A battery model that has the capability of analyzing the internal non-uniformity of local state variables, including the state of charge (SOC), temperature and current density, is proposed in this ...paper. The model is built using a set of distributed parameter equivalent circuits. In order to validate the accuracy of the model, a customized battery with embedded T-type thermocouple sensors inside the battery is tested. The simulated temperature conforms well with the measured temperature at each test point, and the maximum difference is less than 1 degree C. Then, the model is applied to analyze the evolution processes of local state variables' distribution inside the battery during the discharge process. The simulation results demonstrate drastic distribution changes of the local state variables inside the battery during the discharge process. The internal non-uniformity is originally caused by the resistance of positive and negative foils, while also influenced by the change rate of open circuit voltage and the total resistance of the battery. Hence, the factors that affect the distribution of the local state variables are addressed.
•Performed 3D electrochemical-thermal modeling of four battery cooling methods.•Thermal performance of direct air cooling, direct liquid cooling, indirect (jacket) liquid and fin cooling are ...compared.•Merits and limitations of each cooling method for occupying a fixed volume are summarized.•Temperature rise for a fixed load is lower with direct or indirect liquid cooling lower than air and fin cooling.
Choosing a proper cooling method for a lithium-ion (Li-ion) battery pack for electric drive vehicles (EDVs) and making an optimal cooling control strategy to keep the temperature at a optimal range of 15 °C to 35 °C is essential to increasing safety, extending the pack service life, and reducing costs. When choosing a cooling method and developing strategies, trade-offs need to be made among many facets such as costs, complexity, weight, cooling effects, temperature uniformity, and parasitic power. This paper considers four cell-cooling methods: air cooling, direct liquid cooling, indirect liquid cooling, and fin cooling. To evaluate their effectiveness, these methods are assessed using a typical large capacity Li-ion pouch cell designed for EDVs from the perspective of coolant parasitic power consumption, maximum temperature rise, temperature difference in a cell, and additional weight used for the cooling system. We use a state-of-the-art Li-ion battery electro-chemical thermal model. The results show that under our assumption an air-cooling system needs 2 to 3 more energy than other methods to keep the same average temperature; an indirect liquid cooling system has the lowest maximum temperature rise; and a fin cooling system adds about 40% extra weight of cell, which weighs most, when the four kinds cooling methods have the same volume. Indirect liquid cooling is a more practical form than direct liquid cooling though it has slightly lower cooling performance.
•A capacity model based on charging process is proposed to estimate SOH.•The accuracy of the model is validated on commercial lithium ion batteries.•The universality of the model is verified on ...different batteries and statuses.
The incremental capacity (IC) analysis method is widely used to analyze the aging origins and state of health (SOH) of lithium ion batteries. This paper analyzes the technical difficulties during the application of the IC analysis method at first. A universal capacity model based on charging curve is then proposed, which not only inherits the advantages of IC analysis method but also avoids the tedious data preprocessing procedure, to estimate SOH of lithium ion batteries. The feasibility and accuracy of the model are demonstrated. To verify the accuracy and flexibility of the proposed capacity model, it is applied on different types of lithium ion batteries including LiFePO4,LiNi1/3Co1/3Mn1/3O2, and Li4/3Ti5/3O4. Furthermore, the proposed capacity model is applied on the aged cells to validate the model accuracy during the whole life span of lithium ion batteries. The results show that the model error is less than 4% of the nominal capacity for each case.
Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune blistering disease associated with underlying neoplasms. Currently, this disease is very difficult to treat.
We reported a rare case of ...paraneoplastic pemphigus associated with small lymphocytic lymphoma responsive to desmoglein 3 (Dsg3) and bullous pemphigoid (BP) antigen 180.
The initial diagnosis was hypothesized to be Stevens-Johnson syndrome based on the severe mucosal erosion and polymorphous skin lesions. However, the histopathological examination of the skin biopsy and immunology revealed PNP.
Anti-tumor therapy, immunosuppression and anti-infective therapy were administered.
After a series of treatments, the skin lesions had been alleviated remarkably. Enzyme-linked immunoassays indices for Dsg3 and bullous pemphigoid antigen 180 decreased (Dsg3, 32; bullous pemphigoid antigen 180, 70.44). Unfortunately, 2 months later, the patient suffered respiratory failure due to the lung impairment of small lymphocytic lymphoma and infection. Eventually, the patient chose to be discharged from the hospital and lost the opportunity for follow-up treatment as he could not afford the expensive treatment costs.
It is highly susceptible to misdiagnosis due to polymorphous skin lesions. In this case, it was also initially misdiagnosed as Stevens-Johnson syndrome. Therefore, we should pay great attention to differential diagnosis. When refractory stomatitis and mucosal erosions occur, the possibility of PNP should be considered first. At the same time, pathology, immunology and other related tests as well as the examination of primary tumors should be carried out as soon as possible.
Ferroptosis has emerged as a therapeutic tactic to trigger cancer cell death driven by abnormal accumulation of reactive oxygen species (ROS). However, a single ferroptosis treatment modality is ...often limited. In this work, a combination therapy of ferroptosis and immunotherapy for cancer was proposed. Specifically, a versatile nanodrug was designed for the multiple treatment of hepatocellular carcinoma (HCC) by loading dihydroartemisinin (DHA) on Fe3+-doped MnO2 nanosheets (Fe-MnO2/DHA). Firstly, Fe-MnO2/DHA was degraded by glutathione (GSH) in the tumor microenvironment (TME) to release Fe2+, Mn2+ and DHA, leading to aberrant ROS accumulation due to Fenton/Fenton-like reaction. Secondly, breakage of endoperoxide bridge from DHA was caused by Fe2+ to further induce oxidative stress. Thirdly, the depleted GSH promoted the inactivation of glutathione peroxidase 4 (GPX4), resulting in lipid peroxide (LPO) accumulation. The resulting LPO and ROS could induce ferroptosis and apoptosis of liver cancer cells. Furthermore, Fe-MnO2/DHA mediated three-pronged stimulation of oxidative stress, resulting in high levels of targeted immunogenic cell death (ICD). It could enhance the infiltration of CD4+ T and CD8+ T cells, and promote macrophage polarization. DHA also acted as an immunomodulator to inhibit regulatory T cells (Tregs) for systemic antitumor. Overall, Fe-MnO2/DHA presents a multi-modal therapy for HCC driven by ferroptosis, apoptosis and immune activation, significantly advancing synergistic cancer treatment.
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•A simple, economical and time-saving method to prepare Fe-MnO2/DHA nanosheets.•Fe-MnO2/DHA induces ferroptosis by Fenton/Fenton-like reaction, breakage of endoperoxide bridge from DHA and inhibiting GPX4 expression.•Fe-MnO2/DHA induces immunotherapy by stimulating ICD to enhance the infiltration of CD4+ and CD8+ T cells as well as promote macrophage polarization.
Previously, the total bioflavonoids extract from Selaginella doederleinii (SDTBE) presented favorable in vitro and in vivo activities against non-small cell lung cancer (NSCLC), hinting at its ...medicinal potential. However, up to nowadays, targets and integrative action mechanisms of SDTBE are still not very clear, which presents an obstacle to the development of herbal medicine.
Aim of the study: The present study aimed to disclose the potential targets and integrative action mechanism of SDTBE against NSCLC.
A system pharmacology-based strategy including target fishing, network pharmacology analysis and molecular docking were applied to predict the potential targets and pathways for the seven main active ingredients in SDTBE. A proteomics study was subsequently performed for validating the affected pathways and possible targets. Western blot assay, mouse xenograft tumor model and immunofluorescence assays were used to further confirm the key targets and integrative action mechanisms of SDTBE against NSCLC.
By system pharmacology, it was inferred that SDTBE could mainly act on mitogen-activated protein kinase (MAPK) and PI3K-AKT signaling pathways by targeting epidermal growth factor receptor (EGFR), protein kinase B (AKT) and mitogen-activated or extracellular signal-regulated protein kinase (MEK), which was validated by proteomics results, and further confirmed in vitro and in vivo by Western blot and immunofluorescence assays.
SDTBE targeting multi-targets including EGFR, AKT and MEK could exert its anti-NSCLC effect mainly via MAPK and PI3K-AKT signaling pathways.
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Amentoflavone, robustaflavone, 2″,3″-dihydro-3′,3‴-biapigenin, 3′,3‴-binaringenin, and delicaflavone are five major hydrophobic components in the total biflavonoids extract from Selaginella ...doederleinii (TBESD) that display favorable anticancer properties. The purpose of this study was to develop a new oral delivery formulation to improve the solubilities, dissolution rates, and oral bioavailabilities of the main ingredients in TBESD by the solid dispersion technique. Solid dispersions of TBESD with various hydrophilic polymers were prepared, and different technologies were applied to select the suitable carrier and method. TBESD amorphous solid dispersion (TBESD-ASD) with polyvinylpyrrolidone K-30 was successfully prepared by the solvent evaporation method. The physicochemical properties of TBESD-ASD were investigated by scanning electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. As a result, TBESD was found to be molecularly dispersed in the amorphous carrier. The solubilities and dissolution rates of all five ingredients in the TBESD-ASD were significantly increased (nearly 100% release), compared with raw TBESD. Meanwhile, TBESD-ASD showed good preservation stability for 3 months under accelerated conditions of 40 °C and 75% relative humidity. A subsequent pharmacokinetic study in rats revealed that C
max
and AUC
0-
t
of all five components were significantly increased by the solid dispersion preparation. An in vivo study clearly revealed that compared to raw TBESD, a significant reduction in tumor size and microvascular density occurred after oral administration of TBESD-ASD to xenograft-bearing tumor mice. Collectively, the developed TBESD-ASD with the improved solubility, dissolution rates and oral bio-availabilities of the main ingredients could be a promising chemotherapeutic agent for cancer treatment.
Delicaflavone (DF), a natural active ingredient from
Selaginella doederleinii
Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. ...However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and
in silico
methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30–60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.
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