ABSTRACT
Prediabetes is an early phase before diabetes. Diabetes and dietary inflammation are two crucial factors that are strongly associated with cardiovascular diseases (CVDs). Dietary interventions slowed the progression of diabetes and CVD. However, the associations between CVDs and dietary inflammation in different stages of pathoglycaemia have not been investigated. To explore the effect of a proinflammatory diet on CVD incidence at different stages of diabetes, NHANES (2001-2018) data were collected and analysed. A total of 3137 CVD patients with a comparable non-CVD group (n = 3137) were enrolled after propensity score matching (PSM) analysis. These patients were subsequently categorized into three subgroups: those with diabetes (n = 3043), those with prediabetes (n = 1099) and those with normoglycemia (n = 2132). The DII (Dietary inflammatory index) is a risk factor for CVD, both in overall individuals and in each subgroup of population-based information. In diabetic individuals, the odds ratios (ORs) (95% CIs) of CVD incidence for the DII were 1.10 (1.05, 1.15) and 1.08 (1.03, 1.13) according to the crude and adjusted models, respectively. For individuals with prediabetes, the ORs (95% CIs) of CVD risk for DII were 1.05 (0.97, 1.14) and 1.11 (1.01, 1.22) according to the crude and adjusted models, respectively. After adjusting for population-based information and hypertension status, the DII appeared to have the highest OR for individuals with prediabetes, and no significant association was found between the DII score and CVD risk in the normoglycemia group. Moreover, the OR of CVD for DII in the uncontrolled diabetes group was 1.06 (0.98, 1.16)*. These results suggest that the DII is more closely associated with the risk of CVDs in prediabetic and diabetic populations, and we should pay more attention to diet control before a person develops diabetes to prevent CVD progression.
Subject(s)
Cardiovascular Diseases , Diet , Inflammation , Nutrition Surveys , Prediabetic State , Humans , Prediabetic State/epidemiology , Prediabetic State/complications , Male , Female , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Middle Aged , Inflammation/epidemiology , Prevalence , Adult , Risk Factors , Incidence , Aged , Diabetes Mellitus/epidemiology , United States/epidemiologyABSTRACT
Objectives: Informal practice (i.e., brief meditation practices incorporated spontaneously into daily activities) may be important for increasing the efficacy and accessibility of meditation-based interventions (MedBIs). However, the facilitators and barriers to engaging in informal practice are largely unknown. The current study aimed to investigate factors associated with the implementation of informal practice. Method: Participants were drawn from a randomized trial testing the effects of 5- versus 15-min daily meditation practice in a 4-week smartphone-delivered meditation training. Qualitative interviews on informal practice were conducted with 17 participants (mean age: 37.12 years; 82.35% female; 52.94% non-Latinx White) following the intervention. Given that prior knowledge on this topic is limited, inductive content analysis was utilized to characterize participants' experiences in relation to implementing informal practice. Results: Four overarching categories emerged from the data, namely (a) reported benefits of informal practice, (b) integration of informal practice, (c) perceived barriers to informal practice, and (d) recommended facilitators of informal practice. Conclusion: This study underscores the importance of addressing barriers and facilitators (e.g., providing personalized app features, reminders, social support, and repeating intervention content) to encourage individuals' informal practice. Findings provide suggestions for methods to increase engagement in informal practice, which may, in turn, increase the accessibility and effectiveness of MedBIs. Preregistration: The larger trial from which the qualitative interview participants were drawn was preregistered through clinicaltrials.gov (NCT05229406) and the Open Science Framework (https://osf.io/fszvj/?view_only=039b14ccbf8848bd99808c983070b635). The qualitative analyses reported here were not preregistered.
ABSTRACT
This study presents an innovative electrostatic spray flame synthesis (ESFS) reactor that combines the advantages of electrostatic spray and flame synthesis for precise spray control and efficient single-step continuous synthesis. To overcome the limitations of conventional ESFS systems, which often suffer from low atomized precursor flux, we successfully demonstrated a high-flux disk electrostatic atomizer coupled low-swirl flame reactor, achieving a precursor flux of up to 30 ml/h about 30 times higher than that of typical ESFS devices. The atomized precursor being rapidly carried away from the burner is undergoing high-temperature pyrolysis and particle formation through lifted premixed turbulent flames. The ESFS system provides extensive control over parameters such as flame temperature, equivalence ratio, residence time, initial droplet sizes, and precursor concentrations. For illustrative purposes, the ESFS system was utilized to synthesize silica nanoparticles, demonstrating the capability of synthesizing nanoparticles with various properties. By manipulating the collection position and height, the particle size has made a substantial leap from the nanoscale to the micrometer level. This remarkable achievement underscores the system's enormous potential for precise particle size regulation and one-step synthesis of complex structured thin films.
ABSTRACT
Calcium ions (Ca2+) play crucial roles in sperm motility and fertilization. The copine (CPNE) family comprises several Ca2+-dependent phospholipid-binding proteins. Of these, CPNE1 is extensively expressed in mammalian tissues; however, its precise role in testicular development and spermatogenesis is yet to be fully characterized. In this study, we used proteomics to analyze testicular biopsies and found that levels of CPNE1 were significantly reduced in patients with non-obstructive azoospermia (defective spermatogenesis) compared to those in patients with obstructive azoospermia (physiological spermatogenesis). In mice, CPNE1 is expressed at various stages of germ cell development and is associated with the Golgi apparatus. Ultimately, CPNE1 is expressed in the flagella of mature sperms. To further examine the role of CPNE1, we developed a Cpne1 knockout mouse model. Analysis showed that the loss of Cpne1 did not impair testicular development, spermatogenesis, or sperm morphology and motility in physiological conditions. When treated with gadolinium (III) chloride or 2-aminoethoxydiphenyl borate, known inhibitors of store-operated Ca2+ entry, Ca2+ signals and sperm motility were significantly compromised in wild-type mice; however, both mechanisms were conserved in KO mice. These results suggested that CPNE1 is dispensable for testicular development, spermatogenesis or sperm motility in physiological conditions. In addition, CPNE1 may represent a target of Ca2+ channel inhibitors and may therefore be implicated in the regulation of Ca2+ signaling and sperm motility.
ABSTRACT
Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.
Subject(s)
CD8-Positive T-Lymphocytes , Cholesterol , Colorectal Neoplasms , Signal Transduction , Transforming Growth Factor beta1 , Colorectal Neoplasms/immunology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Humans , Animals , Cholesterol/metabolism , Mice , Cell Line, Tumor , Transforming Growth Factor beta1/metabolism , Immunologic Memory , Vacuolar Proton-Translocating ATPases/metabolism , Tumor Microenvironment/immunology , Liver X Receptors/metabolism , Hydroxycholesterols/metabolism , Hydroxycholesterols/pharmacology , Pyrrolidines/pharmacology , Smad3 Protein/metabolism , Mice, Inbred C57BL , Carbamates/pharmacologyABSTRACT
Contaminant accumulation in organisms can be influenced by both biological traits and environmental conditions. However, delineating the main factors affecting contaminant burdens in organisms remains challenging. Here, we conducted an initial investigation into the impact of diet and habitat on the accumulation of short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in Indo-Pacific humpback dolphins (2003-2020, n = 128) from the Pearl River Estuary (PRE), a highly polluted estuary in China. The detected levels of SCCPs (5897 ± 3480 ng g-1 lw) and MCCPs (13,960 ± 8285 ng g-1 lw) in blubber samples of humpback dolphin are the highest among recorded values marine mammals. Both SCCPs and MCCPs exhibited biomagnification factor values exceeding 1, suggesting their biomagnification potential within the dolphins and their diet. Quantitative diet analysis using the dolphin fatty acid signatures revealed that humpback dolphins inhabiting the western PRE consumed a larger proportion of carnivorous fish than those from the eastern PRE. However, spatial analysis showed that humpback dolphins in the western PRE contained lower SCCP/MCCP concentrations than those from the eastern PRE. Based on these findings we suggest that, compared to diet differences, spatial variations of SCCPs/MCCPs in humpback dolphins may be predominantly influenced by their space-use strategies, as the eastern PRE is closer to the pollutant discharge source and transfer routes.
ABSTRACT
Β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) is a crucial protease in the production of amyloid-ß (Aß) in Alzheimer's disease (AD) patients. However, the side effects observed in clinical trials of BACE1 inhibitors, including reduction in brain volume and cognitive worsening, suggest that the exact role of BACE1 in AD pathology is not fully understood. To further investigate this, we examined cerebrospinal fluid (CSF) levels of BACE1 and its cleaved product sAPPß that reflects BACE1 activity in the China Aging and Neurodegenerative Disorder Initiative cohort. We found significant correlations between CSF BACE1 or sAPPß levels and CSF Aß40, Aß42, and Aß42/Aß40 ratio, but not with amyloid deposition detected by 18F-Florbetapir PET. Additionally, CSF BACE1 and sAPPß levels were positively associated with cortical thickness in multiple brain regions, and higher levels of sAPPß were linked to increased cortical glucose metabolism in frontal and supramarginal areas. Interestingly, individuals with higher baseline levels of CSF BACE1 exhibited slower rates of brain volume reduction and cognitive worsening over time. This suggests that increased levels and activity of BACE1 may not be the determining factor for amyloid deposition, but instead, may be associated with increased neuronal activity and potentially providing protection against neurodegeneration in AD.
Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Amyloid beta-Peptides , Aspartic Acid Endopeptidases , Brain , Humans , Amyloid Precursor Protein Secretases/cerebrospinal fluid , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/cerebrospinal fluid , Aspartic Acid Endopeptidases/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/cerebrospinal fluid , Male , Aged , Female , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Brain/pathology , Brain/metabolism , Positron-Emission Tomography , Aged, 80 and over , Middle Aged , Cognition/physiology , Biomarkers/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Peptide Fragments/metabolismABSTRACT
Background: Early-onset Alzheimer's disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer's disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated. Objective: Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD. Methods: We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort. Results: We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified: SH3BGRL3, LRP8, and LY6âH, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6âH reduction was confirmed via ELISA, which was consistent with our proteomic results. Conclusions: This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins.
Subject(s)
Alzheimer Disease , Biomarkers , Proteomics , Humans , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Biomarkers/cerebrospinal fluid , Male , Female , Proteomics/methods , Middle Aged , Aged , Machine Learning , Cohort Studies , Age of OnsetABSTRACT
Chemical derivatization is a widely employed strategy in metabolomics to enhance metabolite coverage by improving chromatographic behavior and increasing the ionization rates in mass spectroscopy (MS). However, derivatization might complicate MS data, posing challenges for data mining due to the lack of a corresponding benchmark database. To address this issue, we developed a triple-dimensional combinatorial derivatization strategy for nontargeted metabolomics. This strategy utilizes three structurally similar derivatization reagents and is supported by MS-TDF software for accelerated data processing. Notably, simultaneous derivatization of specific metabolite functional groups in biological samples produced compounds with stable but distinct chromatographic retention times and mass numbers, facilitating discrimination by MS-TDF, an in-house MS data processing software. In this study, carbonyl analogues in human plasma were derivatized using a combination of three hydrazide-based derivatization reagents: 2-hydrazinopyridine, 2-hydrazino-5-methylpyridine, and 2-hydrazino-5-cyanopyridine (6-hydrazinonicotinonitrile). This approach was applied to identify potential carbonyl biomarkers in lung cancer. Analysis and validation of human plasma samples demonstrated that our strategy improved the recognition accuracy of metabolites and reduced the risk of false positives, providing a useful method for nontargeted metabolomics studies. The MATLAB code for MS-TDF is available on GitHub at https://github.com/CaixiaYuan/MS-TDF.
Subject(s)
Metabolomics , Software , Humans , Metabolomics/methods , Lung Neoplasms/metabolism , Pyridines/chemistryABSTRACT
The classification system and the higher level phylogenetic relationships of Pentatomomorpha, the second largest infraorder of Heteroptera (Insecta: Hemiptera), have been debated and remain controversial over decades. In particular, the placement and phylogenetic relationship of Idiostoloidea are not well resolved, which hampers a better understanding of the evolutionary history of Pentatomomorpha. In this study, for the first time, we reported the complete mitochondrial genome for two narrowly distributed families of Idiostoloidea (including Idiostolidae and Henicocoridae), respectively. The length of the mitochondrial genome of Monteithocoris hirsutus and Henicocoris sp. is 16,632 and 16,013 bp, respectively. The content of AT is ranging from 75.15% to 80.48%. The mitogenomic structure of Idiostoloidea is highly conservative and there are no gene arrangements. By using the Bayesian inference, maximum likelihood, and Bayesian site-heterogeneous mixture model, we inferred the phylogenetic relationships within Pentatomomorpha and estimated their divergence times based on concatenated mitogenomes and nuclear ribosomal genes. Our results support the classification system of six superfamilies within Pentatomomorpha and confirm the monophyletic groups of each superfamily, with the following phylogenetic relationships: (Aradoidea + (Pentatomoidea + (Idiostoloidea + (Coreoidea + (Pyrrhocoroidea + Lygaeoidea))))). Furthermore, estimated divergence times revealed that most pentatomomorphan superfamilies and families diverged during the Late Jurassic to Early Cretaceous, which coincides with the explosive radiation of angiosperms.
ABSTRACT
This paper reports results of a hybrid effectiveness-implementation randomized trial that systematically varied levels of human oversight required to support implementation of a digital medicine intervention for persons with mild to moderate alcohol use disorder (AUD). Participants were randomly assigned to three groups representing possible digital health support models within a health system: self-monitored use (n = 185), peer-supported use (n = 186), or a clinically integrated model (n = 187). Across all three groups, percentage of risky drinking days dropped from 38.4% at baseline (95%CI [35.8%, 41%]) to 22.5% (19.5%, 25.5%) at 12 months. The clinically integrated group showed significant improvements in mental health quality of life compared to the self-monitoring group (p = 0.011). However, higher rates of attrition in the clinically integrated group warrants consideration in interpreting this result. Results suggest that making a self-guided digital intervention available to patients may be a viable option for health systems looking to promote alcohol risk reduction.
ABSTRACT
Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.
Subject(s)
Allergens , Caseins , Mice, Inbred BALB C , Th1 Cells , Th2 Cells , Animals , Humans , Mice , Th2 Cells/immunology , Caseins/immunology , Caseins/chemistry , Th1 Cells/immunology , Allergens/immunology , Allergens/chemistry , Caco-2 Cells , Female , Glycosylation , Cattle , Homeostasis , Food Hypersensitivity/immunologyABSTRACT
We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.
Subject(s)
ATP Binding Cassette Transporter 1 , CD68 Molecule , Mice, Inbred C57BL , Mice, Transgenic , Animals , ATP Binding Cassette Transporter 1/metabolism , ATP Binding Cassette Transporter 1/genetics , Female , Mice , Group II Phospholipases A2/metabolism , Group II Phospholipases A2/genetics , PPAR gamma/metabolism , Cholesterol, HDL/blood , Cholesterol, HDL/metabolism , Lung/metabolism , Lung/pathology , Antigens, Differentiation, Myelomonocytic/metabolism , Antigens, CD/metabolism , Antigens, CD/genetics , Spleen/metabolism , Bone Marrow Transplantation , Humans , Lipids/bloodABSTRACT
We investigated whether informal meditation practice (i.e., self-reported application of meditative techniques outside a period of formal meditation) was associated with outcomes in smartphone-based loving-kindness and compassion training. Meditation-naïve participants (n = 351) with clinically elevated symptoms completed measures of psychological distress, loneliness, empathy, and prosociality at baseline and following a two-week intervention. Informal practice, psychological distress, and loneliness were also assessed daily. Steeper increases in informal practice had small associations with pre-post improvements in distress (r = -.18, p = .008) and loneliness (r = -.19, p = .009) but not empathy or prosociality. Using a currently recommended approach for establishing cross-lagged effects in longitudinal data (latent curve model with structured residuals), higher current-day informal practice was associated with decreased next-day distress with a very small effect size (ßs = -.06 to -.04, p = .018) but not decreased next-day loneliness. No cross-lagged associations emerged from distress or loneliness to informal practice. Findings suggest that further investigation into a potential causal role of informal practice is warranted. Future studies experimentally manipulating informal practice are needed.
Subject(s)
Empathy , Loneliness , Meditation , Humans , Male , Female , Loneliness/psychology , Adult , Meditation/psychology , Middle Aged , Psychological Distress , Young Adult , Love , Mindfulness , Smartphone , Stress, Psychological/psychology , Stress, Psychological/therapyABSTRACT
BACKGROUND: Oral squamous cell carcinoma (OSCC) is originating from oral mucosal epithelial cells. Autophagy plays a crucial role in cancer treatment by promoting cellular self-degradation and eliminating damaged components, thereby enhancing therapeutic efficacy. In this study, we aim to identify a novel autophagy-related biomarker to improve OSCC therapy. METHODS: We firstly utilized Cox and Lasso analyses to identify that ATF6 is associated with OSCC prognosis, and validated the results by Kaplan-Meier survival analysis. We further identified the downstream pathways and related genes by enrichment analysis and WGCNA analysis. Subsequently, we used short interfering RNA to investigate the effects of ATF6 knockdown on proliferation, migration, apoptosis, and autophagy in SCC-9 and SCC-15 cells through cell viability assay, transwell assay, EdU incorporation assay, flow cytometry analysis, western blot analysis and immunofluorescence analysis, etc. RESULTS: Bioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. In vitro studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis. CONCLUSION: We propose that ATF6 holds potential as a prognostic biomarker linked to autophagy in OSCC. This study provides valuable clues for further exploration of targeted therapy against OSCC.
Subject(s)
Activating Transcription Factor 6 , Autophagy , Biomarkers, Tumor , Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Mouth Neoplasms , Humans , Activating Transcription Factor 6/genetics , Activating Transcription Factor 6/metabolism , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Cell Line, Tumor , Autophagy/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Apoptosis/genetics , Kaplan-Meier EstimateABSTRACT
Cascade radical cyclization constitutes an atom- and step-economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox-active metal catalysts has recently shown robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium-based N-heterocyclic carbene (NHC)-boryl radical is capable of catalyzing cascade cyclization reactions in both intra- and intermolecular pathways, assembling [5,5] fused bicyclic and [6,6,6] fused tricyclic molecules, respectively. The catalytic reactions start with the chemo- and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal [3+2] or an intermolecular [2+2+2] cycloaddition process to construct bicyclo[3.3.0]octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a ß-elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control.
ABSTRACT
Tobacco polysaccharides were extracted by hot water extraction, and purified and separated using DEAE-52 cellulose chromatography columns, and three purified polysaccharide fractions, YCT-1, YCT-2, and YCT-3, were finally obtained. The physicochemical properties of the three fractions were analyzed by ultraviolet spectroscopy, high-performance liquid chromatography and high-performance gel chromatography. The in vitro antioxidant activity of tobacco polysaccharides was compared among different fractions by using DPPH radical, hydroxyl radical scavenging assay and potassium ferricyanide method. The in vitro hypoglycemic activity was compared using α-amylase and α-glucosidase activity inhibition assay. And the in vitro hypolipidemic activity were investigated by using pancreatic lipase activity inhibition assay and HepG-2 intracellular lipid accumulation assay. All the results showed that the constituent monosaccharides of the three tobacco polysaccharide fractions were similar, but the molar percentages of each monosaccharide were different. The average molecular weights of the three components were 27,727 Da, 27,587 Da, and 66,517 Da, respectively, and the scavenging activities on DPPH radicals and hydroxyl radicals were at a high level with good quantitative-effect relationships. The reducing power were much lower than that of the positive control VC, and the three polysaccharide fractions had a weak inhibitory ability on α-amylase activity, but showed excellent inhibitory ability on α-glucosidase and pancreatic lipase activity. In addition, the results of cellular experiments showed that all three fractions were able to inhibit lipid over-accumulation in HepG-2 cells by increasing the mRNA expression levels of PPAR-α, CPT-1A, and CYP7A1 genes, and the tobacco polysaccharide YCT-3 showed the best effect. The mechanism by which YCT-3 ameliorated the over-accumulation of intracellular lipids in HepG-2 cells was found to be related to its influence on the expression of miR-155-3p and miR-17-3p in the exosomes of HepG-2 cells.
ABSTRACT
Background: Insects represent one of the most diverse groups in the organism world with extremely rich species and morphological diversity, playing important roles in natural and city ecosystems. Regional compilation of insect species lists helps to clarify the richness of insect species in a region, enhances our understanding the structure and function of a local ecosystem and promotes the protection and development of insect resources. Moreover, it also serves as a valuable reference for cities with small area, large population and high urbanisation like Macao. Macao (Macau) Special Administrative Region (SAR) is situated at the Pearl River Delta on the southeast coast of mainland China. With urban development accelerating at great rate in a quite restricted area, Macao still has rich fauna, within which the insect diversity is surprisingly high. New information: In this study, we systematically sorted out major references items of manuals or handbooks, monographs, articles, dissertations, official websites and other publicly available information sources about the insects recorded in Macao and, thus, generated a checklist of 15 orders, 166 families, 868 genera, 1,339 species and 118 subspecies. During this process, the preliminarily summarised list was re-examined to eliminate synonyms and invalid species, based on many more extensive literature reviews. Besides, spelling errors of scientific names, authors and years were corrected. Meanwhile, the catalogue revealed a different composition pattern of species diversity between orders from those of the world and China. Even based on the most conservative estimates, the number of insect species in Macao should not be lower than 3,340 species, which hints at the necessity of deeper investigations with adequate collecting in the future to achieve more comprehensive recognition and understanding of Macao's insect biodiversity.
ABSTRACT
PURPOSE: To look at the diagnostic value of the CELSR receptor 3 (CELSR3) gene in head and neck squamous cell carcinoma (HNSCC) and its effect on tumor immune invasion, which is important for enhancing HNSCC treatment. METHODS: Several bioinformatics tools were employed to investigate CELSR3's putative oncogenic pathway in HNSCC, and datasets from The Tumor Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Gene Expression Profile Interaction Analysis (GEPIA) and LinkedOmics were extracted and evaluated. CELSR3 has been linked to tumor immune cell infiltration, immunological checkpoints, and immune-related genes. CELSR3's putative roles were investigated using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and pathway enrichment analysis. The expression level of CELSR3 in HNSCC tissues and cells was detected by RT-qPCR. The effects of CELSR3 on proliferation of HNSCC cells were detected by CCK-8 assay. RESULTS: CELSR3 was shown to be expressed differently in different types of cancer and normal tissues. CELSR3 gene expression was linked to pN-stage and pM-stage. Patients with high CELSR3 expression also have a well prognosis. CELSR3 expression was found to be an independent predictive factor for HNSCC in both univariate and multivariate Cox regression analyses. We discovered the functional network of CELSR3 in HNSCC using GO and KEGG analysis. CELSR3 expression levels were found to be favorably associated with immune cell infiltration levels. Furthermore, CELSR3 expression levels were significantly correlated with the expression levels of many immune molecules, such as MHC genes, immune activation genes, chemokine receptors, and chemokines. CELSR3 is highly expressed in HNSCC tissues and cells. CELSR3 overexpression significantly inhibited the proliferation of HNSCC cells. CELSR3 expression may affect the immune microenvironment and, as a result, the prognosis of HNSCC. CONCLUSION: CELSR3 expression is elevated in HNSCC tumor tissues, and high CELSR3 expression is associated with well prognosis, which inhibited the proliferation of NHSCC cells. CELSR3 has the potential to influence tumor formation by controlling tumor-infiltrating cells in the tumor microenvironment (TME). As a result, CELSR3 may have diagnostic significance in HNSCC.
Subject(s)
Biomarkers, Tumor , Cadherins , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Female , Humans , Male , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Prognosis , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Cadherins/genetics , Cadherins/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolismABSTRACT
Palaeogeological events and climate oscillations profoundly impact the demographics and distributions of small-range species, increasing the extinction risk. The largest water strider worldwide, Gigantometra gigas (Hemiptera: Gerridae), exhibits restricted distributions in Vietnam and southern China. Herein, we generated three genomic datasets (mitogenomes, 146 nuclear protein-coding genes and single nucleotide polymorphisms) with ecological niche modelling (ENM) to explicitly test whether the present-day distribution of G. gigas actually resulted from geographical and climatic effects. We found that the origin of this largest water strider reached the divergence time of the genus within Gerridae, providing a greater opportunity to explore its response to geographic movements. The right-lateral motion of the Red River Fault facilitated the divergence of two phylogeographic lineages, resulting in the "north-south component" genetic pattern in G. gigas. The Hainan and southeast Vietnam populations of the southern linage were completely separated by the Beibu Gulf but exhibited similar genetic compositions, confirming that Hainan had a continental origin and that Hainan Island joined with the Indo-China Peninsula to promote gene exchange among populations. Additionally, we noticed the low genetic diversity but long demographic history of the northern lineage, which displayed population dynamics opposite to those of other organisms. Integrating the demographic changes and ENM findings revealed that suitable habitat contraction and rapid demographic decline during the Last Glacial Maximum (LGM) triggered the low genetic diversity of the northern lineage. Overall, the demographic history of the largest water strider was mainly shaped by geographical features, and first provided evidence from the phylogeographic perspective of aquatic insects to support the hypothesis of Hainan Island shifting.