Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China.Interestingly,our previous work has found that R.crenulate extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced colitis.Thus,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against colitis.The chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were identified.Meanwhile,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds.The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis.The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid metabolism.Correspondingly,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

Leisure-time physical activity and all-cause mortality and cardiovascular disease in adults with type 2 diabetes:Cross-country comparison of cohort studies

Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 diabetes.Methods:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China.Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national registries.Results:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response relationship.PA below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese adults.Associations with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes.Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.

Numerical analysis of anisotropic stiffness and strength for geomaterials

In numerical modelling,selection of the constitutive model is a critical factor in predicting the actual response of a geomaterial.The use of oversimplified or inadequate models may not be sufficient to reproduce the actual geomaterial behaviour.That selection is especially relevant in the case of aniso-tropic rocks,and particularly for shales and slates,whose behaviour may be affected,e.g.well stability in geothermal or oil and gas production operations.In this paper,an alternative anisotropic constitutive model has been implemented in the finite element method software CODE_BRIGHT,which is able to account for the anisotropy of shales and slates in terms of both deformability and strength.For this purpose,a transversely isotropic version of the generalised Hooke’s law is adopted to represent the stiffness anisotropy,while a nonuniform scaling of the stress tensor is introduced in the plastic model to represent the strength anisotropy.Furthermore,a detailed approach has been proposed to determine the model parameters based on the stressestrain results of laboratory tests.Moreover,numerical analyses are performed to model uniaxial and triaxial tests on Vaca Muerta shale,Bossier shale and slate from the northwest of Spain(NW Spain slate).The experimental data have been recovered from the literature in the case of the shale and,in the case of the slate,performed by the authors in terms of stress-strain curves and strengths.A good agreement can be generally observed between numerical and experi-mental results,hence showing the potential applicability of the approach to actual case studies.Therefore,the presented constitutive model may be a promising approach for analysing the anisotropic behaviour of rocks and its impact on well stability or other relevant geomechanical problems in aniso-tropic rocks.

The role of flavonoids in mitigating food originated heterocyclic aromatic amines that concerns human wellness

Meat products are an important part in our daily diet,providing valuable nutrients for the human body.However,heating processes cause the meat to become more appetizing with changes in texture,appearance,flavor,and chemical properties by the altering of protein structure and other ingredients.As one kind of cooking-induced contaminants,heterocyclic aromatic amines(HAAs)are widely present in protein aceous food products with strong carcinogenic and mutagenic properties.In order to promote the safety of traditional meat products,this review focused on the formation,metabolism,biological monitoring and inhibitory mechanism of HAA.An overview of the formation pathways,hazards,and control methods of HAAs during food processing in recent years was studied,aiming to provide some valuable information for exploring effective methods to inhibit the production of associated hazards during food processing.Systematic selection of different types of flavonoids to explore their effects on the formation of HAAs in an actual barbecue system can provide theoretical reference for effectively controlling the formation of HAAs and reducing their harm to human health.

Dose-response associations,physical activity intensity and mortality risk:A narrative review

Physical activity is consistently associated with reduced mortality,decreased risk for non-communicable diseases,and improved mental health in observational studies.Randomized controlled trials and observational Mendelian randomization studies support causal links between physical activity and health outcomes.However,the scarcity of evidence from randomized controlled trials,along with their inherent challenges like exposure contrasts,healthy volunteer biases,loss to follow-up,and limited real-world dose-response data,warrants a comprehensive approach.This review advocates synthesizing insights from diverse study designs to better understand the causal relationship between physical activity,mortality risk,and other health outcomes.Additionally,it summarizes recent research since the publication of current physical activity recommendations.Novel observational studies utilizing device-measured physical activity underscore the importance of every minute of activity and suggest that all intensity levels confer health benefits,with vigorous-intensity potentially requiring lower volumes for substantial benefits.Future guidelines,informed by device-measured physical activity studies,may offer refined age-specific recommendations,emphasize vigorous-intensity physical activity,and include daily step counts as a simple,easily assessable metric using commercial wearables.

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.

Ground reaction curves for circular excavations in non-homogeneous,axisymmetric strain-softening rock masses

Fast methods to solve the unloading problem of a cylindrical cavity or tunnel excavated in elasto-perfectly plastic, elasto-brittle or strain-softening materials under a hydrostatic stress feld can be derived based on the self-similarity of the solution. As a consequence, they only apply when the rock mass is homogeneous and so exclude many cases of practical interest. We describe a robust and fast numerical technique that solves the tunnel unloading problem and estimates the ground reaction curve for a cylindrical cavity excavated in a rock mass with properties depending on the radial coordinate, where the solution is no longer self-similar. The solution is based on a continuation-like approach(associated with the unloading and with the incremental formulation of the elasto-plastic behavior), fnite element spatial discretization and a combination of explicit sub-stepping schemes and implicit techniques to integrate the constitutive law, so as to tackle the diffculties associated with both strong strain-softening and elasto-brittle behaviors. The developed algorithm is used for two practical ground reaction curve computation applications. The frst application refers to a tunnel surrounded by an aureole of material damaged by blasting and the second to a tunnel surrounded by a ring-like zone of reinforced(rock-bolted) material.

Particle flow code simulation of intact and fissured granitic rock samples

This study presents a calibration process of three-dimensional particle flow code(PFC3D)simulation of intact and fissured granite samples.First,laboratory stressestrain response from triaxial testing of intact and fissured granite samples is recalled.Then,PFC3D is introduced,with focus on the bonded particle models(BPM).After that,we present previous studies where intact rock is simulated by means of flatjoint approaches,and how improved accuracy was gained with the help of parametric studies.Then,models of the pre-fissured rock specimens were generated,including modeled fissures in the form of“smooth joint”type contacts.Finally,triaxial testing simulations of 1 t 2 and 2 t 3 jointed rock specimens were performed.Results show that both elastic behavior and the peak strength levels are closely matched,without any additional fine tuning of micro-mechanical parameters.Concerning the postfailure behavior,models reproduce the trends of decreasing dilation with increasing confinement and plasticity.However,the dilation values simulated are larger than those observed in practice.This is attributed to the difficulty in modeling some phenomena of fissured rock behaviors,such as rock piece corner crushing with dust production and interactions between newly formed shear bands or axial splitting cracks with pre-existing joints.

Verification of a laboratory-based dilation model for in situ conditions using continuum models

With respect to constitutive models for continuum modeling applications, the post-yield domain remains the area of greatest uncertainty. Recent studies based on laboratory testing have led to the development of a number of models for brittle rock dilation, which account for both the plastic shear strain and confining stress dependencies of this phenomenon. Although these models are useful in providing an improved understanding of how dilatancy evolves during a compression test, there has been relatively little work performed examining their validity for modeling brittle rock yield in situ. In this study, different constitutive models for rock dilation are reviewed and then tested, in the context of a number of case studies, using a continuum finite-difference approach(FLAC). The uncertainty associated with the modeling of brittle fracture localization is addressed, and the overall ability of mobilized dilation models to replicate in situ deformation measurements and yield patterns is evaluated.

Potential of soluble CD26 as a serum marker for colorectal cancer detection

Colorectal cancer is characterized by a low survival rate even though the basis for colon cancer development,which involves the evolution of adenomas to carcinoma,is known.Moreover,the mortality rates continue to rise in economically transitioning countries although there is the opportunity to intervene in the natural history of the adenoma–cancer sequence through risk factors,screening,and treatment.Screening in particular accounted for most of the decline in colorectal cancer mortality achieved in the USA during the period 1975-2000.Patients show a better prognosis when the neoplasm is diagnosed early.Among the variety of screening strategies,the methods range from invasive and costly procedures such as colonoscopy to more low-cost and non-invasive tests such as the fecal occult blood test(guaiac and immunochemical).As a non-invasive biological serum marker would be of great benefit because of the performance of the test,several biomarkers,including cytologic assays,DNA and mRNA,and soluble proteins,have been studied.We found that the soluble CD26(sCD26)concentration is diminished in serum of colorectal cancer patients compared to healthy donors,suggesting the potential utility of a sCD26 immunochemical detection test for early diagnosis.sCD26 originates from plasma membrane CD26 lacking its transmembrane and cytoplasmic domains.Some 90%–95%of sCD26 has been associated with serum dipeptidyl peptidase IV(DPPIV)activity.DPP-IV,assigned to the CD26 cluster,is a pleiotropic enzyme expressed mainly on epithelial cells and lymphocytes.Our studies intended to validate this test for population screening to detect colorectal cancer and advanced adenomas are reviewed here.

Predicting scenic beauty of forest stands in Catalonia （North-east Spain）

森林看台，相片和虚拟现实图象的 90 幅图象的相对偏爱被因特网调查为在看台水平估计美景偏爱开发一个量的模型。从 259 个法官的一个总数的问询表获得的相对优先级价值为对用回归方法被分析明智的比较。二个模型基于看台的二个不同的组被开发。两个模型显示一个森林的优先级承受增加与一在灌木丛和树的数字的 augment，并且另外与树的吝啬的直径。在另一方面，优先级与松和小树的大数字是低的。相片代表的看台比虚拟现实图象代表的那些收到更好的优先级价值。当法官(性，国家或职业) 的背景作为另外的预言者被包括进模型时，没有重要改进被完成。

Central nervous system stimulation therapies in phantom limb pain:a systematic review of clinical trials

Phantom limb pain is a chronic pain syndrome that is difficult to cope with.Despite neurostimulation treatment is indicated for refractory neuropathic pain,there is scant evidence from randomized controlled trials to recommend it as the treatment choice.Thus,a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain.A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases.Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed.There were a total of 10 full-text articles retrieved and included in this review.Deep brain stimulation,repetitive transcranial magnetic stimulation,transcranial direct current stimulation,and motor cortex stimulation were the treatment strategies used in the selected clinical trials.Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception,as well as to relieve anxiety and depression symptoms in phantom limb pain patients.Conversely,invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial.However,the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients.

Electro-Chemical Impedance Spectral (EIS) Study of Patinated Bronze Corrosion in Sulfate Media: Experimental Design Approach

The aim of the present investigation was to model the experimental conditions of tin bronze patination using full factorial experimental design. In this sense, a full factorial design approach was developed to model the corrosion behavior of patinated tin bronze alloy in sulfate electrolyte. Three experimental factors (the immersion time in the chloride electrolyte, the potential limit for the anodic sweep Elim, and the potential scan rate) were chosen to identify the significant factor on the patina growth process at the bronze substrate. The experimental responses were the kinetic parameters extracted from the electro-chemical spectra (EIS) for eight different experiments. An equivalent electrical circuit containing an electrolyte resistance (Re), a double layer capacitance (CPEdl), a charge transfer resistance (Rt) and Gerischer element (G), was developed to model the patinated bronze corrosion process. The electro-chemical spectra (EIS) show that the corrosion process of the patinated bronze alloy occurred from a chemical reaction is followed by an electrochemical one. Analysis of the experimental responses showed that while the scan rate is the most influent factor for the corrosion potential (Ecorr), the electrolyte resistance (Re), and the double layer capacitance CPEdl variation, the potential limit is the significant factor for charge transfer resistance Rt, reciprocal of the admittance parameter Y0 and the effective transfer rate of the chemical reaction k variation.

Optimal and synchronized germination of Robinia pseudoacacia,Acacia dealbata and other woody Fabaceae using a handheld rotary tool:concomitant reduction of physical and physiological seed dormancy

The Fabaceae(legume family) is one of the largest families of plants with a worldwide distribution and a major role in agriculture and in agroforestry.A hard seed coat impermeable to water is a typical feature of several species.Physical dormancy delays and reduces germination so that mechanical,physical and chemical scarification methods have been classically used to break seed dormancy of many species.We evaluate the effectiveness of a methodology to scarify seeds of several woody Fabaceae of ecological and economical importance,including Robinia pseudoacacia and Acacia dealbata and the shrubs Cytisus scoparius,C.multiflorus and Ulex europaeus.We describe the optimized use of a handheld rotary tool(HRT),and compare its effectiveness with other scarification methods reported to break dormancy such as boiling or dry heating.Total germination and/or speed of germination were enhanced after the application of the HRT,with germination percentages significantly higher than those achieved by other methods of scarification.Based on a thorough literature review,a mode of action for the HRT is suggested which could operate by breaking the physical and physiological dormancy of treated seeds through thecombined action of coat abrasion and moderate temperatures.Considering these results,we recommend the application of this rapid,effective,low-cost and highly reproducible HRT method to break seed dormancy and enhance germination of these species and others with similar dormancy constraints.

Analysis of Naval Ship Evacuation Using Stochastic Simulation Models and Experimental Data Sets

The study of emergency evacuation in public spaces,buildings and large ships may present parallel characteristic in terms of complexity of the layout but there are also significant differences that can hinder passengers to reach muster stations or the lifeboats.There are many hazards on a ship that can cause an emergency evacuation,the most severe result in loss of lives.Providing safe and effective evacuation of passengers from ships in an emergency situation becomes critical.Recently,computer simulation has become an indispensable technology in various fields,among them,the evacuation models that recently evolved incorporating human behavioral factors.In this work,an analysis of evacuation in a Landing Helicopter Dock(LHD)ship was conducted.Escape routes specified by the ship’s procedures were introduced in the model and the six emergency scenarios of the Naval Ship Code were simulated.The crew and embarked troops were introduced with their different evacuation behavior,in addition,walking speeds were extracted from data set collected in experiments conducted at other warships.From the results of the simulations,the longest time was chosen and confidence intervals constructed to determine the total evacuation time.Finally,results show that evacuation time meets regulatory requirements and the usefulness and low cost of the evacuation simulation for testing and refining possible ships’layouts and emergency scenarios.

Corrigendum to “Verification of a laboratory-based dilation model for in situ conditions using continuum models” [J Rock Mech Geotech Eng6 (2014) 522e534]

The authors regret that the photographic image in Fig. 4a of the published article was used in error, and therefore without proper referencing or permission from the originator or copyright holder. The image used in Fig. 4a of the original manuscript has been previously published by and remains under copyright by the Society for Mining, Metallurgy, and Exploration, Inc. (SME) associated with the following paper.Moalli S, Redmond S, Brox D, Procter P, Jezek D, van der Pouw Kraan M, Blanchet R, Kulka R. TBM Tunneling at the Ashlu Hydro Power Project, Squamish, BC. In: Almeraris G, Mariucci B. editors. Proceedings of Rapid Excavation and Tunnelling 2009. The Society for Mining,Metallurgy, and Exploration, Inc. (SME). 2009. pp. 1208e1217.To correct this error though this Corrigendum, Fig. 4 in this article is replaced with the following set of images. The caption remains unchanged from the original but is included here for convenience and clarity.

Perceived Barriers to Physical Activity and Related Factors in Spanish University Students

Objective: The purpose of this study was to identify the influence of readiness of change for physical activity (PA), sociodemographic factors, lifestyle and physical activity status (PAS) on perceived barriers among Spanish university students. Participants: Seven hundred and seventy two (n = 772) men and women ages 17-39 at a north-west regional university in Spain participated in the study. Methods: The International Physical Activity Questionnaire, the States of Change for Physical Activity Behaviour Questionnaire and the Self-perceived Barriers for Physical Activity Questionnaire were used. Description, correlation and multiple regression analyses were completed. Results: Participants self-perceived low average-score barriers (2.6 ± 1.4 over 10.0). The 3-higher scores barriers corresponded to “too much work”;“lack of time for exercise” and “laziness”. Gender, PAS and self-perceived health were shown to be associated with perceived barriers. Conclusions: University institutions should consider those factors that predict barriers to PA to develop effective intervention programs.