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Background Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. Methods A tumour necrosis factor (TNF)‐α‐induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)‐treated 8‐week‐old model mice and 23‐month‐old (aged) mice were used to examine the therapeutic effects of handelin on cachexia‐ and aging‐induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. Results Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF‐α‐induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin‐like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin‐1 expression, inhibited nuclear factor‐κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS‐treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross‐sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti‐inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant‐related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL‐1β levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy. Conclusions Handelin ameliorated cachexia‐ and aging‐induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.

Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1β activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS.

In recent years, cultural and creative industry park is becoming a kind of hot industry to promote industrial restructuring and to improve the quality of urban space. For this reason, cultural and creative industrial parks are planning to build across the country. Currently, cultural and creative industrial parks that develop better than others thank to the government’s overall planning, construction, marketing, and management. At the same time, the new cultural and creative industry parks face enormous challenges, such as how to have together the cultural and creative industries and related groups or how to have area cultural creativity. And it is frequently regarded as a multiattribute group decision-making (MAGDM) process. Thus, a novel MAGDM process is needed to tackle it. Depending on the conventional grey relational analysis (GRA) method and intuitionistic fuzzy sets (IFSs), this paper designs a novel intuitive distance-based IF-GRA method for development potentiality evaluation of cultural and creative garden. First of all, some necessary theories related to IFSs are briefly reviewed. In addition, since subjective randomness frequently exists in determining criteria weights, the weights of criteria are decided objectively by utilizing the CRITIC method. Afterwards, relying on novel distance measures between IFSs, the GRA method is extended to the IFSs to calculate assessment score of each alternative. Eventually, an application about development potentiality evaluation of cultural and creative garden and some comparative analysis is given. The results think that the designed method is useful for development potentiality evaluation of cultural and creative garden.

Energy circulation in geospace lies at the heart of space weather research. In the inner magnetosphere, the steep plasmapause boundary separates the cold dense plasmasphere, which corotates with the planet, from the hot ring current/plasma sheet outside. Theoretical studies suggested that plasmapause surface waves related to the sharp inhomogeneity exist and act as a source of geomagnetic pulsations, but direct evidence of the waves and their role in magnetospheric dynamics have not yet been detected. Here, we show direct observations of a plasmapause surface wave and its impacts during a geomagnetic storm using multi-satellite and ground-based measurements. The wave oscillates the plasmapause in the afternoon-dusk sector, triggers sawtooth auroral displays, and drives outward-propagating ultra-low frequency waves. We also show that the surface-wave-driven sawtooth auroras occurred in more than 90% of geomagnetic storms during 2014–2018, indicating that they are a systematic and crucial process in driving space energy dissipation. Theoretical studies suggested that plasmapause surface waves related to the sharp inhomogeneity exist and act as a source of geomagnetic pulsations. Here, the authors show direct observations of a plasmapause surface wave and its impacts during a geomagnetic storm using multi-satellite and ground-based observations.

This article presents a systematic review on autism care, diagnosis, and intervention based on mobile apps running on smartphones and tablets. Here, the term “intervention” means a carefully planned set of activities with the objective of improving autism symptoms. We guide our review on related studies using five research questions. First, who benefits the most from these mobile apps? Second, what are the primary purposes of these mobile apps? Third, what mechanisms have been incorporated in these mobiles apps to improve usability? Fourth, what guidelines have been used in the design and implementation of these mobile apps? Fifth, what theories and frameworks have been used as the foundation for these mobile apps to ensure the intervention effectiveness? As can be seen from these research questions, we focus on the usability and software development of the mobile apps. Informed by the findings of these research questions, we propose a taxonomy for the mobile apps and their users. The mobile apps can be categorized into autism support apps, educational apps, teacher training apps, parental support apps, and data collection apps. The individuals with autism spectrum disorder (ASD) are the primary users of the first two categories of apps. Teachers of children with ASD are the primary users of the teacher training apps. Parents are the primary users of the parental support apps, while individuals with ASD are usually the primary users of the data collection apps and clinicians and autism researchers are the beneficiaries. Gamification, virtual reality, and autism-specific mechanisms have been used to improve the usability of the apps. User-centered design is the most popular approach for mobile app development. Augmentative and alternative communication, video modeling, and various behavior change practices have been used as the theoretical foundation for intervention efficacy.

The terrestrial bow shock is the boundary where supersonic solar wind slows down abruptly near the magnetopause. The shock front geometry could be modulated by surface waves to form rippled structures, which impact the acceleration process of the solar wind particles. However, the rippled structures are hard to be identified unambiguously due to the similar signatures in single‐spacecraft observations between rippled shocks and reforming shocks. Here, we utilize the four‐spacecraft observations from the MMS mission to investigate an event of quasi‐perpendicular bow shock crossing. The periodic oscillations of shock normal directions and normal velocities support the scenario of surface wave propagation in the tangential direction. We also reconstruct the shock profile along the normal direction, and its monotonic shape further excludes the occurrence of shock reformation. These ripples are found to modulate the reflected ions and whistler wave packets, which adds to the complexity of the bow shock plasma environments. Plain Language Summary Collisionless shocks are ubiquitous structures in the space and astrophysical plasma environments where significant energy conversion occurs between electromagnetic energy, kinetic energy, and thermal energy. These structures often exhibit nonstationary signatures, from which important information on the associated plasma dynamics can be extracted. In this paper, we report the spacecraft observations of a bow shock crossing with periodic enhancements of the magnetic field strength. Such signatures have been previously attributed either to the rippled shock structures or to the shock reformation process. These two potential processes are examined via simultaneous observations at four different locations, which shows the periodic oscillations of the local shock normal directions indicative of rippled rather than reforming shocks. We also show that the rippled shocks could spatially modulate the reflected ions and whistler wave packets, so they can also be detected periodically by the spacecraft. This phenomenon has been reported on other planets across a wide range of Mach numbers, indicating that the shock ripples, universal in the plasma universe, play a critical role in impacting particle dynamics and shock evolution processes. Key Points Periodic magnetic strength enhancements are observed during the bow shock crossing of the MMS spacecraft Multi‐spacecraft analysis supports the scenario of shock ripples rather than the shock reformation process The surface waves alter the shock geometry, modulating the reflected ions and whistler wave packets

Plasmapause surface waves (PSWs) near the plasmapause boundary are regarded to be the magnetospheric source of ionospheric auroral giant undulations (GUs) located at the equatorward boundary of diffuse aurora. However, the observational evidence of wave‐particle interaction connecting PSWs and GUs is absent. In this letter, we demonstrate GUs are driven by pitch‐angle scattering of time domain structures modulated by the PSWs, based on the conjugated ionospheric and magnetospheric observations. Specifically, ionospheric GUs are lighted by the pitch‐angle scattering of <1 keV thermal electron and ions and energetic ions with energy up to dozens of keV near the plasmapause. Further, the total fluxes during one PSW period and energy of scattered electron and ions determine the size and luminosity of GUs. Our research provides observational evidence that PSWs cause periodic electron precipitation via modulating the time domain structures rather than the previously predicted chorus or electron cyclotron harmonic waves. Plain Language Summary Boundary surface waves usually act as a kind of special oscillation along the boundary layer and are the widely existing physical phenomena in the universe. In our Earth, there are magnetopause surface wave and plasmapause surface wave. For the latter, the plasmapause surface wave has been confirmed to be a kind of sawtooth‐type auroral structures locating on the equatorial edge of aurora oval, named as giant undulations. But how can the plasmapause surface wave produce the auroral giant undulations is still unknown. Based on this question, we have provided the observational evidence of auroral giant undulations being driven by the periodic pitch‐angle scattering of time domain structures modulated by plasmapause surface waves. Our new results in this research would help us to better understand the energy conversion controlled by boundary dynamics and the crucial effect of boundary dynamics on the near‐surface space environment. Key Points Giant undulations (GUs) are lighted by the pitch‐angle scattering of <1 keV thermal electron and ions and energetic ions with energy up to dozens of keV Total fluxes during one plasmapause surface wave (PSW) period and energy of scattered electron and ions determine the size and luminosity of GUs PSWs can cause periodic electron precipitation by modulating time domain structures

Background The rice leaf folder Cnaphalocrocis medinalis Güenée is a serious insect pest of rice in Asia. This pest occurs in summer, and it is sensitive to high temperature. However, the larvae exhibit heat acclimation/adaptation. To understand the underlying mechanisms, we established a heat-acclimated strain via multigenerational selection at 39 °C. After heat shock at 41 °C for 1 h, the transcriptomes of the heat-acclimated (S-39) and unacclimated (S-27) larvae were sequenced, using the unacclimated larvae without exposure to 41 °C as the control. Results Five generations of selection at 39 °C led larvae to acclimate to this heat stress. Exposure to 41 °C induced 1160 differentially expressed genes (DEGs) between the heat-acclimated and unacclimated larvae. Both the heat-acclimated and unacclimated larvae responded to heat stress via upregulating genes related to sensory organ development and structural constituent of eye lens, whereas the unacclimated larvae also upregulated genes related to structural constituent of cuticle. Compared to unacclimated larvae, heat-acclimated larvae downregulated oxidoreductase activity-related genes when encountering heat shock. Both the acclimated and unacclimated larvae adjusted the longevity regulating, protein processing in endoplasmic reticulum, antigen processing and presentation, MAPK and estrogen signaling pathway to responsed to heat stress. Additionally, the unacclimated larvae also adjusted the spliceosome pathway, whereas the heat-acclimated larvae adjusted the biosynthesis of unsaturated fatty acids pathway when encountering heat stress. Although the heat-acclimated and unacclimated larvae upregulated expression of heat shock protein genes under heat stress including HSP70 , HSP27 and CRYAB , their biosynthesis, metabolism and detoxification-related genes expressed differentially. Conclusions The rice leaf folder larvae could acclimate to a high temperature via multigenerational heat selection. The heat-acclimated larvae induced more DEGs to response to heat shock than the unacclimated larvae. The changes in transcript level of genes were related to heat acclimation of larvae, especially these genes in sensory organ development, structural constituent of eye lens, and oxidoreductase activity. The DEGs between heat-acclimated and unacclimated larvae after heat shock were enriched in the biosynthesis and metabolism pathways. These results are helpful to understand the molecular mechanism underlying heat acclimation of insects.

Canonical inflammasomes are innate immune protein scaffolds that enable the activation of inflammatory caspase-1, and subsequently the processing and release of interleukin (IL)-1β, IL-18, and danger signals, as well as the induction of pyroptotic cell death. Inflammasome assembly and activation occurs in response to sensing of infectious, sterile and self-derived molecular patterns by cytosolic pattern recognition receptors, including the Nod-like receptor NLRP3. While these responses are essential for host defense, excessive and uncontrolled NLRP3 inflammasome responses cause and contribute to a wide spectrum of inflammatory diseases, including gout. A key step in NLRP3 inflammasome assembly is the sequentially nucleated polymerization of Pyrin domain (PYD)- and caspase recruitment domain (CARD)-containing inflammasome components. NLRP3 triggers polymerization of the adaptor protein ASC through PYD-PYD interactions, but ASC polymerization then proceeds in a self-perpetuating manner and represents a point of no return, which culminates in the activation of caspase-1 by induced proximity. In humans, small PYD-only proteins (POPs) lacking an effector domain regulate this key process through competitive binding, but limited information exists on their physiological role during health and disease. Here we demonstrate that POP1 expression in macrophages is sufficient to dampen MSU crystal-mediated inflammatory responses in animal models of gout. Whether MSU crystals are administered into a subcutaneous airpouch or into the ankle joint, the presence of POP1 significantly reduces neutrophil infiltration. Also, airpouch exudates have much reduced IL-1β and ASC, which are typical pro-inflammatory indicators that can also be detected in synovial fluids of gout patients. Exogenous expression of POP1 in mouse and human macrophages also blocks MSU crystal-induced NLRP3 inflammasome assembly, resulting in reduced IL-1β and IL-18 secretion. Conversely, reduced POP1 expression in human macrophages enhances IL-1β secretion. We further determined that the mechanism for the POP1-mediated inhibition of NLRP3 inflammasome activation is through its interference with the crucial NLRP3 and ASC interaction within the inflammasome complex. Strikingly, administration of an engineered cell permeable version of POP1 was able to ameliorate MSU crystal-mediated inflammation in vivo , as measured by neutrophil infiltration. Overall, we demonstrate that POP1 may play a crucial role in regulating inflammatory responses in gout.

Cervical cancer is a common malignant cancer among women worldwide. Changes in the vaginal microecological environment lead to multiple gynecological diseases, including cervical cancer. Recent research has shown that may play an important role in the occurrence and development of cervical cancer. This review explores the role of in cervical cancer. A total of 29 articles were included after identification and screening. The pertinent literature on in cervical cancer from two perspectives, including clinical studies and experimental studies, was analyzed. An association network for the mechanism by which induces cervical cancer was constructed. In addition, we provide direction and insight for further research on the role of in cervical cancer.