ABSTRACT
Nesprins comprise a family of multi-isomeric scaffolding proteins, forming the linker of nucleoskeleton-and-cytoskeleton complex with lamin A/C, emerin and SUN1/2 at the nuclear envelope. Mutations in nesprin-1/-2 are associated with Emery-Dreifuss muscular dystrophy (EDMD) with conduction defects and dilated cardiomyopathy (DCM). We have previously observed sarcomeric staining of nesprin-1/-2 in cardiac and skeletal muscle, but nesprin function in this compartment remains unknown. In this study, we show that specific nesprin-2 isoforms are highly expressed in cardiac muscle and localize to the Z-disc and I band of the sarcomere. Expression of GFP-tagged nesprin-2 giant spectrin repeats 52 to 53, localized to the sarcomere of neonatal rat cardiomyocytes. Yeast two-hybrid screening of a cardiac muscle cDNA library identified telethonin and four-and-half LIM domain (FHL)-2 as potential nesprin-2 binding partners. GST pull-down and immunoprecipitation confirmed the individual interactions between nesprin-2/telethonin and nesprin-2/FHL-2, and showed that nesprin-2 and telethonin binding was dependent on telethonin phosphorylation status. Importantly, the interactions between these binding partners were impaired by mutations in nesprin-2, telethonin, and FHL-2 identified in EDMD with DCM and hypertrophic cardiomyopathy patients. These data suggest that nesprin-2 is a novel sarcomeric scaffold protein that may potentially participate in the maintenance and/or regulation of sarcomeric organization and function.
Subject(s)
Connectin , LIM Domain Proteins , Muscle Proteins , Myocytes, Cardiac , Nerve Tissue Proteins , Nuclear Proteins , Sarcomeres , Animals , Humans , Mice , Rats , Connectin/metabolism , Connectin/genetics , Cytoskeletal Proteins/metabolism , Cytoskeletal Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins/metabolism , LIM Domain Proteins/genetics , LIM-Homeodomain Proteins , Microfilament Proteins/metabolism , Microfilament Proteins/genetics , Muscle Proteins/metabolism , Muscle Proteins/genetics , Myocytes, Cardiac/metabolism , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Protein Binding , Sarcomeres/metabolism , Transcription FactorsABSTRACT
The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.
Subject(s)
Breast Neoplasms , Organoids , Precision Medicine , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Organoids/drug effects , Organoids/pathology , Organoids/metabolism , Precision Medicine/methods , Animals , Xenograft Model Antitumor Assays , Mice , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor/methods , Middle AgedABSTRACT
The microscopic visualization of large-scale three-dimensional (3D) samples by optical microscopy requires overcoming challenges in imaging quality and speed and in big data acquisition and management. We report a line-illumination modulation (LiMo) technique for imaging thick tissues with high throughput and low background. Combining LiMo with thin tissue sectioning, we further develop a high-definition fluorescent micro-optical sectioning tomography (HD-fMOST) method that features an average signal-to-noise ratio of 110, leading to substantial improvement in neuronal morphology reconstruction. We achieve a >30-fold lossless data compression at a voxel resolution of 0.32 × 0.32 × 1.00 µm3, enabling online data storage to a USB drive or in the cloud, and high-precision (95% accuracy) brain-wide 3D cell counting in real time. These results highlight the potential of HD-fMOST to facilitate large-scale acquisition and analysis of whole-brain high-resolution datasets.
Subject(s)
Brain/diagnostic imaging , Imaging, Three-Dimensional/methods , Microscopy/methods , Microtomy/methods , Signal-To-Noise Ratio , Tomography/methodsABSTRACT
Background: Left atrial appendages (LAAs) play an important role in regulating left atrial function, and much evidence supports the possibility that changes in left atrial structure may cause or worsen mitral regurgitation. This study intended to investigate the outcomes of patients with mitral regurgitation who underwent left atrial appendage closure (resection or endocardial closure) during isolated surgical ablations. Methods: Patients with mild or moderate mitral regurgitation who received isolated surgical ablations for atrial fibrillation (AF) in our center from 2013 to 2022 were referred. During follow-up, each clinical visit was composed of medical interrogation, a 24 h Holter, and echocardiographic evaluation. Death, atrial fibrillation, worsening of mitral regurgitation, and stroke were evaluated as outcomes. Freedom from outcomes whose results were adjusted by inverse probability of treatment weighting for causal effects after acquiring propensity scores. Results: A total of 456 patients were enrolled in this study. During a median follow-up of 48 months, 30 deaths and 11 cases of stroke were observed. After adjustments, no significant differences in terms of death or stroke were observed among the three groups. Patients who underwent resection or endocardial closure during surgical ablations had a higher risk of mitral regurgitation worsening during follow-up (p < 0.05). During the whole follow-up, patients who underwent left atrial appendage interventions showed significantly larger left atrial and mitral annular diameters, as well as lower tethering height than those who had left atrial appendage preserved (all p < 0.05). Conclusions: Mitral regurgitation was more likely to get worse when patients with fundamental mitral diseases underwent LAA interventions during isolated surgical AF ablations. In the absence of LAA, the dilation of the left atrium and mitral annulus may ultimately lead to worsening of regurgitation.
ABSTRACT
Background: Coronary artery calcification (CAC) is a crucial marker for coronary atherosclerosis, and the extent of CAC is closely linked to the incidence and progression of cardiovascular diseases. The interleukin-2 (IL-2) receptor (IL-2R), which plays a critical role in mediating the proliferation and differentiation of immune cells, may also be involved in the development of CAC. The study aimed to investigate the relationship between IL-2R and CAC, with the goal of providing new insights into cardiovascular diseases. Methods: In this study, we enrolled 606 patients diagnosed with coronary artery disease to assess CAC. Based on coronary artery calcification score (CACS), patients were divided into two groups: the non-severe CAC group (CACS ≤ 400 Agatston units, AU) and the severe CAC group (CACS > 400 AU). Results: The results showed that IL-2R levels were significantly higher in patients with severe CAC compared to those with non-severe CAC (383 vs. 352 pg/mL, p = 0.002). Moreover, the level of IL-2R was positively correlated with the severity of CAC, independent of other clinical risk factors. According to Receiver Operating Characteristic (ROC) curve, the IL-2R prediction model demonstrated a good capability in distinguishing severe CAC with the Area Under the Curve (AUC) value of 0.726. Conclusions: Our study suggests that IL-2R is independently associated with the occurrence of severe CAC in coronary artery disease (CAD) patients. Additionally, IL-2R may play a crucial role in the development of advanced atherosclerosis. Consequently, therapeutic strategies targeting the IL-2/IL-2R pathway may be effective in preventing or treating CAD.
ABSTRACT
BACKGROUND: Near-infrared II theranostic agents have gained great momentum in the research field of AD owing to the appealing advantages. Recently, an array of activatable NIR-II fluorescence probes has been developed to specifically monitor pathological targets of AD. Furthermore, various NIR-II-mediated nanomaterials with desirable photothermal and photodynamic properties have demonstrated favorable outcomes in the management of AD. METHODS: We summerized amounts of references and focused on small-molecule probes, nanomaterials, photothermal therapy, and photodynamic therapy based on NIR-II fluorescent imaging for the diagnosis and treatment in AD. In addition, design strategies for NIR-II-triggered theranostics targeting AD are presented, and some prospects are also addressed. RESULTS: NIR-II theranostic agents including small molecular probes and nanoparticles have received the increasing attention for biomedical applications. Meanwhile, most of the theranostic agents exhibited the promising results in animal studies. To our surprise, the multifunctional nanoplatforms also show a great potential in the diagnosis and treatment of AD. CONCLUSIONS: Although NIR-II theranostic agents showed the great potential in diagnosis and treatment of AD, there are still many challenges: 1) Faborable NIR-II fluorohpores are still lacking; 2) Biocompatibility, bioseurity and dosage of NIR-II theranostic agents should be further revealed; 3) New equipment and software associated with NIR-II imaging system should be explored.
Subject(s)
Alzheimer Disease , Infrared Rays , Theranostic Nanomedicine , Humans , Theranostic Nanomedicine/methods , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/therapy , AnimalsABSTRACT
BACKGROUND: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.
Subject(s)
Heart Failure , Sodium Potassium Chloride Symporter Inhibitors , Adult , Aged , Humans , Acute Disease , Bias , Cause of Death , Heart Failure/drug therapy , Infusions, Intravenous , Injections, Intravenous , Length of Stay , Randomized Controlled Trials as Topic , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Sodium Potassium Chloride Symporter Inhibitors/adverse effectsABSTRACT
INTRODUCTION: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. METHODS: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. RESULTS: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. CONCLUSION: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Longevity/physiology , Sertraline/pharmacology , Sertraline/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , AMP-Activated Protein Kinases/metabolism , Lipofuscin/metabolism , Lipofuscin/pharmacology , Insulin , Forkhead Transcription Factors/geneticsABSTRACT
Two-dimensional (2D) nanosheets-based membranes, which have controlled 2D nano-confined channels, are highly desirable for molecular/ionic sieving and confined reactions. However, it is still difficult to develop an efficient method to prepare large-area membranes with high stability, high orientation, and accurately adjustable interlayer spacing. Here, we present a strategy to produce metal ion cross-linked membranes with precisely controlled 2D nano-confined channels and high stability in different solutions using superspreading shear-flow-induced assembly strategy. For example, membranes based on graphene oxide (GO) exhibit interlayer spacing ranging from 8.0±0.1â Å to 10.3±0.2â Å, with a precision of down to 1â Å. At the same time, the value of the orientation order parameter (f) of GO membranes is up to 0.95 and GO membranes exhibit superb stability in different solutions. The strategy we present, which can be generalized to the preparation of 2D nano-confined channels based on a variety of 2D materials, will expand the application scope and provide better performances of membranes.
ABSTRACT
Increasing carbon dioxide (CO2 ) promotes photosynthesis and mitigates heat stress-induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800, and 1000 µmol mol-1 ) accumulated increased levels of melatonin (N-acetyl-5-methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon, and hot pepper. Elevated CO2 (eCO2 ; 800 µmol mol-1 ) caused a 6.8-fold increase in leaf melatonin content, and eCO2 -induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2 -induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II, and transcript levels of chloroplast- and nuclear-encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB, and atpA, significantly increased in COMT1 overexpressing (COMT1-OE) tomato plants, but not in melatonin-deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild-type and COMT1-OE, melatonin deficiency compromised eCO2 -induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1-OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2 -induced thermotolerance was closely linked to the melatonin-dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection, and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2 -induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants.
Subject(s)
Melatonin , Solanum lycopersicum , Thermotolerance , Carbon Dioxide/metabolism , PhotosynthesisABSTRACT
AIMS: Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored. METHODS AND RESULTS: FNDC5/irisin was reduced in natural ageing, senescence, and angiotensin II (Ang II)-treated conditions. The deletion of FNDC5 shortened lifespan in mice. Additionally, FNDC5 deficiency aggravated vascular stiffness, senescence, oxidative stress, inflammation, and endothelial dysfunction in 24-month-old naturally aged and Ang II-treated mice. Conversely, treatment of recombinant irisin alleviated Ang II-induced vascular stiffness and senescence in mice and vascular smooth muscle cells. FNDC5 was triggered by exercise, while FNDC5 knockout abrogated exercise-induced protection against Ang II-induced vascular stiffness and senescence. Intriguingly, FNDC5 was detected in human and mouse blood-derived EVs, and exercise-induced FNDC5/irisin-enriched EVs showed potent anti-stiffness and anti-senescence effects in vivo and in vitro. Adeno-associated virus-mediated rescue of FNDC5 specifically in muscle but not liver in FNDC5 knockout mice, promoted the release of FNDC5/irisin-enriched EVs into circulation in response to exercise, which ameliorated vascular stiffness, senescence, and inflammation. Mechanistically, irisin activated DnaJb3/Hsp40 chaperone system to stabilize SIRT6 protein in an Hsp70-dependent manner. Finally, plasma irisin concentrations were positively associated with exercise time but negatively associated with arterial stiffness in a proof-of-concept human study. CONCLUSION: FNDC5/irisin-enriched EVs contribute to exercise-induced protection against vascular ageing. These findings indicate that the exerkine FNDC5/irisin may be a potential target for ageing-related vascular comorbidities.
Subject(s)
Extracellular Vesicles , Sirtuins , Humans , Mice , Animals , Aged , Child, Preschool , Fibronectins/metabolism , Transcription Factors/metabolism , Mice, Knockout , Aging , Angiotensin II/pharmacology , Inflammation/metabolism , Muscle, Skeletal/metabolism , HSP40 Heat-Shock Proteins/metabolismABSTRACT
BACKGROUND: Platelet concentrates combined with calcium silicate cements may promote reparative dentin formation. However, few studies have reported their effect on dental pulp inflammation. This study aimed to evaluate the effects of concentrated growth factor (CGF) combined with iRoot BP Plus on inflammatory human dental pulp stem cells (hDPSCs) in vitro and inflamed pulp in rats in vivo. METHODS: The proliferation of LPS-stimulated hDPSCs treated with 50% CGF with/without 25% iRoot BP Plus was evaluated using Cell Counting Kit-8 on days 1, 4 and 7. The expression of genes associated with inflammation on day 1 and differentiation on day 14 was analysed by real-time polymerase chain reaction. The exposed pulp of rat maxillary molars was injected with 10 mg/mL LPS and directly capped with CGF membrane with/without iRoot BP Plus extract for 1, 7 and 28 days. The teeth were subjected to histologic analyses and immunohistochemistry. RESULTS: The proliferation rates of the inflammatory hDPSCs after the combination treatment were significantly higher than those after the other treatments on days 4 and 7 (P < 0.05). IL-1ß, IL-6, and TNF-α levels were increased in inflammatory hDPSCs but decreased after treatment with CGF combined with iRoot BP Plus extract, whereas IL-4 and IL-10 showed the opposite expression patterns. Expression of the odontogenesis-related genes OCN, Runx2, and ALP was dramatically enhanced by combined treatment with CGF and iRoot BP Plus extract. In rat pulp, the average inflammation scores of the CGF and CGF-iRoot BP Plus groups significantly decreased in comparison with those of the LPS group (P < 0.05), and the CGF-iRoot BP Plus group had more reparative dentin than the CGF and BP groups. Immunohistochemical staining showed fewer M1 macrophages on day 1 and more M2 macrophages on day 7 in the CGF-iRoot BP Plus group than in the other groups. CONCLUSIONS: The combination of CGF and iRoot BP Plus showed a synergistic effect on anti-inflammatory potential and promoted greater pulp healing than CGF or iRoot BP Plus alone.
Subject(s)
Dental Pulp , Tooth , Humans , Rats , Animals , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Cell Differentiation , Cell ProliferationABSTRACT
The implementation of ultra-low emission (ULE) limits (SO2: 35 mg/m3, NOx: 50 mg/m3, PM: 10 mg/m3) promoted the development of flue gas treatment technologies in China. Pollutant control technology development for Chinese coal-fired power plants was summarized and an analysis of the applicability and cost of pollutant control technologies was conducted. Detailed data were collected from 30 ultra-low emission coal-fired units across China. Based on a cost analysis model, the average unit power generation incremental costs were 0.0144 and 0.0095 CNY/(kW·hr) for SO2 and NOx control technologies, respectively. The unit power generation incremental cost of twin spray tower technology was 7.2% higher than that of dual-loop spray tower technology. The effect of key parameters on operating cost was analyzed. The unit power generation incremental cost increased because of increments in the electricity price for SO2 control technology and the price of the reductant in NOx control technology. With high sulfur content or NOx concentration, the unit power generation incremental cost caused by pollutant control increased, whereas the unit pollutant abatement cost decreased. However, the annual operating hours or load increased, thereby leading to a decline in unit power generation incremental cost and unit pollutant abatement cost.
Subject(s)
Air Pollutants , Air Pollution , Environmental Pollutants , Air Pollutants/analysis , Industrial Development , Environmental Pollutants/analysis , Power Plants , Coal/analysis , Costs and Cost Analysis , China , Air Pollution/prevention & control , Air Pollution/analysisABSTRACT
Fair distribution of resources matters to both individual interests and group harmony during social cooperation. Different allocation rules, including equity- and equality-based rules, have been widely discussed in reward allocation research; however, it remains unclear whether and how individuals' cooperative manner, such as interpersonal coordination, influence their subsequent responsibility attribution and reward allocation. Here, 46 dyads conducted a time estimation task-either synergistically (the coordination group) or solely (the control group)-while their brain activities were measured using a functional near-infrared spectroscopy hyperscanning approach. Dyads in the coordination group showed higher behavioral synchrony and higher interpersonal brain synchronization (IBS) in the dorsal lateral prefrontal cortex (DLPFC) during the time estimation task than those in the control group. They also showed a more egalitarian tendency of responsibility attribution for the task outcome. More importantly, dyads in the coordination group who had higher IBS in the dorsal medial prefrontal cortex (DMPFC) were more inclined to make egalitarian reward allocations, and this effect was mediated by responsibility attribution. Our findings elucidate the influence of interpersonal coordination on reward allocation and the critical role of the prefrontal cortex in these processes.
Subject(s)
Brain Mapping , Interpersonal Relations , Humans , Brain , Cooperative Behavior , Reward , Spectroscopy, Near-InfraredABSTRACT
BACKGROUND: CC chemokine receptor 5 (CCR5) has been demonstrated to be correlated to activation of pro-inflammatory immune cells and tissue injury. This study focused on the role of CCR5 in myocardial injury in rats with diabetic cardiomyopathy (DCM) and the mechanism of action. METHODS: A rat model of DCM was induced by streptozotocin (STZ). CCR5 was knocked down in rats to determine its role in myocardial injury and immune cell infiltration. The upstream regulators of CCR5 were bioinformatically predicted and the binding between nuclear receptor subfamily 4 group A member 2 (NR4A2) and CCR5 was validated. The portion of M1 and M2 macrophages in tissues was determined by flow cytometry or double-labeling immunofluorescence. Rat bone marrow mononuclear cells (BMMCs) were treated with granulocyte/macrophage colony stimulating factor (GM-CSF/M-CSF) and co-cultured with H9C2 cells for in vitro experiments. RESULTS: STZ-treated rats had impaired cardiac function and increased levels of creatine kinase-MB, cardiac troponin I and lactate dehydrogenase. CCR5 inhibition significantly alleviated myocardial injury in rats and reduced the portion of M1 macrophages in rat cardiac tissues. NR4A2, which could suppress CCR5 transcription, was poorly expressed in rats with DCM. NR4A2 overexpression played a similar myocardium-protective role in rats. In vitro, overexpression of NR4A2 induced M2 polarization of macrophages, which protected the co-cultured H9C2 cells from high glucose-induced damage, but the protective role was blocked after CCR5 overexpression. CONCLUSION: This study demonstrated that NR4A2 suppresses CCR5 expression and promotes M2 polarization of macrophages to alleviate cardiomyocyte loss and myocardial injury.
Subject(s)
Diabetic Cardiomyopathies , Macrophages , Myocytes, Cardiac , Nuclear Receptor Subfamily 4, Group A, Member 2 , Receptors, CCR5 , Transcription, Genetic , Animals , Male , Cell Line , Coculture Techniques , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/immunology , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Disease Models, Animal , Down-Regulation , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Nuclear Receptor Subfamily 4, Group A, Member 2/genetics , Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism , Phenotype , Rats, Sprague-Dawley , Receptors, CCR5/genetics , Receptors, CCR5/metabolism , Signal TransductionABSTRACT
Pollutant removal and resource recovery from high-humidity flue gas after desulfurization in a thermal power plant are crucial for improving air quality and saving energy. This study developed a flue gas treatment method involving phase transition enhanced by corona discharge based on laboratory research and established a field-scale unit for demonstration. The results indicate that an adequate increase in size will improve the ease of particle capture. A wet electrostatic precipitator is applied before the condensing heat exchangers to enhance the particle growth and capture processes. This results in an increase of 58% in the particle median diameter in the heat exchanger and an emission concentration below 1 mg/m3. Other pollutants, such as SO3 and Hg, can also be removed with emission concentrations of 0.13 mg/m3 and 1.10 µg/m3, respectively. Under the condensation enhancement of the method, it is possible to recover up to 3.26 t/h of water from 200â¯000 m3/h saturated flue gas (323 K), and the quality of the recovered water meets the standards stipulated in China. Additionally, charge-induced condensation is shown to improve heat recovery, resulting in the recovery of more than 43.34 kJ/h·m3 of heat from the flue gas. This method is expected to save 2628 t of standard coal and reduce carbon dioxide emission by 2% annually, contributing to environmental protection and global-warming mitigation.
Subject(s)
Air Pollutants , Environmental Pollutants , Air Pollutants/analysis , Coal , Environmental Monitoring/methods , Hot Temperature , Power Plants , WaterABSTRACT
Abdominal aortic aneurysm (AAA) is defined as a dilated aorta in diameter at least 1.5 times of a normal aorta. Our previous studies found that activating α7 nicotinic acetylcholine receptor (α7nAChR) had a protective effect on vascular injury. This work was to investigate whether activating α7nAChR could influence AAA formation and explore its mechanisms. AAA models were established by angiotensin II (Ang II) infusion in ApoE-/- mice or in wild type and α7nAChR-/- mice. In vitro mouse aortic smooth muscle (MOVAS) cells were treated with tumor necrosis factor-α (TNF-α). PNU-282987 was chosen to activate α7nAChR. We found that cell pyroptosis effector GSDMD and NLRP3 inflammasome were activated in abdominal aorta, and inflammatory cytokines in serum were elevated in AAA models of ApoE-/- mice. Activating α7nAChR reduced maximal aortic diameters, preserved elastin integrity and decreased inflammatory responses in ApoE-/- mice with Ang II infusion. While α7nAChR-/- mice led to aggravated aortic injury and increased inflammatory cytokines with Ang II infusion when compared with wild type. Moreover, activating α7nAChR inhibited NLRP3/caspase-1/GSDMD pathway in AAA model of ApoE-/- mice, while α7nAChR deficiency promoted this pathway. In vitro, N-acetylcysteine (NAC) inhibited NLRP3 inflammasome activation and NLRP3 knockdown reduced GSDMD expression, in MOVAS cells treated with TNF-α. Furthermore, activating α7nAChR inhibited oxidative stress, reduced NLRP3/GSDMD expression, and decreased cell pyroptosis in MOVAS cells with TNF-α. In conclusion, our study found that activating α7nAChR retarded AAA through inhibiting pyroptosis mediated by NLRP3 inflammasome. These suggested that α7nAChR would be a potential pharmacological target for AAA.
Subject(s)
Aortic Aneurysm, Abdominal , Inflammasomes , Acetylcysteine , Angiotensin II/metabolism , Animals , Aortic Aneurysm, Abdominal/drug therapy , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/prevention & control , Apolipoproteins E/metabolism , Caspase 1/metabolism , Cytokines/metabolism , Disease Models, Animal , Elastin , Inflammasomes/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Tumor Necrosis Factor-alpha/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolismABSTRACT
BACKGROUND: It remains unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for pregnancy complications in women undergoing assisted reproductive technology (ART) treatment. For the integrative treatment of PCOS patients, it is still important to investigate the pregnancy outcomes of PCOS patients after adjusting for potential biases, such as body mass index, embryo quality and endometrial preparation method. METHODS: This retrospective cohort study ultimately included a total of 336 PCOS patients who conceived after single thawed blastocyst transfer in the PCOS group and 2,325 patients in the control group from January 2018 to December 2020. A propensity score matching (PSM) model was used, and 336 PCOS patients were matched with 336 patients in the control group. RESULTS: Before PSM, no differences in the miscarriage rate, pregnancy complication rate, preterm birth rate, or live birth rate were found between the PCOS group and the control group. After PSM, the late miscarriage rate of the PCOS group was significantly higher than that of the control group (3.3% vs. 0.6%, P = 0.040), although the early miscarriage rates were similar (14.0% vs. 13.7%). The rates of pregnancy complications, preterm birth and live birth in the PCOS group were comparable to those in the matched control group (P = 0.080, P = 0.105, P = 0.109, respectively). The neonatal weights of male infants and female infants were similar between the two groups (P = 0.219, P = 0.169). Subgroup analysis showed that PCOS patients with homeostasis model assessment of insulin resistance (HOMA-IR) levels ≥ 2.49 had a significantly increased risk of preterm birth compared with those with HOMA-IR levels < 1.26 and 1.26 ≤ HOMA-IR levels < 2.49 (26.0% vs. 6.0% vs. 9.8%, P = 0.005). PCOS patients with total testosterone levels ≥ 0.7 ng/ml had a higher early miscarriage rate but a lower late miscarriage rate than those with total testosterone levels < 0.7 ng/ml (29.4% vs. 12.3%, 0% vs. 3.6%, respectively, P = 0.032). CONCLUSIONS: PCOS is an independent risk factor for late miscarriage in patients conceived after a single thawed blastocyst transfer, even after adjusting for biases. Among PCOS patients, insulin resistance and hyperandrogenism are associated with a higher risk of preterm birth and early miscarriage, respectively.
Subject(s)
Abortion, Spontaneous , Insulin Resistance , Polycystic Ovary Syndrome , Pregnancy Complications , Premature Birth , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , Embryo Transfer/methods , Female , Humans , Infant, Newborn , Male , Polycystic Ovary Syndrome/complications , Pregnancy , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Propensity Score , Retrospective Studies , TestosteroneABSTRACT
Abdominal aortic aneurysm is defined as a dilated aorta with a diameter at least 1.5 times of the normal aorta.There is no effective drug for AAA.We summarized the high-risk factors,pathologic features,current therapies,and animal models in the pre-clinical study to gain comprehensive understanding of AAA.With this review,we aim to provide scientific support for the mining of therapeutic targets for AAA.
Subject(s)
Aortic Aneurysm, Abdominal , Animals , Aorta , Disease Models, Animal , Risk FactorsABSTRACT
Charitable donations are an altruistic behavior whereby individuals donate money or other resources to benefit others while the recipient is normally absent from the context. Several psychological factors have been shown to influence charitable donations, including a cost-benefit analysis, the motivation to engage in altruistic behavior, and the perceived psychological benefits of donation. Recent work has identified the ventral medial prefrontal cortex (MPFC) for assigning value to options in social decision making tasks, with other regions involved in empathy and emotion contributing input to the value computation (e.g. Hare et al., 2010; Hutcherson et al., 2015; Tusche et al., 2016). Most impressively, multivariate pattern analysis (MVPA) has been applied to fMRI data to predict donation behavior on a trial-by-trial basis from ventral MPFC activity (Hare et al., 2010) while identifying the contribution of emotional processing in other regions to the value computation (e.g. Tusche et al., 2016). MVPA of EEG data may be able to provide further insight into the timing and scalp topography of neural activity related to both value computation and emotional effects on donation behavior. We examined the effect of incidental emotional states and the perceived urgency of the charitable cause on donation behavior using support vector regression on EEG data to predict donation amount on a trial by trial basis. We used positive, negative, and neutral pictures to induce incidental emotional states in participants before they made donation decisions concerning two types of charities. One category of charity was oriented toward saving people from current suffering, and the other was to prevent future suffering. Behaviorally, subjects donated more money in a negative emotional state relative to other emotional states, and more money to alleviate current over future suffering. The data-driven multivariate pattern analysis revealed that the electrophysiological activity elicited by both emotion-priming pictures and charity cues could predict the variation in donation magnitude on a trial-by-trial basis.