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This work proposes a novel method, namely contour-extraction-based (CEB) method, which extracts the wake flow contours in the channels as the geometry contours of the pin fin to enhance thermal and hydraulic performances of micro-pin-fin heat sink (MPFHS). By employing this method, a novel heat sink with bream-body-like fins, namely micro-bream-fin heat sink (MBFHS), is generated by improving the geometry of the micro-circular-fin heat sink (MCFHS). The fluid flow and heat transfer characteristics of the novel MBFHS are simulated using a conjugate 3D numerical model with RNG k-ε turbulence model which is analytically validated by the energy balance theory. The thermal and hydraulic performances of the novel MBFHS are evaluated in terms of the junction temperature, Nusselt number, friction factor, and overall performance indexes. It is found that MBFHS has a larger convection heat transfer surface area, a better fluid-solid interaction, a higher flow velocity, a better fluid mixing, and more solid materials compared to the conventional MCFHS, which all contribute to the enhancement in the heat transfer performance. And the promotion is more pronounced at high spacing ratios and Reynolds numbers. The pin convection performance of the novel bream fin could be up to 34% higher than that of the original circular fin, and the thermal resistance and bottom-wall temperature difference of MBFHS are lower by 26% and 38% than those of MCFHS, respectively. [ABSTRACT FROM AUTHOR]

During metal additive manufacturing, porosity is one of the main quality defects of products. Laser post-processing is an effective method of reducing porosity of the metal surface and sub-surface. Herein, the evolution mechanism of multi pores during this process is studied. Two samples for each alloy, Ti6Al4V and AlSi10Mg, were fabricated by laser powder bed fusion (LPBF), and the upper surface of one sample of each alloy was scanned using a laser beam for comparison. Then, the inner layer morphology and pores distribution of these four samples were measured by micro-computed tomography (micro-CT) technology. It was found that the porosity reduced from 0.7961% to 0.6034% for Ti6Al4V and from 3.7105% to 3.6287% for AlSi10Mg after laser post-processing and the phenomenon of combination of pores was obvious for AlSi10Mg alloy. Next, the laser post-processing mechanisms of Ti6Al4V and AlSi10Mg alloys, including heat transfer, Marangoni flow, mass transfer related to recoil pressure and other phenomena, were numerically simulated, and the evolution of pores was tracked by the level-set method. Moreover, the effects of preheating temperature on porosity reduction were discussed. • The porosity of Ti6Al4V alloy and AlSi10Mg alloy with and without laser post-processing was detected by micro-computed tomography. • The evolution of multi pores during laser post-processing was discussed. • The differences between Ti6Al4V alloy and AlSi10Mg alloy during laser post-progressing were analyzed. • The effects of preheating temperature on porosity reduction during laser post-processing was studied. [ABSTRACT FROM AUTHOR]

• High laser energy density lead to the spatter connected with the molten pool. • An in situ monitoring method for acquiring spatter images in SLM. • A novel image processing algorithm for spatter signature eliminated three errors. • Spatter signature variation with changing laser energy density. Although selective laser melting (SLM) has the advancements of fabricating complex geometric, multi-material and multi-functional structures, several defects still affect the process stability, in particular spatter. The formation of spatter in SLM depends on the process parameters, and these can potentially be used to tune the process to obtain better product quality. However, there is still a lack of efficient methods for processing spatter images to allow in situ detection of the onset of spatter. In this paper, an in situ monitoring method for acquiring spatter images in SLM was presented. A maximum-entropy double-threshold image processing algorithm based on genetic algorithm (MEDTIA-GA) was proposed to recognize spatter from images, and its results were compared with three conventional threshold segmentation methods: Otsu's method, Triangle threshold segmentation algorithm, and K -means clustering algorithm. Results show that MEDTIA-GA method was able to eliminate three types of errors: noise sensitivity, spatter conglutination, and spatter omission. In addition, the average processing time of 37 ms for MEDTIA-GA method was far shorter than those for other three conventional threshold segmentation methods. Finally, the relationship between the spatter area as well as the number and the laser energy density were analyzed [ABSTRACT FROM AUTHOR]

In laser powder bed fusion (LPBF) processes, critical defect issues such as porosity limit the quality of the fabricated part. This work investigates the mechanism of pore evolution during the laser post-processing of an LPBF part. A laser beam was utilized to scan the top surface of a Ti–6Al–4V alloy part. The morphologies of the internal layers as well as the distribution of the porosity inside the Ti–6Al–4V sample were experimentally measured and compared using micro-computed tomography (micro-CT). It was found that the void fraction was significantly decreased, from 2.51% to 0.77%, by laser post-processing. A multi-physics coupled finite element model based on the Level-set method was built to analyze the evolution mechanism of the pore. This model simulated the effects of the energy density, Marangoni flow and mass transfer on the pore evolution. Typical processes were studied in detail, and a table summarizing the pore evolution under different post-processing parameters is given. Image 1 • Internal morphologies of Ti–6Al–4V sample measured by micro-CT. • A Level-set model is built to analyze the evolution mechanism of porosity. • Mass transfer on the bubble surface is the essence of pore evolution. • Main factor impacting gas bubble rising is from Marangoni effect rather than buoyancy. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that they have no competing interests., (© 2024 Liu et al.)

Background: The pentose phosphate pathway (PPP) plays a crucial role in the material and energy metabolism in cancer cells. Targeting 6-phosphogluconate dehydrogenase (6PGD), the rate-limiting enzyme in the PPP metabolic process, to inhibit cellular metabolism is an effective anticancer strategy. In our previous study, we have preliminarily demonstrated that gambogic acid (GA) induced cancer cell death by inhibiting 6PGD and suppressing PPP at the cellular level. However, it is unclear whether GA could suppress cancer cell growth by inhibiting PPP pathway in mouse model., Purpose: This study aimed to confirm that GA as a covalent inhibitor of 6PGD protein and to validate that GA suppresses cancer cell growth by inhibiting the PPP pathway in a mouse model., Methods: Cell viability was detected by CCK-8 assays as well as flow cytometry. The protein targets of GA were identified using a chemical probe and activity-based protein profiling (ABPP) technology. The target validation was performed by in-gel fluorescence assay, the Cellular Thermal Shift Assay (CETSA). A lung cancer mouse model was constructed to test the anticancer activity of GA. RNA sequencing was performed to analyze the global effect of GA on gene expression., Results: The chemical probe of GA exhibited high biological activity in vitro. 6PGD was identified as one of the binding proteins of GA by ABPP. Our findings revealed a direct interaction between GA and 6PGD. We also found that the anti-cancer activity of GA depended on reactive oxygen species (ROS), as evidenced by experiments on cells with 6PGD knocked down. More importantly, GA could effectively reduce the production of the two major metabolites of the PPP in lung tissue and inhibit cancer cell growth in the mouse model. Finally, RNA sequencing data suggested that GA treatment significantly regulated apoptosis and hypoxia-related physiological processes., Conclusion: These results demonstrated that GA was a covalent inhibitor of 6PGD protein. GA effectively suppressed cancer cell growth by inhibiting the PPP pathway without causing significant side effects in the mouse model. Our study provides in vivo evidence that elucidates the anticancer mechanism of GA, which involves the inhibition of 6PGD and modulation of cellular metabolic processes., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aging is a process that represents the accumulation of changes in organism overtime. In biological level, accumulations of molecular and cellular damage in aging lead to an increasing risk of diseases like sarcopenia. Sarcopenia reduces mobility, leads to fall-related injuries, and diminishes life quality. Thus, it is meaningful to find out novel therapeutic strategies for sarcopenia intervention that may help the elderly maintain their functional ability. Oxidative damage-induced dysfunctional mitochondria are considered as a culprit of muscle wasting during aging. Herein, we aimed to demonstrate whether myricanol (MY) protects aged mice against muscle wasting through alleviating oxidative damage in mitochondria and identify the direct protein target and its underlying mechanism. We discovered that MY protects aged mice against the loss of muscle mass and strength through scavenging reactive oxygen species accumulation to rebuild the redox homeostasis. Taking advantage of biophysical assays, peroxiredoxin 5 was discovered and validated as the direct target of MY. Through activating peroxiredoxin 5, MY reduced reactive oxygen species accumulation and damaged mitochondrial DNA in C2C12 myotubes. Our findings provide an insight for therapy against sarcopenia through alleviating oxidative damage-induced dysfunctional mitochondria by targeting peroxiredoxin 5, which may contribute an insight for healthy aging., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment., (© The Author(s) 2024. Published by Oxford University Press.)

Taking advantage of a hybrid generator to simultaneously collect polynary energy from a single energy source provides a feasible solution for the energy dilemma in the new era. Herein, we integrate a triboelectric nanogenerator and a thermoelectric generator for polynary energy harvesting and self-powered sensing of heatwaves in large-scale industrial factory buildings, which contains both thermal energy and wind energy. The new design of the fan-shaped rotation triboelectric nanogenerator (FR-TENG) makes it more compact and easily integrated. After structure modeling, the energy conversion efficiency of the FR-TENG can reach a maximum of 37.2%, which can successfully power a Bluetooth hygrothermograph transmitting environmental information wirelessly every 30 s at a wind speed of 4.67 m s -1 . An all-inorganic flexible thermoelectric generator (iThEG) is developed based on copper and constantan with an output power density of 0.73 W m -3 , and maintains its original mechanical properties after 10 000 bending tests. Moreover, a self-powered hot wind sensing system based on Labview is established which can display wind-speed and wind-temperature in real time. The working concept presented here is also applicable to other single energy sources containing multiple energy forms, such as falling raindrops and sunlight, which can lift energy utilization and conversion efficiency and alleviate the energy crisis.

Malaria continues to pose a serious global health threat, and artemisinin remains the core drug for global malaria control. However, the situation of malaria resistance has become increasingly severe due to the emergence and spread of artemisinin resistance. In recent years, significant progress has been made in understanding the mechanism of action (MoA) of artemisinin. Prior research on the MoA of artemisinin mainly focused on covalently bound targets that are alkylated by artemisinin-free radicals. However, less attention has been given to the reversible noncovalent binding targets, and there is a paucity of information regarding artemisinin targets at different life cycle stages of the parasite. In this study, we identified the protein targets of artemisinin at different stages of the parasite's intraerythrocytic developmental cycle using a photoaffinity probe. Our findings demonstrate that artemisinin interacts with parasite proteins in vivo through both covalent and noncovalent modes. Extensive mechanistic studies were then conducted by integrating target validation, phenotypic studies, and untargeted metabolomics. The results suggest that protein synthesis, glycolysis, and oxidative homeostasis are critically involved in the antimalarial activities of artemisinin. In summary, this study provides fresh insights into the mechanisms underlying artemisinin's antimalarial effects and its protein targets., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Background: 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 Artemisia annua L . 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., Methods: 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., Results: 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., Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI., Competing Interests: None of the authors have any conflicts of interest to disclose., (© 2024 Zhang et al.)

Preparing hybrid microstructures on flexible substrates is a crucial approach to achieving highly sensitive flexible pressure sensors. However, the preparation of hybrid microstructures on soft materials often faces complex, time-consuming, and costly problems, which hampers the advancement of highly sensitive flexible sensors. Herein, based on a 3D-printing template and a household microwave oven, a simple, green, and one-step microwave irradiation process using glucose porogen is applied to develop a flexible pressure sensor with a volcano-sponge-like porous dome structure based on porous polydimethylsiloxane (PDMS). Due to the easily deformable porous dome on the porous PDMS substrate, the flexible pressure sensor showcases exceptional sensitivity of 611.85 kPa -1 in 0-1 and 50.31 kPa -1 over a wide range of 20-80 kPa. Additionally, the sensor takes only 43 ms to respond, 123 ms to recover, and presents excellent stability (>1100 cycles). In application testing, the sensor effectively captures pulse signals, speech signals, tactile signals from a mechanical gripper, and gesture signals, demonstrating its potential applications in medical diagnosis and robotics. In conclusion, the microwave irradiation method based on template and glucose porogen provides a new way for the simple, low-cost, and green preparation of porous-surface hybrid microstructures on polymers and high-performance flexible pressure sensors.

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.

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Despite the rapid developments in diagnostic techniques and medical sciences, pathologic diagnosis is still recognized as the gold standard for disease diagnose. Pathologic diagnosis is a time-consuming task performed for pathologists, needing profound professional knowledge and long-term accumulated diagnostic experience. Therefore, the development of automatic and precise histopathological image classification is essential for medical diagnosis. In this study, an improved VGG network was used to classify the breast cancer histopathological image from intraoperative rapid frozen sections. We adopt a transformed loss function by adding a penalty to cross-entropy in our training stage, which improved the accuracy on test data by 4.39%. Laplacian-4 was used for the enhancement of images, which contributes to the improvement of the accuracy. The accuracy of the proposed model on training data and test data reached 88.70% and 82.27%, respectively, which outperforms the original model by 9.39% of accuracy in test data. The process time was less than 0.25 s per image on average. Meanwhile, the heat maps of predictions were given to show the evidential regions in histopathological images, which could drive improvements in the accuracy, speed, and clinical value of pathological diagnoses. In addition to helping with the actual diagnosis, this technology may be a benefit to pathologists, surgeons, and patients. It might prove to be a helpful tool for pathologists in the future., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Over 766 million people have been infected by coronavirus disease 2019 (COVID-19) in the past 3 years, resulting in 7 million deaths. The virus is primarily transmitted through droplets or aerosols produced by coughing, sneezing, and talking. A full-scale isolation ward in Wuhan Pulmonary Hospital is modeled in this work, and water droplet diffusion is simulated using computational fluid dynamics (CFD). In an isolation ward, a local exhaust ventilation system is intended to avoid cross-infection. The existence of a local exhaust system increases turbulent movement, leading to a complete breakup of the droplet cluster and improved droplet dispersion inside the ward. When the outlet negative pressure is 4.5 Pa, the number of moving droplets in the ward decreases by approximately 30% compared to the original ward. The local exhaust system could minimize the number of droplets evaporated in the ward; however, the formation of aerosols cannot be avoided. Furthermore, 60.83%, 62.04%, 61.03%, 60.22%, 62.97%, and 61.52% of droplets produced through coughing reached patients in six different scenarios. However, the local exhaust ventilation system has no apparent influence on the control of surface contamination. In this study, several suggestions with regards to the optimization of ventilation in wards and scientific evidence are provided to ensure the air quality of hospital isolation wards., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic flexibility is the ability to adapt to physiological and environmental changes in metabolic demand. Irisin was originally discovered as an exercise-induced myokine involved in fat browning. In this review, we summarize emerging evidence for the roles of irisin in regulating glucose metabolism and insulin sensitivity in skeletal muscle, neuroplasticity and satiety in central nervous system, β cell function and insulin secretion in the pancreas, bone remodeling, and adipose tissue function, which together orchestrate whole-body metabolic flexibility. Irisin is a key communicating mediator between skeletal muscle and other organs, and its manipulation could be a promising therapeutic strategy for treating obesity and related metabolic disorders., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

There are rarely new therapeutic breakthroughs present for neurodegenerative diseases in the last decades. Thus, new effective drugs are urgently needed for millions of patients with neurodegenerative diseases. Celastrol, a pentacyclic triterpenoid compound, is one of the main active ingredients isolated from Tripterygium wilfordii Hook. f. that has multiple biological activities. Recently, amount evidence indicates that celastrol exerts neuroprotective effects and holds therapeutic potential to serve as a novel agent for neurodegenerative diseases. This review focuses on the therapeutic efficacy and major regulatory mechanisms of celastrol to rescue damaged neurons, restore normal cognitive and sensory motor functions in neurodegenerative diseases. Importantly, we highlight recent progress regarding identification of the drug targets of celastrol by using advanced quantitative chemical proteomics technology. Overall, this review provides novel insights into the pharmacological activities and therapeutic potential of celastrol for incurable neurodegenerative diseases., Competing Interests: Competing interests The authors declare that there are no disputes of interest., (Copyright: © 2022 Liu et al.)

Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.

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.

Myricanol is a diarylheptanoid isolated from Chinese bayberry. Through virtual docking strategy, myricanol was discovered as an AMP-activated protein kinase (AMPK) activator among a series of structural analogs, with high affinity for the γ subunit of AMPK. Myricanol was also evaluated for regulatory effects on lipid accumulation and insulin sensitivity in 3T3-L1 adipocytes and adiposity in high-fat diet-fed zebrafish. Myricanol suppressed lipid accumulation in 3T3-L1 cells in the initial stage (days 0-2) by suppressing adipogenesis and in the terminal stage (days 4-7) by inducing lipolysis and lipid combustion through activating AMPK. Moreover, myricanol enhanced insulin-stimulated glucose uptake by activating the insulin signaling pathway. In high-fat diet-fed zebrafish, myricanol inhibited lipid accumulation by suppressing adipogenic factors including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). In summary, the results indicate that myricanol could be a potential therapeutic agent against obesity by activating the AMPK signaling pathway., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

It has been reported that high corticosterone level could damage the normal hippocampal neurons both in vitro and in vivo. Furthermore, high concentration of corticosterone induced impair in PC12 cells has been widely used as in vitro model to screen neuroprotective agents. Cajaninstilbene acid (CSA), a natural stilbene isolated from Cajanus cajan leaves, has various activities. In present study, we investigated the effect of CSA on corticosterone-induced cell apoptosis and explored its possible signaling pathways in PC12 cells. We demonstrated that pretreatment with CSA at the concentrations of 1-8 μmol/L remarkably reduced the cytotoxicity induced by 200 μmol/L of corticosterone in PC12 cells by MTT, and further confirmed the neuroprotection by Hoechst 33342 and PI double staining and lactate dehydrogenase release (LDH) assay at the concentration of 8 μmol/L. Moreover, the cytoprotection of CSA was proved to be associated with the homeostasis of intracellular Ca(2+), relieving corticosterone-induced oxidative stress by decreasing the contents of ROS and malondialdehyde (MDA), increasing the activities of superoxide dismutase (SOD) and catalase (CAT), and the stabilization of ER stress via down-regulating the expression of ER chaperone protein glucose-regulated protein 78 (GRP78), ER stress associated transcription factor C/EBP homologous protein (CHOP/GADD153), and the X box-binding protein-1 (XBP-1), as well as the expression of ER stress-specific protein caspase-12 and its downstream protein caspase-9. Considering all the findings, it is suggested that the neuroprotective activity of CSA against the impairment induced by corticosterone in PC12 cells was through the inhibition of oxidative stress and ER stress-mediated pathway., (Copyright © 2014 Elsevier Ltd. All rights reserved.)