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Myasthenia gravis (MG) is characterized by fatigable skeletal muscle weakness with a fluctuating and unpredictable disease course and is caused by circulating autoantibodies and pathological T helper cells. Regulation of B-cell function and the T-cell network may be a potential therapeutic strategy for MG. MicroRNAs (miRNAs) have emerged as potential biomarkers in immune disorders due to their critical roles in various immune cells and multiple inflammatory diseases. Aberrant miR-146a signal activation has been reported in autoimmune diseases, but a detailed exploration of the relationship between miR-146a and MG is still necessary. Using an experimental autoimmune myasthenia gravis (EAMG) rat model, we observed that miR-146a was highly expressed in the spleen but expressed at low levels in the thymus and lymph nodes in EAMG rats. Additionally, miR-146a expression in T and B cells was also quite different. EAMG-specific Th17 and Treg cells had lower miR-146a levels, while EAMG-specific B cells had higher miR-146a levels, indicating that targeted intervention against miR-146a might have diametrically opposite effects. Metformin, a drug that was recently demonstrated to alleviate EAMG, may rescue the functions of both Th17 cells and B cells by reversing the expression of miR-146a. We also investigated the downstream target genes of miR-146a in both T and B cells using bioinformatics screening and qPCR. Taken together, our study identifies a complex role of miR-146a in the EAMG rat model, suggesting that more caution should be paid in targeting miR-146a for the treatment of MG.

The antifungal activities and chemical composition of neem seed extract (Azadirachta indica) were investigated. An agar diffusion assay showed that neem seed extract (optimum concentration: 10%) inhibited the growth of Trametes versicolor and Gloeophyllum trabeum. The minimum inhibitory concentration and minimum fungicidal concentration were 2% and 4%, respectively, against the two fungal species. Scanning electron microscopy revealed severe morphological damage to fungal hyphae, including reduction of spores and hyphal shriveling. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry analyses identified 17 compounds that represented 80.3% of the total extract, including astaxanthin (34.3%), cinobufagin (16.9%), anodendro-side A (6.65%), 16-acetoxy-4,8,14-trimethyl-3,11-dioxo-, methyl ester (5.09%). Furthermore, T. versicolor-infected wood and G. trabeum-infected wood treated with 10% neem seed extract displayed mass decreases of 11.4 ± 5.8% and 25.8 ± 7.5%, respectively, compared with distilled water treatment (21.6 ± 4.2% and 46.9 ± 4.3%, respectively). These findings suggest the potential use of neem seed extract for antifungal wood protection.

A sucrose nonfermenting protein kinase 1 (SNF1) complex is an important metabolic regulator in fungi that is critical to cell metabolism and stress response. In this study, the role of an SNF1 β-subunit in the oleaginous fungus Mortierella alpina (MaSip2) was investigated. The MaSip2 contained a glycogen-binding domain and a conserved SNF1-complex interaction region; its transcriptional level during lipogenesis shared high consistency with a previously reported SNF1 γ-subunit (MaSnf4). Overexpression of MaSip2 in M. alpina significantly promoted glucose uptake and resulted in 34.1% increased total biomass, leading to 44.8% increased arachidonic acid yield after 7 day fermentation. MaSip2 also regulated the balance between polyunsaturated fatty acids and carbohydrates in M. alpina. Intracellular metabolite analysis revealed increased carbohydrate-related metabolite accumulation in MaSip2 overexpression strains. On the contrary, knockdown of MaSip2 increased the total fatty acid unsaturation degree, especially under low-temperature conditions. This research improved our knowledge of SNF1 complex in M. alpina and provided a target gene for enhancing glucose utilization and modulating fatty acid composition for better application of oleaginous fungi.

Piezoelectric energy harvesters have been widely developed in last decade due to their simplicity and practicality, but they suffer from low energy density. To increase the energy density, ferroelectric/ferroelastic switching could be an effective alternative energy harvesting approach. However, the nonlinearity and irreversibility of ferroelectric switching produces difficulty in establishing a stable working cycle. In this work, novel, practical and stable energy harvesting cycles using ferroelectric/ferroelastic switching are established and explored under quasi-static experimental conditions. A prototype device with a simple ‘sandwich’ configuration is tested. The results show that the cycle energy density can reach 11 mJ/cm3 under tensile loading and 3.2 mJ/cm3 under compression, demonstrating great potential for practical applications.

The fabrication of complex hierarchical heterostructures with π-electronic nanomaterials has attracted the interest of many researchers because the functions and properties of the resulting nanomaterials are related to their length-size distribution. Here, a complex multi-dimensional hierarchical heterostructure created via a sequential 2D seeded self-assembly is reported using a series of small organic molecules (1–3). Interestingly, we first discovered that the amount of kinetically trapped off-pathway aggregates could affect the dimension of the heterostructure. The co-assembly method was used to develop seeds with controlled luminescence that changed from blue to yellow emission to increase the complexity of the hierarchical heterostructure. Different luminescent seeds can induce the formation of hierarchical heterostructures possessing different luminescence properties. This strategy can then be extended to fabricate other complex hierarchical heterostructures from small organic molecules.

Sensing nutrient levels and coordinating metabolism are requisites for all living organisms. In eukaryotes, heterotrimeric adenosine monophosphate-activated protein kinase/sucrose nonfermenting 1 (...

In order to explore the effects of arginine (Arg) treatment on postharvest rot of jujube caused by Alternaria alternata (A. alternata), winter jujube was treated with different concentrations of Arg (0, 20, 200, and 1000 μmol/L). Results showed that Arg treatment substantially inhibited the expansion of lesion diameter, and jujubes treated with 200 μmol/L Arg had the smallest lesion diameter. In vitro experiments demonstrated that Arg could not inhibit spore germination and mycelial growth of A. alternata. Further experimental results showed that Arg treatment reduced the production rate of O2–. and H2O2 content and improved the activities of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase in comparison with the control; Arg treatment enhanced the activities of chitinase and β-1,3-glucanase. Furthermore, Arg treatment significantly increased the activity of phenylalamine ammonia lyase and the contents of flavonoids, phenolics, and lignin. Results indicated that, although Arg could not directly inhibit the growth of pathogenic fungi as a fungicide, it can induce resistance to Alternaria rot by maintaining the balance of reactive oxygen species, increasing the activities of pathogenesis-related protein, and promoting the phenylpropane metabolism in jujube fruit tissue. Therefore, Arg treatment can be a novel measure for inducing the resistance of jujube to postharvest Alternaria rot.

The aim of this study was to provide reference for improving the quality of future guidelines by evaluating present guidelines for nutrition in critically ill adults using Report Items for Practice Guidelines in Healthcare (RIGHT) and Appraisal of Guidelines for Research and Evaluation (AGREE II).Electronic databases and guideline websites published from 2000 to 2020 were searched. We examined the included guidelines according to RIGHT and AGREE II.Ten guidelines were involved in the study. Among seven domains of RIGHT, background received the highest report rate, whereas review and quality assurance received the lowest. Items 1a, 1c, 6, 7a, 7b were reported by all included guidelines, and items 3, 8b, 14a, 16, 18b, 21 were barely reported. As for AGREE II, scores of six domains were 69% (scope and purpose), 34% (stakeholder involvement), 47% (rigor of development), 71% (clarity of presentation), 20% (applicability), and 52% (editorial independence), respectively.Report and methodological quality of guidelines for nutrition in critically ill adults were relatively high. The evaluation results of RIGHT and AGREE II are consistent, with higher scores in the field of background and lower scores in the part on quality control and applicability. To facilitate application of guidelines, RIGHT and AGREE II should be used as criteria by guideline developers.

In oleaginous micro-organisms, nitrogen limitation activates adenosine monophosphate deaminase (AMPD) and promotes lipogenesis via the inhibition of isocitrate dehydrogenase. We found that the overexpression of homologous AMPD in Mortierella alpina favored lipid synthesis over cell growth. Total fatty acid content in the recombinant strain was 15.0-34.3% higher than that in the control, even though their biomass was similar. During the early fermentation stage, the intracellular AMP level reduced by 40-60%, together with a 1.9-2.7-fold increase in citrate content compared with the control, therefore provided more precursors for fatty acid synthesis. Moreover, the decreased AMP level resulted in metabolic reprogramming, reflected by the blocked TCA cycle and reduction of amino acids, distributing more carbon to lipid synthesis pathways. By coupling the energy balance with lipogenesis, this study provides new insights into cell metabolism under nitrogen-limited conditions and targets the regulation of fatty acid accumulation in oleaginous micro-organisms.

The experiment was conducted to improve the decay resistance of wood by increasing the wood preservatives uptake and penetration depth by bioincising with Coriolus versicolor. The mechanical properties of bioincised Populus davidiana sapwood were measured. The changes of wood components (lignin, cellulose and hemicellulose) were analyzed by FTIR. The staining treatment using potassium permanganate was to measure the preservatives uptake and penetration depth in wood specimens. The decay resistance of bioincised specimens impregnated with IPBC and CA was assessed against C. versicolor and Gloeophyllum trabeum using bioincised P. davidiana sapwood and untreated controls. The results showed that the mechanical properties of the bioincised specimens were changed with the incubation time and mass loss. The mechanical strength was decreased after 17 days compared to that of the specimens bioincised

Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR(97–116))-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4(+)/Bcl-6(+) T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.

Qingyangshen (Cynanchum otophyllum C.K.Schneid.PI.Wilson.) is the folk medicine of Yunnan which is renowned for its use in the management of neuropsychiatric diseases. The isolated glycosides from Qingyangshen have demonstrated relief in the social defeat stress, however, mechanism of action has not yet been elucidated.This study is aimed to elucidate the effect of Qingyangshen glycosides (QYS) on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism.In mice, CSDS model was developed, and the effect of QYS was evaluated by observing the behavioral performance of these mice exposed to tasks related to depression-like activities. Moreover, microscopic pathological examinutesation was also done. Furthermore, the protein expressions related to social defeat stress were also determined to elucidate the possible underlying mechanism.Our results indicated that QYS treatment reversed the CSDS-induced depressive-like behaviors as measured by the increased sucrose preference, open field activity, and social interactions among mice. The reversal of the morphological changes in the hippocampus of the CSDS mice was also noted. Additionally, QYS treatment also upregulated the silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fibronectin III domain containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and mitogen-activated protein kinase (MAPK) proteins.Our study indicated that QYS had a good anti-social defeat stress effect on CSDS-induced depression in mice, mainly through SIRT1/PGC-1α/FNDC5/BDNF-TrkB signaling pathway activation.

Mortierella alpina is an oleaginous filamentous fungus with considerable lipid productivity, and it has been widely used for industrial production of arachidonic acid. The fermentation process of M. alpina is complicated and can be affected by various factors; therefore, a comprehensive knowledge of its metabolic characteristics and key factors governing lipid biosynthesis is required to further improve its industrial performance. In this review, we discuss the metabolic features and extracellular factors that affect lipid biosynthesis in M. alpina. The current progress in fermentation optimisation and metabolic engineering to improve lipid yield are also summarised. Moreover, we review the applications of M. alpina in the food industry and propose fermentation strategies for better utilisation of this genus in the future. In our opinion, the economic performance of M. alpina should be enhanced from multiple levels, including strains with ideal traits, efficient fermentation strategies, controllable fermentation costs, and competitive products of both high value and productivity. By reviewing the peculiarities of M. alpina and current progress to improve its suitability for biotechnological production, we wish to provide more efficient strategies for future development of M. alpina as a high-value lipid cell factory. KEY POINTS: • Understanding M. alpina metabolism is helpful for rational design of its fermentation processes. • Nitrogen source is a key point that affects PUFA's component and fermentation cost in M. alpina. • Dynamic fermentation strategy combined with breeding is needed to increase lipid yield in M. alpina.

Alternaria alternata is a pathogenic fungus that infects jujube fruit and leads to serious economic losses. In this paper, the antifungal activity of chitosan combined with sodium silicate against A. alternata in vitro and in vivo was investigated, and the possible antimicrobial mechanisms were explored. Results showed that the spore germination and colony expansion of A. alternata were significantly inhibited by chitosan. Chitosan treatment induced the leakages of intercellular electrolytes, nucleic acids, and soluble protein of A. alternata. Meanwhile, chitosan damaged the cell morphology and membrane integrity of A. alternata. The combination of chitosan and sodium silicate was more effective than chitosan alone. In addition, the effect of chitosan and sodium silicate could significantly decrease natural rot rate and delay lesion expansion of winter jujube. Collectively, chitosan combined with sodium silicate had the potential to control postharvest diseases of fruit caused by A. alternata.

Sensing nutrient levels and coordinating metabolism are requisites for all living organisms. In eukaryotes, heterotrimeric adenosine monophosphate-activated protein kinase/sucrose nonfermenting 1 (SNF1) is an energy monitor that primarily functions by regulating cell metabolism with its γ-subunit being responsible for energy sensing. Because of its strong lipogenesis capacity and dependence on nutrient availability

The oleaginous fungus Mortierella alpina has distinct advantages in long-chain PUFAs production, and it is the only source for dietary arachidonic acid (ARA) certificated by FDA and European Commission. This review provides an overall introduction to M. alpina, including its major research methods, key factors governing lipid biosynthesis, metabolic engineering and omics studies. Currently, the research interests in M. alpina focus on improving lipid yield and fatty acid desaturation degree by enhancing fatty acid precursors and the reducing power NADPH, and genetic manipulation on PUFAs synthetic pathways is carried to optimise fatty acid composition. Besides, multi-omics studies have been applied to elucidate the global regulatory mechanism of lipogenesis in M. alpina. However, research challenges towards achieving a lipid cell factory lie in strain breeding and cost control due to the coenocytic mycelium, long fermentation period and insufficient conversion rate from carbon to lipid. We also proposed future research goals based on a multilevel regulating strategy: obtaining ideal chassis by directional evolution and high-throughput screening; rewiring central carbon metabolism and inhibiting competitive pathways by multi-gene manipulation system to enhance carbon to lipid conversion rate; optimisation of protein function based on post-translational modification; application of dynamic fermentation strategies suitable for different fermentation phases. By reviewing the comprehensive research progress of this oleaginous fungus, we aim to further comprehend the fungal lipid metabolism and provide reference information and guidelines for the exploration of microbial oils from the perspectives of fundamental research to industrial application.

Osteopontin (OPN) is a multifunctional extracellular matrix phosphoprotein that has a specific and complicated structure, and contributes to numerous physiological and pathological activities. The mechanism of OPN in many diseases has been confirmed; however, the role of OPN in myasthenia gravis (MG) remains unclear. In this study, we recombined rat OPN protein in vitro, and assessed how OPN affects the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. The results showed that the concentration of OPN in serum was up-regulated. Both mRNA and protein levels in splenocytes increased in the EAMG model. OPN treatment in vitro strongly promoted the differentiation of Th1 cells, and inhibited the differentiation of Treg cells. Intraperitoneal injection of OPN revealed the early incidence of EAMG, and more serious disease. This effect was accompanied by an increased percentage of Th1 cells. In conclusion, OPN likely exacerbates the pathogenesis of EAMG by promoting the differentiation of Th1 cells and inhibiting the differentiation of Treg cells.

Branched-chain amino acids (BCAAs) play an important role in lipid metabolism by serving as signal molecules as well as a potential acetyl-CoA source. Our previous study found that in the oleaginous fungus Mucor circinelloides, beta-isopropylmalate dehydrogenase (IPMDH), an important enzyme participating in the key BCAA leucine biosynthesis, was differentially expressed during lipid accumulation phase and has a positive role on lipogenesis. To further analyze its effects on lipogenesis in another oleaginous fungus Mortierella alpina, the IPMDH-encoding gene MaLeuB was homologously expressed. It was found that the total fatty acid content in the recombinant strain was increased by 20.2% compared with the control strain, which correlated with a 4-fold increase in the MaLeuB transcriptional level. Intracellular metabolites analysis revealed significant changes in amino acid biosynthesis and metabolism, tricarboxylic acid cycle and butanoate metabolism; specifically, leucine and isoleucine levels were upregulated by 6.4-fold and 2.2-fold, respectively. Our genetic engineering approach and metabolomics study demonstrated that MaLeuB is involved in fatty acid metabolism in M. alpina by affecting BCAAs metabolism, and this newly discovered role of IPMDH provides a potential bypass route to increase lipogenesis in oleaginous fungi.

In oleaginous micro-organisms, nitrogen limitation activates adenosine monophosphate deaminase (AMPD) and promotes lipogenesis via the inhibition of isocitrate dehydrogenase. We found that the overexpression of homologous

The mechanical performances of sandwiched morphing skin used for morphing aircraft are principally determined by the cellular substructure undertaking morphing stress. In this paper, in order to guide the design of sandwiched morphing skins utilized in different morphing applications, several optimal topologies of cellular-based structures are calculated, and the mechanical properties of them are evaluated. Initially, the topology optimization technique is utilized to minimize stiffness in the direction of deformation. This is followed by establishing 3D models through post-processing. Then the experiments and finite element analyses are performed to evaluate the designs and compare them with conventional regular honeycomb structure as well as zero Poisson’s ratio structure. Among them, a novel load transmitting block is designed for transferring shear load using axial movement. The simulated and experimental results show the superiority of optimized topologies. Also, the consistency of them guarantees the reliability of finite element model. Based on it, this research investigates the mechanical performances of periodic cellular structures and the influence depending on the number of cells. The results of the effective transverse modulus, the effective shear modulus, the out-of-plane displacement and the twist angle give support for the development of sandwiched morphing skins in real applications.

Microcapsules of neem extract (MNE) were observed using an optical microscope (OM) and scanning electron microscope (SEM). The antifungal activity of the extract was evaluated by an agar diffusion assay. The MNE were induced into the wood material by a full-cell process. The diameters of the microcapsules were measured by OM, and the distribution of microcapsules in wood was observed by SEM. Wood blocks of Populus tomentosa were treated with the MNE, neem extract (NE), and an acid mixture of melamine formaldehyde resin (MF) and sodium dodecyl sulfate (AMS); their antifungal properties against Penicillium citrinum, Trichoderma virens, and Aspergillus niger were visually assessed. The microcapsules prepared by MF, 1% sodium dodecyl sulfate (SDS), and 10% NH4Cl showed regular shape and good dispersion. The agar diffusion assay showed that the neem extract had significant inhibition against all tested fungi, and the optimum concentration of NE was 10%. The diameters of the microcapsules were normally distributed in a range of 0.4 μm to 4 μm, and the microcapsules were unevenly distributed in the vessels and surface of Populus tomentosa. Wood specimens treated with MNE observed complete inhibition to all studied fungi, and the mark grades of specimens treated with MNE against three fungi all reached 5 (no growth of fungi).

Synchronized switch damping (SSD)techniques using piezoelectric materials have been used by different researchers for many years for the structure vibration control. In these techniques, a piezoelectric patch is bonded on or embedded into the vibrating structure and connected to or disconnected from a network of electrical components through an electronic switch, which is controlled by a digital signal processor (DSP), in synchronous with the structure motion. Recently, Self-powered SSD techniques have emerged in which the DSP is replaced by a low pass filter, thus making the whole system self-powered. The control performance of the previously used Self-powered SSD techniques heavily relied on the electrical quality factor of the shunt circuit, thus limiting their control performance as the electrical quality factor could not be increased beyond certain limit. However, in order to bypass the influence of the electrical quality factor on the control performance, a new Self-powered SSD technique has been proposed in this paper in which the inductance in the previous Self-powered SSD techniques has been replaced with a negative capacitance thus making the whole circuit capacitive without resonance. However, it is found that the voltage on the piezoelectric patch can still be inverted. In order to access the control performance of the proposed technique in comparison with the previous Self-powered SSD techniques, experiments are performed on a cantilever beam subjected to both single mode and multimode excitations. Keeping the value of negative capacitance slightly greater than the inherent capacitance of the piezoelectric patch gave the optimum damping performance. Experiments results confirmed the effectiveness of the proposed technique as compared to the previous SSD techniques.

Structural vibration control using a piezoelectric shunt is an established control technique. This technique involves connecting a piezoelectric patch, which is bonded onto or embedded into the vibrating structure, to an electric shunt circuit. Thus, vibration energy is converted into electrical energy and is dissipated through a network of electrical components. Different configurations of shunt have been researched, among which the negative capacitance-inductance shunt has gained prominence recently. It is basically an analog, active circuit consisting of operational amplifiers and passive elements to introduce real and imaginary impedance on the vibrating structure. The present study attempts to model the behavior of a negative capacitance-inductance shunt in terms of power output and efficiency using circuit modeling software. The shunt model is validated experimentally and is used to control the structural vibration of an aluminum beam, connected to a pair of piezoelectric patches, under broadband excitation. The model is also used to determine the optimal parameters of a negative capacitance-inductance shunt to increase the efficiency and predict the voltage output limit of op-amp against the supply voltage.

Metformin, the most widely used medicine for type 2 diabetes, displays anti-inflammatory functions via activating AMP-activated protein kinase (AMPK). Circulating autoantibodies and disequilibrium of helper T cells and regulatory T cells are pathological hallmarks of myasthenia gravis (MG). Rectify the imbalance of different T cell populations has become an important therapeutic strategy to treat MG. In this study, we assessed the effect of metformin on the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. We first provided evidence that oral administration of metformin attenuated the onset of EAMG. This effect was accompanied by a substantial decrease of circulating auto-antibody levels with no effect on blood glucose level. While metformin treatment in vitro showed little effect on inducible Treg, metformin strongly inhibited Th17 cell differentiation through the increase of reactive oxygen species and AMPK. Furthermore, an attenuation of antigen-induced IgG2b antibody production by two different doses of metformin was also observed in the AChR-specific recall response. In conclusion, the above results indicate that metformin may have therapeutic value for the clinical treatment of MG.

The debate whether power is a kind of resource or an application of resources shows the complexities of the concept of power. By combining both perspectives, the authors argue that it is possible to develop a new categorization of power: soft power, soft hard-power, hard soft-power and hard power. Compared with the US and the European Union, the authors argue that if the American power strategy could be seen as “omnidirectional American primacy” and EU “omnidirectional post-sovereignty”, China’s power strategy at the moment could be mainly described as an “attraction-defence” one. With relatively limited tangible and intangible power resources, China relies more on attraction than coercion, and focuses more on defence rather than shaping. Finally, the authors propose to improve China’s power strategy by prioritizing its soft economic hard-power, upgrading soft power, extending soft military hard-power, moderately developing hard power and hard soft-power, and expanding its shaping function while maintaining the central defensive role.