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1.
Anal Biochem ; 693: 115594, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38897269

RESUMO

The development of a sensitive and isothermal technique with a greatly enhanced miRNA detection signal is still technically problematic due to the low abundance of miRNA and high sequence similarities with homologous miRNAs. Herein, we propose a novel fluorescence approach for sensitive and reliable miRNA detection by integrating the palindrome sequence mediated target recycling with self-priming assisted signal reaction. In this method, a dual toehold DNA nano-probe (HT) with two functional arms is designed to mediate specific target recognition and signal amplification. In the presence of target miRNA, it binds to the recognition module of HT probe, releasing the "2" sequence to initiate strand displacement amplification (SDA) and a self-priming-induced signal reaction. Based on the elegant design, the proposed method exhibits a wide linear response range exceeding five orders of magnitude and a low limit of detection of 0.96 fM according to the 3δ rule. The non-specific signal is below 5 % for non-target miRNA detection. Taking the merits of excellent sensitivity, desirable specificity, and superior anti-interference ability, the proposed approach shows a promising prospect for detecting miRNAs in complicated biological environments and early diagnosis of diseases.


Assuntos
Sequências Repetidas Invertidas , MicroRNAs , Técnicas de Amplificação de Ácido Nucleico , MicroRNAs/análise , MicroRNAs/genética , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Limite de Detecção , Sondas de DNA/química , Sondas de DNA/metabolismo , Espectrometria de Fluorescência
2.
Chemistry ; 30(27): e202304100, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38451027

RESUMO

Using computer-aided design (TCAD) simulation, the impact of the Fe doping profile, including concentration, decay rate, and depth of the doping region on current-collapse magnitude (▵CC) in 0.5-µm gated GaN-based high electron mobility transistors (HEMTs) is systematically investigated. Accurate simulation models are established and developed to facilitate the fabrication of electronics. It is elucidated that the intricate interplay between trapping and de-trapping of Fe-related traps at the gate-drain edge is responsible for current collapse. The concentration and decay rate of the doping region have a more significant impact on current collapse than the depth. Increased trap state density near two-dimensional electron gas (2DEG) channel caused by deep-level acceptors would boost ▵CC. However, a minor dynamic reduction in 2DEG density (nT) induces a relatively small ▵CC. By adjusting the concentration, decay rate, and depth of the doping region, ▵CC of GaN-based Radio Frequency (RF) HEMTs can be reduced by approximately 50.3 %. The optimized distribution of Fe doping discussed in this work helps to prepare GaN-based RF HEMTs with a limited current collapse effect.

3.
Brain Res Bull ; 204: 110798, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37890595

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a frequently observed underlying pathology of both Alzheimer's disease (AD) and vascular dementia (VD), which is a common consequence of cerebral blood flow (CBF) dysregulation. Synaptic damage has been proven as a crucial causative factor for CCH-related cognitive impairment. This study aimed to investigate the neuroprotective impact of environmental enrichment (EE) intervention on CCH-induced synaptic destruction and the consequent cognitive impairment. Furthermore, the underlying mechanism of this neuroprotective effect was explored to provide new insights into therapeutic interventions for individuals suffering from AD or VD. METHODS: In this experiment, all rats were initially acclimatized to a standard environment (SE) for a period of one week. On the seventh day, rats underwent either bilateral common carotid artery occlusion (2VO) surgery or sham surgery (Sham) before being subjected to a four-week procedure of exposure to an EE, except for the control group. During the EE or SE procedure, intraperitoneal injection of chloroquine (CQ) into rats was performed once daily for four weeks. Following this, cognitive function was assessed using the Morris water maze (MWM) test. The synapse ultrastructure was subsequently observed using transmission electron microscopy. Expression levels of autophagy-related proteins (LC3, LAMP1, and P62) and synapse-related proteins (Synapsin I and PSD-95) were detected through Western blotting. Finally, immunofluorescence was used to examine the expression levels of Synapsin I and PSD-95 and the colocalization of LAMP-1 and LC3 in the hippocampus. RESULTS: After undergoing 2VO, rats exposed to SE exhibited cognitive impairment, autophagic dysfunction, and synapse damage. The synapse damage was evidenced by ultrastructural damage and degradation of synapse-related proteins. However, these effects were significantly mitigated by exposure to an EE intervention. Moreover, the intervention led to an improvement in autophagic dysfunction. CONCLUSION: The study found that EE had a positive impact on CCH-induced synaptic damage. Specifically, EE was found to increase synaptic plasticity-associated proteins and postsynaptic density thickness, while decreasing synaptic space. This multifaceted effect resulted in an amelioration of CCH-induced cognitive impairment. It was shown that this beneficial outcome was mediated via the activation of the autophagy-lysosomal pathway. Overall, the findings suggest that EE may have a therapeutic potential for cognitive impairments associated with CCH through autophagy-mediated synaptic improvement.


Assuntos
Doença de Alzheimer , Isquemia Encefálica , Disfunção Cognitiva , Demência Vascular , Ratos , Animais , Sinapsinas/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/metabolismo , Isquemia Encefálica/patologia , Transdução de Sinais/fisiologia , Autofagia/fisiologia , Demência Vascular/metabolismo , Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto/fisiologia
4.
Front Cell Neurosci ; 17: 985246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37265581

RESUMO

Chronic cerebral hypoperfusion (CCH) is increasingly recognized as a common cognitive impairment-causing mechanism. However, no clinically effective drugs to treat cognitive impairment due to CCH have been identified. An abnormal distribution of neural oscillations was found in the hippocampus of CCH rats. By releasing various neurotransmitters, distinct afferent fibers in the hippocampus influence neuronal oscillations in the hippocampus. Enriched environments (EE) are known to improve cognitive levels by modulating neurotransmitter homeostasis. Using EE as an intervention, we examined the levels of three classical neurotransmitters and the dynamics of neural oscillations in the hippocampus of the CCH rat model. The results showed that EE significantly improved the balance of three classical neurotransmitters (acetylcholine, glutamate, and GABA) in the hippocampus, enhanced the strength of theta and slow-gamma (SG) rhythms, and dramatically improved neural coupling across frequency bands in CCH rats. Furthermore, the expression of the three neurotransmitter vesicular transporters-vesicular acetylcholine transporters (VAChT) and vesicular GABA transporters (VGAT)-was significantly reduced in CCH rats, whereas the expression of vesicular glutamate transporter 1 (VGLUT1) was abnormally elevated. EE partially restored the expression of the three protein levels to maintain the balance of hippocampal afferent neurotransmitters. More importantly, causal mediation analysis showed EE increased the power of theta rhythm by increasing the level of VAChT and VGAT, which then enhanced the phase amplitude coupling of theta-SG and finally led to an improvement in the cognitive level of CCH. These findings shed light on the role of CCH in the disruption of hippocampal afferent neurotransmitter balance and neural oscillations. This study has implications for our knowledge of disease pathways.

5.
Front Endocrinol (Lausanne) ; 14: 1030736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139337

RESUMO

Background: To a great extent, genetic factors contribute to the susceptibility to type 1 diabetes (T1D) development, and by triggering immune imbalance, Toll-like receptor (TLR) 9 is involved in the development of T1D. However, there is a lack of evidence supporting a genetic association between polymorphisms in the TLR9 gene and T1D. Methods: In total, 1513 individuals, including T1D patients (n=738) and healthy control individuals (n=775), from the Han Chinese population were recruited for an association analysis of the rs352140 polymorphism of the TLR9 gene and T1D. rs352140 was genotyped by MassARRAY. The allele and genotype distributions of rs352140 in the T1D and healthy groups and those in different T1D subgroups were analyzed by the chi-squared test and binary logistic regression model. The chi-square test and Kruskal-Wallis H test were performed to explore the association between genotype and phenotype in T1D patients. Results: The allele and genotype distributions of rs352140 were significantly different in T1D patients and healthy control individuals (p=0.019, p=0.035). Specifically, the T allele and TT genotype of rs352140 conferred a higher risk of T1D (OR=1.194, 95% CI=1.029-1.385, p=0.019, OR=1.535, 95% CI=1.108-2.126, p=0.010). The allele and genotype distributions of rs352140 were not significantly different between childhood-onset and adult-onset T1D and between T1D with a single islet autoantibody and T1D with multiple islet autoantibodies (p=0.603, p=0.743). rs352140 was associated with T1D susceptibility according to the recessive and additive models (p=0.015, p=0.019) but was not associated with T1D susceptibility in the dominant and overdominant models (p=0.117, p=0.928). Moreover, genotype-phenotype association analysis showed that the TT genotype of rs352140 was associated with higher fasting C-peptide levels (p=0.017). Conclusion: In the Han Chinese population, the TLR9 polymorphism rs352140 is associated with T1D and is a risk factor for susceptibility to T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/epidemiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor Toll-Like 9/genética , Genótipo
6.
Sci Total Environ ; 867: 161544, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36642277

RESUMO

With the increasing use of veterinary antibiotics, quinolone antibiotics may enter farmland systems after livestock manure has been composted. However, the phytotoxicity mechanism of antibiotics in crops is still unclear. In this study, the oxidative responses of rice (Oryza sativa L.) seedlings to three typical quinolone antibiotics and their underlying mechanisms were investigated. The bioconcentration factor values were 1.47, 0.55, and 0.23 in the levofloxacin, enrofloxacin and norfloxacin treatment, respectively. The inhibitory effects on rice seedlings were in the order of levofloxacin > enrofloxacin > norfloxacin, which may be due to the high uptake of levofloxacin. The H2O2 level, MDA content, and ion leakage rate increased significantly (p < 0.05), and cell plasmolysis was observed, showing that antibiotics can cause membrane lipid peroxidation and damage the cell membrane structure. Antioxidant enzyme activities (superoxide dismutase, catalase, and peroxidase) changed with the antibiotic concentration. Integrated biomarker response analysis showed that levofloxacin caused the greatest oxidative stress in rice seedlings. Transcriptomic analysis identified 5880 differentially expressed genes, and these were annotated as 20 biological functions; the greatest abundances were cellular and metabolic processes, cell part, and membrane part and organelle; SOD and CAT related genes were up-regulated. The richness and diversity of the phyllosphere microbial community decreased significantly (p < 0.05) and the microbiome changed at the phylum and genus levels. The H2O2 level was correlated with changes in phyllosphere microbial communities. The number of antibiotic resistance genes (ARGs) and mobile genetic elements decreased, while their abundance increased. In conclusion, enrofloxacin exposure not only affects the microbial community but may also affect the ARGs carried by microbes. The relative abundance of MGEs and ARGs was significantly positively correlated (R2 = 0.760, p = 0.0148), indicating that MGEs can significantly promote the spread of ARGs.


Assuntos
Oryza , Oryza/genética , Plântula , Antibacterianos/farmacologia , Levofloxacino , Enrofloxacina , Norfloxacino , Peróxido de Hidrogênio/farmacologia , Antioxidantes/metabolismo , Resistência Microbiana a Medicamentos/genética , Estresse Oxidativo , Genes Bacterianos , Esterco
7.
Microbiol Spectr ; 11(1): e0379422, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36622214

RESUMO

Mupirocin, a topical antimicrobial agent, is an important component in the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. The molecular characteristics of 46 mupirocin-resistant MRSA (MR-MRSA) clinical isolates were analyzed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec element (SCCmec) typing, spa typing, and analysis of virulence genes. All 26 MRSA isolates with low-level mupirocin resistance possessed a V588F mutation in ileS. Among 20 MRSA isolates with high-level resistance to mupirocin, all carried mupA; 2 isolates also possessed the V588F mutation in ileS, and 1 possessed the V631F mutation in ileS (isoleucyl-tRNA synthetase). The majority of MR-MRSA isolates were resistant to erythromycin, clindamycin, tetracycline, ciprofloxacin, and gentamicin, but the rates of resistance to rifampin and fusidic acid were 8.7% and 6.5%, respectively. Eight sequence types (STs) were found among the 46 MR-MRSA isolates, of which ST764 was the most prevalent (76.1%). The most frequent spa type identified was t1084 (52.2%). The SCCmec type most frequently found was type II (80.4%). The most common clone among low-level MR-MRSA isolates was ST764-MRSA-SCCmec type II-t1084 (23 isolates), while ST764-MRSA-SCCmec type II-t002 (9 isolates) was the most common clone among high-level MR-MRSA isolates. Additionally, all toxin genes except the seb gene were not identified among ST764 isolates. Among clonal complex 5 (CC5) isolates, immune evasion cluster (IEC)-associated genes (chp, sak, and scn) and seb were present in ST764 but absent in ST5, while sec, sel1, tsst-1, and hlb genes were identified in ST5 but absent in ST764. In conclusion, the spread of CC5 clones, especially a novel ST764-MRSA-SCCmec type II-t1084 clone with high-level resistance to mupirocin, was responsible for the increase in mupirocin resistance. These findings indicated that the emergence of the ST764 MR-MRSA clone involves a therapeutic challenge for treating serious MRSA infections. IMPORTANCE Mupirocin, a topical antibiotic that is commonly used for the nasal decolonization of MRSA and methicillin-sensitive Staphylococcus aureus in hospital settings and nursing homes, was introduced as a highly effective antibiotic against MRSA. Mupirocin acts by competitively binding isoleucyl-tRNA synthetase, thereby disrupting protein synthesis. This drug shows bacteriostatic and bactericidal activity at low and high concentrations, respectively. However, with the increase in mupirocin use, low-level and high-level resistance during nasal mupirocin treatment has been reported. In a previous study, the proportion of MRSA strains with high-level mupirocin resistance in a Canadian hospital increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% (2000 to 2004).


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Mupirocina/farmacologia , Mupirocina/uso terapêutico , Tipagem de Sequências Multilocus , Isoleucina-tRNA Ligase/genética , Genótipo , Canadá , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Testes de Sensibilidade Microbiana
8.
Brain Res Bull ; 193: 117-130, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36577190

RESUMO

BACKGROUND: Vascular cognitive impairment (VCI) is the second most common type of dementia after Alzheimer's disease (AD) in elderly people. Chronic cerebral hypoperfusion (CCH) is the early pathophysiological basis of VCI. ß-Hydroxybutyrate (BHB) is one of the important components of ketone bodies, an intermediate product of endogenous energy metabolism, which can mitigate neuroinflammation in stroke and neurodegenerative diseases. The present study aimed to investigate whether BHB can improve cognitive impairment caused by CCH and the underlying mechanism. METHODS: The CCH model was established by permanent bilateral common carotid artery occlusion (2VO). CCH rats were intraperitoneally injected with BHB (1.5 mmol/kg/d) every day for 8 consecutive weeks from 2 weeks before surgery. The hippocampal blood flow of rats was measured by using a laser Doppler velocimetry. Used the Morris water maze test (MWM) to assess spatial learning and memory of rats, and harvested brain tissues for molecular, biochemical, and pathological tests. RESULTS: We found that BHB intervention for 8 weeks could effectively restore hippocampal blood flow and improve spatial learning and memory in CCH rats. BHB can protect the blood-brain barrier (BBB), as manifested by reducing the ultrastructural damage and leakage of the BBB, restoring the expression of tight junction-related proteins and reducing the expression of Matrix Metalloproteinases-9 (MMP-9). Additionally, after BHB intervention, microglia activation was reduced, oligodendrocyte motility was active, and the expression levels of pro-inflammatory factors such as tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), nuclear factor-κB (NF-κB) and advanced glycation end-products (RAGE) were lower, which also indicated that BHB had a beneficial effect in mitigating neuroinflammation. CONCLUSION: BHB can improve the cognitive impairment caused by CCH. The potential mechanisms of BHB may be through reducing neuroinflammation and protecting BBB.


Assuntos
Isquemia Encefálica , Disfunção Cognitiva , Ratos , Animais , Barreira Hematoencefálica/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Doenças Neuroinflamatórias , Aprendizagem em Labirinto , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças
9.
Front Immunol ; 13: 1030728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457997

RESUMO

Background: Type 1 diabetes mellitus (T1DM) is caused by immune cell-mediated ß-cell dysfunction. In recent decades, N6-methyladenosine (m6A) has attracted widespread attention in the scientific research field because it plays vital roles in the pathogenesis of immunity-related diseases, including autoimmune diseases. However, neither the m6A modification profile nor the potential role it plays in T1DM pathogenesis has been investigated to date. Materials and Methods: An m6A mRNA epitranscriptomic microarray analysis was performed to analyze m6A regulator expression patterns and m6A methylation patterns in immune cells of T1DM patients (n=6) and healthy individuals (n=6). A bioinformatics analysis was subsequently performed to explore the potential biological functions and signaling pathways underlying T1DM pathogenesis. Furthermore, mRNA expression and m6A methylation levels were subsequently verified by qRT-PCR and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), respectively, in the T1DM and healthy groups (n=6 per group). Results: Among the multiple m6A regulators, METTL3 and IGF2BP2 had significantly downregulated expression, and YTHDC1 and HNRNPA2B1 had significantly upregulated expression in the T1DM group relative to the healthy group. The microarray analysis revealed 4247 differentially methylated transcripts, including 932 hypermethylated and 3315 hypomethylated transcripts, and 4264 differentially expressed transcripts, including 1818 upregulated transcripts and 2446 downregulated transcripts in the T1DM group relative to the healthy group. An association analysis between methylation and gene expression demonstrated that the expression of 590 hypermethylated transcripts was upregulated, and that of 1890 hypomethylated transcripts was downregulated. Pearson correlation analysis showed significant correlations between the expression levels of differentially expressed m6A regulators and the methylation levels of differentially methylated transcripts and significant correlations between the expression levels of differentially expressed m6A regulators and that of differentially expressed transcripts. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that differentially methylated transcripts were involved in pathways related to immunity, including some closely associated with T1DM. Conclusions: Our study presents m6A regulator expression patterns and m6A methylation patterns of immune cells in T1DM, showing that the m6A mark and m6A regulators are promising targets for T1DM diagnosis and treatment.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Humanos , Metilação , Diabetes Mellitus Tipo 1/genética , Processamento de Proteína Pós-Traducional , Ontologia Genética , Metiltransferases , Proteínas de Ligação a RNA
10.
Brain Res Bull ; 187: 98-110, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35798222

RESUMO

BACKGROUND: People exposed to prolonged chronic unpredictable mild stress (CUMS) are easy to suffer from depression and cognitive impairment. Environmental enrichment (EE) had a beneficial effect on depressive-like and cognition-like behaviors by inhibiting inflammation. However, the specific mechanism involved in the inflammation inhibition that occurs after EE treatment for the depression and cognitive decline induced by CUMS remains unclear. In this study, we evaluated the possible mechanism of the beneficial effects on depression and cognition by EE. METHODS: Rats were randomly divided into 5 groups as follows: (1) Control + standard environment (SE), (2) CUMS + SE, (3) CUMS + EE, (4) CUMS + EE+ 3-methiladenine (3-MA), (5) CUMS + SE + 3-MA. They were exposed to CUMS procedure for 5 weeks except the control group. After CUMS procedure, rats were housed in the EE or SE for 3 weeks. During EE or SE treatment, rats were injected with normal saline or 3-MA every day. 3-MA as an autophagy inhibitor suppresses autophagy via inhibition of class III PI3K. Behavioral tests were used to investigate depressive-like and cognition-like behaviors after EE treatment. Then, autophagy-related proteins, inflammation-related molecules, transmission electron microscopy (TEM) and immunofluoresence were determined. RESULTS: We found that CUMS induced depressive-like behaviors and cognitive impairment, reflected in worse behavioral test, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, prolonged immobility and spatial learning and memory impairment. In addition, CUMS rats exhibited the reduced expression of autophagy related proteins including LC3 and Beclin-1 and the increased inflammation activation including microglia cells, NLRP3 inflammasome and proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). After EE treatment, these changes were reversed. However, 3-MA, the inhibitor of autophagy, eliminated the neuroprotective effects of EE on depressive-like behaviors and cognitive decline. CONCLUSION: This study demonstrates that EE can play neuroprotective effects on depression and cognitive impairment by inducing autophagy-mediated inflammation inhibition, which accounts for the reduction of proinflammatory cytokines, including IL-1ß, IL-6 and TNF-α.


Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Animais , Antidepressivos/farmacologia , Autofagia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/terapia , Citocinas/metabolismo , Depressão/etiologia , Depressão/metabolismo , Depressão/terapia , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Interleucina-6 , Ratos , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Estresse Psicológico/terapia , Fator de Necrose Tumoral alfa
12.
Small Methods ; 6(9): e2200429, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35676230

RESUMO

Hollow metal-organic frameworks (MOFs) with careful phase engineering have been considered to be suitable candidates for high-performance microwave absorbents. However, there has been a lack of direct methods tailored to MOFs in this area. Here, a facile and safe Ni2+ -exchange strategy is proposed to synthesize graphite/CoNi alloy hollow porous composites from Ni2+ concentration-dependent etching of Zeolite imidazole frame-67 (ZIF-67) MOF and subsequent thermal field regulation. Such a special combination of hollow structure and carefully selected hybrid phase are with optimized impedance matching and electromagnetic attenuation. Especially, the suitable carrier transport model and the rich polarization site enhance the dielectric loss, while more significant hysteresis loss and more natural resonance increase the magnetic loss. As a result, excellent microwave absorbing (MA) performances of both broadband absorption (7.63 GHz) and high-efficiency loss (-63.79 dB) are obtained. Moreover, the applicability and practicability of the strategy are demonstrated. This work illustrates the unique advantages of ion-exchange strategy in structure design, component optimization, and electromagnetic regulation, providing a new reference for the 5G cause and MA field.

13.
Front Endocrinol (Lausanne) ; 13: 835054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528000

RESUMO

Background and Aims: The NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients. Methods: In total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student's t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons. Results: 1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models. Conclusion: rs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients.


Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Anticorpos , Autoanticorpos/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Glutamato Descarboxilase/imunologia , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único
15.
J Affect Disord ; 310: 198-212, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35461822

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) has been gradually regarded as a common etiologic mechanism for cognitive and psychiatric disturbances. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) played an important role in adult hippocampal neurogenesis (AHN), neuronal circuits formation, cognition and psychiatric disorders. Enriched environment (EE) showed a beneficial effect on cognition and depression via effectively regulating AHN and glial reactivity. This study aimed to assess which strategy was feasible to improve cognition and psychiatric disturbances by comparing the TET1 hippocampal microinjection and EE in CCH models and to investigate the possible mechanisms. METHOD: CCH rats were established via permanent bilateral common carotid artery occlusion (2-VO). Rats were stereotaxically injected with the human catalytic domain of TET1 (hTET1) to overexpress the hTET1 in the hippocampus 10 days before 2-VO. 3 days after 2-VO, rats were subjected to standard environment or EE with free access to food and water. Behavioral tests were used to appraise depression and cognition before sacrifice. Epigenetic molecules, adult neurogenesis, synaptic proteins expression, and glial activation were analyzed using immunofluorescent staining, qRT-PCR and western blot. RESULTS: In the present study, we found both EE and genetical treatment with overexpressing hTET1 were sufficient for stimulating AHN. However, promoting ANH could not deal with the cognitive dysfunction and depressive-like behaviors in CCH rats. Notably, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. Meanwhile, astrocytes were involved in the cognitive regulating process of neurons, presynaptic function and microglia. In general, we held that depressive disturbances were determined by BDNF levels, neuronal and presynaptic function, as well as glial activation containing astrocytes and microglia. To further support this point, we investigated severe depressive symptoms that were strongly correlated with the activation of astroglia and microglia. Importantly, causal mediation analysis showed significant mediation by the presence of reactive glial cells in the relation between neural plasticity and depressive symptoms. Finally, we showed EE performed better than hTET1 treatment for cognitive deficits and depression. EE with less glial reactivity was much more resistant to depression, while hTET1 with more glial activation was more vulnerable to depressive disorders. CONCLUSIONS: EE was likely to be superior to TET1 hippocampal administration for cognition and psychiatric behaviors in CCH rats. Furthermore, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. More glial activation, and more vulnerable to depressive disorders. These results were important for our understanding of disease mechanisms and provided valuable tools for the overall management of CCH patients.


Assuntos
Isquemia Encefálica , Hipocampo , Transtornos Mentais , Oxigenases de Função Mista , Proteínas Proto-Oncogênicas , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto/fisiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Microinjeções , Oxigenases de Função Mista/administração & dosagem , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Plasticidade Neuronal/fisiologia , Proteínas Proto-Oncogênicas/administração & dosagem , Ratos
16.
Zhongguo Zhen Jiu ; 42(2): 150-4, 2022 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-35152578

RESUMO

OBJECTIVE: To observe the effect of conventional ovulation induction protocol and acupuncture combined with conventional ovulation induction protocol on pregnancy outcomes of frozen embryo transfer (FET) in patients with anovulatory infertility. METHODS: A total of 60 patients with anovulatory infertility were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional ovulation induction protocol was applied to prepare endometrium. On the basis of the control group, acupuncture was started on the 2nd day of menstrual cycle in the observation group,Baihui (GV 20), Mingmen (GV 4), Geshu (BL 17), Guanyuan (CV 4), Qihai (CV 6), etc. were selected, once every other day, until 1 day before transplantation. The clinical pregnancy rate, embryo implantation rate, endometrial morphology on HCG trigger day, ovulation rate and cycle cancellation rate were compared in the two groups. The endometrial thickness before treatment and on HCG trigger day, TCM symptom score before and after treatment were observed in the two groups. RESULTS: In the observation group, the embryo implantation rate and clinical pregnancy rate were higher than the control group (P<0.05), endometrial thickness and endometrial morphology on HCG trigger day were superior to the control group (P<0.05). After treatment, the TCM symptom score in the observation group was decreased compared with before treatment (P<0.05), and the variation was greater than the control group (P<0.01). CONCLUSION: On the basis of the conventional ovulation induction protocol, acupuncture could enhance the embryo implantation rate and clinical pregnancy rate of FET, improve the endometrial receptivity of patients with anovulatory infertility.


Assuntos
Terapia por Acupuntura , Infertilidade Feminina , Transferência Embrionária , Feminino , Humanos , Infertilidade Feminina/terapia , Gravidez , Resultado da Gravidez , Taxa de Gravidez
17.
J Colloid Interface Sci ; 606(Pt 2): 1852-1865, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507176

RESUMO

Low melting point liquid metal alloys are progressively utilized in different research fields due to their unique physicochemical properties. Among them, EGaIn is liquid at room temperature with an excellent solubility for reactive metal atoms such as Al. Combined with their characteristic flexible surface, large area and atomically flat interfaces, a library of two-dimensional materials can be generated. Liquid metal synthesis routes provide a highly reproducible thickness of nanosheets with fast, simple, scalable, inexpensive, high yield and non-toxic methods, especially for Al oxides and hydroxides. At the same time, Al-based heterojunction structure also shows a good application prospect in the field of electromagnetic wave absorption, therefore, the use of liquid metal synthesis methods to find the synthesis methods of Al-based layered double hydroxide (LDH) and its derivatives remains to be explored. In this work, EGaIn was used as an aluminum reservoir to prepare LDH and metal organic framework (MOFs) nano-arrays. The prepared CoAl-LDH@ZIF 67 can be transformed into CoAl-LDO@Co-C in the subsequent annealing process performed under nitrogen environments. Interestingly, a series of samples with different morphologies can be obtained by changing the synthesis parameters. The excellent electromagnetic wave interactions are fully characterized. It has an effective absorption bandwidth of 8.48 GHz at 2.6 mm. The findings demonstrated in this work pave the way for the application of lightwave and ductile complex nanoarrays obtained from liquid metals.

18.
Nanoscale ; 13(30): 12896-12909, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477773

RESUMO

MOFs with high tunability are considered ideal candidates as microwave-absorbing materials. Strict experimental conditions can ensure the repeatability and maximize the potential of such materials. In this study, cubic ZIF-67 carbides synthesized at different solution temperatures showed an adjustable average size, and then by adjusting the calcination temperature we could control the degree of graphitization, so as to explore the synergistic effect of these two aspects to achieve an in-depth understanding of the electromagnetic properties and microwave absorption properties. The results showed that sample 30-600 (with the former number referring to the synthesis temperature and the latter to the calcination temperature) showed the widest effective absorption bandwidth (5.75 GHz, 1.8 mm) and the optimal reflection loss (-56.92 dB, 2.1 mm). The best matching electromagnetic parameters were obtained under the synergistic action of a smaller particle size and appropriate degree of graphitization, so as to achieve strong attenuation characteristics under low electromagnetic wave reflection. The microwave loss mechanism of the sample mainly involved dielectric losses, such as from conductance loss, dipole polarization, and interface polarization. Starting from the experimental details, this work proposes a dual control strategy for developing microwave-absorbing materials with both simplicity and practicability, which provides a useful reference for other microwave absorbents synthesized at room temperature.

19.
Nanoscale ; 13(25): 11017-11040, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34152349

RESUMO

Biosensors are essential components for effective healthcare management. Since biological processes occur on molecular scales, nanomaterials and nanosensors intrinsically provide the most appropriate landscapes for developing biosensors. Low-dimensional materials have the advantage of offering high surface areas, increased reactivity and unique physicochemical properties for efficient and selective biosensing. So far, nanomaterials and nanodevices have offered significant prospects for glucose sensing. Targeted glucose biosensing using such low-dimensional materials enables much more effective monitoring of blood glucose levels, thus providing significantly better predictive diabetes diagnostics and management. In this review, recent advances in using low dimensional materials for sensing glucose are summarized. Sensing fundamentals are discussed, as well as invasive, minimally-invasive and non-invasive sensing methods. The effects of morphological characteristics and size-dependent properties of low dimensional materials are explored for glucose sensing, and the key performance parameters such as selectivity, stability and sensitivity are also discussed. Finally, the challenges and future opportunities that low dimensional materials can offer for glucose sensing are outlined.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Glucose
20.
Sci Total Environ ; 788: 147819, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34029823

RESUMO

Due to the extensive use and incomplete removal, pharmaceutical and personal care products (PPCPs) are introduced into the water continuously. It has been proved that the unique properties of PPCPs are influential to organisms and the environment, and gradually affect human health. In this paper, the toxicological effects of typical PPCPs, and the environmental behavior of PPCPs in aquatic are reviewed. The risk assessments of PPCPs in the water are summarized. The research directions of environmental toxicology research of PPCPs in the future are proposed. Many PPCPs were found to be toxic or even highly toxic toward aquatic organisms, and have the potential for bioaccumulation. It is essential to study the acute and long-term toxicity of PPCPs and their metabolites, evaluate the environmental behaviors and make a reasonable assessment of ecotoxicology and human health risks of PPCPs.


Assuntos
Cosméticos , Preparações Farmacêuticas , Poluentes Químicos da Água , Cosméticos/análise , Cosméticos/toxicidade , Ecotoxicologia , Monitoramento Ambiental , Humanos , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
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