Search Results (115)

Exosomes (EXs) mediate intercellular communication in the tissue microenvironment. We previously demonstrated that endothelial progenitor cell-derived exosomes (EPC-EXs) from exercised mice protect neurons and cerebral endothelial cells from hypoxia- and hypertension- induced injury ex vivo, suggesting their therapeutic potential in hypertensive ischemic injury. Here, we investigated whether exercise-conditioned EPC-EXs (ET-EPC-EXs) confer protection against acute ischemic injury. Hypertensive transgenic mice were divided into donor and recipient groups. Donor mice underwent treadmill exercise to generate ET-EPC-EXs. Recipient mice was subjected to middle cerebral artery occlusion and received ET-EPC-EXs via tail vein injection (2 × 10⁸/100 μL saline) two hours after stroke onset. Cerebral blood flow (CBF) was assessed, and brains were collected on day two for histological and molecular analyses. Our data showed that ET-EPC-EXs were robustly taken up by cerebral cells, predominantly in the penumbra in the ipsilateral hemisphere. ET-EPC-EXs reduced cell death and microglia activation and restored tight-junction proteins. Moreover, ET-EPC-EX treatment preserved CBF and improved sensorimotor function on day two post-stroke. Mechanistically, ET-EPC-EXs suppressed p38 activation, accompanied by reduced matrix metalloproteinase-3 and cytochrome c levels in the ipsilateral brain. Collectively, these findings demonstrate that EPC-EXs from exercise mice improve sensorimotor functions and confer protection in hypertensive ischemic brain injury, likely through attenuation of neuroinflammation and preservation of vascular integrity via modulation of the p38 signaling. Full article

In China, antibiotic fermentation residue has been listed as a “hazardous waste” due to its high residual concentrations of antibiotics. There are many ways to deal with antibiotic fermentation residue; however, effective methods are still lacking. In the present work, steam explosion (SE), thermal, and aerobic composting treatments were performed to investigate the resource utilization of cephalosporin C fermentation residue (CFR). The results show that 0 mg/kg, 50.2 mg/kg and 150.5 mg/kg cephalosporin C (CEPC) remained after the SE, composting, and thermal treatments. The total abundance of antibiotic resistance genes (ARGs) decreased by 62.2% and 47.2% after the SE and thermal treatments and increased by 1.4 times in the samples subjected to composting. Nitrogen analysis showed that the nitrogen loss (N loss) was only 1.9% in the SE-treated samples. The antibiotic inhibition zone was reduced by 80.3%, 71.2% and 40.8% in the samples subjected to SE, composting, and thermal treatments. LC/MS showed that the β-lactam ring and dihydrothiazine ring of CEPC were largely destroyed via SE. These results suggest that the SE treatment not only decreased the residual cephalosporin and ARG levels and antimicrobial activity but also preserved most of the nitrogen. SE is therefore a feasible treatment that can be used to deal with CFR. Full article

Anaerobic digestion (AD) is an environmentally friendly, promising solution for the recycling of agro-industrial wastes. However, overloading an anaerobic digester with substrate may cause the inhibition of the AD process. The present study investigated the effects of the substrate/inoculum (S/I) ratio on the AD of potato chip processing (PCP) waste from the potato chip processing industry (PCPI). The PCP waste included expired potato chips (EPCs), recovered potato starch (RPS), and potato peel (PP). Mesophilic AD was carried out in batch-wise static reactors at 35 ± 1 °C using four different S/I ratios (0.5, 1.0, 1.5, and 2.0 g VS/g VS) for each type of waste. Different optimum S/I ratios were obtained for the different wastes; however, the pH ranges were comparable (7.0 to 7.5) for all batches. The optimum S/I ratios for EPCs, RPS, and PP were 1.0, 1.5, and 2.0, respectively. The cumulative biogas yields for EPCs, RPS, and PP were 367.5 ± 6.3, 310.0 ± 5.5, and 202.5 ± 4.9 mL/g VS added, respectively. The methane content of the biogas yields ranged between 60% and 70%. There was a variable remarkable shift in the microbial population at the optimum S/I ratio of each type of waste. The abundance of Firmicutes increased in the case of EPCs and RPS but decreased in the case of PP. Conversely, Proteobacteria increased when using PP as a substrate and decreased in the case of EPCs. Herein, the results of the AD of PCP wastes confirm its potential for the onsite production of renewable bioenergy and reductions in energy bills in the PCPI. In addition, this study provides guidance for optimizing the AD of PCP wastes for large-scale applications. Full article

Circulating levels of endothelial progenitor cells (EPCs) involved in endothelial homeostasis are often reduced in people with type 1 diabetes (T1D). The Glycemia Risk Index (GRI) quantifies the quality of glucose control by assessing both hypo- and hyperglycemia risk. We aim to investigate the association between the GRI and circulating EPC levels in people with T1D. This cross-sectional study included 132 adults with T1D, on intensive insulin therapy. We calculated GRI from 14 days continuous glucose monitoring-derived metrics and quantified EPCs count by flow cytometry, stratifying results by GRI zones, ranging from A (lowest risk) to E (highest risk). Higher GRI scores were significantly associated with poorer metabolic parameters. Circulating levels of CD34⁺, CD133⁺, KDR⁺, and CD34⁺KDR⁺ cells were lower in participants with a worse GRI compared to adults with a better GRI. Linear regression analyses showed a negative association between GRI and CD34⁺ (β = −1.079, p = 0.006), CD34⁺CD133⁺ (β = −0.581, p = 0.008), and CD34⁺KDR⁺ (β = −0.147, p = 0.010). No significant association was found between HbA_1c and any EPC phenotype. Adults with T1D and a high GRI level had a lower EPCs count. GRI was significantly associated with certain EPC phenotypes, suggesting its potential role as a biomarker for cardiovascular risk assessment. Full article

Historic buildings are often assumed to have poor energy performance, and energy optimization of the buildings is perceived as threatening their cultural values. This study tests these assumptions. First, it examines the energy performance of Danish historic apartment buildings (buildings constructed before 1950 with a high preservation value, according to the national SAVE system (Survey of Architectural Values in the Built Environment)). Second, it assesses the extent to which the energy improvements in the historic buildings conflict with their historic value. An analysis of energy performance certificates (EPC) in 13,000 Danish historic apartment buildings reveals that they perform no differently than apartment buildings with a low preservation value, with 46% of historic apartment buildings achieving an EPC rating of “C”. Nevertheless, significant potential for further energy improvements is identified. Expert interviews and three case studies indicate that typical interventions for enhancing buildings’ energy performance rarely interfere with its historic values. This is partly due to structural conditions where shoulder-by-shoulder location, high building compactness, and supply with district heating gives a beneficial foundation for a high energy performance. Potential conflicts between energy improvements and historic values exist but are often resolved through dialogue between local authorities and owners about the interventions. Full article

Residential heritage buildings (RHBs) are facing complex conservation challenges due to national policies aimed at achieving carbon emission reductions and associated retrofit recommendations. This long-term study (2007–ongoing) focuses on how such nationwide policies, particularly energy performance certificates (EPCs) and minimum energy efficiency standards (MEES), affect a cluster of 12 RHBs on the National Trust’s Wallington Estate in Northumberland, England. Data were collected using a combination of building measurements and survey observations, alongside assessment of tenant behaviours through an interview process. The research findings revealed a 53% average improvement in EPC ratings following a retrofit. However, the tenant interviews exposed some key limitations in current policy tools, including their failure to reflect actual energy use and behavioural patterns. For instance, despite improved EPC scores, some tenants reported high fuel costs and continued to experience heat loss and dampness in the RHBs. These novel findings of this longitudinal study challenge the suitability of current retrofit metrics and advocate for a people-centric and context-specific approach to energy efficiency in heritage buildings. They also highlight the drawback of proposed minimum EPC ‘C’ standards within the UK’s existing housing stock, particularly in relation to idiosyncratic RHBs. Full article

The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients’ condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D. Full article

The You Only Look Once (YOLO) object detection model has been widely applied to electric power operation violation identification, owing to its balanced performance in detection accuracy and inference speed. However, it still faces the following challenges: (1) insufficient detection capability for irregularly shaped objects; (2) objects with low object-background contrast are easily omitted; (3) improving detection accuracy while maintaining computational efficiency is difficult. To address the above challenges, a novel real-time object detection model is proposed in this paper, which introduces three key innovations. To handle the first challenge, an edge perception cross-stage partial fusion with two convolutions (EPC2f) module that combines edge convolutions with depthwise separable convolutions is proposed, which can enhance the feature representation of irregularly shaped objects with only a slight increase in parameters. To handle the second challenge, an adaptive combination of local and global features module is proposed to enhance the discriminative ability of features while maintaining computational efficiency, where the local and global features are extracted respectively via 1D convolutions and adaptively combined by using learnable weights. To handle the third challenge, a parameter sharing of a multi-scale detection heads scheme is proposed to reduce the number of parameters and improve the interaction between multi-scale detection heads. The ablation study on the Ali Tianchi competition dataset validates the effectiveness of three innovation points and their combination. EAP-YOLO achieves the mAP@0.5 of 93.4% and an mAP@0.5–0.95 of 70.3% on the Ali Tianchi Competition dataset, outperforming 12 other object detection models while satisfying the real-time requirement. Full article

EPCs play important roles in the maintenance of vascular repair and health. Aging is associated with both reduced numbers and functional impairment of EPCs, leading to diminished angiogenic capacity, impaired cardiac repair, and increased risk for cardiovascular disease (CVD). The molecular mechanisms that govern EPC function in cardiovascular health are not fully understood, but there is increasing evidence that microRNAs (miRNAs) play key roles in modulating EPC functionality, endothelial homeostasis, and vascular repair. We aimed to determine how aging alters endothelial progenitor (EPC) health and functionality by altering key miRNA-mRNA pathways. To identify key miRNA-mRNA pathways contributing to diminished EPC functionality associated with aging, microRNA and mRNA profiling were conducted in EPCs from young and aged C57BL/6 mice. We identified a complex aging-associated regulatory network involving two miRNAs—miR-29c-3p and -126a—that acted in tandem to impair vascular endothelial growth factor signaling through targeting Klf2 and Spred1, respectively. The modulation of components of the miR-29c-3p–Klf2–miR-126a–Spred-1–Vegf signaling pathway altered EPC self-renewal capacity, vascular tube formation, and migration in vitro, as well as cardiac repair in vivo. The miR-29c-3p–Klf2–miR-126a–Spred1–Vegf signaling axis plays a critical role in regulating the aging-associated deficits in EPC-mediated vascular repair and CVD risk. Full article

Background/Objectives: Aberrant hypermethylation in the promoter regions of tumor suppressor genes facilitates the pathogenesis and progression of cancer. Therefore, inhibitors targeting DNA methyltransferase (DNMT) have been tested in clinical studies. However, the current monotherapy of DNMT inhibitors shows limited efficacy. Furthermore, the mechanism of action of DNMT inhibitors is DNA replication-dependent. To address these limitations, we developed a novel core–shell-type “epigenetics control (EpC) nanocarrier” that encapsulated decitabine (5-aza-dC) in the PLGA core nanoparticle and hybridized TET1 gene-encoding pDNA on the lipid shell surface. This study aimed to evaluate whether the dual delivery of DNMT inhibitors and pDNA of TET1 could synergistically enhance tumor suppressor gene expression and induce cell cycle arrest and/or apoptosis in cancer cells. Herein, we demonstrate the potential of the EpC carrier in HCT116 human colon cancer cells to upregulate tumor suppressor gene expression and rapidly achieve cell cycle arrest. Methods: PLGA core nanoparticles were prepared by the W/O/W double emulsion method. The formation of core–shell nanoparticles and complexation with pDNA were investigated and optimized by dynamic light scattering, zeta potential measurement, and agarose gel electrophoresis. The cellular uptake and transfection efficiency were measured by confocal laser scanning microscopy and a luciferase assay, respectively. The expression of p53 protein was detected by Western blotting. The anti-tumor effects of the EpC nanocarrier were evaluated by cell cycle analysis and an apoptosis assay. Results: The EpC nanocarrier delivered the DNMT inhibitor and TET gene-encoding pDNA into HCT116 cells. It promoted the expression of the tumor suppressor protein p53 and induced rapid cell cycle arrest in the G2/M phase in HCT116 cells. Conclusions: Our findings suggest that the dual-targeting of DNMT and TET enzymes effectively repairs aberrant DNA methylation and induces growth arrest in cancer cells, and the dual-targeting strategy may contribute to the advancement of epigenetic cancer therapy. Full article

The worm Enchytraeus buchholzi is a new pest injuring American ginseng Panax quinquefolium. To explore its reproductive potential and then estimate its population dynamics, the authors conducted two related experiments: (1) measuring individual fecundity in its lifetime by rearing each of the parent adults alone in a wet sandy dish at 18 and 21 °C indoors; (2) testing population growth by rearing each of the parent adults together with its offspring for a time longer than two generations at 21 °C. In Experiment I, five dependent variables, namely daily mean cocoons (DMC), cumulative cocoons (CC), eggs per cocoon (EPC), daily mean eggs (DME) and cumulative eggs (CE), were extracted, with each of them subject to a stepwise regression analysis on rearing time (T) and its power series as independent variables. Equaling to the net reproductive rate (R₀), the generational adult equivalent (GAE) was calculated via a conversion of F₁ generational eggs into adult equivalents (AE). In Experiment II, both an exponential and a logistic function were applied to construct regression equations. The results indicated that (1) a parent adult of E. buchholzi was able to live for a period as long as 10 and 13 full generations at the two temperatures tested and lay 84.8 and 110.6 cocoons containing 545 and 714 eggs, respectively; (2) DMC reached its maximum between 7 and 9 days of rearing and then declined slowly along a straight regression line; (3) CC rose steadily along a quadratic curve; (4) both EPC and DME varied following a cubic curve; (5) CE increased steadily along a cubic curve; (6) the new polynomial models suitably reflected the numerical growth trends of cocoons and eggs in the F₁ generation in a broad sense, while corresponding derivative equations quantified both the daily reproductive potential and resistance of the worm, thus revealed its daily reproductive capacity; (7) R₀ was 41.2 AE at 21 °C and 42.5 AE at 18 °C when a population of E. buchholzi lived in a niche with unlimited ambient resources; (8) this kind of temporal population generated by individual reproduction had fully demonstrated its significant, generational reproductive potential; and (9), through living in such a limited area as the wet sandy dish, bypassing an exponential growth process, the laboratory population grew up along a logistic curve from the F₁ to F₃ generations. The statistical relationships help to comprehend the individual reproduction of E. buchholzi, understand deeply the logical sequence and the difference between individual and population reproductions, predict population dynamics of the worm, and provide its integrated pest management with a solid basis. The experimental study has expanded theories on bionomics and population ecology, opening up a new area for research work in related fields. Full article

Human parvovirus B19 (B19V) is a major human pathogen in which the ssDNA genome is replicated within the nucleus of infected human erythroid progenitor cells (EPCs) through a process involving both cellular and viral proteins, including the non-structural protein (NS)1. We previously characterized the interaction between NS1 classical nuclear localization signal (cNLS: GACHAKKPRIT-182) and host cell importin (IMP)α and proposed it as a potential target for antiviral drug development. Here, we further extend on such findings. First, we demonstrate that NS1 nuclear localization is required for viral production since introducing the K177T substitution in a cloned, infectious viral genome resulted in a non-viable virus. Secondly, we demonstrate that the antiparasitic drug ivermectin (IVM), known to inhibit the IMPα/β dependent nuclear import pathway, could impair the NS1-NLS:IMPα interaction and suppress viral replication in UT7/EpoS1 cells in a dose-dependent manner. We also show that a panel of structurally related avermectins (AVMs) can dissociate the NS1-NLS:IMPα complex with half-maximal inhibitory concentrations in the nanomolar range. Among them, Eprinomectin emerged as the most selective inhibitor of B19V replication, with a selectivity index of c. 5.0. However, when tested in EPCs generated from peripheral blood mononuclear cells, which constitute a cellular population close to the natural target cells in bone marrow, the inhibitory effect of IVM and Eprinomectin was demonstrated to a lesser extent, and both compounds exhibited high toxicity, thus highlighting the need for more specific inhibitors of the NS1-NLS:IMPα interaction. Full article

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer. Full article

Viperin is an interferon-stimulated gene (ISG) that plays an important role in the congenital antiviral immunity of vertebrates. In this study, the common carp viperin (cc-viperin) gene is characterized, and we determine whether it has the ability to inhibit spring viremia of carp virus (SVCV) replication in EPC cells. The results showed that the full-length cDNA of the cc-viperin gene was 1044 bp and it encoded 348 amino acids. The cc-viperin sequence contained a leucine zipper in the N-terminal, a CxxxCxxC motif in the SAM domain, and a conservative C-terminus. The cc-viperin gene’s nucleotide and amino acid sequence alignment revealed that cc-viperin displayed relatively high sequence identity compared with other species. Phylogenetic analysis displayed the close relation of cc-viperin with Carassius auratus and Mylopharyngodon piceus. Subcellular localization analysis indicated that the cc-viperin protein was located in the cytoplasm. The gene expression results showed that cc-viperin was expressed in all of the tissues tested. Its expression level significantly increased in EPC cells after 24 h to 72 h compared to the control during SVCV infection. Moreover, cc-viperin significantly inhibited SVCV replication when it was overexpressed, whereas it increased SVCV replication when it had reduced expression in EPC cells, respectively. To summarize, the results obtained in this work show that cc-viperin shares similar sequence characteristics with other vertebrates, and it could inhibit SVCV replication in EPC cells, displaying an antiviral effect in common carp. Full article

The general-purpose Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN is used to study the production of new particles in proton–proton collisions at an LHC center of mass energy of 13.6 TeV. The detector includes a magnet based on a 6 m diameter superconducting solenoid coil operating at a current of 18.164 kA. This current creates a central magnetic flux density of 3.8 T that allows for the high-precision measurement of the momenta of the produced charged particles using tracking and muon subdetectors. The CMS magnet contains a 10,000 ton flux-return yoke of dodecagonal shape made from the assembly of construction steel blocks distributed in several layers. These steel blocks are magnetized with the solenoid returned magnetic flux and wrap the muons escaping the hadronic calorimeters of total absorption. To reconstruct the muon trajectories, and thus to measure the muon momenta, the drift tube and cathode strip chambers are located between the layers of the steel blocks. To describe the distribution of the magnetic flux in the magnet yoke layers, a three-dimensional computer model of the CMS magnet is used. To validate the calculations, special measurements are performed, with the flux loops wound in 22 cross-sections of the flux-return yoke blocks. The measured voltages induced in the flux loops during the CMS magnet ramp-ups and -downs, as well as during the superconducting coil fast discharges, are integrated over time to obtain the initial magnetic flux densities in the flux loop cross-sections. The measurements obtained during the seven standard ramp-downs of the magnet were analyzed in 2018. From that time, three fast discharges occurred during the standard ramp-downs of the magnet. This allows us to single out the contributions of the eddy currents, induced in steel, to the flux loop voltages registered during the fast discharges of the coil. Accounting for these contributions to the flux loop measurements during intentionally triggered fast discharges in 2006 allows us to perform the validation of the CMS magnet computer model with better precision. The technique for the flux loop measurements and the obtained results are presented and discussed. The method for measuring magnetic flux density in steel blocks described in this study is innovative. The experience of 3D modeling and measuring the magnetic field in steel blocks of the magnet yoke, as part of a muon detector system, has good prospects for use in the construction and operation of particle detectors for the Future Circular Electron–Positron Collider and the Circular Electron–Positron Collider. Full article