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Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.
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Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Tálamo , Humanos , Tálamo/crescimento & desenvolvimento , Tálamo/diagnóstico por imagem , Feminino , Masculino , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Nascimento Prematuro/patologiaRESUMO
BACKGROUND: Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear. METHODS: We evaluated the expression pattern of SENP1 based on RNA sequencing data obtained from OHSU, TCGA, TARGET, and MILE datasets. Clinical samples were used to verify the expression of SENP1 in the AML cells. Lentiviral vectors shRNA and sgRNA were used to intervene in SENP1 expression in AML cells, and the effects of SENP1 on AML proliferation and anti-apoptosis were detected using in vitro and in vivo models. Chip-qPCR, MERIP-qPCR, CO-IP, RNA pulldown, and dual-luciferase reporter gene assays were used to explore the regulatory mechanisms of SNEP1 in AML. RESULTS: SENP1 was significantly upregulated in high-risk AML patients and closely related to poor prognosis. The AKT/mTOR signaling pathway is a key downstream pathway that mediates SENP1's regulation of AML proliferation and anti-apoptosis. Mechanistically, the CO-IP assay revealed binding between SENP1 and HDAC2. SUMO and Chip-qPCR assays suggested that SENP1 can desumoylate HDAC2, which enhances EGFR transcription and activates the AKT pathway. In addition, we found that IGF2BP3 expression was upregulated in high-risk AML patients and was positively correlated with SENP1 expression. MERIP-qPCR and RIP-qPCR showed that IGF2BP3 binds SENP1 3-UTR in an m6A manner, enhances SENP1 expression, and promotes AKT pathway conduction. CONCLUSIONS: Our findings reveal a distinct mechanism of SENP1-mediated HDAC2-AKT activation and establish the critical role of the IGF2BP3/SENP1signaling axis in AML development.
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Adenosina , Proliferação de Células , Cisteína Endopeptidases , Histona Desacetilase 2 , Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-akt , Proteínas de Ligação a RNA , Sumoilação , Animais , Feminino , Humanos , Masculino , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Progressão da Doença , Regulação Leucêmica da Expressão Gênica , Histona Desacetilase 2/metabolismo , Histona Desacetilase 2/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.
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Antígenos de Superfície da Hepatite B , Análise Espectral Raman , Antígenos de Superfície da Hepatite B/sangue , Análise Espectral Raman/métodos , Humanos , Vírus da Hepatite B/isolamento & purificação , Nanopartículas Metálicas/química , Hepatite B/sangue , Hepatite B/diagnóstico , Propriedades de Superfície , Limite de DetecçãoRESUMO
PURPOSE: Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-ß (Aß) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aß PET imaging in clinical AD cohort. METHODS: We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18F]DPA-714) and Aß ([18F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC). Immune-related differentially expressed genes (IREDGs), identified based on AlzData, were screened and verified using blood samples from ADIMIC. Correlation and mediation analyses were applied to investigate the relationships between immune-related genes expression, TSPO and Aß PET imaging. RESULTS: TSPO uptake increased significantly both in aMCI (P < 0.05) and AD participants (P < 0.01) and showed a positive correlation with Aß deposition (r = 0.42, P < 0.001). Decreased expression of TGFBR3, FABP3, CXCR4 and CD200 was observed in AD group. CD200 expression was significantly negatively associated with TSPO PET uptake (r =-0.33, P = 0.013). Mediation analysis indicated that CD200 acted as a significant mediator between TSPO uptake and Aß deposition (total effect B = 1.92, P = 0.004) and MMSE score (total effect B =-54.01, P = 0.003). CONCLUSION: By integrating transcriptomics and TSPO PET imaging in the same clinical AD cohort, this study revealed CD200 played an important role in regulating neuroinflammation, Aß deposition and cognitive dysfunction.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Perfilação da Expressão Gênica , Doenças Neuroinflamatórias , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Receptores de GABA/genética , Receptores de GABA/metabolismoRESUMO
The properties of polyethylene are highly dependent on the variety and quantity of substitutions. Generally, polyethylene can only be fully substituted with fluorine atoms, mainly e. g., polytetrafluoroethylene and nafion, because atomic radius of fluorine atom is small enough. The preparation of fully substituted polyethylene analogues (FSPEA) and their non-traditional intrinsic luminescence (NTIL) are attractive, especially for substitutions with relatively larger atomic radii than a fluorine atom. Here, Barbier polymerization-induced emission (PIE) is demonstrated as a universal method for the molecular design of NTIL type FSPEAs with intriguing aggregation-induced emission (AIE) behaviors. Through Barbier polymerization of diphenyldichloromethane and different peroxyesters in the presence of Mg in one pot, a series of FSPEAs, including polytriphenylethanol (PTPE), polydiphenylfurylethanol (PDPFE), polydiphenylthiophenylethanol (PDPTE) and polydiphenylnaphthylethanol (PDPNE) have been successfully prepared. Further potential applications for explosive detection, artificial light-harvesting system and white phosphor-converted light-emitting diode are investigated. Therefore, this work opens up a new approach for the molecular design of FSPEA with non-conjugated luminescence, which may cause inspirations to different research fields like polyolefin and luminescent materials.
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Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since the LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice. Finally, CYP monooxygenase mediates the pro-cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota-dependent mechanisms. Overall, these results support that CYP monooxygenase-mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.
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Neoplasias do Colo , Ácido Linoleico , Humanos , Camundongos , Animais , Ácido Linoleico/farmacologia , Ácido Linoleico/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Eicosanoides , Sistema Enzimático do Citocromo P-450/metabolismo , Dieta , Neoplasias do Colo/etiologiaRESUMO
BACKGROUND: Alzheimer's disease (AD), the most prevalent type of dementia, still lacks disease-modifying treatment strategies. Recent evidence indicates that maintaining gut microbiota homeostasis plays a crucial role in AD. Targeted regulation of gut microbiota, including probiotics, is anticipated to emerge as a potential approach for AD treatment. However, the efficacy and mechanism of multi-strain probiotics treatment in AD remain unclear. METHODS: In this study, 6-month-old senescence-accelerated-mouse-prone 8 (SAMP8) and senescence-accelerated-mouse-resistant 1 (SAMR1) were utilized. The SAMP8 mice were treated with probiotic-2 (P2, a probiotic mixture of Bifidobacterium lactis and Lactobacillus rhamnosus) and probiotic-3 (P3, a probiotic mixture of Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus rhamnosus) (1 × 109 colony-forming units) once daily for 8 weeks. Morris water maze (MWM) and novel object recognition (NOR) tests were employed to assess the memory ability. 16S sequencing was applied to determine the composition of gut microbiota, along with detecting serum short-chain fatty acids (SCFAs) concentrations. Neural injury, Aß and Tau pathology, and neuroinflammation level were assessed through western blot and immunofluorescence. Finally, potential molecular mechanisms was explored through transcriptomic analysis and western blotting. RESULTS: The MWM and NOR test results indicated a significant improvement in the cognitive level of SAMP8 mice treated with P2 and P3 probiotics compared to the SAMP8 control group. Fecal 16S sequencing revealed an evident difference in the α diversity index between SAMP8 and SAMR1 mice, while the α diversity of SAMP8 mice remained unchanged after P2 and P3 treatment. At the genus level, the relative abundance of ten bacteria differed significantly among the four groups. Multi-strain probiotics treatment could modulate serum SCFAs (valeric acid, isovaleric acid, and hexanoic acid) concentration. Neuropathological results demonstrated a substantial decrease in neural injury, Aß and Tau pathology and neuroinflammation in the brain of SAMP8 mice treated with P3 and P2. Transcriptomic analysis identified the chemokine signaling pathway as the most significantly enriched signaling pathway between SAMP8 and SAMR1 mice. Western blot test indicated a significant change in the phosphorylation level of downstream AKT/GSK-3ß between the SAMP8 and SAMR1 groups, which could be reversed through P2 and P3 treatment. CONCLUSIONS: Multi-strain probiotics treatment can ameliorate cognitive impairment and pathological change in SAMP8 mice, including neural damage, Aß and Tau pathology, and neuroinflammation. This effect is associated with the regulation of the phosphorylation of the AKT/GSK-3ß pathway.
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Doença de Alzheimer , Disfunção Cognitiva , Modelos Animais de Doenças , Microbioma Gastrointestinal , Glicogênio Sintase Quinase 3 beta , Probióticos , Proteínas Proto-Oncogênicas c-akt , Animais , Probióticos/farmacologia , Probióticos/uso terapêutico , Camundongos , Doença de Alzheimer/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Disfunção Cognitiva/metabolismo , Masculino , Envelhecimento/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lacticaseibacillus rhamnosus , Proteínas tau/metabolismoRESUMO
Edible mushroom polysaccharides (EMPs) as a natural macromolecular carbohydrate have a very complex structure and composition. EMPs are considered ideal candidates for developing healthy products and functional foods and have received significant research attention due to their unique physiological activities such as immunomodulatory, anti-inflammatory, anti-tumor/cancer, gut microbiota regulation, metabolism improvement, and nervous system protection. The structure and monosaccharide composition of edible mushroom polysaccharides have an unknown relationship with their functional activity, which has not been widely studied. Therefore, we summarized the preparation techniques of EMPs and discussed the association between functional activity, preparation methods, structure and composition of EMPs, laying a theoretical foundation for the personalized nutritional achievements of EMP. We also establish the foundation for the further investigation and application of EMPs as novel functional foods and healthy products.
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Lipid-based delivery systems (LDS) have emerged as cornerstone techniques for bolstering the bioavailability of lipophilic bioactive compounds, addressing challenges related to solubility, stability, and absorption. This critical review examined a substantial dataset of 6,907 scientific articles and 3,021 patents from 2001-2023, elucidating the multifaceted evolution of LDS, with a particular focus on its industrial and patent-driven perspective. Notably, there were pronounced surges in functional food patent applications in 2004, 2011, and 2019. The trajectory revealed a shift from foundational nanoemulsions to more complex structures, such as double/multiple emulsions, solid lipid nanoparticles, Pickering emulsions, and bigels. The review further identified the top 10 leading institutions shaping this domain. Technologies like spray-drying, microfluidics, and phase gelation had revolutionized the landscape, resulting in refined sensory experiences, innovative reduced-fat formulations, enriched beverages, tailor-made infant nutrition, and nuanced release mechanisms for flavors. The review also spotlighted current research frontiers, notably Pickering emulsions, bigels, and multiple emulsions. These emerging technologies not only exemplified the ongoing innovation in the field but also underscored their potential in reshaping the future landscape of value-added functional foods.
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Pollution of surface water by heavy metal hexavalent chromium ions poses a serious threat to human health; herein, a two-dimensional (2D) cationic breathing Ni-MOF with free nitrate ions between the layers was designed and synthesized according to the characteristics of hexavalent chromium ions, {[Ni(L)2](NO3)2·5H2O}n (L = 1,3,5-tris[4-(imidazol-1-yl)phenyl]benzene). The flexible layer spacing of the 2D breathing Ni-MOF allows the exchange of NO3- by CrO42- without destroying the original structure. Electrostatic and hydrogen bonding interactions between CrO42- and Ni-MOF facilitate its exchange with NO3-. Moreover, CrO42- exhibits a higher binding energy with Ni-MOF compared to NO3-, and the hydrophobic channels of Ni-MOF favor CrO42- trapping due to its lower hydration energy. Consequently, Ni-MOF demonstrates both effective sorption and electrochemical sensing of Cr(VI), achieving a sensitivity of 2.091 µA µM-1 and a detection limit of 0.07 µM.
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Antibiotic-induced inflammation involves the release of myeloperoxidase (MPO), an enzyme whose expression in tissues is associated with the inflammatory pathway. However, existing methods for detecting MPO in cells are limited. In this study, a DNAzyme nanorobot was developed using a scaffold of gold nanoparticles (AuNPs) decorated with functional DNAzyme strands and their fluorophore-labeled substrate strands. The DNAzyme remains inactive due to a self-assembled hairpin structure, with a phosphorothioate (PT) modification inserted into the stem domain. When MPO is present, it triggers a halogenation process that generates hypochlorous acid (HClO). HClO specifically catalyzes the cleavage of the PT-site, releasing free DNAzyme strands to cleave their substrates and generating an increasing fluorescent signal. The detection limit for MPO and its primary product, HClO, were determined to be 0.038 µg/mL and 0.013 µM, respectively. The DNAzyme nanorobot can be readily introduced into cells and function autonomously to differentiate increased MPO/HClO levels caused by antibiotics. This approach was applied to image RAW264.7 cells exposed to four prevalent antibiotics found in the environment (phorbol 12-myristate 13-acetate, erythromycin, penicillin, and tetracycline) as well as antibiotic production wastewater. This nanorobot offers novel strategies for monitoring inflammation to evaluate the health impacts of antibiotic exposure.
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Non-traditional intrinsic luminescent (NTIL) polymer is an emerging field, and its color-tunable modification is highly desirable but still rarely investigated. Here, a click chemistry approach for the color-tunable modifications of NTIL polymers by introducing clickable polymerization-induced emission luminogen (PIEgen), is demonstrated. Through Cu-catalyzed azide-alkyne cycloaddition click chemistry, a series of PIEgens is successful prepared, which is further polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Interestingly, after clickable modification, these monomers are nonemissive in both solution and aggregation states; while, the corresponding polymers exhibit intriguing aggregation-induced emission (AIE) characteristics, confirming their PIEgen characteristics. By varying alkynyl substitutions, color-tunable NTIL polymers are achieved with emission wavelength varying from 448 to 498 nm, revealing a series of PIEgens and verifying the importance of modification of NTIL polymers. Further luminescence energy transfer application is carried out as well. This work therefore designs a series of clickable PIEgens and opens a new avenue for the modification of NTIL polymers via click chemistry, which may cause inspirations to the research fields including luminescent polymer, NTIL, click chemistry, AIE and modification.
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Química Click , Cor , Luminescência , Polimerização , Polímeros , Polímeros/química , Polímeros/síntese química , Estrutura Molecular , Catálise , Substâncias Luminescentes/química , Substâncias Luminescentes/síntese química , Azidas/química , Alcinos/químicaRESUMO
Spiro-hydrocarbons are potentially a type of novel alternative jet fuel due to their high density and net heat of combustion. In this work, the pyrolysis study of two spiro-hydrocarbons (spiro[cyclopropane-1,6'-tricyclo[3.2.1.02,4]octane] (C10H14) as Fuel 1 and spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropane] (C9H14) as Fuel 2) is performed via molecular dynamics (MD) simulations, with a neural network potential energy surface (NNPES), deep potential (DP) model, adopted. The data set for the DP model of each fuel is constructed after 31 and 27 iterations, respectively. The high precision of the DP model is demonstrated, and the temperature transferability of each model is observed. The overall pyrolysis performance is evaluated with the fuel decomposition rate, showing that both fuels have comparable gas-reactivity to commercial aviation fuels, such as JP-10. The reaction networks of initial pyrolysis for Fuels 1 and 2 are constructed, and the contribution of each pathway is discussed. Fuel 1 tends to form an unsaturated six-membered ring structure, while Fuel 2 generates unsaturated open-chain hydrocarbons. Further analyses of the MD results provide time-evolution information on each component in the pyrolysis species pool. Compared to Fuel 1, the initial pyrolysis of Fuel 2 leads to more hydrogen, alkenes, and alkanes, as well as fewer monocyclic aromatic hydrocarbons (MAHs), demonstrating a reduced tendency for afterward coking. This work might contribute to the development of the mechanism of the two spiro-hydrocarbons and guide the research of other similar structural fuels.
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Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.
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Dopamina , Metanfetamina , Camundongos Endogâmicos C57BL , Animais , Metanfetamina/administração & dosagem , Metanfetamina/farmacologia , Dopamina/metabolismo , Masculino , Camundongos , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ácido Glutâmico/metabolismo , Receptores de Dopamina D2/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Sulpirida/farmacologia , Sulpirida/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismoRESUMO
A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in autumn and spring from Harbin, a megacity in China, using GC-MS/MS base quantitative trace analysis. The results showed that a total of 33 pesticides were detected in road dust and green-belt soil, with the total concentrations of 650 and 236 ng/g (dry weight = dw), respectively. The concentrations of pesticides in road dust were significantly higher than that in green-belt soil. Pesticides in the environment were influenced by the seasons, with the highest concentrations of insecticides in autumn and the highest levels of herbicides in spring. In road dust, the concentrations of highways in autumn and spring (with the mean values of 94.1 and 68.2 ng/g dw) were much lower than that of the other road classes (arterial roads, sub-arterial roads and branch ways). Whereas in the green-belt soil, there was no significant difference in the concentration of pesticides between the different road classes. A first risk assessment was conducted to evaluate the potential adverse health effects of the pesticides, the results showed that the highest hazard index (HI) for a single pesticide in dust and soil was 0.12, the hazard index for children was higher than that for adults, with an overall hazard index of less than 1. Our results indicated that pesticide levels do not have a significant health impact on people.
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Cidades , Poeira , Exposição Ambiental , Monitoramento Ambiental , Praguicidas , China , Praguicidas/análise , Humanos , Exposição Ambiental/análise , Poeira/análise , Monitoramento Ambiental/métodos , População Urbana , Estações do Ano , Poluentes do Solo/análise , Ensaios de Triagem em Larga EscalaRESUMO
INTRODUCTION: Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging (1H-MRSI), is spatially heterogeneous and underpins cognitive impairments in Alzheimer's disease (AD). However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations. METHODS: We used a novel whole-brain high-resolution 1H-MRSI technique, with simultaneously acquired 18F-florbetapir positron emission tomography (PET) imaging, to investigate the relationship between neurometabolic topography and cognitive functions in 117 participants, including 22 prodromal AD, 51 AD dementia, and 44 controls. RESULTS: Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N-acetylaspartate, and increases in myo-inositol. Reduced N-acetylaspartate and increased myo-inositol were associated with worse global cognitive performance, and N-acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions. DISCUSSION: Whole-brain high-resolution 1H-MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression. HIGHLIGHTS: Whole-brain high-resolution 1H-MRSI unveils neurometabolic topography in AD. Spatially distinct reductions in NAA, and increases in mI, are demonstrated. NAA and mI topography correlates with global cognitive performance. NAA topography correlates with specific cognitive performance.
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Doença de Alzheimer , Ácido Aspártico , Encéfalo , Inositol , Tomografia por Emissão de Pósitrons , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Masculino , Feminino , Idoso , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Inositol/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Cognição/fisiologia , Espectroscopia de Ressonância Magnética , Etilenoglicóis , Compostos de Anilina , Testes Neuropsicológicos , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Humic acids (HAs) would be excessively released during thermal hydrolysis pretreatment (THP) and deeply disturb anaerobic digestion (AD) of waste activated sludge (WAS). The molecular weights of HAs could affect HAs entering microbial cells, binding with digestive enzymes and participating in electron transfer, thereby determining its influences on sludge AD. Results in this study confirmed the different influences of HAs from diverse sources on sludge AD indeed had significant correlations with their molecular weights. The presence of commercial HAs (SAHA) inhibited methane production by 53.3% at 0.5 g/L while HAs extracted from raw sludge (WNHA) increased methane production by 20.5% at the same concentration, which attribute to the comprehensive impacts from their differences in functional group compositions and molecular weights. Moreover, comparing to WNHA, the HAs extracted from thermally hydrolyzed sludge (THHA) showed unchanged functional group compositions but reduced methane generation facilitation to 5.1%, which only be due to its decreased molecular weights. In-depth research indicated that HAs influences on enzymes were closely relative to its molecular weight. HAs with greater molecular weights presented more significant inhibition to extracellular enzymes while micromolecular HAs affected intracellular enzymes more. Furthermore, macromolecular HAs promoted sludge solubilization and acidification but hindered hydrolysis and methanogenesis, whereas micromolecular HAs promoted acidification but inhibited methanogenesis. This study underscored the importance of changes in molecular weight of HAs during sludge THP, offering insights into previous discrepancies in reports on HAs effects on sludge AD.
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BACKGROUND: Agarose, mainly composed of 3,6-anhydro-α-l-galactopyranose (LA) and ß-d-galactopyranose (G) units, is an important polysaccharide with wide applications in food, biomedical and bioengineering industries. Carbohydrate-binding modules (CBMs) are favorable tools for the investigations of polysaccharides. Few agarose-binding CBMs have been hitherto reported, and their binding specificity is unclear. RESULTS: An unknown domain with a predicted ß-sandwich fold was discovered from a ß-agarase of the marine bacterium Wenyingzhuangia fucanilytica CZ1127T . The expressed protein WfCBM101 could bind to agarose and exhibited relatively weak affinity for porphyran, with no affinity for the other seven examined polysaccharides. The protein binds to the tetrasaccharide (LA-G)2 , but not to the major tetrasaccharide contained in porphyran. The sequence novelty and well-defined binding function of WfCBM101 shed light on a novel CBM family (CBM101). Furthermore, the feasibility of WfCBM101 for visualizing agarose in situ was confirmed. CONCLUSION: A novel CBM, WfCBM101, with a desired specificity for agarose was discovered and characterized, which represents a new CBM family. The CBM could be utilized as a promising tool for studies of agarose. © 2023 Society of Chemical Industry.
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Galactose , Polissacarídeos , Sefarose , Polissacarídeos/química , OligossacarídeosRESUMO
BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.
Assuntos
Dieta Hiperlipídica , Fibras na Dieta , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Obesidade , Animais , Fibras na Dieta/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/dietoterapia , Obesidade/microbiologia , Camundongos , Masculino , Fígado/metabolismo , Humanos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Avena/química , Daucus carota/químicaRESUMO
The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.