Clinical Practice Report of Contrast-Enhanced Ultrasound in Renal Artery Disease.

OBJECTIVES: To evaluate the diagnostic performance of renal artery contrast-enhanced ultrasound (CEUS) with modified inspection section and summarize subsequent changes in imaging assessment of renal artery disease. METHODS: A total of 1015 patients underwent renal artery CEUS were included in the study. Among them, 79 patients (156 renal arteries) suspected with renal artery stenosis (RAS) underwent digital subtraction angiography (DSA) subsequently. DSA was used as the gold standard to evaluate the diagnostic performance of CEUS in detecting RAS (≥30%) and severe stenosis (≥70%), as well as the diagnostic accuracy of classification of stenosis degree. Besides, 127 of the 1015 patients underwent other imaging examinations such as computed tomography angiography (CTA) or magnetic resonance angiography (MRA) after CEUS and annual proportion of these imaging examinations was assessed. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CEUS for detecting RAS (≥30%) was 96.4%, 88.6%, 94.2%, 95.6% and 90.7%, respectively and the kappa value was .857 (P < .01). CEUS had a good performance in distinguishing severe stenosis (≥70%) with a sensitivity of 91.1%, specificity of 95.5%, accuracy of 92.9%, PPV of 96.5%, NPV of 88.7% and the kappa value was 0.857(P < .01). There was no significant difference between CEUS and DSA in detecting stenosis (P = 1.0) and severe stenosis (P = .227). The diagnostic accuracy of CEUS in grading RAS was 85.3% and the kappa value was 0.753 (P < .01). Besides, the annual proportion of other imaging examinations decreased for 4 consecutive years. CONCLUSIONS: CEUS is a non-invasive, safe and valuable technique for the assessment of renal artery disease and worthy of promotion.

Comprehensive DNA Methylation Profiling of Medullary Thyroid Carcinoma: Molecular Classification, Potential Therapeutic Target, and Classifier System.

PURPOSE: Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date. EXPERIMENTAL DESIGN: Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments. RESULTS: Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the "mutual exclusivity" of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. In vitro experiments further affirmed NNAT's therapeutic potential. Moreover, we built an elastic-net logistic regression model with a relatively high AUC encompassing 68 probes, intended for future validation and systematic clinical application. CONCLUSIONS: Conducting research on diseases with low incidence poses significant challenges, and we provide a robust resource and comprehensive research framework to assist in ongoing MTC case inclusion and facilitate in-depth dissection of its molecular biological features.

Wide QRS Complex Tachycardia Change to Narrow QRS Complex Tachycardia After ß-Blocker Administration.

This case report describes a patient in their 80s with a history of paroxysmal atrial fibrillation who presented with palpitation, dizziness, nausea, and vomiting.

Auto-accelerated dehydrogenation of alkane assisted by in-situ formed olefins over boron nitride under aerobic conditions.

Oxidative dehydrogenation (ODH) of alkane over boron nitride (BN) catalyst exhibits high olefin selectivity as well as a small ecological carbon footprint. Here we report an unusual phenomenon that the in-situ formed olefins under reactions are in turn actively accelerating parent alkane conversion over BN by interacting with hydroperoxyl and alkoxyl radicals and generating reactive species which promote oxidation of alkane and olefin formation, through feeding a mixture of alkane and olefin and DFT calculations. The isotope tracer studies reveal the cleavage of C-C bond in propylene when co-existing with propane, directly evidencing the deep-oxidation of olefins occur in the ODH reaction over BN. Furthermore, enhancing the activation of ethane by the in-situ formed olefins from propane is successfully realized at lower temperature by co-feeding alkane mixture strategy. This work unveils the realistic ODH reaction pathway over BN and provides an insight into efficiently producing olefins.

Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis.

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

In Situ Generated Boron Peroxo as Mild Oxidant in Propane Oxidative Dehydrogenation Revealed by Density Functional Theory Study.

Boron-based materials catalyzing oxidative dehydrogenation is emerging as a promising protocol for efficient conversion of light alkanes to olefins, while the origin of its remarkable selectivity remains unclear. By means of density functional theory calculations, this work addresses the crucial role of boron peroxo as the mild oxidant in propane ODH: (1) Surface boron peroxo species can be generated in situ in the presence of peroxo species, preferably at the >B-O-B< sites of the zigzag edge, and show high activity to dehydrogenate propane (ΔG⧧ = 13.5 kcal/mol, ΔG = 8.9 kcal/mol). (2) The >B-O-O· site shows high discriminability of secondary H over primary H of the propane molecule, leading to significantly higher yield of iso-propyl (CH3CHCH3) than n-propyl (CH3CH2CH2); thus, propene formation is favored over deep oxidation. This provides physical insights into the origin of the remarkable olefin selectivity in the boron-containing ODH catalytic systems.

3D hierarchical ZnCo2S4@Ni(OH)2 nanowire arrays with excellent flexible energy storage and electrocatalytic performance.

It is essential for energy storage and conversion systems to construct electrodes and electrocatalysts with superior performance. In this work, ZnCo2S4@Ni(OH)2 nanowire arrays are synthesized on nickel foam by hydrothermal methods. As a supercapacitor electrode, the ZnCo2S4@Ni(OH)2 structure exhibits a specific capacitance of 1,263.0C g-1 at 1 A g-1. The as-fabricated ZnCo2S4@Ni(OH)2//active carbon device can achieve a maximum energy density of 115.4 Wh kg-1 at a power density of 5,400 W kg-1. As electrocatalysts, the ZnCo2S4@Ni(OH)2 structure delivers outstanding performance for oxygen evolution reaction (an overpotential of 256.3 mV at 50 mA cm-2), hydrogen evolution reaction (141.7 mV at 10 mA cm-2), overall water splitting (the cell voltage of 1.53 V at 50 mA cm-2), and a high stability for 13 h.

Effect of chitosan oligosaccharide glycosylation on the emulsifying property of lactoferrin.

There is fast increasing interest in the development of alimentary protein stabilized emulsions due to their potential applications in functional food fields. This work studied the effect of glycation degree with chitosan oligosaccharide (COS) on the emulsifying properties of lactoferrin (LF) through Maillard reaction. In the present study, SDS-PAGE and FT-IR were used to confirm LF and COS covalently binding together successfully. Intrinsic fluorescence showed that glycation with COS led more hydrophobic groups exposed to the surface of the structure and particle size increase of LF. Emulsions with 50% (v/v) oil phase and protein concentration of 2% (w/v) was fabricated through one-step shear method. Compared with native LF, emulsions stabilized by LF-COS conjugates showed smaller droplet size and lower creaming index (CI). Among these samples, LF-COS conjugates under 4 h had the best emulsifying efficiency and stability, the emulsion droplet size and the CI of which decreased 39.66% and 28.55% compared with LF, respectively. Furthermore, glycation with COS enhanced the interfacial activity of LF leading to more adsorbing amount and forming thicker layer on the droplets and gel network in the emulsions. This finding would make sense to further understand the modification of emulsifying properties of alimentary proteins through glycosylation with saccharides and develop novel protein-based emulsifiers.

Boryl Radical Activation of Benzylic C-OH Bond: Cross-Electrophile Coupling of Free Alcohols and CO2 via Photoredox Catalysis.

A new strategy for the direct cleavage of the C(sp3)-OH bond has been developed via activation of free alcohols with neutral diphenyl boryl radical generated from sodium tetraphenylborate under mild visible light photoredox conditions. This strategy has been verified by cross-electrophile coupling of free alcohols and carbon dioxide for the synthesis of carboxylic acids. Direct transformation of a range of primary, secondary, and tertiary benzyl alcohols to acids has been achieved. Control experiments and computational studies indicate that activation of alcohols with neutral boryl radical undergoes homolysis of the C(sp3)-OH bond, generating alkyl radicals. After reducing the alkyl radical into carbon anion under photoredox conditions, the following carboxylation with CO2 affords the coupling product.

PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer.

PRDM16 (known as MEL1), a member of the PR domain zinc finger family, has been implicated in multiple biological processes, including cancers. It is not clear yet whether PRDM16 is involved in tumor progress of papillary thyroid cancer (PTC). We identified the PRDM16 expression level in PTC tissues by qRT-PCR and analyzed its relationship with clinical characteristics in both Fudan University Shanghai Cancer Center (FUSCC) and TCGA cohorts. We tested the function of PRDM16 in PTC cells both in vivo and in vitro. We found a direct downstream target of PRDM16, pyruvate carboxylase (PC), by RNA-sequencing, rescue experiments, luciferase assay, and chromatin immunoprecipitation assay. PRDM16 was downregulated in papillary thyroid cancer tissues and was significantly related with lymph node metastases and extrathyroidal extension in both FUSCC and TCGA cohorts. Overexpression of PRDM16 could attenuate proliferation and migration of PTC cells via inhibiting the epithelial-to-mesenchymal transition process. PC was upregulated in papillary thyroid cancer tissues. Knockdown of PC could inhibit proliferation and migration in TPC-1 and K1 cells. The repression effect on cell proliferation and migration from PRDM16 was PC dependent. PRDM16 could directly bind to the PC promoter and inhibit its expression at the transcription level. Moreover, the mRNA expression level of PRDM16 and PC was negatively related in human PTC tissues. In conclusion, PRDM16 exhibited an antitumor effect and EMT inhibition function in PTC by directly binding with the PC promoter. PRDM16 may be a novel therapeutic target in papillary thyroid cancer.

Understanding the Unique Antioxidation Property of Boron-Based Catalysts during Oxidative Dehydrogenation of Alkanes.

Boron-based catalysts show excellent performance in oxidative dehydrogenation (ODH) of light alkanes to alkenes with high selectivity and extremely good antioxidation properties. However, the anti-deep-oxidation mechanism remains unclear. Herein, we chose h-BN and B2O3 as representative boron-based catalysts to investigate their reactions with two important intermediates in the light alkane ODH, Et· (evolving to ethene) and EtO· (evolving to ethene or COx), to elucidate the origin of the antioxidation of alkanes. The density functional theory calculations reveal that surface boron sites could eliminate alkoxy in their vicinity, resulting in exceptional inhibition of alkane deep-oxidation. The analysis of the electronic and geometric structures of key stationary points showed that the oxophilicity of B determined the low deep-oxidation of alkanes, and the homoleptic coordination of B with all three ligating atoms being O moderately enhanced its oxophilicity. This work represents a novel conceptual advance in the mechanistic understanding of alkane ODH.

Plasma Tuning Local Environment of Hexagonal Boron Nitride for Oxidative Dehydrogenation of Propane.

Hexagonal boron nitride (h-BN) has lately received great attention in the oxidative dehydrogenation (ODH) reaction of propane to propylene for its extraordinary olefin selectivity in contrast to metal oxides. However, high crystallinity of commercial h-BN and elusive cognition of active sites hindered the enhancement of utilization efficiency. Herein, four kinds of plasmas (N2 , O2 , H2 , Ar) were accordingly employed to regulate the local chemical environment of h-BN. N2 -treated BN exhibited a remarkable activity, i.e., 26.0 % propane conversion with 89.4 % selectivity toward olefins at 520 °C. Spectroscopy demonstrated that "three-boron center" N-defects in the catalyst played a pivotal role in facilitating the conversion of propane. While the sintering effect of the "BOx " species in O2 -treated BN, led to the suppressed catalytic performance (12.4 % conversion at 520 °C).

SNHG9, a Papillary Thyroid Cancer Cell Exosome-Enriched lncRNA, Inhibits Cell Autophagy and Promotes Cell Apoptosis of Normal Thyroid Epithelial Cell Nthy-ori-3 Through YBOX3/P21 Pathway.

Thyroid cancer is the most common type of endocrine malignancy. Although the general prognosis is good, the treatment of advanced disease is still challenging. Exosomes are vesicle units containing specific components that transmit information between cells. In order to explore its role in papillary thyroid cancer (PTC), our study screened exosome enriched lncRNA SNHG9 by lncRNA chip and explored its biological function. We used lncRNA chips combined with bioinformatics analysis to screen lncRNA SNHG9 enriched in exosomes. GO analysis suggested its relationship with autophagy and apoptosis. Quantitative PCR showed SNHG9 was highly expressed in PTC cells and exosomes and its correlation with PTC tumor size was analyzed by clinical characteristics. SNHG9 could inhibit the protective cell autophagy induced by starvation of human normal thyroid epithelial cell line Nthy-ori-3 and promote its apoptosis through PTC cell exosomes. RNA-pull down combined with protein spectrum showed that SNHG9 could interact with YBOX3. Western blot and RNA immunoprecipitation further confirmed their interaction. Western blot showed that SNHG9 could induce degradation of YBOX3, thus interfering with the stability of P21 mRNA and inducing cell apoptosis. In conclusion, our study identified SNHG9 as a PTC cell exosome-enriched lncRNA. SNHG9 could inhibit cell autophagy and promote apoptosis of Nthy-ori-3 cell through YBOX3/P21 pathway.

Prognostic and clinical significance of HOXC9 and HOXD10 in papillary thyroid cancer.

BACKGROUND: The homebox superfamily play an important role in tumorigenesis. HOXC9 and HOXD10 were reported playing critical roles in tumor progression in many malignant tumors. This study aimed to research the expression of HOXC9 and HOXD10 in papillary thyroid cancer, and to verify the prognostic and clinical significance of HOXC9 and HOXD10. METHODS: Immunohistochemistry was used to determine the expression of HOXC9 and HOXD10 in 98 pairs of papillary thyroid cancer and paracancer tissues. Clinicopathologic data were collected and analyzed to verify the prognostic and clinical significance of HOXC9 and HOXD10. RESULTS: The expression of HOXC9 and HOXD10 decreased in papillary thyroid cancer. The low expression of HOXC9 was associated with Hashimoto's thyroiditis and lymph node metastasis (P<0.05). The low expression of HOXD10 was associated with extrathyroidal extension and lymph node metastasis (P<0.05). The co-expression rates of HOXC9 and HOXD10 was 44.90%. The low expression of both HOXC9 and HOXD10 was associated with lymph node metastasis (P<0.05). CONCLUSIONS: The expression of HOXC9 and HOXD10 was downregulated in papillary thyroid cancer. Low expression of HOXC9 and HOXD10 might be related to the malignancy of papillary thyroid cancer. HOXC9 and HOXD10 may be used as diagnostic and prognostic biomarkers in the future.

Oxidative dehydrogenation of light alkanes to olefins on metal-free catalysts.

Metal-free boron- and carbon-based catalysts have shown both great fundamental and practical value in oxidative dehydrogenation (ODH) of light alkanes. In particular, boron-based catalysts show a superior selectivity toward olefins, excellent stability and atom-economy to valuable carbon-based products by minimizing CO2 emission, which are highly promising in future industrialization. The carbonaceous catalysts also exhibited impressive behavior in the ODH of light alkanes helped along by surface oxygen-containing functional groups. This review surveyed and compared the preparation methods of the boron- and carbon-based catalysts and their characterization, their performance in the ODH of light alkanes, and the mechanistic issues of the ODH including the identification of the possible active sites and the exploration of the underlying mechanisms. We discussed different boron-based materials and established versatile methodologies for the investigation of active sites and reaction mechanisms. We also elaborated on the similarities and differences in catalytic and kinetic behaviors, and reaction mechanisms between boron- and carbon-based metal-free materials. A perspective of the potential issues of metal-free ODH catalytic systems in terms of their rational design and their synergy with reactor engineering was sketched.

Glycation mechanism of lactoferrin-chitosan oligosaccharide conjugates with improved antioxidant activity revealed by high-resolution mass spectroscopy.

Glycosylation has a great effect on the antioxidant ability of proteins, which is due to the structural conformational change of peptides in the protein. In this study, a chitosan oligosaccharide (COS) was selected as the saccharide for glycation with lactoferrin (LF) by a wet-heat method, and a new stripe at a higher molecular zone in the gel of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and a change in the bond revealed by Fourier transform infrared (FT-IR) and fluorescence spectroscopy analyses were used to confirm that the chitosan oligosaccharide was successfully covalently bound to lactoferrin. The ABTS and oxygen radical absorbance capacity (ORAC) assays indicated that lactoferrin exhibited a stronger antioxidant activity after glycation with the chitosan oligosaccharide. High-resolution mass spectroscopy further illuminated the relationship of enhanced antioxidant capacity and structural conformational change of peptides in lactoferrin at a molecular level.

IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro.

The impact of Hashimoto's thyroiditis (HT) on the progression of papillary thyroid cancer (PTC) is still unclear. Interleukin-2 (IL-2) is a growth factor and crucial for HT development. This study aimed at investigating the effect of IL-2 on MHC class I expression in PTC cells and immune activation with experimental treatment for PTC using PTC cell lines. We assessed the expression of IL-2, HLA class I, PD-L1, CD3, CD8 and CD16 molecules in paired PTC tissues and HLA-ABC and PD-L1 expression in IL-2 pre-treated K1, TPC-1 and BCPAP cells by immunohistochemistry, qPCR, flow cytometry and Western blotting. The effect of IL-2 on immunogenicity of PTC cells to stimulate activated human T cells was determined for the percentages of activated CD8+ T cells and their cytokine production as well as PD-1 and PD-L1 expression. Compared with non-tumor tissues, we found that IL-2 expression was up-regulated in PTC tissues, particularly in PTC+HT tissues and correlated positively with HLA-class I, CD3 and CD8 expression in PTC+HT tissues. Conversely, PD-L1 expression decreased in PTC+HT tissues. Treatment with IL-2 significantly up-regulated HLA-class I expression, but down-regulated PD-L1 expression in PTC cells. Co-culture with IL-2-pre-treated PTC cells significantly promoted the proliferation of activated CD8+ T cells and their IL-2 secretion, but decreased their PD-1 expression, accompanied by decreased PD-L1 expression in IL-2-treated PTC cells in vitro. In conclusion, IL-2 up-regulated HLA-class I expression and enhanced anti-tumor T cell immunity during the development of PTC and HT. IL-2 may be a promising immunotherapy for PTC.

Correction to: MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming.

An amendment to this paper has been published and can be accessed via the original article.

Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer, which is the most common endocrine cancer, has shown a drastic increase in incidence globally over the past decade. The present study investigated the thyroid cancer-inhibitory potential of jatrorrhizine-platinum(II) complex (JR-P(II) in vitro and in vivo. MATERIAL AND METHODS The JR-P(II)-mediated cytotoxicity in thyroid carcinoma cells was determined by using MTT assay. Assessment of acetylated histones, tubulin, and DNA repair proteins was made by Western blot assays. Flow cytometry was used for apoptosis and ROS accumulation measurement. RESULTS The JR-P(II) suppressed proliferative capacity of SW1736, BHP7-13, and 8305C cells. JR-P(II) treatment markedly promoted expression of acetylated histone H3, H4, and tubulin in a dose-dependent manner. Treatment with JR-P(II) significantly elevated the proportion of cells in sub-G1 and promoted cleaved caspase-3 and -9. In JR-P(II)-treated cells, DCFH-DA fluorescence was much higher relative to control cells. The JR-P(II) treatment consistently suppressed expression of pS6, p-ERK1/2, p-4E-BP1, and p-AKT, and increased p-H2AX expression and suppressed KU70 and KU80 protein levels. The level of RAD51 was repressed in JR-P(II)-treated cells. JR-P(II) administration in mice caused no significant change in body weight, and it inhibited SW1736 tumor growth in mice. CONCLUSIONS The JR-P(II) induced cytotoxicity in thyroid cancer cells by inhibiting the mechanism responsible for repair of double-stranded DNA. The in vivo data also revealed that JR-P(II) effectively inhibits thyroid tumor growth by inducing DNA damage. Thus, our results suggest that further evaluation of JR-P(II) as a therapeutic candidate for thyroid cancer is warranted.

IL-10 Restores MHC Class I Expression and Interferes With Immunity in Papillary Thyroid Cancer With Hashimoto Thyroiditis.

The incidence of papillary thyroid cancer (PTC) with concomitant Hashimoto thyroiditis (HT) is increasing. Interleukin (IL)-10 is a cytokine previously reported to be elevated in this condition. Evidence from multiple human malignancies showed IL-10 participated in tumor immunity and exhibited therapeutic potential. The aim of this study is to investigate whether IL-10 interferes with tumor immunity in PTC with concomitant HT. Expression of IL-10 and major histocompatibility complex (MHC) class Ⅰ were compared with PTC tissues with or without concomitant HT. PTC cell lines K1 and TPC-1 were stimulated with IL-10 and analyzed for MHC class Ⅰ expression afterward. T-cell activation, production of IL-2 and interferon (IFN)-γ and programmed death-1 (PD-1) expression were assessed by coculture of donor peripheral blood lymphocytes (PBLs) with IL-10-pretreated PTC cells. Programmed death-ligand 1 (PD-L1) expression was measured in PTC tissues and IL-10-pretreated cells of K1 and TPC-1. Increased levels of IL-10 and MHC class Ⅰ were observed in PTC with concomitant HT. IL-10 stimulation increased MHC class Ⅰ expression of PTC cells in vitro. Coculture of PBLs with IL-10-pretreated PTC cells enhanced T-cell activation (% cluster of differentiation [CD]25+ of CD3+T cells) and increased IL-2 production along with decreased IFN-γ secretion and PD-1 expression. Reduced PD-L1 expression was seen in PTC + HT tissue samples and IL-10-stimulated PTC cell lines. Elevated IL-10 expression in PTC with concomitant HT restores MHC class Ⅰ expression and interferes with tumor immunity. The potential mechanism of IL-10 in tumor immunity needs further investigation.