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Compared with young liver donors, aged liver donors are more susceptible to ischemia-reperfusion injury (IRI) following transplantation, which may be related to excessive inflammatory response and macrophage dysfunction, but the specific mechanism is unclear. Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, and plays an important regulatory role in inflammation response and macrophage function regulation. But its role in IRI following aged-donor liver transplantation is still unclear. This study demonstrates that MSR1 expression is decreased in macrophages from aged donor livers, inhibiting their efferocytosis and pro-resolving polarisation. Decreased MSR1 is responsible for the more severe IRI suffered by aged donor livers. Overexpression of MSR1 using F4/80-labeled AAV9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ultimately ameliorating IRI following aged-donor liver transplantation. In vitro co-culture experiments further showed that overexpression of MSR1 promoted an increase in calcium concentration, which further activated the PI3K-AKT-GSK3ß pathway, and induced the upregulation of ß-catenin. Overall, MSR1-dependent efferocytosis promoted the pro-resolving polarisation of macrophages through the PI3K-AKT-GSK3ß pathway-induced up-regulating of ß-catenin leading to improved IRI following aged-donor liver transplantation.
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BACKGROUND: Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT). METHODS: Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism. RESULTS: Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin. CONCLUSIONS: In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients.
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Morganella morganii, encompassing two subspecies, subsp. morganii and subsp. sibonii, is a common opportunistic pathogen, notable for intrinsic resistance to multiple antimicrobial agents. Despite its clinical significance, research into the potential evolutionary dynamics of M. morganii remains limited. This study involved the analysis of genome sequences from 431 M. morganii isolates, comprising 206 isolates that cause host infections, obtained from this study and 225 from the NCBI genome data sets. A diverse array of antimicrobial resistance genes (ARGs) was identified in M. morganii isolates, including mcr-1, tet(X4), tmexCD-toprJ, and various carbapenemase genes. In addition, a novel blaKPC-2-bearing plasmid with demonstrated conjugative capability was discovered in M. morganii. The majority of virulence-related genes (VRGs), except for the hlyCABD gene cluster, were found in almost all M. morganii. Three novel genospecies of M. morganii were identified, designated as M. chanii, M. variant1, and M. variant2. Compared to M. sibonii, M. chanii genospecies possessed a greater number of flagellar-related genes, typically located within mobile genetic elements (MGEs), suggesting potential for better environmental adaptability. Phylogenetic analysis further disclosed that M. morganii was divided into 12 sequence clusters (SCs). Particularly, SC9 harbored an elevated abundance of ARGs and VRGs, mainly toxin-related genes, and was associated with a higher presence of MGEs compared to non-SC9 strains. The collective findings suggest that M. morganii undergoes evolution driven by the influence of MGEs, thereby significantly enhancing its adaptability to selective pressures of environmental changes and clinical antimicrobial agents.IMPORTANCEThe growing clinical significance of Morganella morganii arises from its abundant virulence factors and antimicrobial resistance genes, resulting in elevated infection rates and increased clinical scrutiny. However, research on the molecular epidemiology and evolutionary trends of M. morganii has been scarce. Our study established a list of virulence-related genes (VRGs) for M. morganii and conducted a large-scale epidemiological investigation into these VRGs. Based on genomic classification, three novel genotypes of M. morganii were identified, representing evolutionary adaptations and responses to environmental challenges. Furthermore, we discovered the emergence of a sequence cluster enriched with antimicrobial resistance genes, VRGs, and mobile genetic elements, attributed to the selective pressure of antimicrobial agents. In addition, we identified a novel conjugative plasmid harboring the blaKPC-2 gene. These findings hold significance in monitoring and comprehending the epidemiology of M. morganii.
Subject(s)
Molecular Epidemiology , Morganella morganii , Phylogeny , Morganella morganii/genetics , Morganella morganii/drug effects , Morganella morganii/isolation & purification , Morganella morganii/pathogenicity , Humans , Evolution, Molecular , Genome, Bacterial , Anti-Bacterial Agents/pharmacology , Virulence Factors/genetics , Plasmids/genetics , Microbial Sensitivity Tests , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiologyABSTRACT
BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenationï¼H/Rï¼-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.
Subject(s)
Diterpenes, Kaurane , Liver , Macrophages , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Reperfusion Injury , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/drug effects , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Mice , Liver/metabolism , Liver/drug effects , Liver/pathology , Macrophages/metabolism , Macrophages/drug effects , Diterpenes, Kaurane/pharmacology , Male , Pyruvate Kinase/metabolism , Inflammasomes/metabolism , Inflammasomes/drug effects , Liver Diseases/metabolism , Liver Diseases/drug therapyABSTRACT
Quantum key distribution allows secret key generation with information theoretical security. It can be realized with photonic integrated circuits to benefit the tiny footprints and the large-scale manufacturing capacity. Continuous-variable quantum key distribution is suitable for chip-based integration due to its compatibility with mature optical communication devices. However, the quantum signal power control compatible with the mature photonic integration process faces difficulties on stability, which limits the system performance and causes the overestimation of a secret key rate that opens practical security loopholes. Here, a highly stable chip-based quantum signal power control scheme based on a biased Mach-Zehnder interferometer structure is proposed, theoretically analyzed, and experimentally implemented with standard silicon photonic techniques. Simulations and experimental results show that the proposed scheme significantly improves the system stability, where the standard deviation of the secret key rate is suppressed by an order of magnitude compared with the system using traditional designs, showing a promising and practicable way to realize a highly stable continuous-variable quantum key distribution system on chip.
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In the realm of federated learning (FL), the conventional dual-layered architecture, comprising a central parameter server and peripheral devices, often encounters challenges due to its significant reliance on the central server for communication and security. This dependence becomes particularly problematic in scenarios involving potential malfunctions of devices and servers. While existing device-edge-cloud hierarchical FL (HFL) models alleviate some dependence on central servers and reduce communication overheads, they primarily focus on load balancing within edge computing networks and fall short of achieving complete decentralization and edge-centric model aggregation. Addressing these limitations, we introduce the multicenter HFL (MCHFL) framework. This innovative framework replaces the traditional single central server architecture with a distributed network of robust global aggregation centers located at the edge, inherently enhancing fault tolerance crucial for maintaining operational integrity amidst edge network disruptions. Our comprehensive experiments with the MNIST, FashionMNIST, and CIFAR-10 datasets demonstrate the MCHFL's superior performance. Notably, even under high paralysis ratios of up to 50%, the MCHFL maintains high accuracy levels, with maximum accuracy reductions of only 2.60%, 5.12%, and 16.73% on these datasets, respectively. This performance significantly surpasses the notable accuracy declines observed in traditional single-center models under similar conditions. To the best of our knowledge, the MCHFL is the first edge multicenter FL framework with theoretical underpinnings. Our extensive experimental results across various datasets validate the MCHFL's effectiveness, showcasing its higher accuracy, faster convergence speed, and stronger robustness compared to single-center models, thereby establishing it as a pioneering paradigm in edge multicenter FL.
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Endometritis is a sort of general reproductive disease, which can lead to infertility in both humans and animals. Escherichia coli (E. coli) is recognised as the main bacterial etiology of endometritis among livestock and causes huge economic losses to dairy farming industry. Antibiotics are frequently used in the clinical treatment of endometritis; nevertheless, long-term use may result in adverse effects, including bacterial resistance and food safety concerns. TSAIII, one of the active pharmacological components of A. asphodeloides, has exhibited multiple biological activities, including anticancer, anti-angiogenesis, and anti-inflammatory properties. However, the protective effects of TSAIII in E. coli-challenged endometritis remain unclear. This study aimed to clarify the role of TSAIII in E. coli-induced endometritis in mice and elucidate its specific molecular mechanisms. In the present research, TSAIII treatment markedly alleviated the E. coli-induced uterine histopathological injury, and decreased myeloperoxidase (MPO) activity and pro-inflammatory cytokines levels in uterine tissue. Our results further demonstrated that TSAIII improved uterine epithelial barrier function by restoring the expressions of tight junction proteins. Furthermore, TSAIII administration noticeably suppressed the activation of the TLR4/NF-κB pathway and the NLRP3 inflammasome. Importantly, we found that TSAIII could regulate the uterine microbiota structure and composition in E. coli-induced mouse endometritis. In conclusion, these data demonstrate that treatment with TSAIII protects against E. coli-induced endometritis via modulating uterine microbiota composition, inhibiting TLR4/NF-κB pathway and NLRP3 inflammasome activation, in addition to improving uterine epithelial barrier function. Therefore, the results of this study provide a new therapeutic to potentially prevent endometritis.
Subject(s)
Endometritis , Saponins , Steroids , Humans , Female , Animals , Mice , Endometritis/chemically induced , NF-kappa B/metabolism , Escherichia coli/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Signal Transduction , Toll-Like Receptor 4/metabolism , Inflammasomes , Lipopolysaccharides/pharmacologyABSTRACT
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has had a significant impact on global social and economic stability. To combat this, researchers have turned to omics approaches, particularly epitranscriptomics, to limit infection and develop effective therapeutic strategies. Multi-omics can provide the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes. Epitranscriptomics focuses on the mechanisms of gene transcription in cells and tissues and the relationship between genetic material and epigenetic regulation. This review highlights the role of post-transcriptional regulation in SARS-CoV-2, which affect various processes such as virus infection, replication, immunogenicity, and pathogenicity. The review also explains the formation mechanism of post-transcriptional modifications and how they can be regulated to combat viral infection and pathogenicity.
Subject(s)
COVID-19 , Humans , COVID-19/genetics , SARS-CoV-2 , Epigenesis, Genetic , Pandemics , VirulenceABSTRACT
Aztreonam-avibactam, eravacycline, and cefoselis are three novel antimicrobial agents for the treatment of serious infections caused by Gram-negative bacteria. We evaluated the in vitro activities of the above-mentioned three antimicrobial agents against clinical Enterobacterales isolates. A total of 1,202 Enterobacterales isolates, including 10 genera or species, were collected from 26 hospitals that cover seven regions of China. The susceptibilities of the 30 antimicrobial agents were interpreted based on the combination of U.S. Food and Drug Administration and Clinical and Laboratory Standards Institute guidelines. The results indicated that all Enterobacterales isolates showed high susceptibility to aztreonam-avibactam (98.25%), eravacycline (85.69%), and cefoselis (62.73%). The first two antimicrobial agents also demonstrated potent activities against multidrug-resistant and carbapenem-resistant Enterobacterales independent of antimicrobial resistance mechanisms. The rates of susceptibility to aztreonam-avibactam, eravacycline, and cefoselis were lowest in Morganella spp. (84.42%), Proteus spp. (33.65%), and Escherichia coli (40.14%), respectively. In general, the lower rates of susceptibility to eravacycline and cefoselis were in the older inpatient group. The strains isolated from urinary tract exhibited the lowest rate of susceptibility (78.97%) to eravacycline, and the lowest rate of susceptibility (45.83%) to cefoselis was observed in nervous system specimens. The strains isolated from intensive care unit (ICU) wards showed significantly reduced susceptibility to cefoselis compared with those isolated from non-ICU wards. The MIC values of aztreonam-avibactam and ceftazidime-avibactam have poor consistency (weighted kappa = 0.243), as did eravacycline and tigecycline (weighted kappa = 0.478). Cefoselis and cefepime showed highly similar activities against Enterobacterales (weighted kappa = 0.801). Our results support the clinical development of aztreonam-avibactam, eravacycline, and cefoselis to treat infections caused by Enterobacterales. IMPORTANCE Infections caused by multidrug-resistant (MDR) Enterobacterales, especially carbapenem-resistant Enterobacterales (CRE), have been a challenging clinical problem due to the limited therapeutic options. Therefore, the need to develop novel antimicrobial agents and evaluate their activities against Enterobacterales in vitro is urgent. Our results show that the novel antimicrobial agents aztreonam-avibactam and eravacycline retain activities against MDR and CRE isolates, including carbapenemase producers and non-carbapenemase producers. Further analysis combined with clinical information on the strains tested revealed that no significant differences were observed in susceptibility rates of strains with different demographic parameters to aztreonam-avibactam. Age, specimen source, and department were associated with the susceptibility of strains to eravacycline and cefoselis (P ≤ 0.01). Compared with ceftazidime-avibactam, aztreonam-avibactam has its advantages and limitations against Enterobacterales. The potent activity of eravacycline against Enterobacterales was higher than that of tigecycline. Cefoselis and cefepime showed a highly consistent activity against Enterobacterales.
Subject(s)
Anti-Bacterial Agents , Aztreonam , Aztreonam/pharmacology , Aztreonam/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Tigecycline , Cefepime , beta-Lactamases , Carbapenems , Microbial Sensitivity TestsABSTRACT
Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL-1, consisted of a conserved signature sequence WPD loop and a single C(X)5 R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL-1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding-based RNA-interference method, knockdown of prl-1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl-1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin-like growth factor 1 signaling pathway, and SIR-2.1 but through a DAF-16-dependent pathway. Moreover, knockdown of prl-1 induced the nuclear translocation of DAF-16, and upregulated the expression of daf-16, sod-3, mtl-1, and ctl-2. Finally, suppression of prl-1 also reduced the ROS. In conclusion, suppression of prl-1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Phosphoric Monoester Hydrolases , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Forkhead Transcription Factors/metabolism , Liver/metabolism , Longevity , Phosphoric Monoester Hydrolases/metabolismABSTRACT
This study applied a life cycle assessment (LCA) methodology for a comparative environmental analysis between an innovative algae resource recovery and near zero-liquid discharge potable reuse system (i.e., the main system) versus a conventional potable reuse system (i.e., the benchmark system) through energy use and greenhouse gas (GHG) emissions. The objective of this study is to demonstrate that pilot-scale data coupled with LCA would provide valuable information for system optimization, integration, and improvements for the design of environmentally sustainable full-scale systems. This study also provides decision-makers valuable information regarding the energy demand and environmental impact of this innovative main system compared to a typical tried-and-true system for potable water reuse. The main system consists of a novel algal-based wastewater treatment coupled with a dual forward osmosis and seawater reverse osmosis (Algal FO-SWRO) membranes system for potable water recovery and hydrothermal liquefaction (HTL) to recover biofuels and valuable nutrients from the harvested algal biomass. The benchmark system refers to the current industry standard technologies for potable water reuse and waste management including a secondary biological treatment, microfiltration (MF), brackish water reverse osmosis (BWRO), ultraviolet/advanced oxidation process (UV-AOP), and granular activated carbon (GAC), as well as anaerobic digestion for sludge treatment. Respective energy and GHG emissions of both systems were normalized and compared considering 1 m3 of water recovered. Based on an overall water recovery of 76% designed for the benchmark system, the energy consumption totaled 4.83 kWh/m3, and the system was estimated to generate 2.42 kg of CO2 equivalent/m3 with most of the emissions coming from the biological treatment. The main system, based on an overall water recovery of 88%, was estimated to consume 4.76 kWh/m3 and emit 1.49 kg of CO2 eq/m3. The main system has high environmental resilience and can recover bioenergy and nutrients from wastewater with zero waste disposal. With the application of energy recovery devices for the HTL and the SWRO, increase in water recovery of the FO membrane, and replacement of the SWRO membrane with BWRO, the main system provides an energy-competitive and environmentally positive alternative with an energy demand of 2.57 kWh/m3 and low GHG emissions of 0.94 kg CO2 eq/m3.
Subject(s)
Drinking Water , Greenhouse Gases , Water Purification , Animals , Carbon Dioxide , Water Purification/methods , Wastewater , Seawater , Osmosis , Life Cycle StagesABSTRACT
This study developed a comprehensive techno-economic assessment (TEA) framework to evaluate an innovative algae resource recovery and near zero-liquid discharge potable reuse system (i.e., the main system) in comparison with a conventional potable water reuse system (i.e., the benchmark system). The TEA study aims to estimate the levelized costs of water of individual units and integrated processes including secondary wastewater treatment, advanced water purification for potable reuse, and sludge treatment. This would provide decision-makers valuable information regarding the capital and operational costs of the innovative main system versus a typical potable water reuse treatment train, along with possible routes of cost optimization and improvements for the design of full-scale facilities. The main system consists of (i) a novel algal-based wastewater treatment coupled with a dual forward osmosis and seawater reverse osmosis (Algal FO-SWRO) membranes system for potable water reuse and hydrothermal liquefaction (HTL) to produce bioenergy and subsequent nutrients extraction from the harvested algal biomass. The benchmark system includes (ii) an advanced water purification facility (AWPF) that consists of a conventional activated sludge biological treatment (CAS), microfiltration (MF), brackish water reverse osmosis (BWRO), ultraviolet/advanced oxidation process (UV-AOP), and granular activated carbon (GAC), with anaerobic digestion for sludge treatment. Capital expenditures (CAPEX) and operational expenditures (OPEX) were calculated for each unit of both systems (i.e., sub-systems). Based on a 76% overall water recovery designed for the benchmark system, the water cost was estimated at $2.03/m3. The highest costs in the benchmark system were found on the CAS and the anaerobic digester, with the UV-AOP combined with GAC for hydrogen peroxide (H2O2) quenching as the driving factor in the increased costs of the system. The cost of the main system, based on an overall 88% water recovery, was estimated to be $1.97/m3, with costs mostly driven by the FO and SWRO membranes. With further cost reduction and optimization for FO membranes such as membrane cost, water recovery, and flux, the main system can provide a much more economically viable alternative in its application than a typical benchmark system.
Subject(s)
Drinking Water , Water Purification , Wastewater , Sewage , Hydrogen Peroxide , Charcoal , Osmosis , Membranes, ArtificialABSTRACT
Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p < 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2.
ABSTRACT
In this paper, phase-change material (PCM) and ceramsite were used to increase the heat resistance of the asphalt mixture. The ceramsite asphalt mixture with PCM can bring a specific cooling effect to the road surface and alleviate the rapid deterioration at high temperature. Two phase-change materials, PCM-43 and PCM-48, were compared and selected as the heat absorption material of the asphalt mixture. It is found that PCM-43 has better thermal stability, temperature regulation performance, higher enthalpy value, and a less adverse effect on the rheological properties of asphalt. According to the road performance of the asphalt mixture, it suggests that the maximum content of ceramsite is 40%. The specific heat capacity of asphalt mixtures was studied by the method of the insulation bucket test, and the thermal conductivity coefficient of asphalt mixtures was tested by a thermal conductivity instrument. The results show that the specific heat capacity and thermal conductivity of the asphalt mixture can be reduced by adding PCM and ceramsite. The effect of ceramsite asphalt concrete with PCM on the temperature field of road structure was further analyzed by finite element method. Due to the thermal resistance of ceramsite in the upper layer, the cooling range and depth in the middle and lower surface layers can be improved. Meanwhile, the heat absorption of phase-change material can alleviate the heating phenomenon of the upper layer. Therefore, ceramsite asphalt concrete with PCM is effective for decreasing the high temperatures in the asphalt pavements.
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The data in this report are associated with "Characterization of Produced Water and Surrounding Surface Water in the Permian Basin, the United States" (Jiang et al. 2022) and include raw data on produced water (PW) quality and Pecos River water quality in the Permian Basin, which is one of the major oil and gas producing areas in the U.S. The data include 46 samples for PW and 10 samples for Pecos River water. The data include wet chemistry, mineral salts, metals, oil and grease, volatile and semi-volatile organic compounds, radionuclides, ammonia, hydraulic fracturing additives, and per- and polyfluoroalkyl substances. The PW samples were collected from five different locations in the Permian Basin. Twenty-four of the PW samples and the ten Pecos River samples were analyzed by the authors. The information for the rest of PW samples (22 samples) was provided by industrial collaborators in the Permian Basin. Statistical analyses were performed on the combined data to obtain Mean, Max, Min, 25th percentile, 50th percentile, and 75th percentile of each analyte.
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BACKGROUND: Acute rejection (AR) after liver transplantation (LT) is closely related to the survival of patients after surgery. Enhancement of the ability of Kupffer cells (KCs) to eliminate apoptotic cells can effectively alleviate AR. METHODS: Rubicon lentivirus (LV) and Rubicon small interfering RNA (siRNA) were transfected into KCs extracted from the liver tissue of mice. Primary KCs were extracted and cocultured with zymosan and apoptotic T lymphocytes. The levels of CD86, CD163, IL-10, TNF-α, TGF-ß, JAK1, STAT6, AKT1, mTOR and peroxisome proliferator-activated receptor-γ (PPARγ) were assessed via Western blotting (WB) and q-PCR. The levels of CD86 and CD163 were assessed via flow cytometry. mCherry-GFP-LC3 adenovirus (AV) was transfected into KCs. The recruitment of LC3II and the fusion of phagosomes and lysosomes were detected using immunofluorescence. Rubicon adeno-associated virus (AAV) was transfected into the liver tissue of mice via the portal vein, and models of immune tolerance (IT) and AR following LT were established. Pathological changes in the liver tissue were detected using HE staining. Apoptotic cells were assessed via TUNEL staining. The polarization state of KCs was detected via immunohistochemical staining. RESULTS: Rubicon-mediated LC3-associated phagocytosis (LAP) promotes the ability of KCs to degrade and clear apoptotic T lymphocytes. Polyunsaturated fatty acids (PUFAs), the product of apoptotic T lymphocyte degradation, activate PPARγ, which further promotes the M2 polarization of KCs. Enhanced degradation mediated by Rubicon contributes to promoting the M2 polarization of KCs and a microenvironment supportive of IT. CONCLUSIONS: Rubicon-mediated LAP promotes the clearance capability and M2 polarization of KCs via PUFA-dependent PPARγ activation to improve LT.
Subject(s)
Intracellular Signaling Peptides and Proteins , Kupffer Cells , Liver Transplantation , Phagocytosis , Animals , Intracellular Signaling Peptides and Proteins/metabolism , Kupffer Cells/metabolism , Liver/pathology , Mice , PPAR gamma/metabolismABSTRACT
Photoinduced charge transfer (CT) mechanisms of two Donor-π-Donor-π-Acceptor conjugates composed of ferrocene (Fc), zinc-porphyrin (ZnP), and fullerene (C60) linked by phenylene-acetylene/acetylene during the one- (OPA) and the two-photon absorption (TPA) processes are analyzed theoretically based on the density functional theory calculations and visualization methods to study the effects of linkage between the two donors on the excitation characteristics. The change of bridge affects the efficiency of superexchange CT from Fc to ZnP in the OPA process. The one-photon excitations are dominated by local transitions of ZnP and Fc, and there is almost no efficient CT from the donors to the acceptor for both the two researched structures. In contrast, the advantage of superexchange CT from ZnP to C60 becomes much larger than the other transition forms during the TPA process when the linkage between ZnP and Fc is changed from acetylene to phenylene-acetylene. This linkage effect in TPA would have great significance in designing novel optoelectronic devices.
Subject(s)
Acetylene , Fullerenes , Fullerenes/chemistryABSTRACT
Objectives: Although a recent study reported that stimulator of interferon genes (STING) in macrophages has an important regulatory effect on liver ischemia-reperfusion injury (IRI), the underlying mechanism of STING-dependent innate immune activation in liver macrophages (Kupffer cells, KCs) remains unclear. Here, we investigated the effect of STING on liver macrophage pyroptosis and the associated regulatory mechanism of liver IRI. Methods: Clodronate liposomes were used to block liver macrophages. AAV-STING-RNAi-F4/80-EGFP, an adenoassociated virus (AAV), was transfected into the portal vein of mice in vivo, and the liver IRI model was established 14 days later. In vitro, liver macrophages were treated with STING-specific siRNA, and a hypoxia-reoxygenation (H/R) model was established. The level of STING was detected via Western blotting (WB), RT-PCR, and immunostaining. Liver tissue and blood samples were collected. Pathological changes in liver tissue were detected by hematoxylin and eosin (H&E) staining. Macrophage pyroptosis was detected by WB, confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and enzyme-linked immunosorbent assay (ELISA). The calcium concentration was measured by immunofluorescence and analyzed with a fluorescence microplate reader. Results: The expression of STING increased with liver IRI but decreased significantly after the clodronate liposome blockade of liver macrophages. After knockdown of STING, the activation of caspase 1-GSDMD in macrophages and liver IRI was alleviated. More interestingly, hypoxia/reoxygenation (H/R) increased the calcium concentration in liver macrophages, but the calcium concentration was decreased after STING knockdown. Furthermore, after the inhibition of calcium in H/R-induced liver macrophages by BAPTA-AM, pyroptosis was significantly reduced, but the expression of STING was not significantlydecreased. Conclusions: Knockdown of STING reduces calcium-dependent macrophage caspase 1-GSDMD-mediated liver IRI, representing a potential therapeutic approach in the clinic.
Subject(s)
Caspase 1/metabolism , Liver/pathology , Macrophages/metabolism , Phosphate-Binding Proteins/metabolism , Pore Forming Cytotoxic Proteins/metabolism , Reperfusion Injury/physiopathology , Animals , Humans , Male , Mice , Signal Transduction , TransfectionABSTRACT
A thorough understanding of produced water (PW) quality is critical to advance the knowledge and tools for effective PW management, treatment, risk assessment, and feasibility for beneficial reuse outside the oil and gas industry. This study provides the first step to better understand PW quality to develop beneficial reuse programs that are protective of human health and the environment. In total, 46 PW samples from unconventional operations in the Permian Basin and ten surface water samples from the Pecos River in New Mexico were collected for quantitative target analyses of more than 300 constituents. Water quality analyses of Pecos River samples could provide context and baseline information for the potential discharge and reuse of treated PW in this area. Temporal PW and river water quality changes were monitored for eight months in 2020. PW samples had total dissolved solids (TDS) concentrations ranging from 100,800-201,500 mg/L. Various mineral salts, metals, oil and grease, volatile and semi-volatile organic compounds, radionuclides, ammonia, hydraulic fracturing additives, and per- and polyfluoroalkyl substances were detected at different concentrations. Chemical characterization of organic compounds found in Pecos River water showed no evidence of PW origin. Isometric log-ratio Na-Cl-Br analysis showed the salinity in the Pecos River samples appeared to be linked to an increase in natural shallow brine inputs. This study outlines baseline analytical information to advance PW research by describing PW and surrounding surface water quality in the Permian Basin that will assist in determining management strategies, treatment methods, potential beneficial reuse applications, and potential environmental impacts specific to intended beneficial use of treated PW.
Subject(s)
Hydraulic Fracking , Water Pollutants, Chemical , Humans , Oil and Gas Fields , Salinity , United States , Water Pollutants, Chemical/analysis , Water QualityABSTRACT
Produced water (PW) is a hypersaline waste stream generated from the shale oil and gas industry, consisting of numerous anthropogenic and geogenic compounds. Despite prior geochemical characterization, the comprehensive toxicity assessment is lacking for evaluating treatment technologies and the beneficial use of PW. In this study, a suite of in vitro toxicity assays using various aquatic organisms (luminescent bacterium Vibrio fischeri, fish gill cell line RTgill-W1, and microalgae Scenedesmus obliquus) were developed to investigate the toxicological characterizations of PW from the Permian Basin. The exposure to PW, PW inorganic fraction (PW-IF), and PW salt control (PW-SC) at 30-50% dilutions caused significant toxicological effects in all model species, revealing the high salinity was the foremost toxicological driver in PW. In addition, the toxicity level of PW was usually higher than that of PW-IF, suggesting that organic contaminants might also play a critical role in PW toxicity. When comparing the observed toxicity with associated chemical characterizations in different PW samples, strong correlations were found between them since higher concentrations of contaminants could generally result in higher toxicity towards exposed organisms. Furthermore, the toxicity results from the pretreated PW indicated that those in vitro toxicity assays had different sensitives to the chemical components present in PW. As expected, the combination of multiple pretreatments could lead to a more significant decrease in toxicity compared to the single pretreatment since the mixture of contaminants in PW might exhibit synergistic toxicity. Overall, the current work is expected to enhance our understanding of the potential toxicological impacts of PW to aquatic ecosystems and the relationships between the chemical profiles and observed toxicity in PW, which might be conducive to the establishment of monitoring, remediation, treatment, and reuse protocols for PW.