Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD + -dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. SIRT3 overexpression promoted macroautophagy in LDs from P/O-treated hepatocytes through activating AMP-activated protein kinase (AMPK) and unc-51-like kinase 1, to boost LDs digestion. Gain of SIRT3 expression stimulated the formation of lysosome-associated membrane protein 2A (LAMP-2A)-heat shock cognate 71 kDa protein (HSC70)-perilipin-2 (PLN2) complex, to promote CMA process and reduce the stability of LDs in hepatocytes. Moreover, SIRT3 reduced the expression of stearoyl-CoA desaturase 1, to suppress lipogenesis. In addition, SIRT3 overexpression promoted LDs dispersion on detyrosinated microtubules, and directly deacetylated long-chain acyl-CoA dehydrogenase to enhance mitochondrial energetics. Taken together, SIRT3 ameliorates lipotoxicity in hepatocytes, which might be a potential target for the treatment of nonalcoholic fatty liver disease.

Background Muscle atrophy and weakness are adverse effects of high dose or the sustained usage of glucocorticoids. Loss of mitochondria and degradation of protein are highly correlated with muscle dysfunction. The deacetylase sirtuin 1 (SIRT1) plays a vital role in muscle remodelling. The current study was designed to identify myricanol as a SIRT1 activator, which could protect skeletal muscle against dexamethasone‐induced wasting. Methods The dexamethasone‐induced atrophy in C2C12 myotubes was evaluated by expression of myosin heavy chain, muscle atrophy F‐box (atrogin‐1), and muscle ring finger 1 (MuRF1), using western blots. The mitochondrial content and oxygen consumption were assessed by MitoTracker staining and extracellular flux analysis, respectively. Muscle dysfunction was established in male C57BL/6 mice (8–10 weeks old, n = 6) treated with a relatively high dose of dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, forced swimming capacity, muscle weight, and muscle histology were assessed. The expression of proteolysis‐related, autophagy‐related, apoptosis‐related, and mitochondria‐related proteins was analysed by western blots or immunoprecipitation. Results Myricanol (10 μM) was found to rescue dexamethasone‐induced muscle atrophy and dysfunction in C2C12 myotubes, indicated by increased expression of myosin heavy chain (0.33 ± 0.14 vs. 0.89 ± 0.21, * P < 0.05), decreased expression of atrogin‐1 (2.31 ± 0.67 vs. 1.53 ± 0.25, * P < 0.05) and MuRF1 (1.55 ± 0.08 vs. 0.99 ± 0.12, ** P < 0.01), and elevated ATP production (3.83 ± 0.46 vs. 5.84 ± 0.79 nM/mg protein, ** P < 0.01), mitochondrial content (68.12 ± 10.07% vs. 116.38 ± 5.12%, * P < 0.05), and mitochondrial oxygen consumption (166.59 ± 22.89 vs. 223.77 ± 22.59 pmol/min, ** P < 0.01). Myricanol directly binds and activates SIRT1, with binding energy of −5.87 kcal/mol. Through activating SIRT1 deacetylation, myricanol inhibits forkhead box O 3a transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, and increases peroxisome proliferator‐activated receptor γ coactivator‐1α activity to promote mitochondrial biogenesis. In dexamethasone‐induced muscle wasting C57BL/6 mice, 5 mg/kg myricanol treatment reduces the loss of muscle mass; the percentages of quadriceps and gastrocnemius muscle in myricanol‐treated mice are 1.36 ± 0.02% and 0.87 ± 0.08%, respectively (cf. 1.18 ± 0.06% and 0.78 ± 0.05% in dexamethasone‐treated mice, respectively). Myricanol also rescues dexamethasone‐induced muscle weakness, indicated by improved grip strength (70.90 ± 4.59 vs. 120.58 ± 7.93 g, ** P < 0.01) and prolonged swimming exhaustive time (48.80 ± 11.43 vs. 83.75 ± 15.19 s, **...

Background and Purpose Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle–adipose tissue crosstalk. Experimental Approach The therapeutic effect of myricanol was evaluated on palmitic acid (PA)‐treated C2C12 myotubes and high‐fat diet (HFD)‐fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria‐related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit. Key Results Myricanol increased mitochondrial quantity and function through activating AMP‐activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin‐stimulated glucose uptake, in PA‐treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3‐L1 adipocytes. In HFD‐fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat. Conclusions and Implications Myricanol modulates skeletal muscle–adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity.

Filtering Facepiece Respirator (FFR) is the most common respirator users in the health care environment utilize for personal protection from outside particles. Comfort and fit are important while wearing an FFR. This paper proposes a novel technology to produce customized face seal design for improving the wearing comfort and fit of FFR wearers. In order to customize the design of face seals, we scanned the faces of three subjects using three-dimensional (3D) laser scanning method. A customized face seal for a 3M 8210 N95 FFR for each headform was designed using reverse engineering technique. Next, the face seal prototypes were fabricated with Acrylonitrile Butadiene Styrene (ABS) plastic using the 3D printing method. A force sensing system based on Arduino Uno R3 was developed, and the force sensor of this system was inserted between the FFR and headform to measure contact pressure. Experimental results showed that the newly designed FFR face seal provided the subjects with an improved contact pressure.

This article presents a reverse modeling of the headform when wearing a filtering facepiece respirator (FFR) and a computational fluid dynamics (CFD) simulation based on the modeling. The whole model containing the upper respiratory airway, headform, and FFR was directly recorded by computed tomography (CT) scanning, and a medical contrast medium was used to make the FFR "visible." The FFR was normally worn by the subject during CT scanning so that the actual deformation of both the FFR and the face muscles during contact can be objectively conserved. The reverse modeling approach was introduced to rebuild the geometric model and convert it into a CFD solvable model. In this model, we conducted a transient numerical simulation of air flow containing carbon dioxide, thermal dynamics, and pressure and wall shear stress distribution in the respiratory system taking into consideration an individual wearing a FFR. The breathing cycle was described as a time-dependent profile of the air velocity through the respiratory airway. The result shows that wearing the N95 FFR results in CO2 accumulation, an increase in temperature and pressure elevation inside the FFR cavity. The volume fraction of CO2 reaches 1.2% after 7 breathing cycles and then is maintained at 3.04% on average. The wearers re-inhale excessive CO2 in every breathing cycle from the FFR cavity. The air temperature in the FFR cavity increases rapidly at first and then stays close to the exhaled temperature. Compared to not wearing an FFR, wearers have to increase approximately 90 Pa more pressure to keep the same breathing flow rate of 30.54 L/min after wearing an FFR. The nasal vestibule bears more wall shear stress than any other area in the airway.