Mitochondrial dysfunction leads to osteoarthritis (OA) and disc degeneration. Hypoxia inducible factor-1α (HIF-1α) mediated mitophagy has a protective role in several diseases. However, the ...underlying mechanism of HIF-1α mediated mitophagy in OA remains largely unknown. This current study was performed to determine the effect of HIF-1α mediated mitophagy on OA. Therefore, X-ray and tissue staining including HE staining, safranin O-fast green (S-O) and Alcian Blue were used to assess imageology and histomorphology differences of mouse knee joint. Transcriptional analysis was used to find the possible targets in osteoarthritis. Western blot analysis, RT-qPCR and immunofluorescence staining were used to detect the changes in gene and protein levels in the vitro experiment. The expression of HIF-1α was increased in human and mouse OA cartilage. HIF-1α knockdown by siRNA further impair the hypoxia-induced mitochondrial dysfunction; In contrast, HIF-1α mediated protective role was reinforced by prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG). In addition, HIF-1α stabilization could alleviate apoptosis and senescence via mitophagy in chondrocytes under hypoxia condition, which could also ameliorate surgery-induced cartilage degradation in mice OA model. In conclusion, HIF-1α mediated mitophagy could alleviate OA, which may serve as a promising strategy for OA treatment.
Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex organic architectures. In ...contrast to the well-established 3,3-rearrangement, 1,3 O-to-C rearrangement has been far less vigorously investigated, and stereospecific 1,3-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/1,3-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations.
Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that ...high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown.
TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry.
In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo.
The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.
We examine production and decay of heavy neutral SUSY Higgs bosons pp→H,A→ττ¯ within the hMSSM and compare against a perhaps more plausible natural supersymmetry scenario dubbed mh125(nat) which ...allows for a natural explanation for mweak≃mW,Z,h∼100 GeV while maintaining mh≃125 GeV. We evaluate signal against various Standard Model backgrounds from γ,Z→ττ¯, tt¯ and vector boson pair production VV. We combine the transverse mass method for back-to-back (BtB) taus along with the ditau mass peak mττ method for acollinear taus as our signal channels. This technique ultimately gives a boost to the signal significance over the standard technique of using just the BtB signal channel. We evaluate both the 95% CL exclusion and 5σ discovery reach in the mA vs. tanβ plane for present LHC with 139 fb−1, Run 3 with 300 fb−1 and high luminosity LHC (HL-LHC) with 3000 fb−1 of integrated luminosity. For tanβ=10, the exclusion limits range up to mA∼1, 1.1 and 1.4 TeV, respectively. These may be compared to the range of mA values gleaned from a statistical analysis of the string landscape wherein mA can range up to ∼8 TeV.
The importance of humble leadership has garnered attention from both researchers and practitioners. Unfortunately, despite the accumulation of recent findings on the effects of leader humility, a ...quantitative review remains scant. In addressing this void, this study is among the first to conduct a meta-analytic review of humble leadership and its outcomes. Eighty-four correlations (
= 16,534) from 53 independent studies are synthesized. The authors found that: (a) humble leadership is positively related to affective commitment (ρ = 0.56), affective trust (ρ = 0.62), creativity (ρ = 0.39), engagement (ρ = 0.40), leader-member exchange (LMX) (ρ = 0.58), job satisfaction (ρ = 0.51), organizational identification (ρ = 0.48), psychological empowerment (ρ = 0.33), self-efficacy (ρ = 0.24), task performance (ρ = 0.33), and voice (ρ = 0.34); and that (b) humble leadership contributes a significant incremental variance beyond transformational, servant, and ethical leadership in several crucial criterion variables, providing solid evidence for the construct's uniqueness. However, humble leadership does not explain incremental variance in some criterion variables, indicating that future studies should control for the influence of some positive leadership (e.g., transformational and servant leadership). Age, gender, study design, country, and year partially moderate the correlations of interest. We discuss our findings with caution and propose future research directions.
Speeded up robust feature (SURF) is one of the most popular feature-based algorithms handling image matching. Compared to emerging deep learning neural network-based image matching algorithms, SURF ...is much faster with comparable accuracy. Currently, it is still one of the dominant algorithms adopted in majority of real-time applications. With the increasing popularity of video-based computer vision applications, image matching between an image and different frames of a video stream is required. Traditional algorithms could fail to deal with live video because spatiotemporal differences between frames could cause significant fluctuation in the results. In this study, we propose a self-adaptive methodology to improve the stability and precision of image–video matching. The proposed methodology dynamically adjusts threshold in feature points extraction to control the number of extracted feature points based on the content of the previous frame. Minimum ratio of distance (MROD) matching is integrated to preclude false matches while keeping abundant sample sizes. Finally, multiple homography matrix (H-Matrix) are estimated using progressive sample consensus (PROSAC) with various reprojection errors. The model with lowest mean square error (MSE) will be selected for image-to-video frame matching. The experimental results show that the self-adaptive SURF offers more accurate and stable results while balancing single frame processing time in image-video matching.
In supersymmetry (SUSY) models with low electroweak naturalness (natSUSY), which have been suggested to be the most likely version of SUSY to emerge from the string landscape, higgsinos are expected ...at the few hundred GeV scale, whilst electroweak gauginos inhabit the TeV scale. For TeV-scale heavy neutral SUSY Higgs bosons H and A, as currently required by LHC searches, the dominant decay modes of H,A are gaugino plus higgsino provided these decays are kinematically open. The light higgsinos decay to soft particles, so are largely invisible, whilst the gauginos decay to W, Z or h plus missing transverse energy (ET). Thus, we examine the viability of H,A→W+ET, Z+ET and h+ET signatures at the high luminosity LHC (HL-LHC) in light of large standard model (SM) backgrounds from (mainly) tt¯, VV and Vh production (where V=W,Z). We also examine whether these signal channels can be enhanced over backgrounds by requiring the presence of an additional soft lepton from the decays of the light higgsinos. We find significant regions in the vicinity of mA∼1–2 TeV of the mA vs. tanβ plane, which can be probed at the high luminosity LHC, using these dominant signatures by HL-LHC at 5σ and at the 95% confidence level (CL).
We continue our examination of prospects for the discovery of heavy Higgs bosons of natural SUSY (natSUSY) models at the high luminosity LHC (HL-LHC), this time focusing on charged Higgs bosons. In ...natSUSY, higgsinos are expected at the few hundred GeV scale whilst electroweak gauginos inhabit the TeV scale and the heavy Higgs bosons, H, A and H± could range up tens of TeV without jeopardizing naturalness. For TeV-scale heavy SUSY Higgs bosons H, A and H±, as currently required by LHC searches, SUSY decays into gaugino plus higgsino can dominate H± decays provided these decays are kinematically accessible. The visible decay products of higgsinos are soft making them largely invisible, whilst the gauginos decay to W, Z or h plus missing transverse energy (ET). Charged Higgs bosons are dominantly produced at LHC14 via the parton subprocess, gb→H±t. In this paper, we examine the viability of observing signatures from H±→τν, H±→tb and H±→W,Z,h+ET events produced in association with a top quark at the HL-LHC over large Standard Model (SM) backgrounds from (mainly) tt¯, tt¯V and tt¯h production (where V=W,Z). We find that the greatest reach is found via the SM H±(→τν)+t channel with a subdominant contribution from the H±(→tb)+t channel. Unlike for neutral Higgs searches, the SUSY decay modes appear to be unimportant for H± searches at the HL-LHC. We delineate regions of the mA vs. tanβ plane, mostly around mA∼ 1–2 TeV, where signals from charged Higgs bosons would serve to confirm signals of a heavy, neutral Higgs boson at the 5σ level or, alternatively, to exclude heavy Higgs bosons at the 95% confidence level at the high luminosity LHC.
Previous studies only considered the impact of personal or environmental factors on intensive smartphone use separately, while largely ignoring the impact of person-environment (P-E) fit on it. ...Drawing on the P-E fit theory, we proposed that perceived overqualification (POQ), an indicator of person-job misfit, positively affects intensive smartphone use
job boredom, and affective commitment moderates this indirect effect. We examined our hypotheses using four-wave time-lag data of 450 workers from 62 teams. The results revealed that POQ raised job boredom of an individual and thus increased their intensive smartphone use. In addition, when the affective commitment was high, the indirect effect from POQ to intensive smartphone use
job boredom was weaker. The implications, limitations, and future directions of this research were discussed.
Sentiment analysis has been extensively studied recently for developing methodologies to automatically extract information from online reviews, which is important for manufacturers to improve their ...products or services. Unfortunately, most of current studies don’t take several key factors (e.g., sentiment strength, background of customer) into account. In this study, after building feature, sentiment, and degree vocabulary from online reviews using part-of-speech and word similarity analysis, a review-feature sentiment value (R-FSV) matrix is developed and classified by a model combining the long short-term memory and gated recurrent unit ensemble. The R-FSV matrix and online rating associated with the review are analyzed by a multivariate linear regression model to derive customer satisfaction. Since the sentiment values for each feature of the product are calculated with consideration of sentiment strength, more accurate sentiment orientation is obtained for each review, which is used to develop a set of rules to identify customer requirements based on the Kano model. By taking into account of both product perspective (e.g., product upgrade) and customer perspective (e.g., background of customers), a multidimensional analysis model is proposed to further analyze customer requirements. This sheds light on the dynamic and diversity of customer satisfaction, which help manufacturers to gain insight on not only how the customer satisfaction correlates with product improvements, but also how to develop products for particular group of customers. The proposed method is deployed to study the online reviews of mobile phones from one of the main e-commerce companies in China (i.e., JD.com). The results show that our method is capable to identify the change of customer requirements over time and the preferences of different types of users (i.e., iOS or Android). Hence, the proposed method is more effective in extracting information from the online reviews for manufacturer to improve customer satisfaction efficiently.
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