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A G-quadruplex (G4) is a typical non-B DNA structure and involved in various DNA-templated events in eukaryotic genomes. PEG and PDS chemicals have been widely applied for promoting the folding of in vivo or in vitro G4s. However, how PEG and PDS preferentially affect a subset of G4 formation genome-wide is still largely unknown. We here conducted a BG4-based IP-seq in vitro under K++PEG or K++PDS conditions in the rice genome. We found that PEG-favored IP-G4s+ have distinct sequence features, distinct genomic distributions and distinct associations with TEGs, non-TEGs and subtypes of TEs compared to PDS-favored ones. Strikingly, PEG-specific IP-G4s+ are associated with euchromatin with less enrichment levels of DNA methylation but with more enriched active histone marks, while PDS-specific IP-G4s+ are associated with heterochromatin with higher enrichment levels of DNA methylation and repressive marks. Moreover, we found that genes with PEG-specific IP-G4s+ are more expressed than those with PDS-specific IP-G4s+, suggesting that PEG/PDS-specific IP-G4s+ alone or coordinating with epigenetic marks are involved in the regulation of the differential expression of related genes, therefore functioning in distinct biological processes. Thus, our study provides new insights into differential impacts of PEG and PDS on G4 formation, thereby advancing our understanding of G4 biology.
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Quadruplex G , Oryza , Epigenômica , Oryza/genética , Genômica , DNARESUMO
BACKGROUND: New-onset atrial fibrillation (NOAF) is a common adverse outcome of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) and is closely correlated with hospital stay and prognosis. In recent years, serum fibrinogen-to-albumin ratio (FAR), a novel biomarker for inflammation and thrombosis, has been used to predict the severity and prognosis of coronary artery disease. Our study aimed to investigate the relationship between FAR and NOAF during hospitalization after PCI in patients with AMI. METHODS: We retrospectively analyzed the incidence of NOAF during hospitalization and follow-up in 670 patients with AMI after PCI. Data were collected on patient age, sex, body mass index, medical history, current medication, heart failure, laboratory tests, culprit blood vessels, echocardiographic characteristics, and AMI type. The enrolled patients were divided into NOAF and non-NOAF groups. The baseline characteristics of patients in the two groups were compared, and the predictive correlation between FAR and NOAF was evaluated using logistic regression analysis and the receiver operating characteristic curve. RESULTS: Fifty-three (7.9%) patients developed NOAF during hospitalization. The occurrence of NOAF was found to be independently associated with higher FAR besides older age, higher neutrophil count, greater left atrial size, worse Killip class upon admission, lower body mass index, lower platelet count, lower left ventricle ejection fraction, and target left circumflex artery disease. FAR exhibited a better predictive value for the occurrence of NOAF during hospitalization (area under the curve, 0.732; 95% confidence interval, 0.659-0.808). CONCLUSIONS: FAR is a robust tool for predicting NOAF risk during hospitalization in patients with AMI after PCI and has a better predictive value than serum fibrin and serum albumin levels alone.
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Fibrilação Atrial , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Estudos Retrospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Hospitalização , Fibrinogênio , AlbuminasRESUMO
The heterogeneous Fenton process is a strategy for overcoming the greatest shortcomings of traditional homogeneous Fenton, i.e. the high generation of ferric hydroxide sludge and effectivity in a limited pH range. In this study, we constructed a heterogeneous Fenton system with natural iron-bearing clay mineral (nontronite) and dimethoxyhydroquinone (DMHQ) to degrade lincomycin (LCM) without the addition of H2O2. The degradation mechanism was derived from the hydroxyl radicals (â¢OH) produced from the oxygenation of Fe(II) in nontronites, which was reduced by DMHQ. Acidic conditions and low concentrations of LCM were favourable for LCM degradation. When the solution pH increased from 3 to 7, the final LCM removal ratio decreased from 95 to 46%. However, LCM can still be degraded by 46% under neutral conditions and 20% at the LCM concentration of 500 µmol/L. The nontronite has good reusability, and the LCM degradation efficiency in the fourth cycle still exceeded 90% of the original efficiency. The degradation sites of LCM mainly occurred in the methyl thioether moiety and the aliphatic amine group on the pyrrolidine ring, with the final product of CO2. This research presents a new eco-friendly and cost-effective method for the heterogenous Fenton process without external H2O2.
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Radical Hidroxila , Ferro , Ferro/química , Radical Hidroxila/química , Argila , Peróxido de Hidrogênio/química , Minerais/química , OxirreduçãoRESUMO
A finite model updating method that combines dynamic-static long-gauge strain responses is proposed for highway bridge static loading tests. For this method, the objective function consisting of static long-gauge stains and the first order modal macro-strain parameter (frequency) is established, wherein the local bending stiffness, density and boundary conditions of the structures are selected as the design variables. The relationship between the macro-strain and local element stiffness was studied first. It is revealed that the macro-strain is inversely proportional to the local stiffness covered by the long-gauge strain sensor. This corresponding relation is important for the modification of the local stiffness based on the macro-strain. The local and global parameters can be simultaneously updated. Then, a series of numerical simulation and experiments were conducted to verify the effectiveness of the proposed method. The results show that the static deformation, macro-strain and macro-strain modal can be predicted well by using the proposed updating model.
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Obesity is becoming increasingly prevalent in China and worldwide and is closely related to the development of hypertension. The pathophysiology of obesity-associated hypertension is complex, including an overactive sympathetic nervous system (SNS), activation of the renin-angiotensin-aldosterone system (RAAS), insulin resistance, hyperleptinemia, renal dysfunction, inflammatory responses, and endothelial function, which complicates treatment. Sodium-glucose cotransporter protein 2 (SGLT-2) inhibitors, novel hypoglycemic agents, have been shown to reduce body weight and blood pressure and may serve as potential novel agents for the treatment of obesity-associated hypertension. This review discusses the beneficial mechanisms of SGLT-2 inhibitors for the treatment of obesity-associated hypertension. SGLT-2 inhibitors can inhibit SNS activity, reduce RAAS activation, ameliorate insulin resistance, reduce leptin secretion, improve renal function, and inhibit inflammatory responses. SGLT-2 inhibitors can, therefore, simultaneously target multiple mechanisms of obesity-associated hypertension and may serve as an effective treatment for obesity-associated hypertension.
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Melatonin improves chronic stress-induced hippocampal damage and depression-like behaviors, but the mechanism needs further study. This study was to explore the mechanism of melatonin inhibiting microglia pyroptosis. In virtro experiments, melatonin improved corticosterone-induced the ultrastructure and microstructure damage of HAPI cells by inhibiting pyroptosis, thereby increasing cell survival rate. Protein-protein interaction network and molecular autodocking predicted that Cathespin B might be the target of melatonin inhibition of NLRP3-mediated pyroptosis. Melatonin inhibited corticosterone-induced Cathespin B expression. Both Cathepsin B inhibitor CA-074Me and NLRP3 knockout inhibited the HAPI cells pyroptosis. Similarly, melatonin inhibited Cathepsin B agonist Pazopanib-induced activation of Cathepsin B/NLRP3 signaling pathway and HAPI cells pyroptosis. In vivo studies, melatonin inhibited chronic restraint stress (CRS)-induced activation of Cathepsin B/NLRP3 signaling pathway and alleviated hippocampal microglia pyroptosis in rats. Inhibition of microglia pyroptosis improved CRS-induced depression-like behaviors of rats. In addition, inhibition of Cathepsin B and NLRP3 alleviated hippocampal pyroptosis. Melatonin inhibited Pazopanib-induced activation of Cathepsin B/NLRP3 signaling pathway and hippocampal pyroptosis. These results demonstrated that melatonin could alleviate CRS-induced hippocampal microglia pyroptosis by inhibiting Cathepsin B/NLRP3 signaling pathway, thereby improving depression-like behaviors in rats. This study reveals the molecular mechanism of melatonin in the prevention and treatment of chronic stress-related encephalopathy.
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Catepsina B , Indazóis , Melatonina , Pirimidinas , Sulfonamidas , Animais , Ratos , Melatonina/farmacologia , Corticosterona , Depressão/tratamento farmacológico , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Transdução de Sinais , HipocampoRESUMO
Multiferroic materials, which simultaneously exhibit ferroelectricity and magnetism, have attracted substantial attention due to their fascinating physical properties and potential technological applications. With the trends towards device miniaturization, there is an increasing demand for the persistence of multiferroicity in single-layer materials at elevated temperatures. Here, we report high-temperature multiferroicity in single-layer CuCrSe2, which hosts room-temperature ferroelectricity and 120 K ferromagnetism. Notably, the ferromagnetic coupling in single-layer CuCrSe2 is enhanced by the ferroelectricity-induced orbital shift of Cr atoms, which is distinct from both types I and II multiferroicity. These findings are supported by a combination of second-harmonic generation, piezo-response force microscopy, scanning transmission electron microscopy, magnetic, and Hall measurements. Our research provides not only an exemplary platform for delving into intrinsic magnetoelectric interactions at the single-layer limit but also sheds light on potential development of electronic and spintronic devices utilizing two-dimensional multiferroics.
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Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/farmacologia , Glucose , Sódio , Hipertrofia/tratamento farmacológicoRESUMO
Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal. The transient receptor potential cation channel subfamily V member 1 (TRPV1), a nonselective cation channel, has been shown to be universally expressed in the cardiovascular system. Increasing evidence has shown that the activation of TRPV1 channel has a potential protective influence on the cardiovascular system. Numerous studies show that activating TRPV1 channels can improve the occurrence and progression of diabetes-related complications, including cardiomyopathy; however, the specific mechanisms and effects are unclear. In this review, we summarize that TRPV1 channel activation plays a protective role in the heart of diabetic models from oxidation/nitrification stress, mitochondrial function, endothelial function, inflammation, and cardiac energy metabolism to inhibit the occurrence and progression of DCM. Therefore, TRPV1 may become a latent target for the prevention and treatment of diabetes-induced cardiovascular complications.
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Cardiomiopatias , Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus , Humanos , Sistema Cardiovascular/metabolismo , Estresse Oxidativo , Canais de Cátion TRPV/genéticaRESUMO
Fumonisin B1 (FB1) contaminates various crops, causing huge losses to agriculture and livestock worldwide. This review summarizes the occurrence regularity, toxicity, toxic mechanisms and management strategies of FB1. Specifically, FB1 contamination is particularly serious in developing countries, humid and hot regions. FB1 exposure can produce different toxic effects on the nervous system, respiratory system, digestive system and reproductive system. Furthermore, FB1 can also cause systemic immunotoxicity. The mechanism of toxic effects of FB1 is to interfere with the normal pathway of sphingolipid de novo biosynthesis by acting as a competitive inhibitor of ceramide synthase. Meanwhile, the toxic products of sphingolipid metabolic disorders can cause oxidative stress and apoptosis. FB1 also often causes feed contamination by mixing with other mycotoxins, and then exerts combined toxicity. For detection, lateral flow dipstick technology and enzyme linked immunosorbent assay are widely used in the detection of FB1 in commercial feeds, while mainstream detection methods such as high performance liquid chromatography and liquid chromatography-mass spectrometry are widely used in the laboratory theoretical study of FB1. For purification means of FB1, some natural plant extracts (such as Zingiber officinale and Litsea Cubeba essential oil) and their active compounds have been proved to inhibit the toxic effects of FB1 and protect livestock due to their antifungal and antioxidant effects. Natural plant extract has the advantages of high efficiency, low cost and no contamination residue. This review can provide information for comprehensive understanding of FB1, and provide reference for formulating reasonable treatment and management strategies in livestock production.
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Fumonisinas , Micotoxinas , Fumonisinas/toxicidade , Fumonisinas/química , Micotoxinas/toxicidade , Estresse Oxidativo , Esfingolipídeos/farmacologiaRESUMO
Lycopene (LYC) exerts a strong neuroprotective and antipyroptotic effects. This study explored the effects and mechanisms of LYC on chronic stress-induced hippocampal microglial damage and depression-like behaviors. The caspase-1 inhibitor VX-765 attenuated chronic restrain stress (CRS)-induced hippocampal microglial pyroptosis and depression-like behaviors. Moreover, the alleviation of CRS-induced hippocampal microglial pyroptosis and depression-like behaviors by LYC was associated with the cathepsin B/NLRP3 pathway. In vitro, the caspase-1 inhibitor Z-YVAD-FMK alleviated pyroptosis in highly aggressively proliferating immortalized (HAPI) cells. Additionally, the alleviation of corticosterone-induced HAPI cell damage and pyroptosis by LYC was associated with the cathepsin B/NLRP3 pathway. Furthermore, the cathepsin B agonist pazopanib promoted HAPI cell pyroptosis, whereas LYC inhibited pazopanib-induced pyroptosis via the cathepsin B/NLRP3 pathway. Similarly, Z-YVAD-FMK inhibited pazopanib-induced HAPI cell pyroptosis. These results suggest that LYC alleviates chronic stress-induced hippocampal microglial pyroptosis via the cathepsin B/NLRP3 pathway inhibition. This study provides a new strategy for treating chronic stress encephalopathy.
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Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Licopeno/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Microglia , Transdução de Sinais , Hipocampo , Inflamassomos/genética , Inflamassomos/metabolismoRESUMO
Purpose: Lymphocyte to C-reactive protein ratio (LCR) is a recognized systemic inflammatory marker and novel prognostic indicator for several cancers. This study investigated the relationship between preoperative LCR and new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Patients and Methods: Patients with AMI (n=662) with no history of atrial fibrillation (AF) were enrolled and classified into NOAF and non-NOAF groups based on the occurrence of postoperative NOAF during hospitalization. Logistic regression models were used to analyze NOAF risk factors and to assess the association between preoperative LCR and NOAF incidence. We constructed a new nomogram from the selected NOAF risk factors, and tested its predictive performance, degree of calibration, and clinical utility using receiver operating characteristic and calibration curves, decision curve analysis, and clinical impact curves. Results: Overall, 84 (12.7%) patients developed NOAF during hospitalization. The LCR was significantly lower in the NOAF group. Preoperative LCR accurately predicted NOAF after AMI and was correlated with increased NOAF risk. Age, body mass index, diabetes, serum albumin levels, uric acid levels, left atrium (LA) diameter, left ventricular ejection fraction, left circumflex artery stenosis > 50%, and Killip class II status were independent predictors of NOAF after AMI. In addition, a new nomogram combined with LCR was constructed to stratify the risk of NOAF in patients with AMI. The performance of the new nomogram was satisfactory, as shown by the receiver operating characteristic curve, calibration curve, decision curve analysis and clinical impact curve. Conclusion: Preoperative LCR was an independent predictor of NOAF in patients with AMI after PCI. The novel nomogram combined with LCR could rapidly and individually identify and treat patients at a high risk of NOAF.
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Combined exposure of chronic stress and alumina nanoparticles (AlNPs) aggravates hippocampal injury, but the pathogenesis is unevaluated. This study aimed to investigate the effect and mechanism of co-exposure to chronic stress and AlNPs on hippocampal microglia pyroptosis. In this study, chronic restraint stress (CRS) alone caused NLRP3-mediated hippocampal microglia pyroptosis, but AlNPs did not. Moreover, co-exposure to CRS and AlNPs exacerbated hippocampal microglia pyroptosis, resulting in more severe hippocampal damage and behavioral deficits in rats. Protein-protein interaction network predicted that cathepsin B was a potential regulatory protein of NLRP3. CRS up-regulated cathepsin B expression which had a more pronounced increase in co-exposure group. Whereas, caspase-1 inhibitor VX-765 alleviated hippocampal microglia pyroptosis and behavioral deficits in rats. Consistent with in vivo results, co-exposure of corticosterone and AlNPs aggravated NLRP3-mediated pyroptosis and cathepsin B expression in HAPI cells. Nevertheless, the pyroptosis of HAPI cells was inhibited by cathepsin B inhibitor CA-074Me and NLRP3 knockout, respectively. NLRP3 agonist nigericin failed to promote the pyroptosis of HAPI cells in the presence of cathepsin B inhibition. These results demonstrated that co-exposure to chronic stress and AlNPs could aggravate hippocampal microglia pyroptosis by activating cathepsin B/NLRP3 signaling pathway, resulting in hippocampal damage and behavioral deficits.
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Nanopartículas , Piroptose , Óxido de Alumínio/metabolismo , Animais , Catepsina B/metabolismo , Catepsina B/farmacologia , Hipocampo/metabolismo , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nanopartículas/toxicidade , Piroptose/fisiologia , Ratos , Transdução de SinaisRESUMO
Recently, hierarchical hybrid structures based on the combination of semiconductor micro/nanostructures and noble metal nanoparticles have become a hot research topic in the area of surface-enhanced Raman scattering (SERS). In this work, two core-satellite nanostructures of metal oxide/metal nanoparticles were successfully introduced into SERS substrates, assembling monodispersed small silver nanoparticles (Ag NPs) on large polydispersed ZnO nanospheres (p-ZnO NSs) or monodispersed ZnO nanospheres (m-ZnO NSs) core. The p-ZnO NSs and m-ZnO NSs were synthesized by the pyrolysis method without any template. The Ag NPs were prepared by the thermal evaporation method without any annealing process. An ultralow limit of detection (LOD) of 1 × 10-13 M was achieved in the two core-satellite nanostructures with Rhodamine 6G (R6G) as the probe molecule. Compared with the silicon (Si)/Ag NPs substrate, the two core-satellite nanostructures of Si/p-ZnO NSs/Ag NPs and Si/m-ZnO NSs/Ag NPs substrates have higher enhancement factors (EF) of 2.6 × 108 and 2.5 × 108 for R6G as the probe molecule due to the enhanced electromagnetic field. The two core-satellite nanostructures have great application potential in the low-cost massive production of large-area SERS substrates due to their excellent SERS effect and simple preparation process without any template.
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The natural biomaterial sarcosine as an electron transport layer (ETL) to modify ITO or ITO/ZnO was successfully introduced into inverted organic solar cells (OSCs) with PM6:BTP-BO-4Cl as the active layer. The introduction of sarcosine on the surface of ITO or ITO/ZnO resulted in lower work function (WF) and higher surface energy. The active layers processed on the surfaces of ITO or ITO/ZnO presented a more optimized morphology and a more ordered molecular arrangement after their modification with sarcosine. The introduction of sarcosine as an ETL promoted charge transport and collection in the OSCs. Therefore, the power conversion efficiency (PCE) of the OSCs increased to 13.53% from 3.86% by modifying ITO with sarcosine. The PCE of the OSCs with ZnO as ETLs improved to 16.45% from 14.85% by modifying ZnO with sarcosine. The improved PCEs benefited from the simultaneously improved short-circuit current density (JSC), fill factor (FF), and open-circuit voltage (VOC). Therefore, this work demonstrates that sarcosine has great potential as an ETL to improve the performance of OSCs.
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Land use change affects ecosystem services by changing the structure and function of ecosystems. Carbon flows throughout natural and socioeconomic systems can effectively reveal this process. The Manas River Basin has experienced rapid oasis expansion for decades, and land use change in the basin is very typical. Oasis expansion has caused a large amount of cropland to invade natural vegetation, thus affecting ecosystem services. This study used a biomass-based ecosystem service estimation model to assess changes in ecosystem services in the Manas River Basin. The carbon flow model was constructed using energy systems language, and the future development of ecosystem services was simulated based on different land use scenarios. The results show the following: (1) From 1980 to 2015, the river basin provisioning service was continuously optimized, while the regulating, supporting and cultural services were reduced. (2) If the expansion of cropland continues, then carbon will be transferred from the natural ecosystem to the cropland. Regulation, support and cultural services in the basin continue to decrease. Due to the shortage of water resources in the basin, the growth of provisioning services is limited. (3) If the project of returning cropland to grassland is implemented, then the carbon in the natural ecosystem will gradually recover. The regulating, supporting and cultural services of the river basin are rising, but provisioning services are gradually decreasing. In general, the model based on energy systems language can reflect the ecological process within the system and effectively reveal the carbon flow process between ecosystems. The use of carbon to quantify ecosystem services can harmonize dimensions, facilitate comparisons, and mitigate errors in outcomes due to different evaluation criteria or subjective factors. Therefore, this study combines energy systems language with carbon flow, which helps to more rationally explore the impact of land use change on ecosystem services, thereby providing valuable information for river basin management.
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Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , ChinaRESUMO
OBJECTIVE: To explore the clinical efficacy and the effect mechanism of hooking therapy and safflower injection in the treatment of lumbar disc herniation (LDH). METHODS: Sixty patients of LDH were randomized into an observation group and a control group at ratio of 1 to 1, 30 cases in each one. In the control group, safflower injection was applied to three points of lumbar region, once a day. Seven treatments made one session, and totally 2 sessions were required. In the observation group, under local anesthesia, the big hook needle was used to stimulate the three points of lumbar region first, followed by the safflower injection, once every 6 to 7 days. If the efficacy was not satisfactory enough, the second treatment was given. The visual analogue scale (VAS) and the modified Japanese Orthopaedic Association (M-JOA) scores were observed before and after treatment in the patients of the two groups and the clinical efficacy was evaluated. The levels of peripheral interleukin-6 (IL-6) and nitric oxide (NO) were determined. RESULTS: VAS and M-JOA scores were all improved apparently after treatment as compared with those before treatment in the patients of the two groups (both P < 0.01). The improvements in the observation group were much more obvious than those in the control group (both P < 0.01). In the observation group, the curative and remarkably effective rate was 76.7% (23/30) and the total effective rate was 96.7% (29/ 30), better than 43.3% (13/30) and 70.0% (21/30) in the control group separately (both P < 0.05). After treatment, the levels of IL-6 and NO were all reduced as compared with those before treatment in the two groups; (both P < 0.01). The above indices were changed more obviously in the observation group as compared with those in the control group (both P < 0.01). CONCLUSION: The combined therapy of hooking therapy and safflower injection apparently relieves pain and clinical symptoms of LDH. The effect mechanism is relevant with reducing the levels of IL-6 and NO in the peripheral blood.