Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10-22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.

Several first-line anti-hypertensives act on fibrosarcoma progression and PD1ab blockade therapy.

PURPOSE: Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. METHODS: We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8+ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. RESULTS: Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. CONCLUSION: Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future.

Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality.

Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.

Exploring the correlation between HER2 alterations and 18F-FDG PET/CT metabolic parameters and their prognostic value in EGFR-negative non-small-cell lung cancer patients.

PURPOSE: Our study intended to explore the correlation between HER2 alterations and 18F-FDG PET/CT metabolic parameters and their prognostic value in EGFR-negative non-small-cell lung cancer (NSCLC) patients detected by next-generation sequencing (NGS). METHODS: NGS assay was performed in 1737 NSCLC patients, a total of 88 HER2 alterations and 176 negative HER2 with EGFR-negative patients were randomly selected for this study. RESULTS: When the HER2 status with EGFR-negative group was analyzed, multivariate analysis showed that smoking status, primary tumor SUVmax (pSUVmax) < 13.03 and stage were the independent deterministic factors of HER2 alterations. Multivariate cox regression analysis revealed that HER2 status, age, smoking status and stage were independent risk factors for overall survival (OS) in EGFR-negative NSCLC patients with different HER2 status. When the HER2 alterations group was separately analyzed, multivariate analysis demonstrated that low pSUVmax < 15.32 and histology were the independent deterministic factors of HER2 mutation. Multivariate cox regression analysis revealed that pSUVmax, smoking status, nodal involvement and treatment methods were independent risk factors for OS in EGFR-negative NSCLC patients with HER2 alterations. CONCLUSION: The study revealed that low pSUVmax was associated with HER2 alterations in EGFR-negative NSCLC patients, moreover HER2 mutation and HER2 amplification exhibited distinct 18F-FDG metabolic and clinical characteristics. Furthermore, it explored the prognostic value of HER2 alterations and 18F-FDG PET/CT metabolic parameters of pSUVmax in EGFR-negative NSCLC patients.

Emotion-Semantic-Aware Dual Contrastive Learning for Epistemic Emotion Identification of Learner-Generated Reviews in MOOCs.

Identifying the epistemic emotions of learner-generated reviews in massive open online courses (MOOCs) can help instructors provide adaptive guidance and interventions for learners. The epistemic emotion identification task is a fine-grained identification task that contains multiple categories of emotions arising during the learning process. Previous studies only consider emotional or semantic information within the review texts alone, which leads to insufficient feature representation. In addition, some categories of epistemic emotions are ambiguously distributed in feature space, making them hard to be distinguished. In this article, we present an emotion-semantic-aware dual contrastive learning (ES-DCL) approach to tackle these issues. In order to learn sufficient feature representation, implicit semantic features and human-interpretable emotional features are, respectively, extracted from two different views to form complementary emotional-semantic features. On this basis, by leveraging the experience of domain experts and the input emotional-semantic features, two types of contrastive losses (label contrastive loss and feature contrastive loss) are formulated. They are designed to train the discriminative distribution of emotional-semantic features in the sample space and to solve the anisotropy problem between different categories of epistemic emotions. The proposed ES-DCL is compared with 11 other baseline models on four different disciplinary MOOCs review datasets. Extensive experimental results show that our approach improves the performance of epistemic emotion identification, and significantly outperforms state-of-the-art deep learning-based methods in learning more discriminative sentence representations.

Effect of an inactivated coronavirus disease 2019 vaccine, CoronaVac, on blood coagulation and glucose: a randomized, controlled, open-label phase IV clinical trial.

Background: Billions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered and several cases of thrombocytopenia with thrombosis syndrome (TTS) have been reported after the administration of adenoviral vector vaccines. However, the effects of an inactivated COVID-19 vaccine, CoronaVac, on coagulation are not well understood. Methods: In this randomized, controlled, open-label phase IV clinical trial, 270 participants including 135 adults aged 18-59 years and 135 adults aged 60 years or older, were enrolled and randomized to the CoronaVac group or to the control group in a 2:1 ratio and received two doses of CoronaVac or one dose of the 23-valent pneumococcal polysaccharide vaccine and one dose of inactivated hepatitis A vaccine on days 0 and 28, respectively. Adverse events were collected for 28 days after each dose. Blood samples were taken on days 0, 4, 14, 28, 32, 42, and 56 after the first dose to evaluate neutralizing antibody titers and laboratory parameters of coagulation function and blood glucose. Results: Fourteen days after the second dose of CoronaVac, the seroconversion rates of neutralizing antibodies against the prototype strain and beta, gamma, and delta variants of concern (VOC) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reached peak values of 89.31%, 23.3%, 45.3%, and 53.5%, respectively. The incidence of adverse reactions was 43.6% and 52.2% in the CoronaVac group and in the control group, respectively. All were mild or moderate in severity. For the laboratory parameters, there was no difference in the means of any parameter between the two groups at any time point, except for the D-dimer on day 14. However, the D-dimer in the CoronaVac group decreased on day 14 compared to the value at baseline, while a higher D-dimer value, instead of a decreased D-dimer value, was a risk factor for TTS. Conclusion: CoronaVac showed a good safety profile and could induce a humoral response against the prototype and VOCs of SARS-CoV-2 in adults 18 years or older, with no abnormal effects on laboratory parameters of blood glucose and coagulation function.

Discovery of Dual Lysine Methyltransferase G9a and EZH2 Inhibitors with In Vivo Efficacy against Malignant Rhabdoid Tumor.

In recent years, it has been proposed that G9a/EZH2 dual inhibition is a promising cancer treatment strategy. Herein, we present the discovery of G9a/EZH2 dual inhibitors that merge the pharmacophores of G9a and EZH2 inhibitors. Among them, the most promising compound 15h displayed potent inhibitory activities against G9a (IC50 = 2.90 ± 0.05 nM) and EZH2 (IC50 = 4.35 ± 0.02 nM), superior antiproliferative profiles against RD (CC50 = 19.63 ± 0.18 µM) and SW982 (CC50 = 19.91 ± 0.50 µM) cell lines. In vivo, 15h achieved significant antitumor efficacy in a xenograft mouse model of human rhabdoid tumor with a tumor growth inhibitory rate of 86.6% without causing observable toxic effects. The on-target activity assays illustrated that compound 15h can inhibit tumor growth by specifically inhibiting EZH2 and G9a. Therefore, 15h is a potential anticancer drug candidate for the treatment of malignant rhabdoid tumor.

Immunogenicity and safety of a live attenuated varicella vaccine co-administered with inactive hepatitis A vaccine: A phase 4, single-center, randomized, controlled trial.

Co-administration of vaccines can facilitate the introduction of new vaccines in immunization schedules. This study aimed to evaluate the immunogenicity and safety of co-administration with live attenuated varicella vaccine (VarV) and inactivated hepatitis A vaccine (HepA) among children aged 12 ~ 15 months. In this phase 4 clinical trial, 450 children were randomized with a ratio of 1:1 to receive VarV and Hep A simultaneously (Group A) or separately (Group B). The primary endpoints were the seroconversion rate of anti-varicella-zoster virus (VZV) antibodies 42 days after vaccination of VarV and the seroconversion rate of anti-Hepatitis A virus (HAV) antibodies 30 days after two-dose vaccination of HepA. After full immunization, the seroconversion rates of anti-VZV antibodies were 91.79% in Group A and 92.15% in Group B; the geometric mean titers (GMTs) were 11.80 and 12.19, respectively. The seroconversion rates of anti-HAV antibodies were 99.48% in Group A and 100.0% in Group B; the geometric mean concentrations (GMCs) reached 9499.11 and 9528.36 mIU/ml, respectively. The lower limits of the 95% CI for the seroconversion difference of anti-VZV antibodies and anti-HAV antibodies were -5.86% and -2.90%, which greater than the predefined non-inferiority margin (-10%). The incidence rate of adverse reactions in Group A was lower than Group B (9.33% vs 16.22%), and only one serious adverse event was reported in Group B, which was unrelated to the study vaccine. In conclusion, the co-administration of VarV with HepA has non-inferior immunogenicity and safety profiles were quite comparable with the separate administration of both vaccines.Trial registration number: NCT05526820 (ClinicalTrials.gov).

Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases.

Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of l-Arg, and the powerful anti-inflammatory and eNOS-replenishing effects of budesonide (BUD), we constructed a bi-prodrug minimalist nanoplatform co-loaded with BUD and l-Arg via polysialic acid (PSA) to form BUD-l-Arg@PSA. This promoted vascular normalization by simultaneously regulating vascular endothelial dysfunction and inflammation. Mediated by the special affinity between PSA and E-selectin, which is highly expressed on the surface of activated endothelial cells (ECs), BUD-l-Arg@PSA selectively accumulated in activated ECs, targeted eNOS expression and activation, and promoted NO production. Consequently, the binary synergistic regulation of the NO/eNOS signaling pathway occurred and improved vascular endothelial function. NO-induced nuclear factor-kappa B alpha inhibitor (IκBα) stabilization and BUD-induced nuclear factor-kappa B (NF-κB) response gene site occupancy achieved dual-site blockade of the NF-κB signaling pathway, thereby reducing the inflammatory response and inhibiting the infiltration of inflammation-related immune cells. In a renal ischemia-reperfusion injury mouse model, BUD-l-Arg@PSA reduced acute injury. In an atherosclerosis mouse model, BUD-l-Arg@PSA decreased atherosclerotic plaque burden and improved vasodilation. This represents a revolutionary therapeutic strategy for inflammatory vascular diseases.

Immunogenicity, safety and consistency of seven lots of an inactivated COVID-19 vaccine in healthy children and adolescents: a randomized, double-blind, controlled, phase IV clinical trial.

Background: CoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here. Methods: In this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination. Results: Between July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event. Conclusion: CoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.

Aniline exposure activates receptor-interacting serine/threonineprotein kinase 1 and causes necroptosis of AML12 cells.

With the increased use of aniline, potential impacts on human health cannot be ignored. The hepatotoxicity of aniline is largely unknown and the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the hepatotoxicity of aniline and elucidate the underlying mechanism. AML12 cells were exposed to different concentrations of aniline (0, 5, 10, or 20 mM) to observe changes to reactive oxygen species (ROS) production and the expression patterns of necroptosis-related proteins (RIPK1, RIPK3, and MLKL). The potential mechanism underlying aniline-induced hepatotoxicity was explored by knockout of RIPK1. The results showed that aniline induced cytotoxicity in AML12 cells in a dose-dependent manner in addition to the production of ROS and subsequent necroptosis of AML12 cells. Silencing of RIPK1 reversed upregulation of necroptosis-related proteins in AML12 cells exposed to aniline, demonstrating that aniline-induced ROS production was related to necroptosis of AML12. Moreover, aniline promoted intracellular RIPK1 activation, suggesting that the RIPK1/ROS pathway plays an important role in aniline-induced hepatotoxicity. NAC could quench ROS and inhibit necroptosis. These results provide a scientific basis for future studies of aniline-induced hepatotoxicity for the prevention and treatment of aniline-induced cytotoxicity.

Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

Modeling and Measurement of Thermal-Mechanical-Stress-Creep Effect for RF MEMS Switch Up to 200 °C.

High-temperature processes, such as packaging and annealing, are challenges for Radio-Frequency Micro-Electro-Mechanical-Systems (RF MEMS) structures, which could lead to device failure. Coefficient of thermal expansion (CTE) mismatch and the material's creep effect affect the fabrication and performance of the MEMS, especially experiencing the high temperature. In this paper, the Thermal-Mechanical-Stress-Creep (TMSC) effect during thermal processes from room temperature (RT) to 200 °C is modeled and measured, in which an Au-cantilever-based RF MEMS switch is selected as a typical device example. A novel Isolation-Test Method (ITM) is used to measure precise TMSC variation. This method can achieve resolutions of sub-nanometer (0.5 nm) and attofarad (1 aF). There are three stages in the thermal processes, including temperature ramping up, temperature dwelling, and temperature ramping down. In different stages, the thermal-mechanical stress in anchor and cantilever, the grain growth of gold, and the thermal creep compete with each other, which result in the falling down and curling up of the cantilever. These influencing factors are decoupled and discussed in different stages. The focused ion beam (FIB) is used to characterize the change of the gold grain. This study shows the possibility of predicting the deformation of MEMS structures during different high-temperature processes. This model can be extended for material selection and package temperature design of MEMS cantilever in the further studies.

Autobalanced Multitask Node Embedding Framework for Intelligent Education.

Recently, online education has become popular. Many e-learning platforms have been launched with various intelligent services aimed at improving the learning efficiency and effectiveness of learners. Graphs are used to describe the pairwise relations between entities, and the node embedding technique is the foundation of many intelligent services, which have received increasing attention from researchers. However, the graph in the intelligent education scenario has three noteworthy properties, namely, heterogeneity, evolution, and lopsidedness, which makes it challenging to implement ecumenical node embedding methods on it. In this article, an autobalanced multitask node embedding model is proposed, named MNE, and applied to the interaction graph, settling a few actual tasks in intelligent education. More specifically, MNE builds two purpose-built self-supervised node embedding learning tasks for heterogeneous evolutive graphs. Edge-specific reconstruction tasks are built according to the semantic information and properties of the heterogeneous edges, and an evolutive weight regression task is designed, aiding the model to perceive the evolution of learners' implicit cognitive states. Then, both aleatoric and epistemic uncertainty quantification techniques are introduced, achieving both task-and node-level weight estimation and instructing subtask autobalancing. Experimental results on real-world datasets indicate that the proposed model outperforms the state-of-the-art graph embedding methods on two assessment tasks and demonstrates the validity of the proposed multitask framework and subtask balancing mechanism. Our implementations are available at https://github.com/ccnu-mathits/MNE4HEN.

Pregnancy Does not Affect the Prognoses of Differentiated Thyroid Cancer Patients With Lung Metastases.

CONTEXT: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear. OBJECTIVE: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy. METHODS: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment. RESULTS: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group. CONCLUSION: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients.

Interleukins in Thyroid Cancer: From Basic Researches to Applications in Clinical Practice.

Inflammation is crucial to tumorigenesis and progression of many cancers. Inflammatory molecules in tumor microenvironment exert pro- or anti-tumor effects. Among them, interleukin, mainly produced by CD3+ and CD4+ T lymphocytes, is a class of small molecule proteins which play an important role in intercellular communication. Numerous studies have confirmed that interleukins are closely related to thyroid cancer. Interleukins regulate the proliferation and migration of thyroid cancer cells and they have prospects in discriminating benign and malignant thyroid diseases, predicting the risk of tumorigenesis, evaluating the prognosis and monitoring the recurrence of thyroid cancer. Besides, the effective application of interleukins in treatment of thyroid cancer has been confirmed by some cell and animal researches. The present review will introduce the potential mechanisms of interleukins in thyroid cancer and focus on the applications of interleukins in clinical practice of thyroid cancer, which will help update understanding of the progress of interleukins researches in thyroid cancer.

Suspended tungsten trioxide (WO3) gate AlGaN/GaN heterostructure deep ultraviolet detectors with integrated micro-heater.

A suspended WO3-gate AlGaN/GaN heterostructure photodetector integrated with a micro-heater is micro-fabricated and characterized for ultraviolet photo detection. The transient optical characteristics of the photodetector at different temperatures are studied. The 2DEG-based photodetector shows a recovery (170 s) time under 240 nm illumination at 150 ℃. The measured spectral response of WO3-gate AlGaN/GaN heterostructure shows a high response in deep ultraviolet range. Responsivity at 240 nm wavelength is 4600 A/W at 0.5 V bias. These characteristics support the feasibility of a high accuracy deep UV detector based on the suspended AlGaN/GaN heterostructure integrated with a micro-heater.

High Performance Mixed Potential Type NO2 Gas Sensor Based on Porous YSZ Layer Formed with Graphite Doping.

High performance mixed potential type NO2 sensors using porous yttria-stabilized zirconia (YSZ) layers doped with different concentration graphite as solid electrolyte and LaFeO3 as sensing electrode were fabricated and characterized. LaFeO3 was prepared by a typical citrate sol-gel method and characterized using XRD. The surface morphology and porosity of porous YSZ layers were characterized by field emission scanning electron microscope (FESEM). The sensor doped with 3 wt% graphite shows the highest response (-76.4 mV to 80 ppm NO2) and the response is linearly dependent on the logarithm of NO2 concentration in the range of 10-200 ppm. The sensor measurement results also present good repeatability and cross-sensitivity.

Clinical outcomes and prognostic factors in patients with no less than three distant organ system metastases from differentiated thyroid carcinoma.

OBJECTIVES: For patients with differentiated thyroid carcinoma (DTC), distant metastases are commonly identified in the lungs and bones. However, they are relatively rare in other distant organs, such as the liver, kidneys, or brain. The aim of the current study was to describe the clinical outcomes and evaluate the prognostic factors of patients with no less than three different distant organ system metastases from DTC. METHODS: This study retrospectively identified 717 patients diagnosed with DTC with distant metastases between January 2005 and December 2017. Patient response to radioactive iodine (RAI) therapy was monitored by changes in serum thyroglobulin levels and imaging changes. Five-year and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier methods and Cox proportional hazards. RESULTS: Among the 717 participants, 37 (5.16%) patients had no less than three different distant organ system metastases from DTC. Five-year and 10-year OS were 45.9% and 37.8% in patients with three or more distant organ system metastases while 74.5% and 64.9% in individuals with one or two distant organ system metastases, respectively. RAI avidity and RAIR-DTC were main independent prognostic factors influencing the clinical outcomes for both groups of patients. The presence of 3 or more different distant organ system metastases was the only independent prognostic factors for 10-year OS by multivariate analysis. CONCLUSIONS: Patients with no less than three distant organ system metastases from DTC had poor prognosis. RAI avidity and RAIR-DTC were main factors influencing overall survival for patients with distant metastases from DTC in both groups.

Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells.

Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the αvß3-positive MDA-MB-231 cells. Besides exhibiting greater cytotoxicity in vitro, compared with non-targeted shikonin-loaded liposomes (SSLs-SHK), RGD-SSLs-SHK could also evidently induce apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. It could also inhibit cell proliferation, migration, invasion, and adhesion by reducing the expression of MMP-9 and the level of NF-κB p65, but did not affect the expression of MMP-2 in the MDA-MB-231 cells. Therefore, these findings indicated that the strategy to use RGD-modified liposomes as carriers for targeted delivery of shikonin is a very promising approach to achieve breast cancer targeted therapy.