Numerical investigation of GHz repetition rate fundamentally mode-locked all-fiber lasers.

GHz repetition rate fundamentally mode-locked lasers have attracted great interest for a variety of scientific and practical applications. A passively mode-locked laser in all-fiber format has the advantages of high stability, maintenance-free operation, super compactness, and reliability. In this paper, we present numerical investigation on passive mode-locking of all-fiber lasers operating at repetition rates of 1-20 GHz. Our calculations show that the reflectivity of the output coupler, the small signal gain of the doped fiber, the total net cavity dispersion, and the modulation depth of the saturable absorber are the key parameters for producing stable fundamentally mode-locked pulses at GHz repetition rates in very short all-fiber linear cavities. The instabilities of GHz repetition rate fundamentally mode-locked all-fiber lasers with different parameters were calculated and analyzed. Compared to a regular MHz repetition rate mode-locked all-fiber laser, the pump power range for the mode-locking of a GHz repetition rate all-fiber laser is much larger due to the several orders of magnitude lower accumulated nonlinearity in the fiber cavity. The presented numerical study provides valuable guidance for the design and development of highly stable mode-locked all-fiber lasers operating at GHz repetition rates.

A new risk factor for coronary artery disease can be detected by an ApoA1 mAb-based assay.

BACKGROUND: This study aimed to find coronary artery disease (CAD) related apolipoprotein A1 (ApoA1) monoclonal antibody (mAb) and to evaluate the diagnostic value of the assay based on it. METHODS: Patients with CAD diagnosed by coronary angiography (disease group, n = 180) and healthy subjects (control group, n = 199) were recruited. The correlation between methods and CAD were evaluated by Spearman's rank correlation coefficients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the auxiliary diagnostic value of methods for CAD. Odds ratios (ORs) of the test results in CAD were estimated using logistic regression analysis. RESULTS: Measurements from an ApoA1 mAb were found significantly positively correlated with CAD (r = 0.243, P < 0.01), unlike the measurements from the ApoA1 pAb were negatively correlated with CAD (r = -0.341, P < 0.001). The areas under the ROC curve of the ApoA1 mAb and pAb measurements were 0.704 and 0.563, respectively, in patients with normal HDL-C levels. ApoA1 values from the mAb assay had a significant positive impact on CAD risk. CONCLUSION: An ApoA1 mAb-based assay can distinguish a high-density lipoprotein (HDL) subclass positively related to CAD, which can be used to improve and reappraise CAD risk assessment.

Evaluation of the application of TSH receptor stimulating autoantibodies and the optimization of detection strategy in Graves' disease.

BACKGROUND: We evaluated the use of thyroid stimulating immunoglobulin (TSI) assay to optimize the detection strategy for Graves' disease. METHODS: Five hundred and forty-four well characterized serum samples from the Clinical Laboratory of Shanghai Tongren Hospital were collected from August 2019 to April 2020. The serum samples were obtained from 52 untreated GD patients, 155 treated GD patients, 83 patients with Hashimoto's thyroiditis, 70 patients with thyroid nodules, 83 patients with thyroid cancer, and 101 healthy subjects. All samples were evaluated by both TSI assay and TSH receptor autoantibodies (TRAb) assay. Moreover, 23 patients without a distinct thyroid disease diagnosis at the first visit were monitored for 6 months to make a final diagnosis. RESULTS: The clinical sensitivity of the TSI and TRAb assays was 98.10% and 94.20% respectively, while the clinical specificity was 92.30% and 96.70% respectively. ROC plot analysis based on sera of UT-GD (newly diagnosed GD patients) revealed an area under the curve (AUC) of 0.974 for the TSI assay. The best cutoff value was 0.58 IU/l (98.0% of sensitivity, 92.8% of specificity). The AUC for the TRAb assay was 0.961. Furthermore, combining TSI and TRAb results, the area under the curve was 0.981. In a pilot study of 23 patients with an uncertain initial diagnosis, the follow-up results showed the clinical diagnosis of 22 out of 23 cases were resolved in agreement with the results obtained by the TSI assay, and one case matched the result obtained by TRAb assay. CONCLUSION: The TSI assay presents very promising analytical characteristics and could be adopted in clinical practice to improve GD diagnosis. The TSI assay might be better than TRAb assay in initial differential diagnosis of GD from other thyroid diseases.

Semiconducting polymer photodetectors with electron and hole blocking layers: high detectivity in the near-infrared.

Sensing from the ultraviolet-visible to the infrared is critical for a variety of industrial and scientific applications. Photodetectors with broad spectral response, from 300 nm to 1,100 nm, were fabricated using a narrow-band gap semiconducting polymer blended with a fullerene derivative. By using both an electron-blocking layer and a hole-blocking layer, the polymer photodetectors, operating at room temperature, exhibited calculated detectivities greater than 10(13) cm Hz(1/2)/W over entire spectral range with linear dynamic range approximately 130 dB. The performance is comparable to or even better than Si photodetectors.

Disruption of STAT6 Signal Promotes Cardiac Fibrosis Through the Mobilization and Transformation of CD11b+ Immature Myeloid Cells.

Cardiac fibrosis is an important pathological basis of various cardiovascular diseases. The roles of STAT6 signal in allergy, immune regulation, tumorigenesis, and renal fibrosis have been documented. However, the function and mechanism of STAT6 signal in sympathetic overactivation-induced cardiac fibrosis have not been fully elucidated. This study explores the novel role of STAT6 signal in isoproterenol (ISO)-induced cardiac fibrosis through the regulation of inflammatory response and the differentiation of macrophages from immature myeloid cells. The expression levels of STAT6, ß1-adrenergic receptor (ß1-AR), and inflammatory factors [interleukin α (IL-1α), IL-6, IL-18, and transforming growth factor ß (TGF-ß)] in CD11b+ myeloid cells were analyzed with a microarray study. The levels of IL-6 and TGF-ß1 in the CD11b+ myeloid cells-derived macrophages were detected with reverse transcriptase-polymerase chain reaction (RT-PCR). STAT6-knockout (KO) and WT mice were used to establish a murine cardiac fibrosis model by ISO injection. Cardiac fibroblasts were isolated from the hearts of newborn STAT6-KO and WT mice, and STAT6 expression was measured by Western blotting and RT-PCR after ISO stimulation, while α-smooth muscle actin (α-SMA) expression was detected by immunofluorescence and immunohistochemistry staining. Cardiac function and pathological characteristics were examined by echocardiography and immunohistochemistry staining, respectively. Immunohistochemistry staining with anti-CD11b was performed to detect the infiltration of CD11b+ myeloid cells in heart tissue. Flow cytometry analysis was used to measure the percentages of CD11b+ myeloid cells and CD11b+Ly6C+ macrophages in the peripheral blood. The results showed that STAT6 was highly expressed in CD11b+ myeloid cells located in injured hearts, and STAT6 expression in cardiac fibroblasts was down-regulated after ISO treatment. STAT6 deficiency further aggravated ISO-induced increased expression of α-SMA in cardiac fibroblasts, myocardial fibrosis, and cardiac dysfunction. The activation of ISO/ß1-AR signal aggravated cardiac inflammatory infiltration, promoted CD11b+ myeloid cell mobilization, and enhanced CD11b+Ly6C+/low macrophage differentiation, which was further exacerbated by STAT6 deficiency. Furthermore, ß1-AR mRNA expression significantly increased in splenic CD11b+ myeloid cells compared to their bone marrow-derived controls, and STAT6 deficiency promoted ß1-AR expression in an MI-induced sensitive cardiac fibrosis mouse model. The spleen-derived CD11b+ myeloid cells of STAT6-KO mice produced more IL-1α, IL-18, and TGF-ß than their WT counterparts. Taken together, these results suggest that STAT6 signal plays a critical role in ISO-induced ß1-AR overactivation and systemic inflammatory cascades, contributing to cardiac fibrogenesis. STAT6 should be a promising cardioprotective target against myocardial fibrosis and heart failure after ß1-AR overactivation-induced myocardial injury.

Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice.

Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC-/-) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC-/- mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6-/-) mice had a phenotype similar to that of HDC-/- mice post-MI; however, in contrast to HDC-/- mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6-/- mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway.

TRIB2 inhibits Wnt/ß-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, ß-TrCP, COP1 and Smurf1, in liver cancer cells.

Tribbles homolog 2 (TRIB2) is specifically regulated by Wnt signaling in liver cancer cells but not in colon cancer cells. However, whether and how TRIB2 regulates Wnt signaling in liver cancer cells remains unclear. Here, we report that TRIB2 negatively regulates Wnt activity through a reduction in protein stability of TCF4 and ß-Catenin. Mechanistically, TRIB2 associated-ubiquitin E3 ligases beta-transducin repeat-containing E3 ubiquitin protein ligase (ß-TrCP), COP1 and Smad ubiquitination regulatory factor 1 (Smurf1) reduced TCF4/ß-Catenin expression, and these effects could be enhanced by TRIB2. Moreover, deletion of the binding regions of these E3-ligases within the TRIB2 protein decreased ubiquitination of TCF4/ß-Catenin and reduced nuclear accumulation of ß-TrCP, COP1 and Smurf1, which suggested that TRIB2 regulated-Wnt activity is closely correlated with its associated E3 ligases.

High-detectivity polymer photodetectors with spectral response from 300 nm to 1450 nm.

Sensing from the ultraviolet-visible to the infrared is critical for a variety of industrial and scientific applications. Today, gallium nitride-, silicon-, and indium gallium arsenide--based detectors are used for different sub-bands within the ultraviolet to near-infrared wavelength range. We demonstrate polymer photodetectors with broad spectral response (300 to 1450 nanometers) fabricated by using a small-band-gap semiconducting polymer blended with a fullerene derivative. Operating at room temperature, the polymer photodetectors exhibit detectivities greater than 10(12) cm Hz(1/2)/W and a linear dynamic range over 100 decibels. The self-assembled nanomorphology and device architecture result in high photodetectivity over this wide spectral range and reduce the dark current (and noise) to values well below dark currents obtained in narrow-band photodetectors made with inorganic semiconductors.