Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Ultra-Sensitive and Selective Detection of Arsenic(III) via Electroanalysis over Cobalt Single-Atom Catalysts.

Achieving highly sensitive and selective detection of trace-level As(III) and clarifying the underlying mechanism is still a intractable problem. The electroanalysis of As(III) relies on the electrocatalytic ability of the sensing interface. Herein, we first adopt single-atom catalysts as the electrocatalyst in As(III) detection. Cobalt single-atoms anchored on nitrogen-doped carbon material (Co SAC) were found to have an extraordinary sensitivity of 11.44 µA ppb-1 with excellent stability and repeatability, which so far is the highest among non-noble metal nanomaterials. Co SAC also exhibited a superior selectivity toward As(III) compared with some bivalent heavy metal ions (HMIs). Combining X-ray absorption spectroscopy (XAFS), density functional theory (DFT) calculation, and reaction kinetics simulation, we demonstrated that Co single atoms stabilized in N2C2 support serve as active sites to catalyze H3AsO3 reduction via the formation of Co-O hybridization bond, leading to a lower energy barrier, promoting the breakage of As-O bonds. Importantly, the first electron transfer is the rate-limiting step of arsenic reduction and is found to be more favorable on Co-SAC both thermodynamically and kinetically. This work not only expands the potential applicaiton of single-atom catalysts in the detection and treatment of As(III), but also provides atomic-level catalytic insights into HMIs sensing interfaces.

Identifying Phase-Dependent Electrochemical Stripping Performance of FeOOH Nanorod: Evidence from Kinetic Simulation and Analyte-Material Interactions.

Metal hydroxide nanomaterials are widely applied in the energy and environment fields. The electrochemical performance of such materials is strongly dependent on their crystal phases. However, as there are always multiple factors relating to the phase-dependent electrochemistry, it is still difficult to identify the determining one. The well-defined crystal phases of α- and ß-FeOOH nanorods are characterized through the transmission electron microscopy by a series of rotation toward one rod, where the cross-section shape and the growth direction along the [001] crystalline are first verified for 1D FeOOH nanostructures. The electrosensitivity of the two materials toward Pb(II) is tested, where α-FeOOH performs an outstanding sensitivity whilst it is only modest for ß-FeOOH. Experiments via Fourier transform infrared spectroscopy, X-ray absorption fine structure (XAFS), etc., show that α-FeOOH presents a larger Pb(II) adsorption capacity due to more surficial hydroxyl groups and weaker PbO bond strength. The reaction kinetics are simulated and the adsorption capacity is found to be the determining factor for the distinct Pb(II) sensitivities. Combining experiment with simulation, this work reveals the physical insights of the phase-dependent electrochemistry for FeOOH and provides guidelines for the functional application of metal hydroxide nanomaterials.

Changing the Blood Test: Accurate Determination of Mercury(II) in One Microliter of Blood Using Oriented ZnO Nanobelt Array Film Solution-Gated Transistor Chips.

The measurement of ultralow concentrations of heavy metal ions (HMIs) in blood is challenging. A new strategy for the determination of mercury ions (Hg2+ ) based on an oriented ZnO nanobelt (ZnO-NB) film solution-gated field-effect transistor (FET) chip is adopted. The FET chips are fabricated with ZnO-NB film channels with different orientations utilizing the Langmuir-Blodgett (L-B) assembly technique. The combined simulation and I-V behavior results show that the nanodevice with ZnO-NBs parallel to the channel has exceptional performance. The sensing capability of the oriented ZnO-NB film FET chips corresponds to an ultralow minimum detectable level (MDL) of 100 × 10-12 m in deionized water due to the change in the electrical double layer (EDL) arising from the synergism of the field-induced effect and the specific binding of Hg2+ to the thiol groups (-SH) on the film surface. Moreover, the prepared FET chips present excellent selectivity toward Hg2+ , excellent repeatability, and a rapid response time (less than 1 s) for various Hg2+ concentrations. The sensing performance corresponds to a low MDL of 10 × 10-9 m in real samples of a drop of blood.

Noble-Metal-Free Co0.6Fe2.4O4 Nanocubes Self-Assembly Monolayer for Highly Sensitive Electrochemical Detection of As(III) Based on Surface Defects.

Nanocrystals generally suffer from agglomeration because of the spontaneous reduction of the system surface energy, resulting in blocking the active sites from reacting with target ions, and then severely reducing the electrochemical sensitivity. In this article, a highly ordered self-assembled monolayer array is successfully constructed using ∼14 nm Co0.6Fe2.4O4 nanocubes uniformly and controllably distributed on the surface of a working electrode (glass carbon plate). The large area and high exposure of the surface defects on Co0.6Fe2.4O4 nanocubes are clearly characterized by high-resolution transmission electron microscopy (HRTEM) and atomic-resolution high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM). Expectedly, a considerable sensitivity of 2.12 µA ppb-1 and a low limit of detection of 0.093 ppb are achieved for As(III) detection on this highly homogeneous sensing interface; this excellent electroanalysis performance is even better than that of noble metals electrodes. Most importantly, this approach of uniformly distributing the small-sized defective nanoparticles on the electrode surface provides a new opportunity for modifying the electrodes, as well as the realization of their applications in the field of environmental electroanalysis for heavy metal ions.

Porous Single-Crystalline CdSe Nanobelts: Cation-Exchange Synthesis and Highly Selective Photoelectric Sensing toward Cu2.

Porous single-crystalline nanostructures are of tremendous interest for their application in the catalytic, electronic and sensing fields due to their large active surfaces, favorable diffusion, and good electronic transport. Despite the recent advances of various other components, photoelectric chalcogenides remain almost undeveloped. The present study contributes a facile strategy to prepare porous single-crystalline CdSe nanobelts through a cation-exchange reaction, in which ZnSe⋅0.5 N2 H4 hybrid nanobelts are employed as precursors. The detailed characterizations indicate the preservation of the belt-like morphology of the precursors due to the spatial confinement effect, which arises from the coated surfactant layer during the cation-exchange process. Simultaneously, CdSe nanobelts with porous and single-crystalline structures are formed following a complete exchange between Zn2+ and Cd2+ , the release of N2 H4 , and the atomic arrangement. The native photoelectric properties of the as-prepared porous single-crystalline CdSe nanobelts are systematically addressed based on the nanodevices fabricated with a single nanobelt and assembled nanobelt array. The results indicate that they present a rapid, stable, and repeatable photoelectric response. Moreover, as-prepared nanobelts exhibit highly selective photoelectric sensing toward Cu2+ with a low detection limit down to 0.1 ppm. To illuminate this phenomenon, a possible sensing mechanism is also discussed.

Size-tunable Ag nanoparticles sensitized porous ZnO nanobelts: controllably partial cation-exchange synthesis and selective sensing toward acetic acid.

Porous ZnO nanobelts sensitized with Ag nanoparticles have been prepared via a partial cation-exchange reaction assisted by a thermal oxidation treatment, employing ZnSe·0.5N2H4 nanobelts as precursors. After partially exchanged with Ag+ cations, the belt-like morphology of the precursors is still preserved. Continuously calcined in air, they are in situ transformed into Ag nanoparticles sensitized porous ZnO nanobelts. The size of the Ag nanoparticles can be tuned through manipulating the amount of exchanging Ag+ cations. Considering the porous and belt-like nanostructure, sensing characteristics of ZnO and the catalytic activity of Ag nanoparticles, the gas sensing performances of the as-prepared Ag nanoparticles sensitized porous ZnO nanobelts have been carefully investigated. The results indicate that Ag nanoparticles significantly enhance the sensing performances of porous ZnO nanobelts toward typical volatile organic compounds. Especially, a good selectivity has been demonstrated toward acetic acid gas with a low detection limit less than 1 ppm. Furthermore, they also display a good reproducibility with a short response/recovery time due to the thin, uniform and porous sensing film, which is fabricated with the assembled technique and in situ calcined approach. Finally, their sensing mechanism has been further discussed.

Porous and single-crystalline ZnO nanobelts: fabrication with annealing precursor nanobelts, and gas-sensing and optoelectronic performance.

Porous and single-crystalline ZnO nanobelts have been prepared through annealing precursors of ZnSe · 0.5N2H4 well-defined and smooth nanobelts, which have been synthesized via a simple hydrothermal method. The composition and morphology evolutions with the calcination temperatures have been investigated in detail for as-prepared precursor nanobelts, suggesting that they can be easily transformed into ZnO nanobelts by preserving their initial morphology via calcination in air. In contrast, the obtained ZnO nanobelts are densely porous, owing to the thermal decomposition and oxidization of the precursor nanobelts. More importantly, the achieved porous ZnO nanobelts are single-crystalline, different from previously reported ones. Motivated by the intrinsic properties of the porous structure and good electronic transporting ability of single crystals, their gas-sensing performance has been further explored. It is demonstrated that porous ZnO single-crystalline nanobelts exhibit high response and repeatability toward volatile organic compounds, such as ethanol and acetone, with a short response/recovery time. Furthermore, their optoelectronic behaviors indicate that they can be promisingly employed to fabricate photoelectrochemical sensors.

Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Synthesis and Antifungal Activities of Novel Griseofulvin Derivatives as Potential Anti-Phytopathogenic Fungi Agents.

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.

Intelligent porphyrin nano-delivery system for photostimulated and targeted inhibition of angiogenesis.

As a first-line anticancer drug, sunitinib (SUN) can significantly inhibit tumor growth through an antiangiogenic effect. The nanocarrier drug-delivery strategy has been rapidly developed to improve therapeutic efficiency and drug safety. This study designed an intelligent liposome-like nanoporphyrin to broaden the application range of sunitinib. Additionally, we suggest that this personalized drug decoration and loading design can achieve more different functions. In this study, lipid-purpurin18 conjugates (Pp18-lipids) were synthesized by conjugating photosensitizer purpurin-18 (Pp18) with a phospholipid. Then, a porphyrin nano-delivery system (iPlipo-SUN) was developed by iRGD-modified Pp18-lipids-embedded liposome-carrying SUN. The system confers the targeted light-triggered SUN release, phototoxic properties, and antiangiogenesis onto iPlipo-SUN to multi-directionally suppress tumor growth. IPlipo-SUN was more effective than a maximum-tolerated dose of free SUN with its spatiotemporal control of drug release and intrinsic therapeutic effects. Therefore, the iPlipo-SUN offers new prospects for synergistic treatment that can be extended to explore tumor regrowth inhibition in clinical application.

Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report and review of the literature.

RATIONALE: Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect. PATIENT CONCERNS: A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors. DIAGNOSES: In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made. INTERVENTION: Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively. OUTCOMES: Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery. LESSONS: The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.

Inhibition of BAG3 enhances the anticancer effect of shikonin in hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy.

Hierarchical Morphology-Dependent Gas-Sensing Performances of Three-Dimensional SnO2 Nanostructures.

Hierarchical morphology-dependent gas-sensing performances have been demonstrated for three-dimensional SnO2 nanostructures. First, hierarchical SnO2 nanostructures assembled with ultrathin shuttle-shaped nanosheets have been synthesized via a facile and one-step hydrothermal approach. Due to thermal instability of hierarchical nanosheets, they are gradually shrunk into cone-shaped nanostructures and finally deduced into rod-shaped ones under a thermal treatment. Given the intrinsic advantages of three-dimensional hierarchical nanostructures, their gas-sensing properties have been further explored. The results indicate that their sensing behaviors are greatly related with their hierarchical morphologies. Among the achieved hierarchical morphologies, three-dimensional cone-shaped hierarchical SnO2 nanostructures display the highest relative response up to about 175 toward 100 ppm of acetone as an example. Furthermore, they also exhibit good sensing responses toward other typical volatile organic compounds (VOCs). Microstructured analyses suggest that these results are mainly ascribed to the formation of more active surface defects and mismatches for the cone-shaped hierarchical nanostructures during the process of thermal recrystallization. Promisingly, this surface-engineering strategy can be extended to prepare other three-dimensional metal oxide hierarchical nanostructures with good gas-sensing performances.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

SiO2 nanoparticles change colour preference and cause Parkinson's-like behaviour in zebrafish.

With advances in the development of various disciplines, there is a need to decipher bio-behavioural mechanisms via interdisciplinary means. Here, we present an interdisciplinary study of the role of silica nanoparticles (SiO2-NPs) in disturbing the neural behaviours of zebrafish and a possible physiological mechanism for this phenomenon. We used adult zebrafish as an animal model to evaluate the roles of size (15-nm and 50-nm) and concentration (300 µg/mL and 1000 µg/mL) in SiO2-NP neurotoxicity via behavioural and physiological analyses. With the aid of video tracking and data mining, we detected changes in behavioural phenotypes. We found that compared with 50-nm nanosilica, 15-nm SiO2-NPs produced greater significant changes in advanced cognitive neurobehavioural patterns (colour preference) and caused potentially Parkinson's disease-like behaviour. Analyses at the tissue, cell and molecular levels corroborated the behavioural results, demonstrating that nanosilica acted on the retina and dopaminergic (DA) neurons to change colour preference and to cause potentially Parkinson's disease-like behaviour.

[Subcellular localization of severe fever with thrombocytopenia syndrome virus in macrophages].

OBJECTIVE: To study the subcellular localization of severe fever with thrombocytopenia syndrome virus (SFTSV) in macrophages and understand the replication and assembly mechanism of SFTSV in host cells. METHODS: Using two types of human macrophage cell lines THP-1 and U937, the study analyzed the intracellular colocalization of SFTSV with Golgi apparatus and endoplasmic reticulum by immunefluorescence staining and confocal microscopy. RESULTS: SFTSV infected macrophage cell lines THP-1 and U937. Immunofluorescence staining showed that the SFTSV nuclear protein colocalized with Golgi apparatus and closely surrounded by endoplasmic reticulum in the perinuclear region. CONCLUSION: The results suggested that Golgi complex and endoplasmic reticulum are probably the sites for formation and maturation of SFTSV viral particles.