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Compartment syndrome generates an oxidative condition causing the death of skeletal muscle cells. Hirudin has antioxidant and anti-inflammatory properties. However, its correlation with the pathway of Nrf2/HO-1 for the protection of the skeletal muscle is unknown. We aimed to evaluate the protective efficacy of double-doses of hirudin in compartment syndrome and its association with Nrf2/HO-1 expression. Compartment syndrome was induced in rabbits and double-doses of hirudin (0-8 ATU/kg) were locally administered to select an optimal Hirudin concentration that protects skeletal muscle from damage. The tissue structural changes, W/D ratio, lipid peroxidation level by MDA assay and inflammatory factors were determined in the skeletal muscle. To determine the musculoprotective efficacy of H8 at 72 h timepoint after compartment syndrome, and its association with the Nrf2/HO-1 pathway, the following assays were performed by TUNEL assay and immunofluorescence: necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the HO-1 mRNA was evaluated by qPCR. Hirudin in a dose of 8 ATU/kg (H8) presented the lowest levels of histological damage, fibrosis, W/D ratio and oxidative stress in the studied groups. Moreover, treatment with H8 markedly downregulated the level of inflammatory factors including TNF-a, IL-1β and IL-6. H8 showed a protective effect at 72 h timepoint after compartment syndrome, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining in cytoplasm were increased, and the levels of HO-1 mRNA were also increased. In conclusion, double-doses of H8 alleviate the death of muscle cells induced by oxidative stress 72 h after compartment syndrome in rabbits. This protective effect is associated with the nuclear translocation of Nrf2 and an elevated expression of HO-1. [ABSTRACT FROM AUTHOR]

Long-term enhanced external counterpulsation (EECP) therapy has been recommended for antiatherogenesis in recent clinical observations and trials. However, the precise mechanism underlying the benefits has not been fully clarified. To quantify the effect of EECP intervention on arterial hemodynamic environment, a framework of numerical assessment was introduced using a parallel computing algorithm. A 3D endothelial surface of the carotid artery with mild atherosclerotic plaque was constructed from images of magnetic resonance angiography (MRA). Physiologic boundary conditions were derived from images of the ultrasound flow velocity spectrum measured at the common carotid artery and before and during EECP intervention. Hemodynamic factors relating to wall shear stress (WSS) and its spatial and temporal fluctuations were calculated and analyzed, which included AWSS, OSI, and AWSSG. Measuring and computational results showed that diastole blood pressure, perfusion, and WSS level in carotid bifurcation were significantly increased during EECP intervention. Mean AWSS level throughout the model increased by 16.9%, while OSI level did not show a significant change during EECP. We thus suggested that long-term EECP treatment might inhibit the initiation and development of atherosclerotic plaque via improving the hemodynamic environment in the carotid artery. Meanwhile, EECP performance induced a 19.6% increase in AWSSG level, and whether it would influence the endothelial functions may need a further study. Moreover, the numerical method proposed in this study was expected to be useful for the instant assessment of clinical application of EECP. [ABSTRACT FROM AUTHOR]

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-based approach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries. [ABSTRACT FROM AUTHOR]

Based on panel data of listed companies in China from 2006 to 2020, this study takes the establishment of automatic air quality monitoring stations as a quasi-natural experiment and uses the staggered difference-in-differences method to explore whether the establishment of monitoring stations promotes green innovation of listed companies. The empirical results show that: (1) The green innovation of companies achieves an increase of 3.5% with monitoring stations in their locations, and an increase of 2.3% with the establishment of each additional monitoring station. This conclusion is valid after a series of robustness tests and exclusive tests. (2) The heterogeneity analyses show that monitoring stations have a greater role in promoting green innovation for non-state-owned enterprises, enterprises in heavy polluting industries and enterprises in key cities for environmental protection. (3) The transmission mechanism test results show that the establishment of automatic air monitoring station has crowding-out effect rather than leverage effect on green innovation, substantial innovation rather than strategic innovation. (4) The further analyses manifest the promotion of end-to-end green innovation, independent invention and quality of green patents. • Establishing automatic air monitoring station significantly promotes the company's green innovation. • There are different effects on green innovation, due to ownership, pollution intensity and regulatory pressure. • Establishing monitoring station affects green innovation, displaying crowding-out effect and substantial innovation. • Establishing monitoring station can promote independent invention, end-to-end green innovation and quality of green patents. [ABSTRACT FROM AUTHOR]

Deadwood is an important structural and biological component of forest ecosystems habitating for a variety of soil fungal communities. However, it is unknown how decomposition of deadwood impacts fungal communities in the soil underneath functionally different tree species in forests. This study compared the effects of the barks of seven tree species, differing in physicochemical characteristics, on soil fungal communities during the early stages of deadwood decomposition in a subtropical forest. A field experiment consisting of 3 evergreen broadleaf, 3 deciduous broadleaf and 1 coniferous tree species, was conducted for 18 months to examine the impact of deadwood decomposition on soil fungal community using real-time PCR and high-throughput sequencing. Our results demonstrated that wood decomposition led to significant declines in soil pH. Functionally distinct tree species significantly shaped the distinct soil fungal composition and abundances underneath the deadwood of both broadleaf and coniferous trees after 18 months of decomposition. The fungal ecological guilds underneath the deadwood were altered, with symbiotrophs being more prominent, and a higher proportion of pathogens were observed under certain broadleaf tree species. Out of the soil fungal ASVs detected, only 51 (3 %) were generalists, while 1053 ASVs (52 %) exhibited traits indicating potential fungal specialists. There were stronger coniferous tree species preferences in soil fungal composition, compared to broadleaf trees. The initial bark density from broadleaf and coniferous species illustrated the most obvious difference. Interestingly, tree bark density, rather than soil chemistry, was the key driver causing the fluctuations in fungal composition during deadwood decomposition. Tree species traits notably affected soil fungal community during early wood decomposition. These findings highlight the importance of considering the bark traits in understanding the dynamics of soil fungal communities and its implications for forest health and ecosystem management. [Display omitted] • Wood decomposition during the early stages led to significant declines in soil pH. • Functionally distinct tree species shaped soil fungal composition and abundance. • Proportion of symbiotrophs dominated the soil under deadwood of all tree species. • Coniferous tree exhibited stronger species preferences in soil fungal composition. • Bark density determined fungal composition underneath broadleaf and coniferous trees. [ABSTRACT FROM AUTHOR]

• Multifunctional antibiotic hydrogel doped with lycopene-based liposome was developed. • LT NPs@Gel relives ER stress and promotes cell-migration and angiogenesis. • LT NPs@Gel modulates the inflammation environment by bacteria disinfection. • LT NPs@Gel restores wound regeneration environment by alleviation of oxidative stress. In the daily management of infected diabetic wound, antibiotics resistance derived from broad-spectrum antimicrobe is still inevitable. Together with the complicated inflammatory environment induced by hyperglycemia and bacteria colonization, it's urgent to develop a novel bioactive ingredient integrating both anti-oxidative and modulation on inflammatory environment to be combined with disinfection. In regard of this, lycopene (LYC), an abundant, natural and unsaturated alkene carotenoid extracted from tomatoes was intercalated into the Dipalmitoyl-phosphatidylcholine (DPPC) liposomes loading with tobramycin (TOB), and further formulated with HAMA hydrogel (LT NPs@Gel) to prepare a novel multifunctional antibiotic wound dressing. The in vitro study showed that the intercalation of LYC and the loaded TOB brought LT NPs antioxidative and antibacterial properties, thus effectively inhibit the proliferation of bacteria and relieve endoplasmic reticulum (ER) stress to promote cell migration and angiogenesis. In an infected diabetic wound model on rat, the local administration of LT NPs@Gel significantly promoted wound healing within 14 days. Owing to the synchronized management on the inflammation environment and bacteria colonization, the massive oxidative stress in the wound were significantly alleviated, followed by the distinctive promotion of angiogenesis, re-epithelization, and collagen deposition. We believe that this functional hybrid HAMA hydrogel formulated with novel LYC-intercalated antibiotic liposome can achieve the multi-dimensional management of infected diabetic wounds. [ABSTRACT FROM AUTHOR]

Enhanced external counterpulsation (EECP) is a noninvasive treatment method for coronary artery atherosclerosis that acts on the vascular endothelial cells. The intracoronary hemodynamic parameters that influence long-term treatment effect are the fundamental factors for the inhibition of intimal hyperplasia, which cannot be measured in real time. In order to optimize the long-term treatment effect of coronary heart disease, it is necessary to establish a method for quantified calculation of intracoronary hemodynamic parameters during counterpulsation to research the long-term hemodynamic mechanism of EECP. A geometric multiscale model coupled by the zero-dimensional (0D) lumped parameter model and the three-dimensional (3D) model of narrow coronary artery was established for the simulation of intracoronary hemodynamic environment. The 3D model was used to calculate the hemodynamic parameters such as wall shear stress (WSS) and oscillatory shear index (OSI), while the 0D model was used to simulate the blood circulatory system. Sequential pressure was applied to calves, thighs, and buttocks module in 0D model with the consideration of vessel collapse. Hemodynamic performance was compared with clinical reports to verify the effectiveness of the method. There were significant increases of the diastolic blood pressure (DBP), coronary flow, and the area-averaged WSS during application of EECP, while OSI behind stenosis has some decrease. The waveforms of coronary flow has good similarity with the clinical measured waveforms, and the differences between calculated mean arterial pressures (MAPs) and clinical measurements were within 1%. The fundamental factor in the cure of coronary heart disease by EECP is the improvement of WSS and the decrease of OSI. Comparing with the clinical reports, the immediate hemodynamic changes demonstrate the effectiveness of model. Intracoronary hemodynamic parameters during EECP could be acquired and the method could be used to simulate the long-term treatment effect of EECP. Graphical abstract. [ABSTRACT FROM AUTHOR]

Border pollution is usually a difficult problem in environmental governance. Based on the data at the county level in China from 2005 to 2019, this study takes the 12th Five-Year Plan (FYP) for atmospheric pollution as a policy shock, and uses the difference-in-differences (DID) method to explore the impact of regional joint prevention and control (JPC) of atmospheric pollution policy on air pollution of the border regions. Empirical results show that: (1) After implementing the JPC of atmospheric pollution policy, the PM 2.5 concentration in the border regions is reduced by 3.5%. (2) The mechanism analysis shows that there is a spillover effect in the governing behaviors of local governments. In the border areas under low economic growth pressure and high environmental protection pressure, the reduction effect of the JPC of atmospheric pollution policy is more significant on the PM 2.5 concentration of the border regions. The research conclusions have new insights into the role and effect of macro-regional environmental JPC policy and border pollution control, and provide practical guidance for social green governance. • JPC of atmospheric pollution policy can reduce air pollution in border regions. • After implementing the JPC, PM 2.5 is reduced by 3.5% in border regions. • Under low economic growth pressure, PM 2.5 can be better reduced in border regions. • Under high environmental pressure, PM 2.5 can be better reduced in border regions. [ABSTRACT FROM AUTHOR]

Traditional clinical mode of enhanced external counterpulsation is not targeted for different diseases. Specialized strategies in the treatment of enhanced external counterpulsation for coronary heart disease and cerebral ischemic stroke are supposed to be distinguished. The goal of treatment for coronary heart disease is diastolic blood pressure/systolic blood pressure = Q ≥ 1.2 after counterpulsation, while the goal of treatment for cerebral ischemic stroke is the improvement of mean arterial pressure. A computational lumped parameter model was established for the simulation of hemodynamic effect of enhanced external counterpulsation on two diseases. Vessel collapse was considered during the simulation of counterpulsation. Based on different pressurized and decompressed rate, pressurized moment, pressure duration, and pressure amplitude, different counterpulsation modes were applied to the model and the immediate hemodynamic effects were compared. Results showed that the pressure duration and pressure amplitude had most influence on two diseases. For cerebral ischemic stroke, the longer pressure duration and the higher pressure amplitude of thighs, the higher mean arterial pressure; while for coronary heart disease, the value of Q was highest when the pressure end moment was 0.6 s during a 0.88-s cardiac cycle, and Q had a linear increase in the pressure amplitude of buttocks, but little change with the increase of calves and thighs pressure amplitude. For patients with coronary heart disease, the pressure duration was not supposed to be too long to avoid the increase of systolic blood pressure, and the improvement of pressure amplitude of buttocks could promise a positive treatment effect for coronary heart disease. While for patients with cerebral ischemic stroke, both the long pressure duration of each part and the high pressure amplitude of thighs could result in the systolic blood pressure and diastolic blood pressure have a certain increase, thus promoting the maximum mean arterial pressure and a best treatment.The specialized treatment strategies of EECP for cardiovascular and cerebrovascular disease [ABSTRACT FROM AUTHOR]

Examining transcriptomic and metabolic responses of earthworms to microplastic-contaminated soil is critical for understanding molecular-level toxicity of microplastics; yet very little research on this topic exists. We investigated influences of environmentally relevant concentrations (ERC) of polypropylene (PP) and polyethylene (PE) microplastic-contaminated soil on earthworms at the transcriptomic, metabolic, tissue and whole-body levels to study their molecular toxicity. The addition of PP and PE at ERC induced oxidative stress on earthworms, as indicated by the high enrichment of glutathione metabolism and increased glutamine at the transcriptomic and metabolic levels. Digestive and immune systems of earthworms were damaged according to the injuries of the intestinal epithelium, partial shedding of chloragogenous tissues and unclear structure of coelom tissues, which were confirmed by pathway analysis at the transcriptomic level. Significant enrichment of arachidonic acid and glycerolipid metabolisms indicated that PP and PE disturbed the lipid metabolism in earthworms. Significantly increased betaine and myo-inositol, and decreased 2-hexyl-5-ethyl-3-furansulfonate suggested that PP and PE caused differences in osmoregulation extent. In conclusion, most similar responses of earthworm might result from special size rather than type effects of PP and PE microplastics. Contamination of soils with microplastics even at ERC has health risks to earthworms; therefore, proper management of microplastics to reduce their input to the environment is key to reducing the health risks to soil fauna. [Display omitted] • Molecular toxicity of microplastics contaminated soil to earthworm was characterized. • 0.02% polypropylene and polyethylene damaged earthworm digestive and immune systems. • Transcriptomic and metabolic responses of earthworm to PP and PE were similar. • 0.02% PP and PE disturbed earthworm's lipid, osmotic and carbohydrate metabolisms. • The metabolic difference of PP and PE to earthworm was osmoregulation intensity. [ABSTRACT FROM AUTHOR]

Lumped parameter model (LPM) is a common numerical model for hemodynamic simulation of human's blood circulatory system. The numerical simulation of enhanced external counterpulsation (EECP) is a typical biomechanical simulation process based on the LPM of blood circulatory system. In order to simulate patient-specific hemodynamic effects of EECP and develop best treatment strategy for each individual, this study developed an optimization algorithm to individualize LPM elements. Physiological data from 30 volunteers including approximate aortic pressure, cardiac output, ankle pressure and carotid artery flow were clinically collected as optimization objectives. A closed-loop LPM was established for the simulation of blood circulatory system. Aiming at clinical data, a sensitivity analysis for each element was conducted to identify the significant ones. We improved the traditional simulated annealing algorithm to iteratively optimize the sensitive elements. To verify the accuracy of the patient-specific model, 30 samples of simulated data were compared with clinical measurements. In addition, an EECP experiment was conducted on a volunteer to verify the applicability of the optimized model for the simulation of EECP. For these 30 samples, the optimization results show a slight difference between clinical data and simulated data. The average relative root mean square error is lower than 5%. For the subject of EECP experiment, the relative error of hemodynamic responses during EECP is lower than 10%. This slight error demonstrated a good state of optimization. The optimized modeling algorithm can effectively individualize the LPM for blood circulatory system, which is significant to the numerical simulation of patient-specific hemodynamics. [ABSTRACT FROM AUTHOR]

Background: Enhanced external counterpulsation (EECP) is an effective method for treating patients with cerebral ischemic stroke, while hemodynamics is the major contributing factor in the treatment of EECP. Different counterpulsation modes have the potential to lead to different acute and long-term hemodynamic changes, resulting in different treatment effects. However, various questions about appropriate counterpulsation modes for optimizing hemodynamic effects remain unanswered in clinical treatment.Methods: A zero-dimensional/three-dimensional (0D/3D) geometric multiscale model of the cerebral artery was established to obtain acute hemodynamic indicators, including mean arterial pressure (MAP) and cerebral blood flow (CBF), as well as localized hemodynamic details for the cerebral artery, which includes wall shear stress (WSS) and oscillatory shear index (OSI). Counterpulsation was achieved by applying pressure on calf, thigh and buttock modules in the 0D model. Different counterpulsation modes including various pressure amplitudes and pressurization durations were applied to investigate hemodynamic responses, which impact acute and long-term treatment effects. Both vascular collapse and cerebral autoregulation were considered during counterpulsation.Results: Variations of pressure amplitude and pressurization duration have different impacts on hemodynamic effects during EECP treatment. There were small differences in the hemodynamics when similar or different pressure amplitudes were applied to calves, thighs and buttocks. When increasing pressure amplitude was applied to the three body parts, MAP and CBF improved slightly. When pressure amplitude exceeded 200 mmHg, hemodynamic indicators almost never changed, demonstrating consistency with clinical data. However, hemodynamic indicators improved significantly with increasing pressurization duration. For pressurization durations of 0.5, 0.6 and 0.7 s, percentage increases for MAP during counterpulsation were 1.5%, 23.5% and 39.0%, for CBF were 1.2%, 23.4% and 41.6% and for time-averaged WSS were 0.2%, 43.5% and 85.0%, respectively.Conclusions: When EECP was applied to patients with cerebral ischemic stroke, pressure amplitude applied to the three parts may remain the same. Patients may not gain much more benefit from EECP treatment by excessively increasing pressure amplitude above 200 mmHg. However, during clinical procedures, pressurization duration could be increased to 0.7 s during the cardiac circle to optimize the hemodynamics for possible superior treatment outcomes. [ABSTRACT FROM AUTHOR]

Traditional clinical mode of enhanced external counterpulsation is not targeted for different diseases. Specialized strategies in the treatment of enhanced external counterpulsation for coronary heart disease and cerebral ischemic stroke are supposed to be distinguished. The goal of treatment for coronary heart disease is diastolic blood pressure/systolic blood pressure = Q ≥ 1.2 after counterpulsation, while the goal of treatment for cerebral ischemic stroke is the improvement of mean arterial pressure. A computational lumped parameter model was established for the simulation of hemodynamic effect of enhanced external counterpulsation on two diseases. Vessel collapse was considered during the simulation of counterpulsation. Based on different pressurized and decompressed rate, pressurized moment, pressure duration, and pressure amplitude, different counterpulsation modes were applied to the model and the immediate hemodynamic effects were compared. Results showed that the pressure duration and pressure amplitude had most influence on two diseases. For cerebral ischemic stroke, the longer pressure duration and the higher pressure amplitude of thighs, the higher mean arterial pressure; while for coronary heart disease, the value of Q was highest when the pressure end moment was 0.6 s during a 0.88-s cardiac cycle, and Q had a linear increase in the pressure amplitude of buttocks, but little change with the increase of calves and thighs pressure amplitude. For patients with coronary heart disease, the pressure duration was not supposed to be too long to avoid the increase of systolic blood pressure, and the improvement of pressure amplitude of buttocks could promise a positive treatment effect for coronary heart disease. While for patients with cerebral ischemic stroke, both the long pressure duration of each part and the high pressure amplitude of thighs could result in the systolic blood pressure and diastolic blood pressure have a certain increase, thus promoting the maximum mean arterial pressure and a best treatment. Graphical abstract The specialized treatment strategies of EECP for cardiovascular and cerebrovascular disease. [ABSTRACT FROM AUTHOR]