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1.
Immunity ; 56(11): 2492-2507.e10, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37890481

ABSTRACT

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.


Subject(s)
Lipid Metabolism , Nucleotidyltransferases , Animals , Mice , Liver X Receptors/metabolism , Nucleotidyltransferases/metabolism , DNA , Nucleotides, Cyclic/metabolism , Immunity, Innate
2.
J Immunol ; 211(9): 1406-1417, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37695673

ABSTRACT

Activation of the mitochondrial antiviral signaling (MAVS) adaptor, also known as IPS-1, VISA, or Cardif, is crucial for antiviral immunity in retinoic acid-inducible gene I (RIG-I)-like receptor signaling. Upon interacting with RIG-I, MAVS undergoes K63-linked polyubiquitination by the E3 ligase Trim31, and subsequently aggregates to activate downstream signaling effectors. However, the molecular mechanisms that modulate MAVS activation are not yet fully understood. In this study, the mitochondrial solute carrier SLC25A23 was found to attenuate type I IFN antiviral immunity using genome-wide CRISPR/Cas9 screening. SLC25A23 interacts with Trim31, interfering with its binding of Trim31 to MAVS. Indeed, SLC25A23 downregulation was found to increase K63-linked polyubiquitination and subsequent aggregation of MAVS, which promoted type I IFN production upon RNA virus infection. Consistently, mice with SLC25A23 knockdown were more resistant to RNA virus infection in vivo. These findings establish SLC25A23 as a novel regulator of MAVS posttranslational modifications and of type I antiviral immunity.

3.
Hum Hered ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830343

ABSTRACT

Introduction Recessive mutations in the CAPN3 gene can lead to Limb-girdle muscular dystrophy Recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. Methods We performed targeted next-generation sequencing of all exons of the CAPN3 gene in four patients with sporadic LGMD and further analyzed the effects of the novel identified variant using various software tools. Results We found 5 variants in CAPN3 gene in four patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. Discussion Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

4.
J Biol Chem ; 299(7): 104873, 2023 07.
Article in English | MEDLINE | ID: mdl-37257820

ABSTRACT

Dysregulation of long noncoding RNAs (lncRNAs) contributes to tumorigenesis by modulating specific cancer-related pathways, but the roles of N6-methyladenosine (m6A)-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profiles in 18 pairs of NPC and normal tissues as well as in ten paired samples from NPC with or without post-treatment metastases. We discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis both in vitro and in vivo. Mechanistically, by using RNA pull-down assay combined with mass spectrometry, we found that LINC00839 interacted directly with the transcription factor, TATA-box binding protein associated factor (TAF15). Besides, chromatin immunoprecipitation and dual-luciferase report assays demonstrated that LINC00839 coordinated the recruitment of TAF15 to the promoter region of amine oxidase copper-containing 1 (AOC1), which encodes a secreted glycoprotein playing vital roles in various cancers, thereby activating AOC1 transcription in trans. In this study, potential effects of AOC1 in NPC progression were first proposed. Moreover, ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, we showed that silencing vir-like m6A methyltransferase-associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) attenuated the expression level and RNA stability of LINC00839 in an m6A-dependent manner. Taken together, our study unveils a novel oncogenic VIRMA/IGF2BP1-LINC00839-TAF15-AOC1 axis and highlights the significance and prognostic value of LINC00839 expression in NPC carcinogenesis.


Subject(s)
Nasopharyngeal Neoplasms , RNA, Long Noncoding , TATA-Binding Protein Associated Factors , Humans , Amines , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Oxidoreductases/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , TATA-Binding Protein Associated Factors/genetics , TATA-Binding Protein Associated Factors/metabolism
5.
Anal Chem ; 96(1): 67-75, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38153001

ABSTRACT

Origins of pH effects on the kinetics of electrocatalytic reactions involving the transfer of both protons and electrons, including the hydrogen evolution reaction (HER) considered in this study, are heatedly debated. By taking the HER at Au(111) in acid solutions of different pHs and ionic concentrations as the model systems, herein, we report how to derive the intrinsic kinetic parameters of such reactions and their pH dependence through the measurement of j-E curves and the corresponding kinetic simulation based on the Frumkin-Butler-Volmer theory and the modified Poisson-Nernst-Planck equation. Our study reveals the following: (i) the same set of kinetic parameters, such as the standard activation Gibbs free energy, charge transfer coefficient, and Gibbs adsorption energy for Had at Au(111), can simulate well all the j-E curves measured in solutions with different pH and temperatures; (ii) on the reversible hydrogen electrode scale, the intrinsic rate constant increases with the increase of pH, which is in contrast with the decrease of the HER current with the increase of pH; and (iii) the ratio of the rate constants for HER at Au(111) in x M HClO4 + (0.1 - x) M NaClO4 (pH ≤ 3) deduced before properly correcting the electric double layer (EDL) effects to the ones estimated with EDL correction is in the range of ca. 10 to 40, and even in a solution of x M HClO4 + (1 - x) M NaClO4 (pH ≤ 2) there is a difference of ca. 5× in the rate constants without and with EDL correction. The importance of proper correction of the EDL effects as well as several other important factors on unveiling the intrinsic pH-dependent reaction kinetics are discussed to help converge our analysis of pH effects in electrocatalysis.

6.
Anal Chem ; 96(2): 676-684, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38173079

ABSTRACT

Identification of the phosphatidylserine (PS) discrepancies occurring on the cellular membrane during apoptotic processes is of the utmost importance. However, monitoring the quantity of PS molecules in real-time at a single-cell level currently remains a challenging task. Here, we demonstrate this objective by leveraging the specific binding and reversible interaction exhibited by the zinc(II) dipyridinamine complex (ZnDPA) with PS. Lipoic acid-functionalized ZnDPA (LP-ZnDPA) was subsequently immobilized onto the surface of an atomic force microscopy cantilever to form a force probe, ALP-ZnDPA, enabling a PS-specific dynamic imaging and detection mode. By utilizing this technique, we can not only create a heat map of the expression level of PS with submicron resolution but also quantify the number of molecules present on a single cell's surface with a detection limit of 1.86 × 104 molecules. The feasibility of the proposed method is demonstrated through the analysis of PS expression levels in different cancer cell lines and at various stages of paclitaxel-induced apoptosis. This study represents the first application of a force probe to quantify PS molecules on the surface of individual cells, providing insight into dynamic changes in PS content during apoptosis at the molecular level and introducing a novel dimension to current detection methodologies.


Subject(s)
Phosphatidylserines , Single Molecule Imaging , Phosphatidylserines/chemistry , Apoptosis , Cell Membrane/metabolism , Microscopy, Atomic Force/methods , Spectrum Analysis
7.
Small ; : e2400149, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38528389

ABSTRACT

Layered Na2FePO4F (NFPF) cathode material has received widespread attention due to its green nontoxicity, abundant raw materials, and low cost. However, its poor inherent electronic conductivity and sluggish sodium ion transportation seriously impede its capacity delivery and cycling stability. In this work, NFPF by Ti doping and conformal carbon layer coating via solid-state reaction is modified. The results of experimental study and density functional theory calculations reveal that Ti doping enhances intrinsic conductivity, accelerates Na-ion transport, and generates more Na-ion storage sites, and pyrolytic carbon from polyvinylpyrrolidone (PVP) uniformly coated on the NFPF surface improves the surface/interface conductivity and suppresses the side reactions. Under the combined effect of Ti doping and carbon coating, the optimized NFPF (marked as 5T-NF@C) exhibits excellent electrochemical performance, with a high capacity of 108.4 mAh g-1 at 0.2C, a considerable capacity of 80.0 mAh g-1 even at high current density of 10C, and a high capacity retention rate of 81.8% after 2000 cycles at 10C. When assembled into a full cell with a hard carbon anode, 5T-NF@C also show good applicability. This work indicates that co-modification of Ti doping and carbon coating makes NFPF achieve high rate and long cycle performance for sodium-ion batteries.

8.
FEMS Yeast Res ; 242024 Jan 09.
Article in English | MEDLINE | ID: mdl-38592962

ABSTRACT

How mutations in mitochondrial electron transport chain (ETC) proteins impact the cell cycle of Candida albicans was investigated in this study. Using genetic null mutants targeting ETC complexes I (CI), III (CIII), and IV (CIV), the cell cycle stages (G0/G1, S phase, and G2/M) were analyzed via fluorescence-activated cell sorting (FACS). Four CI null mutants exhibited distinct alterations, including extended S phase, shortened G2/M population, and a reduction in cells size exceeding 10 µM. Conversely, CIII mutants showed an increased population in G1/G0 phase. Among four CI mutants, ndh51Δ/Δ and goa1Δ/Δ displayed aberrant cell cycle patterns correlated with previously reported cAMP/PKA downregulation. Specifically, nuo1Δ/Δ and nuo2Δ/Δ mutants exhibited increased transcription of RIM15, a central hub linking cell cycle with nutrient-dependent TOR1 and cAMP/PKA pathways and Snf1 aging pathway. These findings suggest that suppression of TOR1 and cAMP/PKA pathways or enhanced Snf1 disrupts cell cycle progression, influencing cell longevity and growth among CI mutants. Overall, our study highlights the intricate interplay between mitochondrial ETC, cell cycle, and signaling pathways.


Subject(s)
Candida albicans , Mitochondria , Candida albicans/physiology , S Phase , Mitochondria/metabolism , Cell Cycle , Cell Division
9.
Eur Radiol ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38355987

ABSTRACT

OBJECTIVES: Total-body PET/CT scanners with long axial fields of view have enabled unprecedented image quality and quantitative accuracy. However, the ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Therefore, we attempted to generate CT-free attenuation-corrected (CTF-AC) total-body PET images through deep learning. METHODS: Based on total-body PET data from 122 subjects (29 females and 93 males), a well-established cycle-consistent generative adversarial network (Cycle-GAN) was employed to generate CTF-AC total-body PET images directly while introducing site structures as prior information. Statistical analyses, including Pearson correlation coefficient (PCC) and t-tests, were utilized for the correlation measurements. RESULTS: The generated CTF-AC total-body PET images closely resembled real AC PET images, showing reduced noise and good contrast in different tissue structures. The obtained peak signal-to-noise ratio and structural similarity index measure values were 36.92 ± 5.49 dB (p < 0.01) and 0.980 ± 0.041 (p < 0.01), respectively. Furthermore, the standardized uptake value (SUV) distribution was consistent with that of real AC PET images. CONCLUSION: Our approach could directly generate CTF-AC total-body PET images, greatly reducing the radiation risk to patients from redundant anatomical examinations. Moreover, the model was validated based on a multidose-level NAC-AC PET dataset, demonstrating the potential of our method for low-dose PET attenuation correction. In future work, we will attempt to validate the proposed method with total-body PET/CT systems in more clinical practices. CLINICAL RELEVANCE STATEMENT: The ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Our CT-free PET attenuation correction method would be beneficial for a wide range of patient populations, especially for pediatric examinations and patients who need multiple scans or who require long-term follow-up. KEY POINTS: • CT is the main source of radiation in PET/CT imaging, especially for total-body PET/CT devices, and reduced radiopharmaceutical doses make the radiation burden from CT more obvious. • The CT-free PET attenuation correction method would be beneficial for patients who need multiple scans or long-term follow-up by reducing additional radiation from redundant anatomical examinations. • The proposed method could directly generate CT-free attenuation-corrected (CTF-AC) total-body PET images, which is beneficial for PET/MRI or PET-only devices lacking CT image poses.

10.
Inorg Chem ; 63(18): 8329-8335, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38648287

ABSTRACT

Most of the porous materials used for acetylene/carbon dioxide separation have the problems of poor stability and high energy requirements for regeneration, which significantly hinder their practical application in industries. Here, we report a novel calcium-based metal-organic framework (NKM-123) with excellent chemical stability against water, acids, and bases. Additionally, it has exceptional thermal stability, retaining its structural integrity at temperatures up to 300 °C. This material exhibits promising potential for separating C2H2 and CO2 gases. Furthermore, it demonstrates an adsorption heat of 29.3 kJ mol-1 for C2H2, which is lower than that observed in the majority of MOFs used for C2H2/CO2 separations. The preferential adsorption of C2H2 over that of CO2 is confirmed by dispersion-corrected density functional theory (DFT-D) calculations. In addition, the potential of industrial feasibility of NKM-123 for C2H2/CO2 separation is confirmed by transient breakthrough tests. The robust cycle performance and structural stability of NKM-123 during multiple breakthrough tests show great potential in the industrial separation of light hydrocarbons.

11.
Nutr Metab Cardiovasc Dis ; 34(2): 307-316, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37949714

ABSTRACT

BACKGROUND AND AIMS: To explore the relationship between body mass index (BMI), chinese visceral adiposity index (CVAI) and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in populations with different body types defined by BMI. METHODS AND RESULTS: 24 191 participants from the Jinchang cohort were involved in the prospective cohort study with a 2.3-year follow-up. Information from epidemiological investigations, comprehensive health examinations and biochemical examinations was collected. MASLD was assessed by abdominal ultrasonography. BMI and CVAI were calculated using recognized formulas. Cox regressions, Restricted cubic spline (RCS) and Receiver operating characteristic (ROC) analysis were performed. The risk of MASLD increased with the increase in BMI and CVAI (Ptrend <0.001), and there was a nonlinear dose-response relationship. In the total population, BMI and CVAI increased the risk of MASLD with adjusted HR (95%CI) of 1.097 (1.091-1.104) and 1.024 (1.023-1.026), respectively. The results were similar in the lean and overweight/obese groups. There was also a nonlinear relationship between CVAI and MASLD (Pnon-linearity<0.001), no matter in which group. The area under the curve of CVAI was significantly higher than that of BMI in females with different body types, and the areas in the whole females were 0.802 (95%CI: 0.787-0.818) and 0.764 (95%CI: 0.747-0.780), respectively. There was no significant difference in the ability of BMI and CVAI to predict MASLD in all-sex and males, either in lean or overweight/obese groups. CONCLUSIONS: CVAI and BMI were independently associated with the risk of MASLD regardless of body types defined by BMI, and CVAI showed better diagnostic ability for MASLD in females.


Subject(s)
Fatty Liver , Metabolic Diseases , Female , Male , Humans , Body Mass Index , Incidence , Overweight , Prospective Studies , Somatotypes , Obesity/diagnosis , Obesity/epidemiology , China/epidemiology
12.
Cell Mol Life Sci ; 80(5): 119, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37029227

ABSTRACT

Chronic stress significantly elevates the expression levels of various neurotransmitters in the tumour microenvironment, thereby promoting the cell growth and metastasis of lung adenocarcinoma (LUAD). However, the role of chronic stress in the progression of LUAD remains unclear. In this study, we found that chronic restraint stress increases the levels of the neurotransmitter acetylcholine (ACh), and the α5-nicotinic acetylcholine receptor (α5-nAChR) and decreased fragile histidine triad (FHIT) expression in vivo. Crucially, the increased ACh levels promoted LUAD cell migration and invasion via modulation of the α5-nAChR/DNA methyltransferase 1 (DNMT1)/FHIT axis. In a chronic unpredictable stress (CUMS) mouse model, chronic stress promotes tumour development, accompanied by changes in α5-nAChR, DNMT1, FHIT, and vimentin. Together, these findings reveal a novel chronic stress-mediated LUAD signalling pathway: chronic stress enforces lung adenocarcinoma cell invasion and migration via the ACh/α5-nAChR/FHIT axis, which could be a potential therapeutic target for chronic stress-related LUAD.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Receptors, Nicotinic , Animals , Mice , Nicotine/pharmacology , Acetylcholine/pharmacology , Receptors, Nicotinic/genetics , Signal Transduction , Lung Neoplasms/pathology , Cell Line, Tumor , Tumor Microenvironment
13.
BMC Pulm Med ; 24(1): 94, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38395894

ABSTRACT

BACKGROUND: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. METHODS: This retrospective cohort study included 248 children with asthma (aged 4-11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test. RESULTS: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082-2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365-0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170-2.305) and with worse asthma control (OR 3.893, 95% CI 1.699-8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. CONCLUSIONS: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.


Subject(s)
Anti-Asthmatic Agents , Asthma , Humans , Child , Anti-Asthmatic Agents/therapeutic use , Nitric Oxide , Retrospective Studies , Administration, Inhalation , Asthma/drug therapy , Adrenal Cortex Hormones/therapeutic use , Drug Therapy, Combination
14.
Article in English | MEDLINE | ID: mdl-38886247

ABSTRACT

OBJECTIVE: To investigate the effect of urinary PAHs on MAFLD. METHODS: The study included 3,136 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2016. Among them, 1,056 participants were diagnosed with MAFLD and were designated as the case group. The analysis of the relationship between monohydroxy metabolites of seven PAHs in urine and MAFLD was carried out using logistic regression and Bayesian kernel regression (BKMR) models. RESULTS: In single-pollutant models, the concentration of 2-hydroxynaphthalene (2-OHNAP) was positively correlated with MAFLD (OR = 1.47, 95% CI 1.18, 1.84), whereas 3-hydroxyfluorene (3-OHFLU) and 1-hydroxypyrene (1-OHPYR) demonstrated a negative correlation with MAFLD (OR = 0.59, 95% CI 0.48 0.73; OR = 0.70, 95% CI 0.55, 0.89). Conversely, in multi-pollutant models, 2-OHNAP, 2-hydroxyfluorene (2-OHFLU), 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene (2&3-OHPHE) displayed positive correlations with MAFLD (OR = 6.17, 95% CI 3.15, 12.07; OR = 2.59, 95% CI 1.37, 4.89). However, 3-OHFLU and 1-OHPYR continued to exhibit negative correlations with MAFLD (OR = 0.09, 95% CI 0.05, 0.15; OR = 0.62, 95% CI 0.43, 0.88). Notably, the BKMR analysis mixtures approach did not indicate a significant joint effect of multiple PAHs on MAFLD, but identified interactions between 3-OHFLU and 2-OHFLU, 1-OHPYR and 2-OHFLU, and 1-OHPYR and 3-OHFLU. CONCLUSION: No significant association was found between mixed PAHs exposure and the risk of MAFLD. However, interactions were observed between 3-OHFLU and 2-OHFLU. Both 2-OHFLU and 2&3-OHPHE exposure are significant risk factors for MAFLD, whereas 3-OHFLU is a key protective factor for the disease.

15.
Biochem Genet ; 62(1): 1-17, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37266876

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-associated death in the world. However, due to the complexity of HCC, it is urgent for us to find a reliable and accurate biomarker for HCC gene therapy.TopBP1-interacting checkpoint and replication regulator (TICRR), known as Treslin in vertebrate and sld3 in yeast, is involved in the tumorigenesis, progression, matastasis, diagnosis, and predicting prognosis of HCC. Disappointingly, the mechanism of TICRR expression in HCC is still not described in detail and requires further analysis. In this study, TCGA ( www.tcga-data.nci.nih.gov/tcga/ ) datasets and GEO ( www.ncbi.nlm.nih.gov/geo ) datasets were used to analyze the expression of TICRR in HCC, the relevance of TICRR mRNA expression and clinicopathological characteristics in patients with HCC, and the relationship between TICRR expression and immune infiltration level in Patients with HCC. Based on MethSurv database, the impact of TICRR in patients with HCC was investigated. In addition, GO/KEGG enrichment analysis of TICRR co-expression was performed using the R package. TICRR was found drastically highly expressed in a variety of cancer types including HCC.ROC curve analysis showed that TICRR had higher accuracy in predicting HCC compared with AFP. The expression level of TICRR was marked positively correlated with tumor stage and prognosis in Patients with HCC.GO/KEGG enrichment analysis showed that TICRR was associated with cell division and cell cycle as well as p53 signaling pathway. In addition, patients with high TICRR methylation of cg05841809, cg09403165, and cg03312532 CpG sites were significantly correlated with poor prognosis of HCC. This study demonstrated that increased TICRR expression in HCC might play an important role in the tumorigenesis, progression, diagnosis, and predicting prognosis of HCC. Therefore, TICRR might be used as a promising diagnostic and prognostic biomarker for HCC gene therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Carcinogenesis , Computational Biology , Biomarkers , Cell Cycle Proteins
16.
Nano Lett ; 23(3): 835-842, 2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36625647

ABSTRACT

Fractals are quite normal in nature. However, fractal self-assembly of organic semiconductors remains challenging. Herein, we develop a facile solution assembly route to access organic microwires (MWs) comprising an oligo(p-phenylenevinylene) derivative (OPV-A) with and without branching. Instead of kinetically controlled ß-OPV-A microrods (MRs), thermodynamically favored α-OPV-A gives fractal branching MW patterns. As-prepared 9,10-dicyanoanthracene (DCA) alloyed assemblies function as seeds to allow for the heteroepitaxial growth of branching α-OPV-A MWs via either coassembly or two-step seeded growth. Consequently, fractal MWs with single- and multisite growth were both achieved, accompanied by tailorable branching densities and hierarchies. Thermodynamic control and a well-matched epitaxial relationship should be crucial to the formation of fractal MW patterns. Importantly, the aligned α-OPV-A MW array functions as a multichannel optical gain medium and exhibits low-threshold amplified spontaneous emission (ASE). The present work deepens the research into fractal self-assembly of functional organic semiconductors.

17.
J Pediatr Nurs ; 75: 180-186, 2024.
Article in English | MEDLINE | ID: mdl-38163421

ABSTRACT

BACKGROUND: Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. METHODS: We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal-Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. FINDINGS: Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. DISCUSSION: The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. APPLICATION TO PRACTICE: We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators.


Subject(s)
Nursing Research , Translational Research, Biomedical , Humans , Surveys and Questionnaires , China , Cognition
18.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673937

ABSTRACT

As a fruit tree with great economic value, apple is widely cultivated in China. However, apple leaf spot disease causes significant damage to apple quality and economic value. In our study, we found that MdMYB6-like is a transcription factor without auto-activation activity and with three alternative spliced variants. Among them, MdMYB6-like-ß responded positively to the pathogen infection. Overexpression of MdMYB6-like-ß increased the lignin content of leaves and improved the pathogenic resistance of apple flesh callus. In addition, all three alternative spliced variants of MdMYB6-like could bind to the promoter of MdBGLU H. Therefore, we believe that MdMYB6-like plays an important role in the infection process of the pathogen and lays a solid foundation for breeding disease-resistant cultivars of apple in the future.


Subject(s)
Alternaria , Disease Resistance , Malus , Transcription Factors , Alternaria/pathogenicity , Alternaria/genetics , Alternative Splicing , Disease Resistance/genetics , Gene Expression Regulation, Plant , Malus/microbiology , Malus/genetics , Malus/metabolism , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Leaves/microbiology , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
19.
J Sci Food Agric ; 104(10): 6108-6117, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38445510

ABSTRACT

BACKGROUND: Excessive NaCl intake in liquid and semi-solid food (e.g. soup, hot pot base, sauce) poses a high risk to human health, and reducing NaCl intake is a major concern for global health. RESULTS: Using the generalized Labeled Magnitude Scale (gLMS) method, the study verified the possibility of sodium reduction through oil addition. The compromised acceptance threshold (CAT) and hedonic rejection threshold (HRT) were determined. The gLMS results showed that the saltiness intensity of samples containing 0.36% NaCl and 2.29% sunflower seed oil was significantly higher than that of samples containing only 0.36% NaCl (P < 0.05). CAT and HRT results indicated that by adding 3.59% sunflower oil, the NaCl content could be reduced to a minimum of 0.14% without causing sensory rejection in bone broth samples. The quantitative descriptive analysis method was used to determine the effects of NaCl and oil concentrations on the sensory attributes of bone broth samples. Furthermore, it was used to analyze the consumer acceptability drivers in combination with the hedonic scale to optimize the formulation of reduced-salt bone broth products. Notably, sample E (0.36% NaCl, 2.29% fat) not only had a significant salt reduction effect with a 20% decrease in NaCl, but also had improved overall acceptability. CONCLUSION: This study provides theoretical guidance for designing salt-reduction cuisine within the catering and food industries, including bone broth and hot pot bases. © 2024 Society of Chemical Industry.


Subject(s)
Consumer Behavior , Taste , Humans , Adult , Sunflower Oil/chemistry , Female , Male , Food Additives/analysis , Food Additives/chemistry , Sodium Chloride/analysis , Sodium Chloride/chemistry , Young Adult , Middle Aged , Sodium Chloride, Dietary/analysis , Bone and Bones/chemistry
20.
J Youth Adolesc ; 53(1): 159-170, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37794285

ABSTRACT

Research has demonstrated the predictive effect of maternal childhood maltreatment on adolescent internalizing problems. However, few studies have explored the mediating mechanisms of how mothers' experiences of childhood maltreatment are transmitted to their offspring's internalizing problems over time. The present multi-informant study investigated the potential mediating effects of maternal depressive symptoms and offspring's childhood maltreatment experiences on the relation between maternal childhood maltreatment and adolescent internalizing problems. A total of 823 Chinese youth (43.4% girls; Mage = 10.26 years, SD = 0.94) and their mothers participated in a two-wave longitudinal study with one-year intervals. Mothers reported their experiences of childhood maltreatment and depressive symptoms, while youth reported their childhood maltreatment experiences and internalizing problems. Findings of path analysis indicated that maternal emotional abuse at T1 could significantly predict adolescent internalizing problems at T2, after controlling for a baseline of adolescent internalizing problems. Maternal emotional abuse, emotional neglect, and physical neglect at T1 can influence adolescent internalizing problems at T2 through maternal depressive symptoms at T1 to adolescent internalizing problems at T1. Maternal emotional abuse at T1 displayed statistically significant indirect effects on adolescent internalizing problems at T2 successively through the pathway from adolescent emotional abuse at T1 to adolescent internalizing problems at T1. The findings supported the cycle of maltreatment hypothesis. The present study highlights the intergenerational link between maternal childhood maltreatment and adolescent internalizing problems, as well as reveals the mediating mechanisms in this relation.


Subject(s)
Child Abuse , Depression , Child , Female , Humans , Adolescent , Male , Longitudinal Studies , Child Abuse/psychology , Mothers/psychology , Emotions
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