Search

Patients with refractory erythema of rosacea have limited treatment options. To evaluate the efficacy and safety of a 12-week course of paroxetine for moderate-to-severe erythema of rosacea. In a multicenter, randomized, double-blinded, placebo-controlled trial, patients with refractory erythema of rosacea were randomly assigned (1:1) to receive paroxetine 25 mg daily or placebo for 12 weeks. Overall, 97 patients completed the study (paroxetine: 49; placebo: 48). The primary end point was the proportion of participants achieving Clinical Erythema Assessment success (defined as Clinical Erythema Assessment score of 0, 1, or ≥2-grade improvement from baseline) at week 12; this was significantly greater in the paroxetine group than in the placebo group (42.9% vs 20.8%, P =.02). Some secondary end points were met, such as flushing success with point reductions ≥2 (44.9% vs 25.0%, P =.04) and improvement in overall flushing (2.49 ± 3.03 vs 1.68 ± 2.27, P =.047), burning sensation (46.9% vs 18.8%, P =.003), and depression (P =.041). The most reported adverse events associated with paroxetine were dizziness, lethargy, nausea, dyspepsia, and muscle tremors. Only a single-dosage regimen of paroxetine within a 12-week study was evaluated. Paroxetine is an effective and well-tolerated alternative treatment for moderate-to-severe erythema of rosacea. [ABSTRACT FROM AUTHOR]

Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-β and TP53 pathways were significantly associated with worse DFS. Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-β and TP53 pathways may provide more prognostic information beyond commonly used clinical factors. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the mutations in mucinous adenocarcinoma of the appendix (MAA). SNV was detected in 15 patients with MAA, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and reactome pathway analyses were performed. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), microsatellite instability (MSI) was analysis. Finally, the human leukocyte antigen (HLA) typing of the samples was detected. The results showed that TP53 (27 %) and KRAS (20 %) were the highest mutation frequency in the sample, mainly occur in p53 pathway and RTK-RAS pathway. GO analysis reveals mutated genes are closely related to the regulation of GTPase activity, regulation of small GTPase mediated signal transduction and other BP, related to the CC and MF. Analysis of KEGG pathways indicated that the top canonical pathways associated with SNV was Wnt signaling pathway. Reactome pathway analysis further revealed that the mutant genes were closely related to muscle contraction. Only one patient had moderate TMB level and one patient with high MSI. In conclusion, the most common mutated genes and the signaling pathways closely related to MAA development were detected in this study, which will contribute to the development of immunotherapy for patients with MAA. • Patients with MAA generally had lower TMB, MATH levels and lower MSI status. • MAA Patients have an opportunity for immunotherapy and a longer effective survival. • TP53 and KRAS mutations are more common in MAA patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is well known that melanin synthesis in melanoma cells is controlled by melanogenic enzymes, which regulate the cAMP-PKA signaling pathway. Estrogen was previously reported to upregulate melanogenesis that is associated with human skin pigmentation. Objective: To investigate the influence and mechanism of diethylstilbestrol (DES) on melanogenesis in mouse B16 melanoma cells. Methods: The effects of diethylstilbestrol on cell viability, melanin content, tyrosinase activity, cAMP level, expression of the tyrosinase family and microphthalmia related transcription factor (MITF) were measured in B16 melanoma. Estrogen receptor (ER) expression were detected in B16 melanoma and A375 melanoma. Diethylstilbestrol-induced melanin synthesis were evaluated in the presence and absence of H89 (a PKA-specific inhibitor) and ICI182, 780 (a pure ER antagonist). Tyrosinase activity, the mRNA levels of tyrosinase and MITF were evaluated in the presence and absence of H89. Results: In B16 cells, diethylstilbestrol increased cell proliferation, melanin synthesis, tyrosinase activity and expression of the tyrosinase family and MITF. ER expression have not difference in human and mouse melanoma. When ER were inhibited by ICI182, 780, DES-induced melanogenesis was significantly reduced. Diethylstilbestrol enhanced the level of cAMP. The upregulation of melanin content and tyrosinase activity stimulated by diethylstilbestrol was significantly attenuated in the presence of H89. Further, diethylstilbestrol-induced upregulation of tyrosinase and MITF were significantly attenuated when the PKA pathway was blocked. Conclusions: Diethylstilbestrol can enhance melanin synthesis in melanoma cells. This effect is associated with activation of the cAMP-PKA pathway and upregulation of expression and activity of the melanogenesis-related enzyme tyrosinase and MITF. [Copyright &y& Elsevier]

• The expression of FUNDC1 reached its peak 12 h after ICH. • FUNDC1 siRNA aggravates ICH-induced brain injury, while inhibit mitophagy. • Mitophagy specific inhibitor(mdivi-1) aggravates the inflammatory response after ICH. • FUNDC1 overexpression alleviates ICH-induced inflammation, and mdivi-1 reverses this response. Inflammation is a fundamental element in secondary brain injury (SBI) besides intracerebral hemorrhage (ICH). Pyrin domain that contains 3 inflammasome (NLRP3) was regarded as a key role of the nod-like receptor family and played an important part in the inflammatory response following ICH-induced injury. FUN14 domain containing 1 (FUNDC1) is a kind of mitophagy receptor, which can eliminate mitochondrial dysfunction after hypoxia and mitochondrial stress. Previous research showed that mitophagy prevents inflammation through inhibiting NLRP3 inflammasome pathway. However, the relationship between FUNDC1 and ICH-induced inflammatory response stays uncertain. In this study, we investigate that FUNDC1 inhibit NLRP3 inflammasome activation by promoting mitophagy, thereby alleviate ICH-induced injury. We established ICH model by injecting tail venous blood into the basal ganglia of C57 mice (healthy, male adult). We injected siRNA to knockdown FUNDC1. In order to deeply seek for the mechanisms of FUNDC1 in ICH-induced injury, FUNDC1 was overexpressed by adeno-associated virus (AAV) and mitophagy was suppressed by specific inhibitor (mdivi-1). The protein level of FUNDC1 was upregulated and got peak at 12h after ICH. We noticed that silencing FUNDC1 can suppress mitophagy, promote NLRP3-mediated inflammation and exacerbate ICH injury. Furthermore, the results indicated that mitophagy participated in the inhibitory effect of FUNDC1 on NLRP3-mediated inflammatory response after ICH. Our results showed that FUNDC1 alleviated ICH-induced inflammation in mice by promoting mitophagy. Those data suggested that FUNDC1 may be a potential target for the treatment of ICH. [ABSTRACT FROM AUTHOR]

• Extraction of In from from hydrochloric acid solution and the indium on the loaded organic phase was stripped by water was developed. • N503, P350 and TBP were used as the extractants for In, respectively. • The extracted complexes with N503 and P350 were determined to be [InCl 4 −[2S·H]+; the complex formed with TBP was [InCl 4 −[3S·H]+, where S represents the neutral extractant species. • It was found that 99% of In were extracted and 100% of the indium on the loaded organic phase was stripped by water. • Indium can be extracted from hydrochloric acid and enriched in a low-acidity strip solution. Solvent extraction of indium from hydrochloric acid solution using N,N-di(1-methyl-eptyl) acetamide (N503), di(l-methylheptyl)methyl phosphate (P350), and tributyl phosphate (TBP) diluted in sulfonated kerosene was investigated. Extraction was studied as a function of hydrochloric acid and chloride ion concentrations, organic-phase composition, initial indium concentration, phase contact time, and aqueous/organic (A/O) volumetric ratio. The extraction stoichiometry was determined by slope analysis and confirmed by Fourier-transform infrared spectroscopy. It was found that indium extraction efficiency decreased in the order: N503 > P350 > TBP. The extracted complexes with N503 and P350 were determined to be [InCl 4 −[2S·H]+; the complex formed with TBP was [InCl 4 −[3S·H]+, where S represents the neutral extractant species. N503 was found to be best extractant of the three with respect to extracting indium from solutions containing a high concentration of hydrochloric acid. Almost quantitative (99%) indium extraction was obtained using 0.5 mol·L−1 N503 in three extraction stages at an A/O ratio of 2/1; 100% of the indium on the loaded organic phase was stripped by water in two stages at an A/O ratio of 1/3. Indium can therefore be extracted from hydrochloric acid and enriched in a low-acidity strip solution. [ABSTRACT FROM AUTHOR]

We present a sunlight based handheld smartphone spectrometer. The device first gathers the sunlight to pass through the sample, and then the transmitted light illuminates on a grating to generate spectrum finally recorded by the smartphone monochrome camera. All the optical elements are assembled with the smartphone to integrate a handheld device with the size of 140.2 mm × 67.4 mm × 80.5 mm. Besides, a smartphone application is also developed for automatic spectral calibration, detection, analysis and display. Compared to the white light emitting diode and the halogen lamp, the sunlight has more uniform distribution covering the entire visible spectral range; and the proposed device also avoids the bulky sizes of those broadband light sources. Additionally, the monochrome camera is used instead of the color camera not only to pursue a high spectral resolution as 0.276 nm/pixel but also to avoid the color overlapping. We demonstrate the device capability on detecting avian influenza virus H7N9 and porcine circovirus type 2 antibodies, proving the device has rather high sensitivity similar to the commercial microplate reader. Considering its advantages as compact size, high spectral resolution and detecting sensitivity, it is believed the proposed sunlight based handheld smartphone spectrometer is potential to be broadly applied in on-site detections. For the first time to our best knowledge, we have proposed a sunlight based handheld smartphone spectrometer which has compact size and high spectral resolution; and it has been successfully used for virus detection with favorable sensitivity and detection precision. Image 1 • The first example of sunlight based handheld smartphone spectrometer. • The device has compact size and high spectral resolution. • An Android application simplifies the detection procedures. • The device has favorable sensitivity and detection precision. • The device has been successfully used for virus detection. [ABSTRACT FROM AUTHOR]

Abstract Background Wheat allergy is a major food allergy that has reached significant levels of global public health concern. Potential variation in allergenicity among different wheat genotypes is not well studied at present largely due to the unavailability of validated methods. Here, we developed and validated a novel mouse-based primary screening method for this purpose. Methods Groups of Balb/c mice weaned on-to a plant protein-free diet were sensitized with salt-soluble protein (SSP) extracted from AABB genotype of wheat (durum, Carpio variety). After confirming clinical sensitization for anaphylaxis, mice were boosted 7 times over a 6-month period. Using a pooled-plasma mini bank, a wheat-specific IgE-inhibition (II)-ELISA was optimized. Then the relative allergenicity of SSPs from tetraploid (AABB), hexaploid (AABBDD) and diploid (DD) wheat genotypes were determined. The IC 50 /IC 75 values were estimated using IgE inhibition curves. Results The optimized II-ELISA with an inhibition time of 2.5 h had a co-efficient of variation of <2%. Primary screening for relative allergenicity demonstrated that IgE binding to AABB-SSP was significantly abolished by the other two wheat genotypes. Compared to AABB, the relative allergenicity of SSPs of AABBDD and DD were significantly lower (p <.01). Furthermore, IgE inhibition curves showed significant differences in IC 50 and IC 75 values among the three wheat genotypes. Conclusion We report a novel mouse-based primary screening method of testing relative allergenicity of wheat proteins from three different wheat genotypes for the first time. This method is expected to have broad applications in wheat allergy research. [ABSTRACT FROM AUTHOR]

• Smartphone based optical fiber fluorescence sensor (SOFFS) is designed for remote and on-site Hg2+ detection. • SOFFS is handheld with inner power supply, and fiber probe can be easily replaced, supporting remote and on-site detection. • Highly specific detection of Hg2+ with a linear relation between 1 nM and 1 μM with a detection limit of 1 nM is reached. • Simple and rapid operations within 3 min are required for single Hg2+ detection. In order to detect Hg2+ in remote and on-site mode, we design a smartphone based optical fiber fluorescence sensor (SOFFS), which is composed of a semiconductor laser for fluorescence signal excitation, a quantum dot modified fiber probe for Hg2+ sensing, a smartphone with a filter for fluorescence signal collection, and a fiber coupler for connecting fiber probe, laser and smartphone. With the evanescent wave on the optimized combination tapered fiber probe surface, SOFFS has an ultra-low detection limit of 1 nM and a wide detection range between 1 nM to 1000 nM. Besides, it is handheld with a small size of 79×57×154 mm3 and inner power supply, and the combination tapered fiber probe can be easily replaced, supporting the remote and on-site applications. Additionally, a smartphone application is designed for automatically quantifying the fluorescence signals for accurate and rapid Hg2+ detection. Since SOFFS is compact and cost-effective, moreover, it can measure Hg2+ in fast speed, excellent selectivity, high accuracy and sensitivity, it is a potential tool for remote and on-site applications. [ABSTRACT FROM AUTHOR]

Objective This study investigated the role and mechanism of action of G protein-coupled estrogen receptor (GPER) in melanogenesis. Methods GPER expression was detected in the A375 human melanoma cell line and B16 mouse melanoma cell line. Cell proliferation, melanin content, tyrosinase (TYR) activity, cyclic adenosine monophosphate (cAMP) level, and TYR and microphthalmia-related transcription factor (MITF) expression were measured. GPER activation was altered by agonist and antagonist treatment and its expression was downregulated by gene silencing. Estradiol-induced melanin synthesis and the activation of related signaling pathways were suppressed by inhibiting GPER via antagonist treatment. The relationship between GPER and TYR was evaluated in clinical chloasma samples by immunohistochemistry. Results Upregulation of GPER in A375 cells promoted melanogenesis, favored as indicated by increases in TYR and MITF expression and TYR activity. GPER activated melanin production via the cAMP-protein kinase (PK) A pathway, suggesting that GPER plays an important role in estrogen-induced melanin synthesis. The effect of GPER activation on cAMP-MITF-TYR signaling was also demonstrated in B16 cells. A significant association was observed between GPER and TYR expression in chloasma skin lesions relative to normal skin. Conclusion GPER enhances melanin synthesis via cAMP-PKA-MITF-TYR signaling and modulates the effects of estrogen in melanogenesis. GPER is therefore a potential drug target for chloasma treatment. [ABSTRACT FROM AUTHOR]

We design a honey antibiotic detection system (HADS), which provides honey antibiotic residue rapid on-site detecting solution relying on simple sample preparation tactics, lateral-flow immunochromatographic assay (LFIA)-based strip and handheld sensor reader. Relying on the quantum dot microsphere probes conjugated to the antibiotic monoclonal antibodies, the LFIA strip can simultaneously detect sulfonamides (SAs) and tetracyclines (TCs) in high sensitivity with extremely low detecting limits of 0.4 μg/kg and good specificity. Moreover, the fabricated LFIA strips can be well conserved in vacuum-sealed bags at 4 °C for at least 6 months. Combining with the handheld sensor reader, both SAs and TCs can be quantitatively and automatically measured in high accuracy. All the operations including sample preparation and detection can be finished within 20 min at room temperature on site without any extra devices or complicated operations. • We design honey antibiotic detection system (HADS) for antibiotic residue detection. • HADS can detect sulfonamides (SAs) and tetracyclines (TCs) in high sensitivity. • HADS supports rapid (20 min) and cost-effective (75 cents) antibiotic detection. • HADS is proved with high accuracy, good stability, selectivity and specificity. • HADS supports rapid on-site detection for honey antibiotic residues. [ABSTRACT FROM AUTHOR]

Avian influenza virus (AIV) is a serious zoonotic disease causing severe damages to both poultry industry and human health. To rapidly detect AIV on-site with high sensitivity and accuracy, we design sensitive antibody fluorescence immunosorbent assay (SAFIA) on AIV H9N2 antibody. In SAFIA, hemagglutinin (HA1) protein coated sample chamber specifically binds targets but remarkably reduces non-specific absorption; Protein L coated polystyrene microsphere captures target through secondary antibody to significantly amplify the fluorescence signal; and a portable fluorescence counter automatically measures the fluorescence spot density for AIV H9N2 antibody detection. Proved by practical applications, SAFIA could probe AIV H9N2 antibody in high sensitivity and selectivity, and distinguish positive and negative serum samples in high accuracy. Additionally, SAFIA can rapidly detect AIV H9N2 antibody at room temperature only requiring simple operations as well as cost-effective and compact devices. Therefore, SAFIA is a potential new-generation tool in rapid on-site testing for agricultures. Here, we design sensitive antibody fluorescence immunosorbent assay (SAFIA) for rapid on-site detection on AIV H9N2 antibody based on the hemagglutinin (HA1) protein coated sample chambers, the Protein L coated polystyrene microspheres and the portable fluorescence counter. [Display omitted] • We design sensitive antibody fluorescence immunosorbent assay (SAFIA). • SAFIA is rather sensitive by probing target antibody. • SAFIA only needs simple operations, low cost devices and can be finished in 80 min. • SAFIA is especially suited for rapid on-site testing for agricultures. [ABSTRACT FROM AUTHOR]

• A quantitative ciprofloxacin (CIP) immunochromatographic test strip is designed. • It is very sensitive with an extremely low detection limit of 0.05 ng/mL. • It has wide linear detection range supporting quantitative CIP detection. • It supports automatic, rapid and cost-effective CIP detection. • It is proved with good selectivity, reproducibility and stability. The ciprofloxacin (CIP) abuse has caused many problems threatening to human health. Here, we design the quantum dot microsphere (QDM) based immunochromatographic quantitative CIP test strip: when the sample under detection contains CIP, the QDM-monoclonal antibody (mAb) probes bound with the CIP and cannot be captured by CIP-bovine serum albumin (BSA) conjugation dispersed on the T lines, reducing the fluorescence intensities. These test strips can provide a low detection limit of 0.05 ng/mL and a wide linear detection range from 0.1 ng/mL to 100 ng/mL in high sensitivity and accuracy as well as good selectivity, reproducibility and stability. Moreover, a smartphone based test strip reader with the size of 85 mm × 48 mm × 44 mm is also fabricated using 3-D printing to automatically and quantitatively detect CIP. The whole process of CIP detection can be finished within 15 min, but only cost ~1 RMB (10 cents). [ABSTRACT FROM AUTHOR]