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Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4 α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4 α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4 α expression, while silencing PXR upregulated HNF4 α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4 α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4 α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16 α -carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4 α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4 α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4 α ‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes. Activated PXR directly inhibits hepatocyte nuclear factor 4-alpha (HNF4 α) expression and thus inhibits HNF4 α -mediated transcriptional activation of the SLC2A2/ glucose transporter 2 (GLUT2) in hepatocytes, which reduces GLUT2 expression and hepatic glucose uptake, causing hyperglycemia. [Display omitted] [ABSTRACT FROM AUTHOR]

Antibiotics play an important role in human life, but the abuse of antibiotics not only damages people's health but also poses a potential threat to the environment. Hence, the development of a rapid and efficient antibiotic detection method has profound significance. Herein, a novel terbium-based metal-organic framework (Tb-MOF) [Tb 2 (0.5BPDC) 4 (BPDC)(DMF) 2.DMF] was prepared by a one-step solvothermal method. The framework structure of the synthesized Tb-MOF remained stable not only under different acidic and alkaline environments but also under different organic reagents. In view of the quenching effect of cefixime (CFX) on the fluorescence of Tb-MOF, a method for the detection of CFX was constructed with a linear range of 0.1–150 μM and a detection limit of 31.55 nM. The quenching mechanism was revealed by ultraviolet–visible absorption spectroscopy (UV–vis), fluorescence lifetime and density functional theory (DFT) to be attributed to the internal filtration effect (IFE) and photoinduced electron transfer (PET). Tb-MOF was applied to the quantitative analysis of CFX in environmental water samples and tablets, and the recovery rate was 98.4%–104.8%, which verified its practicability. Therefore, the prepared Tb-MOF is a potential fluorescence sensing platform for rapid and sensitive detection of CFX in actual samples. [Display omitted] • A novel fluorescent Tb-MOF was synthesized by a one-step solvothermal method. • The fluorescence of Tb-MOF can be quenched by cefixime with high selectivity. • A rapid and highly sensitive sensing method for the detection of cefixime was developed. • The possible fluorescence sensing mechanism was deduced by experiments and theoretical calculations. [ABSTRACT FROM AUTHOR]

Nonintubated spontaneous ventilation video-assisted thoracoscopic surgery (NI-VATS) has been investigated to reduce the adverse effects of tracheal intubation, mechanical ventilation, and general anesthesia in several thoracic diseases. We comparatively assess the comparison between NI-VATS vs intubated anesthesia VATS (I-VATS) on early outcomes of mediastinal lesion resection. Patients who underwent VATS resection for a mediastinal tumor between December 2015 and September 2018 were retrospectively included for analysis. Patients were divided into two groups according to anesthesia ventilation type: NI-VATS and I-VATS. Propensity score matching was applied to eliminate population bias. Intraoperative and postoperative variables were compared. A total of 198 patients was included; 75 patients underwent NI-VATS and 123 patients underwent I-VATS. After propensity score matching, both anesthesia time (173.81 vs 227.37 minutes, P <.001) and operation time (82.82 vs 133.49 minutes, P <.001) were shorter in the NI-VATS group. Bleeding (51.80 mL vs 56.73 mL, P =.90) and postoperative morbidity (10.9% vs 15.6%, P =.57) were similar between groups. Chest tube duration (1.11 vs 1.54 days, P =.04) was shorter in the NI-VATS group. Hospital duration after surgery (3.15 vs 5.35 days, P <.001) was shorter in the NI-VATS group. D-dimer after surgery was significantly higher in both groups, but NI-VATS decreased the change (577 vs 1624 μg/L, P <.001). Furthermore, a decrease in the use of postoperative opioids analgesics was seen in the NI-VATS group (31% vs 51%, P =.023). Mediastinal tumor resection is safe and feasible under NI-VATS. Better short-term outcomes suggest NI-VATS facilitates a more rapid recovery. Further multicenter prospective randomized investigation is warranted. [ABSTRACT FROM AUTHOR]

The development of effective and environmentally safe photocatalysts for the removal of antibiotics from aquatic environments remains an important issue. In this work, materials with different metal Pd mass loading ratios were prepared by loading TiO 2 with noble metal Pd after the introduction of oxygen vacancies. After the photocatalytic degradation of TC, it was found that the 0.5% Pd/TiO 2 -Vo photocatalyst showed good photocatalytic activity in the degradation of tetracycline, with a degradation efficiency of 95.04% in 2 h and a reaction rate constant 2.18 times higher than that of TiO 2. It was found that the introduction of oxygen vacancies and Pd loading could enhance the visible light response to overcome the drawback that TiO 2 could only be irradiated by UV while increasing the free carrier density and inhibiting electron-hole recombination to improve its photocatalytic degradation efficiency. Finally, the possible decomposition pathways and degradation products of TC were inferred by combining liquid chromatography mass spectrometry (LC MS). The findings of this work may provide a new approach to improving the photocatalytic activity of TiO 2. [Display omitted] • A Pd-loaded TiO 2 with oxygen vacancies (Pd/TiO 2 -Vo) composite was successfully synthesized. • Photocatalytic activity of TiO 2 was improved by palladium loading and oxygen vacancy introduction. • Pd/TiO 2 -Vo exhibited excellent degradation performance for tetracycline antibiotics. • Photocatalytic degradation mechanism of Pd/TiO 2 -Vo and the possible degradation pathways were revealed. [ABSTRACT FROM AUTHOR]

• A novel model-based optimization model is proposed for the AD plants' planning. • The proposed model determines the networks of the local biogas grid, location and size of facilities, and optimal biomass transportation routes. • A strategy is developed to choose mono-digestion or co-digestion system for AD plants. • The profitability and carbon emission of AD plants is assessed. The biomass resource is very abundant in rural areas because of diverse agricultural activities, which enables the biogas to substitute the natural gas for the energy supply in where the natural gas network cannot extend. Thanks to the flexibility of biogas whose physical characteristic is similar to natural gas, it can not only power the biogas-based generators in the power distribution system but also meet the local biogas demand through a local biogas grid, finally formulating a distributed local biomass-based integrated energy system (IES). In such a system, proper anaerobic digestion (AD) plants planning is of great importance as the cost of transporting biomass feedstock is costly due to its high weight per unit of energy generated. Conventional AD plants planning is usually formulated as optimization problems of biomass supply chain whose focus is the planning of the transportation routes from biomass supply node to the AD plants, neglecting the downstream of the supply chain from the AD plants to the end-users. In this paper, a novel comprehensive optimization model formulated as a mixed-integer second-order-cone problem (MISOCP) is proposed to minimize the total investment and energy supply costs of the local biomass-based IES and to determine the networks of local biogas grid, to plan facilities, e.g., biogas-based generators and AD plants, and to optimize biomass transportation routes. with consideration of the network physical characteristics. Additionally, considering the anaerobic co-digestion (AcoD) technology has better performance on biogas yield compared to anaerobic mono-digestion (AmoD), a strategy is developed to choose mono-digestion or co-digestion system for AD plants as well. This model is demonstrated with a real-world test system, and an environmental and economic assessment for evaluating the profitability of each AD plant is presented. The planning results showed that AcoD plant is most cost-competitive when the food waste and animal manure are locally-sufficient. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence demonstrates that traditional Chinese medicines that act on multiple targets could effectively treat various multi-etiological diseases, including cerebrovascular diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and so on. Previous studies have shown that crocin richments (GJ-4), Gardenia jasminoides J.Ellis extract, provide neuroprotective effects on cognitive impairments in AD mouse models. However, the mechanism how GJ-4 improves cognition remains still unclear.Purpose: The aim of this study was to uncover the protective effects and underlying mechanism of GJ-4 on PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mice.Methods: APP/PS1 mice were given GJ-4 (10, 20, and 50 mg/kg), donepezil (5 mg/kg) and memantine (5 mg/kg) orally at eight months of age for 12 consecutive weeks. Morris water maze and novel object recognition were conducted to assess the cognitive ability of mice. The release of inflammatory cytokines was determined by RT-PCR assay, and the pathological features of neurons and microglia were assayed by immunohistochemistry and immunofluorescence assay. The expression of Aβ-related proteins and signaling pathways were determined by Western blot.Results: The behavioral results revealed that GJ-4 ameliorated the cognitive deficits of APP/PS1 mice measured by Morris water maze and novel object recognition tests. Mechanism studies indicated that GJ-4 significantly decreased β-amyloid (Aβ) level through reducing Aβ production and promoting Aβ degradation. It has been reported that Aβ plaques trigger the hyper-phosphorylation of tau protein in APP/PS1 mice. Consistent with previous studies, hyper-phosphorylation of tau was also occurred in APP/PS1 mice in the present study, and GJ-4 inhibited Tau phosphorylation at different sites. Overwhelming evidence indicates that neuroinflammation stimulated by Aβ and hyperphosphorylated tau is involved in the pathological progression of AD. We found that GJ-4 suppressed neuroinflammatory responses in the brain through regulating phosphatidylinositide 3-kinase/AKT (PI3K/AKT) signaling pathway activation, and subsequent expression of inflammatory proteins and release of inflammatory cytokines.Conclusion: Altogether, GJ-4 ameliorated cognition of APP/PS1 transgenic mice through multiple targets, including Aβ, tau and neuroinflammation. This study provides a solid research basis for further development of GJ-4 as a potential candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Since the power system is undergoing a transition into a more flexible and complex system, it urges improvements in fault diagnosis techniques for the power system protection to avoid cascading damages at the occurrence of faults. Facing with challenges of massive data, several machine-learning based methods for identifying faults were proposed over the past years. In this paper, an overview of conventional and trending machine learning applications for the fault diagnosis are summarized. [ABSTRACT FROM AUTHOR]

• The same building geometries and the same thermal properties of building envelope for different seven climatic cities were assumed. • Energy conservation effect including saving amount and saving ratio were discussed annually and monthly among seven cities. • The inner mechanism of the difference was revealed from the hourly and daily perspectives through two extremely contrast climatic cities. • Guidance and reference were provided for both standard determination and behavioral energy saving for air conditioning systems. Indoor setting temperature is a key controllable parameter by users, highly impacting the total cooling energy usage. In this paper, the hourly cooling load of residential buildings is simulated for seven cities respectively when the cooling setting temperature (CST) increases by 1°C, and the dissimilarity and internal mechanism of the energy saving effect are discussed and revealed from the hourly and daily perspectives through two extremely contrast climatic cities. The results show that although the higher yearly energy saving amount (ESA) can appear in a hotter city, energy saving effect is all significant in different cities. The ESA in hotter months of hotter cities may not be higher than that in the corresponding months of cooler cities, and the hotter cities have more obvious platform features while the cooler cities have single peak features, and the peak value is much higher than the plateau value. The yearly cooling saving ratio (CSR) is higher in cooler cities because CSR depends on both the hourly CSR and its weightiness, and the proportion of the higher ratio hours in cool cities is larger. This study can provide references for both standard determination and behavioral energy saving for air conditioning systems. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine enables quick upgrade of antigen sequence to combat emerging new variants. In an observer-blinded, randomized, placebo-controlled phase 2 trial, immunologically naïve 300 adults and 150 older participants were enrolled and randomized (1:1:1) to receive two doses of 20 µg or 30 µg of a SARS-CoV-2 mRNA vaccine (SYS6006) or placebo. Adverse events (AEs) were recorded through 30 days after the second dose. Live virus neutralizing antibody (Nab), S1 protein-specific binding antibody (S1-IgG) and cellular immunity were tested. Results showed that robust wild-type Nab response was elicited with geometric mean titers of 91.3 and 84.9 in the adults, and 74.0 and 115.9 in the elders, 14 days following the second dose (Day 35) in the 20-µg and 30-µg groups, respectively. All seroconverted for wild-type Nab except two participants. Nab against Omicron BA.5 was mild. Robust wild-type S1-IgG response was induced with geometric mean concentrations of 2751.0 and 3142.2 BAU/mL in adults, and 2474.1 and 2993.5 BAU/mL in elders at Day 35 in the 20-µg and 30-µg groups, respectively. S1-IgG against Omicron BA.2 was induced. Cellular immunity was elicited, particularly in enzyme-linked immunospot assay. The most frequent AEs were injection-site pain and fever. Most reported AEs were grade 1 or grade 2. The AE incidences were similar following the first dose and second dose. No vaccination-associated serious AE was reported. In conclusion, two-dose vaccination with SYS6006 demonstrated good safety, tolerability and immunogenicity in immunologically naïve healthy participants aged 18 years or more. [ABSTRACT FROM AUTHOR]

Objectives Myasthenia gravis (MG) benefits from thymectomy. However, its unpredictable response to muscle relaxants and volatile anesthetic agents may result in muscle weakness and subsequently in postoperative myasthenic crisis. The aim of this study was to determine the surgical outcomes after spontaneous ventilation compared with conventional intubated video-assisted thoracoscopic thymectomy (spontaneous-ventilation video-assisted thoracic thymectomy [SV-VATT] vs intubated video-assisted thoracic thymectomy) in patients with MG. Methods Data from all minimally invasive thymectomy procedures performed at our institute between January 2009 and June 2016 were collected. Patient characteristics, perioperative results, and treatment outcomes between SV-VATT (group 1) and the intubated video-assisted thoracic thymectomy (group 2) groups were compared. Furthermore, a propensity score-matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner. Results Thirty-six patients were included in group 1 and 68 in group 2. Matching of patients according to propensity score resulted in a cohort that consisted of 27 patients in both groups. Patients had similar clinical characteristics in both groups. Operating time ( P = .07) and lowest pulse oxygen saturation ( P = .09) between the procedures were comparable after matching, but peak CO 2 level at the end of expiration was significantly greater in group 1 both before and after matching ( P < .01). Moreover, the incidence of postoperative myasthenic crisis and postoperative prolonged tracheal intubation was lower in group 1. The postoperative pain visual analog scale score ( P < .01) and the length of hospital stay ( P = .03) were shorter in group 1. Conclusions SV-VATT is a feasible procedure in patients with MG. It might be beneficial by reducing postoperative myasthenic crisis and postoperative prolonged tracheal intubation. Further prospective research is needed. [ABSTRACT FROM AUTHOR]

Renewable energy plays a key role in reducing carbon emissions. The electric power system is widely considered a platform to accommodate renewable energy because of the high efficiency in transmitting energy through electricity tie lines. However, most renewable energy generation is weather-dependent, bringing difficulties in balancing generations and electricity demands. There are two major solutions to address the imbalance problem. The first is to balance the fluctuation of renewable energy in time scales by deploying energy storage, but with huge costs and security risks. The other is to balance the fluctuation in spatial scales by enhancing the interconnection among electric power systems, which however results in a sharp increase in the fault current in many countries. The high level of fault current threatens the security of power system. In other words, the overrating fault current of electric power systems is one of the key bottlenecks for carbon neutrality. To mitigate the high-level fault current because of the interconnection, we propose a novel mechanism, namely fault current release. It achieves new functionalities with proven equipment at low cost and will create no impact on the electric power systems in normal operation. The simulation selected six representative electric power systems, including those in the USA, the UK, China, Brazil, Nigeria and IEEE reliable test system. Results show that the fault current release method enables an increase of renewable energy accommodation from 19.2% ∼ 47.2% to over 90%, much higher than the existing methods can do. Correspondingly, the emissions of CO 2 , NO X and SO X in these systems decrease by 67.84% ∼ 88.07%, 61.17% ∼ 88.24% and 58.25% ∼ 88.33%, respectively. The proposed method is also economical in that it can accommodate renewable energy at about one-tenth the cost of energy storage. Our findings hence suggest a promising way to build a carbon-free energy system. • Interconnection enables renewable energy penetration over 90%, but also increases the fault current level. • The proposed fault current release method effectively reduces the fault current with proven equipment at low cost. • Tight interconnection plus with fault current release achieves lower emission with lower cost compared to energy storages. [ABSTRACT FROM AUTHOR]

Pyramidal neuron (Pyn) hyperactivity in the anterior cingulate cortex (ACC) is involved in the modulation of pain. Previous studies indicate that the activation of α2 adrenoceptors (α2-ARs) by dexmedetomidine (DEX) is a safe and effective means of alleviating multiple types of pain. Here, we showed that systemically administered DEX can ameliorate the inflammatory pain induced by hindpaw injection of formalin (FA) and further examined the molecular and synaptic mechanisms of this DEX-elicited antinociceptive effect. We found that FA caused an increase in c -Fos expression in contralateral layer 2/3 (L2/3) ACC, and that intra-ACC infusion of DEX could also relieve phase 2 inflammatory pain behavior. DEX elicited an increase in the amplitude and frequency of miniature inhibitory post-synaptic currents (mIPSCs) and evoked IPSC amplitude, as well as a reduction in the hyperexcitability and both paired-pulse and excitation/inhibition ratios in contralateral L2/3 ACC Pyns of FA mice. These electrophysiological effects were associated with the upregulation of GABA A receptor (GABA A R) subunits. The interaction of phosphorylated Akt (p -Akt) with GABA A R subunits increased in the ACC following administration of DEX. These results suggest that DEX treatment reduces hyperactivity and enhances GABAergic inhibitory synaptic transmission in ACC Pyns, which produces analgesic effects by increasing GABA A R levels and activating the Akt signaling pathway. • DEX relieves FA-induced spontaneous inflammatory pain. • The hyperexcitability of contralateral L2/3 ACC Pyns is reduced by DEX. • DEX enhances GABAergic inhibitory synaptic transmission in ACC Pyns. • DEX alters neuronal and synaptic activity by enhancing active Akt/GABA A R complexes. [ABSTRACT FROM AUTHOR]

Abstract: Repeated injection of pegylated liposomes could elicit the disappearance of long-circulating characteristic, referred to as “accelerated blood clearance phenomenon.” ABC phenomenon typically occurs when entrapped drugs are not cytotoxic, but recently it was reported that multiple doses of pegylated liposomal topotecan, a cytotoxic drug, could also induce the phenomenon in rats. To reveal whether the phenomenon could be induced in dogs and the effect of time interval between doses on the magnitude of ABC, pLT was repeatedly injected into beagle dogs with a time interval of 7, 21 and 28 days. The anti-PEG Ig M levels were detected using ELISA. It was found that ABC phenomenon could be induced in dogs by pLT. Inter-individual difference in anti-PEG antibody production could be observed, and antibody levels were directly correlated with the magnitude of ABC. Furthermore, time interval between doses had marked effect on the magnitude of ABC phenomenon. When the time interval was prolonged from 1 week to 4 weeks, ABC phenomenon could be eliminated. By comparing the pharmacokinetic profiles of lipid vesicles and entrapped topotecan, it was found that “empty pegylated vesicles” be formed in circulation, which might be responsible for the occurrence of ABC phenomenon. [Copyright &y& Elsevier]

Abstract: 3-n-Butylphthalide (NBP) has been shown to have protective effects against ischemic stroke. In the present study, we investigated effects of l-3-n-butylphthalide (l-NBP) on the learning and memory impairment induced by chronic cerebral ischemia in rats. Male Wistar rats were administered 20 mg/kg l-NBP by gavage daily for 30 days after the bilateral common carotid artery clamping (two-vessel occlusion, 2-VO). Results showed that daily treatments of 20 mg/kg l-NBP significantly attenuated spatial learning deficits in Morris water maze (MWM) task. Results of long-term potentiation (LTP) indicated that treatment with 20 mg/kg l-NBP attenuated the inhibition of LTP in rat model of 2-VO. Moreover, l-NBP reduced glial fibrillary acidic protein (GFAP)-positive astrocytes induced by chronic cerebral ischemia. The present findings demonstrate the protective effect of l-NBP on chronic cerebral ischemia-induced hippocampus injury, which supports using l-NBP for therapy of cerebral ischemia in the future. [Copyright &y& Elsevier]

Alzheimer's disease (AD) is the most common neurodegenerative disease. AD has become an important social health problem but there are few therapeutic drugs. Many researchers devote to the development of drugs for the treatment of AD. GJ-4 is crocin enrichments from Gardenia jasminoides J. Ellis, and our previous studies have shown GJ-4 had potent neuroprotective effects on several AD animal models. However, the underlying mechanisms have not been fully elucidated. The aim of the present study was to explore the mechanism of GJ-4 on a Aβ 25-35 -intoxicated mouse model. The results demonstrated that GJ-4 treatment significantly improved spatial learning and memory abilities of the AD mice challenged by Aβ 25-35. Mechanistic study indicated that GJ-4 could alleviate endothelial dysfunction, as GJ-4 markedly reduced endothelial cell edema, as well as improved tight junction structures by up-regulating Zonula occludens-1 (ZO-1), Claudin-5 and Occludin expressions. Moreover, GJ-4 markedly reduced receptor for advanced glycation end products (RAGE) expression and increased low-density lipoprotein receptor-related protein-1 (LRP-1) expression, suggesting endothelial transduction and clearance of toxic species capabilities improved by GJ-4 treatment. The results also indicated that GJ-4 significantly decreased IL-6 and IL-1β mRNA expressions, as well as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions, implying the inhibition of glial activation and vascular inflammation by GJ-4 treatment. Furthermore, GJ-4 treatment inhibited glial activation mediated neuroinflammation through inhibiting high-mobility group box protein 1(HMGB-1)/RAGE/NF-κB signaling pathway, which might confer to the neuroprotection. In conclusion, our present study proved GJ-4 could protect the neurovascular unit (NVU), through attenuating endothelial cell damage, enhancing tight junction function, inhibiting of glial activation and protecting of neurons. This study provided evidence that the beneficial effects of GJ-4 on AD might be owing to its protection on NVU. [ABSTRACT FROM AUTHOR]