Equalization equal gain combining for a single-input to multiple-output underwater wireless optical communication system under a Gaussian beam.

In this study, we examined the performance of an underwater wireless optical communication (UWOC) system employing a single-input to multiple-output (SIMO) scheme and proposed an equalization equal gain combining (EEGC) algorithm for it under Gaussian beam conditions. Furthermore, based on a Yue spectrum with the instability of oceanic water stratification and a finite outer scale, we derived the closed analytical formulas for the scintillation index and spatial coherence radius in weak oceanic turbulence for a Gaussian beam, from which we could obtain the threshold of the detector spacing and the strength of oceanic turbulence. We then derived the closed-form formula for the upper bound average bit error rate of the EEGC SIMO system with ON-OFF keying modulation by using the hyperbolic tangent distribution function. Our simulations demonstrate two issues if oceanic water stratification is treated as a steady state: the performance of the diversity receiver system will be significantly underestimated in salinity-dominated weak oceanic turbulence channels and will be significantly overestimated in temperature-dominated weak oceanic turbulence channels. Additionally, the SIMO system performance improvement using the proposed EEGC algorithm was more evident with increasing detector spacing, and the EEGC algorithm reduced the impact of the layout of the avalanche photodiode arrays on the UWOC system performance, in contrast to the equal gain combining algorithm.

Gene regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells.

OBJECTIVES: Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of rheumatoid arthritis (RA) at a single-cell resolution using epigenetic technology. METHODS: Peripheral blood mononuclear cells of seven RA patients and seven natural controls were extracted nuclei suspensions for library construction. Subsequently, scATAC-seq was performed to generate a high-resolution map of active regulatory DNA for bioinformatics analysis. RESULTS: We obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in RA pathogenesis by regulating the activity of mitogen-activated protein kinase. Consequently, two genes (PTPRC and SPAG9) regulated by 10 key TFs were found, which may be associated with RA disease pathogenesis, and these TFs were obviously enriched in RA patients (P < .05, fold change value > 1.2). With further quantitative polymerase chain reaction validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs [ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), and MEF2B], showing highly accessible binding sites in RA patients. CONCLUSIONS: These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived peripheral blood mononuclear cells, providing insights into therapy from an epigenetic perspective.

Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome.

BACKGROUND: Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear. RESULTS: In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin. CONCLUSIONS: We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.

The immune characterization of interferon-ß responses in tuberculosis patients.

We aimed to assess the immunoregulatory effects of IFN-ß in patients with tuberculous pleurisy. IFN-ß, IFN-γ and IL-17 expression levels were detected, and correlations among these factors in different culture groups were analyzed. Pleural fluid mononuclear cells (PFMC) from tuberculous pleural effusions, but not peripheral blood mononuclear cells (PBMC) from healthy donors, spontaneously expressed IFN-ß, IL-17 and IFN-γ. Moreover, exogenous IFN-ß significantly inhibited the expression of IL-17 in PFMC. By contrast, IFN-ß simultaneously enhanced the levels of IFN-γ. To further investigate the regulation of IL-17 and IFN-γ by endogenous IFN-ß, an IFN-ß neutralizing antibody was simultaneously added to bacillus Calmette-Guérin (BCG)-stimulated PFMC. IL-17 expression was significantly increased, but IFN-γ production was markedly decreased in the experimental group supplemented with the IFN-ß neutralizing antibody. Simultaneously, IL-17 production was remarkably increased in the experimental group supplemented with the IFN-γ neutralizing antibody. Taken together, in our study, we first found that freshly isolated PFMC, but not PBMC from healthy donors, spontaneously expressed IFN-ß, IL-17 and IFN-γ in vivo. Moreover, IFN-ß suppressed IL-17 expression and increased IFN-γ production. Furthermore, both IFN-ß and IFN-γ down-regulated IL-17 expression. These observations suggest that caution is required when basing anti-tuberculosis treatment on the inhibition of IFN-ß signaling.

miR-16-5p specifically inhibits IFN-γ-regulated memory T helper cell differentiation in malignant pleural effusion of non-small cell lung cancer.

Background: The mechanism for memory T helper (Th) cell differentiation in malignant pleural effusion (MPE) of non-small cell lung cancer (NSCLC) is poorly understood. MicroRNAs (miRNAs), as small non-coding RNA that regulate gene expression, play a crucial role in the regulation of memory Th cell differentiation. However, whether miRNAs can inhibit the differentiation of memory Th cells in MPE of NSCLC has not been reported. This study aimed to explore miR-16-5p specifically inhibits interferon-gamma (IFN-γ)-regulated memory Th cell differentiation in MPE of NSCLC. Methods: A total of 30 patients with NSCLC and 30 age- and sex-matched patients, who were clinically diagnosed as benign pleural effusion (BPE) of lung disease and had not received any intervention, were collected. The expression of nucleic acids, miRNAs, and cytokines was detected by polymerase chain reaction (PCR), miRNA microarray, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blotting. Results: The expression of CD4+CD69+ T cells in NSCLC with MPE was lower than that in lung disease BPE. CD4+CD69+ T cells highly express CD45RO+ and mainly secrete anti-tumor cytokines IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). The expression of miR-16-5p in CD4+CD69+ CD45RO+ T cells in MPE was higher than that in BPE. Moreover, miR-16-5p can bind to both IFN-γ promoter and its 5'untranslated region (5'-UTR), suggesting that IFN-γ may be the target gene directly affected by miR-16-5p. IFN-γ also affects the differentiation of memory CD4+ T cells by regulating T-bet. Conclusions: We believe that miR-16-5p may regulate the decrease of differentiation of naïve CD4+ T cells into memory CD4+CD69+ T cells through its target gene IFN-γ in MPE, thus reducing the number of cytokines that produce anti-tumor effects. It may be the main reason for the low response rate of lung cancer with MPE immunotherapy.

CRIP1 supports the growth and migration of AML-M5 subtype cells by activating Wnt/ß-catenin pathway.

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous hematopoietic disorder. To effectively eradicate AML, it is urgent to develop new therapeutic approaches and identify novel molecular targets. In silico analysis indicated that the expression of cysteine-rich intestinal protein 1 (CRIP1) was significantly elevated in AML cells and correlated with worse overall survival of the AML patients. However, its specific roles in AML remain elusive. Here we demonstrated that CRIP1 acted as a key oncogene to support AML cell survival and migration. Using a loss-of-function analysis, we found that CRIP1 silencing in U937 and THP1 cells by lentivirus-mediated shRNAs resulted in a decrease in cell growth, migration and colony formation, and an increase in chemosensitivity to Ara-C. CRIP1 silencing induced cell apoptosis and G1/S transition arrest. Mechanically, CRIP1 silencing caused inactivation of Wnt/ß-catenin pathway through upregulating axin1 protein. The Wnt/ß-catenin agonist SKL2001 markedly rescued the cell growth and migration defect induced by CRIP1 silencing. Our findings reveals that CRIP1 may contribute to AML-M5 pathogenesis and represent a novel target for AML-M5 treatment.

Label-free quantitative proteomic and phosphoproteomic analyses of renal biopsy tissues in membranous nephropathy.

PURPOSE: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. However, the underlying mechanisms of its occurrence and development are not completely clear. Thus, it is essential to explore the mechanisms. EXPERIMENTAL DESIGN: Here, we employed label-free quantification and liquid chromatography-tandem mass spectrometry analysis techniques to investigate the proteomic and phosphoproteomic alterations in renal biopsy tissues of MN patients. Samples were collected from 16 MN patients and 10 controls. Immunohistochemistry (IHC) was performed to validate the hub phosphoprotein. RESULTS: We focused on the changes in the phosphoproteome in MN group versus control group (CG). Totally, 1704 phosphoproteins containing 3241 phosphosites were identified and quantified. The phosphorylation levels of 216 phosphoproteins containing 297 phosphosites were differentially regulated in stage II MN group versus CG, and 333 phosphoproteins containing 461 phosphosites were differentially phosphorylated in stage III MN group versus CG. In each comparison, several differential phosphoproteins were factors, kinases and receptors involved in cellular processes, biological regulation and other biological processes. The subcellular location of most of the differential phosphoproteins was the nucleus. Protein-protein interaction analysis showed that the connections among the differential phosphoproteins were extremely complex, and several signalling pathways probably associated with MN were identified. The hub phosphoprotein was validated by IHC. CONCLUSIONS AND CLINICAL RELEVANCE: This investigation can provide direct insight into the global phosphorylation events in MN group versus CG and may help to shed light on the potential pathogenic mechanisms of MN.

Coenzyme Q10 supplementation improves cholesterol efflux capacity and antiinflammatory properties of high-density lipoprotein in Chinese adults with dyslipidemia.

OBJECTIVES: Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia. METHODS: A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein-mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk. RESULTS: CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus -0.12±2.94; P = 0.014) and reduced HII (mean change, -0.32±0.58 versus -0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention. CONCLUSIONS: This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.