Clinical efficacy and safety of coseasonal initiation of Artemisia annua sublingual immunotherapy on patients with Artemisia-induced rhinoconjunctivitis.

PURPOSE: Patients with seasonal allergic rhinoconjunctivitis (SARC) might seek evaluation and treatment when symptoms appear during the pollen season. It is unclear whether coseasonal-initiated sublingual immunotherapy (SLIT) would be effective and safe for SARC. This study aims to identify the feasibility of initiating Artemisia annua SLIT during the pollen season. MATERIALS AND METHODS: Sixty patients with Artemisia-induced SARC were equally recruited into the SLIT and control groups during the pollen season in 2021. The SLIT group was treated with standardized Artemisia annua SLIT drops using a modified dosing schedule combined with pharmacotherapy, while the control group only received pharmacotherapy. Diary cards for clinical symptoms, rescue medication use, and adverse events (AEs) were recorded during the pollen seasons. Objective measures, including average daily combined scores of medication and rhinoconjunctivitis symptoms (CSMRS), total rhinoconjunctivitis symptom score (TRSS), total medication score (TMS), and the score of visual analog scale (VAS) were calculated to evaluate the efficacy of SLIT. Safety was assessed through the occurrence and severity of AEs. RESULTS: In total, 80.0 % (24/30) patients in the SLIT group and 86.67 % (26/30) patients in the control group completed the study. The severity of SARC, which was assessed by objective measures including CSMRS, TRSS, TMS, and VAS of the SLIT group and the control group, was generally at the same level during the 2021 pollen season, except for the medical consumption, which the score of TMS was slightly higher in the SLIT group. After one year of treatment, the scores of CSMRS, TRSS, and VAS in the SLIT group were significantly improved compared with the control group (all P < 0.001), and the difference in the TMS between the two groups disappeared (P > 0.05). Moreover, clinical improvement of the four objective measures was also observed in the SLIT group compared with the baseline value (P < 0.001). Overall, 9/24 patients in the SLIT group experienced mild local AEs, and two patients experienced mild systemic AEs during the SLIT period. CONCLUSIONS: This controlled preliminary study identified that coseasonal-initiated Artemisia annua SLIT treatment for one year was generally safe and effective in improving the symptoms of SARC patients induced by Artemisia annua pollen.

Electrotaxis of alveolar epithelial cells in direct-current electric fields.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Retracted: Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκB-PUMA Signaling.

The in vitro experiments of TGF-ß1 and the results of RT-PCR could not be repeated. In order not to affect others, the authors have asked for a retraction. Reference: Qiang Yin, Shan Liu, Anbing Dong, Xiufang Mi, Fengyun Hao, Kejun Zhang. Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFkappakB-PUMA Signaling. Med Sci Monit 2016; 22: 2267-2277. DOI: 10.12659/MSM.898702.

Retracted: The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.

This publication has been retracted by the Editor due to the identification of falsified figure images and manuscript content that raise concerns regarding the credibility of the study and the manuscript. Reference: Vemurafenib Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang. The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib. Med Sci Monit, 2018; 24: 3002-3010. DOI: 10.12659/MSM.910084.

The diagnostic model for early detection of gestational diabetes mellitus and gestational diabetic nephropathy.

BACKGROUND: Gestational diabetes mellitus (GDM) and gestational diabetic nephropathy (GDN) have become an increasingly serious problem worldwide, which can cause a large number of adverse pregnancy consequences for mothers and infants. However, the diagnosis of GDM and GDN remains a challenge due to the lack of optimal biomarkers, and the examination has high requirements for patient compliance. We aimed to establish a simple early diagnostic model for GDM and GDN. METHODS: We recruited 50 healthy pregnant (HP), 99 GDM patients, 99 GDN patients at Daping Hospital. Renal function indicators and blood cell indicators were collected for all patients. RESULTS: Compared with HP, GDM, and GDN patients exhibited significantly higher urea/creatinine ratio and NEU. The diagnostic model1 based on the combination of urea/creatinine ratio and NEU was built using logistic regression. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the diagnostic model was 0.77 (0.7, 0.84) in distinguishing GDM from HP, and the AUC of the diagnostic model was 0.94 (0.9, 0.97) in distinguishing GDN from HP. Meanwhile, the diagnostic model2 based on the combination of ß2-mG, PLT, and NEU in GDM and GDN patients was built using logistic regression, and the area under the ROC curve (AUC ROC) was 0.79 (0.73, 0.85), which was larger than the individual biomarker AUC. CONCLUSION: Our study demonstrated that the diagnostic model established by the combination of renal function indicators and blood cell indicators could facilitate the differential diagnosis of GDM and GDN patients.

Medical Image Authentication Method Based on the Wavelet Packet and Energy Entropy.

The transmission of digital medical information is affected by data compression, noise, scaling, labeling, and other factors. At the same time, medical data may be illegally copied and maliciously tampered with without authorization. Therefore, the copyright protection and integrity authentication of medical information are worthy of attention. In this paper, based on the wavelet packet and energy entropy, a new method of medical image authentication is designed. The proposed method uses the sliding window to measure the energy of the detail information. In the time-frequency data distribution, the local details of the data are mined. The complexity of energy is quantitatively described to highlight the valuable information. Based on the energy weight, the local energy entropy is constructed and normalized. The adjusted entropy value is used as the feature vector of the authentication information. A series of experiments show that the authentication method has good robustness against shearing attacks, median filtering, contrast enhancement, brightness enhancement, salt-and-pepper noise, Gaussian noise, multiplicative noise, image rotation, scaling attacks, sharpening, JPEG compression, and other attacks.

Measuring Public Reaction to Violence Against Doctors in China: Interrupted Time Series Analysis of Media Reports.

BACKGROUND: Violence against doctors in China is a serious problem that has attracted attention from both domestic and international media. OBJECTIVE: This study investigates readers' responses to media reports on violence against doctors to identify attitudes toward perpetrators and physicians and examine if such trends are influenced by national policies. METHODS: We searched 17 Chinese violence against doctors reports in international media sources from 2011 to 2020. We then tracked back the original reports and web crawled the 19,220 comments in China. To ascertain the possible turning point of public opinion, we searched violence against doctors-related policies from Tsinghua University ipolicy database from 2011 to 2020, and found 19 policies enacted by the Chinese central government aimed at alleviating the intense patient-physician relationship. We then conducted a series of interrupted time series analyses to examine the influence of these policies on public sentiment toward violence against doctors over time. RESULTS: The interrupted time series analysis (ITSA) showed that the change in public sentiment toward violence against doctors reports was temporally associated with government interventions. The declarations of 10 of the public policies were followed by increases in the proportion of online public opinion in support of doctors (average slope changes of 0.010, P<.05). A decline in the proportion of online public opinion that blamed doctors (average level change of -0.784, P<.05) followed the declaration of 3 policies. CONCLUSIONS: The government's administrative interventions effectively shaped public opinion but only temporarily. Continued public policy interventions are needed to sustain the reduction of hostility toward medical doctors.

Applied electric fields suppress osimertinib-induced cytotoxicity via inhibiting FOXO3a nuclear translocation through AKT activation.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor against T790M-mutant non-small cell lung cancer (NSCLC). Acquired resistance to osimertinib is a growing clinical challenge that is not fully understood. Endogenous electric fields (EFs), components of the tumor microenvironment, are associated with cancer cell migration and proliferation. However, the impact of EFs on drug efficiency has not been studied. In this study, we observed that EFs counteracted the effects of osimertinib. EFs of 100 mV/mm suppressed osimertinib-induced cell death and promoted cell proliferation. Transcriptional analysis revealed that the expression pattern induced by osimertinib was altered by EFs stimulation. KEGG analysis showed that differential expression genes were mostly enriched in PI3K-AKT pathway. Then, we found that osimertinib inhibited AKT phosphorylation, while EFs stimulation resulted in significant activation of AKT, which could override the effects generated by osimertinib. Importantly, pharmacological inhibition of PI3K/AKT by LY294002 diminished EF-induced activation of AKT and restored the cytotoxicity of osimertinib suppressed by EFs, which proved that AKT activation was essential for EFs to attenuate the efficacy of osimertinib. Furthermore, activation of AKT by EFs led to phosphorylation of forkhead box O3a (FOXO3a), and reduction in nuclear translocation of FOXO3a induced by osimertinib, resulting in decreased expression of Bim and attenuated cytotoxicity of osimertinib. Taken together, we demonstrated that EFs suppressed the antitumor activity of osimertinib through AKT/FOXO3a/Bim pathway, and combination of PI3K/AKT inhibitor with osimertinib counteracted the effects of EFs. Our findings provided preliminary data for therapeutic strategies to enhance osimertinib efficacy in NSCLC patients.

Backscattering ratios of soot-contaminated dusts at triple LiDAR wavelengths: T-matrix results.

This paper reports on accurate calculations of backscattering properties of transported and soot-contaminated dust at triple wavelengths (0.355, 0.532, and 1.064 µm, respectively) by using the invariant imbedding T-matrix method. The changes of backscattering ratios from bare to soot-contaminated dust were systematically investigated by employing super-spheroidal dust and fractal soot models. The impacts of morphology change and soot absorptivity on backscattering ratios of soot-contaminated dust were clarified. In addition, it was found that adhesion has a large impact on the backscattering ratios. However, the results of non-contact soot-contaminated dust appear to be closer to observations than those of contact mixing.

S100A4 Knockout Sensitizes Anaplastic Thyroid Carcinoma Cells Harboring BRAFV600E/Mt to Vemurafenib.

BACKGROUND/AIMS: Anaplastic thyroid cancer (ATC), with 25% BRAFV600E mutation, is one of the most lethal human malignancies that currently has no effective therapy. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials, including ATC patients, but is being hampered by the acquisition of drug resistance. Therefore, combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. METHODS: ATC cell lines 8505C (BRAFV600E/mt), SW1736 (BRAFV600E/mt), KAT18 (BRAFV600E/wt) and Cal-62(BRAFV600E/wt) cells were used in the study. The ability of S100A knockout or /and in combination with the BRAF inhibitor vemurafenib on growth, apoptosis, invasion and apoptosis in ATC cells in vitro was demonstrated by MTT and BrdUrd incorporation assay, Annexin-V-FITC staining analyzed by flow cytometry, Transwell migration and Matrigel invasion assay. S100A4,pERK1/2, pAKT and pROCK1/2 protein was detected by western blot assay; Small molecule inhibitors of Y27632, U0126, MK-2206 and constitutively active forms of pCDNA-Myc-pERK, pCMV6-HA-Akt, pCMV-RhoA were employed, and the mechanistic studies were performed. We assessed the efficiency of in vivo combination treatment with S100A4 knockout and Vemurafenib on tumors. RESULTS: S100A4 knockout induced apoptosis and reduced proliferation by inactivation of pAKT and pERK signals, and inhibited invasion and migration by inactivation of pAKT and RhoA/ROCK1/2 signals in 8505C or Cal-62 cells in vitro, and vice versa in SW1736 and KAT18 cells. Vemurafenib did not affect apoptosis of both 8505C and SW1736 cells, but reduced proliferation via arresting cell cycle, and promoted cell migration and invasion in vitro. Combination treatment with S100A4 knockdown and vemurafenib reduced cell proliferation, migration and invasion in vitro compared to the S100A4 knockdown or Vemurafenib alone. Vemurafenib treatment resulted in a transient inhibition of pERK expression and gradually activation of pAKT expression, but quickly recovery from ERK1/2 activation inhibition by vemurafenib treatment in 4 h for SW1736 and 8505C cells. Combined treatment completely inhibited ERK1/2 and AKT activation during 48 h. In an in vivo mouse model of SW1736 and 8505C, vemurafenib treatment alone did not significantly inhibit tumor growth in both of the tumors, but inhibited tumor growth in combined groups. CONCLUSION: Our results show S100A4 knockout alone inhibits ATC cells (rich endogenous S100A4) survival and invasion, regardless of the BRAFV600E status, and potentiates the effect of vemurafenib on tumor regression in vitro and in vivo. In addition, S100A4 knockout potently inhibits the recovery from ERK1/2 activation inhibition and the AKT activation following vemurafenib treatment and reversed the vemurafenib resistance. This therapeutic combination may be of benefit in patients with ATC.

Assessing the depolarization capabilities of nonspherical particles in a super-ellipsoidal shape space.

Here we use the state-of-the-art invariant imbedding T-matrix method to theoretically assess the backscattering linear depolarization ratio (LDR) of nonspherical particles in a super-ellipsoidal shape space. Super-ellipsoids have inherent flexibility to model the particle aspect ratio, roundness, and concavity, these being salient characteristics of most atmospheric particles (e.g., sea salt and dust aerosols). The complex refractive index of super-ellipsoids was set up with the real part ranging from 1.1 to 2.0 and the imaginary part from 10-7 to 0.5. To constrain the computational burden, the maximum size parameters for spheroids and super-ellipsoids were set as 100 and 50, respectively. From the LDRs of spheroids, we found that enhanced LDRs (>~60%) are common for optically soft particles. However, as the real part of the refractive index increases (larger than ~1.33), the enhanced LDRs (>~60%) are in high probability observed for nearly-spherical particles, and then disappear as the refractive index exceeds 1.7. To produce the enhanced LDRs, the imaginary part of the refractive index should also be less than ~0.01 such that the backscattered waves from particle-to-air transmission have sizable contributions, as the external reflection of spheroids produces no depolarization. This finding has particular relevance to LiDAR observations of atmospheric particles because the refractive index of most aerosols and hydrometeors at the LiDAR wavelength (e.g., 0.532µm) locates in this region, and aerosols and hydrometeors could have nearly-spherical morphologies. From the LDRs for general super-ellipsoids, we found that the enhanced LDRs (>~60%) exist for nearly-spherical particles with the aspect ratio close to unity, but disappear for super-ellipsoids with an aspect ratio at unity. In addition, the LDRs trend to decrease as the real part of the refractive index increases for convex super-ellipsoids, but show different features for concave super-ellipsoids. Furthermore, super-ellipsoids with different roundness parameters have a distinct dependence on the aspect ratio, which is significantly different from spheroids. The results presented here provide comprehensive references for understanding the LDR change of atmospheric aerosols as the particle shape and refractive index for interpreting LiDAR backscattering signals.

The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.

BACKGROUND [i]BRAF[/i]V600E mutation occurs in approximately 45% of papillary thyroid cancer (PTC) cases, and 25% of anaplastic thyroid cancer (ATC) cases. Vemurafenib/PLX4032, a selective BRAF inhibitor, suppresses extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) signaling and shows beneficial effects in patients with metastatic melanoma harboring the [i]BRAFV600E[/i] mutation. However, the response to vemurafenib is limited in BRAF-mutant thyroid cancer. The present study evaluated the effect of vemurafenib in combination with the selective MEK1/2 inhibitor AZD6244 on cell survival and explored the mechanism underlying the combined effect of vemurafenib and AZD6244 on thyroid cancer cells harboring BRAFV600E. MATERIAL AND METHODS Thyroid cancer 8505C and BCPAP cells harboring the [i]BRAFV600E[/i] mutation were exposed to vemurafenib (0.01, 0.1, and 1 µM) and AZD6244 (0.01, 0.1, and 1 µM) alone or in the indicated combinations for the indicated times. Cell viability was detected by the MTT assay. Cell cycle distribution and induction of apoptosis were detected by flow cytometry. The expression of cyclin D1, P27, (P)-ERK1/2 was evaluated by Western blotting. The effect of vemurafenib or AZD6244 or their combination on the growth of 8505C cells was examined in orthotopic xenograft mouse models [i]in vivo[/i]. RESULTS Vemurafenib alone did not increase cell apoptosis, whereas it decreased cell viability by promoting cell cycle arrest in BCPAP and 8505C cells. AZD6244 alone increased cell apoptosis by inducing cell cycle arrest in BCPAP and 8505C cells. Combination treatment with AZD6244 and vemurafenib significantly decreased cell viability and increased apoptosis in both BCPAP and 8505C cells compared with the effects of each drug alone. AZD6244 alone abolished phospho-ERK1/2 (pERK1/2) expression at 48 h, whereas vemurafenib alone downregulated pERK1/2 at 4-6 h, with rapid recovery of expression, reaching the highest level at 24-48 h. Combined treatment for 48 h completely inhibited pERK1/2 expression. Combination treatment with vemurafenib and AZD6244 inhibited cell growth and induced apoptosis by causing cell-cycle arrest, with the corresponding changes in the expression of the cell cycle regulators p27Kip1 and cyclin D1. Co-administration of vemurafenib and AZD6244 [i]in vivo[/i] had a significant synergistic antitumor effect in a nude mouse model. CONCLUSIONS Vemurafenib activated pERK1/2 and induced vemurafenib resistance in thyroid cancer cells. Combination treatment with vemurafenib and AZD6244 inhibited ERK signaling and caused cell cycle arrest, resulting in cell growth inhibition. Combination treatment in patients with thyroid cancer harboring the [i]BRAFV600E[/i] mutation may overcome vemurafenib resistance and enhance the therapeutic effect.

Effects of auxiliary atmospheric state parameters on the aerosol optical properties retrieval errors of high-spectral-resolution lidar.

A detailed assessment is carried out in relation to the influence of the uncertainties associated with the input auxiliary atmospheric state parameters on retrieving aerosol optical properties from high-spectral-resolution lidar (HSRL) observations. The study starts from a review of the main spectral structure of the Rayleigh backscattering followed by evaluating the temperature effects on a backscattering cross section of atmospheric molecules based on numerical simulation. It shows that the transmittance of the background interference filter should be taken into account, depending on the full width at half maximum, although overall temperature dependence is negligible. Based on the Taylor expansion of the Tenti S6 model, the systematic errors arising from input temperature and pressure profiles are analyzed. It is demonstrated that the atmospheric pressure profiles have limited effects on the inversion results of aerosol optical parameters, as the atmospheric pressure is usually quite stable. The relative errors of the aerosol backscatter coefficient mainly stem from temperature profile errors and highly depend on the aerosol concentration. Quantitatively, the aerosol backscatter coefficient error could be larger than 5% with a 3 K deviation of temperature when the backscatter ratio is larger than 1.1. The accuracy of aerosol extinction coefficient retrieval is affected not only by the error in temperature, but also by the error in temperature lapse rate; the retrieval accuracy is more sensitive to the latter than the former. Further analysis based on the sounding temperature data shows that the variation of the temperature inversion layer during the night could induce a bias larger than 0.04 km-1 on the aerosol extinction coefficient retrieval. Therefore, the time resolution of temperature measurement from sounding balloons twice per day is too low to obtain an accurate retrieval of the aerosol optical properties from the HSRL.

Use of Debye's series to determine the optimal edge-effect terms for computing the extinction efficiencies of spheroids.

The extinction efficiencies of atmospheric particles are essential to determining radiation attenuation and thus are fundamentally related to atmospheric radiative transfer. The extinction efficiencies can also be used to retrieve particle sizes or refractive indices through particle characterization techniques. This study first uses the Debye series to improve the accuracy of high-frequency extinction formulae for spheroids in the context of Complex angular momentum theory by determining an optimal number of edge-effect terms. We show that the optimal edge-effect terms can be accurately obtained by comparing the results from the approximate formula with their counterparts computed from the invariant imbedding Debye series and T-matrix methods. An invariant imbedding T-matrix method is employed for particles with strong absorption, in which case the extinction efficiency is equivalent to two plus the edge-effect efficiency. For weakly absorptive or non-absorptive particles, the T-matrix results contain the interference between the diffraction and higher-order transmitted rays. Therefore, the Debye series was used to compute the edge-effect efficiency by separating the interference from the transmission on the extinction efficiency. We found that the optimal number strongly depends on the refractive index and is relatively insensitive to the particle geometry and size parameter. By building a table of optimal numbers of edge-effect terms, we developed an efficient and accurate extinction simulator that has been fully tested for randomly oriented spheroids with various aspect ratios and a wide range of refractive indices.

Nanostructured Bimetallic Iron Molybdenum Nitride as a Non-Precious Cathode Catalyst for Li­O2 Batteries.

Herein we report the facile fabrication and electrocatalytic activity of nanostructured bimetallic iron molybdenum nitride (Fe3Mo3N), which was prepared by an ammonolysis process directly towards the solid state mixture of Mo precursor and Fe precursor. The prepared nanostructured Fe3Mo3N presented remarkable electrocatalytic activities towards both oxygen reduction reaction and oxygen evolution reaction in nonaqueous phase, due to the modulation of electronic configuration of catalyst by Fe element and porous structure. Then, lithium-O2 batteries with nanostructured Fe3Mo3N as cathode catalysts were assembled, which show alleviated polarization and enhanced cyclability.

Effects of a nonideal half-wave plate on the gain ratio calibration measurements in polarization lidars.

A half-wave plate (HWP) is a critical component for calibrating the gain ratio in polarization lidars. In this paper, the effects of a nonideal HWP on the gain ratio calibration measurements are analyzed. We focus on the ±45° method and the multi-rotation HWP method, which are the two main approaches for calibrating the gain ratio. Specifically, we discuss the influences of a nonideal HWP from two scenarios: an HWP with nonideal polarization properties and an ideal HWP under nonideal external conditions. The allowable ranges of relevant parameters for the nonideal polarization properties of HWPs are obtained, which can help to determine qualified HWPs in polarization lidars. Several external conditions, including ambient temperature variations, wavelength differences, and the tilt angles of HWPs, are also analyzed in detail. To the best of our knowledge, this paper represents the first comprehensive study on the effects of nonideal HWPs on the gain ratio calibration measurements, offering some guidelines on choosing a qualified HWP for proper use in polarization lidars.

miR-199a-3p downregulation in thyroid tissues is associated with invasion and metastasis of papillary thyroid carcinoma.

BACKGROUND AND AIMS: miR-199a-3p may play an important role in tumour inhibition. The aim of the present study was to determine any link between miR-199a-3p expression in thyroid tissues and clinicopathologic features, as well as to assess potential usefulness of miR-199a-3p in prediction for invasion and metastasis of papillary thyroid carcinoma (PTC). METHODS: A total of 188 tissue samples (136 PTCs, 52 normal thyroid tissue) were collected. We measured the levels of miR-199a-3p with quantitative reverse-transcriptase PCR (RT-qPCR) in all subjects. In addition, the correlation between the expression levels of miR-199a-3p and clinicopathological factors was explored. RESULTS: qRT-PCR indicated that the expression levels of miR-199a-3p was 7.1 (95% CI, 3.9-12.4) in PTCs, which was significantly lower than that of in the normal thyroid tissues 31.4 (95% CI, 15.4-44.3) (p = 0.002). Receiver operating characteristic curve (ROC) analyses revealed that miR-199a-3p could be promising biomarkers for PTC, with relatively high area under the curve (AUC) values was 0.87 (95% CI, 0.66-0.90; p = 0.001). Low miR-199a-3p expression levels were linked to TNM stage (p = 0.026), extra-thyroidal extension (p = 0.02), lymph node (LN) metastasis (p = 0.036), distant metastasis (p = 0.002) and recurrence of LN metastasis (p = 0.03). CONCLUSIONS: Our data suggest that downregulation of miR-199a-3p in thyroid tissues is linked to invasion and metastasis of PTC and may be a potential target for therapeutic intervention.

Surface Roughness Modulates Diffusion and Fibrillation of Amyloid-ß Peptide.

The presence of surfaces influences the kinetics of amyloid-ß (Aß) peptide fibrillation. Although it has been generally recognized that the fibrillation process can be assisted or accelerated by surface chemistry, the impact of surface topography, i.e., roughness, on peptide fibrillation is relatively little understood. Here we study the role of surface roughness on surface-mediated fibrillation using polymer coatings of varying roughness as well as polymer microparticles. Using single-molecule tracking, atomic force microscopy, and the thioflavin T fluorescence technique, we show that a rough surface decelerates the two-dimensional (2D) diffusion of peptides and retards the surface-mediated fibrillation. A higher degree of roughness that presents an obstacle to peptide diffusion is found to inhibit the fibrillation process.

Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκkB-PUMA Signaling.

BACKGROUND The transforming growth factor-beta (TGF-ß) signaling pathway plays a critical role in promoting tumor growth. TGF-ß1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-ß1 inhibits tumorigenesis of ATC cells. MATERIAL AND METHODS Effects of TGF-ß1 stimulation or TGF-ß1 inhibition by small interfering RNA (TGF-ß1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-ß1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-ß1 inhibition on tumorigenesis development. RESULTS TGF-ß1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-ß1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-ß1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-ß1siRNA requires pERK1/2 inhibition. TGF-ß1 shRNA inhibited tumor growth in vivo. CONCLUSIONS Therapies targeting the TGF-ß1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling.