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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.

Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics to treat various diseases. The endophytic Aspergillus is a filamentous fungus renowned for its extraordinary ability to produce active natural products of high therapeutic value and economic importance. This review is the first to focus on Aspergillus-derived alkaloids. Through an extensive literature review and data analysis, 263 alkaloids are categorized according to their structural features into those containing cytochalasans, diketopiperazine alkaloids, quinazoline alkaloids, quinoline alkaloids, indole alkaloids, pyrrolidine alkaloids, and others. These metabolites exhibited diverse biological activities, such as antibacterial activity, cytotoxicity, anti-inflammatory activity, and α-glucosidase, ACE, and DPPH inhibitory activities. The bioactivity, structural diversity, and occurrence of these alkaloids are reviewed in detail.

Plasma arc additive manufacturing (PAM) is an additive manufacturing technology that has been widely used in the past and has practical applications in many fields. The non-destructive testing methodology of PAM workpiece quality monitoring requires high level of accuracy and real-time capability. The characteristics of the melt pool and plasma arc are the keys to characterizing the dynamic manufacturing process during the powder feed PAM process, allowing for process prediction and real-time feedback control. This paper describes a new image recognition system that uses a fully convolutional network (FCN) to acquire melt pool and plasma arc morphologies simultaneously. Its image segmentation performance is compared with four conventional methods and three artificial intelligence methods. Results show that the FCN method can extract melt pool and plasma arc quickly and accurately, even in a complex manufacturing environment. The image segmentation-based FCN’s accuracy is 95.1%, and the average processing time is only 84 ms, according to the results. The performance is far superior to the existing seven methods. The relationship between average captured areas (melt pool and plasma arc) and parameters of the plasma arc (current intensity and scanning speed) is then analyzed. Finally, the quality of products in terms of sample surface roughness is measured, and its relationship with the average areas of the melt pool and plasma arc is clarified.

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, **P < 0.01). Myricanol prevents dexamethasone‐induced muscle atrophy and weakness by activating SIRT1, to reduce muscle protein degradation, enhance autophagy, and promote mitochondrial biogenesis and function in mice. Conclusions Myricanol ameliorates dexamethasone‐induced skeletal muscle wasting by activating SIRT1, which might be developed as a therapeutic agent for treatment of muscle atrophy and weakness.

Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from . that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.

Thermal stress is one of the main sources of micro-electro-mechanical systems (MEMS) devices error. The Wheatstone bridge is the sensing structure of a typical piezoresistive MEMS pressure sensor. In this study, the thermal stress induced by potting adhesive in MEMS pressure sensor was investigated by experiments, calculated by analytics and analyzed by simulations. An experiment system was used to test the sensor at different air pressures and temperatures. The error becomes greater with the decrease in pressure. A set of novel formulas were proposed to calculate the stress–strain on Wheatstone bridge. The error increases with the temperature deviating from 25 °C. A full-scale geometric model was developed, and finite element simulations were performed, to analyze the effect of the stress on MEMS pressure sensor induced by different temperatures and thicknesses of potting adhesive. Simulation results agree well with the experiments, which indicated that there is a 3.48% to 6.50% output error in 0.35 mm potting adhesive at 150 °C. With the thickness of potting adhesive increasing, the variations of output error of the Wheatstone bridge present an N-shaped curve. The output error meets a maximum of 5.30% in the potting adhesive of 0.95 mm and can be reduced to 2.47%, by increasing the potting adhesive to 2.40 mm.

Ganoderma lucidum spores are widely consumed natural functional materials; however, the influence of sporoderm disruption on the physicochemical characteristics and biological performance of spore polysaccharides remains insufficiently understood. In this study, polysaccharides extracted from intact spores (GLSP-I) and sporoderm-broken spores (GLSP-SB) were systematically compared to clarify how industrial processing affects their physicochemical properties and cytoprotective activity. Chemical characterization demonstrated that sporoderm disruption increased extraction yield and modified molecular weight distribution, monosaccharide composition, and spectroscopic features without fundamentally altering the polysaccharide backbone. Both polysaccharide fractions alleviated TBHP-induced oxidative injury, whereas GLSP-SB exhibited enhanced cytoprotective efficacy. Quantitative proteomic analysis revealed that GLSP-SB regulated a broader set of proteins associated with mitochondrial organization, oxidative stress response, autophagy, and cellular energy metabolism. Functional assays further showed that GLSP-SB promoted mitochondrial biogenesis, restored ATP production, and maintained mitochondrial morphology under oxidative stress conditions. Mechanistic validation demonstrated activation of the SIRT1/AMPK signaling pathway, indicating that modulation of this pathway contributes to mitochondrial adaptive responses. These findings suggest that sporoderm disruption reshapes polysaccharide characteristics and is associated with enhanced mitochondrial protective activity, providing mechanistic insight into the rational processing and functional utilization of G. lucidum spore products.

This article presents an improved Filtering Facepiece Respirator (FFR) designed to increase the comfort of wearers during low-moderate work. The improved FFR aims to lower the deadspace temperature and CO2 level by an active ventilation fan. The reversing modeling is used to build the 3D geometric model of this FFR; the Computational Fluid Dynamics (CFD) simulation is then introduced to investigate the flow field. Based on the simulation result, the ventilation fan of the improved FFR can fit the flow field well when placed in the proper blowing orientation; streamlines from this fan show a cup-shape distribution and are perfectly matched to the shape of the FFR and human face when the fan blowing inward. In the deadspace of the improved FFR, the CO2 volume fraction is controlled by the optimized flow field. In addition, an experimental prototype of the improved FFR has been tested to validate the simulation. A wireless temperature sensor is used to detect the temperature variation inside the prototype FFR, deadspace temperature is lowered by 2 K compared to the normal FFR without a fan. An infrared camera (IRC) method is used to elucidate the temperature distribution on the prototype FFR's outside surface and the wearer's face, surface temperature is lowered notably. Both inside and outside temperature results from the simulation are in agreement with experimental results. Therefore, adding an inward-blowing fan on the outer surface of an N95 FFR is a feasible approach to reducing the deadspace CO2 concentration and improve temperature comfort.

Additive manufacturing of aluminum (Al) alloys has attracted significant attention in the aerospace industry. However, achieving ultrahigh-strength (>500 MPa) Al alloys remains challenging due to their intrinsic poor printability. Here, we report a novel hybrid additive manufacturing (HAM) approach to process ultrahigh-strength AlMgSc alloy, which combines laser powder bed fusion (LPBF) with interlayer ultrasonic shot peening (USP). The results show that the interlayer ultrasonic shot peening depth reached ∼700 µm, leading to almost full density and residual stress convection from tension to compression. The HAM method promotes equiaxed grain formation and refines grain due to grain recrystallizations. Interestingly, the HAM followed by aging treatment tailors the hierarchically multi-gradient structures, inhibits Mg element intragranular segregation, and promotes the multi-nanoprecipitates (e.g. Al 3 (Sc, Zr) and Al 6 Mn) precipitation. Remarkably, the HAM followed by aging treatment achieves yield strength of 609 MPa and breaks elongation of 7.5%, demonstrating ultrahigh strength and good ductility compared with other Al alloys manufactured by AM and forging as reported in the literature. The strength enhancement mechanisms in this AlMgSc alloy are discussed. The high-density Al 3 (Sc, Zr) precipitates are the main strengthening contributor, and unique hetero-deformation induced (HDI) strengthening (originates from the heterogeneous microstructures) further enhances the strength of the material. This work highlights a novel approach for processing complex-structured ultrahigh strength Al alloy components by hybrid additive manufacturing. Hybrid additive manufacturing for processing ultrahigh strength Al alloy. Hierarchically gradient microstructures involving grain and dislocation gradients. Achieved ultrahigh yield strength (>600 MPa) together with a good elongation of 7.5%. Hybrid additive manufacturing enhances strength without evidently sacrificing ductility.

Chloroquine is a common antimalarial drug and is listed in the World Health Organization Standard List of Essential Medicines because of its safety, low cost and ease of use. Besides its antimalarial property, chloroquine also was used in anti-inflammatory and antivirus, especially in antitumor therapy. A mount of data showed that chloroquine mainly relied on autophagy inhibition to exert its antitumor effects. However, recently, more and more researches have revealed that chloroquine acts through other mechanisms that are autophagy-independent. Nevertheless, the current reviews lacked a comprehensive summary of the antitumor mechanism and combined pharmacotherapy of chloroquine. So here we focused on the antitumor properties of chloroquine, summarized the pharmacological mechanisms of antitumor progression of chloroquine dependent or independent of autophagy inhibition. Moreover, we also discussed the side effects and possible application developments of chloroquine. This review provided a more systematic and cutting-edge knowledge involved in the anti-tumor mechanisms and combined pharmacotherapy of chloroquine in hope of carrying out more in-depth exploration of chloroquine and obtaining more clinical applications.