In order to make full use of the advantages of PD (particle damper) and TLD (tuned liquid damper) technologies, a new kind of damping system combining these two already-existing dampers is proposed ...and was named as PDAL (tuned particle damper with additional liquid). A shaking table test of a steel frame structure with a PDAL system is conducted here for the purpose of vibration control analysis. The results of the test demonstrate well the reliability and effectiveness of the PDAL system under various seismic waves. Seismic responses (mainly acceleration value) are investigated thoroughly for parameter analysis based on the experimental data, and some suggestions are proposed for future designs, including the necessity for parameter optimization and awareness of the dynamic characteristic changes that might occur in actual structures if attached with a PDAL system. This paper constitutes a preliminary study for the PDAL system, and it can serve as a baseline and conceptual reference for future investigations.
In order to solve the shortcomings of traditional TLDs (tuned liquid dampers), such as their narrow frequency bands and their occupation of large amounts of space, based on deep-water theory, a new ...type of TLD incorporating Karmen vortex street theory is proposed and named as KV-TLD. A shaking table experimental test is conducted to fully analyze its vibration damping characteristics and its effectiveness in terms of vibration control is confirmed. Through comparison with a traditional TLD, the superiority of KV-TLD is verified. By analyzing parameters such as the mass ratio and the frequency ratio, it is found that a larger mass ratio means a better damping effect. When the frequency ratio is close to 1.0, the damping effect is better, while the vibration damping advantage of KV-TLD is much lower. Good performance in terms of installation, a wide frequency band, and damping effect means that KV-TLD is superior in terms of actual engineering application possibilities, and can also act as a good reference for subsequent engineering projects.
Abstract Background Duchenne muscular dystrophy (DMD) is a progressive and devastating muscle disease, resulting from the absence of dystrophin. This leads to cell membrane instability, ...susceptibility to contraction-induced muscle damage, subsequent muscle degeneration, and eventually disability and early death of patients. Currently, there is no cure for DMD. Our recent studies identified that lipin1 plays a critical role in maintaining myofiber stability and integrity. However, lipin1 gene expression levels are dramatically reduced in the skeletal muscles of DMD patients and mdx mice. Methods To identify whether increased lipin1 expression could prevent dystrophic pathology, we employed unique muscle-specific mdx:lipin1 transgenic (mdx:lipin1 Tg/0 ) mice in which lipin1 was restored in the dystrophic muscle of mdx mice, intramuscular gene delivery, as well as cell culture system. Results We found that increased lipin1 expression suppressed muscle degeneration and inflammation, reduced fibrosis, strengthened membrane integrity, and resulted in improved muscle contractile and lengthening force, and muscle performance in mdx:lipin1 Tg/0 compared to mdx mice. To confirm the role of lipin1 in dystrophic muscle, we then administered AAV1-lipin1 via intramuscular injection in mdx mice. Consistently, lipin1 restoration inhibited myofiber necroptosis and lessened muscle degeneration. Using a cell culture system, we further found that differentiated primary mdx myoblasts had elevated expression levels of necroptotic markers and medium creatine kinase (CK), which could be a result of sarcolemmal damage. Most importantly, increased lipin1 expression levels in differentiated myoblasts from mdx:lipin1 Tg/0 mice substantially inhibited the elevation of necroptotic markers and medium CK levels. Conclusions Overall, our data suggest that lipin1 is a promising therapeutic target for the treatment of dystrophic muscles.
The signaling enzyme phospholipase D (PLD) and the lipid second messenger it generates, phosphatidic acid (PA), are implicated in many cell biological processes, including Ras activation, cell ...spreading, stress fiber formation, chemotaxis, and membrane vesicle trafficking. PLD production of PA is inhibited by the primary alcohol 1-butanol, which has thus been widely employed to identify PLD/PA-driven processes. However, 1-butanol does not always effectively reduce PA accumulation, and its use may result in PLD-independent deleterious effects. Consequently, identification of potent specific small-molecule PLD inhibitors would be an important advance for the field. We examine one such here, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), which was identified recently in an in vitro chemical screen for PLD2 inhibitors, and show that it rapidly blocks in vivo PA production with subnanomolar potency. We were surprised to find that several biological processes blocked by 1-butanol are not affected by FIPI, suggesting the need for re-evaluation of proposed roles for PLD. However, FIPI does inhibit PLD regulation of F-actin cytoskeleton reorganization, cell spreading, and chemotaxis, indicating potential utility for it as a therapeutic for autoimmunity and cancer metastasis.
Prefabricated concrete structure is an important aspect of the building structure development in China, while the grouted sleeve connection represents a key tool for connection on prefabricated ...concrete structure parts. Various grouting defects may arise during the prefabrication and actual construction processes, thereby causing unsafe connection among components. Here, we report determination of the mechanical properties of a full-grouted sleeve with grouting defects，using the defect position (end defect, middle defect, uniform defect, unilateral defect, and horizontal defect) and the defect length as test variables. We generated a total of 11 groups of full-grouted sleeve specimens, with one group as a full-grouted standard specimen. All specimens were subjected to a unidirectional tensile test, and failure mode, ultimate bearing capacity, load-slip curve, load-displacement curve as well as load-stress curve obtained. Meanwhile, the ANSYS software was used for numerical simulation. Notably, our numerical results corroborated experimental findings. The detailed profiles of mechanical properties of full-grouted sleeve connection with defects, described in this paper, are expected to serve both as a baseline and reference for further investigations.
The formation of new and functional cardiomyocytes requires a 3-step process: dedifferentiation, proliferation, and redifferentiation, but the critical genes required for efficient dedifferentiation, ...proliferation, and redifferentiation remain unknown. In our study, a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive (PCM1+) cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction (MI) on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation, proliferation, and redifferentiation of cardiomyocytes after injury. We identified four top actin-remodeling regulators, namely Tmsb4x, Tmsb10, Dmd, and Ctnna3, which we collectively referred to as 2D2P. Transiently expressed changes of 2D2P, using a polycistronic non-integrating lentivirus driven by Tnnt2 (cardiac-specific troponin T) promoters (Tnnt2-2D2P-NIL), efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult hearts. Furthermore, the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation, thickened septum, or fatal arrhythmia for at least 4 months. In conclusion, this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.
Transient transfection of the 2D2P genes (Tmsb4x, Tmsb10, Dmd, and Ctnna3) promotes actin cytoskeletal remodeling and cardiac regeneration, which is associated with the dedifferentiation, proliferation, and redifferentiation of cardiomyocytes. Display omitted
ABSTRACT
Autophagy of mitochondria (mitophagy) is essential for maintaining muscle mass and healthy skeletal muscle. Patients with heritable phosphatidic acid phosphatase lipin‐1–null mutations ...present with severe rhabdomyolysis and muscle atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the underlying mechanisms leading to muscle atrophy as a result of lipin‐1 deficiency are still not clear. In this study, we found that lipin‐1 deficiency in mice is associated with a marked accumulation of abnormal mitochondria and autophagic vacuoles in glycolytic muscle fibers. Our studies using lipin‐1–deficient myoblasts suggest that lipin‐1 participates in B‐cell leukemia (BCL)‐2 adenovirus E1B19 kDa protein–interacting protein 3 (Bnip3)–regulated mitophagy by interacting with microtubule‐associated protein 1A/1B‐light chain (LC)3, which is an important step in the recruitment of mitochondria to nascent autophagosomes. The requirement of lipin‐1 for Bnip3–mediated mitophagy was further verified in vivo in lipin‐1–deficient green fluorescent protein‐LC3 transgenic mice (lipin‐1–/–‐GFP‐LC3). Finally, we showed that lipin‐1 deficiency in mice resulted in defective mitochondrial adaptation to starvation‐induced metabolic stress and impaired contractile muscle force in glycolytic muscle fibers. In summary, our study suggests that deregulated mitophagy arising from lipin‐1 deficiency is associated with impaired muscle function and may contribute to muscle rhabdomyolysis in humans.—Alshudukhi, A. A., Zhu, J., Huang, D., Jama, A., Smith, J. D., Wang, Q. J., Esser, K. A., Ren, H. Lipin‐1 regulates Bnip3–mediated mitophagy in glycolytic muscle. FASEB J. 32, 6796–6807 (2018). www.fasebj.org
Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models ...of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated muscle fiber cross-sectional areas compared with wild-type mice in response to injury. Our results from a series of in vitro experiments suggest that lipin1 is up-regulated and translocated to the nucleus during myoblast differentiation and plays a key role in myogenesis by regulating the cytosolic activation of ERK1/2 to form a complex and a downstream effector cyclin D3-mediated cell cycle withdrawal. Overall, our study reveals a previously unknown role of lipin1 in skeletal muscle regeneration and expands our understanding of the cellular and molecular mechanisms underlying skeletal muscle regeneration.
Background: Previous human and animal studies suggest lipin1 plays a role in myopathies, but whether lipin1 regulates skeletal muscle regeneration remains unknown.
Results: Lipin1 regulates myoblast differentiation through cytosolic activation of ERK1/2 and a downstream effector cyclin D3-mediated cell cycle withdrawal.
Conclusion: Lipin1 is a key regulator of myoblast differentiation.
Significance: Our study reveals a previously unknown pathway in skeletal muscle regeneration.
Haze and dust pollution have a significant impact on human production, life, and health. In order to understand the pollution process, the study of these two pollution characteristics is important. ...In this study, a one-year observation was carried out at the Beijing Southern Suburb Observatory using the MAX-DOAS instrument, and the pollution characteristics of the typical haze and dust events were analyzed. First, the distribution of aerosol extinction (AE) and H2O concentrations in the two typical pollution events were studied. The results showed that the correlation coefficient (r) between H2O and AE at different heights decreased during dust processes and the correlation slope (|k|) increased, whereas r increased and |k| decreased during haze periods. The correlation slope increased during the dust episode due to low moisture content and increased O4 absorption caused by abundant suspended dry crustal particles, but decreased during the haze episode due to a significant increase of H2O absorption. Secondly, the gas vertical column density (VCD) indicated that aerosol optical depth (AOD) increased during dust pollution events in the afternoon, while the H2O VCD decreased; in haze pollution processes, both H2O VCD and AOD increased. There were significant differences in meteorological conditions during haze (wind speed (WD) was <2 m/s, and relative humidity (RH) was >60%) and dust pollution (WD was >4 m/s, and RH was <60%). Next, the vertical distribution characteristics of gases during the pollution periods were studied. The AE profile showed that haze pollution lasted for a long time and changed slowly, whereas the opposite was true for dust pollution. The pollutants (aerosols, NO2, SO2, and HCHO) and H2O were concentrated below 1 km during both these typical pollution processes, and haze pollution was associated with a strong temperature inversion around 1.0 km. Lastly, the water vapor transport fluxes showed that the water vapor transport from the eastern air mass had an auxiliary effect on haze pollution at the observation location. Our results are of significance for exploring the pollution process of tropospheric trace gases and the transport of water vapor in Beijing, and provide a basis for satellite and model verification.
Antioxidants have shown great promise in stroke prevention. Diarylheptanoids (also known as diphenylheptanoids) are a small class of plant secondary metabolites that possess antioxidant activity ...greater than that of α-tocopherol. Curcumin is the best known member and is mainly extracted from turmeric. This study aimed to explore whether curcumin has a preventive effect on stroke.
Stroke-prone spontaneously hypertensive rats (SHRsp) were randomly divided into control group (n = 10) and curcumin group (n = 10), and saline or curcumin (100 mg/kg/day) was administrated daily. Vascular endothelial function was examined by the relaxation of the artery in response to acetylcholine (ACH). The levels of reactive oxygen species (ROS) and nitric oxide (NO) were measured by using dihydroethidium (DHE) and 4, 5-diaminofluorescein (DAF-2 DA), respectively. The expression of uncoupling protein 2 (UCP2) was examined by RT-PCR and immunoblotting.
Administration of curcumin significantly delayed the onset of stroke and increased the survival of SHRsp, which was ascribed to decreased ROS and improved endothelial dependent relaxation of carotid arteries. In the presence of UCP2 inhibitor genipin, both curcumin-mediated decrease of ROS and increase of NO production were blocked.
Our study suggests that curcumin exerts a stroke preventive effect by attenuating oxidative stress to improve vascular endothelial function, which might be associated with UCP2 signaling.
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