Prediction value of pericoronary fat attenuation index for coronary in-stent restenosis.

OBJECTIVES: As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level. RESULTS: A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was - 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (△area under the curve = + 0.064; p = 0.001). CONCLUSION: Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR. CLINICAL RELEVANCE STATEMENT: Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis. KEY POINTS: • Pericoronary fat attenuation index reflects the local coronary inflammation. • Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. • Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis.

Additive-Free Construction of Tetrahydropyrimidine Skeleton by using 1,3,5-Triazinane as Four-Atom Synthon.

Herein, an unprecedented [4 + 2] cycloaddition of enaminone with 1,3,5-triazinane has been developed. The representative semihydrogenated aromatic heterocycle 1,2,3,4-tetrahydropyrimidines have been synthesized with a broad substrate scope, demonstrating potential antitumor activity. This approach has been smoothly conducted under additive-free and environmentally friendly conditions that are compatible with various functional groups. Furthermore, the condition optimization process reveals that the tetrahydropyrimidine product is regulated via the reaction temperature.

Bimetal loaded graphitic carbon nitride with synergistic enhanced peroxidase-like activity for colorimetric detection of p-phenylenediamine.

In recent years, great progress has been made on the study of nanozymes with enzyme-like properties. Here, bimetallic Fe and Ni nanoclusters were anchored on the nanosheets of nitrogen-rich layered graphitic carbon nitride by one-step pyrolysis at high temperature (Fe/Ni-CN). The loading content of Fe and Ni on Fe/Ni-CN is as high as 8.0%, and Fe/Ni-CN has a high specific surface area of 121.86 m2 g-1. The Fe/Ni-CN can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and exhibits efficient peroxidase-like activity, leading to a 17.2-fold increase compared to pure graphitic carbon nitride (CN). Similar to the natural horseradish peroxidase (HRP), the Fe/Ni-CN nanozyme follows catalytic kinetics. The Michaelis-Menten constant (Km) value of the Fe/Ni-CN nanozyme for TMB is about 8.3-fold lower than that for HRP, which means that the Fe/Ni-CN nanozyme has better affinity for TMB. In addition, the catalytic mechanism was investigated by combination of free radical quenching experiments and density-functional theory (DFT) calculations. The results show that the high peroxidase-like activity is due to the easy adsorption of H2O2 after bimetal loading, which is conducive to the production of hydroxyl radicals. Based on the extraordinary peroxidase-like activity, the colorimetric detection of p-phenylenediamine (PPD) was constructed with a wide linear range of 0.2-30 µM and a low detection limit of 0.02 µM. The sensor system has been successfully applied to the detection of residual PPD in real dyed hair samples. The results show that the colorimetric method is sensitive, highly selective and accurate. This study provides a new idea for the efficient enhancement of nanozyme activity and effective detection of PPD by a bimetallic synergistic strategy.

High-temperature PTT/CDT coordination nanoplatform realizing exacerbated hypoxia for enhancing hypoxia-activated chemotherapy to overcome tumor drug resistance.

BACKGROUND: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. RESULTS: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn2+-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. CONCLUSIONS: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.

Evaluating the Efficacy of Chinese Patent Medicine Paiteling in Treating Vaginal Stump Disease VaIN: An Analysis of 67 Clinical Cases.

Background: Vaginal Intraepithelial Neoplasia (VaIN) is a prevalent condition that can progress to invasive carcinoma if left untreated. Despite its significance, effective treatments for VaIN remain limited. Objective: This study aimed to analyze the efficacy of Paiteling in treating VaIN among patients who have undergone total hysterectomy due to high cervical lesions or invasive cervical cancer. Design: This study employed a retrospective design. Settings: The study was conducted at Ningxia General Hospital of Medical University from January 2019 to January 2023. Participants: A total of 67 cases diagnosed with VaIN were included in the study. Inclusion criteria comprised patients who had undergone total hysterectomy for high cervical lesions or invasive cervical cancer and had confirmed VaIN diagnosis through abnormal ThinPrep Cytology Test (TCT) and/or High-risk Human Papillomavirus (HR-HPV) results with colposcopy biopsy. Intervention: Patients were treated with Chinese patent medicines Paiteling and patulin according to their specific VaIN classification: VaIN1, VaIN2, and VaIN3. Primary Outcome Measures: The primary outcome measures included complete negative conversion rates for VaIN1, VaIN2, and VaIN3, as well as overall effective rate and complete negative rate across all VaIN cases. Statistical analysis was performed using IBM SPSS 24.0, with significance set at P < .05. Results: Patients with VaIN1, VaIN2, and VaIN3 were treated with Chinese patent medicines Paiteling, and patulin, respectively. Complete negative conversion rates were 100% for VaIN1, 72.73% for VaIN2, and 75.67% for VaIN3, resulting in an overall effective rate of 88.89% and a complete negative rate of 72.22% across all VaIN cases. Conclusion: This study underscores the efficacy of Chinese patent medicine Paiteling in managing post-total hysterectomy VaIN. It presents a conservative treatment option for vaginal stump diseases, addressing a crucial gap in therapeutic strategies. The findings advocate for further exploration of Paiteling's potential in VaIN management.

2D-materials-integrated optoelectromechanics: recent progress and future perspectives.

The discovery of two-dimensional (2D) materials has gained worldwide attention owing to their extraordinary optical, electrical, and mechanical properties. Due to their atomic layer thicknesses, the emerging 2D materials have great advantages of enhanced interaction strength, broad operating bandwidth, and ultralow power consumption for optoelectromechanical coupling. The van der Waals (vdW) epitaxy or multidimensional integration of 2D material family provides a promising platform for on-chip advanced nano-optoelectromechanical systems (NOEMS). Here, we provide a comprehensive review on the nanomechanical properties of 2D materials and the recent advances of 2D-materials-integrated nano-electromechanical systems and nano-optomechanical systems. By utilizing active nanophotonics and optoelectronics as the interface, 2D active NOEMS and their coupling effects are particularly highlighted at the 2D atomic scale. Finally, we share our viewpoints on the future perspectives and key challenges of scalable 2D-materials-integrated active NOEMS for on-chip miniaturized, lightweight, and multifunctional integration applications.

Residual Risk in Non-ST-Segment Elevation Acute Coronary Syndrome: Quantitative Plaque Analysis at Coronary CT Angiography.

Background Lipid-rich plaques detected with intravascular imaging are associated with adverse cardiovascular events in patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). But evidence about the prognostic implication of coronary CT angiography (CCTA) in NSTE ACS is limited. Purpose To assess whether quantitative variables at CCTA that reflect lipid content in nonrevascularized plaques in individuals with NSTE ACS might be predictors of subsequent nonrevascularized plaque-related major adverse cardiovascular events (MACEs). Materials and Methods In this multicenter prospective cohort study, from November 2017 to January 2019, individuals diagnosed with NSTE ACS (excluding those at very high risk) were enrolled and underwent CCTA before invasive coronary angiography (ICA) within 1 day. Lipid core was defined as areas with attenuation less than 30 HU in plaques. MACEs were defined as cardiac death, myocardial infarction, hospitalization for unstable angina, and revascularization. Participants were followed up at 6 months, 12 months, and annually thereafter for at least 3 years (ending by July 2022). Multivariable analysis using Cox proportional hazards regression models was performed to determine the association between lipid core burden, lipid core volume, and future nonrevascularized plaque-related MACEs at both the participant and plaque levels. Results A total of 342 participants (mean age, 57.9 years ± 11.1 [SD]; 263 male) were included for analysis with a median follow-up period of 4.0 years (IQR, 3.6-4.4 years). The 4-year nonrevascularized plaque-related MACE rate was 23.9% (95% CI: 19.1, 28.5). Lipid core burden (hazard ratio [HR], 12.6; 95% CI: 4.6, 34.3) was an independent predictor at the participant level, with an optimum threshold of 2.8%. Lipid core burden (HR, 12.1; 95% CI: 6.6, 22.3) and volume (HR, 11.0; 95% CI: 6.5, 18.4) were independent predictors at the plaque level, with an optimum threshold of 7.2% and 10.1 mm3, respectively. Conclusion In NSTE ACS, quantitative analysis of plaque lipid content at CCTA independently predicted participants and plaques at higher risk for future nonrevascularized plaque-related MACEs. Chinese Clinical Trial Registry no. ChiCTR1800018661 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tavakoli and Duman in this issue.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants.

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.

SNARE proteins VAMP721 and VAMP722 mediate the post-Golgi trafficking required for auxin-mediated development in Arabidopsis.

The plant hormone auxin controls many aspects of plant development. Membrane trafficking processes, such as secretion, endocytosis and recycling, regulate the polar localization of auxin transporters in order to establish an auxin concentration gradient. Here, we investigate the function of the Arabidopsis thaliana R-SNAREs VESICLE-ASSOCIATED MEMBRANE PROTEIN 721 (VAMP721) and VAMP722 in the post-Golgi trafficking required for proper auxin distribution and seedling growth. We show that multiple growth phenotypes, such as cotyledon development, vein patterning and lateral root growth, were defective in the double homozygous vamp721 vamp722 mutant. Abnormal auxin distribution and root patterning were also observed in the mutant seedlings. Fluorescence imaging revealed that three auxin transporters, PIN-FORMED 1 (PIN1), PIN2 and AUXIN RESISTANT 1 (AUX1), aberrantly accumulate within the cytoplasm of the double mutant, impairing the polar localization at the plasma membrane (PM). Analysis of intracellular trafficking demonstrated the involvement of VAMP721 and VAMP722 in the endocytosis of FM4-64 and the secretion and recycling of the PIN2 transporter protein to the PM, but not its trafficking to the vacuole. Furthermore, vamp721 vamp722 mutant roots display enlarged trans-Golgi network (TGN) structures, as indicated by the subcellular localization of a variety of marker proteins and the ultrastructure observed using transmission electron microscopy. Thus, our results suggest that the R-SNAREs VAMP721 and VAMP722 mediate the post-Golgi trafficking of auxin transporters to the PM from the TGN subdomains, substantially contributing to plant growth.

Precisely controlled polydopamine-mediated antibacterial system: mathematical model of polymerization, prediction of antibacterial capacity, and promotion of wound healing.

In this work, the polydopamine (PDA)-mediated antibacterial system is synthesized to carry out antimicrobial activities in vitro and in vivo. First, to precisely control the surface modification of nanodiamonds (NDs), a mathematical kinetics model of PDA deposition is established, and the conditions of synthesis reaction are discussed including influencing factors such as the concentrations of dopamine, reaction time, and the kinetic constant k1, which is a function of several variables associated with the reaction temperature, light irradiance (especially at ultraviolet wavelengths), pH value and concentration of dissolved O2 in the solution. A simulated visualization demonstrates that the deposition thickness of PDA is positively correlated with temperature and light irradiance, and PDA is easier to deposit in an alkaline solution and will be terminated if the dissolved O2 is insufficient. Then, the precisely controlled thickness of PDA can control the growth of AgNPs, rendering the intensity of Raman peaks increased and providing a predictable antibacterial effect against E. coli in vitro. An optimized antibacterial hydrogel containing NDs-PDA/Ag is prepared and characterized by the Fourier transform infrared spectroscopy and field emission scanning electron microscopy. Finally, the antibacterial experiments to promote wound healing in vivo are performed, which are verified by pathological and immunohistochemical-stained sections. This work provides a theoretical basis of predicting the PDA-assisted surface modification of NDs, giving a divinable antibacterial effect, and promoting wounds healing in vivo.

Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer.

BACKGROUND: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. RESULTS: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. CONCLUSIONS: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Non-Steady State NMR Effect and Application on Time-Varying Magnetic Field Measurement.

The measurement of a time-varying magnetic field is different from a constant magnetic field, due to its field intensity variation with time. Usually, the time-varying magnetic field measurement converts the solution of the magnetic induction intensity into the calculation of the induced electromotive force (EMF); then, the magnetic induction intensity is obtained by the time integration of the EMF, but the process is vulnerable to external interference. In this paper, a non-steady state nuclear magnetic resonance (NSS-NMR) scheme for the measurement of a time-varying magnetic field is proposed. In a time-varying magnetic field environment, an RF excitation signal with a certain frequency bandwidth is applied to excite the nuclear spin system. The NSS-NMR signal, which varies with time in the frequency range corresponding to the frequency bandwidth of the RF excitation, could finally be obtained after a series of processing of the probe output signal. During the NSS-NMR experiment, an orthogonal dual-coil probe is adopted to synchronously generate the RF excitation and induce the probe output signal. Moreover, a directional coupler that utilized in the experiment outputs a reference signal from the coupling port for the subsequent signal processing. The experimental results show that the weak NSS-NMR signal is indeed observed. The longitudinal time-varying magnetic field ranges from 0.576 T to 0.582 T, which is inverted by the Larmor precession relationship, have been successfully detected based on the so-called NSS-NMR effect.

Insights into regulatory characteristics of the promoters of Sericin 1 and Sericin 3 in transgenic silkworms.

Sericin, produced in the middle silk gland (MSG) of silkworms, is a group of glue proteins that coat and cement silk fibers. Several genes are known to encode sericin, but their spatiotemporal regulation has yet to be fully elucidated. Here, we report in detail the expression profiles of the promoters of two major sericin-coding genes, Sericin 1 (Ser1)and Sericin 3 (Ser3), by analyzing Gal4/UAS transgenic silkworms. We found that UAS-linked EGFP fluorescence in transgenic silkworms driven by Ser1-Gal4was detected in only the R3, R4 and R5 regions of MSG starting inday-3 fifth-instar larvae and was continuously expressed until silk gland degradation. In transgenic silkworms driven by Ser3-Gal4, EGFP fluorescence was detected at a low level in the R2 region of MSG since the last day of fifth-instar larvae, and the expression increased during the wandering stages and was continuously detected until silk gland degradation. The molecular detection of EGFP expression in each of the Gal4/UAS transgenic silkworms was consistent with fluorescence observations. These findings reveal clear differences in the regulatory characteristics of the promoters of Ser1and Ser3 and provide new insights into the regulatory mechanism of the expression of sericin-coding genes.

The intronic promoter of Actin4 mediates high-level transgene expression mainly in the wing and epidermis of silkworms.

The cytoplasmic actin gene Actin4 (A4) in silkworm (Bombyx mori) was isolated 20 years ago and has a distal promoter upstream of the first exon and a proximal promoter within the first intron; however, how the promoter regulates gene expression has yet to be fully elucidated. Here, we characterized the function and expression of the proximal promoter (named A4IP) by analyzing transgenic Gal4/UAS silkworms, A4IP-Gal4/UAS-EGFP. We demonstrated that A4IP drives the expression of Gal4 and thereby activates UAS-linked EGFP in transgenic silkworms beginning in day-3 embryos through adults. Further detection revealed that EGFP was expressed at a low level in tissues including the trachea, fat body and midgut but was highly expressed in the wing disks/wings and inner epidermis of transgenic silkworms. No EGFP signals were detected in other tissues by western blot assay. Interestingly, EGFP fluorescence had a spot-like distribution on the epidermis of transgenic larvae. These observations are quite different from those in transgenic silkworms driven by the promoter of Actin3 (A3), another cytoplasmic actin gene in B. mori. These findings reveal the expression profiles of the A4IP promoter and provide new insights into the regulatory mechanism of cytoplasmic actin genes in silkworms.

Silencing microRNA-210 in Hypoxia-Induced HUVEC-Derived Extracellular Vesicles Inhibits Hemangioma.

BACKGROUND: Hemangioma (Hem) is a benign tumor commonly seen in infancy with a relative high morbidity. Human umbilical vein endothelial cell (HUVEC)-derived extracellular vesicles (EVs) are actively participated in Hem. Therefore, this study is designed to figure out the underlying mechanism of HUVEC-derived EVs in Hem. METHODS: Initially, EVs were separated from HUVECs and identified. HUVEC-derived EVs in normoxia or hypoxia were then cultivated with Hem endothelial cells (HemECs) to test the proliferation, apoptosis, and migration of HemECs. Microarray analysis was performed to select microRNAs (miRs) with differential expression. miR-210 in hypoxia-induced HUVECs was silenced, and the relevant EVs were extracted and then co-cultured with HemECs to perform biological effect experiments. Then, the target relation between miR-210 and homeobox A9 (HOXA9) was identified by the dual luciferase reporter gene assay and RNA immunoprecipitation assay. Moreover, xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS: Hypoxia-induced HUVECs promoted release of EVs, which were absorbed by HemECs. Hypoxia-induced HUVEC-EVs promoted HemEC proliferation and migration and inhibited apoptosis. miR-210 from the hypoxia-induced HUVEC-EVs was highly expressed and promoted HemEC growth. Silencing miR-210 expression in the hypoxia-induced HUVEC-EVs suppresses Hem development in vivo. In addition, miR-210 targeted HOXA9. CONCLUSION: Silencing miR-210 in HUVEC-derived EVs could suppress Hem by targeting HOXA9. This investigation may provide novel insights for Hem treatment.

Differential expression patterns of specific long noncoding RNAs and competing endogenous RNA network in alopecia areata.

BACKGROUND: Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs) and indirectly interact with messenger RNA (mRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in alopecia areata (AA) are not fully understood. METHODS: The blood lncRNA profiles were obtained by microarray from 10 samples, including five alopecia areata samples and five normal samples. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in alopecia areata. RESULTS: We found 154 differentially expressed lncRNAs and 46 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of focal adhesion, Mucin type O-glycan biosynthesis, and so on. The differentially expressed lncRNA (DElncRNA) involved in the pathway of thyronamine and iodothyronamine metabolism and so on. Through integrated lncRNA-mRNA and miRNA-mRNA pairs, the ceRNA network was constructed, thereafter, six ceRNA subnetworks were identified and subnetwork 1 were found to be significantly associated with the occurrence of alopecia areata. CONCLUSION: Our results showed blood lncRNA expression patterns and a complex ceRNA network in alopecia areata. However, futher studies on blood and tissue verification of these lncRNAs and relative pathways are needed.

Identification of blood microRNA alterations in patients with severe active alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common inflammatory disease characterized by cellular infiltration of T cells targeting the anagen-stage hair follicle. Lack of efficacious treatment for AA may be due to little knowledge about its exact cellular mechanism. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of inflammatory skin diseases such as atopic dermatitis and psoriasis. However, little is known about the role of miRNAs in AA. OBJECTIVE: The present study aimed to explore the blood miRNAs alterations in patients with severe active AA. METHODS: We constructed a bipartite miRNA-messenger RNA (mRNA) regulatory network by the validated miRNA-mRNA relationships. Subsequently, the miRNA-miRNA synergistic network was formed in consideration of the Gene Ontology function enrichment of coregulated target genes. Lastly, the functional network was identified by the ingenuity pathway analysis. RESULTS: By using an Agilent microarray that covers 2549 human miRNAs, we identified 36 significantly differentially expressed miRNAs in severe active AA patients. miRNA target gene prediction and functional annotation analysis showed significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, transforming growth factor-ßsignaling, and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the active phase of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time polymerase chain reaction validation. Among the miRNAs, miR-210 and miR-1246 had high prediction with high accuracy. CONCLUSION: Blood dysregulated miRNAs are potentially associated with the severe active AA. These miRNAs could function synergistically and might be promising targets for the development of novel treatments for AA in the future.

Amplification of 18 OAM modes in a ring-core erbium-doped fiber with low differential modal gain.

We theoretically propose two orbital angular momentum (OAM) erbium-doped ring-core fiber (RCF) amplifiers capable of providing relatively uniform gain for 22 modes with 18 OAM ones over the C-band. Two schemes of doping profile are discussed, one with single layer erbium doping and the other with double layer erbium doping. Theoretical analyses and numerical simulations suggest that the proposed first OAM erbium-doped fiber amplifier (OAM-EDFA) can obtain a gain larger than 20 dB for all 22 modes with differential modal gain (DMG) lower than 0.71 dB. The second OAM-EDFA performs better and can provide a larger gain over 21.5 dB for all 22 modes, with a smaller DMG below 0.27 dB and the noise figure (NF) lower than 3.9 dB over the whole C band. The presented OAM-EDFA may open up new perspectives for long-distance transmission in capacity scaling fiber-optic communications using OAM modes.

Effect of 410 nm photodynamic therapy with hemoporfin on the expression of vascular endothelial growth factor (VEGF) in cultured human vascular endothelial cells.

Photodynamic therapy (PDT) is considered an effective alternative for the treatment of port-wine stains (PWS) using hemoporfin (hematoporphyrin monomethyl ether, HMME), a novel photosensitizer with better efficacy and lower recurrence. Vascular endothelial growth factor (VEGF) plays an important role in the development of PWS. Therefore, we conducted this study to investigate the effect of HMME-PDT on VEGF expression. Human vascular endothelial cells (HUVECs) were treated with different doses of HMME and irradiated with 410-nm light emitting-diode (LED) light. To assess cell viability, CCK-8 assays were performed. At 48 h after PDT, the expression of VEGF/VEGF receptor (VEGFR) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Measurement of VEGF protein was carried out using western blotting assays. Cell viability was significantly inhibited after HMME-PDT and was dose-dependent within a certain range. HMME-PDT decreased secretion of VEGF 48 h after irradiation in HUVECs as compared to controls. The downregulation of VEGF and VEGFR mRNA as well as VEGF protein expression was more significant in the high HMME concentration group (4 µg/mL) than in the lower concentration group (2 µg/mL). Our outcomes provide evidence, that HMME-PDT can downregulate VEGF expression in cultured HUVECs and may explain the efficacy of hemoporfin PDT for PWS treatment.