Identification of genetic susceptibility for Chinese migraine with depression using machine learning

BackgroundMigraine is a common primary headache that has a significant impact on patients’ quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background.ObjectiveThe aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort.MethodsIn this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom’s MALDI-TOF iPLEX platform.ResultsIn univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS).ConclusionThe study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients

Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats

There is increasing evidence indicating that inflammation represents a key pathological component of Alzheimer’s disease (AD). A possible factor that may contribute to this process is netrin-1, a neuronal guidance molecule. This molecule has been shown to exert an unexpected immunomodulatory function. However, the potential changes and correlations of netrin-1 with T helper 17/regulatory T cells (Th17/Tregs) as related to inflammation in AD has yet to be examined. In this study, netrin-1 and Th17/Tregs balance were investigated, and the relationship among netrin-1, Th17/Tregs and cognitive function were analyzed in a rat model of AD. In this model, a bilateral intracerebroventricular administration of Amyloid β1-42 (Aβ1–42) was used to produce spatial learning and memory deficits, as well as increased neuronal apoptosis, which were detected 7 days after injection for AD7d group and 14 days for AD14d group. Netrin-1 concentrations were significantly down regulated in both serum and cerebrospinal fluid (CSF) of these AD rats, effects which were strongly correlated with cognitive deficits. Increased levels of interleukin (IL)-17 and deceased IL-10 were observed in both the circulation and CSF and were also correlated with the percent of time spent in the target quadrant of AD in these rats. These changes resulted in netrin-1 concentrations being negatively correlated with IL-17 but positively correlated with IL-10 concentrations in the serum and CSF. We also found that the Th17/Tregs balance was disrupted in these AD rats. Collectively, these findings reveal that the reduction in netrin-1 and the correlated disruption of Th17/Tregs balance in AD rats may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis

Application of digital technology in nasal reconstruction

Nasal defects are facial defects caused by trauma, tumors, or congenital diseases that seriously damage a patient’s physical and mental health. Nasal defects, from skin defects to total nasal defects, require surgical repair and reconstruction to restore the appearance and function of the nose, which have always been challenges for rhinoplasty. The development of digital technology has increased the possibility of nasal reconstruction. Digital technology is involved in the preoperative, intraoperative, and postoperative stages of nasal construction and is of great significance in improving the effect of this surgery. This article reviews the application of major digital technologies, including three-dimensional (3D) imaging technology, computer-assisted surgical navigation, and 3D printing, in nasal reconstruction and discusses the shortcomings of the current application of digital technology

Optoelectronic insights into the photovoltaic losses from photocurrent, voltage, and energy perspectives

Photocurrent and voltage losses are the fundamental limitations for improving the efficiency of photovoltaic devices. It is indeed that a comprehensive and quantitative differentiation of the performance degradation in solar cells will promote the understanding of photovoltaic physics as well as provide a useful guidance to design highly-efficient and cost-effective solar cells. Based on optoelectronic simulation that addresses electromagnetic and carrier-transport responses in a coupled finite-element method, we report a detailed quantitative analysis of photocurrent and voltage losses in solar cells. We not only concentrate on the wavelength-dependent photocurrent loss, but also quantify the variations of photocurrent and operating voltage under different forward electrical biases. Further, the device output power and power losses due to carrier recombination, thermalization, Joule heat, and Peltier heat are studied through the optoelectronic simulation. The deep insight into the gains and losses of the photocurrent, voltage, and energy will contribute to the accurate clarifications of the performance degradation of photovoltaic devices, enabling a better control of the photovoltaic behaviors for high performance

Photonic Design and Electrical Evaluation of Dual-Functional Solar Cells for Energy Conversion and Display Applications

Abstract Colored solar cells (SCs) are highly useful for applications in esthetic building-integrated photovoltaics (BIPVs). However, the theoretical designs mostly focus on the color quality with rarely addressing the optoelectronic responses. Here, considering both color display and complete electrical evaluation, we report a color-controlled a-Si:H SC in purely planar configuration, which simultaneously exhibits the desired high-purity color and sustains a relatively high power conversion efficiency. The high-performance color display is realized by thin-film photonic designs with incorporating distributed Bragg reflector and anti-reflection coating layers. Moreover, a comprehensive optoelectronic simulation addressing both the electromagnetic and internal semiconductor physics has been realized, which shows that the power conversion efficiencies of the designed red-green-blue (RGB) SCs can be 4.88%, 5.58%, and 6.54%, respectively. The physical principles of optimizing the colorful SCs with the tunable hue, high saturation, and brightness are explained, and we take the logo of “Soochow University” as an example to demonstrate the wide-angle pattern display by the SCs. The study paves the way of realizing the colored SCs targeting esthetic BIPV applications

The arginine methyltransferase PRMT5 and PRMT1 distinctly regulate the degradation of anti-apoptotic protein CFLARL in human lung cancer cells

Abstract Background CFLARL, also known as c-FLIPL, is a critical anti-apoptotic protein that inhibits activation of caspase 8 in mammalian cells. Previous studies have shown that arginine 122 of CFLARL can be mono-methylated. However, the precise role of arginine methyltransferase of CFLARL remains unknown. PRMT5 and PRMT1, which are important members of the PRMT family, catalyze the transfer of methyl groups to the arginine of substrate proteins. PRMT5 can monomethylate or symmetrically dimethylate arginine residues, while PRMT1 can monomethylate or asymmetrically dimethylate arginine residues. Methods Lung cancer cells were cultured following the standard protocol and the cell lysates were prepared to detect the given proteins by Western Blot analysis, and the protein interaction was assayed by co-immunoprecipitation (Co-IP) or GST pull-down assay. CFLARL ubiquitination level was evaluated by proteasomal inhibitor treatment combined with HA-Ub transfection and WB assay. PRMT1 and PRMT5 genes were knocked down by siRNA technique. Results We show that PRMT5 up-regulated the protein levels of CFLARL by decreasing the ubiquitination and increasing its protein level. Additionally, PRMT1 down-regulated the protein level of CFLARL by increasing the ubiquitination and degradation. The overexpression of PRMT5 can inhibit the interaction between CFLARL and ITCH, which has been identified as an E3 ubiquitin ligase of CFLARL, while overexpressed PRMT1 enhances the interaction between CFLARL and ITCH. Furthermore, we verified that dead mutations of PRMT5 or PRMT1 have the same effects on CFLARL as the wild-type ones have, suggesting it is the physical interaction between CFLAR and PRMT1/5 that regulates CFLARL degradation other than its enzymatic activity. Finally, we showed that PRMT5 and PRMT1 could suppress or facilitate apoptosis induced by doxorubicin or pemetrexed by affecting CFLARL in NSCLC cells. Conclusions PRMT5 and PRMT1 mediate the distinct effects on CFLARL degradation by regulating the binding of E3 ligase ITCH in NSCLC cells. This study identifies a cell death mechanism that is fine-tuned by PRMT1/5 that modulate CFLARL degradation in human NSCLC cells

Glucocorticoid modulatory element-binding protein 1 (GMEB1) interacts with the de-ubiquitinase USP40 to stabilize CFLARL and inhibit apoptosis in human non-small cell lung cancer cells

Abstract Background GMEB1 was originally identified via its interaction with GMEB2, which binds to the promoter region of the tyrosine aminotransferase (TAT) gene and modulates transactivation of the glucocorticoid receptor gene. In the cytosol, GMEB1 interacts with and inhibits CASP8, but the molecular mechanism is currently unknown. Methods Human non-small cell lung cancer cells and 293FT cells were used to investigate the function of GMEB1/USP40/CFLARL complex by WB, GST Pull-Down Assay, Immunoprecipitation, Immunofluorescence and Flow cytometry analysis. A549 cells overexpressing green fluorescent protein and GMEB1 shRNA were used for tumor xenograft using female athymic nu/nu 4-week-old mice. Results We found GMEB1 interacted with CFLARL (also known as c-FLIPL) in the cytosol and promoted its stability. USP40 targeted CFLARL for K48-linked de-ubiquitination. GMEB1 promoted the binding of USP40 to CFLARL. USP40 knockdown did not increase CFLARL protein level despite GMEB1 overexpression, suggesting GMEB1 promotes CFLARL stability via USP40. Additionally, GMEB1 inhibited the activation of pro-caspase 8 and apoptosis in non-small cell lung cancer (NSCLC) cell via CFLARL stabilization. Also, GMEB1 inhibited the formation of DISC upon TRAIL activation. CFLARL enhanced the binding of GMEB1 and CASP8. Downregulation of GMEB1 inhibited A549 xenograft tumor growth in vivo. Conclusions Our findings show the de-ubiquitinase USP40 regulates the ubiquitination and degradation of CFLARL; and GMEB1 acts as a bridge protein for USP40 and CFLARL. Mechanistically, we found GMEB1 inhibits the activation of CASP8 by modulating ubiquitination and degradation of CFLARL. These findings suggest a novel strategy to induce apoptosis through CFLARL targeting in human NSCLC cells