Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome.

OBJECTIVE: The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis. RESULTS: We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-ß signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model. INTERPRETATION: We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.

Multi-omics profiling reveals microRNA-mediated insulin signaling networks.

BACKGROUND: MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells. RESULTS: We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network. CONCLUSIONS: In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes.

Vaginal microbiome variances in sample groups categorized by clinical criteria of bacterial vaginosis.

BACKGROUND: One of the most common and recurrent vaginal infections is bacterial vaginosis (BV). The diagnosis is based on changes to the "normal" vaginal microbiome; however, the normal microbiome appears to differ according to reproductive status and ethnicity, and even among individuals within these groups. The Amsel criteria and Nugent score test are widely used for diagnosing BV; however, these tests are based on different criteria, and so may indicate distinct changes in the vaginal microbial community. Nevertheless, few studies have compared the results of these test against metagenomics analysis. METHODS: Vaginal flora samples from 77 participants were classified according to the Amsel criteria and Nugent score test. The microbiota composition was analyzed using 16S ribosome RNA gene amplicon sequencing. Bioinformatics analysis and multivariate statistical analysis were used to evaluate the microbial diversity and function. RESULTS: Only 3 % of the participants diagnosed BV negative using the Amsel criteria (A-) were BV-positive according to the Nugent score test (N+), while over half of the BV-positive patients using the Amsel criteria (A+) were BV-negative according to the Nugent score test (N-). Thirteen genera showed significant differences in distribution among BV status defined by BV tests (e.g., A - N-, A + N- and A + N+). Variations in the four most abundant taxa, Lactobacillus, Gardnerella, Prevotella, and Escherichia, were responsible for most of this dissimilarity. Furthermore, vaginal microbial diversity differed significantly among the three groups classified by the Nugent score test (N-, N+, and intermediate flora), but not between the Amsel criteria groups. Numerous predictive microbial functions, such as bacterial chemotaxis and bacterial invasion of epithelial cells, differed significantly among multiple BV test, but not between the A- and A+ groups. CONCLUSIONS: Metagenomics analysis can greatly expand our current understanding of vaginal microbial diversity in health and disease. Metagenomics profiling may also provide more reliable diagnostic criteria for BV testing.

A Three-MicroRNA Signature as a Potential Biomarker for the Early Detection of Oral Cancer.

Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen the differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays in the training phase (n = 72) and validation phase (n = 178). The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. The three-plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.

Integrated MicroRNA-mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A.

Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA-mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.

Fabrication and characterization of back-side illuminated InGaN/GaN solar cells with periodic via-holes etching and Bragg mirror processes.

In this study, the design and fabrication schemes of back-side illuminated InGaN/GaN solar cells with periodic via-holes etching and Bragg mirror processes are presented. Compared to typical front-side illuminated solar cells, the improvements of open-circuit voltage (V(oc)) from 1.88 to 1.94 V and short-circuit current density (J(sc)) from 0.84 to 1.02 mA/cm(2) are observed. Most significantly, the back-side illuminated InGaN/GaN solar cells exhibit an extremely high fill factor up to 85.5%, leading to a conversion efficiency of 1.69% from 0.66% of typical front-side illuminated solar cells under air mass 1.5 global illuminations. Moreover, the effects of bottom Bragg mirrors on the photovoltaic characteristics of back-side illuminated solar cells are studied by an advanced simulation program. The results show that the J(sc) could further be improved with a factor of 10% from the original back-side illuminated solar cell by the structure optimization of bottom Bragg mirrors.

Reduced efficiency droop in blue InGaN light-emitting diodes by thin AlGaN barriers.

The phenomenon of efficiency droop in blue InGaN light-emitting diodes (LEDs) is studied numerically. Simulation results indicate that the severe Auger recombination is one critical mechanism corresponding to the degraded efficiency under high current injection. To solve this issue, LED structure with thin AlGaN barriers and without the use of an AlGaN EBL is proposed. The purpose of the strain-compensation AlGaN barriers is to mitigate the strain accumulation in a multiquantum well (MQW) active region in this thin-barrier structure. With the proposed LED structure, the hole injection and transportation of the MQW active region are largely improved. The carriers can thus distribute/disperse much more uniformly in QWs, and the Auger recombination is suppressed accordingly. The internal quantum efficiency and the efficiency droop are therefore efficiently improved.

Highly efficient CdS-quantum-dot-sensitized GaAs solar cells.

We demonstrate a hybrid design of traditional GaAs-based solar cell combined with colloidal CdS quantum dots. With anti-reflective feature at long wavelength and down-conversion at UV regime, the CdS quantum dot effectively enhance the overall power conversion efficiency by as high as 18.9% compared to traditional GaAs-based device. A more detailed study showed an increase of surface photoconductivity due to UV presence, and the fill factor of the solar cell can be improved accordingly.

Investigation of InGaN green light-emitting diodes with chirped multiple quantum well structures.

The effect of using chirped multiple quantum-well (MQW) structures in InGaN green light-emitting diodes (LEDs) is numerically investigated. An active structure, which is with both thick QWs with low indium composition on the p-side and thin QWs with high indium composition next to the n-region, is presented in this study. The thickness and indium composition in each single QW is specifically tuned to emit the same green emission spectrum. Comparing with conventional active structure design of green LEDs, which is using uniform MQWs, the output power is increased by 27% at 20 mA, and by 15% at 100 mA current injections. This improvement is mainly attributed to the enhanced efficiency of carrier injection into QWs and the improved capability of carrier transport.

Packing-Shape Effects of Optical Properties in Amplified Spontaneous Emission through Dynamics of Orbit-Orbit Polarization Interaction in Hybrid Perovskite Quantum Dots Based on Self-Assembly.

This paper reports packing-shape effects of amplified spontaneous emission (ASE) through orbital polarization dynamics between light-emitting excitons by stacking perovskite (MAPbBr3) quantum dots (QDs sized between 10 nm and 14 nm) into rod-like and diamond-like aggregates. The rod-like packing shows a prolonged photoluminescence (PL) lifetime (184 ns) with 3 nm red-shifted peak (525 nm) as compared to the diamond-like packing (PL peak, 522 nm; lifetime, 19 ns). This indicates that the rod-like packing forms a stronger interaction between QDs with reduced surface-charged defects, leading to surface-to-inside property-tuning capability with an ASE. Interestingly, the ASE enabled by rod-like packing shows an orbit-orbit polarization interaction between light-emitting excitons, identified by linearly/circularly polarized pumping conditions. More importantly, the polarization dynamics is extended to the order of nanoseconds in the rod-like assembly, determined by the observation that within the ASE lifetime (2.54 ns) the rotating pumping beam polarization direction largely affects the coherent interaction between light-emitting excitons.

Vacuum-Deposited Organometallic Halide Perovskite Light-Emitting Devices.

In this work, a sequential vacuum deposition process of bright, highly crystalline, and smooth methylammonium lead bromide and phenethylammonium lead bromide perovskite thin films are investigated and the first vacuum-deposited organometallic halide perovskite light-emitting devices (PeLEDs) are demonstrated. Exceptionally low refractive indices and extinction coefficients in the emission wavelength range are obtained for these films, which contributed to a high light out-coupling efficiency of the PeLEDs. By utilizing these perovskite thin films as emission layers, the vacuum-deposited PeLEDs exhibit a very narrow saturated green electroluminescence at 531 nm, with a spectral full width at half-maximum bandwidth of 18.6 nm, a promising brightness of up to 6200 cd/m2, a current efficiency of 1.3 cd/A, and an external quantum efficiency of 0.36%.

DDX3 Represses Stemness by Epigenetically Modulating Tumor-suppressive miRNAs in Hepatocellular Carcinoma.

Studies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion, and most importantly, DDX3 knockdown promotes tumorigenesis. Moreover, we found positive correlations between DDX3 level and expressions of tumor-suppressive miR-200b, miR-200c, miR-122 and miR-145, but not miR-10b and miR-519a, implying their involvement in DDX3 knockdown-induced CSC phenotypes. In addition, DDX3 reduction promoted up-regulation of DNA methyltransferase 3A (DNMT3A), while neither DNMT3B nor DNMT1 expression was affected. Enriched DNMT3A binding along with hypermethylation on promoters of these tumor-suppressive miRNAs reflected their transcriptional repressions in DDX3-knockdown cells. Furthermore, individual restoration of these tumor-suppressive miRNAs represses DDX3 knockdown-induced CSC phenotypes. In conclusion, our study suggested that DDX3 prevents generation of CSCs through epigenetically regulating a subset of tumor-suppressive miRNAs expressions, which strengthens tumor suppressor role of DDX3 in HCC.

Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality.

Some previous studies have identified bacteria in semen as being a potential factor in male infertility. However, only few types of bacteria were taken into consideration while using PCR-based or culturing methods. Here we present an analysis approach using next-generation sequencing technology and bioinformatics analysis to investigate the associations between bacterial communities and semen quality. Ninety-six semen samples collected were examined for bacterial communities, measuring seven clinical criteria for semen quality (semen volume, sperm concentration, motility, Kruger's strict morphology, antisperm antibody (IgA), Atypical, and leukocytes). Computer-assisted semen analysis (CASA) was also performed. Results showed that the most abundant genera among all samples were Lactobacillus (19.9%), Pseudomonas (9.85%), Prevotella (8.51%) and Gardnerella (4.21%). The proportion of Lactobacillus and Gardnerella was significantly higher in the normal samples, while that of Prevotella was significantly higher in the low quality samples. Unsupervised clustering analysis demonstrated that the seminal bacterial communities were clustered into three main groups: Lactobacillus, Pseudomonas, and Prevotella predominant group. Remarkably, most normal samples (80.6%) were clustered in Lactobacillus predominant group. The analysis results showed seminal bacteria community types were highly associated with semen health. Lactobacillus might not only be a potential probiotic for semen quality maintenance, but also might be helpful in countering the negative influence of Prevotella and Pseudomonas. In this study, we investigated whole seminal bacterial communities and provided the most comprehensive analysis of the association between bacterial community and semen quality. The study significantly contributes to the current understanding of the etiology of male fertility.

Numerical study of passive Q switching of a Tm:YAG laser with a Ho:YLF solid-state saturable absorber.

In a previous work [Appl. Phys. Lett. 65, 3060 (1994)] we experimentally demonstrated that passive Q switching of a 2,017-nm, flashlamp-pumped Tm,Cr:YAG laser with a Ho:YLF saturable absorber could be obtained with an internal focusing lens. We numerically investigate the optical performance of the Ho:YLF Q-switched Tm:YAG laser system by solving the coupled rate equations. The simulation results indicate that the results obtained numerically are in good agreement with those obtained experimentally. With typical laser configuration, a Q-switched laser pulse of 35 mJ in 30 ns is obtained.