Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening.

BACKGROUND: Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. METHODS: PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. RESULTS: In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. CONCLUSIONS: ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

Thyroid disorders and gastrointestinal dysmotility: an old association.

Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.

Polysarcosine-Coated liposomes attenuating immune response induction and prolonging blood circulation.

HYPOTHESIS: Liposomes coated with long polysarcosine (PSar) chains at a high density might enable long blood circulation and attenuate accelerated blood clearance (ABC) phenomenon. EXPERIMENTS: In this study, we controlled the length (23, 45, 68 mers) and density (5, 10, 15 mol%) of PSar on liposomal coatings and, furthermore, investigated the effects of PSar length and density on the blood circulation time, biodistribution, immune response, and ABC phenomenon induction. Length-controlled PSar-bound lipids (PSar-PEs) were synthesized using a click reaction and inserted into bare liposomes at different combinations of chain lengths and proportions. FINDINGS: Although all PSar-coated liposomes (PSar-lipos) had similar morphological, physical, and chemical properties, they had different blood circulation times and biodistribution, and exerted varied effects on the immune system. All PSar-lipos with different PSar length and density showed a similar anti-PSar IgM response. Liposomes modified with the longest PSar chain (68 mers) at a high density (15 mol%) showed the longest blood circulation time and, additionally, attenuated ABC phenomenon compared with PEG-lipo. The ex vivo analysis of the biodistribution of liposomes revealed that a thick PSar layer enhanced the blood circulation time of liposomes due to the reduction of the accumulation of liposomes in the liver and spleen. These findings provide new insights into the relationship between IgM expression and ABC phenomenon inhibition.

Direct contact with endothelial cells drives dental pulp stem cells toward smooth muscle cells differentiation via TGF-ß1 secretion.

AIM: Prevascularization is vital to accelerate functional blood circulation establishment in transplanted engineered tissue constructs. Mesenchymal stem cells (MSCs) or mural cells could promote the survival of implanted endothelial cells (ECs) and enhance the stabilization of newly formed blood vessels. However, the dynamic cell-cell interactions between MSCs, mural cells and ECs in the angiogenic processes remain unclear. This study aimed to explore the interactions of human umbilical vein ECs (HUVECs) and dental pulp stem cells (DPSCs) in an in vitro cell coculture model. METHODOLOGY: Human umbilical vascular ECs and DPSCs were directly cocultured or indirectly cocultured with transwell inserts in endothelial basal media-2 (EBM-2) supplemented with 5% FBS for 6 days. Expression of SMC-specific markers in DPSCs monoculture and HUVEC+DPSC cocultures was assessed by western blot and immunofluorescence. Activin A and transforming growth factor-beta 1 (TGF-ß1) in conditioned media (CM) of HUVECs monoculture (E-CM), DPSCs monoculture (D-CM) and HUVEC+DPSC cocultures (E+D-CM) were analysed by enzyme-linked immunosorbent assay. TGF-ß RI kinase inhibitor VI, SB431542, was used to block TGF-ß1/ALK5 signalling in DPSCs. RESULTS: The expression of SMC-specific markers, α-SMA, SM22α and Calponin, were markedly increased in HUVEC+DPSC direct cocultures compared to that in DPSCs monoculture, while no differences were demonstrated between HUVEC+DPSC indirect cocultures and DPSCs monoculture. E+D-CM significantly upregulated the expression of SMC-specific markers in DPSCs compared to E-CM and D-CM. Activin A and TGF-ß1 were considerably higher in E+D-CM than that in D-CM, with upregulated Smad2 phosphorylation in HUVEC+DPSC cocultures. Treatment with activin A did not change the expression of SMC-specific markers in DPSCs, while treatment with TGF-ß1 significantly enhanced these markers' expression in DPSCs. In addition, blocking TGF-ß1/ALK5 signalling inhibited the expression of α-SMA, SM22α and Calponin in DPSCs. CONCLUSIONS: TGF-ß1 was responsible for DPSC differentiation into SMCs in HUVEC+DPSC cocultures, and TGF-ß1/ALK5 signalling pathway played a vital role in this process.

Fracture Resistance of Endodontically Treated Maxillary Premolars with Non-carious Cervical Lesions Restored with Different Post Systems.

OBJECTIVE: To test the hypothesis that the (i) presence of non-carious cervical lesions (NCCLs) and (ii) type of post system have no effect on the fracture resistance and pattern in endodontically treated maxillary premolars. METHODS: Human maxillary first premolars (n=60) with two root canals were randomly allocated into four groups (n=15). Buccal wedge-shaped NCCLs were prepared in 45 teeth specimens. Following root canal treatment, the specimens were randomly divided into (i) composite resin core (CRC); (ii) NCCLs + composite resin core (NCCL+CRC); (iii) NCCLs+prefabricated fibre-reinforced composite post + composite resin core (NCCL+PFRC+CRC); (iv) NCCLs+custom fibre posts + composite resin core (NCCL+CFP+CRC). All specimens were subjected to thermocycling (5°C to 55°C/5000 cycles). The compressive load was applied non-axially to the palatal cusp with a universal testing machine at a crosshead speed of 0.5 mm/min at a 30° angle until fracture. Fracture patterns were examined using a loupe magnification (2.5×) under transillumination. Statistical analyses were performed using non-parametric tests and pairwise comparisons of the load-to-fracture among the groups. Chi-square test was used to analyse the fracture patterns (P=0.05). RESULTS: Fracture resistance of NCCL+PFRC+CRC was significantly higher than NCCL+CRC (P=0.011), while NCCL+CFP+CRC did not show any significant difference when compared to NCCL+CRC (P=0.089). No statistical difference was found between CRC, NCCL+PFRC+CRC and NCCL+CFP+CRC (P=1.000). The frequencies of favourable fracture patterns in descending orders were as follows: CRC (80%), NCCL+CFP+CRC (73%), NCCL+PFRC+CRC (60%), and NCCL+CRC (40%). Chi-square test did not show significant differences in fracture patterns among all groups (P=0.110). CONCLUSION: Restoration of the endodontically treated maxillary premolars with NCCLs, with or without post, resulted in similar fracture resistance as their counterparts without NCCLs. Placement of a prefabricated fibre-reinforced composite post exhibited greater fracture resistance to the maxillary premolars with restored NCCLs than those without a post. (EEJ-2022-06-077).

Effects of L-Chg10-Teixobactin on Viability, Proliferation, and Osteo/Odontogenic Differentiation of Stem Cells from Apical Papilla.

INTRODUCTION: Intracanal medicament is one of the essential steps for ensuring success in regenerative endodontic procedures. L-Chg10-teixobactin is a novel antimicrobial agent that exhibited potent antibacterial and antibiofilm effects against Enterococcusfaecalis at low concentrations compared with ampicillin. At the same time, its cytotoxicity on dental stem cells has not been studied. This study aimed to investigate the effects of L-Chg10-teixobactin on the viability, proliferation, migration, and osteo/odontogenic differentiation of stem cells from apical papilla (SCAPs). MATERIALS AND METHODS: SCAPs isolated from immature human third molars were treated with various concentrations of L-Chg10-teixobactin, calcium hydroxide, and dimethyl sulfoxide. The viability and proliferation of SCAPs were assessed using the LIVE/DEAD Viability/Cytotoxicity Kit and Cell Counting Kit-8. A scratch wound healing test was used to evaluate the lateral migration capacity of SCAPs. Alkaline phosphatase (ALP) activity, calcium mineralization ability tests -ie, ALP staining and alizarin red S staining, and quantitative real-time polymerase chain reaction were performed to assess the osteo /odontogenic differentiation of SCAPs. RESULTS: The tested concentrations of L-Chg10-teixobactin (0.01, 0.02, and 0.03 mg/mL), 1 mg/mL calcium hydroxide, and 0.03% dimethyl sulfoxide had no significant cytotoxic effect on SCAPs at any time point (P > .05). Besides, there were no significant differences between the control and experimental groups in SCAPs' viability, proliferation, and migration. L-Chg10-teixobactin upregulated the gene expression of osteo/odontogenic markers in SCAPs, while no significant difference was found in the ALP activity and alizarin red S staining. CONCLUSIONS: L-Chg10-teixobactin demonstrated excellent biocompatibility on SCAPs at concentrations from 0.01 to 0.03 mg/mL and potentially enhance the osteo/odontogenic differentiation of SCAPs; suggesting its promising role as root canal medicament for regenerative endodontic procedures.

High-performance visible-near-infrared photodetector based on the N2200/Sb2Se3 nanorod arrays organic-inorganic hybrid heterostructure.

Antimony selenide (Sb2Se3) is a suitable candidate for a broadband photodetector owing to its remarkable optoelectronic properties. Achieving a high-performance self-powered photodetector through a desirable heterojunction still needs more efforts to explore. In this work, we demonstrate a broadband photodetector based on the hybrid heterostructure of Sb2Se3 nanorod arrays (NRAs) absorber and polymer acceptor (P(NDI2OD-T2), N2200). Owing to the well-matched energy levels between N2200 and Sb2Se3, the recombination of photogenerated electrons and holes in N2200/Sb2Se3 hybrid heterostructure is greatly inhibited. The photodetector can detect the wavelength from 405 to 980 nm, and exhibit high responsivity of 0.39 A/W and specific detectivity of 1.84 × 1011 Jones at 780 nm without bias voltage. Meanwhile, ultrafast response rise time (0.25 ms) and fall time (0.35 ms) are obtained. Moreover, the time-dependent photocurrent of this heterostructure-based photodetector keeps almost the same value after the storge for 40 days, indicating the excellent stability and reproducibility. These results demonstrate the potential application of a N2200/Sb2Se3 NRAs heterojunction in visible-near-infrared photodetectors.

Trans-cinnamaldehyde-Biosurfactant Complex as a Potent Agent against Enterococcus faecalis Biofilms.

Enterococcus faecalis is an opportunistic microbial pathogen frequently associated with diverse infections, including those of the skin and teeth, as well as those from surgical wounds. It forms robust biofilms that are highly tolerant to most antimicrobials and first-line antibiotics. Therefore, investigating alternative strategies to eradicate its biofilms is a critical need. We recently demonstrated that trans-cinnamaldehyde (TC) potently kills E. faecalis biofilm cells and prevents biofilm recovery, and yet, the extreme hydrophobicity of TC hampers clinical translation. Here, we report that a complex of TC with an FDA-approved biosurfactant (acidic sophorolipid/ASL) significantly reduces the bacterial viability and biomass of E. faecalis biofilms, compared to TC alone. A confocal laser-scanning microscopic analysis demonstrated that the TC-ASL treatment significantly decreased the biofilm thickness and volume. In conclusion, our study highlights the anti-biofilm potential of the newly developed TC-ASL.

A techno-psychological approach to understanding problematic use of short-form video applications: The role of flow.

Short-form video applications (SVAs) have been gaining increasing popularity among users, which has raised the concern of problematic SVA use. Flow-a positive experience in which individuals feel immersion, enjoyment, temporal dissociation, and curiosity-contributes to the development of problematic SVA use. Most of the prior research examined the motivations of flow and the self-traits that trigger flow, but paid limited attention to the technological affordances of smartphone applications that facilitate users' flow. Algorithm recommendation, multimodality, and low-cost interaction are three affordances of SVAs. Thus, drawing upon the stimulus-organism-response (S-O-R) framework, this study proposes a mediation model to examine how these affordances influence problematic SVA use through flow. An online survey (N = 621) showed that algorithm recommendation was negatively associated with problematic SVA use but was not significantly correlated to flow. Multimodality was directly and positively associated with problematic SVA use. Meanwhile, the relationship between these two variables were mediated by flow. Low-cost interaction had an indirect link with problematic SVA use via flow, while the direct link between them was not significant. The results suggest that low-cost interaction is the affordance that is most likely to trigger flow and problematic SVA use, followed by multimodality. However, algorithm recommendation seems to be an affordance that is less likely to facilitate flow or cause problematic SVA use. Our proposed model not only enriches the S-O-R framework in the digital environment, but also denotes a techno-psychological approach to examine problematic use of SVAs and other digital applications. Moreover, the findings offer practical implications for optimizing SVAs' technological affordances to properly manage problematic SVA use.

Health Effects of Probiotics on Nonalcoholic Fatty Liver in the Life Cycle Based on Data Analysis.

Objective: To observe the effect of intestinal probiotics in the treatment of nonalcoholic fatty liver disease (NAFLD) and the effect on liver function and inflammatory factors. Methods: 34 healthy rats were selected for the study and divided into 10 rats in the control group, 12 rats in the model group, and 12 rats in the treatment group according to the random number table method. The control group was given behavioral and lifestyle interventions, and the treatment group was given Bifidobacterium minus Black enteric capsules 5 g/(kg-d) by strong feeding method on the basis of the control group. The fatty liver index (FLI), liver ultrasound examination results, liver function, and inflammatory factor levels were compared among the three groups. After 8 weeks of treatment, there were statistically significant differences between the FLI values and liver ultrasound results of the three groups, and the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacylglycerol (TG), and total cholesterol (TC) levels of the observation group were lower than those of the control group and the model group. The levels of serum high molecular weight lipocalin (HMW-APN) and interleukin 22 (IL-22) in the observation group were higher than those in the control group, and the levels of tumor necrosis factor-α (TNF-α) were lower than those in the control and model groups, and the differences were statistically significant (P < 0.05). Conclusion: Intestinal probiotics can improve the clinical efficacy of patients with NAFLD, improve liver function, and alleviate the inflammatory response, in order to provide a theoretical basis for the clinical treatment of patients with NAFLD.

Antimicrobial Effects of L-Chg10-Teixobactin against Enterococcus faecalis In Vitro.

Objective: Teixobactin and its analogues are a new class of antibiotics that have no detectable bacterial resistance. This study was designed to determine the antibacterial and antibiofilm activities of a novel teixobactin analogue, L-Chg10-teixobactin, against two strains of Enterococcus faecalis (E. faecalis). Materials and Methods: The efficacy of L-Chg10-teixobactin against two strains of E. faecalis (ATCC 29212 and 47077) was determined using Clinical and Laboratory Standards Institute methods. L-Chg10-teixobactin was prepared at a stock concentration of 1 mg/mL in 5% DMSO. The minimum inhibitory concentration (MIC) was calculated using a two-fold serial broth dilution method, utilizing a 96-well plate. The minimum bactericidal concentration (MBC) was determined by plating the bacteria onto agar to define the concentration that resulted in 99.9% of bacterial death. Ampicillin was used as the control. The effect of L-Chg10-teixobactin on the inhibition of ATCC 47077 strain biofilm formation was determined by measuring the minimum biofilm inhibitory concentration (MBIC) using the safranin assay, while the eradication of the preformed biofilm was determined by measuring the minimum biofilm eradication concentration (MBEC) using the XTT assay. For nonlinear data, the log dose-response curve was plotted to calculate the optimum concentration using Excel (version 16.51, Microsoft® excel. 2021, Microsoft Corporation, Reymond, WA, USA). The data are presented as mean ± standard deviation (SD). Results: The MIC and MBC values of L-Chg10-teixobactin against both strains of E. faecalis were 0.8 µg/mL. The MIC of ampicillin was 1.25 µg/mL for ATCC 29212 and ranged from 1.25 to 5 µg/mL for ATCC 47077. The MBC of ampicillin for ATCC 29212 and ATCC 47077 was 10 and 20 µg/mL, respectively. The MIC and MBC of ampicillin were much higher compared with those of L-Chg10-teixobactin. The MBEC80 of L-Chg10-teixobactin was 4.60 µg/mL for ATCC 47077, which was much lower than that of ampicillin (20 µg/mL). Conclusions:L-Chg10-teixobactin demonstrated potent antibacterial and antibiofilm effects against E. faecalis, suggesting its potential role an effective antibacterial and antibiofilm agent in endodontic treatment.

Metabolomics analysis reveals the renal protective effect of Panax ginseng C. A. Mey in type 1 diabetic rats.

The dry root and rhizome of Panax ginseng C. A. Mey has garnered much interest owing to its medicinal properties against diabetes and cardiovascular diseases. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS)-based metabolomics approach was used to illustrate the therapeutic mechanisms of ginseng extract on the serum and urinary metabolic profiles in streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. Pharmacological and renal parameters in response to the administration of ginseng were also evaluated. In total, 16 serum endogenous metabolites and 14 urine endogenous metabolites, including pyruvic acid, indoleacetic acid, and phenylacetylglycine, were identified as potential biomarkers for diabetes. Pathway enrichment and network analysis revealed that the biomarkers modulated by ginseng were primarily involved in phenylalanine and pyruvate metabolism, as well as in arginine biosynthesis. Moreover, the levels of several renal injury-related biomarkers in T1DM rats were significantly restored following treatment with ginseng. The administration of the extract helped maintain tissue structure integrity and ameliorated renal injury. The findings suggest that the regulatory effect of ginseng extract on T1DM involves metabolic management of diabetic rats, which subsequently attenuates T1DM-induced early renal dysfunction.

Correction: Investigation of plasma metabolomics and neurotransmitter dysfunction in the process of Alzheimer's disease rat induced by amyloid beta 25-35.

[This corrects the article DOI: 10.1039/C9RA00302A.].

Exploring Stress and Problematic Use of Short-Form Video Applications among Middle-Aged Chinese Adults: The Mediating Roles of Duration of Use and Flow Experience.

The pervasiveness of smartphones and the popularity of short-form video applications (SVAs), such as TikTok, among middle-aged Chinese adults have raised concerns about problematic SVAs use. Although a plethora of research has examined problematic smartphone use among teenagers and young adults, scarce attention has been paid to the middle-aged group. This study integrates the psychopathological approach and the compensatory use approach to explicate problematic SVAs use among middle-aged Chinese adults. We aim to examine the relationship between stress and problematic SVAs use via the mediating roles of duration of use and flow experience. A total of 194 middle-aged adults from across the nation participated in an online survey. The results showed that stress was positively associated with problematic SVAs use. We also found that duration of use positively mediated the relationship between stress and problematic SVAs use. Furthermore, a serial mediation effect of duration of use and flow experience was found. The findings suggest that the aforementioned two approaches are complementary to each other in explicating problematic SVAs use, but the compensatory use approach explains more than the psychopathological approach does. Flow experience extends the original compensatory use approach and demonstrates the importance of incorporating techno-psychological predictors in understanding problematic SVAs use.

Large and Dense Organic-Inorganic Hybrid Perovskite CH3NH3PbI3 Wafer Fabricated by One-Step Reactive Direct Wafer Production with High X-ray Sensitivity.

Lead halide perovskites with good optoelectronic properties and high attenuation of high-energy radiation are great candidates for X-ray radiation detectors. Large area, dense, and thick films or wafers are a prerequisite for these applications. In this paper, a one-step heat-assisted high-pressure press method is developed to directly prepare a large (the largest has a diameter of 80 mm) and thickness- and shape-controlled phase-pure organic-inorganic hybrid CH3NH3PbI3 wafer of densely packed large microcrystals from raw powder materials. Meanwhile, this method uses no solvent to achieve essentially 100% material utilization. The obtained wafers show good ambipolar carrier mobilities of ∼20 cm2 V-1 s-1 and a µτ product as high as 3.84 × 10-4 cm2 V-1. Under an X-ray source using an acceleration voltage of 40 kV, the perovskite wafer-based X-ray detector shows an X-ray sensitivity as large as 1.22 × 105 µC Gyair-1 cm-2 under a 10 V bias, the highest reported for any perovskite material. The method provides a convenient strategy for producing large perovskite wafers with good optoelectronic properties, which will facilitate the development of large perovskite devices.

Urinary and plasmatic metabolomics strategy to explore the holistic mechanism of lignans in S. chinensis in treating Alzheimer's disease using UPLC-Q-TOF-MS.

Schisandra chinensis (Turcz.) Baill (S. chinensis), a functional food, is used as a tonic and sedative agent in traditional Chinese medicine. Modern pharmacological research has proved that S. chinensis could prevent and treat age-related neurodegenerative diseases. The presence of bioactive lignans in S. chinensis is the main reason for its neuroprotective and cognitive enhancement effects. This study aimed to clarify the mechanism of lignans in S. chinensis in ameliorating learning and memory deficits in Alzheimer's disease (AD) animals. The step-down test and Morris water maze (MWM) test were used to verify the effects of lignans in S. chinensis on learning and memory in AD animals. Then, metabolomics approaches based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were used to clarify the mechanism of lignans in S. chinensis in treating AD. Finally, quantitative analysis of AD-related neurotransmitters in the brain was conducted after treatment with lignans in S. chinensis. In the MWM and step-down tests, lignans in S. chinensis showed a clear ability to ameliorate the impaired learning and memory of AD animals. A total of 31 endogenous metabolites were identified after treatment with lignans in S. chinensis, which were associated with lignans ameliorating learning and memory. These biomarkers were mainly associated with polyunsaturated fatty acid metabolism and amino acid and vitamin metabolism. Moreover, lignans in S. chinensis upregulated the levels of γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and glycine (Gly) and downregulate the level of aspartic acid (Asp). Lignans in S. chinensis might alleviate the neurotoxic effects of neurological inflammation and oxidative stress, Aß deposition, and tau phosphorylation via the regulation of multiple endogenous metabolic pathways during pathological AD. The research might provide useful support for the further study of pharmacology and new drug development of lignans in S. chinensis.

Systematically Characterize the Anti-Alzheimer's Disease Mechanism of Lignans from S. chinensis based on In-Vivo Ingredient Analysis and Target-Network Pharmacology Strategy by UHPLC⁻Q-TOF-MS.

Lignans from Schisandra chinensis (Turcz.) Baill can ameliorate cognitive impairment in animals with Alzheimer's disease (AD). However, the metabolism of absorbed ingredients and the potential targets of the lignans from S. chinensis in animals with AD have not been systematically investigated. Therefore, for the first time, we performed an in-vivo ingredient analysis and implemented a target-network pharmacology strategy to assess the effects of lignans from S. chinensis in rats with AD. Ten absorbed prototype constituents and 39 metabolites were identified or tentatively characterized in the plasma of dosed rats with AD using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Based on the results of analysis of the effective constituents in vivo, the potential therapeutic mechanism of the effective constituents in the rats with AD was investigated using a target-network pharmacology approach and independent experimental validation. The results showed that the treatment effects of lignans from S. chinensis on cognitive impairment might involve the regulation of amyloid precursor protein metabolism, neurofibrillary tangles, neurotransmitter metabolism, inflammatory response, and antioxidant system. Overall, we identified the effective components of lignans in S. chinensis that can improve the cognitive impairment induced by AD and proposed potential therapeutic metabolic pathways. The results might serve as the basis for a fundamental strategy to explore effective therapeutic drugs to treat AD.

Pharmacodynamic and urinary metabolomics studies on the mechanism of Schisandra polysaccharide in the treatment of Alzheimer's disease.

Schisandra chinensis (Turcz.) Baill is produced mainly in northeast China, Korea and Japan. Its fruit has been used in food as a nutritional and functional ingredient for centuries. Polysaccharide is an important chemical component in Schisandra. Previous studies have shown that Schisandra polysaccharide (SCP) could be used to improve cognitive function clinically and treat age-related neurodegenerative disorders. In this study, a urinary metabolomics method based on ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was established to investigate the change of endogenous metabolites in an amyloid ß-protein (Aß) 25-35-induced Alzheimer's disease (AD) rat model. Meanwhile, levels of 9 neurotransmitters were evaluated with ultrahigh-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-TQ-MS) to explore the therapeutic mechanisms of SCP on the AD rat model. Additionally, the synthesis of phosphorylated tau protein (p-tau), acetylcholinesterase (AchE) activity and oxidative damage in the brain of the AD rats were assessed using glycogen synthase kinase-3ß (GSK3ß), AchE and antioxidant assays, NOS (nitric oxide synthase) and SOD (superoxide dismutase), respectively. The results indicated that the AD model was established successfully and the inducement of Aß25-35 caused the phosphorylation of tau protein and the deposition of Aß. In the AD model rats, the levels of AchE, GSK-3ß and NOS were significantly elevated and SOD activity was reduced. In the hippocampus of the model rats, the contents of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, taurine, serotonin and dopamine were significantly decreased and the contents of glutamate and aspartic acid were increased significantly. However, SCP could reduce the degree of phosphorylation of tau protein, the deposition of Aß and oxidative damage and reverse these changes of neurotransmitters in the AD rats. In a metabolomics study, a total of 38 metabolites were finally identified as potential biomarkers of AD and all of them had a significant recovery compared with the AD model after SCP administration. Metabolomics studies have shown that SCP plays a role in protecting the central nervous system, regulating intestinal microbial metabolism, regulating energy metabolism, and promoting antioxidant effects by regulating the levels of endogenous metabolites in related pathways. This is first report of the use of urine metabolomics combined with the evaluation of 9 neurotransmitter levels to investigate the mechanism of SCP on the treatment of AD.

Investigation of plasma metabolomics and neurotransmitter dysfunction in the process of Alzheimer's disease rat induced by amyloid beta 25-35.

Alzheimer's disease (AD) has become one of the major diseases endangering the health of the elderly. Clarifying the features of each AD animal model is valuable for understanding the onset and progression of diseases and developing potential treatments in the pharmaceutical industry. In this study, we aimed to clarify plasma metabolomics and neurotransmitter dysfunction in the process of AD model rat induced by amyloid beta 25-35 (Aß 25-35). Firstly, Morris Water Maze (MWM) test was used to investigate cognitive impairment in AD rat after 2, 4 and 8 weeks of modelling. Based on this, the effects on levels of AD-related enzymes and eight neurotransmitters were analyzed. And plasma metabolomics analysis based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to research the metabolic disturbances in the process of AD rat. The results shown the injury on the spatial learning ability of AD rats was gradually aggravated within 4 weeks, reached the maximum at 4 weeks and then was stable until 8 weeks. During 8 weeks of modeling, the levels of enzymes including ß-secretase, γ-secretase, glycogen synthase kinase-3ß (GSK-3ß), acetyl cholinesterase (AchE) and nitric oxide synthase (NOS) were significant increased in the plasma of AD rats. The neurotransmitter dysfunction was mainly involved in γ-aminobutyric acid (GABA), acetyl choline (Ach), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE). 17 endogenous metabolites correlated with AD were successfully detected in the metabolomics analysis. These metabolites were mainly involved in fatty acids, sphingolipids, and sterols metabolisms, vitamin metabolism, and amino acid metabolism. These metabolites might be the potential biomarkers that correctly mark different stages of AD. The study on peripheral plasma indices reflecting the process of AD laid the foundation for understand the pathophysiology of AD and find an effective and radical cure. And the rules of endogenous metabolic disorder in AD rats also have a certain guiding significance for the future study of food-drug interactions at different stages of AD.

Multi-inch single-crystalline perovskite membrane for high-detectivity flexible photosensors.

Single crystalline perovskites exhibit high optical absorption, long carrier lifetime, large carrier mobility, low trap-state-density and high defect tolerance. Unfortunately, all single crystalline perovskites attained so far are limited to bulk single crystals and small area wafers. As such, it is impossible to design highly demanded flexible single-crystalline electronics and wearable devices including displays, touch sensing devices, transistors, etc. Herein we report a method of induced peripheral crystallization to prepare large area flexible single-crystalline membrane (SCM) of phenylethylamine lead iodide (C6H5C2H4NH3)2PbI4 with area exceeding 2500 mm2 and thinness as little as 0.6 µm. The ultrathin flexible SCM exhibits ultralow defect density, superior uniformity and long-term stability. Using the superior ultrathin membrane, a series of flexible photosensors were designed and fabricated to exhibit very high external quantum efficiency of 26530%, responsivity of 98.17 A W-1 and detectivity as much as 1.62 × 1015 cm Hz1/2 W-1 (Jones).