The Sensitization Differences of Pollen Allergen Components in Patients with Asthma and/or Rhinitis in Southern China.

INTRODUCTION: This study aim to analyzed the main pollen allergen components that cause allergic asthma and/or rhinitis and the cross-reactions between the allergen components. METHODS: Twenty one allergic rhinitis patients and 23 allergic asthma patients with pollen sensitization from the China Biological Information Repository of Respiratory Diseases were included. All the patients were detected serum pollen allergens components specific immunoglobulin E (sIgE) including Betula verrucosa (Bet v 1, Bet v 2, Bet v 4), Quercus alba (Pla a 1, Pla a 2), Ambrosia elatior (Amb a 1), Artemisia vulgaris (Art v 1, Art v 3, Art v 4), Bermuda grass (Cyn d 1, Cyn d 12), Phleum pratense (Phl p 5, Phl p 1, Phl p 4, Phl p 7, Phl p 12), and cross-reactive carbohydrate determinants. RESULTS: In patients with asthma, Phl p 4 had the highest positive rate (60.9%), followed by Phl p 1 (43.5%) and Pla a 2 (34.8%), while in patients with rhinitis, Amb a 1 had the highest positive rate (71.4%), followed by Phl p 4 (61.9%) and Pla a 2 (42.9%). Meanwhile, Phl p 1 (43.5%) in asthma patients was higher than that in rhinitis (4.7%, p = 0.03), while Amb a 1 (71.4%) in rhinitis patients was higher than that in asthma (26.1%, p = 0.03). Interestingly, optimal scale analysis show that the severity of both asthma and rhinitis is related to Bet v 4 (Cronbach's Alpha = 95.0%). CONCLUSIONS: In general, Phl p 4 is the main allergenic component in pollen sensitized asthma patients, while Amb a 1 is the main allergenic component in pollen sensitized rhinitis patients. Sensitization to Bet v 4 may lead to more severe symptoms, and this result may be applied in future clinical precise diagnosis.

Chemical Compositions of Scutellaria baicalensis Georgi. (Huangqin) Extracts and Their Effects on ACE2 Binding of SARS-CoV-2 Spike Protein, ACE2 Activity, and Free Radicals.

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals. A total of 76 compounds were tentatively identified from the extracts. The water extract showed a greater inhibition on the interaction between SARS-CoV-2 spike protein and ACE2, but less inhibition on ACE2 activity than that of the ethanol extract on a per botanical weight concentration basis. The total phenolic content was 65.27 mg gallic acid equivalent (GAE)/g dry botanical and the scavenging capacities against HO●, DPPH●, and ABTS●+ were 1369.39, 334.37, and 533.66 µmol trolox equivalent (TE)/g dry botanical for the water extract, respectively. These values were greater than those of the ethanol extract, with a TPC of 20.34 mg GAE/g, and 217.17, 10.93, and 50.21 µmol TE/g against HO●, DPPH●, and ABTS●+, respectively. The results suggested the potential use of huangqin as a functional food ingredient in preventing COVID-19.

Formation of Maillard Reaction Products in Aged Sorghum Vinegar during Ageing and Protective Effects of Pure Vinegar Melanoidin Against CCl4-Induced Rat Hepatic Damage.

Research background: The processing method generally affects the toxicity and biological activity of aged sorghum vinegar. This study investigates the changes in the intermediate Maillard reaction products of sorghum vinegar during ageing and the in vivo hepatoprotective effects of pure melanoidin obtained from it. Experimental approach: High-performance liquid chromatography (HPLC) and fluorescence spectrophotometry were utilized to quantify intermediate Maillard reaction products. The CCl4-induced liver damage in rats was used to evaluate the protective role of pure melanoidin in rat liver. Results and conclusions: Compared with the initial concentration, the 18-month ageing process caused a 1.2- to 3.3-fold increase in the concentrations of intermediate Maillard reaction products, i.e. 5-hydroxymethylfurfural (HMF), 5-methylfurfural (MF), methyglyoxal (MGO), glyoxal (GO) and advanced glycation end products (AGEs). The concentrations of HMF in the aged sorghum vinegar were 6.1-fold higher than the 450 µM limit standard for honey, implying the need for shortening the ageing of the vinegar in practice for safety concerns. Pure melanoidin (Mr>3.5 kDa) demonstrated significant protective effects against CCl4-induced rat liver damage, as evidenced by normalized serum biochemical parameters (transaminases and total bilirubin), suppressing hepatic lipid peroxidation and reactive oxygen species, as well as increasing glutathione amount and restoring antioxidant enzyme activities. Histopathological analysis revealed that melanoidin in vinegar reduced cell infiltration and vacuolar hepatocyte necrosis in rat liver. The findings demonstrated that a shortened ageing process should be considered in practice to ensure the safety of aged sorghum vinegar. Vinegar melanoidin is a potential alternative for the prevention of hepatic oxidative damage. Novelty and scientific contribution: This study demonstrates that the manufacturing process had a profound influence on the generation of vinegar intermediate Maillard reaction products. In particular, it revealed the in vivo hepatoprotective effect of pure melanoidin from aged sorghum vinegar, and provides insight into the in vivo biological activity of melanoidin.

MicroRNA-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition.

OBJECTIVE: Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition. RESULTS: Our results show that miR­1246 suppresses the proliferation, migration, and invasion of TNBC cells, DYRK1A is a novel target of miR-1246 and Importin-8 mediated miR-1246 nuclear translocation. MiR­1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. Overexpression of PGRN and DYRK1A promoted cell proliferation and migration of TNBC, but this effect was reversed by co-expression of miR-1246 mimics.DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246. CONCLUSION: MiR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis and preventing the epithelial-mesenchymal transition. The MiR-1246/DYRK1A/PGRN axis regulates TNBC progression, suggesting that MiR-1246 could be promising therapeutic targets for the treatment of TNBC.

CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.

Electrocatalytic Hydrogen Evolution by Cobalt Complexes with a Redox Non-Innocent Polypyridine Ligand.

Novel cobalt and zinc complexes with the tetradentate ppq (8-(1″,10″-phenanthrol-2″-yl)-2-(pyrid-2'-yl)quinoline) ligand have been synthesized and fully characterized. Electrochemical measurements have shown that the formal monovalent complex [Co(ppq)(PPh3)]+ (2) undergoes two stepwise ligand-based electroreductions in DMF, affording a [Co(ppq)DMF]-1 species. Theoretical calculations have described the electronic structure of [Co(ppq)DMF]-1 as a low-spin Co(II) center coupling with a triple-reduced ppq radical ligand. In the presence of triethylammonium as the proton donor, the cobalt complex efficiently drives electrocatalytic hydrogen evolution with a maximum turnover frequency of thousands per second. A mechanistic investigation proposes an EECC H2-evolving pathway, where the second ligand-based redox process (E), generating the [Co(ppq)DMF]-1 intermediate, initiates proton reduction, and the second proton transfer process (C) is the rate-determining step. This work provides a unique example for understanding the role of redox-active ligands in electrocatalytic H2 evolution by transition metal sites.

Morphologic analysis of alveolar bone in maxillary and mandibular incisors on sagittal views.

PURPOSE: The aim of this study was to analyze the morphologic features of alveolus in relatively healthy maxillary and mandibular incisors using cone-beam-computed tomography (CBCT). METHODS: CBCT images of 318 patients were retrospectively acquired. Alveolar bone in incisive area was divided into: type 1 (thick), type 2 (relatively thick with mono-plate concavity), type 3 (thin with double-plate concavities), and type 4 (vulnerably thin). Alveolus prevalence and widths were analyzed statistically relative to age, gender, and molar relationship. RESULTS: Prevalence of type 1 alveolus was 78.9% in maxillary central incisors, 15.1% in maxillary lateral incisors, 24.1% in mandibular central incisors, and 5.0% in mandibular lateral incisors. Type 2 alveolus was commonly observed in the maxillary lateral incisors (82.2%), mandibular central incisors (66.2%), and mandibular lateral incisors (87.9%). Prevalence of type 3 and 4 alveoli ranged from 0.0 to 9.4%. As for maxillary central incisors, type 1 was the widest both at the alveolar crest (7.77 ± 0.58 mm) and apical area (9.05 ± 1.86 mm), while type 3 had the lowest width at the apical region (4.08 ± 0.51 mm). Among maxillary central incisors, prevalence of type 1 tended to decrease with age. At all maxillary and mandibular incisor sites, alveolus widths were significantly thicker in males than in females. At maxillary lateral incisor and mandibular incisor sites, prevalence of alveolus type was significantly different among three molar relationships. CONCLUSION: A 4-type classification system was suggested for alveolus morphology in incisive region. Identification of alveolus type might aid in the corresponding treatment.

Immune-related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) show multiple functions, including immune response. Recently, the immune-related lncRNAs have been reported in some cancers. We first investigated the immune-related lncRNA signature as a potential target in hepatocellular carcinoma (HCC) survival. The training set (n = 368) and the independent external validation cohort (n = 115) were used. Immune genes and lncRNAs coexpression were constructed to identify immune-related lncRNAs. Cox regression analyses were perfumed to establish the immune-related lncRNA signature. Regulatory roles of this signature on cancer pathways and the immunologic features were investigated. The correlation between immune checkpoint inhibitors and this signature was examined. In this study, the immune-related lncRNA signature was identified in HCC, which could stratify patients into high- and low-risk groups. This immune-related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our immune-related lncRNA signature was still a powerful tool in predicting survival in each stratum of age, gender, and tumor stage. This signature mediated cell cycle, glycolysis, DNA repair, mammalian target of rapamycin signaling, and immunologic characteristics (i.e., natural killer cells vs. Th1 cells down, etc). This signature was associated with immune cell infiltration (i.e., macrophages M0, Tregs, CD4 memory T cells, and macrophages M1, etc.,) and immune checkpoint blockade (ICB) immunotherapy-related molecules (i.e., PD-L1, PD-L2, and IDO1). Our findings suggested that the immune-related lncRNA signature had an important value for survival prediction and may have the potential to measure the response to ICB immunotherapy. This signature may guide the selection of the immunotherapy for HCC.

Highly Active Manganese-Based CO2 Reduction Catalysts with Bulky NHC Ligands: A Mechanistic Study.

Because of the strong σ-donor and weak π-acceptor of the N-heterocyclic carbene (NHC), Mn-NHC complexes were found to be active for the reduction of CO2 to CO with high activity. However, some NHC-based manganese complexes showed low catalytic activity and required very negative potentials. We report herein that complex fac-[MnI(bis-MesNHC)(CO)3Br] [1; bis-MesNHC = 3,3-bis(2,4,6-trimethylphenyl)-(1,1'-diimidazolin-2,2'-diylidene)methane] could catalyze the electrochemical reduction of CO2 to CO with high activity (TOFmax = 3180 ± 6 s-1) at a less negative potential. Due to the introduction of the bulky Mes groups, a one-electron-reduced intermediate {[Mn0(bis-MesNHC)(CO)3]0 (2•)} was isolated as a packed "dimer" and crystallographically characterized. Stopped-flow Fourier-transform infrared spectroscopy was used to prove the direct reaction between doubly reduced intermediate fac-[Mn(bis-MesNHC)(CO)3]- and CO2; the tetracarbonyl Mn complex [Mn+(bis-MesNHC)(CO)4]+ ([2-CO]+) was captured, and its further reduction proposed as the rate-limiting step.

Value of serum tumor markers for predicting EGFR mutations in non-small cell lung cancer patients.

OBJECTIVES: We investigated whether serum tumor markers (STMs) represent a valuable noninvasive tool to predict epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. METHODS: A retrospective analysis was performed for 143 NSCLC patients at the Peking University International Hospital from December 2014 to December 2019. EGFR mutations in the tumor tissues were identified by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS). The relationships between EGFR mutation and several clinicopathological features were analyzed. RESULT: EGFR mutation were found more frequently in female (56.67%, P = 0.01), never-smokers (55.26%, P = 0.004), and those with lung adenocarcinoma (ADC) (52.17%, P < 0.001). The positive mutation rate for the EGFR gene were higher in the squamous cell carcinoma antigen (SCCA)group (≤1.5 ng/ml) and in the gastrin-releasing peptide precursor (preGRP) increased group (≥69.2 pg/ml), and this difference was statistically significant (P < 0.05). Univariate logistic regression analysis demonstrated that females (Odd ratio [OR]: 2.435, 95% confidence interval [CI]: 1.232, 4.813, P = 0.01) and never-smokers (OR = 0.370; CI = 0.186, 0.734; P = 0.004), lung adenocarcinoma patients (OR = 9.091; CI = 2.599, 21.800; P = 0.001), the SCC group (≤1.5 ng/ml) (OR = 0.331, CI = 0.120, 0.914; P = 0.033), and the preGRP group (≥69.2 pg/ml) (OR = 5.478, CI = 1.462, 20.528; P = 0.012) patients were risk factors for EGFR gene mutation. Multivariate logistic regression analysis demonstrated that lung ADC and proGRP elevation were independent risk factors for predicting EGFR gene positivity (P < 0.05). CONCLUSION: STMs are associated with mutant EGFR status and could be integrated with other clinical factors to facilitate the classification of EGFR mutation status among NSCLC patients.