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Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.
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This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.
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Demyelination is a proper syndrome in plenty of central nervous system (CNS) diseases, which is the main obstacle to recovery and still lacks an effective treatment. To overcome the limitations of the brain-blood barrier on drug permeability, we modified an exosome secreted by neural stem cells (NSCs), which had transfected with lentivirus armed with platelet-derived growth factors A (PDGFA)-ligand. Through the in vivo and in vitro exosomes targeting test, the migration ability to the lesion areas and OPCs significantly improved after ligand modification. Furthermore, the targeted exosomes loaded with 3,5, 30-L-triiodothyronine (T3) have a critical myelination ability in CNS development, administrated to the cuprizone animal model treatment. The data shows that the novel drug vector loaded with T3 significantly promotes remyelination compared with T3 alone. At the same time, it improved the CNS microenvironment by reducing astrogliosis, inhibiting pro-inflammatory microglia, and alleviating axon damage. This investigation provides a straightforward strategy to produce a targeting exosome and indicates a possible therapeutic manner for demyelinating disease.
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Doenças Desmielinizantes , Exossomos , Animais , Camundongos , Doenças Desmielinizantes/terapia , Doenças Desmielinizantes/tratamento farmacológico , Oligodendroglia , Ligantes , Exossomos/metabolismo , Tri-Iodotironina/metabolismo , Tri-Iodotironina/farmacologia , Tri-Iodotironina/uso terapêutico , Cuprizona/toxicidade , Camundongos Endogâmicos C57BL , Bainha de Mielina/patologia , Modelos Animais de DoençasRESUMO
In the evolving landscape of water treatment, membrane technology has ascended to an instrumental role, underscored by its unmatched efficacy and ubiquity. Diverse synthesis and modification techniques are employed to fabricate state-of-the-art liquid separation membranes. Click reactions, distinguished by their rapid kinetics, minimal byproduct generation, and simple reaction condition, emerge as a potent paradigm for devising eco-functional materials. While the metal-free thiol-ene click reaction is acknowledged as a viable approach for membrane material innovation, a systematic elucidation of its applicability in liquid separation membrane development remains conspicuously absent. This review elucidates the pre-functionalization strategies of substrate materials tailored for thiol-ene reactions, notably highlighting thiolation and introducing unsaturated moieties. The consequential implications of thiol-ene reactions on membrane properties-including trade-off effect, surface wettability, and antifouling property-are discussed. The application of thiol-ene reaction in fabricating various liquid separation membranes for different water treatment processes, including wastewater treatment, oil/water separation, and ion separation, are reviewed. Finally, the prospects of thiol-ene reaction in designing novel liquid separation membrane, including pre-functionalization, products prediction, and solute-solute separation membrane, are proposed. This review endeavors to furnish invaluable insights, paving the way for expanding the horizons of thiol-ene reaction application in liquid separation membrane fabrication.
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The optimization of membrane bioreactors (MBRs) involves a critical challenge in structural design for mitigation of membrane fouling. To address this issue, a three-dimensional computational fluid dynamics (CFD) model was utilized in this study to simulate the hydrodynamic characteristics of a flat sheet (FS) MBR. The optimization of the membrane module configuration and operating conditions was performed by investigating key parameters that altered the shear stress and liquid velocity. The mixed liquor suspended solids (MLSS) concentration was found to increase the shear stress, leading to a more uniform distribution of shear stress. By optimizing the appropriate bubble diameter to 5 mm, the shear stress on the membrane surface was optimized with relatively uniform distribution. Additionally, extending the side baffle length dramatically improved the uniformity of the shear stress distribution on each membrane. A novel in-situ aeration method was also discovered to promote turbulent kinetic energy by 200 times compared with traditional aeration modes, leading to a more uniform bubble streamline. As a result, the novel in-situ aeration method demonstrated superior membrane antifouling potential in the MBR. This work provides a new approach for the structural design and optimization of MBRs. The innovative combination of the CFD model, optimization techniques, and novel in-situ aeration method has provided a substantial contribution to the advancement of membrane separation technology in wastewater treatment.
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Hidrodinâmica , Eliminação de Resíduos Líquidos , Eliminação de Resíduos Líquidos/métodos , Membranas Artificiais , Reatores Biológicos , Estresse MecânicoRESUMO
This case report presents the electrocardiogram findings of a patient in their 50s with intermittent compression-like pain in the chest and a history of hypertension and diabetes.
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Objective@#To understand the association between sugar sweetened beverage consumption with physical fitness index among college students, so as to provide a reference for the improvement and intervention of college students physical fitness.@*Methods@#From September to December 2021, a total of 5 520 college students from universities in Jilin, Anhui, Jiangxi, Xinjiang, and Shanghai, were surveyed with sugar sweetened beverage consumption and physical fitness using stratified cluster sampling. One way ANOVA and Logistic regression analysis were used to analyze the association between sugary drink consumption and physical fitness index (PFI).@*Results@#The frequencies of sugar-sweetened beverage consumption among college students were 10.3% , 67.2%, 13.9% , and 8.6% for 0, 1-3, 4-5, and ≥ 6 times/week, respectively. The differences in waist circumference, grip strength, standing long jumping, sit and reach, 50-meter running, and 1 000/800 meter running performance were statistically significant among college students with varying sugar-sweetened beverage consumption ( F =8.67, 7.22, 11.20, 13.47, 3.98, 2.86 , P <0.05). Logistic regression analysis showed that those who had sugary drinks 4-5 times/week, ≥ 6 times/week had a higher risk of low PFI compared to those who reported no sugary drinks ( OR =1.48, 1.56, P <0.05). With respect to gender, the risk of low PFI was also higher among male students who consumed sugary drinks ≥6 times/week ( OR =2.01, P <0.05), while there was no significant difference among female students.@*Conclusion@#Sugar-sweetened beverage consumption is negatively associated with the physical fitness index among college students with significant gender differences. College students, especially males, should be targeted to improve health literacy, reduce the consumption of sugar-sweetened beverages, so as to improve physical fitness.
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ETHNOPHARMACOLOGICAL RELEVANCE: The dried pericarp of Citrus reticulata Blanco (CP) occupies an important position in the history of clinical applications of traditional Chinese medicine (TCM). In traditional use, CP is used to treat diseases related to the digestive, respiratory, and cardiovascular systems, as well as to regulate Qi and promote blood circulation throughout the body. In China, a special cultivar of CP named Guang Chen Pi (GCP) which is collected exclusively from Citrus reticulata Blanco's cultivars 'Chachi', is considered to be the best CP with high medicinal and dietary value. Modern pharmacology shows that CP has high effect on regulating metabolic disorders and cardiovascular systems diseases. Atherosclerosis (AS) is not only an inflammatory disease but also cardiovascular lipid metabolism disorder. Foam cells formation is the hallmark of AS. Several reports indicated that CP can mitigate the development of AS, but involved signaling pathway and its role in foam cell formation is unclear. Since the main components of GCP has protective effects in cardiovascular diseases, we evaluated its effect of inhibiting foam cell formation to support the traditional usage of GCP. AIM OF THE STUDY: The objective of this study aims to investigate the effects of GCP on suppressing RAW264.7 foam cell formation and anti-inflammatory in vitro. MATERIALS AND METHODS: To evaluate the anti-foam cell formation and anti-inflammatory activity of GCP, oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 macrophages model was involved. Meantime, foam cell developing status was also closely monitored. RT-qPCR and Western blot were then applied to further investigate receptors in associated signaling pathways. RESULTS: GCP shown inhibitory effect on macrophage-derived foam cell formation in Oil Red O staining analysis, which was further confirmed by flow cytometry of Dil-ox-LDL staining and TG and TC analysis. The HDL-mediated cholesterol efflux was also promoted by GCP. Mechanistic studies showed that GCP significantly down-regulate SRA1 and CD36 protein expression, while significantly increasing the expression of PPARγ, LXRα, SRB1 and ABCG1. Also, GCP reduced ox-LDL-induced inflammatory factors level, and inhibited phosphorylation of p38 MAPK, ERK1/2, JNK1/2, NF-κB p65 and IKKα/ß. CONCLUSIONS: GCP exhibited anti-atherogenic ability by interfering RAW264.7 foam cell formation, through inhibiting lipid uptake and promoting HDL-mediated cholesterol. PPARγ-LXRα-ABCG1/SRB1 pathway and its anti-inflammatory effect may involve. This proposed anti-foam cell formation activity is expected to provide new insight on comprehensive utilization of GCP.
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Aterosclerose , Citrus , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Colesterol/metabolismo , Células Espumosas , Lipoproteínas LDL/metabolismo , Macrófagos , PPAR gama/metabolismoRESUMO
Demyelination is a critical neurological disease, and there is still a lack of effective treatment methods. In the past two decades, stem cells have emerged as a novel therapeutic effector for neural regeneration. However, owing to the existence of the blood-brain barrier (BBB) and the complex microenvironment, targeted therapy still faces multiple challenges. Targeted exosome carriers for drug delivery may be considered a promising therapeutic method. Exosomes were isolated from mice neural stem cells. To develop targeting exosomes, we generated a lentivirus armed PDGFRα ligand that could anchor the membrane. Exosome targeting tests were carried out in vitro and in vivo. The modified exosomes showed an apparent ability to target OPCs in the lesion area. Next, the exosomes were loaded with Bryostatin-1 (Bryo), and the cuprizone-fed mice were administered with the targeting exosomes. The data show that Bryo exhibits a powerful therapeutic effect compared with Bryo alone after exosome encapsulation. Specifically, this novel exosome-based targeting delivery of Bryo significantly improves the protection ability of the myelin sheath and promotes remyelination. Moreover, it blocks astrogliosis and axon damage, and also has an inhibitory effect on pro-inflammatory microglia. The results of this investigation provide a straightforward strategy to produce targeting exosomes and indicate a potential therapeutic approach for demyelinating disease.
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Doenças Desmielinizantes , Exossomos , Esclerose Múltipla , Células-Tronco Neurais , Fármacos Neuroprotetores , Remielinização , Animais , Briostatinas/farmacologia , Cuprizona/farmacologia , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Neuroproteção , Fármacos Neuroprotetores/farmacologia , OligodendrogliaRESUMO
BACKGROUND: Brazil is exceptionally abundant in medicinal plant resources and has a rich ethnopharmacological history. Brazilian Pharmacopoeia (BP) acts as a national standard that regulates drug quality and has six published editions. Recent genomic approaches have led to a resurgence of interest in herbal drugs. The genomic data of plants has been used for pharmaceutical applications, protecting natural resources, and efficiently regulating the market. However, there are few genomic databases specifically for medicinal plants, and the establishment of a database that focuses on the herbs contained in the BP is urgently required. METHODS: The medicinal plant species included in each edition of the BP were analyzed to understand the evolution of the Brazilian herbal drugs. The data of 82 plants in the BP were collected and categorized into four sections: DNA barcodes, super-barcodes, genomes, and sequencing data. A typical web server architecture pattern was used to build the database and website. Furthermore, the cp-Gs of the Aloe genus in the database were analyzed as an illustration. RESULTS: A new database, the Brazilian Pharmacopoeia Genomic Database (BPGD) was constructed and is now publicly accessible. A BLAST server for species identification and sequence searching with the internal transcribed spacer 2 (ITS2), the intergenic region (psbA-trnH), and the chloroplast genome (cp-G) of Brazilian medicinal plants was also embedded in the BPGD. The database has 753 ITS2 of 76 species, 553 psbA-trnH and 190 genomes (whole genome and chloroplast genome) of 57 species. In addition, it contains 37 genome sequence data sets of 24 species and 616 transcriptome sequence data sets of 34 species and also includes 187 cp-Gs representing 57 medicinal species in the BP. Analyses of the six cp-Gs of three Aloe species identified the variable regions in the cp-Gs. These can be used to identify species and understand the intraspecific relationships. CONCLUSIONS: This study presents the first genomic database of medicinal plants listed in the latest BP. It serves as an efficient platform to obtain and analyze genomic data, accelerate studies regarding Brazilian medicinal plants and facilitate the rational development on their market regulation.
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Gradient properties facilitate the correlation of chemical and physical features of particles on the structure and adherent fate. Herein, performance enhancement is explored by particle gradient assembly patterning (PGAP) formed with magnetic field gradient (MFG) by magnetolithography (ML) in the electrochemiluminescence (ECL) measurement. Magnetic Fe3O4 nanoparticles were selected as nanocarriers and coated with a SiO2 layer for immobilization of primary antibodies. CdTe quantum dots with protein G coatings were selected as signal labels and conjugated with secondary antibodies. Magnetized 500-nm pillar, 1 µm- and 3 µm-line arrays of nickel were placed behind the working electrode modifying the sandwich-structured ECL immunosensor to form various PGAPs. A performance enhancement of ca. 2.4 times was observed when comparing the PGAP-free immunosensor to the researched gradient immunosensor, formed with a magnetized 3 µm-line array of nickel. This concludes that the sensitivity of an ECL immunosensor has been enhanced due to PGAP properties. When the immunosensor with PGAP properties was used to quantify human serum albumin, it exhibited a wide linear range (10-480 ng/mL), and a limit of detection of 10 ng/mL. PGAP properties, formed with MFG by ML, provides a simple method to improve the ECL performance.
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Técnicas Biossensoriais , Compostos de Cádmio , Nanopartículas Metálicas , Pontos Quânticos , Técnicas Eletroquímicas , Humanos , Imunoensaio , Limite de Detecção , Medições Luminescentes , Albumina Sérica Humana , Dióxido de Silício , TelúrioRESUMO
Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR-FTIR spectroscopy to identify biomolecular changes in rat liver post-exposure to B[a]P and BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm-1 . B[a]P and BDE-47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)-stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants.
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Benzo(a)pireno/toxicidade , Éteres Difenil Halogenados/toxicidade , Fígado/efeitos dos fármacos , Animais , Feminino , Fígado/patologia , Fígado/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Haloketones (HKs) is one class of disinfection by-products (DBPs) which is genetically toxic and mutagenic. Monitoring HKs in drinking water is important for drinking water safety, yet it is a time-consuming and laborious job. Developing predictive models of HKs to estimate their occurrence in drinking water is a good alternative, but to date no study was available for HKs modeling. This study was to explore the feasibility of linear, log linear regression models, back propagation (BP) as well as radial basis function (RBF) artificial neural networks (ANNs) for predicting HKs occurrence (including dichloropropanone, trichloropropanone and total HKs) in real water supply systems. Results showed that the overall prediction ability of RBF and BP ANNs was better than linear/log linear models. Though the BP ANN showed excellent prediction performance in internal validation (N25 = 98-100%, R2 = 0.99-1.00), it could not well predict HKs occurrence in external validation (N25 = 62-69%, R2 = 0.202-0.848). Prediction ability of RBF ANN in external validation (N25 = 85%, R2 = 0.692-0.909) was quite good, which was comparable to that in internal validation (N25 = 74-88%, R2 = 0.799-0.870). These results demonstrated RBF ANN could well recognized the complex nonlinear relationship between HKs occurrence and the related water quality, and paved a new way for HKs prediction and monitoring in practice.
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Redes Neurais de Computação , Água , DesinfecçãoRESUMO
Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice.
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Oócitos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Triterpenos/farmacologia , Animais , Desidroepiandrosterona , Modelos Animais de Doenças , Feminino , Metformina/farmacologia , Camundongos , Oócitos/metabolismo , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamenteRESUMO
Salvia plebeia has been in use as traditional Chinese medicine (TCM) for more than 500 years. In this study, the complete chloroplast (cp) genome of S. plebeia was sequenced, assembled and compared to those of other five published Salvia cp genomes. It was found that the cp genome structure of S. plebeia was well conserved and had a total size of 151 062 bp. Four parameters were used to display the usage conditions of the codons of the amino acids in Salvia genus. Although the number of protein-coding genes in each species was the same, the total number of codons was different. Except for amino acids Trp and Met whose Relative Synonymous Codon Usage (RSCU) value of one condon was equal to 1, the remaining 19 amino acids had 1-3 preferred codons. The preferred codon names of each amino acid were coincident. The period size for the tandem repeats of six species ranged from 9 to 410 bp. Salvia cp genomes mainly possessed tandem repeats with a copy number less than or equal to 3. The sequence length of tandem repeats of the six species ranged from 25 to 824 bp. Highly viarable regions including four intergenic spacers and six partial genes were discovered as potential specific barcodes for Salvia species through cp genome-wide comparison. Finally, we performed phylogenetic analyses based on the complete cp genome and coding sequences respectively. These results provide information to help construct the cp genome library for Salvia, which may support studies of phylogenetics, DNA barcoding, population and transplastomics.
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Genes de Plantas , Genoma de Cloroplastos , Plantas Medicinais/genética , Salvia/genética , China , Códon/genética , Código de Barras de DNA Taxonômico , Variação Genética , FilogeniaRESUMO
Previous studies have demonstrated differences in the distribution of intracranial and/or extracranial atherosclerosis (I-ECAS) by region and race. Despite this, few studies have examined the distribution of arterial stenosis in ischemic stroke patients of the Zhuang population in Guangxi, China. We therefore aimed to investigate the distribution of cerebrovascular stenosis in ischemic stroke patients across different ethnicities in Guangxi province. A total of 1,101 patients were divided into 2 groups according to their ethnicity: the Zhuang group and Han group. All patients underwent 64-slice spiral computed tomographic angiography (CTA) scanning to document the presence of intracranial or extracranial stenosis. Results showed that: (I) intracranial atherosclerosis (ICAS) a higher incidence of ECAS (51.1% vs. 48.9%); (II) I-ECAS was the most common lesion type, followed by ICAS; (III) Zhuang patients had a higher rate of ECAS ( 20.2% vs. 15.2%, P=0.047) and a lower rate of I-ECAS (35.8% vs. 42.3%, P=0.041) than that of the Han group. Furthermore, Zhuang patients had a higher percentage of stenosis in the posterior circulation (23.0% vs. 13.1%, P<0.001) and a lower percentage of stenosis in the anterior circulation (29.3% vs. 41.5%, P<0.001) than Han patients; (IV) large artery atherosclerosis (LAA) was the most commonly identified cause of stroke, and the Zhuang group had a lower proportion of LAA than the Han group (47.7% vs. 55.4%; P=0.020); (V) smoking and drinking were independent risk factors for ICAS; older age, male gender, and drinking were independent risk factors for ECAS; older age, male gender, hypertension, and drinking were independent risk factors for I-ECAS; age, hypertension, diabetes, hyperlipidemia, smoking, and drinking were independent risk factors for LAA. These outcomes indicate that there are ethnicity differences in the distribution of cerebrovascular stenosis in Guangxi. The variability in the risk factors involved may explain the variation in the distribution of cerebral atherosclerosis between ethnic groups.
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Povo Asiático/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Arteriosclerose Intracraniana/etiologia , Arteriosclerose Intracraniana/fisiopatologia , AVC Isquêmico/complicações , AVC Isquêmico/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Geografia , Humanos , Arteriosclerose Intracraniana/epidemiologia , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Fine particulate matter (PM2.5) has an adverse effect on reproductive function, in particular causing reduced male reproductive function, but relatively few studies have directly targeted its effects on female reproduction. To investigate the effects of PM2.5 exposure on female reproduction, we exposed female mice to PM2.5 by intratracheal instillation for 28 days, and evaluated apoptosis of ovarian granulosa cells and oocytes and the quality embryos after insemination. Our results showed increased numbers of apoptotic granulosa cells and oocytes after exposure to elevated concentrations of PM2.5, which had adverse effects on female fertility via compromising embryo development and quality. We conclude that PM2.5 induced apoptosis of ovarian granulosa cells and oocytes leading to disrupted embryo development and female fertility in mice.
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Poluentes Atmosféricos , Oócitos , Material Particulado , Animais , Apoptose , Feminino , Masculino , Camundongos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Material Particulado/toxicidade , ReproduçãoRESUMO
This study aims to investigate thermodynamic mechanisms of filtration behaviors of ultrafiltration (UF) process with polyacrylamide (PAM) flocculation for surface water treatment, which has not been investigated previously. It was interestingly found that, filtration of durably mixed sodium alginate (SA) solution corresponded to an extraordinarily high specific filtration resistance (SFR) (3.28 × 1014 m·kg-1 without polyacrylamide addition) and a V-shaped profile of SFR characterized by a sharp fall followed by a correspondingly sharp rise along with the increase in PAM addition concentration. Experimental characterizations suggested that, membrane fouling was mainly caused by the gel layer formation rather than the pore clogging and cake/floc formation. Rather than the chemical composition change, the changes of the solution physicochemical properties (pH and zeta potential) and foulant morphology are associated with above-mentioned interesting filtration behaviors. Accordingly, the thermodynamic mechanisms of the filtration behaviors were proposed. It was proposed that, the thermodynamics of polymeric network described by the Flory-Huggins lattice theory were responsible for the extraordinarily high SFR of SA gel layer. Low dosage of PAM addition decreased the negative zeta potential and homogeneity of the gel system, causing the reduced SFR. In contrast, further PAM addition increased the negative zeta potential and homogeneity of the gel system, and then increased the SFR of the gel layer. These results reasonably explained the V-shaped profile of SFR. This study provided significant insights into the effects of PAM addition on ultrafiltration behaviors of alginate solution.
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AIM: Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of intracranial aneurysms (IAs). This study aimed to explore miRNA levels in plasma exosomes of patients with IA to identify potential biomarkers that predict the development and progress of IA. METHODS: A total of 69 patients with IA and 30 healthy controls (HC) were recruited, among whom 30 had unruptured IA (UA), and 39 had ruptured IA (RA). The miRNA expression profiles of plasma exosomes in 12 IA patients (4 UA and 8 RA) and 4 HC were determined using next-generation sequencing. In addition, significantly differentially expressed miRNAs were further analyzed by Quantitative Real-Time PCR (qRT-PCR) in a validation cohort of 99 subjects. RESULTS: From the sequencing analysis, 181 miRNAs were identified to be differently (pï¼0.05) expressed. Of these, 9 miRNAs were up-regulated, and 20 were down-regulated in patients with UA compared with HC. Also, 21 were up-regulated, and 10 were down-regulated in patients with RA compared with HC. In addition, compared with UA, 92 miRNAs were up-regulated in RA, whereas 29 were down-regulated. Furthermore, qRT-PCR analysis confirmed that miR-145-5p and miR-29a-3p were up-regulated in IA samples. To distinguish IA patients from controls, the area under the receiver operating characteristic curve was 0.791 for miR-29a-3p, while that of miRNA-145-5p was 0.773 in terms of discriminating whether the aneurysm was ruptured. CONCLUSIONS: Circulating exosomal miRNAs can serve as biomarkers of the development and progression of IA.
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Aneurisma Roto , Exossomos/genética , Aneurisma Intracraniano , MicroRNAs/genética , Hemorragia Subaracnóidea , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico , Aneurisma Roto/epidemiologia , Aneurisma Roto/genética , China/epidemiologia , Progressão da Doença , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/genética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologiaRESUMO
Molecular mechanisms responsible for the filtration behaviors of sodium alginate (SA) in presence of different iron(III) ion concentration were explored in this study. It was found that specific filtration resistance (SFR) of alginate mixtures (1.0 gSA/L) firstly increased and then decreased to a trough with iron(III) concentration increase from 0 to 2.5â¯mM. Alginate mixture interacting with 0.1â¯mM iron(III) possessed an SFR as high as 1.65â¯×â¯1014â¯mâ¯kg-1, which could be explained by Flory-Huggins lattice theory related with gel filtration. Optical observation showed significant morphology transition (from gel to granular solids) of foulant layers with iron(III) concentration increase. A series of characterizations indicated the change of microstructure, pH and surface charge of alginate mixture with iron(III) concentration. Density functional theory (DFT) simulation suggested that iron(III) ion preferentially forms coordination bonds with three terminal carboxyl groups of alginate chains, facilitating elongation and cross-linking of alginate chains. Such a coordination mode induces formation of a slime and homogeneous gel, corresponding to high SFR. Continuous increase in iron(III) concentration leads to non-terminal coordination, which makes alginate chains more clustered and coiled. This effect, together with effects of the reduced surface charge and electric double layer compression, significantly decrease SFR of alginate mixtures. This study provided deep molecular insights into effects of iron(III) ions on alginate fouling.