SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Remote Charging and Degradation Suppression for the Quantum Battery.

The quantum battery (QB) makes use of quantum effects to store and supply energy, which may outperform its classical counterpart. However, there are two challenges in this field. One is that the environment-induced decoherence causes the energy loss and aging of the QB, the other is that the decreasing of the charger-QB coupling strength with increasing their distance makes the charging of the QB become inefficient. Here, we propose a QB scheme to realize a remote charging via coupling the QB and the charger to a rectangular hollow metal waveguide. It is found that an ideal charging is realized as long as two bound states are formed in the energy spectrum of the total system consisting of the QB, the charger, and the electromagnetic environment in the waveguide. Using the constructive role of the decoherence, our QB is immune to the aging. Additionally, without resorting to the direct charger-QB interaction, our scheme works in a way of long-range and wireless-like charging. Effectively overcoming the two challenges, our result supplies an insightful guideline to the practical realization of the QB by reservoir engineering.

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image.

PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

[Analysis of peptides and proteins from Asini Corii Colla using nano LC-Q-Exactive-MS/MS].

This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 µm×2 cm, 5 µm, C_(18)) as precolumn, Thermo Scientific EASY column(75 µm×100 mm, 3 µm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.

[Research progress on quality control methods of traditional Chinese medicine glues].

Traditional Chinese medicine( TCM) glues,including leather glues,horn glues,nail glues and bone glues,have a long application history and unique characteristics. In recent years,their market demand has increased year by year because of their remarkable curative efficacy and nourishing effects,which leads to insufficient supply of raw material resources,and widespread use of fake and inferior products,seriously affecting the reputation of TCM glues and drug safety. In this context,the establishment of a more specific quality detection method for the TCM glues according to their specific characteristics can effectively improve the quality control level,promote rational use,and have a far-reaching impact on the industrial development of TCM glues. In this paper,the classification of TCM glues,as well as the production and application status of their representative( Ejiao) were briefly introduced; the papers on quality control technologies of TCM glues,including traditional identification experience,authenticity identification,physical property determination,protein,peptide and amino acid contents determination,element analysis,biological evaluation,and brand protection technology of TCM glues,were reviewed,and their advantages and disadvantages were summarized and analyzed comprehensively.Based on the specific characteristics of TCM glues,such as complex material basis,unclear pharmacodynamic components and different production processes,it was proposed in this paper to research and develop information-rich,convenient,fast,and non-destructive analytical techniques for the quality control of TCM glues and brand protection of famous products,thus promoting the healthy development of TCM glues industry.

Development of an isothermal amplification-based assay for the rapid visual detection of Salmonella bacteria.

The efficient and timely detection of pathogens is a major concern worldwide. The aim of this study was to establish a rapid detection method for Salmonella bacteria in food samples to facilitate timely treatment. Widely used detection methods currently include culture-based methods and PCR-based methods. The former are time consuming, requiring 2 to 3 d, whereas the latter have higher accuracy but are typically complicated, requiring expertise and expensive instruments. In this study, a sensitive and rapid approach for the visual and point-of-use detection of Salmonella bacteria based on recombinase polymerase amplification (RPA) and a lateral-flow (LF) nucleic acid strip was established. We designed a pair of primers according to the invA gene of Salmonella bacteria: one was modified with digoxin, and the other was modified with biotin. In the presence of the biotin- and digoxin-modified primers and target DNA, the RPA produced a substantial amount of duplex DNA attached to biotin and digoxin. The products were detected using LF strips through immunoreaction: anti-digoxin antibodies on the gold nanoparticles, digoxin on the duplex, streptavidin on the LF test line, and biotin on the duplex. The developed RPA-LF assay allowed detection of Salmonella genomic DNA in less than 20 min with simple water bath equipment or portable thermal equipment. In addition, the RPA-LF assay was highly sensitive, with a detection limit as low as 20 fg of target DNA or 1.05 × 101 cfu of bacteria in pure culture, and highly specific, exhibiting no cross-reaction with Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, Shigella, Enterobacter aerogenes, or Campylobacter jejuni. Importantly, Salmonella could be detected in milk and chicken breast at concentrations as low as 1.05 × 100 cfu/mL or 1.05 × 100 cfu/g after enrichment for 2 h and in eggs at 1.05 × 100 cfu/g after enrichment for 4 h. Furthermore, RPA was more sensitive than PCR, which requires a thermal cycling device. In summary, this study describes a sensitive, simple, and point-of-use detection method for Salmonella bacteria.

Effects of 8-week swimming training on carotid arterial stiffness and hemodynamics in young overweight adults.

BACKGROUND: Exercise has been found to either reduce or increase arterial stiffness. Land-based exercise modalities have been documented as effective physical therapies to decrease arterial stiffness. However, these land-based exercise modalities may not be suitable for overweight individuals, in terms of risks of joint injury. The purpose of this study was to determine the effects of 8-week swimming training and 4-week detraining on carotid arterial stiffness and hemodynamics in young overweight adults. METHODS: Twenty young male adults who were overweight were recruited and engaged in 8-week of swimming training and 4-week detraining. Five individuals withdrew due to lack of interest and failure to follow the training protocol. Body Fat Percentage (BFP) and carotid hemodynamic variables were measured on a resting day at the following intervals: baseline, 4 weeks, 8 weeks after swimming training and 4 weeks after detraining. A repeated analysis of variance (ANOVA) was used to assess the differences between baseline and each measurement. When significant differences were detected, Tukey's test for post hoc comparisons was used. RESULTS: Eight-week swimming training at moderate intensity decreased BFP, including the trunk and four extremities. Additionally, the BFP of the right and left lower extremities continued to decrease in these overweight adults 4 weeks after ceasing training. Carotid arterial stiffness decreased, while there were no significant changes in arterial diameters. Blood flow velocity, flow rate, maximal and mean wall shear stress increased, while systolic blood pressure and peripheral resistance decreased. No significant differences existed in minimal wall shear stress and oscillatory shear stress. CONCLUSIONS: Eight-week swimming training at moderate intensity exhibited beneficial effects on systolic blood pressure, arterial stiffness and blood supply to the brain in overweight adults. Moreover, maximal and mean wall shear stress increased after training. It is worth noting that these changes in hemodynamics did not last 4 weeks. Therefore, further studies are still warranted to clarify the underlying relationship between improvements in arterial stiffness and alterations in wall shear stress.

Acute effect of cycling intervention on carotid arterial hemodynamics: basketball athletes versus sedentary controls.

OBJECTIVE: To compare the acute effects of a cycling intervention on carotid arterial hemodynamics between basketball athletes and sedentary controls. METHODS: Ten young long-term trained male basketball athletes (BA) and nine age-matched male sedentary controls (SC) successively underwent four bouts of exercise on a bicycle ergometer at the same workload. Hemodynamic variables at right common carotid artery were determined at rest and immediately following each bout of exercise. An ANCOVA was used to compare differences between the BA and SC groups at rest and immediately following the cycling intervention. The repeated ANOVA was used to assess differences between baseline and each bout of exercise within the BA or SC group. RESULTS: In both groups, carotid hemodynamic variables showed significant differences at rest and immediately after the cycling intervention. At rest, carotid arterial stiffness was significantly decreased and carotid arterial diameter was significantly increased in the BA group as compared to the SC group. Immediately following the cycling intervention, carotid arterial stiffness showed no obvious changes in the BA group but significantly increased in the SC group. It is worth noting that while arterial stiffness was lower in the BA group than in the SC group, the oscillatory shear index (OSI) was significantly higher in the BA group than in the SC group both at rest and immediately following the cycling intervention. CONCLUSION: Long-term basketball exercise had a significant impact on common carotid arterial hemodynamic variables not only at rest but also after a cycling intervention. The role of OSI in the remodeling of arterial structure and function in the BA group at rest and after cycling requires clarification.

Effects of MicroRNA-132 transfection on the proliferation and apoptosis of human liver cancer cells in vitro and in vivo.

OBJECTIVE: To observe the biological role and underlying mechanism of microRNA-132 (miR-132) in liver cancer cell proliferation and apoptosis. METHODS: The expressions of miR-132 in the cancer tissue and their adjacent tissues from 45 liver cancer patients were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The biological effects of miR-132 transfection on human liver cancer MHCC97H cells were assessed by CCK-8 assay, flow cytometry,in vivo experiment in nude mice, and TUNEL test. Western blotting was used to detect the expressions of p-AKT, Survivin, and Caspase 3 in liver cancer cells. Immunohistochemistry was used to detect the positive expressions of Ki-67,Survivin,and Caspase 3 in the xenograft tumors. RESULTS: The expression level of miR-132 was found to be down-regulated in liver cancer tissues compared with the matched adjacent tissues (P<0.05). After transfection,the expression of miR-132 was significantly higher than blank control group and negative control group (P<0.05). The proliferation of liver cancer cells was inhibited significantly by miR-132 transfection (P<0.05). Transfection of miR-132 arrested cells in the G0/G1 phase and triggered apoptosis of MHCC97H cells (P<0.05). After miR-132 transfection,the expression of Caspase 3 was up-regulated, whereas the expressions of p-AKT and Survivin were down-regulated (P<0.05). In addition,the tumor weight in miR-132 transfection group was significantly decreased in comparison with blank control group and negative control group (P<0.05). Apoptosis occurred more frequently in the miR-132 transfection group than in control groups (P<0.05). Compared with the blank control group and negative control group, the miR-132 transfection group had significantly decreased expression of Survivin but increased positive expression of Ki-67 and Caspase 3(P<0.05). CONCLUSIONS: miR-132 is down-regulated in human liver cancer tissues miR-132 transfection can effectively inhibit proliferation and promote apoptosis of MHCC97H cells in vitro and in vivo. Therefore, miR-132 may become a new target in liver cancer treatment.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Study on impurities in naringin extracted from Citrus grandis 'tomentosa'.

OBJECTIVE: To investigate the impurities in naringin extracted from Citrus grandis 'Tomentosa'. METHODS: High performance liquid chromatographies coupled with photodiode array and electrospray ionization mass spectrometry detectors (HPLC-PDA/ESI-MS/MS) were applied to investigate the impurities, and their structures were elucidated by spectral data analyses. Quantification was carried out by main component self-compare with correction factor according to ICH guidelines. RESULTS: Rhoifolin and neoeriocitrin were identified as major impurities. The correction factors of rhoifolin and neoeriocitrin were 1.82 and 1.02, respectively tested by HPLC method. The content of rhoifolin ranged from 0.742% to 0.926%, and the content of neoeriocitrin ranged from 0.335% to 0.464%. The gross impurities were less than 1.5%. CONCLUSION: The categories and quantities of impurities in naringin product are relatively stable. The research provides a way of specification and verification for the analysis of impurities and objective evidence for security assessment of naringin product.

Effects of movement direction and limb dominance on ankle muscular force in sidestep cutting.

Sidestep cutting is a critical movement in sports. However, biomechanical research on sidestep cutting has not hitherto reached a consensus. In order to investigate the effects of limb dominance and movement direction on ankle and subtalar joints during sidestep cutting, twelve physically active male participants were recruited in the present study. Trajectory and ground reaction force data were collected by the motion capture system and force platform. Kinematics, kinetics, and muscle forces information were obtained by running OpenSim. Two-way repeated measures ANOVA was performed with movement direction and limb dominance as independent variables. We found that movement direction had a significant effect on ankle dorsiflexion angle. In contrast, the factor of limb dominance had no effect on ankle and subtalar joints angles. For ankle joint moment, the plantarflexion moment was greater by performing a 45° sidestep cutting or using the dominant limb, while the subtalar joint moment was not affected by these two variables. In terms of muscle forces, the soleus of the dominant limb generated greater plantarflexion muscle force on the sagittal plane, while the non-dominant limb tended to contract more strongly (peroneus longus and peroneus brevis) on the frontal plane to stabilize the subtalar joint. Meanwhile, a smaller sidestep cutting angle made participants generate greater plantarflexion muscle forces (soleus and gastrocnemius). In conclusion, our findings indicated that participants should take limb dominance and movement direction into consideration for enhancing athletic performance and reducing the risk of injury during sidestep cutting.

Acute Effects of Different Intensities of Cycling Acute Exercise on Carotid Arterial Apparent Elasticity and Hemodynamic Variables.

BACKGROUND: Cardiovascular disease (CVD) is closely related to arterial elasticity and hemodynamics. Exercises have been reported to immediately decrease arterial apparent elasticity and regulate hemodynamic variables. However, the relationship between them and exercise intensity remains elusive. The purpose of this study was to determine the acute effects of different intensities of acute cycling exercise on carotid arterial apparent elasticity and hemodynamics. METHODS: 32 healthy men (age: 19.4 ± 0.6 years) attended the laboratory on five occasions and completed cycling acute exercise for 20 minutes at five intensities (40%, 50%, 60%, 70%, and 80% heart rate reserve (HRR)). At the right carotid artery, center-line velocity and arterial inner diameter waveforms were examined before and immediately after exercise. Based upon the measured data, the classical hemodynamic theory was used to calculate the apparent elasticity and the local hemodynamic variables. RESULTS: The arterial apparent stiffness and the apparent elastic modulus following acute cycling exercise at 60% to 80% HRR were significantly higher than baseline. The mean center-line velocity accelerated from 50% to 80% HRR, but no intensity of intervention altered mean blood flow. Immediately after intervention, the mean wall shear stress and oscillatory shear index increased. CONCLUSIONS: Aerobic cycling intervention, with intensity from 40% to 80% HRR, did not change the brain blood supply. A bout of cycling intervention decreased apparent elasticity, and there was an intensity-dependent effect on apparent elasticity and hemodynamic variables. This study would provide referable data for the further study on the effects of aerobic exercise on arterial hemodynamics and elasticity and underlying physiological mechanisms.

Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations.

Herbal medicines are frequently used for the prevention and treatment of obesity and obesity-related disorders. Our preliminary screening showed that St. John's Wort (SJW) displayed potent inhibition on pancreatic lipase (PL), a key hydrolase responsible for lipid digestion and absorption in mammals. Herein, the inhibition potentials and inhibitory mechanism of SJW extract and its major constituents on PL were fully investigated by a set of in vitro and in silico studies. The results clearly demonstrated that the naphthodianthrones, biflavones and most of flavonoids in SJW displayed strong to moderate inhibition on PL. Among all tested natural compounds, two naphthodianthrones (hypericin and pseudohypericin) and one biflavone (I3,II8-biapigenin) isolated from SJW exhibited potent PL inhibition activity, with the IC50 values of <1 µM. Inhibition kinetics analyses showed that hypericin, pseudohypericin and I3,II8-biapigenin inhibited PL via a mixed manner, while molecular dynamics simulations revealed that three newly identified PL inhibitors could bind on PL at both the catalytic cavity and the interface between colipase and the C-terminal domain of PL. Collectively, our findings suggested that part of major constituents in SJW displayed potent PL inhibition activities, which could be used as lead compounds for the development of novel PL inhibitors.

Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies.

Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC50 = 7.96 µM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K i value of 12.23 µM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents.

Insulin treatment affects leukocyte telomere length in patients with type 2 diabetes: 6-year longitudinal study.

OBJECTIVE: Many studies demonstrated a close relationship between type 2 diabetes mellitus (T2DM) and leukocyte telomere length (LTL). However, how the LTL changes in T2DM and what are the potential causal factors in it, particularly in patients during a long period treatment, have not been studied. Here we performed a longitudinal observation of LTL in trained T2DM patients during a 6-year follow-up and evaluated the possible risk factors that were associated with LTL alteration. METHODS: Seventy-six patients with T2DM were enrolled in this 6-year longitudinal study. The enrolled patients had no severe complication and had never received insulin therapy by the time. Patients were scheduled to visit once every one or two months and their medication changes were recorded. The LTL at the time when patients were enrolled was used as baseline, which was compared with the LTL at 6 year. Multivariable linear regression and exact logistic regression model were adopted to identify independent predictors of telomere length change and telomere length shortening, respectively. RESULTS: Sixty-four patients were successfully followed up. Although mean LTL decreased after 6 years, 30% (19/64) of patients demonstrated LTL lengthening and 70% (45/64) of patients demonstrated LTL shortening. Among them, 18 Patients received insulin treatment during the 6 years. Of these 18 patients, 16 patients showed decreased LTL and only two showed increased LTL. Linear regression analysis demonstrated that change in telomere length during the 6 years was associated inversely with insulin use (ß-coefficients: -0.587, 95% CI: -0.198, -0.085, P < 0.001). Exact logistic regression analysis showed insulin use (OR: 17.355, 95% CI: 2.659, 35.627, P = 0.013) and LDL-C(OR: 3.493, 95% CI: 1.559, 10.063, P = 0.007)were independent predicts of telomere length shortening. CONCLUSIONS: LTL may increase as well as decrease in T2DM who received antidiabetic treatment. Insulin use may accelerate telomere attrition. Insulin use and LDL-C can predict telomere shortening.

ROS and NO Dynamics in Endothelial Cells Exposed to Exercise-Induced Wall Shear Stress.

INTRODUCTION: Intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels are associated with vascular homeostasis and diseases. Exercise can modulate ROS and NO production through increasing frequency and magnitude of wall shear stress (WSS). However, the details of ROS and NO production in endothelial cells and their interplay under WSS induced by exercise at different intensities remain unclear. METHODS: In this study, we developed an in vitro multicomponent nonrectangular flow chamber system to simulate pulsatile WSS waveforms induced by moderate and high intensity exercise. Furthermore, the dynamic responses of ROS and NO in endothelial cells and the relationship between ROS and NO were investigated under the WSS induced by different intensity exercise. RESULTS: After exposing to WSS induced by moderate intensity exercise, endothelial cells produced more NO than those under high intensity exercise-induced WSS. In this process, ROS was found to play a dual role in the generation of intracellular NO. Under WSS induced by moderate intensity exercise, modest elevated ROS promoted NO production, whereas excessive ROS in endothelial cells exposed to WSS induced by high intensity exercise attenuated NO bioavailability. Interestingly, antioxidant N-acetylcysteine (NAC) could increase NO production under WSS induced by high intensity exercise. CONCLUSIONS: Our results provide some cues for selecting appropriate exercise intensities and elevating benefits of exercise on endothelial function. Additionally, owing to the consistency of our results and some in vivo phenomena, this flow chamber system may serve as an in vitro exercise model of arterial vessel for future studies.

Functionalized AuMBA @Ag Nanoparticles as an Optical and SERS Dual Probe in a Lateral Flow Strip for the Quantitative Detection of Escherichia coli O157:H7.

A method combining surface-enhanced Raman scattering (SERS) with a lateral flow strip (LFS) was developed for the quantitative and sensitive analysis of Escherichia coli O157:H7. AuMBA @Ag nanoparticles were prepared as SERS probes, and 4-methylthiobenzoic acid (MBA) as a Raman reporter was inserted into the interior gap of the Au@Ag core-shell nanoparticles, which replaced the Au nanoparticles that serve as SERS nanotags in traditional LFS. Using this developed SERS-LFS, the presence of the target bacteria could be tested through the appearance of a red band on the test line. Furthermore, quantitative analysis of E. coli O157:H7 was achieved by measuring the specific Raman intensity of MBA on the test line. The sensitivity of this SERS-LFS biosensor is 5 × 104 CFU/mL of E. coli O157:H7, which is 10-fold higher than that of a naked eye-based colorimetric LFS. This quantitative detection of E. coli O157:H7 ( Y = 1993.86 X - 6812.17, R2 = 0.9947) was obtained with a wide linear range (5 × 104 to 5 × 108 ) due to the signal enhancement of the SERS nanotags. In addition, the SERS-LFS could differentiate E. coli O157:H7 from closely related bacterial species or nontarget contaminants, suggesting high specificity of this assay. The applicability of SERS-LFS to the analysis of E. coli O157:H7 in milk, chicken breast, and beef was also validated, indicating that the sensitivity was not disturbed by the food matrix. In summary, the SERS-LFS developed in this study could be a powerful tool for the quantitative and sensitive screening of E. coli O157:H7 in a food matrix. PRACTICAL APPLICATION: This study demonstrates that a surface-enhanced Raman scattering (SERS)-based lateral flow strip (LFS) could be used as a rapid and sensitive method for Escherichia coli O157:H7 detection. Furthermore, this SERS-based LFS could achieve quantitative detection of the target, eliminating the defect of the traditional colloidal gold LFS, which is not quantifiable.

Inhibition of human carboxylesterases by ginsenosides: structure-activity relationships and inhibitory mechanism.

BACKGROUND: Human carboxylesterases (hCES) are key serine hydrolases responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters. Although it has been reported that some ginsenosides can modulate the activities of various enzymes, the inhibitory effects of ginsenosides on hCES have not been well-investigated. METHODS: In this study, more than 20 ginsenosides were collected and their inhibitory effects on hCES1A and hCES2A were assayed using the highly specific fluorescent probe substrates for each isoenzyme. Molecular docking simulations were also performed to investigate the interactions between ginsenosides and hCES. RESULTS: Among all tested ginsenosides, Dammarenediol II (DM) and 20S-O-ß-(d-glucosyl)-dammarenediol II (DMG) displayed potent inhibition against both hCES1A and hCES2A, while protopanaxadiol (PPD) and protopanaxatriol (PPT) exhibited strong inhibition on hCES2A and high selectivity over hCES1A. Introduction of O-glycosyl groups at the core skeleton decreased hCES inhibition activity, while the hydroxyl groups at different sites might also effect hCES inhibition. Inhibition kinetic analyses demonstrated that DM and DMG functioned as competitive inhibitors against hCES1A-mediated d-luciferin methyl ester (DME) hydrolysis. In contrast, DM, DMG, PPD and PPT inhibit hCES2A-mediated fluorescein diacetate (FD) hydrolysis via a mixed manner. CONCLUSION: The structure-inhibition relationships of ginsenosides as hCES inhibitors was investigated for the first time. Our results revealed that DM and DMG were potent inhibitors against both hCES1A and hCES2A, while PPD and PPT were selective and strong inhibitors against hCES2A.

Recombinase Polymerase Amplification Combined with Lateral Flow Strip for Listeria monocytogenes Detection in Food.

Listeria monocytogenes is an important food-borne pathogenic bacterium that causes human disease, resulting in economic losses worldwide. The current detection methods for L. monocytogenes are not well suited for direct field testing because they involve complicated, time-consuming operations. A simple, efficient method is vital for L. monocytogenes detection. In this study, we combined isothermal recombinase polymerase amplification (RPA) with a lateral flow (LF) strip to rapidly and reliably detect L. monocytogenes. In the presence of biotin- and digoxin-modified primers, RPA produced numerous digoxin- and biotin-attached duplex DNA products. These products were detected on an LF strip via dual immunoreactions (digoxin on the duplex DNA reacted with the anti-digoxin antibody on the gold nanoparticle (Au-NP) and the biotin on the duplex DNA captured by the streptavidin on the LF test zone). The accumulation of Au-NPs produced characteristic bands, enabling the visual detection of L. monocytogenes without instrumentation. This assay could be used to detect L. monocytogenes within 15 min, including DNA amplification with RPA for 10 min at 39 °C and visualization of the amplicons by LF strips for 5 min. Experiments confirmed a detection limit as low as 300 fg of DNA and 1.5 × 101 CFU in pure cultures. Furthermore, RPA-LF exhibited no cross-reactions with pathogens. Evaluation of the method with food samples indicated that the detection limit was substantially improved to 1.5 × 10° CFU for the original bacterial content in 25 g/mL samples after enrichment for 6 hr. RPA-LF can be used as a sensitive and rapid detection technique for L. monocytogenes. PRACTICAL APPLICATION: Recombinase polymerase amplification (RPA) can amplify target DNA at 37 to 42 °C without a thermal cycler. Lateral flow (LF) strips are portable, cheap and easy to operate. RPA combined with LF strips to detect Listeria monocytogenes can be widely used in remote areas.