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(±)-Melichuniiones A and B (1 and 2), two novel enantiomeric pairs of lignan-phloroglucinol hybrids with an unprecedented beadlike core were isolated from the leaves of Melicope chunii , together with new analogues 3-6. Compounds 1 and 2 possess a unique dispiro [furan-2,5'-cyclopenta[ b ]furan-2',3''-furan] 5/5/5/5 tetracyclic skeleton. Their structures were established by extensive spectroscopic analyses, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 significantly reduces GPX4 levels, leading to the accumulation of lipid reactive oxygen species (lipid ROS) in HT-1080 cells, suggesting its potential to induce ferroptosis for anti-tumor activity.

Objectives: To establish the pharmacokinetic model of linezolid in neonates, and to optimize the administration regimen., Methods: A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy, and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected, and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features., Results: The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination, and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h, respectively. The results of goodness of fit, visualization verification, and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows: 6 mg/kg, q8h, at 28 weeks of gestational age (GA); 8 mg/kg, q8h, at 32 weeks of GA; 9 mg/kg, q8h, at 34-37 weeks of GA; 11 mg/kg, q8h, at 40 weeks of GA., Conclusions: The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Treatment of swine manure by hydrothermal carbonization (HTC) with the aid of different surfactants was first explored in this study. PEG 400 (polyethylene glycol 400) and Tween 80 facilitated the formation of bio-oil. SLS (sodium lignosulfonate) and SDS (sodium dodecyl sulfate) promoted the formation of water-soluble matters/gases. Span 80 enhanced the formation of hydrochar, which resulted in a 50.19 % mass yield, 92.39 % energy yield, and a caloric value of 28.68 MJ/kg. The hydrochar obtained with Span 80 presented a similar combustion performance to raw swine manure and the best pyrolysis performance. The use of Span 80 promoted the transfer of degradation products to hydrochar, especially hydrophobic ester and ketone compounds. Notedly, Span 80 suppressed the synthesis of PAHs during the HTC process, which was reduced to 0.92 mg/kg. Furthermore, the hydrochar produced with Span 80 contained lower contents of heavy metals. On the whole, Span 80 has shown great potential in enhancing the HTC of swine manure. The acting mechanisms of surfactants in the HTC of swine manure included adsorption, dispersion, and electrostatics repulsion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Under purely inorganic conditions, a synthesis route was devised wherein elements were introduced stepwise via coprecipitation based on differences in compound solubility. This synthesis method can change the microscopic morphology of the material without relying on a templating agent, resulting in the formation of the multilayered lamellar Ce/Eu codoped zinc oxide solid solution (ZCEOSS) with a self-assembled nested imbrication structure. The study improves the critical matter of corrosion by focusing on the electron and energy transfer mechanisms. By introduction of the bandgap modulator cerium element and fluorescence enhancer europium element into the ZnO material, the anticorrosion material has been successfully endowed with both photocathodic protection and luminescent initiative/stress dual corrosion defense functions. Due to the energy level staircase protection mechanism synergistically generated by the 4f electron shell of rare-earth elements in concert with semiconductor zinc oxide, the energy band positions were modulated to progressively guide the direction of electron flow, thereby suppressing corrosion reactions. In particular, the ZCEOSS material synthesized by doping 1% cerium and 7% europium and adding rare-earth elements at pH 7 exhibited the best corrosion inhibition performance. After immersion in simulated seawater for 96 h, Tafel polarization test results showed that compared to epoxy resin and ZnO anticorrosion systems, the ZCEOSS anticorrosion system exhibited significantly improved corrosion inhibition efficiency with enhancements of 1028.3 and 402.9%, respectively. This study provides new insights into the development of highly efficient inorganic anticorrosion materials.

Background: Being too light at birth can increase the risk of various diseases during infancy., Aim: To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns., Methods: A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions., Results: Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit ( P ) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%., Conclusion: The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

As the new fashioned nitrogen removal process, short-cut nitrification and denitrification (SHARON) process, anaerobic ammonium oxidation (anammox) process, completely autotrophic nitrogen removal over nitrite (CANON) process, partial nitrification and anammox (PN/A) process and partial denitrification and anammox (PD/A) process entered into the public eye due to its advantages of high nitrogen removal efficiency (NRE) and low energy consumption. However, the above process also be limited by long-term start-up time, unstable operation, complicated process regulation and so on. As intermediates or by-metabolites of functional microorganisms in above processes, hydroxylamine (NH 2 OH) and hydrazine (N 2 H 4 ) improved NRE of the above processes by promoting functional enzyme activity, accelerating electron transport efficiency and regulating distribution of microbial communities. Therefore, this review discussed effects of NH 2 OH and N 2 H 4 on stability and NRE of above processes, analyzed regulatory mechanism from functional enzyme activity, electron transport efficiency and microbial community distribution. Finally, the challenges and limitations for nitric oxide (NO) and nitrous oxide (N 2 O) produced from regulation of NH 2 OH and N 2 H 4 are discussed. In additional, perspectives on future trends in technology development are proposed., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the view of, the manuscript entitled: Regulation Mechanism of Hydrazine and Hydroxylamine in Nitrogen Removal Processes: A Comprehensive Review., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The nitrogen removal efficiency and distribution of microbial community in a denitrification process aided by zero-valent iron (ZVI) under low carbon-to-nitrogen ratio (C/N) were assessed in this study. Experimental results demonstrated that the nitrogen removal efficiency (TNRE) increased to 96.4 ± 2.72% and 63.3 ± 4.02% after continuous addition of ZVI with molar ratio of ZVI to nitrate (NO 3 - -N) (ZVI/N) of 6 at C/N of 3 and 2, respectively, which was 4% and 7.7% higher than the blank one. Meanwhile, extracellular polymeric substance (EPS) could be used as electron transfer medium and endogenous carbon source for denitrification system and also the production of which increased by 28.43% and 53.10% under ZVI stimulation compared to the control group. Finally, a symbiotic system composed by autotrophic and heterotrophic denitrification bacteria was formed by aid of ZVI. This study proposed new insights into denitrification process improved by ZVI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Adolescent obesity is associated with impaired inhibitory control. Acute exercise can improve executive function. However, due to the influence of exercise intensity, cognitive test timing, and cardiorespiratory fitness (CF) level, the most effective exercise program remains controversial., Methods: The current study investigated the time-course effects of moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) on inhibitory control (Stroop) and task-related heart rate variability (HRV) in adolescents with different CF. A mixed experimental design of 2 CF levels (high CF, HCF; low CF, LCF) × 3 exercise methods (MICE, HIIE, CON) × 3 test timing (pre, post-0, post-20) was adopted. Heart rate variability (HRV) and Stroop task tests were conducted before exercise (pre), immediately after exercise (post-0), and 20 min after exercise (post-20)., Results: Individuals with HCF exhibited a positive decrease in Stroop response time immediately and 20 min after MICE and HIIE, compared to pretest response times (RT). Conversely, individuals with LCF showed a slight increase in Stroop task (RT) only immediately after HIIE. All individuals had a slight increase in ACC after MICE and HIIE compared to before exercise. In addition, compared with the control group, the time-domain index (the square root of the mean squared differences of successive NN intervals, RMSSD) of HRV was significantly decreased, the frequency-domain index (the absolute power of the Low-Frequency band/the absolute power of the High-Frequency band ratio, LF/HF) was significantly increased after MICE and HIIE, and the effect of HIIE on RMSSD and LF/HF was significantly greater than that of MICE., Conclusion: The current study found that the acute effects of MICE and HIIE on inhibitory control in obese adolescents were influenced by the interaction of cognitive test timing and cardiorespiratory fitness. Individuals with high cardiorespiratory fitness performed better on the Stroop task than individuals with low cardiorespiratory fitness. The inhibitory control of HIIE in high-cardiorespiratory obese adolescents produced positive effects similar to those in MICE but more lasting, suggesting that HIIE is more beneficial for high-cardiorespiratory obese adolescents. MICE promoted inhibitory control in obese adolescents with low cardiorespiratory fitness, but HIIE impaired inhibitory control in obese adolescents with low cardiorespiratory fitness immediately after exercise, suggesting that low cardiopulmonary fitness obese adolescents may be suitable for MICE rather than HIIE exercise intervention. The shift from balanced HRV to sympathetic dominance after acute exercise reflects increased arousal levels and may be one of the underlying mechanisms by which acute exercise brings benefits to executive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher., (Copyright © 2023 Feng, Mao, Liu and Ou.)

Background: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods., Objective: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration., Methods: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC 0-24 /MIC) and trough concentration for clinical efficacy., Results: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC 0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC 0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC 0-24 /MIC >425.47 and trough concentration >9.45 mg/L., Conclusion: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC 0-24 /MIC and trough concentration can predict the clinical efficacy of antibacterial treatment., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China., Methods: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group ( n =1 189) and non-EUGR ( n =1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined., Results: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR ( P <0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR ( P <0.05)., Conclusions: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

The selective C-C bond deconstruction/refunctionalization via a photoredox/nickel dual-catalyzed hydroalkylation of alkynes is developed under mild reaction conditions. In this protocol, a broad range of alkyl- and aryl-alkynes could react smoothly with cycloalkanols, affording the corresponding distal and site-specific vinyl-substituted ketones with high yields and excellent regioselectivities. Moreover, DFT calculations verified that the electron-rich behavior of aromatics and weak Brønsted bases have a common effect on the photocatalytic oxidant ring-opening of cyclobutanols.

Accurate size analysis of nanoparticles (NPs) is vital for nanotechnology. However, this cannot be realized based on conventional single-nanoparticle collision (SNC) because the current intensity, a thermodynamic parameter of SNC for sizing NPs, is always smaller than the theoretical value due to the effect of NP movements on the electrode surface. Herein, a size-dependent dynamic parameter of SNC, current lifetime, which refers to the time that the current intensity decays to 1/e of the original value, was originally utilized to distinguish differently sized NPs. Results showed that the current lifetime increased with NP size. After taking the current lifetime into account rather than the current intensity, the overlap rates for the peak-type current transients of differently sized Pt NPs (10 and 15 nm) and Au NPs (18 and 35 nm) reduced from 73 and 7% to 45 and 0%, respectively, which were closer to the theoretical values (29 and 0%). Hence, the proposed SNC dynamics-based method holds great potential for developing reliable electrochemical approaches to evaluate NP sizes accurately.

A protocol for the chemically divergent synthesis of β-lactams and α-amino acid derivatives with isothiourea (ITU) catalysis by switching solvents was developed. The stereospecific Mannich reaction occurring between imine and C(1)-ammonium enolate generated zwitterionic intermediates, which underwent intramolecular lactamization and afforded β-lactam derivatives when DCM and CH 3 CN were used as solvents. However, when EtOH was used as the solvent, the intermediates underwent an intermolecular esterification reaction, and α-amino acid derivatives were produced. Detailed mechanistic experiments were conducted to prove that these two kinds of products came from the same intermediates. Furthermore, chemically diversified transformations of β-lactam and α-amino acid derivatives were achieved., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function but also causes great damage psychological.Umbilical acupuncture (UA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of UA in the treatment of insomnia., Methods: Literature on UA for insomnia in PubMed, Excerpt Medica Database, the Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Database were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of UA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy, and safety. RevMan 5.4.1 software was used for mate analysis., Results: This study aimed to evaluate the current status of UA treatment for insomnia, with the aim of illustrating the effectiveness and safety of UA., Conclusion: This study will provides a high-quality evidence to evaluate the effectiveness and safety of UA in treating insomnia., Registration: PROSPERO CRD42021283036., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Preclinical research is essential to the advancement of science but susceptible to insufficient reporting and methodological shortcomings, which compromise internal validity. We aimed to systematically assess the methodological and reporting quality of studies conducted on acupuncture for experimental cerebral ischemia/reperfusion injury (CIRI)., Methods: A comprehensive search in six databases was performed for animal research concerning acupuncture for CIRI. Two authors independently selected articles, extracted data, and assessed the methodological and reporting quality of identified articles using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool, and Animal Research: Reporting In Vivo Experiments (ARRIVE) guideline, respectively., Results: A total of 24 studies were identified. Only 1 article (4%) achieved a decent overall rating in using SYRCLE (percentage of items with "low risk" ⩾50%). Of the 22 items on the SYRCLE tool, only 8 items (37%) were rated as "low risk" of bias in more than 50% of the included studies. Of the 39 items of ARRIVE, 20 (51%) items were rated as "low risk" in more than 50% of the included studies., Conclusions: The methodological and reporting quality of included studies was generally low, which demands further improvement. These findings should inform the development of evidence-based guidelines for future preclinical research assessing the effect of acupuncture on CIRI.

Objective: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms., Methods: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively., Results: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats., Conclusion: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at " Baihui ", " Quchi " and " Zusanli " acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.

We herein report a general organocatalytic enantioselective strategy for the construction of highly strained spiro[2,3]hexane skeletons from methylenecyclopropanes and a broad selection of α,β-unsaturated aldehydes. The reaction proceeds through a Michael addition followed by ring expansion of methylenecyclopropanes and nucleophilic attack of an enamine to realize the construction of spiro[2,3]hexanes. Key to the success of this approach are the utilization of an electron-deficient difluoro-substituted secondary amine catalyst and the intrinsic reactivity of methylenecyclopropanes., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the effect of electroacupuncture (EA) preconditioning on autophagy in cerebral cortex tissues of rats with cerebral ischemia-reperfusion injury (CIRI), so as to explore its mechanisms underlying improvement of CIRI., Methods: Thirty-three male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups ( n =11 in each group). EA (2 Hz/15 Hz, 1 mA) was applied to "Baihui"(GV20), "Quchi" (LI11) and "Zusanli" (ST36) for 30 min, once daily for 5 days, followed by establishment of CIRI model by occlusion of the middle cerebral artery (MCAO) for 1.5 h and reperfusion for 24 h. The neurological deficit score was assessed in reference to Longa's methods, and the infarct volume assessed by 2,3,5-triphenyltetrazolium chloride staining. The density of dendrite spines of neurons in the ischemic cerebral cortex tissue was detected by Golgi's staining, the autophagosome observed by electron microscopy, and the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and p62 (a selective autophagy substrate) were detected by Western blot., Results: Compared with the sham operation group, the neurological deficit score and infarct volume were significantly increased ( P <0.01), the number of autophagosomes and the ratio of LC3-Ⅱ/LC3-Ⅰ also significantly increased ( P <0.01), while the expression level of p62 was notably decreased in the model group ( P <0.01). Following the intervention and in comparison with the model group, the neurological deficit score and infarct volume were significantly reduced ( P <0.01), the number of autophagosomes and the ratio of LC3-Ⅱ/LC3-Ⅰ obviously decreased ( P <0.01), and the expression of p62 was significantly up-regulated in the EA group ( P <0.01)., Conclusion: EA pretreatment is effective in improving CIRI in rats, which may be realized through suppressing autophagy in the ischemic cerebral cortex tissue.

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Long noncoding RNAs (lncRNAs) play important roles in many diseases. Therefore, the aim of this study was to investigate the role of lncRNA ZFAS1 in the development of HCC and to explore its underlying mechanism., Patients and Methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect ZFAS1 expression in tissue samples of HCC patients. Subsequently, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and EdU incorporation assay were performed to detect the function of ZFAS1 in vitro. Furthermore, mechanism assays were performed to explore the interaction between ZFAS1 and miR-193a-3p., Results: ZFAS1 was significantly highly expressed in HCC tissues than that of adjacent normal tissues. The growth ability of HCC cells was markedly inhibited after ZFAS1 was silenced. However, the growth ability of HCC cells was remarkably promoted after ZFAS1 overexpression. Moreover, RT-qPCR results revealed that miR-193a-3p was significantly down-regulated via the overexpression of ZFAS1. However, miR-193a-3p was significantly up-regulated via the knockdown of ZFAS1. Further experiments showed that miR-193a-3p was a direct target of ZFAS1 in HCC., Conclusions: ZFAS1 could enhance the proliferation of HCC cells by suppressing miR-193a-3p, which might be a potential therapeutic target in HCC.

Excessive autophagy is one of the crucial factors of cerebral ischemia-reperfusion injury (CIRI), which has been demonstrated to be one of the targets for acupuncture treatment of ischemic stroke. In the present paper, we make a review about the development of acupuncture intervention induced improvement of CIRI (such as reducing the infarction area, improving learning-memory ability and motor function) by regulating autophagy in animal studies. Outcomes showed that acupuncture intervention can function in 1) inhibiting CIRI-induced increase of the number of lysosomes and autophagic lysosomes, and relieving structural injury of mitochondria, and reducing the number of autophagosome in the central region of the ischemic cerebral cortex tissue; 2) down-regulating the expression of microtubule-associated protein Ⅱ light chain 3 (LC3Ⅱ) and the ratio of LC3-Ⅱ/LC3-Ⅰ in the ischemic cerebral region, and 3) regulating the expression of Beclin 1 (autophagy-related gene), promoting the expression of P62 (autophagy-related adaptor protein). In addition, acupuncture can also regulate phosphoinositide 3 kinase (PI3K)- protein kinase B (AKT)- mammalian target of rapamycin complex 1(mTOR) signaling at different time-points (down-regulation at the early stage and up-regulation at the later stage), and activating AMP-activated protein kinase (AMPK)-mTOR- UNC51-like kinase-1 signaling to relieve cerebral ischemic injury. These results reveal some mechanisms of acupuncture therapy underlying improvement of CIRI and provide experimental basis for clinical application of acupuncture therapy in the treatment of ischemic stroke.

Objective: To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats., Methods: A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF 4 ) and "Yidan" (CO 11 ), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis., Results: ① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all P <0.05); compared with the model group, GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly increased in the EAS group (all P <0.05). ② Compared with the control group, the expression of BDNF and p-CREB in the model group was significantly increased ( P <0.01), and the expression of TrkB in the model group was significantly increased ( P <0.05); the differences of expression of BDNF, TrkB, CREB and p-CREB between the model group and the EAS group had no statistics significance (all P >0.05)., Conclusion: EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway. This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases., Competing Interests: None

Objective: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model., Methods: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD)., Results: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups., Conclusion: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Herein, we describe a novel and efficient method for constructing a series of fluorine-containing γ-keto acid derivatives through combining visible-light photoredox catalysis and chiral Lewis acid catalysis. With this dual catalytic strategy, a variety of chiral γ-keto amides containing a gem-difluoroalkyl group and a series of fluorine-containing α,β-unsaturated-γ-keto esters were successfully constructed with high stereoselectivities, respectively. A series of experiments showed that the chemoselectivity of this process was highly dependent on the fluorine reagents besides the Lewis acid catalysts. This approach facilitates rapid access to γ-keto acid derivatives, an important class of precursors for pharmaceuticals, plasticizers, and various other additives.

A series of inexpensive, easily tunable, and highly reducing organic photocatalysts (PCs) that exhibit strong absorption in the visible region are described. Time-dependent density functional theory calculations were applied to corroborate the experimental observations and explain the relationship between the structure and property. The photocatalytic efficiency of these PCs was demonstrated by catalyzing several challenging reactions and the radical cascade cyclization of 1,6-diyne with superior photocatalytic efficiency to other organic photocatalysts.

Due to the significance of hybrid systems in drug discovery, there is an urgent need to assemble multiple biologically active ingredients into a single molecule. Here, we report a general transition-metal-free selective C-H benzylation of tertiary arylamines in good to excellent yields with a broad substrate scope and high functional-group tolerance under mild conditions. Besides arylamines, some other benzene derivatives also readily furnished the corresponding diaryl methane derivatives with this protocol. A series of control experiments and theoretical calculations indicated that this transition-metal-free reaction is a dearomatization-aromatization process., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPK-mTOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1. In this study, we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-mTOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. Rats were intraperitoneally injected with puerarin, 50 or 100 mg/kg, daily for 7 days. Then, 30 minutes after the final administration, rats were subjected to transient middle cerebral artery occlusion for 90 minutes. Then, after 24 hours of reperfusion, the Longa score and infarct volume were evaluated in each group. Autophagosome formation was observed by transmission electron microscopy. LC3, Beclin-1 p62, AMPK, mTOR and ULK1 protein expression levels were examined by immunofluorescence and western blot assay. Puerarin substantially reduced the Longa score and infarct volume, and it lessened autophagosome formation in the hippocampal CA1 area following cerebral ischemia/reperfusion injury in a dose-dependent manner. Pretreatment with puerarin (50 or 100 mg/kg) reduced Beclin-1 expression and the LC3-II/LC3-I ratio, as well as p-AMPK and pS317-ULK1 levels. In comparison, it increased p62 expression. Furthermore, puerarin at 100 mg/kg dramatically increased the levels of p-mTOR and pS757-ULK1 in the hippocampus on the ischemic side. Our findings suggest that puerarin alleviates autophagy by activating the APMK-mTOR-ULK1 signaling pathway. Thus, puerarin might have therapeutic potential for treating cerebral ischemia/reperfusion injury., Competing Interests: The authors declare that they have no conflicts of interest

Herein we describe a mild method for the dual C(sp 3 )-H bond functionalization of saturated nitrogen-containing heterocycles through a sequential visible-light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well-established use of iminium ion and α-amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp 3 )-H bonds., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent studies have shown that liver dysfunction is an early event in sepsis. Pre-existing liver dysfunction is a risk factor for progression of infection to sepsis. However, the mechanism of the liver immune response in promoting sepsis and the importance of liver function are not completely understood. In the present study, we investigated the protective effect of erythropoietin (EPO) against mitochondrial dysfunction in a lipopolysaccharide (LPS)-induced sepsis model, and examined the underlying signaling mechanisms. Enzyme linked immunosorbent assay (ELISA) and reactive oxygen species (ROS) analysis were used to evaluate the levels of interleukin (IL)-1β and ROS. The effects of EPO on hepatic mitochondrial function were studied by detecting the mitochondrial DNA (mtDNA) copy number using real-time PCR (RT-PCR). To explore the mechanism of action of EPO in sepsis, protein expressions of IL-1β, caspase-1 and NLRP3 were assessed by Western blotting; liver histopathology and ultrastructure of liver mitochondria was examined by transmission electron microscopy. We found that LPS treatment increased serum IL-1β and ROS levels, the effect of which was attenuated by EPO. Moreover, LPS treatment also increased the mtDNA copy number and the protein expressions of IL-11β, caspase-1, and NLRP3, which were suppressed by EPO. Histological examination of liver showed LPS-induced cellular edema in hepatic lobules, lymphocytic infiltration and hepatocellular necrosis; these changes were also alleviated by EPO treatment. On electron microscopy, the size of hepatocellular mitochondria in the LPS group was smaller than that in the control group, and the changes were reversed by EPO in the LPS+EPO group. Our results suggest that EPO alleviated liver and mitochondrial damage induced by LPS, possibly via inhibition of NLRP3 signaling.

To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.

Background: Previous studies indicated that the puerarin injection has been widely employed in China for the treatment of acute ischemic stroke. We aim to evaluate the efficacy and safety of the puerarin injection for the treatment of acute ischemic stroke., Methods: A systematic literature search was performed in PUBMED, EMBASE, SPRINGER LINK, Scopus, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Journals Database, Wanfang database and the China Biological Medicine database before November 2016, randomized controlled clinical trials (RCTs) of puerarin injection treating acute ischemic stroke were included. In addition, we searched reference lists of relevant retrieved articles. Two authors extracted data independently. The effective rate, the neurologic deficit score, the blood rheology indexes, and fibrinogen were assessed and analyzed by the Review Manager 5.3 software. The continuous variables were expressed as MD with 95% CI and dichotomous data used RR or ORs. Adverse reactions related to the puerarin injection were also examined., Results: Thirty-five RCTs with a total of 3224 participants were identified in the meta-analysis. The combined results of 32 trials indicated that the puerarin injection was better than control drugs at the clinical effective rate (RR 1.22, 95% CI 1.17 to 1.28, P < 0.001) and 16 studies showed the neurological deficit was significantly improved (MD -3.69, 95% CI -4.67 to -2.71, P < 0.001); the hemorheology index and fibrinogen were much lower with the puerarin injection when compared with western conventional medicines (WCM) or other control drugs (the whole blood viscosity: MD -0.89, 95% CI -1.37 to -0.41, P < 0.001; the HCT: MD -0.04, 95% CI -0.06 to -0.02, P < 0.001; the fibrinogen: MD -0.64, 95% CI -0.96 to -0.31, P < 0.001). Eleven trials reported that the adverse reactions related to the puerarin injection included facial flushing, dizziness, vomiting, nausea, and other mild gastrointestinal discomfort and allergic reaction. No serious adverse drug reactions were reported., Conclusions: Puerarin injection may be more effective and relatively safe in clinic for treating acute ischemic stroke. However, the current evidence is insufficient due to the poor methodological quality and lack of adequate safety data. Further RCTs are required to examine its efficacy., Competing Interests: The authors have no conflicts of interest to disclose.

The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age. The messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed the SCN2B expressions in the prefrontal cortex, resulting in improved learning and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level by 60.68% resulted in improvement in the hippocampus-dependent spatial recognition memory and long-term potential (LTP) slope of field excitatory postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression. Together, the present findings indicated that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of COX5A and FGF-2. These findings could provide the potential strategy of candidate target to develop antisenescence drugs for the treatment of brain aging.

Objective: To evaluate the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) in preventing extubation failure in neonates., Methods: A literature search was performed using PubMed, Cochrane Library, FMRS, and CNKI to collect the randomized controlled trials (RCTs) and quasi-RCTs which compared the clinical efficacy of HHHFNC and nasal continuous positive airway pressure (NCPAP) in preventing extubation failure in neonates. The identified studies were finally selected after full-text search and quality assessment and then subjected to a Meta analysis using RevMan 5.3., Results: Five eligible trials involving 1040 neonates were included in the Meta analysis. The Meta analysis showed that there was no significant difference in treatment failure rate between the HHHFNC and the NCPAP groups. The HHHFNC group had significantly lower incidence rates of nasal trauma (OR=0.49, 95% CI: 0.34-0.71, P=0.0001) and pneumothorax (OR=0.27, 95% CI: 0.07-0.97, P=0.04) than the NCPAP group, but there were no significant differences in the duration to reach full oral feedings and the incidence rates of serious adverse events or other complications between the two groups, such as in-hospital mortality, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity., Conclusions: HHHFNC is safe and effective in preventing extubation failure in neonates.

Recretohalophytes with specialized salt-secreting structures (salt glands) can secrete excess salts from plant, while discriminating between Na(+) and K(+). K(+)/Na(+) ratio plays an important role in plant salt tolerance, but the distribution and role of K(+) in the salt gland cells is poorly understood. In this article, the in situ subcellular localization of K and Na in the salt gland of the recretohalophyte Limonium bicolor Kuntze is described. Samples were prepared by high-pressure freezing (HPF), freeze substitution (FS) and analyzed using NanoSIMS. The salt gland of L. bicolor consists of sixteen cells. Higher signal strength of Na(+) was located in the apoplast of salt gland cells. Compared with control, 200 mM NaCl treatment led to higher signal strength of K(+) and Na(+) in both cytoplasm and nucleus of salt gland cells although K(+)/Na(+) ratio in both cytoplasm and nucleus were slightly reduced by NaCl. Moreover, the rate of Na(+) secretion per salt gland of L. bicolor treated with 200 mM NaCl was five times that of controls. These results suggest that K(+) accumulation both in the cytoplasm and nucleus of salt gland cells under salinity may play an important role in salt secretion, although the exact mechanism is unknown., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

With the expansion of saline land worldwide, it is essential to establish a model halophyte to study the salt-tolerance mechanism. The salt glands in the epidermis of Limonium bicolor (a recretohalophyte) play a pivotal role in salt tolerance by secreting excess salts from tissues. Despite the importance of salt secretion, nothing is known about the molecular mechanisms of salt gland development. In this study, we applied RNA sequencing to profile early leaf development using five distinct developmental stages, which were quantified by successive collections of the first true leaves of L. bicolor with precise spatial and temporal resolution. Specific gene expression patterns were identified for each developmental stage. In particular, we found that genes controlling salt gland differentiation in L. bicolor may evolve in a trichome formation, which was also confirmed by mutants with increased salt gland densities. Genes involved in the special ultrastructure of salt glands were also elucidated. Twenty-six genes were proposed to participate in salt gland differentiation. Our dataset sheds light on the molecular processes underpinning salt gland development and thus represents a first step towards the bioengineering of active salt-secretion capacity in crops., (© 2015 John Wiley & Sons Ltd.)

Objectives: To observe the expression of the dopamine transporter (DAT) in six cerebral regions of a methamphetamine (MA)-dependent rat, which were frontal cortex, nucleus accumbens septi, striatum, hippocampus, substantia nigra and ventral tegmental area., Methods: The rats were administrated intraperitoneally with 10 mg/kg/day of MA for 10 days consecutively; the behaviour changes were measured via the conditioned place preference (CPP), and the scores of stereotyped behaviour (SB) were used to confirm animal addiction. Then, the animals were further injected with MA respectively for 1, 2, 4 and 8 weeks to establish different periods of MA-dependent models. The expressions of DAT and DAT messenger RNA in six cerebral regions were detected., Results: The results of CPP and SB scores were significant different when comparing all four experimental groups with the control group (p < 0.05). Comparing between different experimental groups, the expression of DAT mainly decreased and had dynamic changes in the same regions (p < 0.05). Comparing the different regions with each other in the same experimental group, the expression of DAT also had significant difference in several regions p < 0.05)., Conclusions: The expression of DAT mainly decreased and had different in the six cerebral regions at the same MA-dependent time period as well as at different time periods in the same cerebral region. It was speculated that DAT might play a crucial role in the mechanism of MA dependence., (© The Author(s) 2014.)

Background: Endoscopic retrograde appendicitis therapy (ERAT) is a new procedure for the treatment of acute uncomplicated appendicitis. The aim of the study was to review the clinical outcomes of ERAT and further examine its effectiveness and safety., Methods: The study was performed on patients who underwent ERAT for acute uncomplicated appendicitis at three tertiary hospitals in China from December 2009 to May 2013. Patient demographics, technique aspects of the ERAT procedures, clinical success (resolution of symptoms and normalization of laboratory tests), time until resumption of diet, and hospital stay were analyzed, and complications and recurrence were followed up., Results: Forty-one patients were entered, among which 34 patients were definitely diagnosed as having acute uncomplicated appendicitis; in 7 patients, acute appendicitis was excluded by endoscopic retrograde appendicography. Thirty-three patients completed ERAT except one patient who failed appendiceal cannulation. Abdominal pain resolved immediately in 32 patients, and clinical success rate was 97 %. There was one failure case (3 %) that complicated perforation after 48 h received emergency appendectomy. The median follow-up period was 12 months (IQR = 9-23 months). During follow-up, there were no long-term complication; 2 patients (6.2 %) had recurrent abdominal pain and received appendectomy (one had a histologically normal appendix)., Conclusions: ERAT is an effective method to diagnose and treat acute uncomplicated appendicitis. Multicenter prospective clinical trials are needed to confirm its utility and place in the management of suspected acute appendicitis.

Objective: To analyze the homology of Zaocys type 1I collagen ( ZC II ) with the C II collagen from other species, and to investigate the effect of ZC II on arthritis in mice with collagen-induced arthritis (CIA)., Methods: ZC II was purified with restriction pepsin digestion. Then SDS-PAGE gel electrophoresis and UV spectrophotometry were used to identify the protein,the homology of the ZC II peptide was analyzed with Mass Spectrometry. The model of CIA mice were induced by subcutaneous injection of Chicken C II into male C57BL/6 mice from the base of the tails. After immunization,ZC II [H,M,L:40,20 and 10 μg/(kgd) ]was administered orally to mice from day 21 to 28 accordingly. The severity of the arthritis in each limb was evaluated using a macroscopic scoring system, and his- topathological change of joint was observed by light microscope with HE staining., Results: The molecular weight of ZC II protein deter- mined by SDS-PAGE gel electrophoresis was between 110 kD and 140 kD, and UV absorption peak appeared at around 230 nm in wave- length. The peptide mass fingerprinting(PMF) of the purified protein by Mass Spectrometry analysis showed that it had at least 4 peptides matched with other species,and the protein score was greater than 95%. Compared with normal group,the CIA model group had significantly higher scores for arthritis and histopathological changes (P <0. 05). Meanwhile,the same scores for the ZC II peptide-treated mice with CIA were significantly lower than the mice from CIA model group(P <0. 05)., Conclusion: Results of Mass Spectrometry analysis demonstrate that ZC II has high homology with the C II from other species. Oral administration of ZC II can suppress arthritis in mice with CIA and ameliorate the histopathological changes of the joint.

Aim: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit., Methods: Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity visually assigned to the protein bands. The markers which showed statistical differences between the NPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparison with established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA., Results: Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative predictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively., Conclusions: EA-D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA-IgA positive subjects.

Objective: To investigate the effect of NK-22 cells isolated from the synovial fluid (SF) of patients with rheumatoid arthritis (RA) on the proliferation of fibroblast-like synoviocytes and explore its possible mechanism., Methods: The proportions of NK-22 cells in the peripheral blood (PB) and the SF of 20 RA patients and 20 healthy individuals were determined by flow cytometry. NK-22 cells in the SF sorted by flow cytometry were cultured for two weeks followed by a 4-h stimulation with 20 ng/ml phorbol 12-myristate 13-acetate and 0.5 µ mol/L ionomycin. The culture supernatant of NK-22 cells was then harvested, in which the levels of IL-22 and TNF-α were measured by ELISA. The fibroblast-like synoviocytes were exposed to the culture supernatant for 24, 48, 72, and 96 h, and the changes in the cell proliferation were detected by MTT assay., Results: RA patients showed a significantly greater proportion of NK-22 cells in both the SF and PB than the normal control subjects (P<0.05). NK-22 cells sorted by flow cytometry reached a purity exceeding 90%, and the levels of IL-22 and TNF-α in the culture supernatant of NK-22 cells cultured for two weeks were 941.16 pg/ml and 368.1 pg/ml, respectively. The culture supernatant of NK-22 cells caused a rapid proliferation of the fibroblast-like synoviocytes at 24, 48, 72, and 96 h after the exposure., Conclusion: NK-22 cells in the SF of RA patients can promote the proliferation of fibroblast-like synoviocytes possibly due to the capacity of NK-22 cells to produce IL-22 and TNF-α.

Objective: To investigate the expression levels of miR-146a and miR -16 in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) and their correlation to the disease activity., Methods: The expression levels of miR-146a and miR-16 in the in PBMCs were measured using real-time RT-PCR in 40 RA patients and 16 healthy individuals. The correlations of miR-146a and miR-16 expressions to the disease activity of RA were analyzed., Results: The expression levels of miR-146a and miR-16 in the PBMCs of RA patients increased significantly compared to those in the healthy individuals (P<0.05). Their expression levels was significantly higher in active RA patients than in patients with disease remission (P<0.05) and healthy individuals (P<0.01). The expression levels of miR-146a and miR-16 were positively correlated to ESR, CRP and the disease activity scores in 28 joints (DAS28) (P<0.01), but not to RF (P>0.05)., Conclusion: The elevated expression levels of miR-146a and miR-16 are correlated to RA disease activity, suggesting their value in assessment of the clinical disease activity of RA.

Objective: To explore the association of the expressions of human leukocyte antigen (HLA)-DR4, peptidyl arginine deiminase type4(PAD4), and signal transducer and activator of transcription 4 (STAT4) in the peripheral blood with the disease activity in patients with rheumatoid arthritis (RA)., Methods: Twenty-four RA patients in active stage (DAS28 score>or=2.6) and 14 RA patients in remission stage (DAS28 score<2.6) were enrolled in this study, with 12 healthy volunteers as the control. The QuantiGene Plex method was used to measure the expression level of HLA-DR4, PAD4, and STAT4 mRNA, and the relationship between the expressions of these genes and the DAS28 score, levels of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and rheumatoid factor (RF) was analyzed., Results: The expressions of HLA-DR4, PAD4, and STAT4 were significantly higher in RA patients than in the healthy controls (P<0.05). The level of HLA-DR4 mRNA in the two RA groups showed no significant difference, but was significantly higher than that in the healthy controls. HLA-DR4 expression was not found to correlated to DAS28 score, anti-CCP antibody level or RF in the RA patients. The expressions of PAD4 and STAT4 were significantly different between the two RA groups (P<0.05). In the RA patients, PAD4 mRNA expression was positively correlated to DAS28 and anti-CCP antibody level (P<0.05), and STAT4 expression showed positive correlations to DAS28 and RF levels (P<0.05)., Conclusion: HLA-DR4, PAD4 and STAT4 are overexpressed in RA patients and may be involved in the pathogenesis of RA. The expressions of PAD4 and STAT4, but not HLA-DR4, are closely related to the disease activity of RA. Detection of peripheral blood PAD4 and STAT4 expressions can be helpful for evaluating the disease activity of RA.

This study examined the protein expression profile changes in the brain of senescence-accelerated mice/prone 8 (SAMP8) model. Two approaches, namely microarray and RT-PCR, were used in the study. Four genes, which are orthologous to human, were found to differentially express in the aging brain of mice. In this study, we examined the differentially expressed genes in the frontal cortex of the SAMP8 mice of two different ages (4 and 12 month old). Four orthologous genes (i.e., guanine nucleotide binding protein-alpha q polypeptide, kinesin family member 1B, sortilin 1, and somatostatin) showed significant changes in expression with aging. This study may provide important information on the mechanism of aging or aging-related diseases such as Alzheimer's diseases.

Objective: To explore the effect of kallikrein-binding protein (KPB) in protecting retinal ganglion cells (RGCs) and promoting axonal regeneration following optical nerve injury in rats., Methods: Crush injury of the optic nerve at 0.5-1.0 mm from the eyeball was induced in rats, which received subsequent KBP injection into the vitreous cavity (experimental group) and PBS injection (control group). At 7, 14 and 21 days after the injury, the rats were sacrificed and frozen sections of the eyeball were prepared to observe the structure and thickness of the retina and count the number of survival RGCs with HE staining. The optic nerves were collected for Western blotting to assess the effect of KBP on the RGCs and axonal regeneration., Results: RGC counts and retinal thickness showed significant differences between the two groups. Western blotting also demonstrated a significant difference in the expression of the nerve regeneration marker protein GAP-43 between the two groups., Conclusion: KBP offers protection on RGCs and promotes regeneration of the optic nerve axons after optic nerve injury in rats.

Objective: To explore the changes in the expressions of glial fibrillary acidic protein (GFAP) and growth- associated protein-43 (GAP-43) in retinal ganglial cells after neural transplantation., Methods: Thirty-nine rats were randomized into normal control group, nerve amputation group and nerve amputation with peripheral nerve transplantation group. Immunohistochemistry was used to detect the changes in the expressions of GFAP and GAP-43 at different time points after the operations, and real-time PCR was employed to detect the mRNA expressions of 13 genes in the retinal ganglial cells of the rats., Results: Immunohistochemistry showed obviously increased GFAP expressions in the retina following the nerve amputation. GFAP expression was down-regulated while GAP-43 expression upregulated in the retinal ganglial cells after peripheral nerve transplantation. Real-time PCR results showed that 5 days after the operations, retinal GFAP and GAP-43 expressions increased significantly in the nerve amputation group and peripheral nerve transplantation groups as compared with those in the control group, but GAP-43 expression decreased significantly in the former two groups afterwards., Conclusion: The regenerated retina may adjust the production of GFAP. The retinal ganglial cells express GAP-43 during retinal regeneration. Up-regulation of the expression of GAP-43 provides the evidence for nerve regeneration following the nerve transplantation.

Aim: To investigate the effect of a new infant formula supplemented with a low level (0.24 g/100 mL) of galacto-oligosaccharide (GOS) on intestinal micro-flora (Bifidobacteria, Lactobacilli and E. coli) and fermentation characteristics in term infants, compared with human milk and a standard infant formula without GOS., Methods: Term infants (n = 371) were approached in this study in three hospitals of China. All infants started breast-feeding. Those who changed to formula-feeding within 4 wk after birth were randomly assigned to one of the two formula groups. Growth and stool characteristics, and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period. Fecal samples were collected from a subpopulation of recruited infants for analysis of intestinal bacteria (culture technique), acetic acid (gas chromatography) and pH (indicator strip)., Results: After 3 mo, the intestinal Bifidobacteria, Lactobacilli, acetic acid and stool frequency were significantly increased, and fecal pH was decreased in infants fed with the GOS-formula or human milk, compared with those fed with the formula without GOS. No significant differences were observed between the GOS formula and human milk groups. Supplementation with GOS did not influence the incidence of crying, regurgitation and vomiting., Conclusion: A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.

This study determined the effects of pcDNA3-beta-nerve growth factor (NGF) gene-modified bone marrow stromal cells (BMSC) on the rat model of Parkinson's disease (PD). The recombinant plasmid pcDNA3-beta-NGF was transfected into BMSC, and NGF expression and its biological activity in vitro were detected. BMSC modified by the NGF gene were then grafted into the corpus striatum of PD rats, and the rotation behavior was evaluated at 1, 2, 4, and 6 weeks post-transplantation. A significant improvement in rotation behavior was observed in PD rats subjected to cell transplantation, especially in PD rats receiving NGF-modified BMSC. The genetically modified BMSC survived and expressed beta-NGF but did not differentiate into tyrosine hydroxylase-positive cells in vivo. The present findings suggested that genetically modified BMSC could be effective for PD treatment, and the mechanisms might involve the neuroprotective effects of beta-NGF.