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Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has shown outstanding efficacy in treating stroke. This study investigated various therapeutic targets of HSHS for ischemic stroke using mRNA transcriptomics. Herein, rats were randomly separated into the sham, model, HSHS 5.25 g/kg (HSHS5.25), and HSHS 10.5 g/kg (HSHS10.5) groups. Rats suffering from stroke were induced by permanent middle cerebral artery occlusion (pMCAO). After seven days of HSHS treatment, behavioral tests were conducted, and histological damage was examined with hematoxylin-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) validated gene expression changes. An analysis of gene ontology and pathway enrichment was conducted to analyze potential mechanisms confirmed using immunofluorescence and western blotting. HSHS5.25 and HSHS10.5 improved neurological deficits and pathological injury in pMCAO rats. The intersections of 666 differentially expressed genes (DEGs) were chosen using transcriptomics analysis in the sham, model, and HSHS10.5 groups. The enrichment analysis suggested that the therapeutic targets of HSHS might regulate the apoptotic process and ERK1/2 signaling pathway, which was related to neuronal survival. Moreover, TUNEL and immunofluorescence analysis indicated that HSHS inhibited apoptosis and enhanced neuronal survival in the ischemic lesion. Western blot and immunofluorescence assay indicated that HSHS10.5 decreased Bax/Bcl-2 ratio and suppressed caspase-3 activation, while the phosphorylation of ERK1/2 and CREB was upregulated in a stroke rat model after HSHS treatment. Effective inhibition of neuronal apoptosis by activating the ERK1/2-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.

Poor long-term cycling stability and rate capability seriously restricted the commercial applications of silicon (Si) anodes, because of the huge volume change and the kinetic problems linked to th...

Despite the high specific capacity of Li-S battery, shuttle effect of lithium polysulfides (LiPSs) and safety issue pose a great challenge to realize its commercial application. Replacing liquid electrolyte with poly (ethylene oxide) (PEO) -based solid-state electrolyte is considered as a promising method to boost the safety, but the shuttle effect of LiPSs cannot be completely eliminated. In this work, a new kind of double-layer PEO-based polymer electrolyte is designed to restrict the LiPSs. The layer next to cathode consists of PEO and poly(vinylpyrrolidone) (PVP). The other layer consists of PEO. PVP with abundant of amide groups has been proved to have strong affinity to LiPSs. The strong interaction between LiPSs and carbonyl groups in amide is verified by Attenuated Total Reflection-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy tests. As a result, the assembled Li-S battery exhibits a specific capacity of 1100 mAh g

Ethnopharmacological relevance Trillium tschonoskii Maxim. is one of traditional Chinese medical herbs that has been utilized to treat brain damages and cephalalgia. The neuroprotective effect of total saponins from Trillium tschonoskii rhizome (TSTT) has been demonstrated efficacy in rats following ischemia. However, the axonal remodeling effect of TSTT and the detailed mechanisms after ischemic stroke have not been investigated. Aim of the study We aimed to estimate therapeutic role of TSTT in axonal remodeling using magnetic resonance imaging (MRI) technique, and explored possible mechanisms underlying this process followed by histological assays in ischemic rats. Methods Male Sprague-Dawley (SD) rats underwent permanently focal cerebral ischemia induced by occluding right permanent middle cerebral artery. TSTT was intragastrically administrated 6 h after surgery and once daily for consecutive 15 days. Neurological function was assessed by the motor deficit score and beam walking test. T2 relaxation mapping and diffusion tensor imaging (DTI) were applied for detecting cerebral tissues damages and microstructural integrity of axons. Luxol fast blue (LFB) and transmission electron microscope (TEM) were performed to evaluate histopathology in myelinated axons. Double immunofluorescent staining was conducted to assess oligodendrogenesis. Furthermore, the protein expressions regarding to axonal remodeling related signaling pathways were detected by Western blot assays. Results TSTT treatment (65, 33 mg/kg) markedly improved motor function after ischemic stroke. T2 mapping MRI demonstrated that TSTT decreased lesion volumes, and DTI further confirmed that TSTT preserved axonal microstructure of the sensorimotor cortex and internal capsule. Meanwhile, diffusion tensor tractography (DTT) showed that TSTT elevated correspondent density and length of fiber in the internal capsule. These MRI measurements were confirmed by histological examinations. Notably, TSTT significantly increased Ki67/NG2, Ki67/CNPase double-labeled cells along the boundary zone of ischemic cortex and striatum. Meanwhile, TSTT treatment up-regulated the phosphorylation level of Ser 9 in GSK-3β, and down-regulated phosphorylated β-catenin and CRMP-2 expression. Conclusion Taken together, our findings indicated that TSTT (65, 33 mg/kg) enhanced post-stroke functional recovery, amplified endogenous oligodendrogenesis and promoted axonal regeneration. The beneficial role of TSTT might be correlated with GSK-3/β-catenin/CRMP-2 modulating axonal reorganization after ischemic stroke.

Background. Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results. 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions. QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically.

Traditional Chinese medicines (TCMs) have been considered as important alternative therapeutics because of their significant medicinal benefits in specific diseases. Chinese herb formula is characterized by a vast molecule that differs in routine medicines. Due to TCMs chemical complexity, proper quality control has been a great challenge. Choosing the appropriate method to identify and qualify these compounds is an important work to ensure its safety, efficacy and quality control. Thus, this study aimed at providing novel information on high-resolution LTQ-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MSn) based identification of Bu Shen Yi Sui capsule (BSYSC), which is used in treating multiple sclerosis as a kind of TCMs. Under the proposed chromatographic conditions, 80 chemical components classified as anthraquinone, phenolic acid and phenylethanoid glycosides were separated and identified from BSYSC. Coupled with the high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) method, eight of them were regarded as marker compounds for the quantitative evaluation of BSYSC. The identification and quantification with precision of UPLC-LTQ-Orbitrap-MSn and UPLC-QTOF-MS/MS could facilitate essential data for further pharmacokinetic studies of BSYSC.

Severe withdrawal symptoms triggered by cessation of long-term opioid use deter many individuals from seeking treatment. Opioid substitution and α2-adrenergic agonists are the current standard of pharmacotherapy for opioid use disorder in western medicine; however, each is associated with significant complications. Heantos-4 is a non-opioid botanical formulation used to facilitate opioid detoxification in Vietnam. While ongoing clinical use continues to validate its safety and effectiveness, a mechanism of action accounting for these promising effects remains to be specified. Here, we assess the effects of Heantos-4 in a rat model of morphine-dependence and present evidence that alleviation of naloxone-precipitated somatic withdrawal signs is related to an upregulation of mesolimbic dopamine activity and a consequent reversal of a hypodopaminergic state in the nucleus accumbens, a brain region implicated in opioid withdrawal. A central dopaminergic mechanism is further supported by the identification of l-tetrahydropalmatine as a key active ingredient in Heantos-4, which crosses the blood–brain barrier and shows a therapeutic efficacy comparable to its parent formulation in attenuating withdrawal signs. The anti-hypodopaminergic effects of l-tetrahydropalmatine may be related to antagonism of the dopamine autoreceptor, thus constituting a plausible mechanism contributing to the effectiveness of Heantos-4 in facilitating opioid detoxification.

Traditional Chinese medicines (TCMs) have been considered as important alternative therapeutics because of their significant medicinal benefits in specific diseases. Chinese herb formula is characterized by a vast molecule that differs in routine medicines. Due to TCMs chemical complexity, proper quality control has been a great challenge. Choosing the appropriate method to identify and qualify these compounds is an important work to ensure its safety, efficacy and quality control. Thus, this study aimed at providing novel information on high-resolution LTQ-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap-MSn) based identification of Bu Shen Yi Sui capsule (BSYSC), which is used in treating multiple sclerosis as a kind of TCMs. Under the proposed chromatographic conditions, 80 chemical components classified as anthraquinone, phenolic acid and phenylethanoid glycosides were separated and identified from BSYSC. Coupled with the high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) method, eight of them were regarded as marker compounds for the quantitative evaluation of BSYSC. The identification and quantification with precision of UPLC-LTQ-Orbitrap-MSn and UPLC-QTOF-MS/MS could facilitate essential data for further pharmacokinetic studies of BSYSC.

A specific, sensitive and rapid ultra high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method was developed and validated for simultaneous determination of six major bioactive constituents in Rhizoma Panacis Japonici (RPJ), including oleanolic acid-type chikusetsusaponin V, IV, hemsgiganoside B, damarane-type ginsenoside Rb1, Rg1 and Re in rat plasma, using estazolam as the internal standard (IS). Plasma samples were pretreated with methanol/acetonitrile (1:1, V/V) for protein precipitation. Chromatographic separation was performed on an Agilent Eclipse Plus C18 column, using a gradient mobile phase consisting of methanol and 0.1% formic acid aqueous solution. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. For all the six analytes of interest, the calibration curves were linear in the concentration range of 2.00–500 ng/mL with r ≥ 0.9956. The intra- and inter-day precisions (in terms of relative standard deviation, RSD) were all below 10.2% and the accuracies (in terms of relative error, RE) were within −5.0% to 6.3% for all six analytes. Extraction recovery, matrix effect and stability data all met the acceptance criteria of FDA guideline for bioanalytical method validation. The developed method was applied to the pharmacokinetic study in rat. After oral administration of the total saponins from RPJ, six analytes were quickly absorbed into the blood and presented the phenomenon of double peaks. Among the six analytes, ginsenoside Rb1 showed slowest elimination from plasma with a t1/2z of 16.00 h, while that of the others were between 1.72 and 5.62 h. In conclusion, the developed method was successfully used to simultaneously analyze major oleanolic acid-type and damarane-type saponins of RPJ in rat plasma after oral administration.

Both introducing oxygen vacancies (OVs) and enhancing charge transfer efficiency (CTE) have been proved to be effective strategies to improve the capability of the catalyst to activate peroxymonosulfate (PMS). The OVs on catalysts can promote the CTE of the catalyst/PMS oxidation system. However, current OVs introduction methods can only lead to very limited CTE enhancement. Here, the synthesis of CoP/CoOx heterostructured nanoparticles with abundant OVs and dramatically enhanced CTE through a reliable partial phosphidation method using ZIF-67 as a precursor was reported. The excellent CTE of the CoP/CoOx/PMS oxidation system was the result of the synergy of increased OVs and introduced CoP with high conductivity. When served as Fenton-like catalyst for tetracycline (TC) degradation via activating PMS, due to the synergy between abundant OVs and high CTE, CoP/CoOx exhibited superior performance for TC removal, with the pseudo-second-order kinetic rate constant ∼ 10.3 and 77.4 times that of CoPx and Co3O4, respectively. Moreover, the cobalt leakage (0.06 mg/L) was only about 1/2 and 1/3 of that of CoPx and Co3O4, respectively. The mechanism study suggested that SO4•−, •OH and O2•− played an important role in TC degradation. The excellent catalytic performance of CoP/CoOx was attributed to its abundant OVs and high CTE to generate more active oxygen species. This work provides new insights for designing and developing efficient catalysts for wastewater treatment via Fenton-like process.

Rationale: Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke. Objective: To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery. Methods and results: The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin–Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro. Conclusion: The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery.

Xiaoshuan enteric-coated capsule (XSECC) is a drug approved by the Chinese State Food and Drug Administration for the treatment of stroke. This study was to investigate the effects of XSECC on white and gray matter injury in a rat model of ischemic stroke by diffusion tensor imaging (DTI) and histopathological analyses. The ischemia was induced by middle cerebral artery occlusion (MCAO). The cerebral blood flow measured by arterial spin labeling was improved by treatment with XSECC on the 3rd, 7th, 14th and 30th days after MCAO. Spatiotemporal white and gray matter changes in MCAO rats were examined with DTI-derived parameters (fractional anisotropy, FA; apparent diffusion coefficient, ADC; axial diffusivity, λ//; radial diffusivity, λ⊥). The increased FA was found in the XSECC treatment group in the corpus callosum, external capsule and internal capsule, linked with the decreased λ//, λ⊥ and ADC on the 3rd day and reduced ADC on the 30th day in the external capsule, suggesting XSECC reduced the axon and myelin damage in white matter after stroke. The relative FA in the striatum, cortex and thalamus in XSECC treatment group was significantly increased on the 3rd, 7th, 14th and 30th days accompanied by the increased λ// on the 3rd day and reduced relative ADC and λ⊥ on the 30th day, indicating that XSECC attenuated cell swelling and membrane damage in the early stage and tissue liquefaction necrosis in the late stage in gray matter after stroke. Additionally, XSECC-treated rats exhibited increased mean fiber length assessed by diffusion tensor tractography. Moreover, histopathological analyses provided evidence that XSECC relieved nerve cell and myelin damage in white and gray matter after stroke. Our research reveals that XSECC could alleviate white and gray matter injury, especially reducing nerve cell damage and promoting the repair of axon and myelin after ischemic stroke.

Along with the process of urbanization in China, the country has clearly put forward The National New-Style Urbanization Plan to promote the integration of urban and rural development, allow all of the people living in rural areas to participate in China’s modernization and share the achievements of development. Meanwhile, the country has launched lots of policies to promote rural stability, agricultural development and farmers’ income. In 2013, China launched the Beautiful Countryside program to strengthen rural ecology, environmental protection and comprehensive improvement, and strive to build a beautiful countryside. This policy is quite flexible and involves more than aesthetics. It can support rural infrastructure construction, industrial and economic development, improvement of living environments, social and cultural development, and protection of natural, historical, and cultural resources as well as beautification projects. In accordance with the policy requirements, all provinces in China have worked out the implementation plans. Guizhou province is located in South Central China, most of the province’s land (92.5%) consists of mountains and hills, water resources are limited. As a poor province, Guizhou has proposed many policies to promote the development of rural areas over the years, and some of them have made great impact. In 2013, the Provincial Government issued a policy document titled “Promote the Development of The Countryside and Build a Beautiful Countryside—Six Point Action Plan Program for Rural Infrastructure”, which emphasizes improving living conditions in rural areas by promoting roads, drinking water and irrigation, electricity, telecommunications, housing, and the environment. This paper will study the policy and focus on the formulation of the policy implementation and management. The research group at Shanghai Tongji Urban Planning & Design Institute’s China Rural Planning and Construction Research Center launched an investigation of the implementation of Guizhou’s Six Point Action Plan in 2015, they conducted an investigation of the planning and implementation process in 10 administrative villages representative of the variety of villages in Guizhou Province, and obtained a set of comprehensive data. On this basis, this paper firstly introduces the policy objectives and the key projects. Then, it introduces the governance and plan implementation in detail. In the end, the paper summarizes the experience of policy implementation, including breaking down and refining policy goals, paying attention to organization and project management, involving civil society and individuals in projects, providing multiple funding channels, promoting citizen participation and so on.

Non-alcoholic fatty liver disease (NAFLD) is becoming a major health concern worldwide. Ilex hainanensis Merr. extract was proved to have anti-inflammation effect on NAFLD, and Ilexhainanoside D (IhD) and ilexsaponin ATo investigate the hepatoprotective effect of the combination of IhD and IsA (IIC) against NAFLD and discuss the potential mechanisms.Male C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD and were treated with IIC (60, 120 or 240 mg/kg) for 8 weeks. Growth parameters, abdominal fat content, serum biochemical markers, hepatic lipid accumulation and insulin tolerance were assessed. Quantitative real-time PCR was used to determine the hepatic gene expression of TLR2, TLR4, TNF-α, IL-6, and IL-1β. Western blot analysis was performed to determine the expression of the epidermal tight junction proteins ZO-1 and occludin. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene.IIC significantly reduced the severity of NAFLD induced by HFD in a dose-dependent manner. IIC decreased the ratio of Firmicutes/Bacteroidetes, reduced the relative abundance of Desulfovibrio and increased the relative abundance of Akkermansia. The intestinal barrier was improved as evidenced by the upregulation of the expression of ZO-1 and occludin in the ileum. IIC thus reduced the entry of LPS into the circulation and decreased the hepatic gene expression levels of proinflammatory cytokines.This approach demonstrated the positive effects of IIC in a mouse model of NAFLD, indicating that it possibly acts by reducing inflammation and improving the intestinal barrier function.

Two dimensional (2D) metal oxide are expected to be better adsorbents for heavy metal ions than their other low dimensional counterparts. In this work, non-layered 2D Fe2O3 nanosheets were synthesized by a simple combustion method and tested for Pb(II) removal from aqueous solution. The 2D Fe2O3 nanosheets exhibited high crystallinity and purity as confirmed by powder x-ray diffraction. As revealed by scanning electron microscope (SEM) and transmission electron microscope (TEM), the nanosheets with lateral size up to hundreds of microns that made it easy to be recollected after water treatment. The results of XRD and TEM indicated that the nanosheets showed preferentially exposed surfaces of (1 0 0), which has strong affinity for Pb(II). The nanosheets exhibited a moderate specific surface area of 12.19 m2/g with a small pore volume of 0.034 mL/g. The nanosheets exhibited excellent adsorption performance for Pb(II) in pH range from 3.0 to 6.0. The adsorption of Pb(II) conformed to the Langmuir isotherm model with the theoretical maximum adsorption capacity of Pb(II) estimated to be 436.83 mg/g. Kinetics study indicated that the adsorption process followed pseudo-second-order kinetics model. Based on the X-ray photoelectron spectroscopy and FTIR results of the nanosheets before and after Pb(II) adsorption, the adsorption of Pb(II) was dominated by the surface complexation and ion exchange of Pb(II) ions with surface hydroxyl groups. Given the low preparation cost and the excellent adsorption capacity, the non-layered 2D Fe2O3 nanosheets holds great potential as adsorbent for Pb(II) removal.

Ethnopharmacological relevance Houshiheisan (HSHS), a classic traditional medicine prescription, has notable effects on patients with stroke Aim of the study To investigate the neurorestorative effects of HSHS on ischemic stroke and explore its mode of action. Materials and methods Focal cerebral ischemia models were induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley (SD) rats were randomly divided into 5 experimental groups: sham vehicle, ischemia vehicle, pMCAO+HSHS at 5.1, 10.2 g/kg, and pMCAO+Ginaton 0.028 g/kg. HSHS or Ginaton was administrated 6 h after pMCAO onset. Neurological function was assessed and then rats were sacrificed 7 days after MCAO. Cerebral ischemic injury was evaluated by hematoxylin and eosin (HE) staining and Neuronal nuclear antigen (NeuN) immunofluorescence analysis. The levels of BDNF were detected by enzyme linked immunosorbent assay (ELISA), and the expression levels of PI3K/Akt and Nogo-A/RhoA/ROCK2 signaling pathway were detected by western blot and quantitative real-time PCR (qRT-PCR). Results Compared with those results of pMCAO group, HSHS 5.1 and HSHS 10.2 groups markedly improved neurological function, alleviated pathological damage, promoted the neuronal survival, increased the expression of BDNF, PI3K, Akt, in protein and mRNA, decreased the expression of Nogo-A, NgR, RhoA and ROCK2 in protein and mRNA 7 days after pMCAO. Conclusions The findings demonstrate that HSHS had significant therapeutic effects on ischemic stroke and it perhaps worked through the activation of BDNF/PI3K/Akt and down-regulation of Nogo-A/RhoA/ROCK signaling pathways.

Salvia miltiorrhiza Bunge is a medicinal plant species commonly used in China and other East Asian countries. There is a large market demand for this herb, and improving its yield and quality is an urgent problem to be solved in production practice. Artificial light sources have been widely used in the production of vegetables and medicinal plants, but little is known about the effects of light quality on the growth and secondary metabolites accumulation in S. miltiorrhiza. In this study, the effects of monochromic blue light (460 nm, B), monochromic red light (635 nm, R), white light, and various combinations of B and R light (9B:1R, 7B:3R, 1B:1R, 3B:7R and 1B:9R) on the growth and phenolic acid accumulation of S. miltiorrhiza were investigated. The results showed that, the growth and contents of rosmarinic acid and salvianolic acid B in S. miltiorrhiza were simultaneously stimulated under 3B:7R. The transcripts of key enzyme-encoding genes involved in the rosmarinic acid pathway were measured, and the expression of SmPAL1 and Sm4CL1 was significantly increased under combined blue and red light. The results of site-directed mutagenesis revealed that the GT1-motif in the SmPAL1 promoter region, I-Box, ATC-motif and TCT-motif in the Sm4CL1 promoter region were related to the responses of these two genes to combined blue and red light. Taken together, the results of this work indicated that, the combined blue and red light promoted the growth of S. miltiorrhiza and enhanced the accumulation of phenolic acids by up-regulating the transcription of SmPAL1 and Sm4CL1 in this herb. Light quality is an important environmental factor that effects yield and quality of S. miltiorrhiza.

Silicon (Si) with high energy density is identified as the most promising candidate for commercial lithium-ion batteries anodes. Unfortunately, the volume expansion severely damages the battery cycle life during cycling, resulting in fast capacity fading during the battery operation. Herein, a facile design was proposed for the preparation of novel tailored mesoporous Si cages (TMSC) to mitigate this issue. The TMSC material, with mesoporous anamorphic spherical shells and nano-sized Si cores, consists of numerous interconnected channels and forms a half open three-dimensional network. When evaluated as electrode material for lithium-ion batteries, it exhibits the reversible capacity of 931.1 mAh/g after 200 cycles at 1 A/g, which is more stable than that of Si pomegranates with intact shells. Moreover, it displays a high rechargeable capacity of 552.3 mA h/g over 500 cycles at 4 A/g and the capacity decay ratio is only 0.11% for each cycle.

Xiaoshuan enteric-coated capsule (XSECC) is a drug approved by the Chinese State Food and Drug Administration for the treatment of stroke. This study was to investigate the effects of XSECC on white and gray matter injury in a rat model of ischemic stroke by diffusion tensor imaging (DTI) and histopathological analyses. The ischemia was induced by middle cerebral artery occlusion (MCAO). The cerebral blood flow measured by arterial spin labeling was improved by treatment with XSECC on the 3rd, 7th, 14th and 30th days after MCAO. Spatiotemporal white and gray matter changes in MCAO rats were examined with DTI-derived parameters (fractional anisotropy, FA; apparent diffusion coefficient, ADC; axial diffusivity, λ//; radial diffusivity, λ⊥). The increased FA was found in the XSECC treatment group in the corpus callosum, external capsule and internal capsule, linked with the decreased λ//, λ⊥ and ADC on the 3rd day and reduced ADC on the 30th day in the external capsule, suggesting XSECC reduced the axon and myelin damage in white matter after stroke. The relative FA in the striatum, cortex and thalamus in XSECC treatment group was significantly increased on the 3rd, 7th, 14th and 30th days accompanied by the increased λ// on the 3rd day and reduced relative ADC and λ⊥ on the 30th day, indicating that XSECC attenuated cell swelling and membrane damage in the early stage and tissue liquefaction necrosis in the late stage in gray matter after stroke. Additionally, XSECC-treated rats exhibited increased mean fiber length assessed by diffusion tensor tractography. Moreover, histopathological analyses provided evidence that XSECC relieved nerve cell and myelin damage in white and gray matter after stroke. Our research reveals that XSECC could alleviate white and gray matter injury, especially reducing nerve cell damage and promoting the repair of axon and myelin after ischemic stroke.

Chronic cerebral hypoperfusion (CCH) is identified as a critical risk factor of dementia in patients with cerebrovascular disease. Xiaoshuan enteric-coated capsule (XSECC) is a compound Chinese medicine approved by Chinese State Food and Drug Administration for promoting brain remodeling and plasticity after stroke. The present study aimed to explore the potential of XSECC to improve cognitive function after CCH and further investigate the underlying mechanisms. CCH was induced by bilateral common carotid artery occlusion (BCCAO) in rats. XSECC (420 or 140 mg/kg) treatment remarkably reversed BCCAO-induced cognitive deficits. Notably, after XSECC treatment, magnetic resonance angiography combined with arterial spin labeling noninvasively demonstrated significantly improved hippocampal hemodynamics, and 18F-FDG PET/CT showed enhanced hippocampal glucose metabolism. In addition, XSECC treatment markedly alleviated neuropathologies and improved neuroplasticity in the hippocampus. More importantly, XSECC treatment facilitated axonal remodeling by regulating the phosphorylation of axonal growth related proteins including protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β) and collapsin response mediator protein-2 (CRMP2) in the hippocampus. Taken together, the present study demonstrated the beneficial role of XSECC in alleviating BCCAO-induced cognitive deficits by enhancing hippocampal glucose metabolism, hemodynamics and neuroplasticity, suggesting that XSECC could be a useful strategy in cerebral hypoperfusion state and dementia.

Repeated mild traumatic brain injury (rmTBI), the most common type of traumatic brain injuries, can result in neurological dysfunction and cognitive deficits. However, the molecular mechanisms and the long-term consequence of rmTBI remain elusive. In this study, we developed a modified rmTBI mouse model and found that rmTBI-induced transient neurological deficits and persistent impairments of spatial memory function. Furthermore, rmTBI mice had long-lasting detrimental effect on cognitive function, exhibiting memory deficits even 12 weeks after rmTBI. Microarray analysis of whole genome gene expression showed that rmTBI significantly altered the expression level of 87 genes which are involved in apoptosis, stress response, metabolism, and synaptic plasticity. The results indicate the potential mechanism underlying rmTBI-induced acute neurological deficits and its chronic effect on memory impairments. This study suggests that long-term monitoring and interventions for rmTBI individuals are essential for memory function recovery and reducing the risk of developing neurodegenerative diseases.

Background Non-alcoholic fatty liver disease (NAFLD) is becoming a major health concern worldwide. Ilex hainanensis Merr. extract was proved to have anti-inflammation effect on NAFLD, and Ilexhainanoside D (IhD) and ilexsaponin A1 (IsA) were the main triterpenoid saponins extracted from it. Purposes To investigate the hepatoprotective effect of the combination of IhD and IsA (IIC) against NAFLD and discuss the potential mechanisms. Methods Male C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD and were treated with IIC (60, 120 or 240 mg/kg) for 8 weeks. Growth parameters, abdominal fat content, serum biochemical markers, hepatic lipid accumulation and insulin tolerance were assessed. Quantitative real-time PCR was used to determine the hepatic gene expression of TLR2, TLR4, TNF-α, IL-6, and IL-1β. Western blot analysis was performed to determine the expression of the epidermal tight junction proteins ZO-1 and occludin. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Results IIC significantly reduced the severity of NAFLD induced by HFD in a dose-dependent manner. IIC decreased the ratio of Firmicutes/Bacteroidetes, reduced the relative abundance of Desulfovibrio and increased the relative abundance of Akkermansia. The intestinal barrier was improved as evidenced by the upregulation of the expression of ZO-1 and occludin in the ileum. IIC thus reduced the entry of LPS into the circulation and decreased the hepatic gene expression levels of proinflammatory cytokines. Conclusion This approach demonstrated the positive effects of IIC in a mouse model of NAFLD, indicating that it possibly acts by reducing inflammation and improving the intestinal barrier function.

Ethnopharmacological relevance Trillium tschonoskii rhizome (TTR), a medicinal herb, has been traditionally used to treat traumatic brain injury and headache in China. Although the potential neuroprotective efficacy of TTR has gained increasing interest, the pharmacological mechanism remains unclear. Steroid saponins are the main bioactive components of the herb. Aim of the study To investigate the protective and repair-promoting effects of the total saponins from TTR (TSTT) on grey and white matter damages in a rat model of middle cerebral artery occlusion (MCAO) using magnetic resonance imaging (MRI) assay. Materials and methods Ischemic stroke was induced by MCAO. TSTT and Ginaton (positive control) were administered orally to rats 6 h after stroke and daily thereafter. After 15 days of treatment, the survival rate of each group was calculated. We then conducted neurological deficit scores and beam walking test to access the neurological function after ischemic stroke. Subsequently, T2-weighted imaging (T2WI) and T2 relaxometry mapping were performed to measure infarct volume and grey and white matter integrity, respectively. Moreover, diffusion tensor imaging (DTI) was carried out to evaluate the grey and white matter microstructural damage. Additionally, arterial spin labelling (ASL) - cerebral blood flow (CBF) and magnetic resonance angiography (MRA) images provided dynamic information about vascular hemodynamic dysfunction after ischemic stroke. Finally, haematoxylin and eosin (HE) staining was carried out to evaluate the stroke-induced pathological changes in the brain. Results The survival rate and neurological behavioural outcomes (Bederson scores and beam walking tests) were markedly ameliorated by TSTT (65 mg/kg) treatment within 15 days after ischemic stroke. Moreover, T2WI and T2 relaxometry mapping showed that TSTT (65 mg/kg) significantly reduced infarct volume and attenuated grey and white matter injury, respectively, which was confirmed by histopathological evaluation of brain tissue. The results obtained from DTI showed that TSTT (65 mg/kg) not only significantly alleviated axonal damage and demyelination, but also promoted axonal remodelling and re-myelination. In addition, TSTT treatment also enhanced vascular signal density and increased CBF in rats after MCAO. Conclusion Our results suggested the potential protective and repair-promoting effects of TSTT on grey and white matter from damage induced by ischemia. This study provides a modern pharmacological basis for the application of TSTT in managing ischemic stroke.

The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues.

Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the pathological hallmark of Alzheimer's disease (AD). Aβ is generated from sequential cleavages of the β-amyloid precursor protein (APP) by the β- and γ-secretases, and β-site APP-cleaving enzyme 1 (BACE1) is the β-secretase essential for Aβ generation. Previous studies have indicated that glycogen synthase kinase 3 (GSK3) may play a role in APP processing by modulating γ-secretase activity, thereby facilitating Aβ production. There are two highly conserved isoforms of GSK3: GSK3α and GSK3β. We now report that specific inhibition of GSK3β, but not GSK3α, reduced BACE1-mediated cleavage of APP and Aβ production by decreasing BACE1 gene transcription and expression. The regulation of BACE1 gene expression by GSK3β was dependent on NF-κB signaling. Inhibition of GSK3 signaling markedly reduced Aβ deposition and neuritic plaque formation, and rescued memory deficits in the double transgenic AD model mice. These data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3β and that inhibition of GSK3 signaling can reduce Aβ neuropathology and alleviate memory deficits in AD model mice. Our study suggests that interventions that specifically target the β-isoform of GSK3 may be a safe and effective approach for treating AD.

Background Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke. Methods Ischemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by 1H-magnetic resonance spectroscopy (1H-MRS). Arterial spin labeling (ASL) – cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU. Results T2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. 1H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL – CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation. Conclusions Our results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism.

Down syndrome (DS), caused by trisomy of chromosome 21, is one of the most common genetic disorders. Patients with DS display growth retardation and inevitably develop characteristic Alzheimer’s disease (AD) neuropathology, including neurofibrillary tangles and neuritic plaques. The expression of amyloid precursor protein (APP) is increased in both DS and AD patients. To reveal the function of APP and elucidate the pathogenic role of increased APP expression in DS and AD, we performed gene expression profiling using microarray method in human cells overexpressing APP. A set of genes are significantly altered, which are involved in cell cycle, cell proliferation and p53 signaling. We found that overexpression of APP inhibits cell proliferation. Furthermore, we confirmed that the downregulation of two validated genes, PSMA5 and PSMB7, inhibits cell proliferation, suggesting that the downregulation of PSMA5 and PSMB7 is involved in APP-induced cell proliferation impairment. Taken together, this study suggests that APP regulates global gene expression and increased APP expression inhibits cell proliferation. Our study provides a novel insight that APP overexpression may contribute to the growth impairment in DS patients and promote AD pathogenesis by inhibiting cell proliferation including neural stem cell proliferation and neurogenesis.

Ethnopharmacological relevance Huang-Lian-Jie-Du-Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) clinical prescription noted for its neuroprotective effects. The total alkaloids, flavonoids, and iridoids are the main active components of HLJDD. In the present study we explored the possible effects of the total alkaloids, flavonoids, and iridoids from HLJDD on behavioral recovery and cortical neurogenesis after stroke. Methods The stroke model was induced by permanent middle cerebral artery occlusion (pMACO). The total alkaloids (44 mg/kg), flavonoids (50 mg/kg), and iridoids (80 mg/kg) from HLJDD were orally administered for 2 h after stroke and daily thereafter. Neurological function was assessed and then rats were sacrificed 7 days after pMACO. Following repeated intraperitoneal injections of the cell proliferation – specific marker 5-bromodeoxyuridine (BrdU) after stroke induction, precursor cell proliferation and differentiation was monitored by immunofluorescent staining. The levels of relevant proteins were determined by western blotting and the mRNA expressions were assessed by quantitative real time-polymerase chain reaction (qRT-PCR). Results Total alkaloids, flavonoids and iridoids from HLJDD showed improved functional outcome after brain ischemia. The total alkaloids and iridoids increased number of BrdU-positive cells and enhanced neuronal differentiation in the cortex. Alkaloids-enhanced neurogenesis might be associated with increased VEGF, Ang-1, and Ang-2 protein expression. And the neuroproliferative effect of alkaloids was partially correlated with increased phosphorylation of AKT, and GSK-3β. Flavonoids treatment was found to promote differentiation of cortical precursor cells into neuronal but not glial cells, which may be at least attributable to the regulation of AKT, GSK-3β mRNA and Ang-1 protein levels. Conclusions Total alkaloids, iridoids and flavonoids from HLJDD promoted functional recovery likely via enhancing cortical neurogenesis and thus have potential as a treatment for ischemic brain injury.

Down syndrome (DS) is one of the most common genetic diseases. Patients with DS display growth delay and intellectual disabilities and develop Alzheimer's disease (AD) neuropathology after middle age, including neuritic plaques and neurofibrillary tangles. Beta-site amyloid β precursor protein (APP) cleaving enzyme 1 (BACE1), essential for Aβ production and neuritic plaque formation, is elevated in DS patients. However, its homolog, β-site APP cleaving enzyme 2 (BACE2), functions as θ-secretase and plays a differential role in plaque formation. In this study, by using Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) and LC-MS/MS proteomic profiling analysis, we found that the SET oncogene protein (SET) expression was associated with BACE1 but not BACE2. SET protein was increased in BACE1 overexpressing cells and was markedly reduced in the BACE1 knockout mice. We found that the overexpression of BACE1 or SET significantly inhibited cell proliferation. Moreover, knockdown of SET in BACE1 overexpression cells significantly rescued BACE1-induced cell growth suppression. Furthermore, both BACE1 and SET protein levels were increased in Down syndrome patients. It suggests that BACE1 overexpression-induced SET upregulation may contribute to growth delay and cognitive impairment in DS patients. Our work provides a new insight that BACE1 overexpression not only promotes neuritic plaque formation but may also potentiate neurodegeneration mediated by SET elevation in Alzheimer-associated dementia in DS.