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Transplanting cell cultured brown adipocytes (BAs) represents a promising approach to prevent and treat obesity (OB) and its associated metabolic disorders, including type 2 diabetes mellitus (T2DM). However, transplanted BAs have a very low survival rate in vivo. The enzymatic dissociation during the harvest of fully differentiated BAs also loses significant cells. There is a critical need for novel methods that can avoid cell death during cell preparation, transplantation, and in vivo. Here, we reported that preparing BAs as injectable microtissues could overcome the problem. We found that 3D culture promoted BA differentiation and UCP-1 expression, and the optimal initial cell aggregate size was 100 μm. The microtissues could be produced at large scales via 3D suspension assisted with a PEG hydrogel and could be cryopreserved. Fabricated microtissues could survive in vivo for long term. They alleviated body weight and fat gain and improved glucose tolerance and insulin sensitivity in high-fat diet (HFD)-induced OB and T2DM mice. Transplanted microtissues impacted multiple organs, secreted protein factors, and influenced the secretion of endogenous adipokines. To our best knowledge, this is the first report on fabricating human BA microtissues and showing their safety and efficacy in T2DM mice. The proposal of transplanting fabricated BA microtissues, the microtissue fabrication method, and the demonstration of efficacy in T2DM mice are all new. Our results show that engineered 3D human BA microtissues have considerable advantages in product scalability, storage, purity, safety, dosage, survival, and efficacy.

Benzodiazepines like midazolam were generally considered one of the possible causes affecting postoperative cognitive recovery. As a new kind of rapid-effect benzodiazepine, remimazolam tosylate was widely used in clinical anesthesia for its pharmacological advantage, but few studies reported its effects on cognitive function in the elderly. Here, we aimed to research the effects of remimazolam tosylate on cognitive function in aged mice and its underlying biological mechanisms. We measured the memory function of aged mice immediately and one month after intraperitoneal injection of remimazolam tosylate compared to the saline control. The brain metabolism level was detected by Positron Emission Tomography/Computed tomography (PET/CT). Compared with the control, we observed a decrease in memory ability， as well as an increase in tau phosphorylation level and a decrease in phosphatase level in the short term; however, one month later, contrary to the previous results, we observed better memory and brain metabolism and lower tau phosphorylation levels in the experimental group compared to the control. Therefore, we concluded that remimazolam tosylate did not cause long-term damage to the cognitive function of aged mice and even delayed the decline of memory function in the aging process to some extent.

Peripheral nerve regeneration remains a significant clinical challenge due to the unsatisfactory functional recovery and public health burden. Exosomes, especially those derived from mesenchymal stem cells (MSCs), are promising as potential cell-free therapeutics and gene therapy vehicles for promoting neural regeneration. In this study, we reported the differentiation of human adipose derived MSCs (hADMSCs) towards the Schwann cell (SC) phenotype (hADMSC-SCs) and then isolated exosomes from hADMSCs with and without differentiation (i.e., dExo vs uExo). We assessed and compared the effects of uExo and dExo on antioxidative, angiogenic, anti-inflammatory, and axon growth promoting properties by using various peripheral nerve-related cells. Our results demonstrated that hADMSC-SCs secreted more neurotrophic factors and other growth factors, compared to hADMSCs without differentiation. The dExo isolated from hADMSC-SCs protected rat SCs from oxidative stress and enhanced HUVEC migration and angiogenesis. Compared to uExo, dExo also had improved performances in downregulating pro-inflammatory gene expressions and cytokine secretions and promoting axonal growth of sensory neurons differentiated from human induced pluripotent stem cells. Furthermore, microRNA (miRNA) sequencing analysis revealed that exosomes and their parent cells shared some similarities in their miRNA profiles and exosomes displayed a distinct miRNA signature. Many more miRNAs were identified in dExo than in uExo. Several upregulated miRNAs, like miRNA-132-3p and miRNA-199b-5p, were highly related to neuroprotection, anti-inflammation, and angiogenesis. The dExo can effectively modulate various peripheral nerve-related cellular functions and is promising for cell-free biological therapeutics to enhance neural regeneration.

The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord injury (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. The current clinical strategy of using autografts for PNI suffers from a source shortage, while the pharmacological treatment for SCI presents dissatisfactory results. Tissue engineering, as an alternative, is a promising approach for regenerating peripheral nerves and spinal cords. Through providing a beneficial environment, a scaffold is the primary element in tissue engineering. In particular, scaffolds with anisotropic structures resembling the native extracellular matrix (ECM) can effectively guide neural outgrowth and reconnection. In this review, the anatomy of peripheral nerves and spinal cords, as well as current clinical treatments for PNI and SCI, is first summarized. An overview of the critical components in peripheral nerve and spinal cord tissue engineering and the current status of regeneration approaches are also discussed. Recent advances in the fabrication of anisotropic surface patterns, aligned fibrous substrates, and 3D hydrogel scaffolds, as well as their in vitro and in vivo effects are highlighted. Finally, we summarize potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth, along with their challenges and prospects., Graphical abstract Image 1, Highlights • The anatomy of peripheral nerves and spinal cords, and their current clinical treatments are summarized. • Recent cutting-edge techniques for fabricating scaffolds with anisotropic features are highlighted. • The effects of anisotropic scaffolds on glial cell behaviors and axon reconnection and remyelination are discussed. • Potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth are reviewed.

Graphical abstract The fractional-order modeling with structure identification, parameter estimation and the ability of revealing natures of battery are considered. The correlative information criterion is proposed based on the 1/f noise assisted I/O data, which is adept in evaluating the reliability of model structure and adaptiveness of model parameters. Experimental results validate the above conclusions., Highlights • Present an integrative modeling method regarding structure, parameters and states. • Parameterization by using online/offline EIS and iterative learning optimization. • Introduce 1/f noise to reveal correlations among parameters and eigen-voltages. • Provide the correlative information criterion to evaluate various battery models. • Present the strong negative correlation of ohmic resistance and state of health., In this paper, the fractional-order modeling of multiple groups of lithium-ion batteries with different states is discussed referring to electrochemical impedance spectroscopy (EIS) analysis and iterative learning identification method. The structure and parameters of the presented fractional-order equivalent circuit model (FO-ECM) are determined by EIS from electrochemical test. Based on the working condition test, a P-type iterative learning algorithm is applied to optimize certain selected model parameters in FO-ECM affected by polarization effect. What’s more, considering the reliability of structure and adaptiveness of parameters in FO-ECM, a pre-tested nondestructive 1/f noise is superimposed to the input current, and the correlative information criterion (CIC) is proposed by means of multiple correlations of each parameter and confidence eigen-voltages from weighted co-expression network analysis method. The tested batteries with different state of health (SOH) can be successfully simulated by FO-ECM with rarely need of calibration when excluding polarization effect. Particularly, the small value of CICα indicates that the fractional-order α is constant over time for the purpose of SOH estimation. Meanwhile, the time-varying ohmic resistance R0 in FO-ECM can be regarded as a wind vane of SOH due to the large value of CICR0. The above analytically found parameter-state relations are highly consistent with the existing literature and empirical conclusions, which indicates the broad application prospects of this paper.

Patients with severe traumatic peripheral nerve injury (PNI) always suffer from incomplete recovery and poor functional outcome. Physical exercise-based rehabilitation, as a non-invasive interventional strategy, has been widely acknowledged to improve PNI recovery by promoting nerve regeneration and relieving pain. However, effects of exercise on chronic plastic changes following severe traumatic PNIs have been limitedly discussed. In this study, we created a long-gap sciatic nerve transection followed by autograft bridging in rats and tested the therapeutic functions of treadmill running with low intensity and late initiation. We demonstrated that treadmill running effectively facilitated nerve regeneration and prevented muscle atrophy and thus improved sensorimotor functions and walking performance. Furthermore, exercise could reduce inflammation at the injured nerve as well as prevent the overexpression of TRPV1, a pain sensor, in primary afferent sensory neurons. In the central nervous system, we found that PNI induced transcriptive changes at the ipsilateral lumber spinal dorsal horn, and exercise could reverse the differential expression for genes involved in the Notch signaling pathway. In addition, through neural imaging techniques, we found volumetric, microstructural, metabolite, and neuronal activity changes in supraspinal regions of interest (i.e., somatosensory cortex, motor cortex, hippocampus, etc.) after the PNI, some of which could be reversed through treadmill running. In summary, treadmill running with late initiation could promote recovery from long-gap nerve transection, and while it could reverse maladaptive plasticity after the PNI, exercise may also ameliorate comorbidities, such as chronic pain, mental depression, and anxiety in the long term.

Accurate power prediction for a battery pack is of great importance for efficient and safe operation of electric vehicles. However, a battery pack typically consists of dozens of cells connected in series, and how to accurately predict its peak power in practical applications has always been a challenging issue. This paper proposes a low-complexity peak power prediction method for a series-connected battery pack, where the peak power of battery pack is predicted depending only on representative cells. Firstly, considering state of charge and voltage limits for power prediction, the representative cells are selected by using two easily available variables, namely characteristic voltage and ohmic resistance. Secondly, the state of charge and voltage of the representative cell are estimated accurately by the dual adaptive extended Kalman filter algorithm. Finally, the multi-parameter limited method for battery pack is developed to predict the peak power under Urban Dynamometer Driving Schedule test at different temperatures. The experimental results verify the feasibility and robustness of the proposed selection method, and the peak power of battery pack is predicted with low complexity and high accuracy.

Blueberry fruits were immersed in 100 mg/L acibenzolar-S-methyl (ASM) for 10 min and then stored at 4 °C with 40–50% relative humidity (RH) to investigate the changes of anti-oxidative enzyme activity, antioxidants and secondary metabolites in reactive oxygen species metabolism and phenylpropanoid pathway. The results indicated that ASM effectively enhanced the activity of superoxide dismutase, ascorbate peroxidase, catalase and the content of reduced glutathione and ascorbic acid in blueberries but decreased the content of H2O2. The activity of phenylalanine ammonialyase, polyphenol oxidase and the content of lignin, flavonoids, total phenolics and anthocyanin in blueberries were also enhanced by ASM treatment. These results suggest that postharvest ASM treatment could maintain the reactive oxygen species balance and enhance phenylpropanoid pathway to keep antioxidant ability of blueberries during low temperature storage.

Black spot caused by Alternaria alternata is an important postharvest disease of apple fruit. In this study, apple fruit (cv. Golden delicious) was used as the materials to study the effects of 0.25, 0.5, 1.0, 2.0 mg/mL trisodium phosphate (TSP) dipping treatment on lesion development of fruit inoculated with A. alternata. In vitro test was conducted to investigate the effect of TSP on mycelia growth of A. alternata. The optimal concentration of TSP was screened to assay its effect on the activity of anti-oxidative enzymes, the content of H2O2 and phenylpropane metabolites in apple fruit. The results showed that the different concentrations of TSP significantly inhibited mycelia growth of A. alternata and indicated dose dependent. TSP treatment also inhibited lesion development of apple fruit inoculated with A. alternata. According these results, 0.5 mg/mL TSP was chose for the following study. The results also indicated that TSP treatment enhanced the activity of phenylalanine ammonialyase, peroxidase, catalase, ascorbate peroxidase, superoxide dismutase, glutathione reductase, increased H2O2 accumulation and total phenolic compounds, flavonoids and lignin contents in apple fruit. All these results suggest that enhanced disease resistance in apple fruits by TSP against A. alternata is associated with increasing anti-oxidative enzymes activities and accumulation of phenylpropane metabolites.

Nanguo pear fruits were used as materials to investigate the effect of exogenous ATP treatment on the quality and sucrose metabolism during storage at room temperature (20 ± 1 °C, RH 45 ± 2%). The changes of weight loss, respiratory intensity, total soluble solids (TSS) content, flesh firmness and the activity of enzymes in sucrose metabolism were studied. The results indicated that ATP at 0.8 mM effectively inhibited respiratory intensity, suppressed the decrease of TSS content and flesh firmness of Nanguo pear fruit. ATP treatment also enhanced the activity of acid invertase (AI), neutral invertase (NI), sucrose synthase-cleavage (SS-synthesis), and sucrose synthase-synthesis (SS-cleavage) in Nanguo pear fruit. These results suggest that ATP treatment can maintain the quality of Nanguo pear fruit by modulating the activity of enzyme in sucrose metabolism.

For the safe operation of electric vehicles, it is of critical importance to quickly detect and accurately identify different types of faults in battery packs. However, the performance characteristics of many faults in the battery system are hidden and similar, therefore a false positive fault detection happens occasionally. This paper presents a multi-fault diagnostic strategy based on an interleaved voltage measurement topology and improved correlation coefficient method, which can diagnose several types of faults (i.e. the internal/external short circuit, sensor faults and connection faults). The proposed voltage measurement method can correlate each battery and contact resistance with two different sensors respectively, so as to accurately identify the location and type of the faults. In order to eliminate the effect of battery inconsistencies and measurement error, the improved correlation coefficient method is utilized to monitor fault signatures. The non-model method proposed in this paper can avoid the aliasing phenomenon and has high sensitivity and robustness. Both theoretical analysis and experimental results validate the feasibility and advantages of the multi-fault diagnostic method.

The pandemic of the coronavirus disease 2019 (COVID-19) has made biotextiles, including face masks and protective clothing, quite familiar in our daily lives. Biotextiles are one broad category of textile products that are beyond our imagination. Currently, biotextiles have been routinely utilized in various biomedical fields, like daily protection, wound healing, tissue regeneration, drug delivery, and sensing, to improve the health and medical conditions of individuals. However, these biotextiles are commonly manufactured with fibers with diameters on the micrometer scale (10 μm). Recently, nanofibrous materials have aroused extensive attention in the fields of fiber science and textile engineering because the fibers with nanoscale diameters exhibited obviously superior performances, such as size and surface/interface effects as well as optical, electrical, mechanical, and biological properties, compared to microfibers. A combination of innovative electrospinning techniques and traditional textile-forming strategies opens a new window for the generation of nanofibrous biotextiles to renew and update traditional microfibrous biotextiles. In the last two decades, the conventional electrospinning device has been widely modified to generate nanofiber yarns (NYs) with the fiber diameters less than 1000 nm. The electrospun NYs can be further employed as the primary processing unit for manufacturing a new generation of nano-textiles using various textile-forming strategies. In this review, starting from the basic information of conventional electrospinning techniques, we summarize the innovative electrospinning strategies for NY fabrication and critically discuss their advantages and limitations. This review further covers the progress in the construction of electrospun NY-based nanotextiles and their recent applications in biomedical fields, mainly including surgical sutures, various scaffolds and implants for tissue engineering, smart wearable bioelectronics, and their current and potential applications in the COVID-19 pandemic. At the end, this review highlights and identifies the future needs and opportunities of electrospun NYs and NY-based nanotextiles for clinical use.

The aim of this study is to investigate the effects of γ-aminobutyric acid (GABA) treatment after harvest on the reactive oxygen species metabolism and phenylpropanoid pathway of blue berry fruit. Blueberry fruit were dipped in 1 mmol/L GABA solution for 10 min and stored at 4 °C and the fruit treated with distilled water were used as the control. The results indicated that GABA increased the activities of phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coumarate/coenzyme A ligase and polyphenol oxidase. In addition, GABA treatment enhanced the activities of superoxide dismutase, catalase, glutathione reductase, ascorbate peroxidase, peroxidase and hydrogen peroxide content. Moreover, the accumulation of total phenolics and flavonoids in the fruit were enhanced by GABA treatment. These results suggest that GABA treatment could prolong the shelf life and delay the senescence of blueberry fruit by regulating phenylpropanoid pathway and reactive oxygen species metabolism.

Development of multifunctional tube-filling materials is required to improve the performances of the existing nerve guidance conduits (NGCs) in the repair of long-gap peripheral nerve (PN) injuries. In this study, composite nanofiber yarns (NYs) based on poly(p-dioxanone) (PPDO) biopolymer and different concentrations of carbon nanotubes (CNTs) were manufactured by utilizing a modified electrospinning apparatus. We confirmed the successful incorporation of CNTs into the PPDO nanofibers of as-fabricated composite NYs. The PPDO/CNT NYs exhibited similar morphology and structure in comparison with pure PPDO NYs. However, the PPDO/CNT NYs showed obviously enhanced mechanical properties and electrical conductivity compared to PPDO NYs. The biological tests revealed that the addition of CNTs had no negative effects on the cell adhesion, growth, and proliferation of rabbit Schwann cells (rSCs), but it better maintained the phenotype of rSCs. We also demonstrated that the electrical stimulation (ES) significantly enhanced the differentiation capability of human adipose-derived mesenchymal stem cells (hADMSCs) into SC-like cells (SCLCs) on the PPDO/CNT NYs. More importantly, a unique combination of ES and chemical induction was found to further enhance the maturation of hADMSC-SCLCs on the PPDO/CNT NYs by notably upregulating the expression levels of SC myelination-associated gene markers and increasing the growth factor secretion. Overall, this study showed that our electrically conductive PPDO/CNT composite NYs could provide a beneficial microenvironment for various cell activities, making them an attractive candidate as NGC-infilling substrates for PN regeneration applications.

Trichothecium roseum is the main pathogen that causes postharvest decay in several fruits and vegetables. e-poly-L-lysine (PL), generally regarded as a safe (GRAS) substance, is a cationic homopolymer that consists of e-amino and α-hydroxyl. The effect of PL at different concentrations (0, 12.5, 25. 50, 100, and 200 μL L−1) on the mycelia growth and spore germination of T. roseum was investigated in this study. The mechanisms of PL inhibition on T. roseum growth were also studied. The results indicated that the mycelia growth and spore germination of T. roseum were significantly inhibited at 100 and 200 μL L−1 PL. Electrical conductivity and extracellular protein showed that PL treatment destroyed the plasma membrane integrity of the mycelia and spores, respectively, and decreased extracellular malondialdehyde (MDA) and sugar content after treatment. Scanning electron microscopy indicated that PL treatment damaged spore morphology, and the surface was rough and shrinking. Transmission electron microscopy indicated that PL severely destroyed the cell wall and the plasma membrane of the T. roseum spore, leading to the loss of cytoplasm and cracking of vacuole. These results suggest that PL effectively inhibits the growth of T. roseum, and the mechanism is related to the damage of cell walls and cell membranes.