Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

CFAP61 knockdown aggravates male infertility by inhibiting testosterone secretion by Leydig cells via the MAPK/COX-2 pathway.

This study aimed to elucidate the roles of cilia- and flagella-associated protein 61 (CFAP61) in male infertility and its underlying mechanisms. CFAP61 expression levels in the testicular tissues of male patients with infertility were determined using quantitative real-time polymerase chain reaction, immunohistochemical assay, and western blotting. Moreover, the specific roles of CFAP61 in male infertility were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays. Here, CFAP61 was expressed at low levels in the testicular tissues of male patients with infertility. Functionally, CFAP61 knockdown reduced the Leydig cell viability and testosterone secretion and enhanced apoptosis. A mechanistic study further revealed that silencing CFAP61 promoted the expression levels of mitogen-activated protein kinase (MAPK)/cyclooxygenase-2 (COX-2) signaling pathway-related proteins (p-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (p-JNK), p-P38, and COX-2). In conclusion, CFAP61 knockdown facilitated male infertility by suppressing Leydig cell viability and testosterone secretion and enhanced cell apoptosis by activating the MAPK/COX-2 pathway. Our data suggest CFAP61 as a potential therapeutic target for male infertility.

ErbB4 processing is involved in OGD/R induced neuron injury.

OBJECTIVE: Our previous study found that ErbB4 gene expression was changed after oxygen-glucose deprivation/reperfusion (OGD/R). However, the exact role and mechanism of ErbB4 in brain ischemia are largely unknown. In this study, we explored the protective effects of ErbB4 and its possible mechanism after OGD/R. METHODS: Cerebral ischemia/reperfusion (I/R) injury model was established in vitro and in vivo. Cell viability, apoptosis, and ROS production were measured by MTT, TUNEL, and fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). Infarct size was evaluated by TTC. We performed bioinformatics analyses to screen for novel key genes involved in ErbB4 changes. RNA-Seq was used to transcriptome analysis. RNA and protein expression were detected by quantitative RT‒PCR and western bloting. RESULTS: The expression of 80-kDa ErbB4 decreased after cerebral I/R injury in vitro and in vivo. Co-expression network analysis revealed that ErbB4 expression was correlated with the changes in Adrb1, Adrb2, Ldlr, and Dab2. Quantitative RT‒PCR revealed that the mRNA expression levels of Adrb1, Adrb2, and Dab2 were upregulated, and that of Ldlr was decreased after OGD/R. Activation of ErbB4 expression by neuregulin 1 (NRG1) significantly promoted cell survival, attenuated hippocampal apoptosis, and decreased ROS production after OGD/R. Furthermore, the elimination of ErbB4 using a specific siRNA reversed these beneficial effects. CONCLUSION: Our data revealed the neuroprotective effects of ErbB4 against OGD/R injury, and the action could be related to changes in the ErbB4 membrane-associated fragment and the expression of Adrb1, Adrb2, Ldlr, and Dab2.

The mechanisms of exosomes in diabetic foot ulcers healing: a detailed review.

As time goes by, the morbidity of diabetes mellitus continues to rise, and the economic burden of diabetic foot ulcers as a common and serious complication of diabetes is increasing. However, currently there is no unified clinical treatment strategy for this complication, and the therapeutic efficacy is unsatisfactory. Recent studies have revealed that biological effects of exosomes involved in multiple stages of the process of wound closure are similar to source cells. Compared with source cells, exosomes possess lowly immunogenicity, highly stability and easily stored, etc. Accumulating evidence confirmed that exosomes promote diabetic wound healing through various pathways such as promoting angiogenesis, collagen fiber deposition, and inhibiting inflammation. The superior therapeutic efficacy of exosomes in accelerating diabetic cutaneous wound healing has attracted an increasing attention. Notably, the molecular mechanisms of exosomes vary among different sources in the chronic wound closure of diabetes. This review focuses on the specific roles and mechanisms of different cell- or tissue-derived exosomes relevant to wound healing. Additionally, the paper provides an overview of the current pre-clinical and clinical applications of exosomes, illustrates their special advantages in wound repair. Furthermore, we discuss the potential obstacles and various solutions for future research on exosomes in the management of diabetic foot ulcer. The aim is to offer novel insights and approaches for the treatment of diabetic foot ulcer.

Progress of Nonmetallic Electrocatalysts for Oxygen Reduction Reactions.

As a key role in hindering the large-scale application of fuel cells, oxygen reduction reaction has always been a hot issue and nodus. Aiming to explore state-of-art electrocatalysts, this paper reviews the latest development of nonmetallic catalysts in oxygen reduction reactions, including single atoms doped with carbon materials such as N, B, P or S and multi-doped carbon materials. Afterward, the remaining challenges and research directions of carbon-based nonmetallic catalysts are prospected.

Recombinant human metallothionein-III alleviates oxidative damage induced by copper and cadmium in Caenorhabditis elegans.

Recombinant human metallothionein III (rh-MT-III) is a genetically engineered product produced by Escherichia coli fermentation technology. Its molecules contain abundant reducing sulfhydryl groups, which possess the ability to bind heavy metal ions. The present study was to evaluate the binding effects of rh-MT-III against copper and cadmium in vitro and to investigate the antioxidant activity of rh-MT-III using Caenorhabditis elegans in vivo. For in vitro experiments, the binding rates of copper and cadmium were 91.4% and 97.3% for rh-MT-III at a dosage of 200 µg/mL at 10 h, respectively. For in vivo assays, the oxidative stress induced by copper (CuSO4 , 10 µg/mL) and cadmium (CdCl2 , 10 µg/mL) was significantly reduced after 72 h of exposure to different doses of rh-MT-III (5-500 µg/mL), indicated by restoring locomotion behavior and growth, and reducing malondialdehyde and reactive oxygen species levels in C. elegans. Moreover, rh-MT-III decreased the deposition of lipofuscin and fat content, which could delay the progression of aging. In addition, rh-MT-III (500 µg/mL) promoted the up-regulation of Mtl-1 and Mtl-2 gene expression in C. elegans, which could enhance the resistance to oxidative stress by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that supplemental rh-MT-III could effectively protect C. elegans from heavy metal stress, providing an experimental basis for the future application and development of rh-MT-III.

Activation of the Akt/FoxO3 signaling pathway enhances oxidative stress-induced autophagy and alleviates brain damage in a rat model of ischemic stroke.

Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following H2O2 injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke.

Controlled flavor release from high internal phase emulsions as fat mimetics based on glycyrrhizic acid and phytosterol.

Animal fat as the key component of sensory experience impacts texture, juiciness, and aroma pleasantness of meat, which indicates the necessity of designing fat mimetics in meat alternatives. In this study, high internal phase emulsions (HIPE) with tunable flavor release as fat mimetics based on glycyrrhizic acid (GA) and phytosterol were prepared, and the effects of GA and phytosterol concentrations on the microstructural, rheological, and flavor release properties of HIPE were evaluated. Phytosterol crystals-enriched oil droplets were trapped inside the GA fibrillar matrix as stabilizers. HIPE containing higher GA and phytosterol concentrations exhibited smaller droplet size and better viscoelastic attributes. Additionally, phytosterol played a synergistic role with GA to form a double-fiber microstructure at the oil-water interface. This hierarchical microstructure of oil phase, interface and aqueous phase in the HIPE could regulate the release of hydrophilic and lipophilic meat volatiles. HIPE as fat mimetics with unique microstructure have potential applications in meat alternatives.

Numerical Analysis of Microcrack Propagation Characteristics and Influencing Factors of Serrated Structural Plane.

The serrated structural plane is the basic unit of structural plane morphology. However, the understanding of its internal stress distribution, failure mode and crack evolution law was not clear enough in previous studies. In this paper, the shear mechanical properties of the serrated structural planes were studied by numerical simulation, and the crack evolution law of the serrated structural planes and the effects of four microscopic parameters on the shear properties were analyzed. The results show that: (1) the number of microcracks increases with the increase in normal stress; the crack expansion rate is slow before the shear stress reaches the peak. After the shear stress reaches the peak, the crack expansion rate continues to increase, and the microcracks keep sprouting and expanding, and the number of microcracks tends to stabilize when the shear stress reaches the residual shear strength. (2) The particle contact stiffness ratio kn∗/ks∗ and parallel bond stiffness ratio kn/ks were negatively correlated with the shear strength; and the particle contact modulus E and parallel bond modulus E∗ were positively correlated with the shear strength. As the particle contact modulus E and parallel bond modulus E∗ increase, the peak shear displacement gradually decreases. The parallel bond stiffness ratio kn/ks has a negative correlation with the peak shear displacement. This study is expected to provide theoretical guidance for the microscopic parameter calibration and shear mechanical analysis of serrated structural planes. (3) Several XGBoost, WOA-XGBoost, and PSO-XGBoost algorithms are introduced to construct the quantitative prediction model, and the comparative analysis found that WOA-XGBoost has the best fitting effect and can be used for the prediction of shear strength. When using this model to calculate the weight shares of micro-parameters, it was found that kn∗/ks∗ has the greatest influence on shear strength, followed by E∗; E and kn/ks had the least influence.

Rheological properties of transglutaminase-treated concentrated pea protein under conditions relevant to high-moisture extrusion processing.

At present, the structural changes of extruded materials under thermal-mechanical stress during high-moisture extrusion are still unclear. In this study, the transglutaminase (TG) treatments on the structure of pea protein isolate (PPI) under conditions relevant to high-moisture extrusion processing (50 wt% PPI at 30°C, 120°C and heated to 120°C and subsequently cooled to 30°C) was studied by using a closed cavity rheometer. Strain and frequency sweeping were carried out under various temperature conditions, and the information obtained was drawn into a texture map. Lissajous curves combined with energy dissipation ratio were introduced to characterize the nonlinear response of the samples. The results showed that the storage modulus of PPI increased with the increase of TG concentration during heat treatment. After cooling to 30°C, PPI with 0.25-1%TG could enhance the elasticity, but treating by 2% TG could inhibit the formation of disulfide bonds, the uniform development of the protein network, thus showing the "tough" character. These findings can help to better understand the relationships of material-structure during the extrusion process, and also provide help for further optimization of the quality of meat substitutes.

Research on Spatiotemporal Association between Tourism and Transportation Based on CGS Model.

Tourism and transportation generally have an inseparable association. However, there are still many limitations in the existing research on it. For example, most scholars only adopt one single model method, which fails to consider geospatial elements. Moreover, some researchers simply use socioeconomic data for analysis and research and ignore the solid spatial characteristics between tourism and transportation, which leads to deviations in the results. To solve these problems, this article proposed a spatiotemporal association model by comprehensively using coupling coordination degree, gravity center model, and spatial coincidence degree. Based on the tourism economic and attraction spatial data, and the transportation and its network spatial data, the association between tourism and transportation can be revealed by the proposed model. This study conducted a quantitative analysis on the tourism and transportation industry in Jiangxi Province, China, from 2005 to 2019, and the results show that: (1) the coupling coordination degree of tourism and transportation increases year by year; (2) the change in gravity center of tourism and transportation is subtle. The mean value of spatial overlap is 80.33 km, while the mean value of inter-annual variation consistency is 0.56; (3) the spatial coincidence degree of tourism and transportation in Jiangxi Province indicates a steady upward trend and reaches 0.78 in 2019; and (4) based on the evolution trend in the coupling coordination degree, gravity center coupling model, and spatial coincidence degree of tourism and transportation, it can be seen that the slopes of their trend functions are similar and consistent-the slopes are 0.0239, 0.0253, and 0.0319, respectively-and the standard deviation of the slopes of the three is only 0.000018.

Spatial-temporal variations of terrestrial evapotranspiration across China from 2000 to 2019.

Terrestrial evapotranspiration (ET) refers to a key process in the hydrological cycle by which water is transferred from the Earth's surface to lower atmosphere. With spatiotemporal variations, ET plays a crucial role in the global ecosystem and affects vegetation distribution and productivity, climate, and water resources. China features a complex, diverse natural environment, leading to high spatiotemporal heterogeneity in ET and climatic variables. However, past and future ET trends in China remain largely unexplored. Thus, by using MOD16 products and meteorological datasets, this study examined the spatiotemporal variations of ET in China from 2000 to 2019 and analyzed what is behind changes, and explored future ET trends. Climate variation in China from 2000 to 2019 was statistically significant and had a remarkable impact on ET. Average annual ET increased at a rate of 5.3746 mm yr-1 (P < 0.01) during the study period. The main drivers of the trend are increasing precipitation and wind speed. The increase in ET can also be explained to some extent by increasing temperature, decreasing sunshine duration and relative humidity. The zonation results show that the increase in temperature, wind speed, and precipitation and the decrease in relative humidity had large and positive effects on ET growth, and the decrease in sunshine duration had either promoting or inhibiting effects in different agricultural regions. Pixel-based variations in ET exhibited an overall increasing trend and obvious spatial volatility. The Hurst exponent indicates that the future trend of ET in China is characterized by significant anti-persistence, with widely distributed areas expected to experience a decline in ET. These findings improve the understanding of the role of climate variability in hydrological processes, and the ET variability in question will ultimately affect the climate system.

An Improved HMM-Based Approach for Planning Individual Routes Using Crowd Sourcing Spatiotemporal Data.

With the rapid development of LBSs (location-based services) in recent years, researchers have increasingly taken an interest in trying to make travel routes more practicable and individualized. Despite the fact that many studies have been conducted on routes using LBS data, the specific routes are deficient in dynamic scalability and the correlations between environmental constraints and personal choices have not been investigated. This paper proposes an improved HMM-based (hidden Markov model) method for planning personalized routes with crowd sourcing spatiotemporal data. It tries to integrate the dynamic public preferences, the individual interests and the physical road network space in the same spatiotemporal framework, ensuring that reasonable routes will be generated. A novel dual-layer mapping structure has been proposed to bridge the gap from brief individual preferences to specific entries of POIs (points-of-interest) inside realistic road networks. A case study on Changsha city has proven that the proposed method can not only flexibly plan people's travel routes under different spatiotemporal backgrounds but also is close to people's natural selection by the perception of the group.

Ecology and geography of hemorrhagic fever with renal syndrome in Changsha, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in mainland China. HFRS is particularly endemic in Changsha, the capital city of Hunan Province, with one of the highest incidences in China. The occurrence of HFRS is influenced by environmental factors. However, few studies have examined the relationship between environmental variation (such as land use changes and climate variations), rodents and HFRS occurrence. The purpose of this study is to predict the distribution of HFRS and identify the risk factors and relationship between HFRS occurrence and rodent hosts, combining ecological modeling with the Markov chain Monte Carlo approach. METHODS: Ecological niche models (ENMs) were used to evaluate potential geographic distributions of rodent species by reconstructing details of their ecological niches in ecological dimensions, and projecting the results onto geography. The Genetic Algorithm for Rule-set Production was used to produce ENMs. Data were collected on HFRS cases in Changsha from 2005 to 2009, as well as national land survey data, surveillance data of rodents, meteorological data and normalized difference vegetation index (NDVI). RESULTS: The highest occurrence of HFRS was in districts with strong temperature seasonality, where elevation is below 200 m, mean annual temperature is around 17.5°C, and annual precipitation is below 1600 mm. Cultivated and urban lands in particular are associated with HFRS occurrence. Monthly NDVI values of areas predicted present is lower than areas predicted absent, with high seasonal variation. The number of HFRS cases was correlated with rodent density, and the incidence of HFRS cases in urban and forest areas was mainly associated with the density of Rattus norvegicus and Apodemus agrarius, respectively. CONCLUSIONS: Heterogeneity between different areas shows that HFRS occurrence is affected by the intensity of human activity, climate conditions, and landscape elements. Rodent density and species composition have significant impacts on the number of HFRS cases and their distribution.

Atmospheric moisture variability and transmission of hemorrhagic fever with renal syndrome in Changsha City, Mainland China, 1991-2010.

BACKGROUND: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991-2010 in Changsha, China. METHODS AND FINDINGS: Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3-4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño-Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity. CONCLUSIONS: The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease.

Effects of age and pulmonary arterial hypertension on the different phases of right atrial function.

To evaluate the effects of age and pulmonary hypertension on phasic right atrial function we measured right atrial volumes at 3 different points in the cardiac cycle in 57 healthy subjects and 33 patients with pulmonary arterial hypertension. Right atrial reservoir function was assessed by systolic filling volume and passive and active emptying by passive and active emptying volume and fraction of total emptying. We compared these phases of right atrial function in 30 healthy subjects <60 and 27 > or = 60 years old, and in a separate analysis, in 33 patients with pulmonary arterial hypertension and 33 matched controls. Healthy subjects > or =60 years had lower passive emptying fraction (46.0 +/- 23.3% vs 59.9 +/- 15.4%, P = 0.011) and larger active emptying volume (7.0 +/- 3.5 vs 4.9 +/- 2.5 ml/m2, P = 0.013 ) and fraction (54.0 +/- 23.3% vs 40.1 +/- 15.4%, P = 0.011) compared to those <60. Patients with pulmonary arterial hypertension had larger right atrial volumes, systolic filling volume (18.3 +/- 6.9 vs 12.3 +/- 4.9 ml/m2, P < or = 0.001) and active emptying volume and fraction (11.2 +/- 6.9 vs 5.4 +/- 3.0 ml/m2, P < or = 0.001; 60.7 +/- 29.9 vs 44.9 +/- 19.0%, P = 0.017 ) and smaller passive emptying fraction (39.3 +/- 29.9% vs 55.1 +/- 19.0%, P = 0.017) compared to controls. Aging and pulmonary arterial hypertension are associated with a decrease in passive right atrial emptying and an increase in right atrial active emptying.

Automated mitral annular tracking: a novel method for evaluating mitral annular motion using two-dimensional echocardiography.

We developed an automated mitral annular tracking method based on a digital processing of high frame rate cineloop images of 2-dimensional echocardiography. In this study, its feasibility and accuracy was validated in 11 healthy volunteers and 16 patients with left ventricular (LV) dysfunction. The mitral annular excursion measured by automated mitral annular tracking agreed well with that measured by 3-dimensional echocardiography and correlated with LV ejection fraction. The longitudinal mitral annular excursion was reduced whereas the radial one was preserved for patients with LV dysfunction compared with control subjects. The novel automated mitral annular tracking method is clinically feasible and has potential capability to quantify the comprehensive mitral annular motion for evaluating LV function in a clinical setting.

Echocardiographic assessment of regional ventricular function after device-based change of left ventricular shape.

We assessed the effects of implantation of Myosplint (Myocor, Maple Grove, Minn), a device that changes left ventricular (LV) cross-sectional shape from circular to bilobar, on regional LV function. A total of 10 open-chest dogs with tachycardia-induced cardiomyopathy were studied before and after Myosplint implantation. LV cross-sectional epicardial echocardiography at the papillary muscle level was performed along with acquisition of hemodynamic data. LV normalized thickening, fractional thickening, end-diastolic thickness, and end-diastolic curvatures were calculated for 10 LV segments. Myosplint implantation did not affect LV hemodynamics, but decreased average end-diastolic curvature (P <.0001) and increased its segmental heterogeneity (P <.0001). There was no change in average fractional thickening, whereas normalized thickening increased (P =.05). In contrast, segmental heterogeneity of both normalized and fractional thickening increased (P =.02 and P =.01, respectively). Structural modeling confirmed that Myosplint implantation increases regional stress heterogeneity and curvature heterogeneity. LV cross-sectional shape markedly affects regional LV performance.

Device based left ventricular shape change: validation of conductance technology in shape changed hearts.

We have reported that device based left ventricular (LV) shape change, accomplished by Myosplint, improved LV systolic function by three-dimensional echocardiography (3-D echo). However, evaluation of this device using the pressure-volume relationship is still important. This study was conducted to validate the use of conductance technology for this evaluation in shape-changed hearts. An ex vivo study using excised ovine hearts (n = 11) and an in vivo study using a canine pacing-induced heart failure model (n = 11) were performed. Three Myosplints were implanted. Before and after the shape changes, volumes measured by a conductance catheter were compared with volumes measured by the amount of saline in the ex vivo study or by 3-D echo in the in vivo study. The conductance volumes were linearly correlated with the saline volumes (r2 = 0.961+/-0.046; p < 0.0001) in the ex vivo study and with 3-D echo volumes (r2 = 0.757+/-0.220; p < 0.0001) in the in vivo study. The conductance volumes were linearly correlated with LV volumes even in the shape-changed hearts. This technology can be used to evaluate pressure-volume loops in the shape-changed hearts as long as the conductance volume is calibrated by a reliable method.