Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Effect of tea polyphenols as an antioxidant on pork for frying at different temperatures and times.

The aim of this study was to investigate the effect of frying on the antioxidant properties of tea phenols added to pork. The antioxidant capacity of tea polyphenols with different concentrations was tested using different assays including total antioxidant capacity (T-AOC) (FRAP method), thiobarbituric acid reactive substance, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) radical scavenging. Our results indicated that tea polyphenols have a great antioxidant capacity and that a high frying temperature causes fat oxidation. Our study confirmed that DPPH assay is more suited to lipophilic compounds or compounds with high lipid content. In a frying temperature of 180°C, the DPPH-free radical scavenging ability of pork was not decreased. Further experiments remain necessary to explore specific temperatures with the same results. This study provides new process parameters and new references for processing techniques of healthy and high-quality pork products.

Integrated transcriptomic analysis systematically reveals the heterogeneity and molecular characterization of cancer-associated fibroblasts in osteosarcoma.

BACKGROUND: Osteosarcoma (OS), with a peak incidence during the adolescent growth spurt, is correlated with poor prognosis for its high malignancy. The tumor microenvironment (TME) is highly complicated, with frequent interactions between tumor and stromal cells. The cancer-associated fibroblasts (CAFs) in the TME have been considered to actively involve in the progression, metastasis, and drug resistance of OS. This study aimed to characterize cellular heterogeneity and molecular characterization in CAFs subtypes and explore the potential targeting therapeutic strategies to improve the prognosis of OS patients. METHODS: The single-cell atlas of human OS tumor lesions were constructed from the GEO database. Then significant marker genes and potential biological functions for each CAFs subtype were identified and explored using the Seurat R package. Next, by performing the survival analyses and constructing the risk scores for CAFs subtypes, we aimed to identify and characterize the prognostic values of specific marker genes and different CAFs subtypes. Furthermore, we explored the therapeutic targets and innovative drugs targeting different CAFs subtypes based on the GDSC database. Finally, prognoses related CAFs subtypes were further validated through immunohistochemistry (IHC) on clinical OS specimens. RESULTS: Overall, nine main cell clusters and five subtypes of CAFs were identified. The differentially expressed marker genes for each CAFs clusters were then identified. Moreover, through Gene Ontology (GO) enrichment analysis, we defined the CAFs_2 (upregulated CXCL14 and C3), which was closely related to leukocyte migration and chemotaxis, as inflammatory CAFs (iCAFs). Likewise, we defined the CAFs_4 (upregulated CD74, HLA-DRA and HLA-DRB1), which was closely related to antigen process and presentation, as antigen-presenting CAFs (apCAFs). Furthermore, Kaplan-Meier analyses showed that CAFs_2 and CAFs_4 were correlated with poor clinical prognosis of OS patients. Meanwhile, therapeutic drugs targeting CAFs_2 and CAFs_4, such as 17-AAG/Docetaxel/Bleomycin and PHA-793887/NG-25/KIN001-102, were also explored, respectively. Finally, IHC assay confirmed the abundant CAFs_2 and CAFs_4 subtypes infiltration in the OS microenvironment compared with adjacent tissues. CONCLUSION: Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME.

Synergetic Effect of Electrical and Topographical Cues in Aniline Trimer-Based Polyurethane Fibrous Scaffolds on Tissue Regeneration.

Processibility and biodegradability of conductive polymers are major concerns when they are applied to tissue regeneration. This study synthesizes dissolvable and conductive aniline trimer-based polyurethane copolymers (DCPU) and processes them into scaffolds by using electrospinning with different patterns (random, oriented, and latticed). The effects of topographic cue changes on electrical signal transmission and further regulation of cell behaviors concerning bone tissue are researched. Results show that DCPU fibrous scaffolds possessed good hydrophilicity, swelling capacity, elasticity, and fast biodegradability in enzymatic liquid. In addition, the conductivity and efficiency of electrical signal transmission can be tuned by changing the surface's topological structure. Among them, oriented DCPU scaffolds (DCPU-O) showed the best conductivity with the lowest ionic resistance value. Furthermore, the viability and proliferation results of bone mesenchymal stem cells (BMSCs) demonstrate a significant increase on three DCPU scaffolds compared to AT-free scaffolds (DPU-R). Especially, DCPU-O scaffolds exhibit superior abilities to promote cell proliferation because of their unique surface topography and excellent electroactivity. Concurrently, the DCPU-O scaffolds can synergistically promote osteogenic differentiation in terms of osteogenic differentiation and gene expression levels when combined with electrical stimulation. Together, these results suggest a promising use of DCPU-O fibrous scaffolds in the application of tissue regeneration.

Chemical composition characteristics and source analysis of PM2.5 in Jiaxing, China: insights into the effect of COVID-19 outbreak.

Jiaxing is a medium-sized city in the Yangtze River Delta (YRD), which showed complex local and surrounding pollution sources. To study the COVID-19 impact on the ambient PM2.5 in Jiaxing, we collected the PM2.5 samples from 2 January to 25 April 2020 and analysed their chemical compositions (including carbon components, water-soluble ions (WSIs), and inorganic elements). The concentration of PM2.5 was 83.13 ± 30.93 µg/m3 before COVID-19 pandemic and then remarkably decreased with COVID-19 outbreak due to the suspension of mobility and industrial activities. Meanwhile, the concentrations of main chemical species (carbon components, water-soluble ions and inorganic elements) of PM2.5 all decreased from period A (2-20 January 2020) to period B (23 January to 10 February 2020). Moreover, Trajectory clustering analysis showed that close-range transport was one of the dominant factors throughout all the periods, except for period D (1-25 April 2020). In addition, the PSCF model indicated that the COVID-19 outbreak resulted in a significant decrease of WPSCF value. This study highlighted the differences in chemical compositions and sources of PM2.5 since COVID-19 pandemic was reported and provided a better understanding of its outbreak on PM2.5.

Microscopic Insights and Optimization of the CH4-CO2 Replacement in Natural Gas Hydrates.

Using the CO2 replacement method to exploit natural gas hydrates and store CO2 has great significance in energy access and environmental protection. Herein, the molecular dynamic method is utilized to analyze and evaluate the CH4-CO2 replacement at different constant temperatures and pressures. For optimization, various temperature oscillations are introduced in the CH4-CO2 replacement. It illustrates that increasing the temperature can improve the amounts of CH4 escape and CO2 capture but is unfavorable to the long-term CO2 storage and hydrate stability. The effects of pressure are not as significant and definite as those of temperature. Appropriate temperature oscillations can achieve comprehensive improvements, which benefit from both the deep diffusion of CO2 in the higher temperature stage and the rapid rebuilding of CO2 hydrate within just nanoseconds caused by the memory effects in the lower temperature stage. The results also reveal that the optimal lower temperature duration and frequency should be moderate. Decreasing the lower temperature value can distinctly enhance CO2 capture and hydrate stability. This study can help understand the mechanisms of CH4-CO2 replacement under different temperature and pressure conditions, especially at temperature transitions, and proposes a potentially effective method to achieve large-scale carbon sequestration in the hydrate.

Effects of physical and mental health factors and family function on the self-perception of aging in the elderly of Chinese community.

BACKGROUND: To examine the effects of physical and mental health factors and family functioning on the self-perception of ageing in elderly people. METHODS: A random cluster sampling method was used to select elderly people aged over 60 from three communities in Handan City. Subjects were evaluated via face-to-face interviews using the Chinese version of the Ageing Perception Questionnaire, the Family Function Scale, the SF-36 Short-Form Health Survey, and a self-compiled general questionnaire. A single factor and stepwise multiple regression analysis were evaluated using SPSS 17.0 software. RESULTS: Among the 1815 elderly people surveyed, the total negative dimension score was 91.67 ± 16.58 with an index of 73.34%, which is higher than the positive dimension score (6.01 ± 0.52, 60.10%). Elderly people with varying degrees of family dysfunction accounted for 11.63%, and the score for self-perceived ageing in elderly participants with good family function was 95.74 ± 12.63. The proportions with poor physical and mental health factors were 45.40% and 28.10%, respectively, and the scores for ageing self-perception in elderly participants with good or moderate mental health were 89.11 ± 12.65 and 86.22 ± 12.58, respectively. A stepwise multiple regression analysis showed that age, presence of a spouse, and family function were positive protective factors for ageing self-perception, while physical health factors were risk factors for the positive dimension of self-perceived ageing. Age and family function were risk factors for the negative dimension of ageing self-perception, while physical and mental health factors were protective factors for the negative dimension of self-perceived ageing. CONCLUSIONS: Younger elderly and elderly people with good family function have positive self-perceptions of ageing, while elderly participants with poor physical and mental health have a negative perception of ageing.

Improved Interactive Genetic Algorithm for Three-Dimensional Vase Modeling Design.

Interactive genetic algorithm (IGA) is an effective way to help users with product design optimization. However, in this process, users need to evaluate the fitness of all individuals in each generation. It will cause users' fatigue when users cannot find satisfactory products after multi-generation evaluations. To solve this problem, an improved interactive genetic algorithm (IGA-KDTGIM) is proposed, which combines K-dimensional tree surrogate model and a graphic interaction mechanism. In this algorithm, the K-dimensional tree surrogate model is built on the basis of users' historical evaluation information to assist the user's evaluation, so as to reduce the times of users' evaluation. At the same time, users are allowed to interact with the graphic interface to adjust the shape of the individual, so as to increase users' creation fun and to make the evolution direction of the population conform to users' expectations. The IGA-KDTGIM is applied to the 3D vase design system and independently experimented with IGA, IGA-KDT, and IGA-GIM, respectively. The average fitness, maximum average fitness, and evaluation times of statistical data were compared and analyzed. Compared with traditional IGA, the number of evaluations required by users decreased by 60.0%, and the average fitness of the population increased by 15.0%. The results show that this method can reduce the users' operation fatigue and improve the ability of finding satisfactory solutions to a certain extent.

Physical Properties and Storage Stability of Buton Rock Asphalt Modified Asphalt.

Buton Rock Asphalt (BRA) refers to the natural rock asphalt natively produced on the Buton island of Indonesia. It is often used as a modifier to enhance the performance of asphaltpavement. However, the segregation of BRA in BRA-Modified Asphalt (BRA-MA) has restricted its application. This study aims to investigate how the particle size and content of BRA affect the physical properties and storage stability of BRA-MA. Penetration, softening point, viscosity, and viscosity-temperature susceptibility (VTS) were analyzed. The evaluation method of storage stability was discussed and determined. The segregation of BRA in BRA-MA of static storage and transportation process were simulated and tested. The results suggest that the softening point and viscosity were positively correlated to BRA content and inversely determined by particle size. Penetration, VTS, and ductility were reduced due to the decline in particle size and increment of BRA content. The index of segregation value based on viscosity difference showed better statistical and quantitative significances than the softening-point difference in evaluating the storage stability. The particle size and content of BRA are positively correlated to the segregation of BRA-MA. Both the storage temperature and time were positively correlated to the segregation of BRA-MA. We prove that the relationship between specific surface area and segregation are power functional. BRA-MA with BRA whose 50% particle sizes are lower than 13.6 µm showed low segregation in transportation.

Effect of Lactobacillus plantarum KSFY01 on the exercise capacity of D-galactose-induced oxidative stress-aged mice.

Objectives: Aging is a process that involves comprehensive physiological changes throughout the body, and improvements in the exercise capacity of individuals may delay aging and relieve fatigue. Probiotics are subject to ongoing research to investigate their antioxidant properties. The purpose of this study was to investigate the effect of the probiotic Lactobacillus plantarum KSFY01 (L. plantarum KSFY01) on exercise tolerance in mice induced into a state of accelerated physiological aging by oxidative stress. Methods: A mouse model of accelerated aging was established using D-galactose to induce oxidative stress. The bacteria L. plantarum KSFY01 was isolated from fermented yak yogurt. The effect of L. plantarum KSFY01 on the improvement of exercise capacity in aging-accelerated mice was evaluated by measuring their running time until exhaustion, histopathological sections, related biochemical indicators, and underlying gene expression. Results: The oral administration of L. plantarum KSFY01 prolonged the running time of mice and reduced their creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferasem (AST) levels. From this study, we observed that L. plantarum KSFY01 significantly improved the exercise capacity of mice and alleviated liver damage. Treatment with L. plantarum KSFY01 reduced the blood urea nitrogen (BUN), lactic acid (LD) accumulation, and lactate dehydrogenase (LDH) elevations produced by the accelerated aging state, and also reversed the changes in muscle glycogen (MG). Overall, L. plantarum KSFY01 could effectively improve metabolite accumulation, thereby relieving fatigue in exercised mice. The results of the antioxidant indices in vivo showed that L. plantarum KSFY01 intervention increased the activity of antioxidant enzymes, decreased the level of malondialdehyde (MDA), and restored the balance between the oxidative and antioxidant systems in fatigued mice. By investigating the underlying molecular mechanism, our results showed that L. plantarum KSFY01 intervention significantly reversed the decline in the expression levels of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway-related factors and improved the body's antioxidant capacity. We determined that the underlying molecular mechanism responsible for the antioxidant effect of L. plantarum KSFY01 mainly involves the activation of the Nrf2 pathway. The effect of L. plantarum KSFY01 was dose-dependent, and the expression level of Nrf2 increased with increasing dosage of the probiotic. Conclusion: This study demonstrated that the probiotic L. plantarum KSFY01 exerts antioxidant effects and improved the athletic ability of mice. These findings are of significance to the development and utilization of probiotic resources.

The Chesapeake Bay Program Modeling System: Overview and Recommendations for Future Development.

The Chesapeake Bay is the largest, most productive, and most biologically diverse estuary in the continental United States providing crucial habitat and natural resources for culturally and economically important species. Pressures from human population growth and associated development and agricultural intensification have led to excessive nutrient and sediment inputs entering the Bay, negatively affecting the health of the Bay ecosystem and the economic services it provides. The Chesapeake Bay Program (CBP) is a unique program formally created in 1983 as a multi-stakeholder partnership to guide and foster restoration of the Chesapeake Bay and its watershed. Since its inception, the CBP Partnership has been developing, updating, and applying a complex linked modeling system of watershed, airshed, and estuary models as a planning tool to inform strategic management decisions and Bay restoration efforts. This paper provides a description of the 2017 CBP Modeling System and the higher trophic level models developed by the NOAA Chesapeake Bay Office, along with specific recommendations that emerged from a 2018 workshop designed to inform future model development. Recommendations highlight the need for simulation of watershed inputs, conditions, processes, and practices at higher resolution to provide improved information to guide local nutrient and sediment management plans. More explicit and extensive modeling of connectivity between watershed landforms and estuary sub-areas, estuarine hydrodynamics, watershed and estuarine water quality, the estuarine-watershed socioecological system, and living resources will be important to broaden and improve characterization of responses to targeted nutrient and sediment load reductions. Finally, the value and importance of maintaining effective collaborations among jurisdictional managers, scientists, modelers, support staff, and stakeholder communities is emphasized. An open collaborative and transparent process has been a key element of successes to date and is vitally important as the CBP Partnership moves forward with modeling system improvements that help stakeholders evolve new knowledge, improve management strategies, and better communicate outcomes.

[Variation Characteristics and Source Analysis of Carbonaceous Aerosols in Winter in Jiashan].

Organic carbon (OC), elemental carbon (EC), and PM2.5 concentration data obtained from Shanxi Super Station in Jiashan County of Jiaxing City, in the winter of 2018 and 2019, were analyzed to determine the variation and potential source areas of carbonaceous aerosols. The results show that OC concentrations in the winter of 2018 and 2019 were 6.90 µg·m-3 and 5.63 µg·m-3, respectively, while EC concentrations were 2.47 µg·m-3 and 1.57 µg·m-3, respectively. The concentrations of OC and EC in the winter of 2019 were lower than those in the winter of 2018, by approximately 18.4% and 36.4%, respectively. In 2018 and 2019, the concentrations of secondary organic carbon (SOC), calculated using the minimum R-squared (MRS) method, were 1.49 µg·m-3 and 1.97 µg·m-3, respectively, and the concentrations of primary organic carbon (POC) were 5.41 µg·m-3 and 3.66 µg·m-3, respectively. The proportion of POC in OC showed a downward trend, from 96.0% in December 2018 to 64.9% in February 2020, indicating a decrease of 31.1 percentage points. SOC showed an upward trend, increasing by 31.1 percentage points from 4.0% in December 2018 to 35.1% in February 2020. It is worth noting that with the increase in PM2.5 concentration, the concentration of OC and EC increased by 474.7% and 408.2%, respectively, although the proportion of OC in PM2.5 decreased from 18.8% to 12.3%. and the percentage of OC decreased from 5.8% to 3.3%. The contribution of POC to PM2.5 did not fluctuate, and only decreased significantly above 150 µg·m-3, while the contribution of SOC to PM2.5 first decreased and then increased. In Jiaxing, the potential sources of OC and EC were mainly southern Jiangsu, southeastern Anhui, local Jiaxing, and northern Zhejiang. In the winter of the contribution concentrations of OC and EC in the main potential source regions were approximately 2 µg·m-3 and 6 µg·m-3 lower, respectively, than in winter 2018. The range of high values in the potential source regions also decreased in 2019. Before the COVID-19 epidemic, it was affected by both motor vehicle exhaust emissions and coal burning. During the Spring Festival and home isolation, due to traffic control and other reasons, motor vehicle emissions were reduced, which leaving coal burning as the main contributor.

The Regulatory Mechanism of Water Activities on Aflatoxins Biosynthesis and Conidia Development, and Transcription Factor AtfB Is Involved in This Regulation.

Peanuts are frequently infected by Aspergillus strains and then contaminated by aflatoxins (AF), which brings out economic losses and health risks. AF production is affected by diverse environmental factors, especially water activity (aw). In this study, A. flavus was inoculated into peanuts with different aw (0.90, 0.95, and 0.99). Both AFB1 yield and conidia production showed the highest level in aw 0.90 treatment. Transcriptional level analyses indicated that AF biosynthesis genes, especially the middle- and later-stage genes, were significantly up-regulated in aw 0.90 than aw 0.95 and 0.99. AtfB could be the pivotal regulator response to aw variations, and could further regulate downstream genes, especially AF biosynthesis genes. The expressions of conidia genes and relevant regulators were also more up-regulated at aw 0.90 than aw 0.95 and 0.99, suggesting that the relative lower aw could increase A. flavus conidia development. Furthermore, transcription factors involved in sexual development and nitrogen metabolism were also modulated by different aw. This research partly clarified the regulatory mechanism of aw on AF biosynthesis and A. flavus development and it would supply some advice for AF prevention in food storage.

Current Situation, Global Potential Distribution and Evolution of Six Almond Species in China.

Almond resources are widely distributed in Central Asia; its distribution has not been studied in detail. Based on the first-hand data of field investigation, climate variables and chloroplast genome data, climatic characteristics of six almond species in China were analyzed, and the global distribution and evolutionary relationship were predicted. The six almond species are concentrated between 27.99°N and 60.47°N. Different almond species have different climatic characteristics. The climate of the almond species distribution has its characteristics, and the distribution of almond species was consistent with the fatty acid cluster analysis. All the test AUC (area under curve) values of MaxEnt model were larger than 0.92. The seven continents except for Antarctica contain suitable areas for the six almond species, and such areas account for approximately 8.08% of the total area of these six continents. Based on the analysis of chloroplast DNA and the distribution characteristics, the evolutionary relationship of the six almond species was proposed, which indicated that China was not the origin of almond. In this study, the construction of a phylogenetic tree based on the chloroplast genome and the characteristics of geographical distribution were constructed. The six almond species in China may have evolved from "Unknown almond species" through two routes. The MaxEnt model for each almond species provided satisfactory results. The prediction results can provide the important reference for Prunus dulcis cultivation, wild almond species development and protection.

Porous Electroactive and Biodegradable Polyurethane Membrane through Self-Doping Organogel.

In order to improve the processability of conductive polyurethane (CPU) containing aniline oligomers, a new CPU containing aniline trimer (AT) and l-lysine (PUAT) are designed and synthesized. Further, the 3D porous PUAT membranes have been prepared by a simple gel cooperated with freeze-drying method. Chemical testings and conductive properties testify a self- doping model of PUAT based on the rich electronic l-lysine and electroaffinity AT moities. The self-doping behavior further endows the PUAT copolymers specific characteristics such as high electrical conductivity and the formation of the polaron lattice like-structure in good solvent dimethyl sulfoxide. The combination of organogel and freeze-drying could prevent the collapse of pore structure when the copolymers are molded as membranes. The synergistic effect of l-lysine and AT components has a strong influence on the dissolution, degradation, thermal stability, and mechanical properties of PUAT. The excellent properties of PUAT would broad the application of conductive polymers in biomedicine field.

Effect of lemon seed flavonoids on the anti-fatigue and antioxidant effects of exhausted running exercise mice.

In this research, mice were gavaged with different doses of lemon seed flavonoids (LSF) for 4 weeks, and vitamin C was used as a positive control to investigate its effects on anti-fatigue and antioxidant capacity in exhaustively exercised mice. The results obtained from the study indicated that both vitamin C and LSF could significantly increase the running exhaustion time of mice, and the exhaustion time of mice was prolonged with increasing LSF concentration. LSF can increase hepatic glycogen and the free fatty acid content and reduce the lactate and urea nitrogen contents in a dose-dependent manner in mice. Serum CK, AST, and ALT levels in mice decreased gradually with increasing LSF concentration. LSF increased SOD and CAT levels and decreased MDA levels in mice in a dose-dependent manner. LSF could also enhance nNOS, eNOS, and ASCT1 mRNA expression and decrease syncytin-1, iNOS and TNF-α expression in the skeletal muscle of mice. By HPLC analysis, LSF was found to contain epigallocatechin, caffeic acid, epicatechin, vitexin, quercetin, and hesperidin, which are common flavonoids of this species. Thus, it was observed that LSF has good anti-fatigue and antioxidant capacities, and its anti-fatigue effect is related to improving the hepatic glycogen reserve capacity, increasing fat mobilization, and reducing lactate accumulation and protein decomposition. The antioxidant capacity of LSF is related to scavenging free radicals and reducing lipid peroxidation, and its antioxidant effect comes from its five antioxidant flavonoids. In conclusion, LSF has high development and application prospects in nutritional supplements. PRACTICAL APPLICATIONS: Lemon seed is the waste of lemon processing, which contains abundant flavonoids. The flavonoids in lemon seed can be used to exert its antioxidant effect and recover from exhausted exercise. Therefore, it can be concluded that lemon seed flavonoids are functional components that can be used as exercise recovery substances.

Extracellular vesicle-mediated delivery of miR-101 inhibits lung metastasis in osteosarcoma.

Rationale: Extracellular vesicles (EVs) have emerged as novel mediators of cell-to-cell communication that are capable of the stable transfer of therapeutic microRNAs (miRNAs), and thus, EVs hold immense promise as a miRNA delivery system for cancer therapy. Additionally, as miRNA-containing EVs are secreted into circulation, miRNAs contained within plasma EVs may represent ideal biomarkers for diseases. The objective of this study was to characterize a potential tumor suppressor miRNA, miR-101, and explore the potential of miR-101 delivery via EVs for in vivo therapy of metastatic osteosarcoma as well as the potential value of plasma EV-packaged miR-101 (EV-miR-101) level for predicting osteosarcoma metastasis. Methods: The relationship of miR-101 expression and osteosarcoma progression was investigated in osteosarcoma specimens by in situ hybridization (ISH), and the potential inhibitory effect of miR-101 was further investigated using in vivo models. Using prediction software analysis, the mechanism of action of miR-101 in osteosarcoma was explored using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and dual-luciferase assay. Adipose tissue-derived mesenchymal stromal cells (AD-MSCs) were transduced with lentiviral particles to obtain miR-101-enriched EVs. A Transwell assay and lung metastasis models of osteosarcoma were used to observe the effect of miR-101-enriched EVs on osteosarcoma invasiveness and metastasis. Detection of plasma EV-miR-101 levels was carried out in osteosarcoma patients and healthy controls by qRT-PCR. Results: miR-101 expression was markedly lower in metastatic osteosarcoma specimens compared to non-metastatic specimens. Significantly fewer metastatic lung nodules were formed by Saos-2 cells overexpressing miR-101 and SOSP-9607 cells overexpressing miR-101 injected into mice. With increased miR-101 expression, B cell lymphoma 6 (BCL6) mRNA and protein expression levels were reduced, and miR-101 was found to exert its effects by directly targeting BCL6. AD-MSCs were successfully engineered to secrete miR-101-enriched EVs. Once taken up by osteosarcoma cells, these EVs showed suppressive effects on cell invasion and migration in vitro, and systemic administration of these EVs effectively suppressed metastasis in vivo with no significant side effects. Finally, the EV-miR-101 level was lower in osteosarcoma patients than in healthy controls and even lower in osteosarcoma patients with metastasis than in those without metastasis. Conclusion: Our data support the function of miR-101 as a tumor suppressor in osteosarcoma via downregulation of BCL6. AD-MSC derived miR-101-enriched EVs represent a potential innovative therapy for metastatic osteosarcoma. EV-miR-101 also represents a promising circulating biomarker of osteosarcoma metastasis.

GRM4 inhibits the proliferation, migration, and invasion of human osteosarcoma cells through interaction with CBX4.

In recent years, the survey of metabolic glutamate receptor 4 (GRM4) in tumor biology has been gradually concerned. There are currently few studies on GRM4 in osteosarcoma, and the biological function is not clear. Analysis of TCGA database showed that there was no substantial deviation in the expression of GRM4 between osteosarcoma and normal tissues. In the subsequent experiments, there is no significant difference in either mRNA or protein levels among immortalized human osteoblasts and various osteosarcoma cells. With the overexpression of GRM4, cell proliferation, migration and invasion were inhibited obviously. It was further revealed that GRM4 can interact with CBX4 to restrict the nuclear localization of CBX4 and affect the transcriptional activity of HIF-1α. This is the evidence supporting the interaction between GRM4 and CBX4, which could inhibit the malignant behavior of osteosarcoma cells through the GRM4/CBX4/HIF-1α signaling pathway.

Triple Archives Particle Swarm Optimization.

There are two common challenges in particle swarm optimization (PSO) research, that is, selecting proper exemplars and designing an efficient learning model for a particle. In this article, we propose a triple archives PSO (TAPSO), in which particles in three archives are used to deal with the above two challenges. First, particles who have better fitness (i.e., elites) are recorded in one archive while other particles who offer faster progress, called profiteers in this article, are saved in another archive. Second, when breeding each dimension of a potential exemplar for a particle, we choose a pair of elite and profiteer from corresponding archives as two parents to generate the dimension value by ordinary genetic operators. Third, each particle carries out a specific learning model according to the fitness of its potential exemplars. Furthermore, there is no acceleration coefficient in TAPSO aiming to simplify the learning models. Finally, if an exemplar has excellent performance, it will be regarded as an outstanding exemplar and saved in the third archive, which can be reused by inferior particles aiming to enhance the exploitation and to save computing resources. The experimental results and comparisons between TAPSO and other eight PSOs on 30 benchmark functions and four real applications suggest that TAPSO attains very promising performance in different types of functions, contributing to both higher solution accuracy and faster convergence speed. Furthermore, the effectiveness and efficiency of these new proposed strategies are discussed based on extensive experiments.

Massive pollutants released to Galveston Bay during Hurricane Harvey: Understanding their retention and pathway using Lagrangian numerical simulations.

Increasing frequency of extreme precipitation events under the future warming climate makes the storm-related pollutant release more and more threatening to coastal ecosystems. Hurricane Harvey, a 1000-year extreme precipitation event, caused massive pollutant release from the Houston metropolitan area to the adjacent Galveston Bay. 0.57 × 106 tons of raw sewage and 22,000 barrels of oil, refined fuels and chemicals were reportly released during Harvey, which would likely deteriorate the water quality and damage the coastal ecosystem. Using a Lagrangian particle-tracking method coupled with a validated 3D hydrodynamic model, we examined the retention, pathway, and fate of the released pollutants. A new timescale, local exposure time (LET), is introduced to quantitatively evaluate the spatially varying susceptibility inside the bay and over the shelf, with a larger LET indicating the region is more susceptible to the released pollutants. We found LET inside the bay is at least one order of magnitude larger for post-storm release than storm release due to a quick recovery in the system's flushing. More than 90% of pollutants released during the storm exited the bay within two days, while those released after the storm could stay inside the bay for up to three months. This implies that post-storm release is potentially more damaging to water quality and ecosystem health. Our results suggest that not only the amount of total pollutant load but also the release timing should be considered when assessing a storm's environmental and ecological influence, because there could be large amounts of pollutants steadily and slowly discharged after storm through groundwater, sewage systems, and reservoirs.