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Coal smouldering fires are global disasters and notoriously challenging to characterize. To better understand combustion and chemistry within these coal fires, TG-DSC experiments were carried out in two different coal samples in nitrogen and oxygen-limited (including ambient air) atmospheres. A mechanism with 8-step reactions simulating coal combustion was proposed, including one drying, two pyrolysis, two oxygen adsorption, and three high-temperature oxidations. The kinetic parameters were optimized via a Genetic Algorithm (GA). It was found that this 8-step mechanism created unnecessary overfitting to the TGA data. Therefore, two alternative schemes were developed with 5- and 4-step, which included and neglected oxygen adsorption, respectively. To compare the two schemes, GA and Gaussian multi-modal fitting were used to quantify the mass change rates in each step and their thermal effects as functions of oxygen concentrations. Moreover, the heat flow rates of coal samples were calculated and compared with measured DSC curves. The results indicated that oxygen adsorption could play a critical role in the transition from water evaporation to high-temperature combustion, and the 5-step scheme could reflect coal's intrinsic oxygen-limited combustion characteristics more accurately. Altogether, this study provides novel insight into coal smouldering under oxygen-limited conditions. • A multi-step scheme governs coal combustion in various oxygen-limited atmospheres. • Only dried coal adsorbs oxygen, while semi-coke oxidation occurs in rapid combustion. • Secondary oxidation of semi-coke creates unnecessary overfitting of TGA data. • Polycondensation and its products' oxidation are prevented by competition in O 2. • Oxygen adsorption is critical to balance overall heat released from coal smouldering. [ABSTRACT FROM AUTHOR]

High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of −0.22 and −0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio‐demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions. • We used the GBD 2019 study for the first time to evaluate the CVD burden attributable to HFPG. • Our results shows that males, elderly, and lower SDI regions have serious burden. • Our findings can help policymakers develop precise prevention strategies. [ABSTRACT FROM AUTHOR]

This study aims to elucidate the cascading effect of entrepreneurial leadership on fostering employee creativity in hospitality and tourism firms. Drawing upon multiple theories (e.g., the affective events theory and conservation of resources theory) and utilizing a multilevel mediation model, this study predicts and examines the cross-level indirect relationship between entrepreneurial leadership and employee creativity, which is sequentially transmitted through employees' surface acting and work-related flow. Based on a 2-wave longitudinal design, survey data were obtained from multiple sources consisting of 47 leaders and 352 employees in Chinese hospitality and tourism firms. Multilevel structural equation modeling (MSEM) analysis provides empirical support for the cross-level mediation model. This study is among the first to provide empirical evidence of the cross-level effect of entrepreneurial leadership on workplace creativity via surface acting and work-related flow in the service industry, which enriches the leadership literature in the tourism discipline. [ABSTRACT FROM AUTHOR]

This paper proposes a novel method for decorating 3D surfaces using a new type of vector graphics, called Poisson Vector Graphics (PVG). Unlike other existing techniques that frequently require local/global parameterization, our approach advocates a parameterization-free paradigm, affording decoration of geometric models with any topological type while minimizing the overall computational expenses. Since PVG supports a set of simple discrete curves, it is straightforward for users to edit colors and synthesize geometry details. Meanwhile, the details could be organized by Poisson Region (PR), leading to much smoother decoration than those of Diffusion Curve (DC). Consequently, it is an ideal tool to create smooth relief. It may be noted that, DC is adequate to create sharp or discontinuous results. But PR is superior to DC, supporting level-of-details editing on meshes thanks to its smoothness. To render PVG on meshes efficiently, we develop a Poisson solver based on harmonic B-splines, which could be constructed using geodesic Voronoi diagram. Our Poisson solver is a local solver for rendering with more flexibility and versatility. We demonstrate the efficacy of our approach on synthetic and real-world 3D models. [ABSTRACT FROM AUTHOR]

[Display omitted] A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC 50 = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment. [ABSTRACT FROM AUTHOR]

• Using a sample of Chinese listed firms between 2001 and 2019, we empirically examine the impact of signing auditors' cultural background on client investment efficiency. • Signing auditors with merchant guilds cultural background increase the audit quality, thus leading to the improvement of investment efficiency. • The positive relationship between signing auditors with merchant guilds cultural background and investment efficiency is more pronounced in firms with high financial constraint and high level of risk taking. This paper explores the effect of signing auditors' cultural background on investment efficiency. Using a sample of Chinese listed firms between 2001 and 2019, we empirically examine the impact of signing auditors' cultural background on client investment efficiency. We find that signing auditors with merchant guilds cultural background significantly increase investment efficiency. Moreover, the increase of client investment efficiency is partly due to improved audit quality brought about by auditors' cultural background. Further tests show that the above relationship is more pronounced in firms with high financial constraint and high level of risk taking. This paper contributes to the literature on the effect of signing auditors' characteristics on corporate behaviors and the long-term consequence of culture on individuals and organizations. [ABSTRACT FROM AUTHOR]

The structure of goldfish ( Carassius auratus ) Tgf2 transposase is still poorly understood, although it can mediate efficient gene transfer in teleost fish. We hypothesized the existence of a nuclear localization signal (NLS) within Tgf2 transposase to assist transport into the nucleus. To explore this, 15 consecutive amino acid residues (656–670 aa) within the C-terminus of Tgf2 transposase were predicted in silico to be a NLS domain. The pEGFP-C1-Tgf2TP △31C plasmid encoding the NLS-domain-deleted Tgf2 transposase fused to EGFP was constructed, and transfected into 293T cells. After transfection with pEGFP-C1-Tgf2TP △31C , EGFP was not detected in the nucleus alone, while 67.0% of cells expressed EGFP only in the cytoplasm. In contrast, after transfection with control plasmids containing C- or N-terminal truncated Tgf2 transposases with an intact NLS domain, EGFP was not detected in the cytoplasm alone, while approximately 40% of cells expressed EGFP only in the nucleus, and the remaining 60% expressed EGFP in both the nucleus and cytoplasm. Our results demonstrated that loss of the NLS domain results in expression in the cytoplasm but not in the nucleus. These findings suggest that 15 aa residues located from 656 to 670 aa within the C-terminus of Tgf2 transposase can function as a NLS to assist the transfer of the transposase into the nucleus where it mediates DNA transposition. [ABSTRACT FROM AUTHOR]

In this paper, we advocate a novel method for analyzing the functionality of parts in 3D objects. In contrast to prior research, our method no longer characterizes the functionality of an object part using its single type of qualities (or attributes), e.g., geometry or interactions, nor by weighing the significance of various qualities. Instead, we consider the latent space of part functions as a semantic feature space comprehensively defined by part qualities. To learn such a space by parameterizing and encoding semantic features from multi-channel, we begin by learning multi-modal latent space using shapes, textures, and interaction scenes. Next, the latent space of part functions is generated by embedding and interweaving these multi-modal spaces into a space with a higher dimension. We devise loss functions to direct the embedding and interweaving of multi-modal spaces while preserving their manifolds. Consequently, the learned functionality latent space can capture the similarities between semantic features related to functionality and encode them into high-level functional representations. We assess this innovative approach on diverse categories of textured 3D shapes. Extensive experiments have exhibited our method's parametric and encoding capability towards functionality-centric shape analysis and synthesis, including shape functionality analysis, functionally-similar shape retrieval, and functionality-aware modeling, all of which are of the essence to new graphics techniques and applications. [Display omitted] • A novel method for functionality analysis using multi-modal latent space embedding. • Encoding different function cues into high-level functionality representations. • New functionality-centric shape analysis and synthesis solutions. [ABSTRACT FROM AUTHOR]

In this paper three-dimensional graphene (3D-GR) was directly formed on the surface of carbon ionic liquid electrode (CILE) by electrodeposition. By using 3D-GR/CILE as the substrate electrode, a new electrochemical biosensor was prepared by immobilization of hemoglobin (Hb) on the electrode surface with a chitosan film. Electrochemical investigation indicated that a pair of well-defined redox peaks appeared on cyclic voltammogram, indicating the realization of direct electron transfer of Hb with the underlying electrode. The result can be ascribed to the porous structure of 3D-GR with high conductivity and big surface area. Based on the electrochemical data, the electron transfer coefficient ( α ) and the apparent heterogeneous electron transfer rate constant ( k s ) were calculated to be 0.426 and 1.864 s −1 , respectively. The modified electrode displayed good electrocatalytic activity to the reduction of trichloroacetic acid (TCA), and the catalytic reduction peak current had a good linear relationship to TCA concentration in the range from 0.4 to 26.0 mmol/L with the detection limit of 0.133 mmol/L (3 σ ). Therefore a new third-generation electrochemical Hb biosensor based on 3D-GR/CILE was constructed with good stability and reproducibility. [ABSTRACT FROM AUTHOR]

A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs 546 conjugates and anti-CEA McAb-QDs 620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5–113% for AFP and 90–97.3% for CEA) and low relative standard deviations (RSDs) (2.8–6.2% for AFP and 4.9–9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. [ABSTRACT FROM AUTHOR]

Using the chemical spray pyrolysis method, nanostructured ZnO films have been synthesized on p-type silicon substrates. The fabricated films are grown at different deposition temperatures (300–500 °C) and are characterized using a combination of microstructural, electrical, and nanoscopic piezoelectric techniques. The X-ray diffraction results, in agreement with piezoresponse force microscopy, confirm that the deposits have a hexagonal wurtzite structure with a change in preferred orientation from (0 0 2) to (1 0 1) with an increase in the deposition temperature above 350 °C. ZnO nanostructures with the optimal crystallinity, electrical mobility, and carrier concentration are obtained at 450 °C. XPS spectra are used to determine the chemical state and elemental composition of the films. The decrease in bandgap with the increase in temperature is well correlated with calculated crystallite size. The samples deposited at lower temperatures show the strongest blue emission due to its defective nature. A comparative nanoscale piezoelectric investigation reveals enhanced piezoelectric response at 350 °C compared to samples fabricated at other deposition temperatures. Our study thus sheds light on the important role of the deposition temperatures in control and tuning the microstructural and piezoelectric properties of the spray pyrolyzed ZnO films. [Display omitted] • Hexagonal wurtzite structure of the deposits with a change in orientation from (0 0 2) to (1 0 1) at or above 350 °C. • +2 oxidation state of Zn is confirmed from XPS spectra. • Maximum electrical mobility and carrier concentration is observed in ZnO films fabricated at 450 °C. • Maximum piezoelectricity is revealed for the films deposited at 350 °C. [ABSTRACT FROM AUTHOR]

Abstract: Recently, studies involving uterine cervical cancer and uterine corpus cancer have been reported from many institutes. The presence of regulatory T cells (Treg cells) in human uterine cancer is crucial for maintaining immunological homeostasis. To improve treatment strategies, I will be reviewing recent studies in the field. This work will discuss the central role that Treg cells play in the development of uterine cancer, which makes these cells a key missing component in current cancer immunotherapy. [Copyright &y& Elsevier]

Abstract: We proposed a fiber-based quantum clock synchronization protocol by employing the dispersion cancellation feature of the frequency anti-correlated entangled source under the quantum interference measurement. It is shown that, the accuracy of the synchronization is mainly dependent on the bandwidth of the frequency entangled biphoton spectrum and on the temperature variation induced fluctuations in both the reference fiber coiling and the fiber link. With this proposal, synchronization between two clocks at a distance of ten kilometers can be implemented with an accuracy below a picosecond. [Copyright &y& Elsevier]

Abstract: Background: Recent studies suggest a potential impact of Th17 cells on tumor. In the present study, we investigated the distribution of Th17 cells in relation to Foxp3-expressing T cells in the tumor-infiltrating lymphocytes (TILs) from patients with uterine cervical cancer (UCC), cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and healthy cervical tissues. Methods: Th17 cells and Foxp3-expressing T cells were evaluated by immunohistochemical staining. IL-6, TGF-β, IL-17 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining for microvessel density (MVD) was performed in order to assess the association of IL-17 expression with angiogenesis. Results: Compared with controls, patients with UCC or CIN had a higher proportion of Th17 cells and Foxp3-expressing T cells, when the ratio of Th17/Foxp3-expressing T cells in TILs was decreased in individual cases, it was more markedly decreased in TILs than normal cervical tissues. Meanwhile, the cytokine(IL-6, TGF-β and IL-10) concentrations were significantly higher in UCC patients than those in healthy controls. Interestingly, the levels of intratumoral Th17 cells were positively correlated with MVD in tumors. Conclusions: The imbalance of Th17/Foxp3-expressing T cells may play critical roles in the development and progression of UCC and Th17 cells may promote tumor progression by fostering angiogenesis. [Copyright &y& Elsevier]

• Comprehensive preoperative screening of patients on the waiting list for liver transplantation (LT) is critical to identify those patients with hepatopulmonary syndrome (HPS) who would maximally benefit from LT. • Survival rates of patients with moderate to severe HPS are significantly increased after LT. • LT should be performed as soon as possible in patients with moderate to severe HPS. Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P =.003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P =.001). Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS. [ABSTRACT FROM AUTHOR]

This paper introduces a method for transferring colors between portrait images. Using a trained neural network to extract facial mask, we vectorize each image with a set of sparse diffusion curves to encode the low-frequency colors, and use the Laplacian of residual colors to represent the high-frequency details. Then we apply optimal mass transport to transfer the boundary colors between the diffusion curves of the source and reference images. Finally, the original or modified Laplacians of colors are added to the transferred diffusion curve image. Unlike the existing methods that either require 3D information or assume the source and reference images have similar poses and dense correspondence, our method is computationally efficient and flexible, which can work for portrait images with large pose and color differences. • An efficient method for transferring skin and hair colors using Poisson vector graphics. • We apply optimal mass transport to transfer the boundary colors between extracted diffusion curves. • It works for portrait images with large pose and color differences. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel convolution neural networks (CNNs) based method for nodule type classification. Compared with classical approaches that are handling four solid nodule types, i.e., well-circumscribed, vascularized, juxta-pleural and pleural-tail , our method could also achieve competitive classification rates on ground glass optical (GGO) nodules and non-nodules in computed tomography (CT) scans. The proposed method is based on multi-view multi-scale CNNs and comprises four main stages. First, we approximate the spherical surface centered at nodules using icosahedra and capture normalized sampling for CT values on each circular plane at a given maximum radius. Second, intensity analysis is applied based on the sampled values to achieve estimated radius for each nodule. Third, the re-sampling (which is the same as the first step but with estimated radius) is conducted, followed by a high frequency content measure analysis to decide which planes (views) are more abundant in information. Finally, with approximated radius and sorted circular planes, we build nodule captures at sorted scales and views to first pre-train a view independent CNNs model and then train a multi-view CNNs model with maximum pooling. The experimental results on both Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) [1] and Early Lung Cancer Action Program(ELCAP) [2] have shown the promising classification performance even with complex GGO and non-nodule types. [ABSTRACT FROM AUTHOR]

High aspect ratio gallium nitride (GaN) nanostructures were fabricated by photochemical etching using hydrofluoric acid as the etchant. Under the etching time of 20 min, the surface pore density is estimated to be ~ 5.6 × 10 9 cm 2 , and the aspect ratio of the pore structure is as high as ~ 10: 1. The biggest photocurrent and strongest photoluminescence intensity of the etched GaN are ~ 3.2 and 9.7 times of that of the as-grown GaN, respectively, which demonstrates high aspect ratio GaN nanostructures have great potential for a series of photoelectric and optical devices. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel classification method for lung nodules from CT images based on hybrid features. Towards nodules of different types, including well-circumscribed, vascularized, juxta-pleural, pleural-tail, as well as ground glass optical (GGO) and non-nodule from CT scans, our method has achieved promising classification results. The proposed method utilizes hybrid descriptors consisting of statistical features from multi-view multi-scale convolutional neural networks (CNNs) and geometrical features from Fisher vector (FV) encodings based on scale-invariant feature transform (SIFT). First, we approximate the nodule radii based on icosahedron sampling and intensity analysis. Then, we apply high frequency content measure analysis to obtain sampling views with more abundant information. After that, based on re-sampled views, we train multi-view multi-scale CNNs to extract statistical features and calculate FV encodings as geometrical features. Finally, we achieve hybrid features by merging statistical and geometrical features based on multiple kernel learning (MKL) and classify nodule types through a multi-class support vector machine. The experiments on LIDC-IDRI and ELCAP have shown that our method has achieved promising results and can be of great assistance for radiologists’ diagnosis of lung cancer in clinical practice. [ABSTRACT FROM AUTHOR]

In this paper a three-dimensional (3D) reduced graphene oxide (RGO) and gold (Au) composite was synthesized by electrodeposition and used for the electrode modification with carbon ionic liquid electrode (CILE) as the substrate electrode. Myoglobin (Mb) was further immobilized on the surface of 3D RGO–Au/CILE to obtain an electrochemical sensing platform. Direct electrochemistry of Mb on the modified electrode was investigated with a pair of well-defined redox waves appeared on cyclic voltammogram, indicating the realization of direct electron transfer of Mb with the modified electrode. The results can be ascribed to the presence of highly conductive 3D RGO–Au composite on the electrode surface that accelerate the electron transfer rate between the electroactive center of Mb and the electrode. The Mb modified electrode showed excellent electrocatalytic activity to the reduction of trichloroacetic acid in the concentration range from 0.2 to 36.0 mmol/L with the detection limit of 0.06 mmol/L (3σ). [ABSTRACT FROM AUTHOR]

Follicular atresia in chickens reduces the number of follicles that can further develop, leading to decrease egg laying. Endoplasmic reticulum stress (ERS) can initiate a unique pathway inducing the apoptosis of follicular granulosa cells, thus reducing egg laying. Melatonin (MEL) is involved in the regulation of follicle development, ovulation, and oocyte maturation, and is closely related to follicle fate. Mammalian target of Rapamycin (mTOR) signaling pathway plays an important role in cell growth regulation, and that there is a possible crosstalk between melatonin and mTOR activity in granular cells maturation and ovulation. This study aimed to investigate whether MEL inhibits ERS and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens. Frist, we established an in vitro ERS cell model using tunicamycin (TM). The results showed that different concentrations of TM exhibited dose-dependent inhibition of cell activity and induction of granulosa cells (P <0.01). Therefore, we chose 5 µg/mL of TM and a treatment time for 6 h as the optimal concentration for the following experiments. Then we investigate whether melatonin can inhibit ERS. TM treatment decreased the cell viability and Bcl-2 expression, increasing ROS levels and the mRNA expression of Grp78, ATF4, CHOP, PERK, eIF-2α , and BAX (P <0.01), whereas TM+MEL treatment significantly inhibited these changes (P <0.01). Then we explored whether melatonin protects follicular granulosa cells from ERS-induced apoptosis through the mammalian target of rapamycin (mTOR) signaling pathway by regulating ATF4, we found that ATF4 knockdown inhibited ERS by decreasing the expression of ERS-related genes and proteins and activating mTOR signaling pathway by increasing the protein expression of p4E-BP1 and pT389-S6K (P <0.001), while these changes were promoted by TM+si-ATF4+MEL treatment (P <0.01). These results indicate that MEL could alleviate TM-induced ERS by regulating ATF4 to activate mTOR signaling pathway in follicular granulosa cells, thus providing a new perspective for prolonging the laying cycle in chickens. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of umbilical cord mesenchymal stem cells (UCMSCs) in acute respiratory distress syndrome (ARDS) is mainly limited by the efficiency of homing of UCMSCs toward tissue damage. C-X-C chemokine receptor type 7 (CXCR7), which is involved in the mobilization of UCMSCs, is only expressed on the surface of a small proportion of UCMSCs. This study examined whether overexpression of CXCR7 in UCMSCs (UCMSCsOE-CXCR7) could improve their homing efficiency, and therefore, improve their effectiveness in fibrosis repair at the site of lung injury caused by ARDS. A lentiviral vector expressing CXCR7 was built and then transfect into UCMSCs. The impacts of CXCR7 expression of the proliferationand homing of UCMSCs were examined in a lipopolysaccharide-induced ARDS mouse model. The potential role and underlying mechanism of CXCR7 were examined by performing scratch assays, transwell assays, and immunoassays. The therapeutic dose and treatment time of UCMSCsOE-CXCR7 were directly proportional to their therapeutic effect on lung injury. In addition, overexpression of CXCR7 increased SDF-1-induced proliferation and migration of lung epithelial cells (Base-2b cells), and upregulation of CXCR7 inhibited α-SMA expression, suggesting that CXCR7 may have a role in alleviating pulmonary fibrosis caused by ARDS. Overexpression of CXCR7 in UCMSCs may improve their therapeutic effect of acute lung injury mouse, The mechanism of fibrosis repair by CXCR7 is inhibition of Jag1 via suppression of the Wnt/β-catenin pathway under the chemotaxis of SDF-1. • UCMSCs' therapeutic efficacy in ARDS is limited by homing efficiency. • CXCR7 promotes MSCs homing, but little is known beyond endothelial adhesion factors. • CXCR7 enhances UCMSC homing and protects lungs from fibrosis in ARDS. • CXCR7 may alleviate pulmonary fibrosis via Jag1 inhibition through the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) has complex neurodevelopmental impairments and origins that are linked to both genetic and environmental factors. Hence, there is an urgency to establish animal models with ASD-like characteristics to understand the underlying mechanisms of ASD. Prenatal exposure to valproic acid (VPA) produced ASD-like symptoms in humans, rats, and recently zebrafish. The present study investigated the use of VPA exposure to generate an ASD model in zebrafish. Early life stage exposures produced ASD-like phenotypes in the developing brain development and behavioral changes in embryonic and larval zebrafish. Our findings revealed that treating zebrafish embryos with VPA starting at 8 h post fertilization (hpf) resulted in significant: increase in the ASD macrocephalic phenotype; hyperactivity of embryo/larvae movement behaviors; and increases of ASD-like larval social behaviors. Further analysis showed increases in cell proliferation, the proportion of mature newborn neurons, and neural stem cell proliferation in the brain region, which may contribute to the brain overgrowth and macrocephaly observed following VPA exposure. Our study demonstrated that VPA exposure generates ASD-like phenotypes and behaviors, indicating that zebrafish is an alternative model to investigate underlying ASD mechanisms. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) metal-semiconductor nanostructures as surface-enhanced Raman scattering (SERS) substrates were designed by in situ electrodeposition of gold nanoparticles (AuNPs) or in situ photodeposition of silver nanoparticles (AgNPs) on gallium nitride (GaN) nanoflowers (NFs) supports fabricated by metal-assisted photochemical etching of single crystalline GaN. 3D AuNPs/GaN NFs and AgNPs/GaN NFs substrates exhibit excellent enhancement effect for Rhodamine 6G (R6G) due to more “hot spots” in the same probing volume compared to 2D GaN based substrates. The enhancement factors of the AuNPs/GaN NFs and AgNPs/GaN NFs substrates are up to 2.1 × 10 7 and 5.9 × 10 7 , respectively, and the corresponding detection limits of R6G are 10 −8 and 10 −10 M, respectively. Moreover, further study reveals both substrates have good reproducibility and long-term stability. The performance of the prepared substrates for biological application was demonstrated by the detection of bovine serum albumin (BSA). A series of characteristic bands of amides suggest BSA can be well adsorbed on the surface of the AuNPs/GaN NFs and AgNPs/GaN NFs substrates, which demonstrates our substrates have good biocompatibility and are promising candidates for SERS biosensors. [ABSTRACT FROM AUTHOR]

Gallium nitride (GaN) nanowires (NWs) were fabricated by metal-assisted photochemical etching (MaPEtch). Gold nanoparticles (AuNPs) as metal catalyst were electrodeposited on the GaN substrate. SEM and HRTEM images show the surface of GaN NWs is smooth and clean without any impurity. SAED and FFT patterns demonstrate GaN NWs have single crystal structure, and the crystallographic orientation of GaN NWs is (0002) face. On the basis of the assumption of localized galvanic cells, combined with the energy levels and electrochemical potentials of reactants in this etching system, the generation, transfer and consumption of electron-hole pairs reveal the whole MaPEtch reaction process. Such easily fabricated GaN NWs have great potential for the assembly of GaN-based single-nanowire nanodevices. [ABSTRACT FROM AUTHOR]

[Display omitted] • 25 novel Afatinib-Poziotinib hybrids were designed via 3D modeling of kinase structure. • Compound 56 could inhibit the growth of tumor cells with various HER2 exon 20 mutations and EGFR mutants both in vitro and in vivo. • Compound 56 could remarkably reduced binding affinity with hERG protein. In previous decades, patients with the most active EGFR mutations in non-small cell lung cancer (NSCLC) have significantly benefited from EGFR tyrosine kinase inhibitors (TKIs). However, a minority with EGFR and HER2 exon 20 mutations are inherently resistant to treatment. Several molecular TKIs (such as TAK788 and Poziotinib) were recently discovered and demonstrated as effective inhibitors against the most prevalent HER2 or EGFR exon 20 mutations. However, low clinical efficiency and uncertain adverse reaction indicated that the development of effective therapies is still demanded. In the present work, we designed several hybrid compounds learning from 3D modeling of kinase structure. One lead compound (compound 56) was found to be the most potent compound with IC 50 value of 0.027 nM against EGFR D770-N771 ins NPG and reduced binding affinity with hERG protein. In vitro and in vivo biological results suggested that compound 56 demonstrated good oral bioavailability, and it was significantly capable of inhibiting the growth of tumor cells with a variety of HER2 exon 20 mutations and EGFR mutants with negligible toxic effects. It was identified that compound 56 might be considered a potential drug candidate for NSCLC target therapy. [ABSTRACT FROM AUTHOR]

Sodium/iodide symporter (NIS) acts as a vital role in regulation of iodide uptake in thyroid cancer. However, the efficient approach to increase NIS expression and the mechanism of NIS-mediated iodide uptake in thyroid cancer remain unclear. Small activating RNA (saRNA) was used to promote NIS expression. And the cell viability, apoptosis, and autophagy were detected using Cell count-kit 8 (CCK-8), Annexin V-FITC/PI double staining, and GFP-LC3 immunofluorescence assays, respectively. The protein levels of caspase 3, Bax, Bcl-2, ATG5, ATG12, LC3B Ⅱ to LC3B Ⅰ, Beclin 1, P62, AMPK, mTOR, P70S6K, actin, and phosphorylation of AMPK, mTOR, P70S6K were determined by western blotting. Moreover, a nude murine node with transplanted NC-dsRNA or NIS-482-transfected SW579 cells was used to examine the effect of NIS-mediated autophagy in vivo. And the levels of caspase 3 and ki67 were examined by immunohistochemical staining assay. saRNA mediated NIS mRNA and protein upregulated in SW579 cells. saRNA-mediated NIS expression inhibited cell proliferation, induced apoptosis and autophagy, and promoted iodide uptake in SW579 cells. Moreover, the effects of NIS on cells were enhanced by autophagy activator Rapamycin whereas reversed by autophagy inhibitor 3-Methyladenine (3-MA). For mechanism analysis, we found that NIS upregulation exerted the effects on cell proliferation, apoptosis, autophagy, and iodide uptake via regulating AMPK/mTOR pathway. We also demonstrated that saRNA-mediated NIS expression promoted iodide uptake in vivo. saRNA-mediated NIS expression acted as a critical role in increasing iodide uptake via AMPK/mTOR pathway in thyroid cancer. [ABSTRACT FROM AUTHOR]

This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/β-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and β-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/β-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC. • M2-like TAMs are enriched in human TC tissues, and promotes TC cells proliferation, migration, invasion and stemness. • ZA weakens the progression of TC cells by inhibition M2-like TAMs. • ZA inhibits β-catenin entry into the nucleus and activation of Wnt/β-catenin pathways induced by M2-like TAMs. • ZA reduces subcutaneous tumor formation and macrophage enrichment in vivo. [ABSTRACT FROM AUTHOR]

Chemotherapy and molecularly targeted therapy are main strategies for treatment of cancers. However, long-term treatment makes cancer cells acquire resistance to anti-cancer drugs, which severely limits the effects of cancer treatment. NcRNAs, especially miRNAs and lncRNAs, have been reported to play key roles in drug resistance and could restore drug responses in resistant cells. We presented a network-based framework to systematically identify drug resistance associated miRNAs and lncRNAs. First, we constructed a comprehensive heterogeneous miRNA-lncRNA regulatory network through integrating curated miRNA regulations to lncRNA, and significantly co-expressed miRNA-miRNA, lncRNA-lncRNA and miRNA-lncRNA interactions for each cancer type. Second, random walk with restart (RWR) was utilized to identify novel drug resistance associated ncRNAs. We predicted 470 associations of 34 miRNAs and 79 lncRNAs for 27 drugs in 10 cancer types. In addition, leave-one-out cross validation (LOOCV) demonstrated the effectiveness of the proposed approach. Next, we also demonstrated that the integrated heterogeneous cancer-specific network achieved better performance than the general curated miRNA-lncRNA regulatory network. What's more, we found that the drug resistance associated ncRNAs validated by high-throughput technology was also a reliable source for prediction. We proposed a new framework to identify novel and reliable drug resistance associated ncRNAs, which provides new perspectives for drug resistance mechanism and new guidance for clinical cancer treatment. [ABSTRACT FROM AUTHOR]