Endoplasmic reticulum stress-related gene expression causes the progression of dilated cardiomyopathy by inducing apoptosis.

Background: Previous studies have shown that endoplasmic reticulum stress (ERS) -induced apoptosis is involved in the pathogenesis of dilated cardiomyopathy (DCM). However, the molecular mechanism involved has not been fully characterized. Results: In total, eight genes were obtained at the intersection of 1,068 differentially expressed genes (DEGs) from differential expression analysis between DCM and healthy control (HC) samples, 320 module genes from weighted gene co-expression network analysis (WGCNA), and 2,009 endoplasmic reticulum stress (ERGs). These eight genes were found to be associated with immunity and angiogenesis. Four of these genes were related to apoptosis. The upregulation of MX1 may represent an autocompensatory response to DCM caused by a virus that inhibits viral RNA and DNA synthesis, while acting as an autoimmune antigen and inducing apoptosis. The upregulation of TESPA1 would lead to the dysfunction of calcium release from the endoplasmic reticulum. The upregulation of THBS4 would affect macrophage differentiation and apoptosis, consistent with inflammation and fibrosis of cardiomyocytes in DCM. The downregulation of MYH6 would lead to dysfunction of the sarcomere, further explaining cardiac remodeling in DCM. Moreover, the expression of genes affecting the immune micro-environment was significantly altered, including TGF-ß family member. Analysis of the co-expression and competitive endogenous RNA (ceRNA) network identified XIST, which competitively binds seven target microRNAs (miRNAs) and regulates MX1 and THBS4 expression. Finally, bisphenol A and valproic acid were found to target MX1, MYH6, and THBS4. Conclusion: We have identified four ERS-related genes (MX1, MYH6, TESPA1, and THBS4) that are dysregulated in DCM and related to apoptosis. This finding should help deepen understanding of the role of endoplasmic reticulum stress-induced apoptosis in the development of DCM.

A Review: The Significance of Toll-Like Receptors 2 and 4, and NF-κB Signaling in Endothelial Cells during Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that begins with endothelial activation followed by a series of inflammatory responses, plaque formation, and finally rupture. An early event in endothelial dysfunction is activation of the nuclear factor-κB (NF-κB) signaling axis. Toll-like receptors (TLRs) in endothelial cells (ECs) play an essential role in recognizing pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). Activation of the canonical NF-κB pathway stimulates the expression of cytokines, chemokines, and an array of additional genes which activate and amplify AS-associated inflammatory responses. In this review, we discuss the involvement of TLR2/4 and NF-κB signaling in ECs during AS initiation, as well as regulation of the inflammatory response during AS by noncoding RNAs, especially microRNA (miRNA) and circular RNA (circRNA).

Diagnostic consistency between admission and discharge of pediatric cases in a tertiary teaching hospital in China.

BACKGROUND: Patient-centered, high-quality health care relies on accurate and timely diagnosis. Diagnosis is a complex, error-prone process. Prevention of errors involves understanding the cause of errors. This study investigated diagnostic discordance between admission and discharge in pediatric cases. METHODS: We retrospectively reviewed the electronic medical records of 5381 pediatric inpatients during 2017-2018 in a tertiary teaching hospital. We analyzed diagnostic consistency by comparing the first 4 digits of admission and discharge ICD-10 codes of the cases and classified them as concordant for "complete and partial match" or discordant for "no match". RESULTS: Diagnostic discordance was observed in 49.2% with the highest prevalence in infections of the nervous and respiratory systems (Ps < 0.001). Multiple (multivariable) logistic regression analysis predicted a lower risk of diagnostic discordance with older children (aOR, 95%CI: 0.94, 0.93-0.96) and a higher risk with infectious diseases (aOR, 95%CI: 1.49, 1.33-1.66) and admission by resident and attending pediatricians (aOR, 95%CI: 1.41, 1.30-1.54). Discordant cases had a higher rate of antibiotic prescription (OR, 95%CI: 2.09, 1.87-2.33), a longer duration of antibiotic use (P = 0.02), a longer length of hospital stay (P < 0.001), and higher medical expenses (P < 0.001). CONCLUSIONS: This study denotes a considerably high rate of discordance between admission and discharge diagnoses with an associated higher and longer prescription of antibiotics, a longer length of stay, and higher medical expenses among Chinese pediatric inpatient cases. Infectious diseases were identified as high-risk clinical conditions for discordance. Considering potential diagnostic and coding errors, departmental investigation of preventable diagnostic discordance is suggested for quality health care and preventing potential medicolegal consequences.

The performance of surface enhanced Raman scattering and spatial resolution with triangular plate dimer from ultra-ultraviolet to near-infrared range.

The theoretical research on surface enhanced Raman spectroscopy (SERS) of triangular plate dimer (TPD) is of great significance for the design of experimental substrates. In this paper, the SERS properties of the TPD with Au, Ag, Al and Cu have been theoretical investigated in the ultra-ultraviolet, visible and near-infrared region. The influence of the TPD configuration, including the tip radian, the dimer distance and the aspect ratio on the electric field, Raman enhancement and spatial resolution are studied by the finite element method. The results show that there are dipole resonance band and quadruple dipole resonance band in the surface plasmon resonance band of TPD. The tip radian and dimer distance play the dominant role in the electric field enhancement, and the aspect ratio can be mainly used to tune the peak position of the electric field. The smaller tip radian and dimer distance will produce a stronger localized electric field and a small red shift of the peak position. Adjusting the aspect ratio can tune the position of electric field peak from ultraviolet (UV) to near-infrared without changing the peak value of the electric field significantly, especially for Al TPD. The maximum Raman enhancement factor of Au, Ag and Cu all reach 11 orders of magnitude, and 9 orders of magnitude for Al. The spatial resolution changes linearly with the gap distance, and the maximum spatial distributions of Au, Ag, Al and Cu achieve 0.65 nm, 0.67 nm, 0.69 nm and 0.70 nm with the dimer distance of 1 nm. Our results not only provide a better theoretical guidance for the optimization of TPD substrates in the SERS experiment, but also extend its application scope from ultra-UV to near-infrared range.

Study on surface enhanced Raman scattering of Au and Au@Al2O3 spherical dimers based on 3D finite element method.

In this paper, the surface enhanced Raman scattering (SERS) characteristics of Au and Au@Al2O3 nanoparticle dimers were calculated and analyzed by using finite element method (3D-FEM). Firstly, the electric field enhancement factors of Au nanoparticles at the dimer gap were optimized from three aspects: the incident angle of the incident light, the radius of nanoparticle and the distance of the dimer. Then, aluminum oxide is wrapped on the Au dimer. What is different from the previous simulation is that Al2O3 shell and Au core are regarded as a whole and the total radius of Au@Al2O3 dimer is controlled to remain unchanged. By comparing the distance of Au nucleus between Au and Au@Al2O3 dimer, it is found that the electric field enhancement factor of Au@Al2O3 dimer is much greater than that of Au dimer with the increase of Al2O3 thickness. The peak of electric field of Au@Al2O3 dimer moves towards the middle of the resonance peak of the two materials, and it is more concentrated than that of the Au dimer. The maximum electric field enhancement factor 583 is reached at the shell thickness of 1 nm. Our results provide a theoretical reference for the design of SERS substrate and the extension of the research scope.