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1.
Sci Adv ; 10(40): eadp5332, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39356764

RESUMO

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.


Assuntos
Adenosina , Homeostase , Queratinócitos , Metabolismo dos Lipídeos , Metiltransferases , Neutrófilos , Pele , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Neutrófilos/metabolismo , Neutrófilos/imunologia , Camundongos , Queratinócitos/metabolismo , Humanos , Metiltransferases/metabolismo , Metiltransferases/genética , Pele/metabolismo , Pele/patologia , Pele/imunologia , Inflamação/metabolismo , Inflamação/patologia , Quimiotaxia , Elongases de Ácidos Graxos/metabolismo , Elongases de Ácidos Graxos/genética
2.
Sci Total Environ ; : 176867, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39414039

RESUMO

Long-term global gridded population data is crucial in deepening our understanding of spatiotemporal population dynamics and essential in disaster exposure assessment studies. Several gridded population datasets exist but only cover a single period of observational, historical, or future. Here, based on a unified data and method framework, we created a coherent and consistent gridded population dataset at 1 km resolution with a 10-year interval spanning from 1870 to 2100. Using the observed population maps (2000-2020), historical population hindcast (1870-2000), and future population projection (2020-2100) under the Shared Socioeconomic Pathways (SSPs) were modeled. The validation shows that the constructed dataset achieves a high quantitative agreement with existing datasets and can better distribute the population within the built-up area, resulting in a more reasonable allocation. The constructed gridded population dataset can clearly show the evolution of population distribution over a long period in a spatially explicit way and exhibit high temporal consistency. From 1870 to 2100 (SSPs), the global population showed an S-shaped growth pattern, increasing by about 4.17 to 8.49 times, which has exerted substantial pressure on global sustainable development. At the local scale, the consistent, long-term, high-resolution gridded population data reveals diverse spatial (cluster, linear, and ring) and temporal (emergence, increase, stable, decrease) dynamics of population patterns across distinct regions, periods, and scenarios. Applying the long-term gridded population data, we revealed a substantial increase in the proportion of the global population exposed to floods, rising from 10.61 % in 1870 to 11.98 %-13.93 % in 2100 (SSPs), highlighting a rapid population expansion within flood-prone areas. In general, this study provides a consistent global gridded population dataset spanning over 200 years, which can provide insights into the whole life cycle of the global population spatiotemporal dynamics and holds great application value in various fields.

3.
Food Chem ; 463(Pt 2): 141210, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39270492

RESUMO

S-nitrosoglutathione (GSNO) is the most important S-nitrosothiol in vivo, which could affect the quality of meat by participating in calcium release, glucose metabolism, proteolysis and apoptosis, therefore may potentially serve as a marker for meat freshness. In this work, a solid-phase extraction (SPE) monolithic spin column modified with gold nanoparticles was prepared for GSNO extraction. The optimized SPE-LC-MS/MS method for GSNO quantification displays low limit of detection (0.01 nM), good precision (RSD < 15 %) and acceptable recovery (> 77.7 %). Furthermore, this approach has been applied to monitor GSNO levels in beef and pork stored at -20 °C for different days, showing that endogenous GSNO level increases during prolonged storage and could be employed as a marker to evaluate the freshness of ice stored meat. Additionally, the monolithic spin column remains in good quality after a half-year storage, which is promising to develop into commercial enrichment kit for endogenous GSNO analysis.

4.
Vet Res ; 55(1): 120, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334337

RESUMO

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that induces an NLRP3-dependent cytokine storm. NLRP3 inflammasome activation triggers not only an inflammatory response but also pyroptosis. However, the exact mechanism underlying S. suis-induced macrophage pyroptosis is not clear. Our results showed that SS2 induced the expression of pyroptosis-associated factors, including lactate dehydrogenase (LDH) release, propidium iodide (PI) uptake and GSDMD-N expression, as well as NLRP3 inflammasome activation and IL-1ß secretion. However, GSDMD deficiency and NLRP3 inhibition using MCC950 attenuated the SS2-induced expression of pyroptosis-associated factors, suggesting that SS2 induces NLRP3-GSDMD-dependent pyroptosis. Furthermore, RACK1 knockdown also reduced the expression of pyroptosis-associated factors. In addition, RACK1 knockdown downregulated the expression of NLRP3 and Pro-IL-1ß as well as the phosphorylation of P65. Surprisingly, the interaction between RACK1 and P65 was detected by co-immunoprecipitation, indicating that RACK1 induces macrophage pyroptosis by mediating the phosphorylation of P65 to promote the transcription of NLRP3 and pro-IL-1ß. Similarly, NEK7 knockdown decreased the expression of pyroptosis-associated factors and ASC oligomerization. Moreover, the results of co-immunoprecipitation revealed the interaction of NEK7-RACK1-NLRP3 during SS2 infection, demonstrating that NEK7 mediates SS2-induced pyroptosis via the regulation of NLRP3 inflammasome assembly and activation. These results demonstrate the important role of RACK1 and NEK7 in SS2-induced pyroptosis. Our study provides new insight into SS2-induced cell death.


Assuntos
Macrófagos , Quinases Relacionadas a NIMA , Piroptose , Receptores de Quinase C Ativada , Infecções Estreptocócicas , Streptococcus suis , Animais , Macrófagos/microbiologia , Macrófagos/metabolismo , Camundongos , Quinases Relacionadas a NIMA/metabolismo , Quinases Relacionadas a NIMA/genética , Receptores de Quinase C Ativada/metabolismo , Receptores de Quinase C Ativada/genética , Infecções Estreptocócicas/veterinária , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/fisiologia , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos Endogâmicos C57BL , Inflamassomos/metabolismo , Inflamassomos/genética , Gasderminas
5.
Small Methods ; : e2401070, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279552

RESUMO

In this work, a horseradish peroxidase (HRP)-encapsulated metal organic framework (MOF)@MOF nanocomposite is developed for detecting H2O2 converted by dismutation of superoxide anions released from live HeLa mitochondria. Initially, an HRP-polyacrylic acid cluster is incorporated on a mesoporous, peroxidase-like Cu/Co-1,4-benzenedicarboxylate (BDC) MOF platform to avoid structural change and deactivation of HRP through its interactions with MOF metal ions. Additionally, a Cu/Co-BDC(HRP)@1,3,5-benzenetricarboxyate (BTC) core-shell MOF/MOF structure, also with peroxide-like properties, serves as a protective matrix for HRP. Then, ultrathin porous carbon shells (UPCS) are adopted to improve the electrical conductivity of the MOF@MOF. The Cu/Co-BDC(HRP)@BTC|UPCS sensing platform exhibits two linear ranges of 0.05-1 µM and 1-1000 µM with a sensitivity of 172 mA mM-1 cm-2 and 1.63 mA mM-1 cm-2, respectively. A limit of detection of 0.057 µM, good selectivity and stability over 35 days for H2O2 detection are also achieved. After treating the mitochondrial complex with specific inhibitors, amperometric results at the sensing platform confirmed complex I and III within mitochondria as the main electron leakage sites in the electron transfer chains. Therefore, this sensing platform provides a tool that may aid in predicting and even developing treatments for some oxidative stress diseases caused by mitochondrial abnormalities.

6.
Proc Natl Acad Sci U S A ; 121(37): e2400002121, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39226348

RESUMO

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study.


Assuntos
Análise de Célula Única , Análise de Célula Única/métodos , Análise por Conglomerados , Humanos , Análise de Sequência de RNA/métodos , Animais , Algoritmos , RNA/genética , Perfilação da Expressão Gênica/métodos , RNA-Seq/métodos
7.
J Hazard Mater ; 480: 135918, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307020

RESUMO

Submerged plants (SP) in the hyporheic sediment (HS) dynamically alter the spatial distributions of heavy metals (HMs) and microplastics (MPs). In this study, we examined the redistribution and combination of HMs and MPs in the HS surrounding the SP (SSP) and non-nearby the SP (NSP) in the Weihe River Basin. The strong bioconcentration capacity of SP directly caused a decrease of HMs in the SSP (Bioconcentration Factors: SSP>NSP, 1.07 >1.00). Algal proliferation at high nutrient concentrations strengthened the interception of MPs by SP (SSP-MPs >NSP-MPs, 495 >315 items/kg). The significant correlation between SSP-HMs and SSP-MPs indicates the formation of MPs-HMs. The concentration of SSP-HMs was greater than NSP-HMs (Mn (462.95 >437.66 mg/kg)>Zn (63.46 >60.51 mg/kg)>V (53.98 >50.67 mg/kg)>Pb (21.98 >18.47 mg/kg)>As (18.36 >15.65 mg/kg). This finding implies that the MPs trapped by the SP indirectly contribute to elevating SSP-HMs, which showed higher pollution risk (Nemerow Pollution Index: 1.37 >1.22; Contamination Factor: V, 0.87 >0.82, Zn, 0.95 >0.90, As, 1.61 >1.41, Pb, 0.98 >0.88). Furthermore, SP can reduce NSP contamination by proactively collecting pollutants into SSP, endangering the integrity of rivers through the ingesting of hydrobiont. Our study provides theoretical suggestions for the application of SP to improve ecological health in the complex environment.

8.
ACS Nano ; 18(32): 21112-21124, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39094075

RESUMO

The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.


Assuntos
Neoplasias Encefálicas , Dextranos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Animais , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Dextranos/química , Ratos , Meios de Contraste/química , Humanos , Linhagem Celular Tumoral , Tamanho da Partícula
9.
J Colloid Interface Sci ; 675: 836-847, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39002234

RESUMO

The persistent hurdles of charge rapid recombination, inefficient use of light and utilization of sacrificial reagents have plagued the field of photocatalytic hydrogen evolution (PHE). In this research, tiny MoO2 nanoparticles of 10 nm in diameter were prepared through a straightforward solvothermal approach with a specific ratio of oleylamine and oleic acid as stabilizers. The critical factor in the synthesis process was found to be the ratio of oleylamine to oleic acid. Moreover, a two-phase interface assembly method facilitated the uniform deposition of MoO2 onto CdS nanorods. Due to the localized plasmonic-thermoelectric effect on the surface of MoO2 along with its abundant oxygen vacancies, the composite catalyst exhibited outstanding photo-utilization efficiency and an abundance of active sites. The CdS-MoO2 composite displayed a unique photochemical property in transforming lactic acid into pyruvic acid and generating hydrogen simultaneously. After exposure to artificial sunlight for 4 h, significant values of 4.7 and 3.7 mmol⋅g-1⋅h-1 were achieved for hydrogen production and pyruvic acid formation, respectively, exceeding CdS alone by 3.29 and 4.02-fold, while the selectivity of pyruvic acid was 95.68 %. Furthermore, the S-Scheme electron transport mechanism in the composites was elucidated using Electron Paramagnetic Resonance (EPR) spectroscopy, radical trapping experiments, energy band structure analysis, and the identification of critical intermediates in the process of selective oxidation. This work sheds light on the design and preparation of high-performance photocatalysts for biorefining coupled with efficient hydrogen evolution.

10.
Food Chem ; 460(Pt 2): 140487, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39067427

RESUMO

The monitoring of antioxidant capacity is very important to evaluate the quality of antioxidant foods or drugs for market regulation. Herein, dechlorination treatment of waste PVC/scrap irons were conducted in subcritical water to obtain carbon-based Fe composites (CM-Fe-dPVC) with peroxidase-like activity. The electron bonding of C 2p and Fe 3d orbital led to strong electron migration ability. CM-Fe-dPVC exhibited excellent activity of simulated peroxidase. Vitamin C (VC) and CM-Fe-dPVC had competitive behaviors on •OH generation in TMB oxidation reaction. A portable paper based colorimetric test kit was developed for monitoring total antioxidant capacity of beverages and pharmaceuticals on the market (with the detection limit of 0.1 µM for Vc). The results of life cycle assessment (LCA) revealed that the proposed strategy had low global warming potential. This research could provide important reference for high value recycling of organic solid wastes.


Assuntos
Antioxidantes , Técnicas Biossensoriais , Carbono , Ferro , Cloreto de Polivinila , Técnicas Biossensoriais/instrumentação , Carbono/química , Antioxidantes/química , Antioxidantes/análise , Ferro/química , Ferro/análise , Cloreto de Polivinila/química , Peroxidase/química , Peroxidase/metabolismo , Oxirredução , Halogenação
11.
Small ; : e2401061, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963320

RESUMO

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

12.
Mass Spectrom Rev ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004897

RESUMO

With the development of analytical technologies especially mass spectrometry, metabolomics is becoming increasingly hot in the field of studying antibiotic-bacterial interactions. On the one hand, metabolomics can reveal metabolic perturbations in bacteria in the presence of antibiotics and expose metabolic mechanisms. On the other hand, through in-depth analysis of bacterial metabolic profiles, biomarkers and bioactive secondary metabolites with great potential as drug precursors can be discovered. This review focuses on the experimental workflow of bacterial metabolomics and its application to study the interaction between bacteria and antibiotics. Metabolomics improves the understanding of antibiotic lethality, reveals metabolic perturbations in antibiotic-resistant bacteria, guides the diagnosis and antibiotic treatment of infectious diseases, and aids in the exploration of antibacterial metabolites in nature. Furthermore, current limitations and directions for future developments in this area are discussed.

14.
Anal Chim Acta ; 1314: 342803, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38876516

RESUMO

BACKGROUND: The detection of plasticizers in the environment is important to prevent environmental risks and people's health hazards. Improving recycling efficiency of waste PVC still faced challenges. RESULTS: In this work, it was found that solid products from waste PVC/coal gangue dechlorination in subcritical water (dPVC) had strong catalysis activity for luminol-H2O2 chemiluminescence (CL) reaction. Phthalates, common plasticizers, could bond and adsorb on dPVC, which greatly inhibited the luminol-H2O2-dPVC CL reaction. Based on this, a low-cost CL analysis was constructed for the detection of phthalates combinations (PACs) and di-(2-ethylhexyl) phthalate (DEHP) in the environment. The detection limit for PACs and DEHP was 0.048 ng/L and 0.13 ng/L, respectively. Compared with HPLC standard method, the dPVC CL analysis had accuracy and reliability for the detection of phthalates in actual environmental samples. Besides, the results of life cycle assessment (LCA) revealed that dPVC for CL sensing materials had significantly small global warming potential (GWP). SIGNIFICANCE: The use of dPVC for CL sensing not only improved the recycling efficiency of PVC, but also reduced carbon emissions of obtaining CL sensing materials.

15.
J Hazard Mater ; 473: 134538, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761759

RESUMO

Both sediments and microplastics (MPs) are medias of heavy metals (HMs) in river ecosystems. This study investigated HMs (Mn, Cr, V, As, Cu, Co, Cd, Pb, and Ni) concentration and driving factors for competitive enrichment between hyporheic sediments versus MPs. The medias basic characteristics indicated that the sediments were mostly sand and rich in Fe2O3; three polymer types were identified, with blue, fragment, less than 500 µm being the main types of MPs. The results have shown that the average content of extracted HMs in MPs was much higher than that of the same metals accumulated in sediments. HMs in sediments and MPs reached heavily polluted at some points, among which As and Cd were ecological risks. Electrostatic adsorption and surface complexation, and biofilm-mediated and organic matter complexation were the interaction mechanism of HMs with sediments and MPs. Further, the driving factors affecting the distribution of HMs in the two carriers were analyzed by multivariate statistical analysis. The results demonstrated that carrier characteristics, hydrochemical factors, and the inherent metal load of MPs were the main causes of the high HMs content. These findings improved our understanding of HMs fate and environmental risks across multiple medias.

16.
Genome Biol ; 25(1): 116, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715020

RESUMO

BACKGROUND: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. RESULTS: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. CONCLUSIONS: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.


Assuntos
Genoma , Variação Estrutural do Genoma , Animais , Sus scrofa/genética , Polimorfismo de Nucleotídeo Único , Suínos/genética , Mapeamento Cromossômico
17.
Mikrochim Acta ; 191(6): 360, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819644

RESUMO

A novel in-tube solid-phase microextraction coupled with an ultra-high performance liquid chromatography-mass spectrometry method has been established for simultaneous quantification of three crucial brain biomarkers N-acetylaspartic acid (NAA), N-acetylglutamic acid (NAG), and N-acetylaspartylglutamic acid (NAAG). A polymer monolith with quaternary ammonium as the functional group was designed and exhibited efficient enrichment of target analytes through strong anion exchange interaction. Under the optimized conditions, the proposed method displayed wide linear ranges (0.1-80 nM for NAA and NAG, 0.2-160 nM for NAAG) with good precision (RSDs were lower than 15%) and low limits of detection (0.019-0.052 nM), which is by far the most sensitive approach for NAA, NAG, and NAAG determination. Furthermore, this approach has been applied to measure the target analytes in mouse brain samples, and endogenous NAA, NAG, and NAAG were successfully detected and quantified from only around 5 mg of cerebral cortex, cerebellum, and hippocampus. Compared with existing methods, the newly developed method in the current study provides highest sensitivity and lowest sample consumption for NAA, NAG, and NAAG measurements, which would potentially be utilized in determining and tracking these meaningful brain biomarkers in diseases or treatment processes, benefiting the investigations of pathophysiology and treatment of brain disorders.


Assuntos
Ácido Aspártico , Encéfalo , Dipeptídeos , Microextração em Fase Sólida , Espectrometria de Massas em Tandem , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Camundongos , Microextração em Fase Sólida/métodos , Encéfalo/metabolismo , Dipeptídeos/análise , Limite de Detecção , Biomarcadores/análise , Masculino , Química Encefálica , Glutamatos
18.
Oncol Lett ; 27(5): 220, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586204

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare and aggressive tumor with an unknown pathogenesis. Myelofibrosis (MF) is a type of myeloproliferative neoplasm. MF can be secondary to several hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndrome and hairy cell leukemia. In the present report, a rare case of BPDCN secondary to MF is described. A 70-year-old male patient developed a large purplish-red rash with recurrent symptoms. BPDCN was confirmed by immunohistochemistry of a biopsy specimen and flow cytometry of bone marrow cells. Bone marrow histopathology revealed MF. Next-generation sequencing of peripheral blood revealed mutations in the Tet methylcytosine dioxygenase 2 and NRAS proto-oncogene GTPase genes. The patient underwent one cycle of chemoimmunotherapy, but the condition progressed, an infection developed and the patient eventually died. The present case suggests that BPDCN can occur in conjunction with MF and that the prognosis of such patients is poor. Pathological examination and genetic testing aided in the diagnosis and treatment. This case emphasizes the need to raise awareness of BPDCN among clinicians and to be alert to the potential for fatal infection in patients with BPDCN combined with MF following myelosuppression triggered during chemotherapy.

19.
Neurorehabil Neural Repair ; 38(6): 425-436, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38676561

RESUMO

BACKGROUND: Corticospinal tract (CST) is the principal motor pathway; we aim to explore the structural plasticity mechanism in CST during stroke rehabilitation. METHODS: A total of 25 patients underwent diffusion tensor imaging before rehabilitation (T1), 1-month post-rehabilitation (T2), 2 months post-rehabilitation (T3), and 1-year post-discharge (T4). The CST was segmented, and fractional anisotropy (FA), axial diffusion (AD), mean diffusivity (MD), and radial diffusivity (RD) were determined using automated fiber quantification tractography. Baseline level of laterality index (LI) and motor function for correlation analysis. RESULTS: The FA values of all segments in the ipsilesional CST (IL-CST) were lower compared with normal CST. Repeated measures analysis of variance showed time-related effects on FA, AD, and MD of the IL-CST, and there were similar dynamic trends in these 3 parameters. At T1, FA, AD, and MD values of the mid-upper segments of IL-CST (around the core lesions) were the lowest; at T2 and T3, values for the mid-lower segments were lower than those at T1, while the values for the mid-upper segments gradually increased; at T4, the values for almost entire IL-CST were higher than before. The highest LI was observed at T2, with a predominance in contralesional CST. The LIs for the FA and AD at T1 were positively correlated with the change rate of motor function. CONCLUSIONS: IL-CST showed aggravation followed by improvement from around the lesion to the distal end. Balance of interhemispheric CST may be closely related to motor function, and LIs for FA and AD may have predictive value for mild-to-moderate stroke rehabilitation. Clinical Trial Registration. URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR1800019474.


Assuntos
Imagem de Tensor de Difusão , Plasticidade Neuronal , Tratos Piramidais , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/fisiopatologia , Tratos Piramidais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto
20.
Obes Rev ; 25(7): e13748, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38590187

RESUMO

Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.


Assuntos
Tecido Adiposo , Biomarcadores , Biologia Computacional , MicroRNAs , Obesidade , Humanos , Obesidade/genética , Obesidade/complicações , MicroRNAs/metabolismo , Tecido Adiposo/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo
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