Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack ...of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC.
The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results.
Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77;
=0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84;
=0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries.
Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.
Dilated cardiomyopathy (DCM) is a non-ischemic cardiomyopathy involving one or more underlying etiologies. It is characterized by structural and functional dysfunction of the myocardium, potentially ...leading to fibrosis and ventricular remodeling, and an elevated risk of heart failure (HF). Although the pathogenesis of DCM remains unknown, compelling evidence suggests that DCM-triggered immune cells and inflammatory cascades play a crucial role in the occurrence and development of DCM. Various factors are linked to myocardial damage, inducing aberrant activation of the immune system and sustained inflammatory responses in DCM. The investigation of the immunopathogenesis of DCM also contributes to discovering new biomarkers and therapeutic targets. This review examines the roles of immune cells and related cytokines in DCM pathogenesis and explores immunotherapy strategies in DCM.
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•DCM is a multifactorial myocardial disease.•DCM has a complex regulatory network of immune cells and related cytokines, potentially with variations among subtypes.•Alternations in the expression of immune cells and related cytokines in different subtypes of DCM may serve as biomarkers.•Targeting immune cells, cytokines, and immunomodulatory approaches are potential therapeutic strategies in DCM.
Aims
Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC.
Methods
A total of 466 ...PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets.
Results
The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5ʹ UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer.
Conclusions
Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.
•Our study reveals that the presence of ANCA, specifically pANCA, was independently associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).•ANCA can reflect the ...inflammatory status of RA patients and serve as a potential biomarker for RA-ILD, complementing the diagnostic value of existing biomarkers.•RA patients with positive ANCA may require enhanced monitoring and tailored treatment approaches to impede ILD progression.
This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients.
The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown.
The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.
The mechanical properties of nano-scale Cu/FeS composite were simulated by molecular dynamics （MD） simulation in this paper. Through the analysis on the stress-strain curves, the results of MD ...simulation were in good agreement with mechanisms of macroscopic deformation. When the size of particles was smaller than a certain value, the relationship between yield strength and size, which was different from the large size crystals abided by the contrary Hall-Petch relationship. Based on the discussion of nano-scale Cu/FeS composite, some interesting conclusions were obtained. For example, the ＂S＂ type curves were discovered in stress-strain curves and the anisotropy of FeS was very evident when the exposures of reinforcing phase （FeS） were different and so on. The basic theories and calculations of the composite that contains nano-scale particles were discussed. At the same time, a new modeling building method of composites, which was close to actual experiences, were considered in this paper.
Broadband light sources emitting in the terahertz spectral range are highly desired for applications such as noninvasive imaging and spectroscopy. Conventionally, THz pulses are generated by optical ...rectification in bulk nonlinear crystals with millimetre thickness, with the bandwidth limited by the phase-matching condition. Here we demonstrate broadband THz emission via surface optical rectification from a simple, commercially available 19 nm-thick indium tin oxide (ITO) thin film. We show an enhancement of the generated THz signal when the pump laser is tuned around the epsilon-near-zero (ENZ) region of ITO due to the pump laser field enhancement associated with the ENZ effect. The bandwidth of the THz signal generated from the ITO film can be over 3 THz, unrestricted by the phase-matching condition. This work offers a new possibility for broadband THz generation in a subwavelength thin film made of an ENZ material, with emerging physics not found in existing nonlinear crystals.
In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the apoptosis of PSCs through ...induced apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and Smad5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting apoptosis and TGF-β/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.
Limited by meteorological conditions, airspace, complex terrain and other factors, airborne millimeter-wave InSAR will inevitably face the situation of no control point layout when acquiring terrain ...data in the difficult mapping areas in Southwest China, which increases the difficulty of subsequent data processing. Moreover, the layout of control points in difficult mapping areas consumes a lot of manpower and time, which is not suitable for large-scale high-precision topographic mapping. To solve these problems, this paper proposes an automatic extraction of tie-points and interferometric calibration technology based on tie-points. This technology develops the automatic extraction algorithm of tie-points based on SAR + SIFT + RANSAC to obtain evenly distributed tie-points of adjacent images, and uses the evenly distributed tie-points as real known points to recalibrate the interference parameters, then carries out elevation transfer and elevation inversion through the tie-points of overlapping areas, thus realizing high-precision mapping without control points for airborne millimeter-wave InSAR. This paper uses measured data to verify the technology, and compares it with the areas with control points and marking points. The comparison results of elevation accuracy prove the feasibility and effectiveness of this method. This paper also discusses the difficulties in the treatment of typical areas, such as water areas, urban areas and mountain areas, and gives reasonable solutions that have good engineering application value.
Four donor-π bridge-acceptor structured boron dipyrromethene type sensitizers bearing triarylamine donors with different rigidities were synthesized and applied in dye-sensitized solar cells. The ...influence of different triarylamine donors on the optical, electrochemical properties and photovoltaic performances of sensitizers was systematically investigated. It was shown that the photovoltaic performance of boron dipyrromethene type sensitizer-based cell increased with increasing the fluorescence quantum yield and fluorescence lifetime of the corresponding sensitizers, which are believed to be closely related to the rigidities of the donor groups in the molecule. The best performance was realized for the cell based on rigid 9-phenyl-carbazole-substituted boron dipyrromethene sensitizer (ZH-b) with a fluorescence quantum yield of 0.516 and a fluorescence lifetime of 4.02 ns, resulting in a short circuit photocurrent density of 14.10 mA/cm2 and an overall conversion efficiency of 4.42%, which are fairly good results achieved for boron dipyrromethene type sensitizer-based solar cell.
•Four boron dipyrromethene (BODIPY) type sensitizers were synthesized.•The BODIPY sensitizers contain triarylamine donors with different rigidities.•These BODIY dyes were applied in dye-sensitized solar cells (DSSCs).•The fluorescence quantum yield and lifetime influenced the cell performance.•The fluorescence quantum yield and lifetime related to molecules' rigidities.
Over-the-horizon radar (OTHR) is an important equipment for the ultralong-range early warning in the military, but the use of constant false-alarm rate (CFAR), which is a traditional detection ...method, makes it difficult in multi-aircraft formation recognition. To solve this problem, a multi-aircraft formation recognition method based on deep transfer learning in OTHR is proposed. First, the range-Doppler images of aircraft formation in OTHR are simulated, which are composed of four categories of samples. Secondly, a recognition model based on Convolutional Neural Network (CNN) and CFAR detection technology is constructed, whose training method is designed as a two-step transfer. Finally, the trained model can well distinguish the spectral characteristics of aircraft formation, and then recognize the aircraft number of a formation. Experiments show that the proposed method is better than the traditional CFAR detection method, and can detect the number of aircraft more accurately in the formation with the same false alarm rate.
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