ZntA maintains zinc and cadmium homeostasis and promotes oxidative stress resistance and virulence in Vibrio parahaemolyticus.

Although metals are essential for life, they are toxic to bacteria in excessive amounts. Therefore, the maintenance of metal homeostasis is critical for bacterial physiology and pathogenesis. Vibrio parahaemolyticus is a significant food-borne pathogen that mainly causes acute gastroenteritis in humans and acute hepatopancreatic necrosis disease in shrimp. Herein, we report that ZntA functions as a zinc (Zn) and cadmium (Cd) homeostasis mechanism and contributes to oxidative stress resistance and virulence in V. parahaemolyticus. zntA is remarkably induced by Zn, copper, cobalt, nickel (Ni), and Cd, while ZntA promotes V. parahaemolyticus growth under excess Zn/Ni and Cd conditions via maintaining Zn and Cd homeostasis, respectively. The growth of ΔzntA was inhibited under iron (Fe)-restricted conditions, and the inhibition was associated with Zn homeostasis disturbance. Ferrous iron supplementation improved the growth of ΔzntA under excess Zn, Ni or Cd conditions. The resistance of ΔzntA to H2O2-induced oxidative stress also decreased, and its virulence was attenuated in zebrafish models. Quantitative real-time PCR, mutagenesis, and ß-galactosidase activity assays revealed that ZntR positively regulates zntA expression by binding to its promoter. Collectively, the ZntR-regulated ZntA is crucial for Zn and Cd homeostasis and contributes to oxidative stress resistance and virulence in V. parahaemolyticus.

Research on the Changes in Catecholamine and Other Indicators during Different Training Phases in Female Volleyball Players.

Objective: This study seeks to assess the functional status and central fatigue state of athletes in the Shanghai women's volleyball team during the training phase of the 2021 Shaanxi National Games. Employing a comprehensive methodology involving functional status assessment and catecholamine index analysis, the research aims to establish a scientific foundation for preparing for the 2025 National Games. Additionally, it aims to provide valuable insights for preventing excessive fatigue and promoting the rational elimination of fatigue. Methods: (1) Participants: Twelve adult female volleyball players from Shanghai participated in the study. The average age of the participants was 26.23±3.39 years, and they had an average training period of 11.92±3.73 years. (2) Training Period: The study spanned a duration of 21 consecutive weeks, during which the training regimen was divided into eight distinct stages based on specific content and tasks. (3) Testing Procedures: Various tests were conducted at specific intervals throughout the training period. These included assessments performed at the conclusion of each upper training stage and the Metamorphosis stage. Additionally, comprehensive testing was carried out before and after both the preliminaries and championship matches of the National Games. Fasting elbow venous blood samples were collected for assessing functional status indicators, including Hemoglobin (HGB), Blood Urea Nitrogen (BUN), Creatine Kinase (CK), Serum Ferritin (SF), Testosterone (T), Cortisol (C), Testosterone/Cortisol ratio (T/C). Moreover, blood catecholamine indicators (Dopamine (DA), Norepinephrine (NE), Epinephrine (E) were analyzed before the National Games, at the end of Metamorphosis stage 2, and at the conclusion of upper phase 3. (4)Data Analysis: The collected data underwent rigorous statistical processing using SPSS 25.0 statistical software package and Microsoft Excel software. This comprehensive analysis was essential for deriving meaningful conclusions and identifying significant patterns in the athletes' functional status and central fatigue states. Results: (1) HGB, T, and T/C showed the same trend throughout the whole period. The upper phase 1 drops significantly to the lowest value and the Metamorphosis stage increases. The training stage 2 fell again, but the decline was less than the training stage 1, and the Metamorphosis stage 2 increased significantly, and there was a significant difference between the basic value and the training stages (P < .05). Testosterone increased significantly to the maximum before the final of the National Games, and there was a significant difference between the baseline and the pre-match (P < .05). (2) At the end of the training stage, DA, and E decreased significantly, and there was no significant difference in NE decline. During the preliminaries of the National Games, DA, NE, and E all declined, but there was no significant difference. In the championship stage, DA, NE, and E both increased, but only NE was significantly different from the Metamorphosis stage and the championship (P < .05). Conclusion: (1) Performance Enhancement: Recognizing and addressing performance dips in the training stage through targeted adjustments can optimize athlete performance. Athletes exhibit improved competitiveness during actual games, indicating the effectiveness of tailored interventions (2) Strategic Fatigue Management: Distinguishing between body and central fatigue is vital. Monitoring sensitive markers like blood dopamine and adrenaline in the training stage enables timely fatigue management. Understanding the relationship between blood testosterone and dopamine offers insights into energy levels and mental resilience, aiding in effective training strategies. (3) Efficient Evaluation Tools: Hemoglobin and blood testosterone serve as efficient markers for evaluating athletes' states. Regular assessment of these indicators allows for proactive adjustments in training, preventing excessive fatigue and promoting overall well-being.

[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

The effect of short-term cranial electrotherapy stimulation on sleep quality in athletes: A pilot study.

BACKGROUND: To verify the effect of a 5-day cranial electrotherapy stimulation (CES) intervention on sleep quality in professional athletes. METHODS: 25 professional athletes with poor sleep quality participated in the study. Athletes belonging to the CES group (12 athletes) received a 5-day CES intervention, and those in the control group did not receive any intervention. Objectively and subjected assessed sleep quality was measured 1 week before and after the intervention using an Actigraphy activity recorder, Pittsburgh sleep quality index (PSQI), and Insomnia Severity Index (ISI). RESULTS: Objectively measured sleep efficiency increased after CES intervention (P = .013), while the difference between the pretest and posttest of the control group was not significant. For total sleep time (TST), the main effects and interaction were not significant. However, the analysis on wake after sleep onset showed wake after sleep onset decreased after CES intervention (P = .015). No significant interaction was found in subjectively assessed sleep quality but only revealed an improvement in both groups. CONCLUSION: The CES intervention of 30 minutes per day for 5 consecutive days enhanced objective sleep quality in athletes with sleep quality problems. The intervention increased sleep efficiency by lowering awake time after falling asleep.

Factors Influencing the Sharing of Personal Health Data Based on the Integrated Theory of Privacy Calculus and Theory of Planned Behaviors Framework: Results of a Cross-Sectional Study of Chinese Patients in the Yangtze River Delta.

BACKGROUND: The health care system in China is fragmented, and the distribution of high-quality resources remains uneven and irrational. Information sharing is essential to the development of an integrated health care system and maximizing its benefits. Nevertheless, data sharing raises concerns regarding the privacy and confidentiality of personal health information, which affect the willingness of patients to share information. OBJECTIVE: This study aims to investigate patients' willingness to share personal health data at different levels of maternal and child specialized hospitals in China, to propose and test a conceptual model to identify key influencing factors, and to provide countermeasures and suggestions to improve the level of data sharing. METHODS: A research framework based on the Theory of Privacy Calculus and the Theory of Planned Behavior was developed and empirically tested through a cross-sectional field survey from September 2022 to October 2022 in the Yangtze River Delta region, China. A 33-item measurement instrument was developed. Descriptive statistics, chi-square tests, and logistic regression analyses were conducted to characterize the willingness of sharing personal health data and differences by sociodemographic factors. Structural equation modeling was used to assess the reliability and validity of the measurement as well as to test the research hypotheses. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies was applied for reporting results. RESULTS: The empirical framework had a good fit with the chi-square/degree of freedom (χ2/df)=2.637, root-mean-square residual=0.032, root-mean-square error of approximation=0.048, goodness-of-fit index=0.950, and normed fit index=0.955. A total of 2060 completed questionnaires were received (response rate: 2060/2400, 85.83%). Moral motive (ß=.803, P<.001), perceived benefit (ß=.123, P=.04), and perceived effectiveness of government regulation (ß=.110, P=.001) had a significantly positive association with sharing willingness, while perceived risk (ß=-.143, P<.001) had a significant negative impact, with moral motive having the greatest impact. The estimated model explained 90.5% of the variance in sharing willingness. CONCLUSIONS: This study contributes to the literature on personal health data sharing by integrating the Theory of Privacy Calculus and the Theory of Planned Behavior. Most Chinese patients are willing to share their personal health data, which is primarily motivated by moral concerns to improve public health and assist in the diagnosis and treatment of illnesses. Patients with no prior experience with personal information disclosure and those who have tertiary hospital visits were more likely to share their health data. Practical guidelines are provided to health policy makers and health care practitioners to encourage patients to share their personal health information.

[Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats].

OBJECTIVE: To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction (POCD), neuronal apoptosis and neuron-inflammation in aged rats. METHODS: Thirty-six male SD rats aged 20 months were randomly divided into sham operation group, model group and electroacupuncture (EA) group, with 12 rats in each group. The POCD rats model was prepared by internal fixation of left tibial fracture. Five days before modeling, EA stimulation (2 Hz/15 Hz, 1 mA, 30 min) was applied to "Zusanli" (ST36), "Hegu" (LI4) and "Neiguan" (PC6) on the unaffected side of rats in the EA group, once a day for consecutive 5 d. The learning and memory abilities of rats were evaluated by water maze test 31-35 days after operation. The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining. The expressions of high mobility group protein B1 (HMGB1) and phosphorylated (p)-nuclear factor (NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining. The expression levels of interleukin (IL)-6 and IL-1ß in the hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency was prolonged (P<0.05); the frequency of crossing the original platform, ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased (P<0.05); the apoptosis rate of hippocampal neurons was significantly increased (P<0.05); the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group. Compared with the model group, the results of the above indexes were all opposite (P<0.05) in the EA group. CONCLUSION: EA preconditioning can regulate hippocampal inflammatory response, alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD, the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

[Changes in physicochemical property and microbial community of Pseudostellaria heterophylla soil at diffe-rent fallow ages]. / 太子参不同休耕年限土壤理化特征和微生物群落变化.

Pseudostellaria heterophylla is authentic traditional Chinese herbal medicine in Fujian Province. P. hete-rophylla suffers from serious consecutive monoculture problems. Fallow can alleviate such problems, but the mecha-nism is still unclear. In this study, high-throughput sequencing was performed to analyze the changes in soil microbial community structure and diversity in the P. heterophylla soil at different fallow ages as well as their relationships with soil physicochemical properties and phenolic acids. The results showed that fungal community diversity decreased but bacterial community diversity increased in fallow soils compared with the control soil of P. heterophy-lla. For bacterial communities, the relative abundance of Acidobacteria increased, while that of Proteobacteria and Actinobacteria decreased in fallow soils. For fungal communities, the relative abundance of dominant phyla had no significant difference between fallow and control soils. Soil acidity and organic matter content showed a trend of weakening and decreasing, respectively, with the increases of fallow years. In addition, with the increases of fallow years, the content of phenolic acids in soil, including benzoic acid and salicylic acid, showed significant decrease, while some other phenolic acids such as p-coumaric acid were accumulated obviously. Taken together, fallow could efficiently ameliorate the structure of soil microbial community and soil properties of P. heterophylla, and thus alleviate the effects of continuous cropping.

Effects of sodium pyruvate supplementation on repeated sprint exercise performance and recovery in male college soccer players: a randomized controlled trial.

BACKGROUND: Sodium pyruvate (PYR) has been reported to improve aerobic metabolism and attenuate metabolic acidosis. Aerobic capacity and the ability to remove hydrogen ions affect the recovery from repeated high intensity activities. However, the effects of PYR supplementation on repeated sprint exercise (RSE) performance have not been elucidated. This study explored the effects of PYR ingestion on RSE ability and recovery. METHODS: A total of 14 male soccer athletes (aged 20±2 years) participated in this double-blinded crossover study. The subjects completed two experimental sessions after randomized ingestion of either PYR or the maltodextrin placebo (PLA) for 1 week. At each session, participants completed high-intensity interval exercise (HIIE) and RSE 60 minutes after supplementation. Additionally, acid-base parameters in venous blood, energy system contributions, and power output were assessed. RESULTS: Compared to PLA, PYR supplementation significantly increased the relative peak power output (PPO) of the first (P=0.034) and fifth (P=0.043) sprints, and the relative mean power output (MPO) of the fifth sprint (P=0.026). In addition, the mean PPO (P=0.031) and MPO (P=0.033) of sprints 1-6 were significantly elevated after PYR supplementation. After PYR administration, the phosphagen energy system [adenosine triphosphate (ATP)-phosphocreatine (PCr)] resynthesis of the fourth (P=0.034) and the overall recovery periods during HIIE (P=0.029) were higher than PLA administration. Additionally, the ATP-PCr resynthesis of the first (P=0.033) and fifth (P=0.019) recovery periods, and the mean of the six recovery periods during RSE (P=0.041) were increased in the PYR group compared to the PLA group. Furthermore, participants on the PYR regimen had higher blood pH, HCO3-, and base excess at pre-HIIE, post-HIIE, and pre-RSE (all P<0.05) compared to participants receiving PLA. CONCLUSIONS: PYR supplementation enhanced RSE performance, and the improvement may be attributed to accelerated restoration of the acid-base balance and ATP-PCr regeneration. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053936.

Efficacy assessment for low-level laser therapy in the treatment of androgenetic alopecia: a real-world study on 1383 patients.

Low-level laser therapy (LLLT) has been a treatment modality by many androgenetic alopecia (AGA) patients in recent years. It remained unclear as to how long the treatment regime should be maintained, and which characteristics of patients should this be recommended. A real-world study was carried out with an FDA-cleared low-level laser helmet for 1383 patients. Ordinal logistic regression analysis with propensity score matching (PSM) was used to investigate the factors related to efficacy assessment. More than 80% of users were between 18 and 40 years old. The median use times were 133 for mild AGA patients and 142 for moderate-to-severe AGA patients, which equated to 38 weeks and 40 weeks, respectively. The overall clinical effectiveness was nearly 80%. PSM analysis revealed that gender (P = 0.002), use period (P = 0.068), scalp conditions with dandruff, rash, and itchy symptoms were associated with the grading of efficacy assessment. Male users (ordinal OR: 1.35, CI: (1.01, 1.79)); use for more than 180 times or use period for 1 year (ordinal OR: 1.40, CI: (1.11, 1.96)); and those with scalp dandruff (ordinal OR: 1.34, CI: (1.01, 1.87)), rash (ordinal OR: 1.47, CI: (1.04, 2.07)), and itchy symptoms (ordinal OR: 1.51, CI: (1.12, 2.03)) had better efficacy assessments. The recommended treatment regime with low-level laser helmet was more than 1 year or 180 use times. Male patients with dandruff, rash, and itchy symptoms in scalps tended to have a better efficacy assessment.

TroR Negatively Regulates the TroABCD System and Is Required for Resistance to Metal Toxicity and Virulence in Streptococcus suis.

Streptococcus suis is an emerging zoonotic pathogen that causes severe swine and human infections. Metals are essential nutrients for life; however, excess metals are toxic to bacteria. Therefore, maintenance of intracellular metal homeostasis is important for bacterial survival. Here, we characterize a DtxR family metalloregulator, TroR, in S. suis. TroR is located upstream of the troABCD operon, whose expression was found to be significantly downregulated in response to excess manganese (Mn). Deletion of troR resulted in reduced growth when S. suis was cultured in metal-replete medium supplemented with elevated concentrations of zinc (Zn), copper (Cu), or cobalt (Co). Mn supplementation could alleviate the growth defects of the ΔtroR mutant under Zn and Co excess conditions; however, it impaired the growth of the wild-type (WT) and complemented (CΔtroR) strains under Cu excess conditions. The growth of ΔtroR was also inhibited in metal-depleted medium supplemented with elevated concentrations of Mn. Moreover, the ΔtroR mutant accumulated increased levels of intracellular Mn and Co, rather than Zn and Cu. Deletion of troR in S. suis led to significant upregulation of the troABCD operon. Furthermore, troA expression in the WT strain was induced by ferrous iron [Fe(II)] and Co and repressed by Mn and Cu; the repression of troA was mediated by TroR. Finally, TroR is required for S. suis virulence in an intranasal mouse model. Together, these data suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis. IMPORTANCE Metals are essential nutrients for life; however, the accumulation of excess metals in cells can be toxic to bacteria. In the present study, we identified a metalloregulator, TroR, in Streptococcus suis, which is an emerging zoonotic pathogen. In contrast to the observations in other species that TroR homologs usually contribute to the maintenance of homeostasis of one or two metals, we demonstrated that TroR is required for resistance to the toxicity conferred by multiple metals in S. suis. We also found that deletion of troR resulted in significant upregulation of the troABCD operon, which has been demonstrated to be involved in manganese acquisition in S. suis. Moreover, we demonstrated that TroR is required for the virulence of S. suis in an intranasal mouse model. Collectively, these results suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis.

Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.

Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice.

Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer's disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L.plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αß levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD.

Effect of Personalized Music Intervention in Mechanically Ventilated Children in the PICU: A Pilot Study.

OBJECTIVES: To determine the feasibility of a personalized music intervention with mechanically ventilated patients in the PICU. DESIGN: Pilot study with a quasi-experimental design. SETTING: Tertiary children's hospital in China with a 40-bed PICU. PATIENTS: Children, 1 month to 7 years, with mechanical ventilation were recruited and assigned to music group (n = 25) and control group (n = 25). INTERVENTIONS: Children in the music group received their own favorite music and listened for 60 minutes three times a day. The control group receive routine care without music. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was comfort measured with the COMFORT Behavior scale 5 minutes before and after the music. Secondary outcome measures were physiologic variables; heart rate, respiration, blood pressure, oxygen saturation. Mechanical ventilation time, length of stay, and sedation medication were also collected. Qualitative analysis revealed that nurses had a positive attitude in delivering the interventions and identified improvements for the main trial. Children in the music group had lower COMFORT Behavior scores (15.7 vs 17.6; p = 0.011). Children in the music group had better physiologic outcomes; heart rate (140 vs 144; p = 0.039), respiration rate (40 vs 43; p = 0.036), systolic blood pressure (93 vs 95 mm Hg; p = 0.031), oxygen saturation (96% vs 95%; p < 0.001), diastolic blood pressure was not significantly (52 vs 53 mm Hg; p = 0.11). Children in the music group had a shorter ventilation time (148.7 vs 187.6; p = 0.044) and a shorter length of stay, but not significant (11.2 vs 13.8; p = 0.071). Children in the control group had higher total amount of on-demand midazolam (29 vs 33 mg; p = 0.040). CONCLUSIONS: Our pilot study indicates that personalized music intervention is feasible and might improve the comfort of children with mechanical ventilation. Further studies are needed to provide conclusive evidence in confirming the effectiveness of music interventions comforting critically ill children in PICUs.

Comparison of Potent Odorants in Raw and Ripened Pu-Erh Tea Infusions Based on Odor Activity Value Calculation and Multivariate Analysis: Understanding the Role of Pile Fermentation.

Infusions prepared from raw pu-erh tea (RAPT) and ripened pu-erh tea (RIPT) showed remarkable aroma differences. Predominant odorants in RAPT and RIPT infusions were identified and compared by the combined use of gas chromatography-olfactometry, aroma extract dilution analysis, odor activity values (OAVs), and multivariate analysis. A total of 35 and 19 odorants (OAV > 1) were detected in RIPT and RAPT, respectively. Odorants in RAPT and RIPT are significantly different in both odor properties and aroma compound intensities. Overall, RAPT contained a complex variety of chemical classes with diverse odors and moderate odor intensities, while RIPT is dominated by structurally and organoleptically similar compounds with high potency. Specifically, stale and musty smelling methoxybenzenes contributed the most to RIPT, while floral-, sweet-, and woody-smelling terpene alcohols, terpene ketones, and phenolic compounds were the predominant odorants in RAPT. Orthogonal partial least squares discriminant analysis revealed that linalool, α-ionone, 1,2,4-trimethoxybenzene, 1,2,3-trimethoxy-5-methylbenzene, 1,2,3,4-tetramethoxybenzene, and 1,2,3-trimethoxybenzene underwent remarkable changes during pile fermentation and could be used as potential odor-active markers for RIPT and RAPT discrimination. The comprehensive aroma characterization of pu-erh tea and determination of the effect of pile fermentation on odorant alteration herein will provide guidance for pu-erh tea flavor quality control and evaluation.

Progress in Development of Interventions to Prevent Birth Defects in Diabetic Pregnancies.

Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on the basic research data, efforts have been made to develop interventional strategies to alleviate the stress conditions and to reduce embryonic malformations. One of the challenges in birth defect prevention is to identify effective and safe agents to be used in pregnancy. One approach is to search and characterize naturally occurring phytochemicals, including flavonoids, curcuminoids and stilbenoids, for use in prevention of diabetic embryopathy.

[Linggui Fang protects the reproductive system of asthenospermia rats: An experimental study based on the L-carnitine pathway].

OBJECTIVE: To explore the protective effect of the Chinese medicinal prescription Linggui Fang (LGF) on the reproductive system of the ornidazole-induced asthenospermia (AS) rat and its possible action mechanisms. METHODS: Forty male SD rats weighing 200－230 g were equally randomized into four groups, blank control, AS model control, LGF treatment and L-carnitine (LC) intervention. The AS models were made in the latter three groups by intragastrical administration of ornidazole at 400 mg/kg. Meanwhile, the rats in the LGF group were treated intragastrically with LGF at 17.5 g/kg, those in the LC group with LC at 100 mg/kg, and the control animals with 0.5% sodium carboxymethylcellulose (CMC-Na), all once a day for 4 successive weeks. Then, all the rats were sacrificed for examination of the semen parameters, determination of the LC content and OCTN2 mRNA expression in the epididymis and observation of the histopathological changes in the testis. RESULTS: Compared with the AS model controls, the rats in the other groups showed significantly higher percentages of progressively motile sperm and total motile sperm (P < 0.01) as well as a higher LC content in the epididymis (P < 0.01), but no statistically significant difference in sperm concentration (P > 0.05). The expression of OCTN2 mRNA was remarkably upregulated in the LGF and LC groups in comparison with that in the AS model control (P < 0.05). Compared with the rats in the blank control group, the AS model controls exhibited markedly increased morphologically abnormal seminiferous tubules, irregularly arranged, with narrowed lumens and reduced numbers of sperm and sperm cells, as well as significantly increased hollow seminiferous tubules with deficient and disorderly arranged spermatogenic cells and partial epithelial degeneration and vacuolization. Those in the LGF and LC groups, however, manifested almost normal testicular histomorphology, with basically regular arrangement of different layers of seminiferous tubules. CONCLUSIONS: ①Ornidazole induces AS in rats by reducing the LC content in the epididymis, while LGF can improve the sperm motility and testicular morphology of the rats and upregulate the expression of OCTN2 mRNA in the epididymis by increasing the LC concentration.

Effect of transcutaneous electrical acupoint stimulation on the EC50 of remifentanil suppressing responses to tracheal extubation in elderly patients.

Transcutaneous electrical acupoint stimulation (TEAS) is a emerging treatment which combines transcutaneous electrical nerve stimulation with traditional acupoint therapy. The present study was aimed to evaluate the effect of TEAS on the effective concentration (EC50) of remifentanil suppressing tracheal extubation response in elderly patients.Fifty-three patients undergoing spine surgery were randomly divided into 2 groups: control group (group C, n = 26) and transcutaneous electrical acupoint stimulation group (group TEAS, n = 27). The EC50 values for remifentanil TCI were determined using sequential method and probit analysis.The remifentanil EC50 of that suppressed responses to extubation during anesthetic emergence was 1.20 ng/mL in group TEAS, a value that was significantly lower than the 1.64 ng/mL needed by patients in group C.The TEAS can enhance the efficacy of remifentanil on suppressing responses to tracheal extubation in elderly patients, the EC50 of remifentanil can reduce approximately 27% compared with group C.

[Qiaoshao Prescription improves premature ejaculation in male rats by increasing the content of 5-hydroxytryptamine].

Objective: To observe the intervention effect of Qiaoshao Prescription (QSP) on premature ejaculation (PE) induced by 8-OH-DPAT in male rats and explore its possible action mechanism. METHODS: Seventy-two male Wistar rats were equally randomized into six groups, blank control, PE model control, low-, medium- and high-dose QSP, and dapoxetine. The PE model was established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord. Four weeks after modeling, the rats in the blank control and PE model control groups with gavaged with normal saline at 10 ml/kg/d, those in the low-, medium- and high-dose QSP groups with QSP at 5, 10 and 20 g/kg/d respectively once a day, and those in the dapoxetine group with dapoxetine hydrochloride at 300 mg/kg at 3 hours before mating. Forty-five female Wistar rats were injected subcutaneously with 20 µg estradiol benzoate after removal of bilateral ovaries to induce estrous estrus. Two and 4 weeks later, the male rats were mated with the female ones for 30 minutes per time and meanwhile observed for the mating behavior of the males, including mounting latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), and ejaculation frequency (EF). After the 4th week of mating, the hypothalamus of the animals was isolated and weighed, and the content of 5-hydroxytryptamine (5-HT) was measured. RESULTS: Compared with the blank control group, the PE model controls showed significantly decreased content of 5-HT in the hypothalamus(1 257.1 vs 923.4 ng/g, P<0.05), ML (ï¼»11.22 ± 3.60ï¼½ vs ï¼»8.69 ± 2.48ï¼½ s, P<0.05), IL (ï¼»22.33 ± 2.45ï¼½ vs ï¼»12.08±1.39ï¼½ s, P<0.05), MF (ï¼»13.28 ± 3.24ï¼½ vs ï¼»7.53 ± 1.84ï¼½ times, P<0.05), and EL (ï¼»712.35 ± 36.77ï¼½ vs ï¼»502.35 ± 46.72ï¼½ s, P<0.05). In comparison with the PE model controls, the rats of the QSP and dapoxetine groups exhibited remarkably increased content of 5-HT (P<0.05) and prolonged EL (P<0.05). CONCLUSIONS: Qiaoshao Prescription can prolong EL in PE rats, which might be associated with the increased content of 5-HT in the hypothalamus. Further studies, however, are needed on its underlying mechanisms.

A new method for hydroxyl radical detection by chemiluminescence of flue-cured tobacco extracts.

Chemiluminescence (CL) reactions usually take place in a severely restricted pH regime, thereby confining their application in media at different pH. In this paper, the CL behavior of tobacco-methanol extract (TME) was explored. Surprisingly, TME exhibited CL behavior upon mixing with Fe2+/H2O2, HRP/H2O2 and gold nanoparticles/H2O2 oxidation systems, i.e., in acidic, neutral and alkaline solution respectively. Addition of different reactive oxygen species scavengers verified that the hydroxyl radical (OH) triggers TME CL reactions. Then, the CL behavior of TME was applied to determine OH in tetrachloro-1,4-benzoquinone (TCBQ)/H2O2 system in acidic, neutral and alkaline solutions. CL intensity correlated most strongly (R2 = 0.99) with TCBQ concentration, which was used as a means to indirectly denote OH concentration. This implies that OH could be determined by a TME CL method in a semi-quantitative way regardless of pH value. Therefore, the TME CL method may be a promising method for OH determination in various OH-generating systems.