Amomum tsaoko (AT) is a dietary botanical with laxative properties; however, the active ingredients and mechanisms are still unclear. The active fraction of AT aqueous extract (ATAE) for promoting defecation in slow transit constipation mice is the ethanol-soluble part (ATES). The total flavonoids of ATES (ATTF) were the main active component. ATTF significantly increased the abundance of Lactobacillus and Bacillus and reduced the dominant commensals, such as Lachnospiraceae, thereby changing the gut microbiota structure and composition. Meanwhile, ATTF changed the gut metabolites mainly enriched in pathways such as the serotonergic synapse. In addition, ATTF increased the serum serotonin (5-HT) content and mRNA expression of 5-hydroxytryptamine receptor 2A (5-HT2A), Phospholipase A2 (PLA2), and Cyclooxygenase-2 (COX2), which are involved in the serotonergic synaptic pathway. ATTF increased Transient receptor potential A1 (TRPA1), which promotes the release of 5-HT, and Myosin light chain 3(MLC3), which promotes smooth muscle motility. Notably, we established a network between gut microbiota, gut metabolites, and host parameters. The dominant gut microbiota Lactobacillus and Bacillus, prostaglandin J2 (PGJ2) and laxative phenotypes showed the most significant associations. The above results suggest that ATTF may relieve constipation by regulating the gut microbiota and serotonergic synaptic pathway and has great potential for laxative drug development in the future.
As China undergoes urbanization, lifestyles and disease profiles are changing. In this study, metabolic syndrome (MetS) was discovered in 53.5% and 42.7% of men and women, respectively. In 3 age cohorts (44, 48, and 52 years), prevalence of MetS among women was 33.3%, 41.4%, and 50.8%, respectively (χ 2 = 10.27, P = .006), whereas among men it was 51.5%, 56.3%, and 52.3%, respectively (χ 2 = 0.46, P = .796). The component contributing to the presence of MetS was increased waist circumference, especially among women. MetS among men results from higher rates of elevated triglycerides, blood pressure, and blood glucose when compared with women. Risk factors for MetS included less than 60 minutes of exercise a week (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.4) and rarely consuming milk (OR = 1.7, 95% CI = 1.2-2.3). Abstaining from or occasionally consuming alcohol (OR = 0.7, 95% CI = 0.4-1.1) and having parents with no chronic disease (OR = 0.4, 95% CI = 0.2-0.6) suggest increased protection against MetS.
As one of the most important components within a vehicle, diesel engines have high requirements for reliability due to the harsh operating environments. However, previous studies have mainly focused on the reliability assessment of diesel engines, while less research has been conducted on the modeling of the diesel engine reliability analysis and its management. For this reason, this paper proposes a comprehensive method for reliability analysis and its management based on the use of 4F integration technology in the early stages of diesel engine design. First of all, an expert group used FEMCA (failure mode, effects and criticality analysis) and FHA (functional hazard analysis) to find the most harmful level of fault mode. At the same time, a new method for the repair of dynamic fault trees to find the weak links at the component level was developed. Finally, a FRACAS (fracture report analysis and corrective action system) was used during the above analysis process. By applying this method to the reliability assessment of a diesel engine in the design stage, the problems of failure information feedback and the reuse of failure information in the actual reliability assessment can be solved.
Abstract Background Abnormal coagulation and fibrinolysis are often observed in malignant tumors, which may contribute to tumor invasion. This study aimed to investigate the potential of using coagulation and fibrinolysis markers for differential diagnosis. Methods The levels of PT, APTT, TT, FIB, FDP, and D-dimer were analyzed in primary tumors (208 benign and 243 malignant) prior to biopsy or treatment. Additionally, a control group consisting of 400 healthy volunteers was included. Results Significantly higher levels of PT, FIB, FDP and D-dimer were found in the malignant tumor group compared with both the benign tumor group and control group (P > 0.01). The AUCs for FIB and D-dimer in diagnosing malignant tumors were 0.829(95% CI:0.780 ~ 0.878)and 0.845(95% CI:0.799 ~ 0.892), respectively. - both exceeding 0.8; their specificities for detecting malignancy were also high at 91.18% and 92.16%, respectively; while their positive predictive values reached up to 91.82% and 92.73%, respectively. Furthermore, the combined detection of PT,FIB,D-dimer,and FDP as well as that of only FIB and D-dimer combined could achieve an even higher diagnostic accuracy with AUCs were 89.22% and 89.26%, respectively;specificities for detecting malignancy were 89.22% and 89.26%,while their positive predictive values were 91.79% and 91.03%. Finally, a combination factor involving these markers could provide valuable assistance in distinguishing between benign and malignant tumors. Conclusion The use of FIB and D-dimer alone and the combined use of coagulation system function-related indicators (such as the combination of D-dimer and FIB or the combination of PT, FIB, FDP and D-dimer) have high auxiliary diagnostic value in the differential diagnosis of benign and malignant tumours.
The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients.The brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG). The functional connectivity maps of each PAG subregion were calculated, and Two sample t-test was applied with age and sex as covariables.Bilateral vlPAG and left dlPAG presented decreased functional connectivity, and the other subregions (bilateral lPAGs, right dlPAG and dmPAG) showed no significant altered functional connectivity in EM compared with NC. The brain regions with decreased functional connectivity mainly located in bilateral prefrontal cortex(PFC), middle temporal gyrus, primary motor area (PMA) and supplementary motor area (SMA) and right ventrolateral PFC (vlPFC) in EM patients in this study. Disease duration was positively related to the functional connectivity of bilateral vlPAG on the bilateral thalamus and putamen, left pallidum and right medial orbitofrontal gyrus in EM patients.The present study suggested that the dysfunction of bilateral vlPAG and left dlPAG presented in EM, and functional evaluation of PAG subregions may be help for the diagnosis and understanding of EM pathogenesis.
Periaqueductal gray (PAG) is the descending pain modulatory center, and PAG dysfunction had been recognized in migraine. Here we propose to investigate altered PAG texture features (quantitative approach for extracting texture descriptors for images) in the patients with medication-overuse headache (MOH) based on high resolution brain structural image to understand the MOH pathogenesis. The brain structural images were obtained from 32 normal controls (NC) and 44 MOH patients on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template, and the individual PAG segment was performed by applying the deformation field to the PAG template after structural image segment. Grey-level co-occurrence matrix (GLCM) was performed to measure the texture parameters including angular second moment (ASM), Contrast, Correlation, inverse difference moment (IDM) and Entropy. Contrast was increased in MOH patients (9.28 ± 3.11) compared with that in NC (7.94 ± 0.65) (P < 0.05), and other texture features showed no significant difference between MOH and NC (P > 0.05). The area under the ROC curve was 0.697 for Contrast in the distinction of MOH from NC, and the cut-off value of Contrast was 8.11 with sensitivity 70.5% and specificity 62.5%. The contrast was negatively with the sleep scores (r = -0.434, P = 0.003). Texture Contrast could be used to identify the altered MR imaging characteristics in MOH in understanding the MOH pathogenesis, and it could also be considered as imaging biomarker in for MOH diagnosis.
Methodology/principal findings: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N -terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts. Conclusion/significance: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body. Keywords: ribosome-inactivating proteins, alpha-momorcharin, momordica anti-HIV protein, antitumor, antivirus, (mPEG) 2 -Lys-NHS (20 kDa), immunogenicity
Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, and AQP8) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor–myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes and Lactobacillus, were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae, Muribaculum, norank__f__Desulfovibrionaceae, and Parasutterella, were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.
The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients based on high resolution brain structural image.The brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template using MRIcron, and the individual PAG was created by applying the deformation field to the PAG template after structural image segment. One-way analysis of covariance, partial correlation analysis and Receiver operating characteristics (ROC) curve were applied.EM had a larger PAG volume (0.35 ± 0.02 ml) than that (0.32 ± 0.02 ml) of NC (P = 0.017). The PAG volume of CM (0.33 ± 0.02 ml) was negatively related to the VAS score (P = 0.03). ROC analysis demonstrated that PAG volume has higher diagnostic efficacy (AUC, 0.731; Sensitivity, 0.556; Specificity, 0.889) for NC vs. EM compared with that NC vs. CM (AUC, 0.634; Sensitivity, 0.438; Specificity, 0.833) and EM vs. CM (AUC, 0.618; Sensitivity, 0.813; Specificity, 0.556).PAG volume expansion may be the direct impairment evidence on the brain in EM, and could be considered as a diagnostic and evaluated imaging biomarker in migraine.
To improve the accuracy of capacitance measurement,aimed at the principle of work of mercury capacitance ac-celeration transducer,the design of micro capacitance measurement circuit is based on the key PIC16LF874 chip.Briefly discusses the application of the capacitance measuring circuit for the background and status of foreign researchers,focusing on the United States PIC16LF874 microcontroller features.Capacitive sensor outputed signal through the dynamics of weak PS021-chip capacitors(capacitance-digital converter) to convert analog data into digital data,the measured data from the PIC16LF874 microcontroller application process,display and preservation.Experimental results show that the fixed capaci-tor 10pF ~ 20pF nominal value of the measured value of relative error is within 1%,but also it canbe seen the value of the measured capacitance larger,measuring value and the nominal value of relative error smaller.
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