Asperosaponin VI facilitates the regeneration of skeletal muscle injury by suppressing GSK-3ß-mediated cell apoptosis.

Asperosaponin VI (ASA VI) is a bioactive triterpenoid saponin extracted from Diptychus roots, of Diptyl, and has previously shown protective functions in rheumatoid arthritis and sepsis. This study investigates the effects and molecular mechanisms of ASA VI on skeletal muscle regeneration in a cardiotoxin (CTX)-induced skeletal muscle injury mouse model. Mice were subjected to CTX-induced injury in the tibialis anterior and C2C12 myotubes were treated with CTX. Muscle fiber histology was analyzed at 7 and 14 days postinjury. Apoptosis and autophagy-related protein expression were evaluated t s by Western blot, and muscle regeneration markers were quantified by quantitative polymerase chain reaction. Docking studies, cell viability assessments, and glycogen synthase kinase-3ß (GSK-3ß) activation analyses were performed to elucidate the mechanism. ASA VI was observed to improve muscle interstitial fibrosis, remodeling, and performance in CTX-treated mice, thereby increased skeletal muscle size, weight, and locomotion. Furthermore, ASA VI modulated the expression of apoptosis and autophagy-related proteins through GSK-3ß inhibition and activated the transcription of regeneration genes. Our results suggest that ASA VI mitigates skeletal muscle injury by modulating apoptosis and autophagy via GSK-3ß signaling and promotes regeneration, thus presenting a probable therapeutic agent for skeletal muscle injury.

Taking full advantage of 'low-quality' datasets in watershed modeling and management: From a perspective of parameter calibration.

The quality of calibration datasets is critical for establishing well-calibrated models for reliable decision-making support. However, the analysis of the influence of calibration dataset quality and the discussion on how to use flawed and/or incomplete datasets are still far from sufficient. An evaluation framework for the impact of model calibration data on parameter identifiability, sensitivity, and uncertainty (ISU) was established. Three quantitative and normalized indicators were designed to describe the magnitude of ISU. With the case study of the upper Daqing River watershed, China and the model SWAT (Soil and Water Assessment Tool), one ideal dataset without quality flaws and 79 datasets with different types of flaws including observation error, low monitoring frequency, short data duration and low data resolution were evaluated. The result showed that 4 of 13 parameters that control canopy, groundwater and channel processes have higher ISU values, indicating the high identifiability, high sensitivity, and low uncertainty. The largest gap of parameter ISU between dataset with quality flaw and ideal dataset was 0.61 due to short data duration, while the smallest gap was -0.28 due to low monitoring data frequency. Although some defective datasets caused unacceptable calibration results and model output, some defective datasets can still be valuable for model calibration which depends on the hydrological processes of interest when applying the model. Equivalent calibration results were yielded by the datasets with similar statistical properties. When using datasets with traditional defective issues for calibration, a new step checking the consistency among decision goal, representative system process, determinative parameters and calibration datasets is suggested. Practices including process-related data selection, dataset regrouping and risk self-reporting when using low-quality datasets are encouraged to increase the reliability of model-based watershed management.

Improvement in municipal wastewater treatment alters lake nitrogen to phosphorus ratios in populated regions.

Large-scale and rapid improvement in wastewater treatment is common practice in developing countries, yet this influence on nutrient regimes in receiving waterbodies is rarely examined at broad spatial and temporal scales. Here, we present a study linking decadal nutrient monitoring data in lakes with the corresponding estimates of five major anthropogenic nutrient discharges in their surrounding watersheds over time. Within a continuous monitoring dataset covering the period 2008 to 2017, we find that due to different rates of change in TN and TP concentrations, 24 of 46 lakes, mostly located in China's populated regions, showed increasing TN/TP mass ratios; only 3 lakes showed a decrease. Quantitative relationships between in-lake nutrient concentrations (and their ratios) and anthropogenic nutrient discharges in the surrounding watersheds indicate that increase of lake TN/TP ratios is associated with the rapid improvement in municipal wastewater treatment. Due to the higher removal efficiency of TP compared with TN, TN/TP mass ratios in total municipal wastewater discharge have continued to increase from a median of 10.7 (95% confidence interval, 7.6 to 15.1) in 2008 to 17.7 (95% confidence interval, 13.2 to 27.2) in 2017. Improving municipal wastewater collection and treatment worldwide is an important target within the 17 sustainable development goals set by the United Nations. Given potential ecological impacts on biodiversity and ecosystem function of altered nutrient ratios in wastewater discharge, our results suggest that long-term strategies for domestic wastewater management should not merely focus on total reductions of nutrient discharges but also consider their stoichiometric balance.

Exploring the discharge characteristics of personal care behaviors for high precision estimation of microplastic emission.

Microplastics (MPs) from personal care and cosmetic products (PCCPs) pose a threat to aquatic environment due to the small size and the complexity of composition. Although the habits of personal care behaviors (PCBs) vary from individuals affecting MPs emissions, quantitative research is not sufficient to support high-precision emission estimates and targeted management decisions. Based on a questionnaire survey about PCBs and laboratory experiments on corresponding PCCPs utilization, this study proposed a bottom-up micro-simulation method to quantify MPs emissions combining multinomial logit model and categorized emission coefficients, and identified the impact of individual attributes on the emissions. The results show that the annual PCBs-derived MPs emissions amounted to 2931.8 trillion particles in China, of which teeth brushing, face washing, and bathing behavior accounted for 29%, 36% and 35%, respectively. The residents discharged an average of 2.18 million particles per capita per year with 95% confidence interval of 0.58-4.34 million particles. Gender, age and living region had greater impacts on PCBs-derived MPs emissions. The effect of living region was significantly related to local temperature and humidity. The estimation based on the MPs discharge characteristics of PCBs provides high-precision method regarding the MPs emission from people's daily life and contributes to further understanding the source of MPs and initiating environmental control strategies.

Evaluation of uncertain signals' impact on deep reinforcement learning-based real-time control strategy of urban drainage systems.

Real-time control (RTC) is a recognized technology to enhance the efficiency of urban drainage systems (UDS). Deep reinforcement learning (DRL) has recently provided a new solution for RTC. However, the practice of DRL-based RTC has been impeded by different sources of uncertainties. The present study aimed to evaluate the impact caused by the uncertainties on DRL-based RTC to promote its application. The impact of uncertainties in the measurement of water level signals was evaluated through large-scale simulation experiments and quantified using measures of statistical dispersion of control performance distribution and relative change of control performance compared to the baseline scenario with no uncertainty. Results show that the statistical dispersion of DRL-based RTC was reduced by 15.48%-81.93% concerning random and systematic uncertainties compared to the conventional rule-based control (RBC) strategy. The findings indicated that DRL-based RTC is robust and could be reliably applied to safety-critical real-world UDS.

The structure design of integrated urban drainage systems: A view of robust optimization.

Rapid urbanization puts a lot of pressure on urban water pollution from point and non-point sources, calling for the practical, specific, and integrated management of urban drainage systems (UDS). The structural design of an integrated UDS is essential for highly complex and uncertain urban water management. In this study, we developed a multi-objective robust optimization model to explore the optimal structures of UDS considering system uncertainty. We applied this model to City B, northern China, to illustrate its effectiveness. The results show that the model can produce optimal designs with a more robust performance in terms of structural uncertainty. When the uncertainty degree ranges from 5% to 20%, a considerable extra cost (increased by 1.10-2.68 times) is required to improve the robustness of UDS. With the increase in structural uncertainty, the fraction of the cost invested in the stormwater subsystem increased from 10.2% to 27.2%. The findings showed that stormwater management is efficient in coping with system uncertainty. The research results promote an understanding of robust urban drainage systems.

Risk factors associated with postoperative complications after liver cancer resection surgery in western China.

OBJECTIVES: Postoperative complications increase the workload of nursing staff as well as the financial and mental distress suffered by patients. The objective of this study is to identify clinical factors associated with postoperative complications after liver cancer resection surgery. METHODS: Data from liver cancer resections occurring between January 1st, 2019 to December 31st, 2019 was collected from the Department of Liver Surgery in West China Hospital of Sichuan University. The Kruskal-Wallis test and logistic regression were used to perform single-factor analysis. Stepwise logistic regression was used for multivariate analysis. Models were established using R 4.0.2 software. RESULTS: Based on data collected from 593 cases, the single-factor analysis determined that there were statistically significant differences in BMI, incision type, incision length, duration, incision range, and bleeding between cases that experienced complications within 30 days after surgery and those did not. Stepwise logistic regression models based on Kruskal-Wallis test and single-factor logistic regression determined that BMI, incision length, and duration were the primary factors causing complications after liver resection. The adjust OR of overweight patients and patients with obesity (stage 1) compared to low weight patients were 0.12 (95% CI:0.02-0.72) with p = 0.043 and 0.18 (95% CI:0.03-1.00) with p = 0.04, respectively. An increase of 1 cm in incision length increased the relative risk by 13%, while an increase of 10 min in surgical duration increased the relative risk by 15%. CONCLUSIONS: The risk of postoperative complications after liver resection can be significantly reduced by controlling factors such as bleeding, incision length, and duration of the surgery.

Application of platelet-rich fibrin grafts following pterygium excision.

PURPOSE: To compare the efficacy, safety and recurrence rate of platelet-rich fibrin (PRF) grafts and limbal conjunctival autografts (LCAs) following pterygium excision. METHODS: A total of 108 patients (108 eyes) with primary pterygium were included in this study and were divided into group A (56 eyes) and group B (52 eyes). Patients in group A underwent excision of the pterygium followed by LCA while patients in group B underwent PRF grafts following pterygium excision. The PRF was produced using the patient's own whole-blood sample by centrifugation and extrusion. The surgery time, intraoperative complications, postoperative complications, recurrence rate, intraocular pressure (IOP) and follow-up period were recorded and evaluated between the two groups. RESULTS: The mean surgery time was significantly shorter in group B (25.0 ± 4.2 min) than in group A (36.5 ± 6.3 min) (P < .001). Recurrence was observed in two cases (3.6%) in group A while no recurrence was observed in group B. No graft loss was observed in either group. No other intra/postoperative complications such as a tear in the graft, injury to the medial rectus muscle, excessive bleeding, scleral necrosis, graft oedema, graft necrosis, pannus formation or symblepharon appeared in either group. CONCLUSIONS: This study presented with a promising outcome of PRF graft applications in primary pterygium surgery. The use of PRF following pterygium excision is a simple, easily applicable, and comfortable method for both patients and surgeons, with less time consumption, recurrence rate and complications, which could be widely used in pterygium management.

Machine learning approaches for the prediction of postoperative complication risk in liver resection patients.

BACKGROUND: For liver cancer patients, the occurrence of postoperative complications increases the difficulty of perioperative nursing, prolongs the hospitalization time of patients, and leads to large increases in hospitalization costs. The ability to identify influencing factors and to predict the risk of complications in patients with liver cancer after surgery could assist doctors to make better clinical decisions. OBJECTIVE: The aim of the study was to develop a postoperative complication risk prediction model based on machine learning algorithms, which utilizes variables obtained before or during the liver cancer surgery, to predict when complications present with clinical symptoms and the ways of reducing the risk of complications. METHODS: The study subjects were liver cancer patients who had undergone liver resection. There were 175 individuals, and 13 variables were recorded. 70% of the data were used for the training set, and 30% for the test set. The performance of five machine learning models, logistic regression, decision trees-C5.0, decision trees-CART, support vector machines, and random forests, for predicting postoperative complication risk in liver resection patients were compared. The significant influencing factors were selected by combining results of multiple methods, based on which the prediction model of postoperative complications risk was created. The results were analyzed to give suggestions of how to reduce the risk of complications. RESULTS: Random Forest gave the best performance from the decision curves analysis. The decision tree-C5.0 algorithm had the best performance of the five machine learning algorithms if ACC and AUC were used as evaluation indicators, producing an area under the receiver operating characteristic curve value of 0.91 (95% CI 0.77-1), with an accuracy of 92.45% (95% CI 85-100%), the sensitivity of 87.5%, and specificity of 94.59%. The duration of operation, patient's BMI, and length of incision were significant influencing factors of postoperative complication risk in liver resection patients. CONCLUSIONS: To reduce the risk of complications, it appears to be important that the patient's BMI should be above 22.96 before the operation, and the duration of the operation should be minimized.

Association of outdoor air pollution with the medical expense of ischemic stroke: The case study of an industrial city in western China.

Ischemic stroke, the most frequent cause of severe disability, imposes a significant mental and economic burden on patients and their families. There is increasing evidence to indicate that air pollution contributes to the risk of ischemic stroke. This study aimed to examine the correlation between air pollution and the expense imposed by an ischemic stroke. Data were obtained from hospitals and environmental monitoring stations in an industry city, Longspring, in western China. We used a generalized additive model to estimate the associations between the two factors, measured during 2015-2017. Counter-intuitively, the medical expenses arising from ischemia were negatively associated with the level of air pollution. The corresponding ER for per interquartile range increase of PM2.5, PM10, SO2 , and NO2 in lag10 was -0.17% (95% confidence interval (95% CI -0.31%, -0.03%), -0.11% (95% CI -0.2%, -0.02%), -1.04% (95% CI -1.92%, -0.17%) and -0.44% (95% CI -0.66%, -0.22%), respectively (p < 0.05). Subgroups based on gender, age, and season were considered in the analysis. The results indicated that pollutants had significant effects on ischaemia's medical expenses, which were stronger for older people, patients who survived, and warm seasons. This study is the first step in optimizing medical resources, which are essential for policymaking and service planning.

Screening and mitigating major threats of regional development to water ecosystems using ecosystem services as endpoints.

Coordinating the coercion of human activities to the ecosystem is a continuous strategic concern. A practical way to conceptualize socioeconomic development and link it to ecosystem response is urgently needed. This study proposed a two-staged method to reveal the threats concealed in socioeconomic development and show the return of water ecosystem services to regulation measures. Eight threat indexes referring to scale, structure and efficiencies of industrial, agriculture and domestic sectors were designed to assess the threats caused by unsustainable development features, while four indexes for evaluating water supply, habitat provision, regulation and quality purification service of ecosystem were set up. For each threat index, the evaluation result is a relative value derived from comparison with a reasonable level. The major threats could be screened out by ranking threat indexes, so that unreasonable development dimension could be identified and subsequent regulation scheme be prepared. On this basis, with the targeted adjustment of socioeconomic development, corresponding improvements in water ecosystem could be expected and quantified. In the case study of Beijing-Tianjin-Hebei District, the most remarkable threats include production inefficiency of the industrial sector and oversized population, of which degrees of deviation from reasonable levels exceed 70%. When all development dimensions were dragged to the suggested levels, the habitat provision and water supply service would witness the largest progress among four services, with the values rising from 0.49 to nearly 1. This method helps discover the critical defect of socioeconomic development in terms of ecosystem response and facilitate the decision maker to establish more sustainable initiatives.

Quantitative analysis of economic and environmental benefits for land fallowing policy in the Beijing-Tianjin-Hebei region.

The Beijing-Tianjin-Hebei region (BTH region) is a major crop-producing region of China suffering from environment deterioration. Land fallowing policy is widely used as the solution of agriculture-related environment pollution, while it is difficult to derive a quantitative basis for policy-making. An indicator system was established to quantitatively analyse economic and environmental benefits of land fallow policies in the BTH region. The system consisted of 8 indicators to describe the water, air and economic influences caused by land fallowing policy such as the amount of nutrient discharged, the emission of PM2.5-related and greenhouse gas, and the input and output of agriculture production. SWAT (Soil and Water Assessment Tool) and IAP-N (Improving Anthropogenic Practices of managing reactive Nitrogen) models were used to quantify environmental indicators. Five scenarios with different planting patterns and fallow intensities were simulated for five years with different hydrological conditions. It is found that the influence of policy on water environment is highly sensitive to hydrological conditions, while the influence on air environment and economy are more affected by different policy settings in scenarios. The marginal utilities of the fallowed area are indicator-dependent. Planting alternative crops can decrease production costs and keep crop yields, while may also cause atmospheric environmental pollution if the crops have nitrogen fixing ability. Indicators also have spatial and temporal heterogeneity under different planting patterns and fallow intensities. A policy evaluation and associated uncertainty analysis is essential for effective implementation. The analysis framework established could support decision-making in regions facing agri-environmental problems.

What the reclaimed water use can change: From a perspective of inter-provincial virtual water network.

Reclaimed water has been used as an alternative water resource for various economic activities, which inevitably is involved in the virtual water trade. However, the effect of reclaimed water on the virtual water trade has not been evaluated in previous studies. For the sake of sustainable water management, this study explored the benefits of reclaimed water use for balancing the water resource allocation at the interprovincial level. Multiregional input-output analysis and ecological network analysis were used to investigate the spatial and structural characteristics of the virtual reclaimed water network (VRWN) among 31 provinces in China and the potential effect of reclaimed water use. The results show that the net export flows of virtual reclaimed water have different spatial patterns from those of freshwater, some provinces that import virtual freshwater are exporters of virtual reclaimed water. Although the exploitative relationship is the dominant ecological relationship in the VRWN (72%), it is confirmed that reclaimed water use contributes to balancing the virtual water trade of China with a more competitive relationship (21%) than in the virtual freshwater network (4%). The virtual freshwater consumption change rate in developed provinces decreases by more than 10% through reclaimed water use. Due to the high food exports and low application of wastewater reclamation in less developed provinces, the effect of reclaimed water use in those provinces is not as obvious as that in developed provinces. This paper offers a new perspective for understanding the current VRWN and guidance for the optimization of the virtual water trade structure.

Inhibition of the ROS-EGFR Pathway Mediates the Protective Action of Nox1/4 Inhibitor GKT137831 against Hypertensive Cardiac Hypertrophy via Suppressing Cardiac Inflammation and Activation of Akt and ERK1/2.

Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action. Treating with GKT137831 prevented cardiac hypertrophy in SHRs. Likewise, decreasing production of reactive oxygen species (ROS) with GKT137831 reduced epidermal growth factor receptor (EGFR) activity in the left ventricle of SHRs. Additionally, EGFR inhibition also reduced ROS production in the left ventricle and blunted hypertensive cardiac hypertrophy in SHRs. Moreover, inhibition of the ROS-EGFR pathway with Nox1/4 inhibitor GKT137831 or selective EGFR inhibitor AG1478 reduced protein and mRNA levels of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß), as well as the activities of Akt and extracellular signal-regulated kinase (ERK) 1/2 in the left ventricle of SHRs. In summary, GKT137831 prevents hypertensive cardiac hypertrophy in SHRs, Nox-deprived ROS regulated EGFR activation through positive feedback in the hypertrophic myocardium, and inhibition of the ROS-EGFR pathway mediates the protective role of GKT137831 in hypertensive cardiac hypertrophy via repressing cardiac inflammation and activation of Akt and ERK1/2. This research will provide additional details for GKT137831 to prevent hypertensive cardiac hypertrophy.

Rutaecarpine prevents hypertensive cardiac hypertrophy involving the inhibition of Nox4-ROS-ADAM17 pathway.

Rutaecarpine attenuates hypertensive cardiac hypertrophy in the rats with abdominal artery constriction (AAC); however, its mechanism of action remains largely unknown. Our previous study indicated that NADPH oxidase 4 (Nox4) promotes angiotensin II (Ang II)-induced cardiac hypertrophy through the pathway between reactive oxygen species (ROS) and a disintegrin and metalloproteinase-17 (ADAM17) in primary cardiomyocytes. This research aimed to determine whether the Nox4-ROS-ADAM17 pathway is involved in the protective action of rutaecarpine against hypertensive cardiac hypertrophy. AAC-induced hypertensive rats were adopted to evaluate the role of rutaecarpine in hypertensive cardiac hypertrophy. Western blotting and real-time PCR were used to detect gene expression. Rutaecarpine inhibited hypertensive cardiac hypertrophy in AAC-induced hypertensive rats. These findings were confirmed by the results of in vitro experiments that rutaecarpine significantly inhibited Ang II-induced cardiac hypertrophy in primary cardiomyocytes. Likewise, rutaecarpine significantly suppressed the Nox4-ROS-ADAM17 pathway and over-activation of extracellular signal-regulated kinase (ERK) 1/2 pathway in the left ventricle of AAC-induced hypertensive rats and primary cardiomyocytes stimulated with Ang II. The inhibition of Nox4-ROS-ADAM17 pathway and over-activation of ERK1/2 might be associated with the beneficial role of rutaecarpine in hypertensive cardiac hypertrophy, thus providing additional evidence for preventing hypertensive cardiac hypertrophy with rutaecarpine.

Understanding the synergistic effect between LID facility and drainage network: With a comprehensive perspective.

In recent years, low impact development (LID) has been deemed as an effective strategy for better storm water management. Among tremendous literature concerning the effectiveness of LID facilities to improve urban drainage system (UDS) performance, the scale, location, variety, and parameters of LIDs are fully discussed while the role of urban drainage network is rarely considered. Since LIDs and drainage network work together to realize the function of UDS, this research aims to explore their synergistic effects on the social, environmental, and technological performance of UDS. To represent different synergistic effects, a case area in Kunming, China is divided into upstream, midstream, and downstream sections. The hydraulic and topological characteristics of the drainage network in different sections are varied and 4 LID siting strategies are designed to distribute LID facilities in one of the 3 sections or in the total catchment evenly. Uncertainties from rainfall intensity and LID distribution are discussed as well. Based on the modeling results, the existence of synergistic effect is confirmed. Different spatial relationships between LIDs and the drainage network lead to disparate UDS performance. The synergistic effect may appear as the aggravation or mitigation of the conflicts among various functions of UDS, such as the reduction of urban flooding, combined sewer overflow, and shock loadings to wastewater treatment plant. The synergistic effect is sensitive to the rainfall intensity, suggesting the necessity of system performance investigation under non-design conditions. Due to the complicated synergistic effect, even distribution of LIDs in the target area can be a regretless and simplified solution. The discoveries reveal the significance of the synergistic effect and its implications for the LID planning.

Diverse and abundant antibiotics and antibiotic resistance genes in an urban water system.

The widespread use of antibiotics has resulted in pollution associated with antibiotics and antibiotic resistance genes (ARGs) in urban water systems, threatening the public health and the ecological security. In this study, the patterns of the diversity and abundance of the antibiotics and ARGs in a typical city (Kunming, China) were analyzed by monitoring their presence in the tap water, the land block sewage discharge units, the sewage pipes, the influent of WWTP, the effluent of WWTP, and the urban river channel. The results showed that although the average concentration of total antibiotics in tap water was 10 ng/L, the concentrations reached hundreds or even thousands of ng/L in all the other sections, indicating antibiotics entering water system through human or pets discharge. The relative abundances of ARG copies to 16S rRNA gene copies in the effluent of WWTP, the urban river channel which was the downstream of WWTP were higher than those of the sewage pipes, increasing risk of ARG transfer after treatment by WWTP. In general, the relative abundance of ARGs in spring was higher than that in winter. There was no significant correlation between antibiotics concentrations and their corresponding ARGs, except for a correlation between tetracyclines and tet-resistance genes. Due to the existence of transposases, the urban water system is exposed to a widespread risk of horizontal transfer of ARGs.

Evidence That ADAM17 Mediates the Protective Action of CGRP against Angiotensin II-Induced Inflammation in Vascular Smooth Muscle Cells.

Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.

The effects of berberine on a murine model of multiple sclerosis and the SPHK1/S1P signaling pathway.

Berberine (BBR) has shown neuroprotective properties. The present study aims to investigate the effects of BBR on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), and SphK1/S1P signaling, which plays a key role in MS. EAE was induced in mice, followed by treatment with BBR at 50, 100, or 300 mg/kg/d. Neurophysiological function was evaluated daily; inflammation, cell infiltration, and the severity of demyelination were also examined. The SphK1, SphK2, and S1P levels in the animals and primary astrocyte culture were measured. We found that treatment with BBR reduced the loss of neurophysiological function and the degree of demyelination. Moreover, BBR was associated with a decrease in SphK1 and S1P levels both in the animals and in culture. These results indicated that BBR suppresses demyelination and loss of neurophysiological function by inhibiting the SphK1/S1P signaling pathway. The use of BBR as a treatment of MS warrant further exploration.

Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena.

The spread of antibiotic resistance represents a global threat to public health, and has been traditionally attributed to extensive antibiotic uses in clinical and agricultural applications. As a result, researchers have mostly focused on clinically relevant high-level resistance enriched by antibiotics above the minimal inhibitory concentrations (MICs). Here, we report that two common water disinfection byproducts (chlorite and iodoacetic acid) had antibiotic-like effects that led to the evolution of resistant E. coli strains under both high (near MICs) and low (sub-MIC) exposure concentrations. The subinhibitory concentrations of DBPs selected strains with resistance higher than those evolved under above-MIC exposure concentrations. In addition, whole-genome analysis revealed distinct mutations in small sets of genes known to be involved in multiple drug and drug-specific resistance, as well as in genes not yet identified to play role in antibiotic resistance. The number and identities of genetic mutations were distinct for either the high versus low sub-MIC concentrations exposure scenarios. This study provides evidence and mechanistic insight into the sub-MIC selection of antibiotic resistance by antibiotic-like environmental pollutants such as disinfection byproducts in water, which may be important contributors to the spread of global antibiotic resistance. The results from this study open an intriguing and profound question on the roles of large amount and various environmental contaminants play in selecting and spreading the antibiotics resistance in the environment.