miR-18a-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates early brain injury following subarachnoid hemorrhage through blockade of the ENC1/p62 axis.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have therapeutic potential in various diseases due to their capacity to transfer bioactive cargoes such as microRNAs (miRNAs or miRs) to recipient cells. The present study isolated EVs from rat MSCs and aimed to delineate their functions and molecular mechanisms in early brain injury following subarachnoid hemorrhage (SAH). We initially determined the expression of miR-18a-5p and ENC1 in hypoxia/reoxygenation (H/R)-induced brain cortical neurons and rat models of SAH induced by the endovascular perforation method. Accordingly, increased ENC1 and decreased miR-18a-5p were detected in H/R-induced brain cortical neurons and SAH rats. After MSC-EVs were co-cultured with cortical neurons, the effects of miR-18a-5p on neuron damage, inflammatory response, endoplasmic reticulum (ER) stress, and oxidative stress markers were evaluated based on ectopic expression and depletion experiments. miR-18a-5p overexpression in brain cortical neurons co-cultured with MSC-EVs was shown to impede neuron apoptosis, ER stress and oxidative stress while augmenting neuron viability. Mechanistically, miR-18a-5p bound to the 3'UTR of ENC1 and reduced its expression, weakening the interaction between ENC1 and p62. Through this mechanism, transfer of miR-18a-5p by MSC-EVs contributed to the eventual inhibition of early brain injury and neurological impairment following SAH. Overall, miR-18a-5p/ENC1/p62 may be a possible mechanism underlying the cerebral protective effects of MSC-EVs against early brain injury following SAH.

Anti-Ferroptotic Effects of bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Loaded with Ferrostatin-1 in Cerebral ischemia-reperfusion Injury Associate with the GPX4/COX-2 Axis.

Accumulating evidence of the critical role of Ferrostatin-1 (Fer-1, ferroptosis inhibitor) in cerebral ischemia has intrigued us to explore the molecular mechanistic actions of Fer-1 delivery by bone marrow mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) in cerebral ischemia-reperfusion (I/R) injury. In vivo middle cerebral artery occlusion (MCAO) in mice and in vitro oxygen-glucose deprivation/reperfusion (OGD/R) in hippocampal neurons were developed to simulate cerebral I/R injury. After Fer-1 was confirmed to be successfully delivered by MSCs-EVs to neurons, we found that MSCs-EVs loaded with Fer-1 (MSCs-EVs/Fer-1) reduced neuron apoptosis and enhanced viability, along with curtailed inflammation and ferroptosis. The regulation of Fer-1 on GPX4/COX2 axis was predicted by bioinformatics study and validated by functional experiments. The in vivo experiments further confirmed that MSCs-EVs/Fer-1 ameliorated cerebral I/R injury in mice. Furthermore, poor expression of GPX4 and high expression of COX-2 were witnessed in cerebral I/R injury models. MSCs-EVs/Fer-1 exerted its protective effects against cerebral I/R injury by upregulating GPX4 expression and inhibiting COX-2 expression. Taken together, our study indicates that MSCs-EVs/Fer-1 may be an attractive therapeutic target for the treatment of cerebral I/R injury due to its anti-ferroptotic properties.

Molecularly imprinted thermosensitive probe based on fluorescent advanced glycation end products to detect α-dicarbonyl compounds and inhibit pyrraline formation.

A thermal-sensitive molecularly imprinted optosensing probe based on fluorescent advanced glycation end products (AGEs) was prepared by one-pot hydrothermal synthesis. Carbon dots (CDs) derived from fluorescent AGEs were used as the luminous centers, while molecularly imprinted polymers (MIPs) were wrapped outside of the CDs to form specific target recognition sites to highly selectively adsorb the intermediate product of AGEs of 3-deoxyglucosone (3-DG). Thermosensitive N-isopropylacrylamide (NIPAM) was combined with acrylamide (AM) as co-functional monomers, and ethylene glycol dimethacrylate (EGDMA) was chosen as a cross-linker for targeting identification and detection of 3-DG. Under optimal conditions, the fluorescence of MIPs could be gradually quenched with the adsorption of 3-DG on the surface of MIPs in the linear range of 1-160 µg/L, and the detection limit was 0.31 µg/L. The spiked recoveries of MIPs ranged from 82.97 to 109.94% in two milk samples, and the relative standard deviations were all less than 1.8%. In addition, the inhibition rate for non-fluorescent AGEs of pyrraline (PRL) was 23% by adsorbing 3-DG in the simulated milk system of casein and D-glucose, indicating that temperature-responsive MIPs not only could detect the dicarbonyl compound 3-DG quickly and sensitively, but also had an excellent inhibitory effect on AGEs.

Red emissive N-doped carbon dots encapsulated within molecularly imprinted polymers for optosensing of pyrraline in fatty foods.

A novel and facile method was proposed for preparation of red emissive N-doped carbon dots encapsulated within molecularly imprinted polymers (RNCDs@MIPs) using a one-pot room-temperature reverse microemulsion polymerization. RNCDs used citric acid and urea as carbon and nitrogen sources by one-step solvothermal synthesis with the optimum emission of 620 nm. Unique optical properties of RNCDs coupled with high selective MIPs make the RNCDs@MIPs conjugate capable to adsorb specific targets of pyrraline (PRL), such a binding event was then transduced to quench fluorescence response signal of the RNCDs. RNCDs@MIPs for PRL showed linearity from 0.1 to 40 µg/L, with a detection limit of 65 ng/L. The RNCDs@MIPs exhibited a good reproducibility of 4.67% obtained from four times of rebinding for PRL. The optosensing probe was successfully applied to the detection of PRL in fatty foods with the spiked recovery of 85.93-106.96%.

Subsurface phase imaging of tapping-mode atomic force microscopy at phase resonance.

The phase image of tapping-mode atomic force microscopy (TM-AFM) contains energy dissipation, which is related to the sample information on the physical properties such as the sample Young's modulus, adhesion, surface morphology and subsurface morphology. When TM-AFM is used for sample measurement, the frequency near the first resonance peak of probe is usually selected to drive the probe vibration. When the probe vibration is driven by the frequency, the probe has a high amplitude sensitivity, but the phase sensitivity is relatively low. In this paper, the frequency at the probe phase resonance peak was selected for driving the probe vibration to measure the sample, which improved the image resolution. Phase imaging was performed on three uniform photoresist samples with different thicknesses and the same structure. When the scanning parameters were fixed and the probe setpoint value was changed alone, it was found that with the decrease of setpoint value the horizontal resolution of the phase subsurface image was decreased, and the depth sensitivity was increased first and then decreased. The result shows that TM-AFM working at the phase resonance peak can better realise the subsurface imaging of samples at different depths. Phase subsurface imaging at the resonance can be used to quantitatively obtain subsurface phase images of different depths.

A Fast-Transient-Response NMOS LDO with Wide Load-Capacitance Range for Cross-Point Memory.

In this paper, a fast-transient-response NMOS low-dropout regulator (LDO) with a wide load-capacitance range was presented to provide a V/2 read bias for cross-point memory. To utilize the large dropout voltage in the V/2 bias scheme, a fast loop consisting of NMOS and flipped voltage amplifier (FVA) topology was adopted with a fast transient response. This design is suitable to provide a V/2 read bias with 3.3 V input voltage and 1.65 V output voltage for different cross-point memories. The FVA-based LDO designed in the 110 nm CMOS process remained stable under a wide range of load capacitances from 0 to 10 nF and equivalent series resistance (ESR) conditions. At the capacitor-less condition, it exhibited a unity-gain bandwidth (UGB) of approximately 400 MHz at full load. For load current changes from 0 to 10 mA within an edge time of 10 ps, the simulated undershoot and settling time were only 144 mV and 50 ns, respectively. The regulator consumed 70 µA quiescent current and achieved a remarkable figure-of-merit (FOM) of 1.01 mV. At the ESR condition of a 1 µF off-chip capacitor, the simulated quiescent current, on-chip capacitor consumption, and current efficiency at full load were 8.5 µA, 2 pF, and 99.992%, respectively. The undershoot voltage was 20 mV with 800 ns settling time for a load step from 0 to 100 mA within the 10 ps edge time.

Effect of trypsin concentration on living SMCC-7721 cells studied by atomic force microscopy.

Trypsin is playing an important role in the processes of cancer proliferation, invasion and metastasis which require the precise information of morphology and mechanical properties on the nano-scale for the related research. In this work, living human hepatoma (SMCC-7721) cells were treated with different concentrations of trypsin solution. The morphology and mechanical properties of the cells were measured via atomic force microscope (AFM). Statistical analyses of measurement data indicated that with the increase of trypsin concentration, the average cell height and the surface roughness were both increased, but the cell viability, the cell surface adhesion and the elasticity modulus were decreased significantly. The force required to puncture the cells was also gradually reduced. It indicates that trypsin not only hydrolyses the proteins between the cell and the substrate but also the membrane proteins. The results offer valuable clues for the cancerous process study, pathological analysis and trypsin inhibitor drug development. And this work provides an effective way for overcoming the cell membrane in drug injection for cell-targeted therapy.

Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels.

BACKGROUND: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. METHODS: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. RESULTS: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006-1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007-1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022-1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022-1.55; p < 0.001). CONCLUSION: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.

A disulfiram-loaded electrospun poly(vinylidene fluoride) nanofibrous scaffold for cancer treatment.

Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, has shown its effectiveness against diverse cancer types. Thus, we developed a disulfiram-loaded scaffold using the electrospinning method to enhance the stability of DSF and to facilitate its appropriate distribution to tumor tissues. The drug release profile of the disulfiram-loaded scaffold was examined by high-performance liquid chromatography. We obtained mechanical and morphological characterizations of A549 cells treated with different scaffolds by various techniques to evaluate its antitumor properties. This work revealed that the cells after the treatment with the disulfiram-loaded scaffold exhibited a lower height and a larger elastic modulus compared with the untreated cells and those treated with the neat electrospun fibers. The changes were the indicators of cell apoptosis. Taken collectively, the results indicate that DSF was successfully incorporated into the electrospun fibers, and the disulfiram-loaded scaffold has great potential for inhibiting the regional recurrence of cancer.

Oxygen glucose deprivation/reperfusion astrocytes promotes primary neural stem/progenitor cell proliferation by releasing high-mobility group box 1.

Cerebral ischemia/reperfusion is known to activate endogenous neural stem/progenitor cell (NS/PC) proliferation, but the mechanisms leading to NS/PC proliferation remain unknown. Astrocytes are vital components of the neurogenic niche and play a crucial role in regulating NS/PC proliferation and differentiation. After focal cerebral ischemia/reperfusion (I/R), astrocytes release a damage-associated molecular-pattern molecule called high-mobility group box 1 (HMGB1). Since HMGB1 is critical for NS/PC proliferation during brain development, we modeled I/R using glucose deprivation/reperfusion (OGD/R) in vitro and examined the effect of HMGB1 released by astrocytes on NS/PC proliferation. Further, we determined the role of the PI3K/Akt signaling pathway in this process. Using conditioned media from OGD/R astrocytes with or without RNA interference for HMGB1, as well as with anti-HMGB1 antibodies, we evaluated the effect of astrocyte-derived HMGB1 on NS/PC proliferation. Using the potent PI3K/Akt inhibitor, LY294002, we explored the likely mechanism of HMGB1-induced NS/PC proliferation. OGD/R astrocyte-conditioned media (ACM) increased NS/PC proliferation, and HMGB1 RNA interference prevented this effect. Using an HMGB1 neutralizing antibody in OGD/R ACM also abrogated NS/PC proliferation. LY294002 effectively reduced phospho-Akt levels and reduced NS/PC proliferation induced by HMGB1 in vitro. Our data demonstrate that HMGB1 released by OGD/R astrocytes promotes NS/PC proliferation through activation of the PI3K/Akt signaling pathway. Local HMGB1 release may induce endogenous NS/PC to proliferate following cerebral I/R and suggests that HMGB1 may play a pivotal role in brain tissue repair after an ischemic event.

Fast detection of tryptamine in meat products with azide-functionalized covalent organic frameworks confined in molecularly imprinted polymers.

Tryptamine is a biogenic amine that affects organoleptic quality through the generation of off-odours in foods. Herein, imine-based covalent organic frameworks (COFs) were synthesized via Schiff base reactions and postmodified with click chemistry to generate azide-functionalized COFs with tunable azide units on the walls. The combination of molecular imprinting with COFs enabled the specific recognition of the targets. The resulting optosensing system (azide-functionalized COFs@MIPs) was used as a sample-to-answer analyser for detecting tryptamine (detection time within 10 min). A linear relationship was observed for the fluorescence response to tryptamine concentrations in the range of 3-120 µg L-1, with a limit of detection of 1.74 µg L-1. The recoveries for spiked samples were satisfactory, with relative standard deviations <9.90%. The optosensing system is a potential tool for the quantitative detection of tryptamine in meat products because of its lower cost, shorter processing time, and simpler processing steps compared to conventional chromatographic techniques.

Stable, porous, light-emitting post-modification covalent organic frameworks conjugated molecularly imprinted polymers for selective detection of pyrraline in salami products.

Molecular imprinting is one of the most frequently occurring post-modification in the preparation of covalent organic frameworks (COFs) to enhance selectivity and specificity. In this study, we prepared a 2D layer structure of methoxy-conjugated COFs with the modification of azide (4-azido-L-phenylalanine), named [4-ALP]0.17-COFs, which exhibited a large specific surface area of 827.6 m2/g, good stability of water, polar solvents, chemistry, and thermodynamics. Fluorescent COF nanosheets ([4-ALP]0.17-CONs) obtained by liquid-assisted ultrasonic stripping have excellent blue luminescence properties and ultra-high absolute fluorescence quantum yield of 33.34 %. The modifiable functional groups in the surface of [4-ALP]0.17-CONs interacted with the targets and functional monomers of molecularly imprinted polymers (MIPs) through hydrogen bonding interactions, to form the 3D holes with recognition sites. The quantitative detection of pyrraline (PRL) could be achieved in the concentration range of 0.05-4 µg/L with the LOD was 34.81 ng/L. The spiked recovery of PRL in meat products was 88.01-106.00 %. The [4-ALP]0.17-CONs@MIPs sensing system showed excellent stability, reliability, reusability, and practicability, promising its potential for targeted monitoring of trace molecules in real matrices.

USP10 is a potential mediator for vagus nerve stimulation to alleviate neuroinflammation in ischaemic stroke by inhibiting NF-κB signalling pathway.

Background: Vagus nerve stimulation (VNS) has a protective effect on neurological recovery in ischaemic stroke. However, its underlying mechanism remains to be clarified. Ubiquitin-specific protease 10 (USP10), a member of the ubiquitin-specific protease family, has been shown to inhibit the activation of the NF-κB signalling pathway. Therefore, this study investigated whether USP10 plays a key role in the protective effect of VNS against ischemic stroke and explore its mechanism. Methods: Ischaemic stroke model was constructed by transient middle cerebral artery occlusion (tMCAO) in mice. VNS was performed at 30 min, 24hr, and 48hr after the establishment of tMCAO model. USP10 expression induced by VNS after tMCAO was measured. LV-shUSP10 was used to establish the model with low expression of USP10 by stereotaxic injection technique. The effects of VNS with or without USP10 silencing on neurological deficits, cerebral infarct volume, NF-κB pathway activation, glial cell activation, and release of pro-inflammation cytokines were assessed. Results: VNS enhanced the expression of USP10 following tMCAO. VNS ameliorated neurological deficits and reduced cerebral infarct volume, but this effect was inhibited by silencing of USP10. Activation of the NF-κB pathway and the expression of inflammatory cytokines induced by tMCAO were suppressed by VNS. Moreover, VNS promoted the pro-to-anti-inflammatory response of microglia and inhibited activation of astrocytes, while silencing of USP10 prevented the neuroprotective and anti-neuroinflammatory effects of VNS. Conclusion: USP10 is a potential mediator for VNS to alleviate neurological deficits, neuroinflammation, and glial cell activation in ischaemic stroke by inhibiting NF-κB signalling pathway.

Ionic liquid-enhanced lemon biomass carbon dots with sustainable use in bionic antibody microspheres for urea capture and ethyl carbamate inhibition.

Herein, we reported the room-temperature fabrication of ionic liquid-modified carbon dots encapsulated in bionic antibodies (IL-modified CDs@BAs) by one-pot green synthesis. In order to enhance the fluorescence intensity of CDs, imidazole ILs and lemon rich in heteroatoms were selected as CDs modifiers and sources. The resulting IL-modified CDs@BAs showed good selectivity and capture toward urea and obviously induced fluorescence quenching by template-binding. The inhibition rate ofIL-modified CDs@BAs on the urea pathway of ethyl carbamate was about 29.07% in the simulated Huangjiu system, indicating a good inhibitory effect. The IL-modified CDs@BAs system was also reproducible after five consecutive uses, thus reducing the economic cost. This research would expand the application fields of BAs-based optical sensing system from the perspectives of energy conservation, environmental protection and resource recovery, focusing on their application in the field of food safety control.

Identification of nitrogen pollution sources and transport transformation processes in groundwater of different landforms using C, H, N, and O isotope techniques: an example from the lower Weihe River.

Nitrogen pollution in groundwater is an environmental issue of global concern. Identifying nitrogen pollution sources and determining migration and transformation processes are the major ways to prevent and control nitrogen pollution in the groundwater on a regional scale. In this study, groundwater in the lower Wei River was investigated by combining multi-isotope tracing techniques with the SIAR hybrid model (source resolution) to trace the nitrate sources and their contribution rate to nitrogen pollution in groundwater of different geomorphological units, considering types of geomorphology as the units. The multi-isotope tracing technique allows dynamic analysis of nitrate sources, and the combination of this technology can improve the accuracy of nitrogen source traceability. The results indicated that the pH of the water bodies in the study area ranged from 6.83 to 8.01, which is neutral and weakly alkaline. The nitrogen pollution was mainly due to nitrates. The significant factors affecting nitrogen migration in groundwater are the geomorphological type, the chemical characteristics of the groundwater, and the age of the groundwater. Nitrogen migration and transformation processes in the study area were dominated by nitrification, and sources of nitrate pollution were mainly animal manure and domestic sewage (32.6%), followed by atmospheric deposition (26.8%), soil nitrogen (20.9%), and chemical fertilizer (19.7%). The main sources of nitrate in groundwater from river flats, alluvial plains, and loess tableland were animal manure and domestic sewage (43.7%), animal manure and domestic sewage (59.1%), and atmospheric deposition (55.5%), respectively. The result is mainly related to the different structural characteristics of various geomorphic units and the intensity of human activities. This study can provide a theoretical basis for the relevant agencies to develop plans to combat groundwater pollution.

Interaction mechanism between nitrogen conversion and the microbial community in the hydrodynamic heterogeneous interaction zone.

To study the inorganic nitrogen in the process of interaction of river and groundwater and the changes in the microbial community, a vertical simulation device was used to simulate groundwater recharge to river water (upwelling) and river water recharge to groundwater (downwelling). The inorganic nitrogen concentrations in the soil and water solution as well as the characteristics of the microbial community were assessed to determine the inorganic nitrogen transformation and microbial community response in the heterogeneous interaction zone under hydrodynamic action, and the interaction mechanism between nitrogen transformation and the microbial community in the interaction zone was revealed. The removal rates of NO3--N in the simulated solution reached 99.1% and 99.3% under the two fluid-groundwater conversion modes, and the prolonged hydraulic retention time (HRT) of the oxidization-reduction layer in the fine clay area and the high organic matter content made the inorganic nitrogen transformation process dominated by microorganisms more complete. The denitrification during upwelling, dominated by denitrifying bacteria in Sphingomonas, Pseudomonas, Bacillus, and Arthrobacter, was stronger than that during downwelling. Dissimilatory nitrate reduction to ammonium (DNRA), controlled by some aerobic bacteria in Pseudomonas, Bacillus, and Desulfovibrio, was more intense in downflow mode than upflow mode.

E-cigarette awareness and use, among adult residents in Shanghai, China.

INTRODUCTION: The widespread popularity of e-cigarettes is considered an important public health concern. However, only some studies have investigated the prevalence of e-cigarette use in Shanghai, China. Research on the perceived harmfulness of e-cigarettes and public support for e-cigarette regulations in China is limited. This study aimed to estimate e-cigarette awareness, prevalence, and associated factors among adults in Shanghai, China. METHODS: This study used data from a representative survey conducted in Shanghai, China, in 2019. The survey was conducted at 64 surveillance points in Shanghai, China, using a multistage, stratified, cluster-randomized sampling design, recruiting community-based Chinese adults aged ≥15 years. Based on the principles outlined in the Global Adult Tobacco Survey (GATS) China Project, data were collected by conducting face-to-face interviews in households. Of the 3200 selected households, 3060 people completed the individual survey. The overall response rate was 97.4%. RESULTS: In all, 72.3% of the respondents had heard of e-cigarettes. The respondents who had used e-cigarettes at some point in their life, used them in the last 12 months, and used them currently were 5.8%, 2.6%, and 1.3%, respectively. Among adult residents who had heard of e-cigarettes, 38.2% thought they were less harmful than traditional cigarettes. The respondents who perceived e-cigarettes as more harmful than traditional cigarettes were less likely to have ever used e-cigarettes (AOR=0.2; 95% CI: 0.1-0.5, p=0.0015) and more likely to support incorporating e-cigarettes into the regulation of smoking control (AOR=3.9; 95% CI: 1.8-8.6, p=0.0008). CONCLUSIONS: Our findings reveal that the awareness about e-cigarettes was high, and the prevalence of e-cigarette use was similar to the findings from previous studies in China. The harmful perception of e-cigarettes warrants further attention from public health practitioners.

Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking.

Backgroud: Vascular dementia is the second most common cause of dementia after Alzheimer's disease, accounting for an estimated 15% of cases. Recently, Epimedium has attracted great attention for its potential neuroprotective benefit. However, the direct role and mechanism of Epimedium on vascular dementia still lack systematic research. To systematically explore the possible pharmacological mechanism of Epimedium for the treatment of vascular dementia, network pharmacology, molecular docking, combined with experiment validation were conducted. Methods: The bioactive compounds and targets of Epimedium were obtained from the TCMSP database. The potential targets of vascular dementia were identified from the DrugBank, OMIM, Genecards, Therapeutic Target Database, and DisGeNET databases. GO and KEGG pathway analyses were performed. Molecular docking was applied to validate the interaction between active components and hub targets. The bilateral common carotid artery occlusion (BCCAO) method was used for construction of a vascular dementia model in mice. The effects of Epimedium on learning and memory ability were examined by behavioral tests. The mechanisms of the cerebral protective effects of Epimedium were evaluated by WB, RT-PCR, and immunofluorescence. Results: A total of 23 Epimedium active ingredients, and 71 intersecting targets of Epimedium against vascular dementia were obtained. The top five hub targets AKT1, TNF, IL1ß, IL6, and MMP9 were identified, and molecular docking showed good binding. GO enrichment showed a total of 602 enrichment results, with 458 (80.56%) key targets mainly focused on biological processes (BP). The response to hypoxia, positive regulation of nitric oxide biosynthetic process, aging, inflammatory response, cellular response to lipopolysaccharide, negative regulation of apoptotic process were well ranked. KEGG pathway enrichment analysis identified the TNF signaling pathway as an important pathway, with the MAPK/extracellular signal-regulated kinase (ERK) and NF-κB signaling pathways as the key pathways involved. Consistently, in vivo experiments showed that Epimedium treatment improved learning and memory functions in mice with vascular dementia. In addition, Epimedium attenuated the activation of microglia and astrocytes in the hippocampal region after BCCAO. RT-qPCR and Western blot analysis showed that Epimedium not only affected the expression of AKT, TNF, IL1ß, IL6, and MMP9, but also suppressed the TNF signaling pathway. Conclusion: Epimedium may exert a protective effect against vascular dementia through the alleviation of oxidative stress, neuroinflammation, BBB dysfunction, apoptosis through TNF signaling pathway. This study explored the mechanism of Epimedium on vascular dementia systematically through network pharmacological and in vivo experiment approach, which provides insight into the treatment of vascular dementia.

Researches on cognitive sequelae of burn injury: Current status and advances.

Burn injury is a devastating disease with high incidence of disability and mortality. The cognitive dysfunctions, such as memory defect, are the main neurological sequelae influencing the life quality of burn-injured patients. The post-burn cognitive dysfunctions are related to the primary peripheral factors and the secondary cerebral inflammation, resulting in the destruction of blood-brain barrier (BBB), as is shown on Computed Tomography (CT) and magnetic resonance imaging examinations. As part of the neurovascular unit, BBB is vital to the nutrition and homeostasis of the central nervous system (CNS) and undergoes myriad alterations after burn injury, causing post-burn cognitive defects. The diagnosis and treatment of cognitive dysfunctions as burn injury sequelae are of great importance. In this review, we address the major manifestations and interventions of post-burn cognitive defects, as well as the mechanisms involved in memory defect, including neuroinflammation, destruction of BBB, and hormone imbalance.

Facile fabrication of micropattern surfaces with controlled wettability on PDMS-modified fiber membranes for cell patterning.

Various cell culture substrates have been developed for cell patterning to control cell distributions and orientations in tissue engineering, drug screening and regenerative medicine. In this study, a preparation method of modified fiber membranes was applied in the field of cell patterning, and the obtained fiber membranes guided the cell distributions and orientations flexibly. The aligned electrospinning fiber membranes were dip-coated with polydimethylsiloxane (PDMS) to improve the stability of wettability, and then it was treated with oxygen plasma with a photomask to obtain a hydrophilic-hydrophobic surface micropattern. The morphologies, wettabilities and chemical structures of the membranes were analyzed by using a scanning electron microscope (SEM), drop shape analysis instrument, energy dispersive spectrometer (EDS) and Fourier transform infrared (FTIR) spectrometer. The L929 cells were cultured on the obtained membranes to observe the controlled cell distributions and orientations by using a SEM and fluorescence microscope. The results indicate that the treated membranes have the ability to control both cell distributions and orientations simultaneously. This method offers a novel approach to develop cell culture substrates for cell patterning in tissue engineering.