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Background: Post-stroke depression (PSD) has been identified as one of the most commonly occurring complications attributed to stroke. Astragaloside VI (AsVI), which is an active Radix Astragali (AR)-derived compound, has been reported to be a potential drug for post-stroke therapy, but its effects on PSD and the underlying mechanisms remain uncovered. Methods: In this study, healthy male SD rats underwent a middle cerebral artery occlusion (MCAO) stroke model. To create a PSD model, these rats were then kept in isolated houses and subjected to chronic unpredictable mild stress. The rats were examined every five days for a series of behavioral tests of depression. The antidepressant properties of AsVI were also investigated in vitro in a corticosterone (CORT)-induced major depression model using a CCK-8 assay. The release of neurotransmitters dopamine (DA)/5-hydroxytryptamine (5-HT) was measured using HPLC. The expression of the neurotrophic factor Neuregulin 1 (NRG-1) in rat brain tissues was detected by immunostaining. The protein expression of NRG-1, p-MEK1, and p-ERK1/2 was analyzed utilizing western blotting. Results: AsVI treatment significantly reduced depression-like behaviors in PSD rats and attenuated the CORT-induced apoptotic cell death in neuronal PC-12 cells. Besides, AsVI treatment remarkably prevented the decrease of the levels of DA and 5-HT in the PSD rat brains and in CORT-induced PC-12 cells. Furthermore, AsVI treatment upregulated the NRG-1-mediated MEK/ERK pathway, which is associated with the improvement of PSD. Conclusions: These findings suggest that AsVI could improve PSD at least partially by upregulating NRG-1-mediated MEK/ERK pathway. AsVI could be a novel therapeutic option for treating PSD. [ABSTRACT FROM AUTHOR]

Aims: Investigate the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia in human esophageal squamous and Barrett esophageal cell lines. Methods: Human esophageal squamous and Barrett esophageal cell lines were transfected with a COX-2 expression vector and a COX-2 siRNA, and then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB(p65), CDX-2, MUC2, c-myb, and BMP-4, and the morphology and microstructure of cells were then observed. Results: The viability of COX-2 overexpressed cells was significantly higher than that of control cells, while the viability of COX-2 siRNA-treated cells was significantly lower than that of control cells. Intestinal metaplasia and atypia were observed in cells overexpressing COX-2. Acid, bile salts, and their mixture inhibited the viability of these two cell lines, but the inhibitory effect of the mixture was stronger than a single treatment in either. SiRNA mediated knockdown of COX-2 strengthened the antiproliferative effects of the mixture on HET-1A and BAR-T cells. The expression of p-p65, CDX-2, and BMP-4 was positively correlated with COX-2 expression, while the expression levels of p65, MUC2, and c-myb remained unchanged. Conclusion: COX-2 may influence the viability, atypia, and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of the p-p65, CDX-2, and BMP-4 signaling pathways by COX-2 may be part of this mechanism. [ABSTRACT FROM AUTHOR]

[Display omitted] Ischemic stroke is one of the leading causes of death worldwide. Recently, neuroprotection is regarded as an important preventative and therapeutic strategy for ischemic stroke. Cajaninstilbene acid (CSA), a unique stilbenoid with a styryl group, is a potential neuroprotective agent. Hence, this study aimed to evaluate the neuroprotective effect and molecular mechanism of CSA against cerebral ischemia/reperfusion (I/R) damages. Cerebral ischemia was modeled by oxygen and glucose deprivation (OGD) in SH-SY5Y cells or transient intraluminal suture middle cerebral artery occlusion (MCAO) in rats, and tert-butyl hydroperoxide (t-BHP) was used to induce oxidative stress in SH-SY5Y cells. CSA (2.5, 5 mg/kg) was intraperitoneally given upon reperfusion after 2 h of MCAO. The signaling pathways were analyzed by Western blotting and inhibitor blocking. CSA possessed significant neuroprotective activity, as evidenced by the reduced cell death in OGD/R or t-BHP injured SH-SY5Y cells, and decreased infarct volume and neurological deficits in MCAO/R rats. Further studies indicated that the protective effect was achieved via the antioxidant activity of CSA, which decreased the oxidative stress and its related mitochondrial dysfunction in SH-SY5Y cells. Notably, Nrf2 was activated in SH-SY5Y cells and MCAO/R rats by CSA, and the inhibition of Nrf2 by brusatol weakened CSA-mediated neuroprotection. Furthermore, after applying a series of kinase inhibitors, CSA-induced Nrf2 activation was markedly inhibited by BML-275 (an AMPK inhibitor), implying that AMPK was the dominant kinase to regulate the Nrf2 pathway for CSA's neuroprotective effects with enhanced AMPK phosphorylation observed both in vivo and in vitro. CSA exerted neuroprotection via activating the AMPK/Nrf2 pathway to reduce I/R-induced cellular oxidative stress and mitochondrial disfunction. CSA could be a potential neuroprotective drug candidate for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Due to the limitation of the theoretical specific capacity of traditional cathode materials, the key to improve the energy density of lithium-ion batteries (LIBs) is to develop high-performance cathode materials. As a promising cathode material for LIBs, Fe-containing lithium-rich manganese-based materials possess high specific capacity and high working voltage. At present, the research on the synthesis and electrochemical reaction mechanism of this kind of material is still imperfect. Here, a facile oxalate co-precipitation method is employed to prepare Li1.2Fe0.16Ni0.24Mn0.4O2 using different lithium sources. The effects of lithium source and electrochemical window on the specific capacity and cyclic stability of the materials are also systematically investigated. When applied in LIBs, the prepared material using LiNO3 as lithium source presents a micro-nano hierarchical structure and exhibits a high first discharge specific capacity of 337.7 mAh g−1 and a high reversible capacity of 208.4 mAh g−1 after 60 cycles at 0.1 C in the voltage range of 1.5 − 4.8 V. The results of this study can provide more selectivity for the lithium source of the electrode material during the preparation process, and select a suitable voltage test range for cathode materials to achieve specific properties. The outstanding performances make this oxalate co-precipitation process a prospective method to prepare high-capacity cathode materials for LIBs. [ABSTRACT FROM AUTHOR]

Aim : To explicit whether the functions of high density lipoprotein (HDL) are impaired in murine atherosclerosis by subcutaneous immunization with recombinant mycobacterial heat shock protein 65 (HSP65). Methods : C57BL/6 mice were fed a normal chow-diet with non immunization as normal group. ApoE knockout (ApoE −/− ) mice on high-fat diet were randomly divided into three groups ( n = 8) and immunized subcutaneously with different concentrations of HSP65 or phosphate-buffered saline (PBS). All animals were treated for 16 weeks. Reverse cholesterol efflux, the anti-oxidant and anti-inflammatory functions of HDL were assayed. Hepatocytes and peritoneal macrophages were isolated to examine the expression of cholesterol transport regulating proteins, including SR-B1, ABCA1, ABCG1, PPAR-γ and LXR-α. Results : In HSP65-immunized mice, paraoxonase1 (PON1) activity and the expression of IL-10 were reduced, while High-density lipoprotein inflammatory index (HII), myeloperoxidase (MPO) activity, and the expression of IFN-γ were elevated gradually. The MPO/PON1 ratio amount was significantly higher in HSP65-immunized group than in normal or PBS-immunized group. In addition, compared with normal or PBS-immunized group, cholesterol efflux rate and the expression of regulating proteins were markedly decreased in HSP65-immunized group. The mice immunized with HSP65 developed significantly larger aorta atherosclerotic plaques when compared with PBS-treated littermates. The high MPO/PON1 ratio was correlated with HII, cholesterol efflux rate and atherosclerotic plaques. Conclusions : This study demonstrates that subcutaneous immunization with HSP65 impairs the properties of HDL, which may contribute to its important pathogenic role of HSP65 in atherogenesis. Also, MPO/PON1 ratio may be a predictor of AS. [ABSTRACT FROM AUTHOR]

In recent years, the market has pushed for higher energy density requirements for secondary rechargeable batteries. Bimetallic oxides are promising candidates for replacing graphite anode materials in lithium-ion batteries with high energy density. To improve the electrochemical performance of NiFe 2 O 4 nanoparticles, a carbon coating layer and single-walled carbon nanotubes (SWCNTs) conductive network were in situ co-constructed simultaneously using a solvothermal method, taking into account the poor inherent conductivity and volume change upon cycling of bimetallic oxides. The cycle stability and rate capability of the obtained NiFe 2 O 4 @C/CNTs composites with varying CNTs amounts were investigated. After 100 cycles at a current density of 200 mA g−1, the reversible capacity of NiFe 2 O 4 @C/CNTs is 1111.8 mAh g−1. The specific capacity can still reach 631.6 mAh g−1, even at 800 mA g−1. NiFe 2 O 4 @C/CNTs exhibits significantly improved cycle stability and rate capability in addition to high capacity. The remarkable electrochemical performance is due to the surface protective effect of the carbon coating layer as well as the conductive effect of the SWCNTs network. By firmly attaching the NiFe 2 O 4 active nanoparticles to the electrode, unhindered electron transport and rapid diffusion of lithium ions can be realized, and volume change during cycling can be inhibited. This research paves the way for the general modification of electrode materials with low conductivity. • A carbon coating layer and conductive network were in-situ constructed. • NiFe 2 O 4 @C/SWCNTs shows a high reversible specific capacity of 1111.8 mAh g−1. • Cycling performance and rate capability are also significantly improved. • Carbon coating layer can protect and support NiFe 2 O 4 @C nanoparticles. • Conductive network helps to speed up electron transport and ion diffusion. [ABSTRACT FROM AUTHOR]

Recent progress suggests that neural stem/progenitor cells can potentially develop into new functional neurons in adult brain, offering hope for regeneration therapies for stroke treatment. Targeting adult neurogenesis becomes a novel and promising therapeutic strategy for brain repair and recovery of neurological functions. Traditional Chinese Medicine (TCM) has a long history with accumulated experiences and case reports using herbal formulas to treat stroke disability. The combination of Chinese herbal medicine and stem cell biology approaches provides great potential for post-stroke rehabilitations. In the last decade, large efforts have been made to investigate the molecular targets for the regulation of adult neurogenesis and to explore the active compounds and molecular targets of herbal medicine for regeneration therapy. Herein, we reviewed the current progress concerning the molecular targets and cellular signaling pathways involved in adult neurogenesis after cerebral ischemia. We then briefly introduced Chinese medical theory and herbs for stroke treatment in TCM. Finally, we reviewed the current knowledge about the effects of Chinese herbal formulas, active fractions and active compounds on promoting adult neurogenesis as well as their molecular targets. Although the precise mechanisms and molecular targets of herbal medicine for neurogenesis are still unclear, current progress at least provides a cue for exploring the therapeutic principles of Chinese herbal medicine and developing new drugs for brain repair after stroke. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Herpes simplex virus 1 (HSV-1) has been widely used to treat various cancers, but its efficacy is limited. Studies indicated that combining HSV-1 and chemotherapy drugs can effectively improve the lethality of HSV-1 in tumor cells, which has a synergistic effect. Here, we explored the oncolytic effect and mechanism of bortezomib and HSV-1 on colorectal cancer cells, HCT116 and Caco-2. First, we selected four drugs to detect cell viability and found that the strongest HSV-1-promoting effect was achieved using bortezomib + HSV-1 treatment. Bortezomib combined with HSV-1 treatment significantly upregulated the expression of heat shock proteins, endoplasmic reticulum stress-related proteins and apoptosis-related proteins, while Bcl-2 was downregulated. JC-1 staining revealed that combining bortezomib and HSV-1 promotes cell apoptosis. In addition, bortezomib + oHSV-1 treatment effectively inhibit tumor growth. These results indicate that bortezomib combined with HSV-1 induce intense endoplasmic reticulum stress and activate the caspase-12 apoptosis pathway, killing tumor cells. • Bortezomib + oHSV-1 combined therapy can significantly improve the therapeutic effect of colorectal cancer. • The combined treatment of protease inhibitors and oHSV-1 with traditional cancer therapy enhanced the colorectal cancer efficacy. • BTZ + oHSV-1 combined therapy is controllable and less toxic. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study developed a novel therapeutic agent alisol B 23-acetate for COVID-19 treatment. • Alisol B 23-acetate has inhibitory effects on different species of coronavirus including MERS-CoV, SARS-CoV-2, SARS-CoV-2.B.1.1.7 lineage (Alpha variant), B.1.617.2 lineage (Delta variant), B.1.1.529 lineage (Omicron variant) and Omicron BA.5.2 lineage. • Alisol B 23-acetate has inhibition potency toward ACE2. • Alisol B 23-acetate protects against SARS-CoV-2 and its variants challenge in several animal models. • Alisol B 23-acetate also shows anti-inflammation activities in vivo and in vitro. Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future. This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment. SARS-CoV-2 and its variants infected several cell lines were applied to evaluate the anti-CoVs activities of alisol B 23-aceate in vitro. The effects of alisol B 23-acetate on in vivo models were assessed by using SARS-CoV-2 and its variants challenged hamster and human angiotensin-converting enzyme 2 (ACE2) transgenic mice. The target of alisol B 23-acetate to ACE2 was analyzed using hydrogen/deuterium exchange (HDX) mass spectrometry (MS). Alisol B 23-acetate had inhibitory effects on different species of coronavirus. By using HDX-MS, we found that alisol B 23-acetate had inhibition potency toward ACE2. In vivo experiments showed that alisol B 23-acetate treatment remarkably decreased viral copy, reduced CD4+ T lymphocytes and CD11b+ macrophages infiltration and ameliorated lung damages in the hamster model. In Omicron variant infected human ACE2 transgenic mice, alisol B 23-acetate effectively alleviated viral load in nasal turbinate and reduced proinflammatory cytokines interleukin 17 (IL17) and interferon γ (IFNγ) in peripheral blood. The prophylactic treatment of alisol B 23-acetate by intranasal administration significantly attenuated Omicron viral load in the hamster lung tissues. Moreover, alisol B 23-acetate treatment remarkably inhibited proinflammatory responses through mitigating the secretions of IFNγ and IL17 in the cultured human and mice lymphocytes in vitro. Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Background: Angong Niuhuang Wan (AGNHW, 安宫牛黄丸), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated. Aims: This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW's multifaceted immunomodulation effects in‐depth, emphasizing previously underexplored areas. Results: AGNHW mitigated monocyte‐derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW‐treated group attenuated their expressions, indicating AGNHW's potential to temper the post‐ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post‐stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries. Conclusion: This study offers a comprehensive portrait of AGNHW's immunomodulation effects on ischemic stroke, illuminating its dual sites of action—both cerebral and systemic—and its nuanced modulation of cellular and molecular dynamics. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neuroinflammatory disease with limited therapeutic effects, eventually developing into handicap. Seeking novel therapeutic strategies for MS is timely important. Active autophagy/mitophagy could mediate neurodegeneration, while its roles in MS remain controversial. To elucidate the exact roles of autophagy/mitophagy and reveal its in-depth regulatory mechanisms, we conduct a systematic literature study and analyze the factors that might be responsible for divergent results obtained. The dynamic change levels of autophagy/mitophagy appear to be a determining factor for final neuron fate during MS pathology. Excessive neuronal autophagy/mitophagy contributes to neurodegeneration after disease onset at the active MS phase. Reactive nitrogen species (RNS) serve as key regulators for redox-related modifications and participate in autophagy/mitophagy modulation in MS. Nitric oxide (•NO) and peroxynitrite (ONOO−), two representative RNS, could nitrate or nitrosate Drp1/parkin/PINK1 pathway, activating excessive mitophagy and aggravating neuronal injury. Targeting RNS-mediated excessive autophagy/mitophagy could be a promising strategy for developing novel anti-MS drugs. In this review, we highlight the important roles of RNS-mediated autophagy/mitophagy in neuronal injury and review the potential therapeutic compounds with the bioactivities of inhibiting RNS-mediated autophagy/mitophagy activation and attenuating MS progression. Overall, we conclude that reactive nitrogen species could be promising therapeutic targets to regulate autophagy/mitophagy for multiple sclerosis treatment. [Display omitted] • Autophagy/mitophagy mediate neurodegeneration in multiple sclerosis (MS). • Reactive nitrogen species (RNS) serve as key regulators for autophagy/mitophagy via redox-related modifications in MS. • Targeting RNS in the regulation of autophagy/mitophagy could be a promising strategy for developing novel drugs for MS. • The potential MS therapeutic compounds for targeting peroxynitrite (ONOO−) have been summarized in this review. [ABSTRACT FROM AUTHOR]

Aims Vascular calcification (VC) predicts the morbidity and mortality in cardiovascular diseases. Vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation is the crucial pathological basis for VC. To date, the molecular pathogenesis is still largely unclear. Notably, C5a-C5aR1 contributes to the development of cardiovascular diseases, and its closely related to physiological bone mineralization which is similar to VSMCs osteogenic transdifferentiation. However, the role and underlying mechanisms of C5a-C5aR1 in VC remain unexplored. Methods and results A cross-sectional clinical study was utilized to examine the association between C5a and VC. Chronic kidney diseases mice and calcifying VSMCs models were established to investigate the effect of C5a-C5aR1 in VC, evaluated by changes in calcium deposition and osteogenic markers. The cross-sectional study identified that high level of C5a was associated with increased risk of VC. C5a dose-responsively accelerated VSMCs osteogenic transdifferentiation accompanying with increased the expression of C5aR1. Meanwhile, the antagonists of C5aR1, PMX 53, reduced calcium deposition, and osteogenic transdifferentiation both in vivo and in vitro. Mechanistically, C5a-C5aR1 induced endoplasmic reticulum (ER) stress and then activated PERK-eIF2α-ATF4 pathway to accelerated VSMCs osteogenic transdifferentiation. In addition, cAMP-response element-binding protein 3-like 1 (CREB3L1) was a key downstream mediator of PERK-eIF2α-ATF4 pathway which accelerated VSMCs osteogenic transdifferentiation by promoting the expression of COL1α1. Conclusions High level of C5a was associated with increased risk of VC, and it accelerated VC by activating the receptor C5aR1. PERK-eIF2α-ATF4-CREB3L1 pathway of ER stress was activated by C5a-C5aR1, hence promoting VSMCs osteogenic transdifferentiation. Targeting C5 or C5aR1 may be an appealing therapeutic target for VC. [ABSTRACT FROM AUTHOR]

In the present study, we tested the hypothesis that caveolin-1 plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a laboratory murine model of Multiple Sclerosis (MS). After active EAE induction, the increased caveolin-1 in serum and CNS tissues was associated with disease incidence and severity in immunized wild-type (WT) mice. After immunization, Cav-1knockout (KO) mice showed remarkable disease resistance with alleviated incidences and clinical symptoms. Cav-1 KO mice had diminished infiltration of encephalitogenic T cells into CNS parenchyma with compromised expressions of adhesion molecules ICAM-1 and VCAM-1 in the white matter of CNS tissues. Consistently, in vitro knockdown of caveolin-1 impaired the up-regulation of ICAM-1 in endothelial cells, and ameliorated trans-endothelial migration of pathogenic T H 1 and T H 17 cells. Therefore, caveolin-1 serves as an active modulator of lymphocyte trafficking into CNS and could be a therapeutic target for multiple sclerosis. [ABSTRACT FROM AUTHOR]

Tissue plasminogen activator (t-PA) has restrict therapeutic window for ischemic stroke and hemorrhagic transformation (HT) is the major complications. High mobility group box protein 1 (HMGB1) and MMPs are critical targets for reducing HT. Glycyrrhizin is an antioxidant isolated from Glycyrrhiza glabr a. We hypothesize that glycyrrhizin could inhibit HMGB1, MMPs, reduce HT and improve survival rates in ischemic stroke with delayed t-PA tretament. Male SD rats were subjected middle cerebral artery occlusion (MCAO) for 5 hours plus 19 hours of reperfusion. T-PA (10 mg/kg) was intravenously administrated at 4.5 hours after MCAO and continuously injected for 30 min. Glycyrrhizin (30 mg/kg) was administrated at onset of t-PA treatment and saline was used as control. Major discoveries are as below: (1) Delayed t-PA treatment had increased mortality rate, brain swelling, hemorrhagic transformation with the increase of HMGB1 and MMP-9 expression. (2) Glycyrrhizin significantly inhibited HMGB1 and MMP-9, attenuated HT, decreased mortality and improved neurological outcomes. In conclusion, glycyrrhizin could be an adjuvant therapy with t-PA to improve the therapeutic outcome for ischemic stroke. [ABSTRACT FROM AUTHOR]

Hemorrhagic transformation (HT) is the severe complication of delayed tissue plasminogen activator (t-PA) treatment in ischemic stroke. Previously we showed that targeting peroxynitrite attenuated HT and improved neurological outcomes in ischemic stroke with thrombolytic therapy. Here we test the hypothesis that baicalin, a natural compound capable of scavenging peroxynitrite, could reduce HT in a rat cerebral ischemia-reperfusion model with delayed t-PA treatment, through targeting peroxynitrite-MMP-9 signaling. Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) 5 hours plus reperfusion 19 hours. T-PA (10 mg/kg) or t-PA plus baicalin (50, 100, 150 mg/kg) was administrated via femoral vein at 4.5 hours after MCAO. Delayed t-PA treatment increased the mortality rates and further exacerbated blood brain barrier (BBB) permeability in surviving rats, leading to HT, increasement of brain edema, and exacerbation of neurological outcomes. Such deleterious effects of t-PA were dose-dependently and significantly attenuated by baicalin co-treatment. Delayed t-PA treatment increased 3-NT (a biomarker of peroxynitrite) formation, leading to MMP-9 overproduction and tight junction ZO-1 reduction, which were also significantly reversed by baicalin co-treatment. Taken together, baicalin could be a potential combination compound to reduce HT and other complications induced by delayed t-PA treatment, possibly via inhibiting peroxynitrite mediated MMP-9 production. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine (TCM) is widely used to treat heart failure (HF). Syndrome differentiation is a unique and crucial component in TCM practice for guiding disease diagnosis and treatment strategies as well as clinical research. The major bottlenecks in TCM syndrome differentiation are the diversity of the syndrome differentiation criteria and the broad spectrum of syndrome patterns, hindering evidence-based studies for clinical research. In the present study, we aim to develop an evidence-based questionnaire for the diagnosis of HF and establish a definitive set of criteria for syndrome differentiation. Methods: We designed a TCM syndrome differentiation questionnaire for heart failure (SDQHF) based on the "TCM expert consensus for diagnosis and treatment of heart failure" (expert consensus), literature review, and various clinical guidelines. To test the reliability and efficiency of the questionnaire, we performed a large-scale multiple-center clinical trial with the recruitment of 661 HF patients. Cronbach's alpha was used to assess the internal consistency of the SDQHF. Content validity was conducted through expert review. Principal component analysis (PCA) was applied to evaluate the construct validity. We constructed a proposed model for syndrome differentiation for HF based on the PCA results. Tongue analysis was performed to verify the accuracy of syndromes derived from the proposed model and the expert consensus. An evidence-based practical questionnaire for TCM syndrome differentiation patients was developed and validated with the data from 661 HF patients. Results: The syndrome differentiation criteria were constructed with five syndrome elements (qi-deficiency, yang-deficiency, yin-deficiency, blood stasis, and phlegm retention). The results revealed good convergent and discriminant validity, satisfactory internal consistency, and feasibility. The significant discoveries include: (1) A total of 91% of the derived TCM syndromes from the proposed model matched with the characterized tongue images of the syndrome patterns; (2) Qi Deficiency Syndrome is the dominant syndrome pattern for HF patients, followed by Yang-Qi Deficiency Syndrome and Qi-yin deficiency Syndrome, and finally, Yin-Yang Dual Deficiency Syndrome; (3) The majority of the HF patients had the combination of Blood Stasis and Phlegm Retention Syndromes; (4) The "Yin-Yang Dual Deficiency" Syndrome was a valid syndrome for HF, suggesting that this syndrome pattern should be included in the criteria for syndrome differentiation; and (5) Through the validation of the expert consensus, several recommendations were proposed to improve the accuracy of syndrome differentiation of HF. Conclusions: The proposed SDQHF and the criteria could be a reliable and valid tool for syndrome differentiation of heart failure with high accuracy. It is recommended to use the proposed model for evidence-based study on Chinese Medicine to diagnose and treat HF. Trial registration number: The trial was registered at the Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16. [ABSTRACT FROM AUTHOR]

Background: As a major risk factor for neurodegenerative diseases, aging has become a heavy health care burden worldwide. Age-related decline in mitochondrial function and oxidative stress is strongly associated with neurodegeneration. The previous study demonstrated that Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula, is effective in reducing neurodegeneration. Methods: This study is the first to investigate the effect of BSYZ on D-gal-induced learning memory in rats. Secondly, the potential metabolic mechanism of BSYZ was explored by 1H-NMR metabolomics analysis. Then based on the comparison of differential metabolites implied that BSYZ ameliorated mitochondrial dysfunction through choline metabolic pathway in D-gal-treated rats. Finally, pharmacological validation was conducted to explore the effects of BSYZ on D-gal-induced oxidative stress, neuroinflammation, and neuronal apoptosis. Results: Our data showed that BSYZ increased aspartate and betaine levels, while decreasing choline levels. Furthermore, BSYZ also increased the proteins level of CHDH and BHMT to regulate choline metabolic pathway. Meanwhile, BSYZ alleviated mitochondrial damage and oxidative stress, including enhanced ATP production and the ratio of NAD+/NADH, reduced the level of MDA, enhanced GSH and SOD activity, upregulated the expressions of p-AMPK, SIRT1 proteins. In addition, BSYZ downregulated the levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, as well as suppressed Bcl-2 proteins family dependent apoptosis. Conclusion: BSYZ treatment effectively rescues neurobehavioral impairment by improving mitochondrial dysfunction, oxidative stress, neuroinflammation and neuroapoptosis via AMPK/SIRT1 pathway in D-gal-induced aging. [ABSTRACT FROM AUTHOR]

Background: Endothelin-1 (ET-1) is a potent vasoconstrictor, and astrocytic ET-1 is reported to play a role in the pathogenesis of cerebral ischemic injury and cytotoxic edema. However, it is still unknown whether astrocytic ET-1 also contributes to vasogenic edema and vasospasm during subarachnoid hemorrhage (SAH). In the present study, transgenic mice with astrocytic endothelin-1 over-expression (GET-1 mice) were used to investigate the pathophysiological role of ET-1 in SAH pathogenesis.Results: The GET-1 mice experienced a higher mortality rate and significantly more severe neurological deficits, blood-brain barrier breakdown and vasogenic edema compared to the non-transgenic (Ntg) mice following SAH. Oral administration of vasopressin V1a receptor antagonist, SR 49059, significantly reduced the cerebral water content in the GET-1 mice. Furthermore, the GET-1 mice showed significantly more pronounced middle cerebral arterial (MCA) constriction after SAH. Immunocytochemical analysis showed that the calcium-activated potassium channels and the phospho-eNOS were significantly downregulated, whereas PKC-α expression was significantly upregulated in the MCA of the GET-1 mice when compared to Ntg mice after SAH. Administration of ABT-627 (ETA receptor antagonist) significantly down-regulated PKC-α expression in the MCA of the GET-1 mice following SAH.Conclusions: The present study suggests that astrocytic ET-1 involves in SAH-induced cerebral injury, edema and vasospasm, through ETA receptor and PKC-mediated potassium channel dysfunction. Administration of ABT-627 (ETA receptor antagonist) and SR 49059 (vasopressin V1a receptor antagonist) resulted in amelioration of edema and vasospasm in mice following SAH. These data provide a strong rationale to investigate SR 49059 and ABT-627 as therapeutic drugs for the treatment of SAH patients. [ABSTRACT FROM AUTHOR]

Wearing masks has been a recommended protective measure due to the risks of coronavirus disease 2019 (COVID‐19) even in its coming endemic phase. Therefore, deploying a "smart mask" to monitor human physiological signals is highly beneficial for personal and public health. This work presents a smart mask integrating an ultrathin nanocomposite sponge structure‐based soundwave sensor (≈400 µm), which allows the high sensitivity in a wide‐bandwidth dynamic pressure range, i.e., capable of detecting various respiratory sounds of breathing, speaking, and coughing. Thirty‐one subjects test the smart mask in recording their respiratory activities. Machine/deep learning methods, i.e., support vector machine and convolutional neural networks, are used to recognize these activities, which show average macro‐recalls of ≈95% in both individual and generalized models. With rich high‐frequency (≈4000 Hz) information recorded, the two‐/tri‐phase coughs can be mapped while speaking words can be identified, demonstrating that the smart mask can be applicable as a daily wearable Internet of Things (IoT) device for respiratory disease identification, voice interaction tool, etc. in the future. This work bridges the technological gap between ultra‐lightweight but high‐frequency response sensor material fabrication, signal transduction and processing, and machining/deep learning to demonstrate a wearable device for potential applications in continual health monitoring in daily life. [ABSTRACT FROM AUTHOR]

Transition metal oxides are considered as promising anode materials of high-performance lithium-ion batteries because of their higher specific capacities than that of commercial graphite. However, they still suffer from huge volume expansion/contraction during cycling, leading to fast decay of the reversible capacity and poor cycle stability. In this work, a graded porous carbon matrix has been in situ constructed successfully to strengthen structural stability of NiFe2O4 nanoparticles via a facile and green low-temperature combustion method. The calcination temperature has a significant effect on the purity and electrochemical performances of the final NiFe2O4/C composites. NiFe2O4/C prepared at 350 °C shows a high first discharge capacity of 1385.8 mAh g−1 at 200 mA g−1, excellent cycle stability, and good rate capability. This excellent electrochemical performance may be attributed to its favorable graded porous structure. The carbon matrix can effectively protect the NiFe2O4 nanoparticles, buffer the surface stress caused by volume expansion/contraction, and facilitate the transmission of electrons and Li+ ions. The symbiotic relationship between NiFe2O4 active nanoparticles and graded porous carbon matrix strengthens the structural stability of the electrode, which expands the way of designing high-performance electrode materials for secondary rechargeable batteries. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is a common complication of delayed tissue plasminogen activator (t-PA) treatment for ischemic stroke. Peroxynitrite plays an important role in the breakdown of blood–brain barrier (BBB) and the development of HT. We tested the hypothesis that Angong Niuhuang Wan (AGNHW), a traditional Chinese medicinal formula, could be used in conjunction with t-PA to protect the BBB, minimize HT, and improve neurological function by suppressing peroxynitrite-mediated matrix metalloproteinase-9 (MMP-9) activation. Methods: We first performed quality control study and chemical identification of AGNHW by using UPLC. In animal experiments, male Sprague–Dawley rats were subjected to 5 h of middle cerebral artery occlusion (MCAO) followed by 19 h of reperfusion plus t-PA infusion (10 mg/kg) at 5 h of cerebral ischemia. AGNHW (257 mg/kg) was given orally at 2 h after MCAO. Hemorrhagic transformation was measured using hemorrhagic scores and hemoglobin levels in ischemic brains. Evans blue leakage was utilized to assess the severity of the blood–brain barrier (BBB) damage. The modified neurologic severity score (mNSS) test was used to assess neurological functions. Peroxynitrite and superoxide was detected by using fluorescent probes. MMP-9 activity and expression were examined by gelatin zymography and immunostaining. The antioxidant effects were also studied by using brain microvascular endothelial b.End3 cells exposed to 5 h of oxygen and glucose deprivation (OGD) plus 5 h of reoxygenation with t-PA treatment (20 µg/ml). Results: AGNHW significantly reduced the BBB damage, brain edema, reduced hemorrhagic transformation, enhanced neurological function, and reduced mortality rate in the ischemic stroke rats with t-PA treatment. AGNHW reduced peroxynitrite and superoxide in vivo and in vitro and six active chemical compounds were identified from AGNHW with peroxynitrite scavenging activity. Furthermore, AGNHW inhibited MMP-9 activity, and preserved tight junction protein claudin-5 and collagen IV in the ischemic brains. Conclusion: AGNHW could be a potential adjuvant therapy with t-PA to protect the BBB integrity, reduce HT, and improve therapeutic outcome in ischemic stroke treatment via inhibiting peroxynitrite-mediated MMP-9 activation. [ABSTRACT FROM AUTHOR]

Abstract: Quality control plays a critical role in the process of translating the traditional/alternative medicines into modern evidence-based therapies. High performance liquid chromatography (HPLC) is widely applied to assess the chemical composition of botanical drug products. The chromatographic fingerprints or chemical profiles are currently used as the de facto quality control metric. As a complement to chemical profiles, a biological quality control assessment offers distinct advantages. This study describes a genome-wide biological response fingerprinting (BioReF) approach to define a set of marker genes that define a signature pattern for a specific botanical formulation. These marker genes are chosen on the basis of the levels of the regulated expression and the involvement in the cellular signaling pathways. Subsequently, qRT-PCR technique is used to simultaneously monitor the gene expression of multiple marker genes in an efficient and quantitative manner. This set of marker genes represents the biological responses of human cells to the chemical composition of the botanical drug that could serve as potential quality control of botanical drugs in terms of the consistency of biological activities. We demonstrate the BioReF approach with a well-documented Chinese Medicine formula, designated as ISF-1, traditionally used for the management of post-stroke disorders. A set of nine marker genes were selected to assess the batch-to-batch consistency of the biological effects of ISF-1. This approach provides a potential comprehensive and cost-effective quality control metric of the biological activities of botanical drugs. [Copyright &y& Elsevier]

Background: Buyang Huanwu Decoction (BHD) is a classical Chinese Medicine formula empirically used for diabetic nephropathy (DN). However, its therapeutic efficacies and the underlying mechanisms remain obscure. In our study, we aim to evaluate the renoprotective effect of BHD on a streptozotocin (STZ)-induced diabetic nephropathy mouse model and explore the potential underlying mechanism in mouse mesangial cells (MCs) treated with high glucose in vitro, followed by screening the active compounds in BHD. Methods: Mice were received 50 mg/kg streptozotocin (STZ) or citrate buffer intraperitoneally for 5 consecutive days. BHD was intragastrically administrated for 12 weeks starting from week 4 after the diabetes induction. The quality control and quantitative analysis of BHD were studied by high-performance liquid chromatography (HPLC). Renal function was evaluated by urinary albumin excretion (UAE) using ELISA. The mesangial matrix expansion and renal fibrosis were measured using periodic acid-schiff (PAS) staining and Masson Trichrome staining. Mouse mesangial cells (MCs) were employed to study molecular mechanisms. Results: We found that the impaired renal function in diabetic nephropathy was significantly restored by BHD, as indicated by the decreased UAE without affecting the blood glucose level. Consistently, BHD markedly alleviated STZ-induced diabetic glomerulosclerosis and tubulointerstitial injury as shown by PAS staining, accompanied by a reduction of renal inflammation and fibrosis. Mechanistically, BHD inhibited the activation of TGF-β1/Smad3 and NF-κB signaling in diabetic nephropathy while suppressing Arkadia expression and restoring renal Smad7. We further found that calycosin-7-glucoside (CG) was one of the active compounds from BHD, which significantly suppressed high glucose-induced inflammation and fibrosis by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways in mesangial cells. Conclusion: BHD could attenuate renal fibrosis and inflammation in STZ-induced diabetic kidneys via inhibiting TGF-β1/Smad3 and NF-κB signaling while suppressing the Arkadia and restoring renal Smad7. CG could be one of the active compounds in BHD to suppress renal inflammation and fibrosis in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background: Syndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. Methods: This is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study) by sharing the parent patient populations but with different aims and independent designed roadmaps to investigate the TCM syndrome pattern distributions and the impacts of syndrome pattern types on the efficacy of QLQX in HF treatment. The clinical trial involves over 100 hospitals in mainland China and Hong Kong SAR with 3080 HF patients. By assessing the morbidity and re-hospitalization, we will verify and apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the "2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure" to evaluate the TCM syndromes for the patients. A pilot study with at least 600 patients will be conducted to evaluate the reliability, feasibility and validity of the modified TCM questionnaire for syndrome differentiation of HF and the sample size is calculated based on the confidence level of 95%, population size of 3080 and 5% margin of error. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect outcomes: To our knowledge, this is the first large scale clinical trial to evaluate the impacts of TCM syndrome differentiation on the progression and therapeutic outcome of HF patients and explore the diagnostic value of TCM Tongue Diagnosis in HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF. Trial Registration: The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS)/reactive nitrogen species (RNS)-mediated ferroptosis becomes a novel effective target for anti-cancer treatment. In the present study, we tested the hypothesis that 18-β-glycyrrhetinic acid (GA), an active compound from medicinal herbal Licorice, could induce the production of ROS/RNS, increase lipid peroxidation and trigger ferroptosis in MDA-MB-231 triple negative breast cancer cells. To confirm the GA's anti-cancer effects, we detected cell viability, apoptosis and ferroptosis in the MDA-MB-231 cells. To explore the effects of GA on inducing ferroptosis, we measured mitochrondrial morphology, ROS/RNS production, lipid peroxidation, ferrous ion, glutathione (GSH), System Xc−, GPX4, glutathione peroxidases (GPX), NADPH oxidase and iNOS in the MDA-MB-231 cells. The major discoveries are included as below: (1) GA treatment selectively decreased cell viability and induced ferroptosis companied with the increased lipid peroxidation and ferrous ion in the MDA-MB-231 triple negative breast cancer cells. Iron chelator deferoxamine mesylate (DFO) and ferroptosis inhibitor Ferrostatin-1 abolished the effects of GA. (2) GA treatment up-regulated the expression and activity of NADPH oxidase and iNOS, and increased ROS/RNS productions (O 2 •−, •OH, NO and ONOO−) in the MDA-MB-231 cells; (3) GA down-regulated the expression of SLC7A11 of System X c −, decreased glutathione (GSH) level and inhibited GPX activity. Taken together, GA could promote the productions of ROS and RNS via activating NADPH oxidases and iNOS, and decreasing GSH and GPX activity, subsequently aggravating lipid peroxidation and triggering ferroptosis in triple-negative breast cancer cells. GA treatment selectively decreased cell viability and induced ferroptosis with the increased lipid peroxidation in the MDA-MB-231 triple negative breast cancer cells. The underlying mechanisms are associated with following aspects: (1) GA promotes the expression and activity of NADPH oxidase and iNOS, increases ROS/RNS productions (O 2 •−, •OH, NO and ONOO−) and mediates lipid peroxidation. (2) GA down-regulates the expression of SLC7A11 of System Xc- and decreased the production of GSH, further inducing lipid peroxidation. The large amount of lipid peroxidation triggered ferroptosis in MDA-MB-231 cells. [Display omitted] • GA treatment selectively decreased cell viability and induced ferroptosis in the MDA-MB-231 cells. • GA induces ROS/RNS-mediated ferroptosis in breast cancer cells via activating NADPH oxidase and iNOS, and depriving GSH level. • GA down-regulated the expression of SLC7A11 of System X c −, decreased glutathione (GSH) level and inhibited GPX activity in the MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

• MCP promotes nerve regeneration after stroke. • MCP promotes nuclear translocation of β -catenin. • MCP enhances Sirt1 activity. The deacetylase SIRT1 has been reported to play a critical role in regulating neurogenesis, which may be an adaptive processes contributing to recovery after stroke. Our previous work showed that the antioxidant capacity of Momordica charantia polysaccharides (MCPs) could protect against cerebral ischemia/reperfusion (I/R) after stroke. However, whether the protective effect of MCPs on I/R injury is related to neural stem cell (NSC) proliferation remains unclear. In the present study, we designed invivo and invitro experiments to elucidate the underlying mechanisms by which MCPs promote endogenous NSC proliferation during cerebral I/R. Invivo results showed that MCPs rescued the memory and learning abilities of rats after I/R damage and enhanced NSC proliferation in the rat subventricular zone (SVZ) and subgrannular zone (SGZ) during I/R. Invitro experiments demonstrated that MCPs could stimulate the proliferation of C17.2 cells under oxygen-glucose deprivation (OGD) conditions. Further studies revealed that the proliferation-promoting mechanism of MCPs relied on increasing the activity of SIRT1, decreasing the level of acetylation of β-catenin in the cytoplasm, and then triggering the translocation of β-catenin into the nucleus. These data provide experimental evidence that the up-regulation of SIRT1 activity by MCPs led to an increased cytoplasmic deacetylation of β-catenin, which promoted translocation of β-catenin to the nucleus to participate in the signaling pathway involved in NSC proliferation. The present study reveals that MCPs function as a therapeutic drug to promote stroke recovery by increasing the activity of SIRT1, decreasing the level of acetylated β-catenin, promoting the nuclear translocation of β-catenin and thereby increasing endogenous NSC proliferation. [ABSTRACT FROM AUTHOR]

This study aims to test the hypothesis that peroxynitrite-mediated inflammasome activation could be a crucial player in the blood-brain barrier (BBB) disruption, hemorrhagic transformation (HT) and poor outcome in ischemic stroke with hyperglycemia. We used an experimental rat stroke model subjected to 90 min of middle cerebral artery occlusion plus 24 h or 7 days of reperfusion with or without acute hyperglycemia. We detected the production of peroxynitrite, the expression of NADPH oxidase, iNOS, MMPs and NLRP3 inflammasome in the ischemic brains, and evaluated infarct volume, brain edema, HT, neurological deficit score and survival rates. Our results show that: (1) Hyperglycemia increased the expression of NADPH oxidase subunits p47phox and p67phox, and iNOS, and the production of peroxynitrite. (2) Hyperglycemia increased infarct volume, aggravated the BBB hyperpermeability, induced brain edema and HT, and worsened neurological outcomes. These brain damages and poor outcome were reversed by the treatments of FeTmPyP (a representative peroxynitrite decomposition catalyst, PDC), peroxynitrite scavenger uric acid, and iNOS inhibitor 1400W. Furthermore, the activations of MMPs and NLRP3 inflammasome including pro/active-caspase-1 and IL-1β were inhibited both PDC and 1400W, indicating the roles of peroxynitrite in the inductions of MMPs and NLRP3 inflammasome in the ischemic brains under hyperglycemia. (3) NLRP3 inflammasome inhibitor MCC950, caspase-1 inhibitor VX-765 and IL-1β inhibitor diacerein attenuated brain edema, minimized hemorrhagic transformation and improved neurological outcome, demonstrating the roles of NLRP3 inflammasome in the hyperglycemia-mediated HT and poor outcome in the ischemic stroke rats with acute hyperglycemia. In conclusion, peroxynitrite could mediate activations of MMPs and NLRP3 inflammasome, aggravate the BBB damage and HT, and induce poor outcome in ischemic stroke with hyperglycemia. Therefore, targeting peroxynitrite–mediated NLRP3 inflammasome could be a promising strategy for ischemic stroke with hyperglycemia. Schematic diagram showing the role of peroxynitrite/NLRP3 inflammasome and MMPs activation in mediating hemorrhagic transformation in ischemic brains with acute hyperglycemia. [Display omitted] • Hyperglycemia increases peroxynitrite in ischemic brains to activate NLRP3 inflammasome. • Targeting peroxynitrite reduces HT of ischemic stroke with hyperglycemia. • Targeting NLRP3 inflammasome reduces HT. [ABSTRACT FROM AUTHOR]

Peroxynitrite (ONOO−)-mediated mitophagy activation represents a vital pathogenic mechanism in ischemic stroke. Our previous study suggests that ONOO− mediates Drp1 recruitment to the damaged mitochondria for excessive mitophagy, aggravating cerebral ischemia/reperfusion injury and the ONOO−-mediated mitophagy activation could be a crucial therapeutic target for improving outcome of ischemic stroke. In the present study, we tested the neuroprotective effects of rehmapicroside, a natural compound from a medicinal plant, on inhibiting ONOO−-mediated mitophagy activation, attenuating infarct size and improving neurological functions by using the in vitro cultured PC12 cells exposed to oxygen glucose deprivation with reoxygenation (OGD/RO) condition and the in vivo rat model of middle cerebral artery occlusion (MCAO) for 2 h of transient cerebral ischemia plus 22 h of reperfusion. The major discoveries include following aspects: (1) Rehmapicroside reacted with ONOO− directly to scavenge ONOO−; (2) Rehmapicroside decreased O 2 − and ONOO−, up-regulated Bcl-2 but down-regulated Bax, Caspase-3 and cleaved Caspase-3, and down-regulated PINK1, Parkin, p62 and the ratio of LC3-II to LC3-I in the OGD/RO-treated PC12 cells; (3) Rehmapicroside suppressed 3-nitrotyrosine formation, Drp1 nitration as well as NADPH oxidases and iNOS expression in the ischemia-reperfused rat brains; (4) Rehmapicroside prevented the translocations of PINK1, Parkin and Drp1 into the mitochondria for mitophagy activation in the ischemia-reperfused rat brains; (5) Rehmapicroside ameliorated infarct sizes and improved neurological deficit scores in the rats with transient MCAO cerebral ischemia. Taken together, rehmapicroside could be a potential drug candidate against cerebral ischemia-reperfusion injury, and its neuroprotective mechanisms could be attributed to inhibiting the ONOO−-mediated mitophagy activation. Image 1 • Rehmapicroside can scavenge ONOO- and suppress Drp1 nitation. • Rehmapicroside attenuates ONOO--mediated mitophagy. • Rehmapicroside ameliorates cerebral ischemia-reperfusion injury. • Rehmapicroside prevented the translocations of PINK1, Parkin and Drp1 into the mitochondria for mitophagy activation in the ischemia-reperfused rat brains. • Rehmapicroside ameliorated infarct sizes and improved neurological deficit scores in the rats with transient MCAO cerebral ischemia. [ABSTRACT FROM AUTHOR]

• Caveolin-1 inhibits neurogenesis in ischemic brain. • Endothelial caveolin-1 inhibits neural differentiation of neural progenitor cells. • Caveolin-1 inhibits Neurogenic Differentiation 1 in neural progenitor cells. • Caveolin-1 inhibits vascular endothelial growth factor in neural progenitor cells. Caveolin-1 (Cav-1) is an important modulator for adult neurogenesis in post stroke brain repair but its underlying mechanisms are largely unknown. In the present study, we report that endothelial Cav-1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) in post ischemic brain via regulating vascular endothelial growth factor (VEGF) and NeuroD1 signaling pathway. We first investigated the dynamic change of Cav-1 and its impact on neuronal differentiation in rat and mouse models of 2 h transient middle cerebral artery occlusion (MCAO) plus 1, 7, 14, 21 and 28 day of reperfusion. We then studied the roles of endothelial Cav-1 in modulating the neuronal differentiation of NPCs which were co-cultured with brain microvascular endothelial cells (BMVECs) under 2 h oxygen-glucose deprivation plus 5 days reoxygenation (OGD/R). The major discoveries include: (1) Cav-1 expression in the hippocampal dentate gyrus (DG) was down-regulated on day 1 after 2 h cerebral ischemia, and gradually recovered with reperfusion time, accompanied with transient increased but gradually reduced neuronal differentiation of NPCs marked by doublecortin (DCX). (2) Cav-1 knockout mice exhibited the increased DCX and VEGF at the granular cell layers of hippocampal DG in post-ischemic brains. (3) Co-cultured with BMVECs, NPCs had remarkably decreased neuronal differentiation under OGD/R. Knockdown of Cav-1 in the BMVECs increased VEGF secretion into the medium and NeuroD1+ cells, and rescued the neuronal differentiation of NPCs without affecting astroglial and oligodendroglial differentiation. (4) Cav-1 exosomes released from BMVECs inhibited neuronal differentiation of NPCs via decreasing the expression of VEGF, p44/42MAPK phosphorylation and NeuronD1 upon OGD/R insults. Taken together, endothelial Cav-1 serves as a niche regulator to inhibit neuronal differentiation via negatively modulating VEGF, p44/42MAPK phosphorylation and NeuronD1 signaling pathway. [ABSTRACT FROM AUTHOR]

Poststroke cognitive impairment (PSCI) is a severe sequela of stroke. There are no effective therapeutic options for it. In this study, we evaluated whether electroacupuncture (EA) on the trigeminal nerve-innervated acupoints could alleviate PSCI and identified the mechanisms in an animal model. The male Sprague-Dawley rat middle cerebral artery occlusion (MCAO) model was used in our study. EA was conducted on the two scalp acupoints, EX-HN3 (Yintang) and GV20 (Baihui), innervated by the trigeminal nerve, for 14 sessions, daily. Morris water maze and novel object recognition were used to evaluate the animal's cognitive performance. Neuroprotection and synaptic plasticity biomarkers were analyzed in brain tissues. Ischemia-reperfusion (I/R) injury significantly impaired spatial and cognition memory, while EA obviously reversed cognitive deterioration to the control level in the two cognitive paradigms. Moreover, EA reversed the I/R injury-induced decrease of brain-derived neurotrophic factor, tyrosine kinase B, N-methyl-D-aspartic acid receptor 1, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, γ-aminobutyric acid type A receptors, Ca2+/calmodulin-dependent protein kinase II, neuronal nuclei, and postsynaptic density protein 95 expression in the prefrontal cortex and hippocampus. These results suggest that EA on the trigeminal nerve-innervated acupoints is an effective therapy for PSCI, in association with mediating neuroprotection and synaptic plasticity in related brain regions in the MCAO rat model. [ABSTRACT FROM AUTHOR]

Selective and sensitive molecular probes for hydrogen peroxide (H2O2), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H2O2. A lack of reliable tools for in vivo imaging has hampered the development of H2O2 mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H2O2‐CL‐510 was developed as a highly selective and sensitive probe for detection of H2O2 both in vitro and in vivo. A rapid 430‐fold enhancement of chemiluminescence was triggered directly by H2O2 without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia‐reperfusion injury‐induced H2O2 fluxes were visualized in rat brains using H2O2‐CL‐510, providing a new chemical tool for real‐time monitoring of H2O2 dynamics in living animals. [ABSTRACT FROM AUTHOR]

Selective and sensitive molecular probes for hydrogen peroxide (H2O2), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H2O2. A lack of reliable tools for in vivo imaging has hampered the development of H2O2 mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H2O2‐CL‐510 was developed as a highly selective and sensitive probe for detection of H2O2 both in vitro and in vivo. A rapid 430‐fold enhancement of chemiluminescence was triggered directly by H2O2 without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia‐reperfusion injury‐induced H2O2 fluxes were visualized in rat brains using H2O2‐CL‐510, providing a new chemical tool for real‐time monitoring of H2O2 dynamics in living animals. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory disease in central nervous system (CNS) with limited therapeutic drugs. In the present study, we explored the anti-inflammatory/neuroprotective properties of Acteoside (AC), an active compound from medicinal herb Radix Rehmanniae (RR), and neuroprotective effects of AC on MS pathology by using an experimental autoimmune encephalomyelitis (EAE) model. We tested the hypothesis that AC could alleviate EAE pathogenesis through inhibiting inflammation and ONOO−-mediated mitophagy activation in vivo and in vitro. The results showed that AC treatment effectively ameliorated neurological deficit score and postponed disease onset in the EAE mice. AC treatment inhibited inflammation/demyelination, alleviated peripheral activation and CNS infiltration of encephalitogenic CD4+ T cells and CD11b+ activated microglia/macrophages in the spinal cord of EAE mice. Meanwhile, AC treatment reduced ONOO− production, down-regulated the expression of iNOS and NADPH oxidases, and inhibited neuronal apoptotic cell death and mitochondrial damage in the spinal cords of the EAE mice. Furthermore, AC treatment decreased the ratio of LC3-II to LC3-I in mitochondrial fraction, and inhibited the translocation of Drp1 to the mitochondria. In vitro studies further proved that AC possessed strong ONOO− scavenging capability and protected the neuronal cells from nitrative cytotoxicity via suppressing ONOO−-mediated excessive mitophagy. Taken together, Acteoside could be a potential therapeutic agent for multiple sclerosis treatment. The suppression of ONOO−-induced excessive mitophagy activation could be one of the critical mechanisms contributing to its anti-inflammatory and anti-demyelinating properties. Image 1 • Acteoside effectively attenuates the disease progress and neurological deficit severity in EAE. • Acteoside inhibits ONOO−-mediated excessive neuronal mitophagy, contributing to its neuroprotection. • Acteoside is one of the active compounds against EAE/MS in Radix Rehmanniae. [ABSTRACT FROM AUTHOR]

Active autophagy/mitophagy could mediate neurodegeneration and motor disabilities in multiple sclerosis (MS). Mitochondrial recruitment of dynamin-related protein 1 (Drp1) is a crucial step to initiate mitophagy. Peroxynitrite (ONOO−) could be a player in MS pathology but the mechanisms remain unknown. We used animal model of experimental autoimmune encephalomyelitis (EAE) and tested whether ONOO− mediates Drp1 assembly in mitochondria for mitophagy and aggravates MS pathology. We found that autophagy/mitophagy activation was coincidently increased with axonal damage, apoptosis and disease progression in active EAE mice, which were remarkably attenuated by mitochondrial division/mitophagy inhibitor Mdivi-1. Importantly, increased ONOO− production was companied with Drp1 mitochondrial recruitment, PINK1/Parkin-mediated mitophagy, axonal degeneration and neuronal cell death, which were reversed by peroxynitrite decomposition catalyst (PDC). Furthermore, ONOO− production induced Drp1 nitration, promoted Drp1 assembly and mitochondrial recruitment for mitophagy activation, contributing to the EAE pathology. Together, we conclude that ONOO− serves as a key mediator in Drp1 nitration modification and assembly for facilitating mitophagy activation. Targeting ONOO−-mediated Drp1 assembly and mitochondrial recruitment could be an important therapeutic strategy for multiple sclerosis treatment. Image 1 • Excessive mitophagy activation leads to axonal degeneration and neuronal cell death in EAE. • ONOO− mediates excessive mitophagy. • ONOO− serves as a key mediator in Drp1 nitration modification and assembly for facilitating mitophagy activation. [ABSTRACT FROM AUTHOR]

(D,E) Percentages of the number of cells located on the lower side of chambers and Matrigel-coated chambers in the presence of ISL with miR-374a interference. (B) Chamber migration and invasion assay analysis of the effect of miR-374a transfection on breast cancer motile ability with ISL interference. [Extracted from the article]

Arsenic, in the trivalent form (AsIII), is a human co-carcinogen reported to enhance mutagenesis effects of other carcinogens such as UV radiation by inhibiting DNA repair. The zinc finger DNA repair protein Poly (ADP-ribose) polymerase 1 (PARP-1) is a sensitive target of AsIII and both reactive oxygen and nitrogen species (ROS/RNS) generated by AsIII contribute to PARP-1 inhibition. However, the mechanisms of ROS/RNS-mediated PARP inhibition and how AsIII-generated ROS/RNS may be interconnected are still unclear. In this study, we found AsIII exposure of normal human keratinocyte (HEKn) cells generated peroxynitrite through superoxide and nitric oxide production in an AsIII concentration dependent manner. Peroxynitrite inhibited PARP-1 activity and caused zinc loss from PARP-1 protein while scavenging peroxynitrite was protective of the impacts on PARP-1. We identified peroxynitrite was responsible for S-nitrosation on cysteine residues resulting in PARP-1 zinc finger conformational changes. Taken together, the evidence indicates AsIII generates peroxynitrite through superoxide and nitric oxide production, induces S-nitrosation on PARP-1, leading to zinc loss and activity inhibition of PARP-1, thus enhancing DNA damage caused by UV radiation. These findings highlight a role for peroxynitrite as a key molecule of ROS/RNS mediated DNA repair inhibition by AsIII which should inform the development of prevention and intervention strategies against AsIII co-carcinogenesis. • AsIII generates peroxynitrite through superoxide and nitric oxide production. • Peroxynitrite contributes to PARP-1 inhibition by AsIII. • Peroxynitrite contributes to AsIII enhancement of UVR-induced DNA damage. [ABSTRACT FROM AUTHOR]

Tissue plasminogen activator (t-PA) remains to be the only FDA-approved drug for ischaemic stroke, but it has a restrictive therapeutic window with 4.5 hours. Beyond the golden time window, thrombolytic treatment carries the risk of haemorrhagic transformation (HT). The blood-brain barrier (BBB) disruption is a critical step in the t-PA-mediated HT. Although large efforts are made to explore the mechanisms of the BBB disruption and HT, the underlying mechanisms are largely unknown. Thrombolytic treatment for recanalization could produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) and mediate cerebral ischaemia-reperfusion injury. RNS, including nitric oxide (NO) and peroxynitrite (ONOO−), are important players in cerebral ischaemia-reperfusion injury. In particular, ONOO− and its derivatives could mediate neurovascular unit damages and induce the BBB disruption and HT possibly through interacting with different cellular signalling pathways including matrix metalloproteinase (MMPs), high mobility group Box 1 (HMGB1), toll-like receptor2/4, poly(ADP-ribose) polymerase, Src, ROCK, and GSK-3β. Herein, we review current progress about the roles of ONOO− in mediating those signalling pathways and their impacts on the t-PA-induced BBB disruption and HT. Subsequently, we discuss the values of natural compounds with the properties of scavenging ONOO− as adjunctive therapies to extend the therapeutic window of t-PA and attenuate haemorrhage transformation in ischaemic stroke. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD), the second most common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although the molecular mechanisms underlying dopaminergic neuronal degeneration in PD remain unclear, neuroinflammation is considered as the vital mediator in the pathogenesis and progression of PD. Bushen-Yizhi Formula (BSYZ), a traditional Chinese medicine, has been demonstrated to exert antineuroinflammation in our previous studies. However, it remains unclear whether BSYZ is effective for PD. Here, we sought to assess the neuroprotective effects and explore the underlying mechanisms of BSYZ in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine- (MPTP-) induced mouse model of PD. Our results indicate that BSYZ significantly alleviates the motor impairments and dopaminergic neuron degeneration of MPTP-treated mice. Furthermore, BSYZ remarkably attenuates microglia activation, inhibits NLPR3 activation, and decreases the levels of inflammatory cytokines in MPTP-induced mouse brain. Also, BSYZ inhibits NLRP3 activation and interleukin-1β production of the 1-methyl-4-phenyl-pyridinium (MPP+) stimulated BV-2 microglia cells. Taken together, our results indicate that BSYZ alleviates MPTP-induced neuroinflammation probably via inhibiting NLRP3 inflammasome activation in microglia. Collectively, BSYZ may be a potential therapeutic agent for PD and the related neurodegeneration diseases. [ABSTRACT FROM AUTHOR]

Hypoxic/ischemic stimulation could mediate growth and differentiation of neural stem/progenitor cells (NSCs) into mature neurons but its underlying mechanisms are largely unclear. Peroxynitrite formation is considered as a crucial pathological process contributing to cerebral ischemia-reperfusion injury. In the present study, we tested the hypothesis that peroxynitrite at low concentration could function as redox signaling to promote the growth of NSCs under hypoxic/ischemic conditions. Increased NSCs proliferation was accompanied by peroxynitrite production in the rat brains with 1 h of ischemia plus 7 days of reperfusion in vivo . Cell sorting experiments revealed that endogenous peroxynitrite level affected the capacity of proliferation and self-renewal in NSCs in vitro . Hypoxia stimulated peroxynitrite production and promoted NSCs self-renewal, proliferation and neuronal differentiation whereas treatments of peroxynitrite decomposition catalysts (PDCs, FeTMPyP and FeTPPS) blocked the changes in NSCs self-renewal, proliferation and neuronal differentiation. Exogenous peroxynitrite treatment revealed similar effects to promote NSCs proliferation, self-renewal and neuronal differentiation. Furthermore, the neurogenesis-promoting effects of peroxynitrite were partly through activating HIF-1α correlated with enhanced Wnt/β-catenin signaling pathway. In conclusion, peroxynitrite could be a cellular redox signaling for promoting NSCs proliferation, self-renewal and neuronal differentiation and peroxynitrite production could contribute to neurogenesis in ischemic/hypoxic NSCs. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of isoliquiritigenin were explored. The results proved that isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by isoliquiritigenin treatment in breast cancer. Further study displayed that isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies. [ABSTRACT FROM AUTHOR]

Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders. In this article, we review current progress about how different growth factors, neurotrophin, neurotransmitters and transcriptional factors work on regulating neurogenic process. In particular, we emphasize the roles of the cellular metabolic factors, such as insulin/IGF signaling, incretins, and lipid metabolic signaling molecules in modulating adult neurogenesis, and discuss their impacts on neurological behaviors. We propose that the metabolic factors could be the new therapeutic targets for adult neurogenesis. Plus, the metabolism-regulating drugs have the potentials for treatment of neurodegenerative diseases and mental disorders. [ABSTRACT FROM AUTHOR]

In order to reduce the ground-borne vibration caused by wheel/rail interaction in the ballastless track of high speed railways, viscoelastic asphalt concrete materials are filled between the track and the subgrade to attenuate wheel/rail force. A high speed train-track-subgrade vertical coupled dynamic model is developed in the frequency domain. In this model, coupling effects between the vehicle and the track and between the track and the subgrade are considered. The full vehicle is represented by some rigid body models of one body, two bogies, and four wheelsets connected to each other with springs and dampers. The track and subgrade system is considered as a multilayer beam model in which layers are connected to each other with springs and damping elements. The vertical receptance of the rail is discussed and the receptance contribution of the wheel/rail interaction is investigated. Combined with the pseudoexcitation method, a solution of the random dynamic response is presented. The random vibration responses and transfer characteristics of the ballastless track and subgrade system are obtained under track random irregularity when a high speed vehicle runs through. The influences of asphalt concrete layer’s stiffness and vehicle speed on track and subgrade coupling vibration are analyzed. [ABSTRACT FROM AUTHOR]

Zinc ions are stored in synaptic vesicles and cerebral ischemia triggers their release from the terminals of neurons. Zinc accumulation in neurons has been shown to play an important role in neuronal death following ischemia. However, almost nothing is known about whether zinc is involved in ischemia-induced blood–brain barrier (BBB) disruption. Herein, we investigated the contribution of zinc to ischemia-induced acute BBB disruption and the possible molecular mechanisms using both cellular and animal models of cerebral ischemia. Zinc greatly increased BBB permeability and exacerbated the loss of tight junction proteins (Occludin and Claudin-5) in the endothelial monolayer under oxygen glucose deprivation conditions. In cerebral ischemic rats, a dramatically elevated level of zinc accumulation in microvessels themselves was observed in isolated microvessels and in situ , showing the direct interaction of zinc on ischemic microvessels. Treatment with a specific zinc chelator N , N , N ′, N ′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), even at 60-min post-ischemia onset, could greatly attenuate BBB permeability in the ischemic rats as measured by Evan's Blue extravasation, edema volume and magnetic resonance imaging. Furthermore, zinc accumulation in microvessels activated the superoxide/matrix metalloproteinase-9/-2 pathway, which leads to the loss of tight junction proteins (Occludin and Claudin-5) and death of endothelial cells in microvessels themselves. Our findings reveal a novel mechanism of cerebral ischemia-induced BBB damage, and implicate zinc as an effective and viable new target for reducing acute BBB damage following ischemic stroke. [ABSTRACT FROM AUTHOR]

B Smart Masks b In article number 2203565 by Ho-yin Chan, Xinge Yu, Jianping Wang, Wen Jung Li, and co-workers, a "smart mask" is developed by using an ultrathin nanocomposite-based soundwave sensor with high sensitivity and wide-bandwidth dynamic range, i.e., integrated with machine/deep learning algorithms, the smart mask can identify breath, two-/tri-phase coughs, and spoken words directly. The smart mask could be a new wearable Internet of Things device for personal health monitoring and respiratory disease identification tool in the future. Wide-Bandwidth Nanocomposite-Sensor Integrated Smart Mask for Tracking Multiphase Respiratory Activities (Adv. Sci. 31/2022). [Extracted from the article]

Nitrative stress is considered as an important pathological process of hepatic ischemia and reperfusion injury but its regulating mechanisms are largely unknown. In this study, we tested the hypothesis that caveolin-1 (Cav-1), a plasma membrane scaffolding protein, could be an important cellular signaling against hepatic I/R injury through inhibiting peroxynitrite (ONOO − )-induced cellular damage. Male wild-type mice and Cav-1 knockout (Cav-1 −/− ) were subjected to 1 h hepatic ischemia following 1, 6 and 12 h of reperfusion by clipping and releasing portal vessels respectively. Immortalized human hepatocyte cell line (L02) was subjected to 1 h hypoxia and 6 h reoxygenation and treated with Cav-1 scaffolding domain peptide. The major discoveries included: (1) the expression of Cav-1 in serum and liver tissues of wild-type mice was time-dependently elevated during hepatic ischemia-reperfusion injury. (2) Cav-1 scaffolding domain peptide treatment inhibited cleaved caspase-3 expression in the hypoxia-reoxygenated L02 cells; (3) Cav-1 knockout (Cav-1 −/− ) mice had significantly higher levels of serum transaminases (ALT&AST) and TNF-α, and higher rates of apoptotic cell death in liver tissues than wild-type mice after subjected to 1 h hepatic ischemia and 6 hour reperfusion; (4) Cav-1 −/− mice revealed higher expression levels of iNOS, ONOO − and 3-nitrotyrosine (3-NT) in the liver than wild-type mice, and Fe-TMPyP, a representative peroxynitrite decomposition catalyst (PDC), remarkably reduced level of ONOO − and 3-NT and ameliorated the serum ALT, AST and TNF-α levels in both wild-type and Cav-1 −/− mice. Taken together, we conclude that Cav-1 could play a critical role in preventing nitrative stress-induced liver damage during hepatic ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Developing high-capacity anode materials is one of the crucial measures to effectively increase the energy density of Li-ion batteries. As a promising anode material, ZnFe 2 O 4 has been widely concerned because of its high specific capacity and low cost. However, the inherent poor conductivity and dramatic volume changes during cycling restrict its further commercial development. In this paper, ZnFe 2 O 4 /C composites have been successfully designed by utilizing the self-swelling effect of gelatin to embed ZnFe 2 O 4 nanoparticles inside 3D porous carbon dispersedly. At 200 mA g–1, ZnFe 2 O 4 /C obtained at 450 °C exhibits a high initial discharge specific capacity of 1367.1 mAh g–1. The excellent electrochemical performances are derived from the synergistic effect of ZnFe 2 O 4 active nanoparticles and 3D porous carbon framework. Nano-sized particles can shorten the transport length of ions and electrons inside the active material. The presence of 3D porous carbon can realize high-speed charge transmission, facilitate the electrolyte infiltration, protect active particles, and buffer the structural destruction caused by volume change of metal oxide upon cycling. In addition, ZnFe 2 O 4 /C composites also show promising potential as anode materials of Na-ion batteries. This work provides a bright direction for the preparation of advanced anode materials for secondary rechargeable batteries. • ZnFe 2 O 4 nanoparticles are embedded dispersedly inside the 3D porous carbon. • The self-expansion of gelatin leads to the formation of 3D porous precursor. • A high reversible capacity and good cycling stability are achieved. • Carbon, porous structure and active nanoparticles play a synergistic role. [ABSTRACT FROM AUTHOR]

In recent years, bimetallic oxides have been widely researched as promising anode materials of Li-ion batteries due to their superior electrochemical capacities compared with single transition metal oxides. However, the low interior conductivity and volume change upon cycling result in poor cycling stability. Here, carbon nanotubes (CNTs) have been employed in a solvothermal method to successfully boost the high capacity and superior cycling stability of ZnFe 2 O 4 /C nanoparticles. The effect of CNTs content on the structure, morphology, and electrochemical property of the composite has been investigated. At 200 mA g–1, ZnFe 2 O 4 /C/CNTs composite shows a high first discharge specific capacity of 1375.7 mAh g–1. After 100 cycles, the specific capacity can be still maintained at 1430.4 mAh g–1. The excellent electrochemical performance of ZnFe 2 O 4 /C/CNTs is attributed to the protective shell of carbon coating layer and three-dimensional channel constructed by high-conductive CNTs, which can alleviate volume change upon cycling and accelerate the transfer of electrons and lithium ions. This work provides a feasible idea for improving the properties of carbon-modified bimetallic oxide anode materials of secondary rechargeable batteries. [Display omitted] • CNTs boost the superior cycling stability of ZnFe 2 O 4 /C nanoparticles. • ZnFe 2 O 4 /C/CNTs composite shows a high reversible capacity of 1430.4 mAh g–1. • CNTs can effectively alleviate the stress caused by repeated cycling of ZnFe 2 O 4 /C. • Carbon, CNTs, and active nanoparticles play a synergistic effect. [ABSTRACT FROM AUTHOR]