FvFT3, and FvSAUR36. Notably, FvWRKY50 directly upregulated the expression of FvCHI and FvDFR by binding their promoter under normal conditions, but at low temperature FvWRKY50 was phosphorylated by FvMAPK3 and then induced protein degradation by ubiquitination, delaying anthocyanin accumulation. In addition, the homozygous mutant of FvWRKY50 was smaller while the biallelic mutant showed normal size. These new findings provide important clues for us to further reveal the regulatory mechanisms of strawberry growth and fruit ripening.

Dietary flavonoid intake is associated with a lower risk of diabetic nephropathy in US adults: data from NHANES 2007-2008, 2009-2010, and 2017-2018.

Few epidemiological studies have investigated the relationship between flavonoids and diabetic nephropathy (DN). Therefore, we explored the association between dietary flavonoid intake and DN among 1949 US adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018. Weighted logistic regression models demonstrated that the total flavonoid intake in the second (OR: 0.642; 95% CI: 0.456-0.906), third (OR: 0.665; 95% CI: 0.447-0.988), and the highest (OR: 0.551; 95% CI: 0.382-0.796) quantiles (versus the lowest) were associated with the decreased risk of DN. Restricted cubic spline (RCS) analyses showed that the total flavonoid intake had a negative linear association with DN (p-value for non-linearity was 0.003). Weighted quantile sum (WQS) regression analyses revealed that flavan-3-ols, flavones, and anthocyanidins were the main contributors for the combined effects of six flavonoid subclasses. Our findings suggested that higher dietary flavonoid intake was associated with a decreased risk of DN, with the greatest influence coming from flavan-3-ols, flavones, and anthocyanidins.