A MnO2 nanosheet-mediated CRISPR/Cas12a system for the detection of organophosphorus pesticides in environmental water.

Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.

Molecular Evolution of SNAREs in Vitis vinifera and Expression Analysis under Phytohormones and Abiotic Stress.

SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) play a key role in mediating a variety of plant biological processes. Currently, the function of the SNARE gene family in phytohormonal and abiotic stress treatments in grapevine is currently unknown, making it worthwhile to characterize and analyze the function and expression of this family in grapevine. In the present study, 52 VvSNARE genes were identified and predominantly distributed on 18 chromosomes. Secondary structures showed that the VvSNARE genes family irregular random coils and α-helices. The promoter regions of the VvSNARE genes were enriched for light-, abiotic-stress-, and hormone-responsive elements. Intraspecific collinearity analysis identified 10 pairs collinear genes within the VvSNARE family and unveiled a greater number of collinear genes between grapevine and apple, as well as Arabidopsis thaliana, but less associations with Oryza sativa. Quantitative real-time PCR (qRT-PCR) analyses showed that the VvSNARE genes have response to treatments with ABA, NaCl, PEG, and 4 °C. Notably, VvSNARE2, VvSNARE14, VvSNARE15, and VvSNARE17 showed up-regulation in response to ABA treatment. VvSNARE2, VvSNARE15, VvSNARE18, VvSNARE19, VvSNARE20, VvSNARE24, VvSNARE25, and VvSNARE29 exhibited significant up-regulation when exposed to NaCl treatment. The PEG treatment led to significant down-regulation of VvSNARE1, VvSNARE8, VvSNARE23, VvSNARE25, VvSNARE26, VvSNARE31, and VvSNARE49 gene expression. The expression levels of VvSNARE37, VvSNARE44, and VvSNARE46 were significantly enhanced after exposure to 4 °C treatment. Furthermore, subcellular localization assays certified that VvSNARE37, VvSNARE44, and VvSNARE46 were specifically localized at the cell membrane. Overall, this study showed the critical role of the VvSNARE genes family in the abiotic stress response of grapevines, thereby providing novel candidate genes such as VvSNARE37, VvSNARE44, and VvSNARE46 for further exploration in grapevine stress tolerance research.

Porous α-Fe2O3 Hollow Rods/Reduced Graphene Oxide Composites Templated by MoO3 Nanobelts for High-Performance Supercapacitor Applications.

Porous α-Fe2O3 hollow rods/reduced graphene oxide (α-Fe2O3 HR/RGO) composites with unique morphological characteristics and a high surface area are prepared through a template strategy, which was systematically studied and found to have outstanding supercapacitive properties. When served as active material in a three-electrode setup, the optimized α-Fe2O3 HR/RGO-30, comprised 76.5 wt% α-Fe2O3 and 23.2 wt% RGO, was able to offer the largest specific capacitance of 426.3 F g-1, an excellent rate capability as well as satisfactory cycle life with capacitance retention of 87.7% and Coulombic efficiency of 98.9% after continuously charging/discharging at 10 A g-1 for beyond 10,000 cycles. Such electrochemical behaviors of the α-Fe2O3 HR/RGO-30 electrode can rival or even surpass those of many Fe2O3-based electrodes documented in the previous literature. Later, a symmetric supercapacitor cell of α-Fe2O3 HR/RGO-30//α-Fe2O3 HR/RGO-30 was fabricated. The assembled device offers the maximum energy density of 18.7 Wh kg-1, and also exhibits commendable rate capability, and features stable cycling durability (with capacitance retention of 83.2% together with a Coulombic efficiency of 99.3% after 10,000-cycle charge/discharge at 5 A g-1). These notable electrochemical performances enable the α-Fe2O3 HR/RGO-30 composite to be a high-potential material for advanced energy storage systems.

Accelerometer-measured sedentary volume and bouts during the segmented school day among Chinese school students.

Background: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1-4 min, 5-9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1-4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1-4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

The RNA-binding protein ZFP36 strengthens innate antiviral signaling by targeting RIG-I for K63-linked ubiquitination.

Innate immunity is the first line of defense against infections, which functions as a significant role in resisting pathogen invasion. Rapid immune response is initiated by pattern recognition receptors (PRRs) quickly distinguishing "self" and "non-self." Upon evolutionarily conserved pathogen-associated molecular pattern (PAMP) is recognized by PRRs, innate immune response against infection is triggered via an orchestration of molecular interaction, cytokines cascades, and immune cells. RIG-I plays a critical role in type I interferon (IFN-I) production by direct recognition of cytoplasmic double-stranded viral RNA. However, the activation mechanism of RIG-I is incompletely understood. In this study, we reported RNA-binding protein ZFP36 as a positive regulator of RIG-I-mediated IFN-I production. ZFP36 is a member of Zinc finger proteins (ZFPs) characterized by the zinc finger (ZnF) motif, which broadly involved gene transcription and signal transduction. However, its role in regulating antiviral innate immune signaling is still unclear. We found that ZFP36 associates with RIG-I and potentiates the FN-ß production induced by SeV. Mechanistically, ZFP36 promotes K63-linked polyubiquitination of RIG-I, mostly at K154/K164/K172, thereby facilitating the activation of RIG-I during infection. While the mutant ZFP36 (C118S/C162S) failed to increase polyubiquitination of RIG-I and SeV induced FN-ß. Our findings collectively demonstrated that ZFP36 acts as a positive regulator in antiviral innate immunity by targeting RIG-I for K63-linked ubiquitination, thus improving our understanding of the activation mechanism of RIG-I.

Molecular characterization and biofilm formation ability of Enterococcus faecium and Enterococcus faecalis bloodstream isolates from a Chinese tertiary hospital in Beijing.

To investigate the molecular characteristics and biofilm-forming ability of 116 Enterococcus faecium (Efm) and 72 Enterococcus faecalis (Efs) isolates obtained from patients with bloodstream infections (BSI) at a Chinese hospital between July 2011 and March 2018. The presence of glycopeptide resistance genes and five virulence genes (esp, gelE, asa1, hyl, and cylA) was screened using two multiplex PCR. MLST was used to assess the clonality. Crystal violet staining was used to detect biofilms. Vancomycin resistance was detected in 30.1% of Efm and 2.8% of Efs isolates, respectively. All VRE strains carried the vanA gene. The esp, gelE, asa1, and cylA genes in 72 Efs strains were detected at 62.5%, 84.7%, 84.7%, and 69.4%, respectively. Among the 116 Efm isolates, 74.1% and 25.8% carried esp and hyl, respectively. The esp gene was significantly associated with vancomycin-resistant Efm (VREfm) compared to vancomycin-susceptible Efm (VSEfm). In total, 91.7% of Efs and 20.0% of Efm produced biofilms. Twenty-six STs were identified among the 72 Efs isolates, with ST4 (29.2%) being the predominant. In total, 116 Efm strains were grouped into 26 STs, with ST78 (46.6%) being the predominant. Both VREfm (41.7%) and VSEfm (48.8%) were dominant in ST78. There is no clear evidence suggesting that some STs are associated with vancomycin resistance or biofilm formation. Both Efm and Efs BSI isolates showed a polyclonal pattern with a dominant clone and many unique types, implying the coexistence of clonal dissemination and an influx of new clones. The horizontal transmission of resistance genes may play a more important role in VREfm prevalence than clonal expansion.

Associations between 24-h movement behaviours and BMI in Chinese primary- and middle- school students.

Purposes: This cross-sectional study aimed to examine the associations between the 24-h movement behaviours and body mass index (BMI) of students from China by using compositional data analysis. Methods: A total of 389 students aged 6-16 years participated in this study. Accelerometers were used to measure moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SED), and sleep. Weight and height were objectively measured. The association between 24-h movement and BMI was analyzed by using compositional data analysis. Results: Time reallocation using minutes and proportions created major differences to the results. Reallocating 10 min from other movement behaviours to MVPA was associated with decreased BMI z-score of 1.372 to 0.158 among primary-school students. Reallocating 10 min from sleep and SED to MVPA, and from sleep and SED to LPA were associated with decreased BMI z-score of 0.505 to 0.017 among middle-school students. Reallocating 10% of time from all other components to SED and sleep were associated with a higher BMI z-score by 0.148 (95%CI: 0.020; 0.276) and 0.125 (95%CI: 0.046; 0.204), while reallocating time to MVPA was associated with a decrease in BMI z-scores of 0.132 (95%CI: -0.193; -0.070) among primary-school students. Reallocating 10% of time from all other components to SED was associated with a higher BMI z-score of 0.254 (95%CI: 0.165; 0.345), whereas reallocating time to MVPA and LPA was associated with a decrease in BMI z-scores of 0.039 (95%CI: -0.073; -0.005) and 0.093 (95%CI: -0.153; -0.033) among middle-school students. Conclusion: Research results of 10-min one-to-one reallocation may be treated cautiously due to uneven distribution of time in 24-h movement behaviours. Based on the results of 10% one-to-remaining reallocation, replacing SED with MVPA may be an appropriate target for adiposity intervention in primary-school students, while increasing MVPA or LPA at the expense of SED may be effective in controlling adiposity of middle-school students in China.

[Recent research on inhaled nitric oxide in preterm infants with a gestational age of <34 weeks]. / 胎龄<34å‘¨æ—©äº§å„¿ä¸€æ°§åŒ–æ°®å¸å ¥çš„ç ”ç©¶è¿›å±•.

Nitric oxide is a messenger molecule for vasodilation of vascular smooth muscle cells, and inhaled nitric oxide (iNO) can dilate pulmonary blood vessels and reduce pulmonary vascular resistance, thereby reducing pulmonary artery pressure, but with no influence on systemic circulation pressure. Guidelines in China and overseas recommend the use of iNO in full-term infants and late preterm infants, and it has been proved that it has a marked effect on persistent pulmonary hypertension and hypoxic respiratory failure in such infants. However, recent studies have shown that there is an increase in the off-label use of iNO in preterm infants with a gestational age of <34 weeks. This article reviews the research progress on the efficacy, safety, timing, dose, and withdrawal mode of iNO and its combination with vasoactive drugs in the treatment of preterm infants with a gestational age of <34 weeks in China and overseas, so as to provide a reference for clinical application.

Outcome and safety of intracardiac echocardiography guided left atrial appendage closure within zero-fluoroscopy atrial fibrillation ablation procedures.

BACKGROUND: Simultaneous atrial fibrillation (AF) catheter ablation and left atrial appendage closure (LAAC) are sometimes recommended for both rhythm control and stroke prevention. However, the advantages of intracardiac echocardiography (ICE) guidance for this combined procedure have been scarcely reported. We aim to evaluate the clinical outcomes and safety of ICE-guided LAAC within a zero-fluoroscopy catheter ablation procedure. METHODS AND RESULTS: From April 2019 to April 2020, 56 patients with symptomatic AF underwent concomitant catheter ablation and LAAC. ICE with a multi-angled imaging protocol mimicking the TEE echo windows was used to guide LAAC. Successful radiofrequency catheter ablation and LAAC were achieved in all patients. Procedure-related adverse event rate was 3.6%. During the 12-month follow-up, 75.0% of patients became free of arrhythmia recurrences and oral anticoagulants were discontinued in 96.4% of patients. No ischemic stroke occurred despite two cases of device-related thrombosis versus an expected stroke rate of 4.8% based on the CHA2 DS2 -VASc score. The overall major bleeding events rate was 1.8%, which represented a relative reduction of 68% versus an expected bleeding rate of 5.7% based on the HAS-BLED score of the patient cohort. The incidence of iatrogenic atrial septal defect secondary to single transseptal access dropped from 57.9% at 2 months to 4.2% at 12 months TEE follow-up. CONCLUSION: The combination of catheter ablation and LAAC under ICE guidance was safe and effective in AF patients with high stroke risk. ICE with our novel protocol was technically feasible for comprehensive and systematic assessment of device implantation.

Nonlinearity-mediated collimation of optical beams.

We investigated the evolutions of optical beams in an optical system composed of free spaces and nonlocal nonlinear media layers in a cascaded manner. From an application point of view, two kinds of evolution processes for Gaussian beams, nonlinearity-mediated collimation and switching from breathers to solitons, were discussed in details. By adjusting the input optical power, the collimating, the compressing and the expanding of optical beams are convenient to be controlled.

Spatial solitons with complicated structure in nonlocal nonlinear media: erratum.

This erratum corrects the range of the degree of nonlocality σ, in which the out-of-phase bound-state solitons can stably exist in our paper [Opt. Express24, 28784 (2016)10.1364/OE.24.028784].

SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS.

Mitochondrial virus-induced signal adaptor (MAVS), also known as VISA, IPS-1, and Cardif, is a crucial adaptor protein in the RIG-I-like receptor (RLR) signaling pathway. Upon viral infection, RIG-I recognizes viral dsRNA and further transfers it to mitochondria, where it binds to MAVS through its CARD domain, generating a series of signal cascades. Transduction through this signaling cascade leads to phosphorylation and nuclear translocation of interferon regulatory factor 3/7 (IRF3/IRF7) and activation of NF-κB, which ultimately produces type I interferon (IFN) and proinflammatory cytokines. Here, our experiments demonstrated that overexpression of SRY-related high-mobility group protein 9 (SOX9) significantly inhibited Sendai virus (SeV)-induced and MAVS-mediated activation of the IFN-ß promoter and ISRE. However, knocking out the expression of SOX9 in cells promoted SeV-induced IFN-ß promoter and ISRE activation. Further studies have shown that SOX9 interacts with MAVS and targets MAVS to inhibit the association of MAVS-TRAF2, thereby inhibiting MAVS-mediated TRAF2 ubiquitination. Taken together, these results indicate that SOX9 downregulates IFN-ß expression and antiviral signal transduction by targeting MAVS.

Associations between sleep duration, sleep quality, and weight status in Chinese children and adolescents.

BACKGROUND AND OBJECTIVE: The high prevalence of obesity is a serious problem, and sleep is considered to be a factor for obesity. This study aimed to examine the relationship between sleep duration, sleep quality, and weight status among children and adolescents in China and to explore whether the relationship between sleep duration and weight status is independent of sleep quality. Sex and age differences were also explored. METHODS: A cross-sectional research was conducted among 2019 children and adolescents (1029 boys and 990 girls) aged 8-16 years in Shanghai. An open-question was used to obtain data on sleep duration, which was categorized into the following four groups based on the age-specific National Sleep Foundation Sleep Duration Recommendations: 1) very short, 2) short, 3) recommended, and 4) long. The Pittsburgh Sleep Quality Index was used to assess sleep quality. Weight and height were measured for all participants. The variable weight status was estimated with the Chinese children and adolescent age- and sex-specific body mass index (BMI) and was categorized into overweight/obesity and normal weight. RESULTS: Short sleep duration (7-8 and 6-7 h for 6-13 and 14-16 years old, respectively) significantly increased odds of overweight/obesity (OR = 1.32, 95% CI: 1.06-1.64) compared with that of the recommended sleep duration (9-11 and 8-10 h for 6-13 and 14-16 years old, respectively). The relationship between the two variables existed independent of sleep quality. No significant relationship was found between sleep quality and overweight/obesity of children and adolescents. Sleep quality (OR = 1.07, 95% CI: 1.01-1.14) and short sleep duration (OR = 1.51, 95% CI: 1.06-2.13) increased the risk for overweight/obesity among girls, whereas no significant relationships between sleep duration, sleep quality, and overweight/obesity were found among boys. Short sleep duration increased the risk of overweight/obesity in children aged 8-13 years (OR = 1.34, 95% CI: 1.05-1.71), independent of sleep quality, but no significant relationships between these two variables existed for adolescents aged 14-16 years. CONCLUSIONS: Overall, short sleep duration increased the risks of overweight/obesity in children and adolescents in China, independent of sleep quality. This relationship is significant for girls and children aged 8-13 years instead of boys and adolescents aged 14-16 years. Interventions to extend the sleep duration of children and adolescents, especially girls and children aged 8-13 years in China, are necessary to improve their weight status.

Migraine and the risk of dementia: a meta-analysis and systematic review.

OBJECTIVES: To conduct a comprehensive systematic review and meta-analysis to explore the correlation between migraine and the risk of dementia. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched systematically. We selected cohort studies (prospective and retrospective) and case-control studies that reported migraine in patients with dementia, including vascular dementia. The pooled effects were analyzed to evaluate relative risk with 95% confidence intervals. RESULTS: In total, nine studies (two case-control and seven cohort studies) including 291,549 individuals were identified. These studies indicated that people with migraine (relative risk = 1.33; 95% confidence interval: 1.16-1.53) have an increased risk of all-cause dementia. Additionally, the pooled results of four studies showed that migraine is associated with an increased risk of vascular dementia (relative risk = 1.85; 95% confidence interval: 1.22-2.81; P = 0.004). CONCLUSIONS: Data from observational studies suggest that migraine may be a risk factor for dementia, particularly vascular dementia. More studies are warranted to explore the association between migraine and dementia and the potential common pathophysiological mechanisms.

Comparison of blood loss between tranexamic acid-soaked absorbable Gelfoam and topical retrograde injection via drainage catheter plus clamping in cervical laminoplasty surgery.

BACKGROUND: To compare the safety and efficacy of tranexamic acid (TXA)-soaked absorbable Gelfoam and the retrograde injection of TXA through a drain with drain-clamping in degenerative cervical laminoplasty patients. METHODS: Patients were assigned into either TXA retrograde injection (TXA-RI), TXA-soaked absorbable Gelfoam (TXA-Gel), or control groups. The demographics, operative measurements, volume and length of drainage, length of hospital stay, complete blood cell count, coagulopathy, postoperative complications, and blood transfusion were recorded. RESULTS: We enrolled 133 patients, with 44, 44, and 45 in the TXA-RI, TXA-Gel, and control groups, respectively. The baseline characteristics did not differ significantly among the three groups. The TXA-RI group exhibited a lower volume and length of postoperative drainage compared to the TXA-Gel and control groups (126.60 ± 31.27 vs. 156.60 ± 38.63 and 275.45 ± 75.27 mL; 49.45 ± 9.70 vs 58.70 ± 10.46 and 89.31 ± 8.50 hours, all P < 0.01). The TXA-RI group also had significantly shorter hospital stays compared to the control group (5.31 ± 1.18 vs 7.50 ± 1.25 days, P < 0.05) and higher hemoglobin and hematocrit levels (12.58 ± 1.67 vs 11.28 ± 1.76 g/dL; 36.62 ± 3.66% vs 33.82 ± 3.57%, both P < 0.05) at hospital discharge. In the TXA-RI and TXA-Gel groups, the D-dimmer (DD) and fibrinogen (FIB) were significantly lower than those in the control group after surgery (P < 0.05). None of the patients required blood transfusion. No complications, including thromboembolic events, were reported. CONCLUSION: Topical retrograde injection of TXA through a drain with drain-clamping at the conclusion of unilateral posterior cervical expansive open-door laminoplasty may effectively reduce postoperative blood loss and the length of hospital stays without increasing postoperative complications.

[Progress in the studies of circular RNA in prostate cancer].

Prostate cancer (PCa) has become one of the most common malignancies in men, and its incidence is increasing year by year in China. When PCa develops into castration-resistant PCa (CRPC), it deteriorates rapidly. So, it is important to find more sensitive molecular markers and effective therapeutic targets for the diagnosis and treatment of the malignancy. Circular RNA (circRNA) is a covalently closed loop non-coding RNA formed by reverse splicing, playing an important regulatory role in a variety of tumors. In recent years, many studies show that circRNA is involved in the regulation of PCa as miRNA sponge, binding with the RNA binding protein and other molecular sponges, and may be a potential molecular marker and therapeutic target for PCa. This review summarizes the advances in recent studies of circRNA in the development and progression of PCa, CRPC, and radiation-resistant PCa.

Adiabatic evolution of optical beams in nonlocal nonlinear media of gradual nonlocality.

We theoretically investigate the evolution of optical beams in nonlocal nonlinear media of gradual nonlocality, which is governed by the nonlocal nonlinear Schrödinger equation with variable coefficient. With the variational approach, the evolution equation of beam width is derived. When the characteristic length of response function gradually changes with any functional forms, beams can exhibit a kind of adiabatic evolution. The variational results are well confirmed by numerical simulations.

The challenge of diagnosis and treatment of neurosyphilis in China: results from a nationwide survey.

Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. METHODS: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. RESULTS: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65-10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63-6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24-4.99) were more likely to follow national guidelines for neurosyphilis treatment. CONCLUSION: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aß1-42 aggregation effectively ranged from 45.9-94.5 % at 20 µM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 µM, and it could disassemble the self-induced Aß1-42 aggregation fibrils with ratio of 57.1 % at 20 µM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aß aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aß1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

[Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway].

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.