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Tendinopathy is a common tendon disorder characterized by pain, swelling, and dysfunction. Current evidence has demonstrated that the depletion of stem cell pool and non-tenogenic differentiation of tendon-derived stem/progenitor cells (TSPCs) might account for the pathogenesis of tendinopathy. FNDC5/Irisin, as a novel exercise-induced myokine, is proved to be involved in the exercise-induced protective effects on musculoskeletal disorders. However, whether irisin can affect TSPCs fate is still unknown. To ascertain the roles of irisin on the proliferation and tenogenic differentiation of TSPCs, rat TSPCs were isolated and incubated with irisin. Cell viability, phenotypic changes, and related signaling pathways were evaluated by CCK-8 assay, colony formation assay, real-time PCR, Western blot, immunofluorescence, and proteasome activity assay. We found that irisin treatment increased the proliferative and colony-forming abilities, and promoted the tenogenic differentiation of TSPCs by upregulating the expression of YAP/TAZ. In conclusion, our work showed for the first time that irisin promotes the proliferation and tenogenic differentiation of rat TSPCs in vitro by activating YAP/TAZ, and the process was associated with a ubiquitin-proteasome proteolytic pathway. In conclusion, irisin and agents targeting YAP/TAZ may be promising therapeutic options for tendinopathy.

There is still A lack of explanation on the influence mechanism of the existing theories of institutional investors on the dual innovation perspective. Based on the resource-based view, this project takes 3093 A-share listed companies from 2015 to 2019 as samples and uses OLS regression analysis to explore the relationship between the shareholding ratio of institutional investors and enterprise exploratory innovation, exploitative innovation and dual innovation. On this basis, the mediating role of TMT stability and the moderating role of digital transformation are analyzed. It is found that the shareholding ratio of institutional investors inhibits firms' exploratory innovation, development innovation and dual innovation. The stability of SENIOR management team plays a partial mediating role in the influence of shareholding ratio of institutional investors on exploratory innovation, developmental innovation and dual innovation. Digital transformation inhibits the influence of shareholding ratio of institutional investors on exploratory innovation, development innovation and dual innovation. This study expands the existing theory of dual innovation and provides experience for enterprise innovation management.

Without additional templating agent or surfactant, porous and sparse MnCO3 was synthesized hydrothermally from Mn2+ with a CO2-storage material (CO2SM). Through thermal decomposition of the as-synthesized MnCO3, ɛ-MnO2 crystals with good catalytic performance and stability in HCHO degradation were prepared. The optimum preparation conditions were determined by tuning the preparation conditions and carrying out response surface studies, and the resulting ɛ-MnO2 crystals could degrade 66.1% of a 10 ml 10 mg l−1 HCHO solution. After the HCHO degradation conditions were optimized, the thermodynamic data could be fitted with the Langmuir isotherm and quasi-secondary kinetic models at T = 25–50°C. The degradation mechanism of HCHO is discussed. This work provides a new strategy for the degradation of HCHO at room temperature.

Hypoxia causes plenty of pathologies in the central nervous system (CNS) including impairment of cognitive and memory function. Dehydroepiandrosterone (DHEA) has been proved to have therapeutic effects on CNS injuries by maintaining the homeostasis of synapses, yet its effect on hypoxia-induced CNS damage remains unknown.In vivo and in vitro models were established. Concentrations of glutamate and γ GABA were tested by ELISA. Levels of synapse-associated proteins were measured by western blotting. Density of dendritic protrusions of hippocampal neurons was assessed by Golgi staining. Immunofluorescence was adopted to observe the morphology of primary neurons. The novel object recognition test (NORT) and shuttle box test were used to evaluate cognition.Dehydroepiandrosterone reversed abnormal elevation of glutamate levels, shortenings of neuronal processes, decreases in the density of dendritic protrusions, downregulation of synaptosome-associated protein (SNAP25), and impaired cognition caused by hypoxia. Hypoxia also resulted in notably downregulation of syntaxin 1A (Stx-1A). Overexpression of Stx-1A dramatically attenuated hypoxia-induced elevation of glutamate. Treatment with DHEA reversed the Stx-1A downregulation caused by hypoxic exposure.Dehydroepiandrosterone may exert a protective effect on hypoxia-induced memory impairment by maintaining synaptic homeostasis. These findings offer a novel understanding of the therapeutic effect of DHEA on hypoxia-induced cognitive dysfunction.

This study investigated the accuracy of the random forest (RF) model in gap filling the sensible (H) and latent heat (LE) fluxes, by using the observation data collected at a site over rice–wheat rotation croplands in Shouxian County of eastern China from 15 July 2015 to 24 April 2019. Firstly, the variable significance of the machine learning (ML) model's five input variables, including the net radiation (Rn), wind speed (WS), temperature (T), relative humidity (RH), and air pressure (P), was examined, and it was found that Rn accounted for 78 % and 76 % of the total variable significance in H and LE calculating, respectively, showing that it was the most important input variable. Secondly, the RF model's accuracy with the five-variable (Rn, WS, T, RH, P) input combination was evaluated, and the results showed that the RF model could reliably gap fill the H and LE with mean absolute errors (MAEs) of 5.88 and 20.97 W m−2, and root mean square errors (RMSEs) of 10.67 and 29.46 W m−2, respectively. Thirdly, four-variable input combinations were tested, and it was found that the best input combination was (Rn, WS, T, P) by removing RH from the input list, and its MAE values of H and LE were reduced by 12.65 % and 7.12 %, respectively. At last, through the Taylor diagram, H and LE gap-filling accuracies of the RF model, the support vector machine (SVM) model, the k nearest-neighbor (KNN) model, and the gradient boosting decision tree (GBDT) model were intercompared, and the statistical metrics showed that RF was the most accurate for both H and LE gap filling, while the LR and KNN model performed the worst for H and LE gap filling, respectively.

Inhibition of EGFR and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non–small cell lung cancer (NSCLC) patients with distinct clinicopathologic features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/ERK–independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of antiapoptotic protein MCL-1. Using a panel of in vitro and in vivo studies, we showed that the regulatory machinery responsible for MCL-1 protein degradation was a step-wise event involving phosphorylation and nucleus translocation. ERK cooperated with GSKβ to phosphorylate MCL-1 Ser159 residue, which enabled MCL-1 to translocate into the nucleus and bind FBW7. Defects in this sequence impaired MCL-1 degradation and cell apoptosis, recapitulating phenotypes observed in FBW7 deficiency. Downregulation of FBW7 was found in EGFR inhibitor–resistant human NSCLC specimens and correlated with increased MCL-1 protein expression. Reactivation of FBW7 sensitized resistant cells to targeted therapy and facilitated MCL-1 degradation. Overall, our study provides proof-of-principle insight into a PI3K/Akt- and MEK/ERK–independent resistant model and suggests that targeting FBW7 can overcome resistance to targeted therapy. Cancer Res; 77(13); 3527–39. ©2017 AACR.

This supplementary figures showed the function of FBW7 in determining the sensitivity to TKIs in NSCLC and highlighted the biochemical pathways of MCL-1 proteolysis.

This supplementary tables contain shRNAs, siRNAs, primers sequences and antibody resources.

Carbon dots (CDs) or CDs/polymer composites have been applied in numerous fields. Here, novel CDs were synthesized by carbonization of egg yolk, and characterized by TEM, FTIR, XPS and photoluminescence spectra. The CDs were found to be approximate sphere in shape with an average size of 4.46 ± 1.17 nm, and emitted bright blue photoluminescence under UV irradiation. The photoluminescence of CDs was found selectively quenched by Fe3+ in a linear manner in the range of 0.05–0.45 mM, meaning they could be applied for Fe3+ detection in solution. Moreover, the CDs could be uptaken by HepG2 cells to exhibit bright blue photoluminescence. The intensity could reflect the level of intracellular Fe3+, indicating they could be further used for cell imaging and intracellular Fe3+ monitoring. Next, dopamine was polymerized on the surface of CDs to obtain the polydopamine (PDA)-coated CDs (CDs@PDA). We found PDA coating could quench the photoluminescence of CDs via inner filter effect, and the degree of quenching was linearly related to the logarithm of DA concentration (Log CDA). Also, the selectivity experiment indicated the method had a high selectivity for DA over a number of possible interfering species. This indicated the CDs in combination with Tris buffer could be potentially applied as the assay kit of dopamine. At last, the CDs@PDA exhibited excellent photothermal conversion capability, and they could efficiently kill HepG2 cells under NIR laser irradiation. Overall, the CDs and CDs@PDA in this work exhibited many excellent advantages, and could be potentially used for multi-applications, such as Fe3+ sensor in solution and cellular, cell imaging, dopamine assay kit, as well as photothermal agents for cancer therapy.

Langdu, known as a traditional Chinese medicine, was identified as the roots of species of Euphorbia ebracteolata Hayata and Euphorbia fischeriana Steud, displaying anti-tuberculosis activity. To clarify the potent quality markers of Langdu, this research first developed a fast and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry method for the quantification of 13 diterpenoids in Langdu. The developed method was further applied in the analyses of 12 authentic E. ebracteolata and E. fischeriana samples collected in northern and southeastern China. Then, the anti-tuberculosis evaluation of 12 batches of Langdu samples was performed in vitro. Finally, partial least squares discrimination analysis was used in the discrimination of E. ebracteolata and E. fischeriana from different origins and processing methods. Jolkinolide A (1), jolkinolide E (3), yuexiandajisu D (6), and ebractenone A (11) were identified as key, potent diterpenoids for the quality control of E. ebracteolata Hayata and E. fischeriana Steud. The present study established a qualitative chemical analysis method for Langdu (E. ebracteolata and E. fischeriana) and suggested the key bioactive components that will improve qualitative control methodology for this important medicine.

Shear thickening fluids (STFs) have been the research focus for decades because of the prospect as a damping ingredient. However, their inherent liquid character confines their practical applications. In this work, inspired by the assembly engineering, novel gelatinous shear thickening fluids (GSTFs) are fabricated by integrating low molecular weight gelators (LMWGs) into STFs and investigated by rheological experiments. The results show that the apparent performances of GSTFs are determined by the LMWGs content. LMWGs inside GSTFs can assemble into three-dimensional network that can constraint the flowability of liquid molecular and their content dominate the density and strength of assembly network. At a moderate content, GSTFs exhibit desired properties with restricted quasi-static flowability and almost undamaged dynamic shear thickening character. While a higher content will disappear shear thickening and a lower content cannot gelate STFs. Besides, three different LMWGs are employed to gelate STFs and all they can gelate STFs in spite of the distinct minimum gelation concentration, indicating the universality for GSTFs preparation and the superiority of a reasonable molecular structure of LMWGs. Further, the temperature sweep experiments suggest that GSTFs can endure higher temperature without flowing due to its higher gel-sol transition temperature. Basing on these advanced mechanical properties, we believe that the GSTFs with more expected characters have significance for the study of non-Newtonian fluids and will broaden the special application field of STFs.

An effective approach to the COS capture and fixation using the alcohol-amine binary systems contained Ethylene Glycol-based polyols (EGs) and Ethylenediamine-based polyamines (EDAs) under ambient conditions is developed. Fourier-Transform Infrared spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS) and X-Ray powder Diffraction (XRD) analyses reveal that COS is converted into thio-alkylcarbonate salts with the special chemical structures of [+H3NR1NH3 +-OC(=S)OR2(R3)O(S=)CO-]n, which are named as a COS-Storage Material (COSSM). Notably, the COSSM is successfully applied to the synthesis of CdS Nano-Particles (NPs) for the photocatalytic conversion of CO2 to CO and CH4, and used as a nitro-sulfur compound fertilizer to promote plant growth. Our work has provided a readily available strategy for the green storage and sustainable utilization of COS.

Circular RNAs have attracted the attention in the research on laryngeal squamous cell carcinoma (LSCC) development. But the function and mechanism of circRNA coronin-1C (circ_CORO1C) in LSCC progression are largely unknown. Circ_CORO1C, microRNA (miR)-654-3p, and ubiquitin-specific protease 7 (USP7) levels in LSCC tissues and cells were determined. Quantitative reverse transcription polymerase chain reaction and western blotting assays were conducted to determine the mRNA and protein levels of genes. Functional assays were further investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), EdU staining, flow cytometry, transwell and xenograft assays. The binding relationship was examined by dual-luciferase reporter assay. Circ_CORO1C expression was elevated in LSCC samples and cells. circ_CORO1C silencing constrained cell proliferation and promoted apoptosis via reducing cell proliferation, inducing cell cycle arrest, inhibiting epithelial-mesenchymal transition, and promoting apoptosis, as well as restraining cell migration and invasion. USP7 is highly expressed in LSCC tissues and cells, and its expression was suppressed by circ_CORO1C silencing. Besides, the up-regulation of USP7 attenuated the influence of circ_CORO1C silencing on LSCC cell progression. Both circ_CORO1C and USP7 could bind to miR-654-3p. circ_CORO1C regulated USP7 expression by modulating miR-654-3p. miR-654-3p knockdown mitigated the influence of circ_CORO1C silence on LSCC cell progression. Furthermore, circ_CORO1C silencing reduced tumor growth in vivo. In conclusion, circ_CORO1C is highly expressed in LSCC tissues and cells, and circ_CORO1C silencing repressed LSCC progression via regulating miR-654-3p/USP7 axis.

The aim of this study is to reveal the relationship between changes in the physical and chemical characterization of eggs during storage and to provide a new way to assess egg freshness at the molecular chemical level. In this study, the Fourier transform infrared (FTIR) spectra of egg albumin from 60 fresh eggs (ISA Brown layer) stored for 1, 10, 20, 30, and 40 days at 4°C and 10°C were measured ( n = 6 ), and the amide I band of the egg albumin spectra was quantified by Fourier deconvolution and curve fitting to obtain the composition of the protein molecular structure. The results showed that different storage temperatures and storage times led to protein denaturation, resulting in changes in the conformation of the protein secondary structure. With increasing storage temperature and storage time, the content of the ordered structures β-sheet and α-helix in the egg protein secondary structure decreased significantly ( p < 0.05 ), and the content of the disordered structure β-turn and random coil increased significantly ( p < 0.05 ). Based on the pattern of protein secondary structure changes during storage, it was found that fresh eggs were better stored at 4°C for up to 15 days. Spearman’s correlation analysis of egg protein height, Haugh unit, egg weight, and protein secondary structure in eggs stored at 4°C showed a significant positive correlation between β-sheet and α-helix and egg weight, protein height, and Haugh unit. And a significant negative correlation between random coil and egg weight, protein height, and Haugh unit. Therefore, a curve fitting method based on Fourier transform infrared spectroscopy of deconvoluted spectra is an effective method for evaluating egg quality and freshness.

This study investigated the accuracy of the Random Forest (RF) model in gap-filling the sensible (H) and latent heat (LE) fluxes, by using the observation data collected at a site over rice–wheat-rotation croplands in Shouxian County of eastern China from 15 July 2015 to 24 April 2019. Firstly, the variable significances of the machine learning (ML) model’s five input variables, including the net radiation (Rn), winds speed (WS), temperature (T), relative humidity (RH), and air pressure (P), were examined, and it was found that Rn accounted for 78 % and 76 % of the total variable significance in H and LE calculating, respectively, showing that it was the most important input variable. Secondly, the RF model's accuracy with the five-variable (Rn, WS, T, RH, P) input combination was evaluated, and the results showed that the RF model could reliably gap-fill the H and LE with mean absolute errors (MAEs) of 5.88 Wm−2 and 20.97 Wm−2, and root mean square errors (RMSEs) of 10.67 Wm−2 and 29.46 Wm−2, respectively. Thirdly, 4-variable input combinations were tested, and it was found that the best input combination was (Rn, WS, T, P) with the MAE of H and LE reduced by 12.65 % and 7.12 %, respectively, after removing RH from the input list. At last, through the Taylor diagram, H and LE gap-filling accuracy of the RF model, the support vector machine (SVM) model, the k-nearest neighbor (KNN) model, and the gradient boosting decision tree (GBDT) model was inter-compared, and the statistical metrics showed that RF was the most accurate for both H and LE gap-filling, while the LR and KNN model performed the worst for H and LE gap-filling, respectively.