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1.
Chem Commun (Camb) ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853589

RESUMO

We found that the interfacially confined self-assembly of pyrene and phenanthrene glutamides can form strong exciplexes and amorphous superhelices, which show intensity-enhanced and sign-inverted CPL activity with improved quantum yield compared to a pyrene excimer. This work unveils the predominant role of supramolecular nanostructures over molecular configurations on CPL performance.

2.
Front Vet Sci ; 11: 1430113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872801

RESUMO

N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.

3.
Nat Commun ; 15(1): 5066, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871716

RESUMO

With the rapid increase in lithium consumption for electric vehicle applications, its price soared during the past decade. To secure a reliable and cost-effective supply chain, it is critical to unlock alternative lithium extraction resources beyond conventional brine. In this study, we develop an electrochemical method to directly leach lithium from α-phase spodumene. We find the H2O2 promoter can significantly reduce the leaching potential by facilitating the electron transfer and changing the reaction path. Upon leaching, ß-phase spodumene shows a typical phase transformation to HAlSi2O6, while leached α-phase remains its original crystal phase with a lattice shrinkage. To demonstrate the scale-up potential of electrochemical leaching, we design a catalyst-modified high-throughput current collector for high loading of suspended spodumene, achieving a leaching current of 18 mA and a leaching efficiency of 92.2%. Electrochemical leaching will revolutionize traditional leaching and recycling processes by minimizing the environmental footprint and energy consumption.

4.
Opt Lett ; 49(11): 3066-3069, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824329

RESUMO

We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.

5.
J Hazard Mater ; 474: 134837, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850945

RESUMO

Multi-component droplets from daily activities and production processes severely degrade indoor air quality. Their health hazards and removal efficiency depend on size and composition, significantly affected by evaporation and growth. The phase transition process is complex, involving a broad spectrum of droplet sizes with diverse heat and mass transfer characteristics. Components within the droplets experience simultaneous phase transitions at differing rates and mass transfer directions. This study aims to refine the existing evaporation model of single-component droplets in continuous flows by theoretically integrating the effects of varying droplet sizes and multiple components. A multi-component droplet evaporation/growth model that spans the entire range of droplet sizes has been developed, and predictions have been made based on this model. Utilizing MATLAB, this model accurately predicts the indoor dynamics of multi-component droplets, with deviations under 16 % from experiments. It improves accuracy by over 25 % across droplet sizes via dimensionless transfer coefficients and boosts precision by over 24 % for multi-component droplets with zero-diffusion transport. The radius of the droplet after phase change can reach 8.42 × 10-6 m and remains suspended in the air for an extended period. This study establishes a solid theoretical foundation for accurately predicting the indoor distribution of multi-component droplets.

6.
J Control Release ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851535

RESUMO

Recovery and survival following traumatic brain injury (TBI) depends on optimal amelioration of secondary injuries at lesion site. Delivering mitochondria-protecting drugs to neurons may revive damaged neurons at sites secondarily traumatized by TBI. Pioglitazone (PGZ) is a promising candidate for TBI treatment, limited by its low brain accumulation and poor targetability to neurons. Herein, we report a ROS-responsive nanosystem, camouflaged by hybrid membranes of platelets and engineered extracellular vesicles (EVs) (C3-EPm-|TKNPs|), that can be used for targeted delivery of PGZ for TBI therapy. Inspired by intrinsic ability of macrophages for inflammatory chemotaxis, engineered M2-like macrophage-derived EVs were constructed by fusing C3 peptide to EVs membrane integrator protein, Lamp2b, to confer them with ability to target neurons in inflamed lesions. Platelets provided hybridized EPm with capabilities to target hemorrhagic area caused by trauma via surface proteins. Consequently, C3-EPm-|PGZ-TKNPs| were orientedly delivered to neurons located in the traumatized hemisphere after intravenous administration, and triggered the release of PGZ from TKNPs via oxidative stress. The current work demonstrate that C3-EPm-|TKNPs| can effectively deliver PGZ to alleviate mitochondrial damage via mitoNEET for neuroprotection, further reversing behavioral deficits in TBI mice. Our findings provide proof-of-concept evidence of C3-EPm-|TKNPs|-derived nanodrugs as potential clinical approaches against neuroinflammation-related intracranial diseases.

7.
BMC Med Educ ; 24(1): 619, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840140

RESUMO

INTRODUCTION/AIM: Radiological imaging is crucial in modern clinical practice and requires thorough and early training. An understanding of cross-sectional imaging is essential for effective interpretation of such imaging. This study examines the extent to which completing an undergraduate ultrasound course has positive effects on the development of visual-spatial ability, knowledge of anatomical spatial relationships, understanding of radiological cross-sectional images, and theoretical ultrasound competencies. MATERIAL AND METHODS: This prospective observational study was conducted at a medical school with 3rd year medical students as part of a voluntary extracurricular ultrasound course. The participants completed evaluations (7-level Likert response formats and dichotomous questions "yes/no") and theoretical tests at two time points (T1 = pre course; T2 = post course) to measure their subjective and objective cross-sectional imaging skills competencies. A questionnaire on baseline values and previous experience identified potential influencing factors. RESULTS: A total of 141 participants were included in the study. Most participants had no previous general knowledge of ultrasound diagnostics (83%), had not yet performed a practical ultrasound examination (87%), and had not attended any courses on sonography (95%). Significant subjective and objective improvements in competencies were observed after the course, particularly in the subjective sub-area of "knowledge of anatomical spatial relationships" (p = 0.009). Similarly, participants showed improvements in the objective sub-areas of "theoretical ultrasound competencies" (p < 0.001), "radiological cross-section understanding and knowledge of anatomical spatial relationships in the abdomen" (p < 0.001), "visual-spatial ability in radiological cross-section images" (p < 0.001), and "visual-spatial ability" (p = 0.020). CONCLUSION: Ultrasound training courses can enhance the development of visual-spatial ability, knowledge of anatomical spatial relationships, radiological cross-sectional image understanding, and theoretical ultrasound competencies. Due to the reciprocal positive effects of the training, students should receive radiology training at an early stage of their studies to benefit as early as possible from the improved skills, particularly in the disciplines of anatomy and radiology.


Assuntos
Competência Clínica , Educação de Graduação em Medicina , Estudantes de Medicina , Ultrassonografia , Humanos , Estudos Prospectivos , Masculino , Feminino , Avaliação Educacional , Adulto Jovem , Adulto , Currículo
8.
J Cancer Res Clin Oncol ; 150(6): 292, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842611

RESUMO

BACKGROUND: Glioblastoma (GBM) is a highly aggressive and prevalent brain tumor that poses significant challenges in treatment. SRSF9, an RNA-binding protein, is essential for cellular processes and implicated in cancer progression. Yet, its function and mechanism in GBM need clarification. METHODS: Bioinformatics analysis was performed to explore differential expression of SRSF9 in GBM and its prognostic relevance to glioma patients. SRSF9 and CDK1 expression in GBM cell lines and patients' tissues were quantified by RT-qPCR, Western blot or immunofluorescence assay. The role of SRSF9 in GBM cell proliferation and migration was assessed by MTT, Transwell and colony formation assays. Additionally, transcriptional regulation of CDK1 by SRSF9 was investigated using ChIP-PCR and dual-luciferase assays. RESULTS: The elevated SRSF9 expression correlates to GBM stages and poor survival of glioma patients. Through gain-of-function and loss-of-function strategies, SRSF9 was demonstrated to promote proliferation and migration of GBM cells. Bioinformatics analysis showed that SRSF9 has an impact on cell growth pathways including cell cycle checkpoints and E2F targets. Mechanistically, SRSF9 appears to bind to the promoter of CDK1 gene and increase its transcription level, thus promoting GBM cell proliferation. CONCLUSIONS: These findings uncover the cellular function of SRSF9 in GBM and highlight its therapeutic potential for GBM.


Assuntos
Neoplasias Encefálicas , Proteína Quinase CDC2 , Movimento Celular , Proliferação de Células , Glioblastoma , Fatores de Processamento de Serina-Arginina , Humanos , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Proteína Quinase CDC2/metabolismo , Proteína Quinase CDC2/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Prognóstico , Feminino , Masculino , Pessoa de Meia-Idade
9.
Epilepsy Behav Rep ; 27: 100676, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826153

RESUMO

Although several previous studies have used resting-state functional magnetic resonance imaging and diffusion tensor imaging to report topological changes in the brain in epilepsy, it remains unclear whether the individual structural covariance network (SCN) changes in epilepsy, especially in pediatric epilepsy with visual cortex resection but with normal functions. Herein, individual SCNs were mapped and analyzed for seven pediatric patients with epilepsy after surgery and 15 age-matched healthy controls. A whole-brain individual SCN was constructed based on an automated anatomical labeling template, and global and nodal network metrics were calculated for statistical analyses. Small-world properties were exhibited by pediatric patients after brain surgery and by healthy controls. After brain surgery, pediatric patients with epilepsy exhibited a higher shortest path length, lower global efficiency, and higher nodal efficiency in the cuneus than those in healthy controls. These results revealed that pediatric epilepsy after brain surgery, even with normal functions, showed altered topological organization of the individual SCNs, which revealed residual network topological abnormalities and may provide initial evidence for the underlying functional impairments in the brain of pediatric patients with epilepsy after surgery that can occur in the future.

10.
J Cell Mol Med ; 28(11): e18447, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837574

RESUMO

The purpose of this study was to identify the mechanisms underlying the involvement of glycolytic genes in pulmonary arterial hypertension (PAH). This study involved downloading 3 datasets from the GEO database at the National Center for Biotechnology Information. The datasets were processed to obtain expression matrices for analysis. Genes involved in glycolysis-related pathways were obtained, and genes related to glycolysis were selected based on significant differences in expression. Gene Ontology functional annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and GSEA enrichment analysis were performed on the DEGs. Combining LASSO regression with SVM-RFE machine learning technology, a PAH risk prediction model based on glycolysis related gene expression was constructed, and CIBERSORTx technology was used to analyse the immune cell composition of PAH patients. Gene enrichment analysis revealed that the DEGs work synergistically across multiple biological pathways. A total of 6 key glycolysis-related genes were selected using LASSO regression and SVM. A bar plot was constructed to evaluate the weights of the key genes and predict the risk of PAH. The clinical application value and predictive accuracy of the model were assessed. Immunological feature analysis revealed significant correlations between key glycolysis-related genes and the abundances of different immune cell types. The glycolysis genes (ACSS2, ALAS2, ALDH3A1, ADOC3, NT5E, and TALDO1) identified in this study play important roles in the development of pulmonary arterial hypertension, providing new evidence for the involvement of glycolysis in PAH.


Assuntos
Biologia Computacional , Glicólise , Hipertensão Arterial Pulmonar , Humanos , Glicólise/genética , Biologia Computacional/métodos , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Ontologia Genética , Regulação da Expressão Gênica , Bases de Dados Genéticas
11.
Plant J ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843154

RESUMO

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

12.
Ecotoxicol Environ Saf ; 280: 116536, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38833983

RESUMO

The anomalies of cadmium (Cd) in karst region pose a severe threat to plant growth and development. In this study, the responses of Rhododendron decorum to Cd stress were investigated at physiological, molecular, and endophytic microbial levels, and the potential correlation among these responses was assessed. The Cd stress impeded R. decorum growth and led to an increase in malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, as well as enhanced superoxide dismutase (SOD) and catalase (CAT) activities. Meanwhile, Cd stress increased the Cd (up to 80 times compared to the control), sodium (Na), aluminum (Al), and zinc (Zn) contents, while decreased the magnesium (Mg) and manganese (Mn) contents in R. decorum leaves. Transcriptome suggested that Cd significantly regulated the pathways including "protein repair", "hormone-mediated signaling pathway", and "ATP-binding cassette (ABC) transporters". Additionally, q-PCR analysis showed that Cd stress significantly up-regulated the expressions of ABCB19-like and pleiotropic drug resistance, while down-regulated the expressions of indole-3-acetic acid-amido synthetase and cytokinin dehydrogenase. The Cd stress influenced the composition of endophytic microbial communities in R. decorum leaves and enhanced the interspecific bacterial associations. Furthermore, the bacterial genera Achromobacter, Aureimonas and fungal genus Vishniacozyma exhibited a high degree of connectivity with other nodes in networks constructed by the metal element contents, differentially expressed genes (DEGs), and microbial communities, respectively. These findings provide a comprehensive insight into the response of R. decorum to Cd-induced stress, which might facilitate the breeding of the Cd-tolerant R. decorum.

13.
J Am Chem Soc ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838245

RESUMO

The activity of Ru-based alkaline hydrogen oxidation reaction (HOR) electrocatalysts usually decreases rapidly at potentials higher than 0.1 V (vs a reversible hydrogen electrode (RHE)), which significantly limits the lifetime of fuel cells. It is found that this phenomenon is caused by the overadsorption of the O species due to the overcharging of Ru nanoparticles at high potentials. Here, Mn1Ox(OH)y clusters-modified Ru nanoparticles (Mn1Ox(OH)y@Ru/C) were prepared to promote charge transfer from overcharged Ru nanoparticles to Mn1Ox(OH)y clusters. Mn1Ox(OH)y@Ru/C exhibits high HOR activity and stability over a wide potential range of 0-1.0 V. Moreover, a hydroxide exchange membrane fuel cell with a Mn1Ox(OH)y@Ru/C anode delivers a high peak power density of 1.731 W cm-2, much superior to that of a Pt/C anode. In situ X-ray absorption fine structure (XAFS) analysis and density functional theory (DFT) calculations reveal that Mn in Mn1Ox(OH)y clusters could receive more electrons from overcharged Ru at higher potentials and significantly decrease the overadsorption of the O species on Ru, thus permitting the HOR on Ru to proceed at high potentials. This study provides guidance for the design of alkaline HOR catalysts without activity decay at high potentials.

14.
Chem Soc Rev ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38841828

RESUMO

Globally, 91% of plant production encounters diverse environmental stresses that adversely affect their growth, leading to severe yield losses of 50-60%. In this case, monitoring the connection between the environment and plant health can balance population demands with environmental protection and resource distribution. Fluorescent chemosensors have shown great progress in monitoring the health and environment of plants due to their high sensitivity and biocompatibility. However, to date, no comprehensive analysis and systematic summary of fluorescent chemosensors used in monitoring the correlation between plant health and their environment have been reported. Thus, herein, we summarize the current fluorescent chemosensors ranging from their design strategies to applications in monitoring plant-environment interaction processes. First, we highlight the types of fluorescent chemosensors with design strategies to resolve the bottlenecks encountered in monitoring the health and living environment of plants. In addition, the applications of fluorescent small-molecule, nano and supramolecular chemosensors in the visualization of the health and living environment of plants are discussed. Finally, the major challenges and perspectives in this field are presented. This work will provide guidance for the design of efficient fluorescent chemosensors to monitor plant health, and then promote sustainable agricultural development.

15.
Cell Death Dis ; 15(6): 389, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830896

RESUMO

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.


Assuntos
Colesterol , Fator 2 Relacionado a NF-E2 , Receptores de LDL , Animais , Receptores de LDL/metabolismo , Colesterol/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Camundongos Knockout , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Masculino , Aterosclerose/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas/genética , Humanos , Fígado/metabolismo , Apolipoproteínas E/metabolismo , Hiperlipidemias/metabolismo
16.
J Cardiothorac Surg ; 19(1): 318, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835049

RESUMO

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma.


Assuntos
Coristoma , Imageamento por Ressonância Magnética , Timoma , Neoplasias do Timo , Tomografia Computadorizada por Raios X , Humanos , Masculino , Pessoa de Meia-Idade , Timoma/cirurgia , Timoma/diagnóstico , Timoma/diagnóstico por imagem , Timoma/patologia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Coristoma/cirurgia , Coristoma/diagnóstico , Coristoma/patologia , Coristoma/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem
17.
Front Public Health ; 12: 1343915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873321

RESUMO

Background: Although epidemiological evidence implies a link between exposure to particulate matter (PM) and Alzheimer's disease (AD), establishing causality remains a complex endeavor. In the present study, we used Mendelian randomization (MR) as a robust analytical approach to explore the potential causal relationship between PM exposure and AD risk. We also explored the potential associations between PM exposure and other neurodegenerative diseases. Methods: Drawing on extensive genome-wide association studies related to PM exposure, we identified the instrumental variables linked to individual susceptibility to PM. Using summary statistics from five distinct neurodegenerative diseases, we conducted two-sample MR analyses to gauge the causal impact of PM on the risk of developing these diseases. Sensitivity analyses were undertaken to evaluate the robustness of our findings. Additionally, we executed multivariable MR (MVMR) to validate the significant causal associations identified in the two-sample MR analyses, by adjusting for potential confounding risk factors. Results: Our MR analysis identified a notable association between genetically predicted PM2.5 (PM with a diameter of 2.5 µm or less) exposure and an elevated risk of AD (odds ratio, 2.160; 95% confidence interval, 1.481 to 3.149; p < 0.001). A sensitivity analysis supported the robustness of the observed association, thus alleviating concerns related to pleiotropy. No discernible causal relationship was identified between PM and any other neurodegenerative diseases. MVMR analyses-adjusting for smoking, alcohol use, education, stroke, hearing loss, depression, and hypertension-confirmed a persistent causal relationship between PM2.5 and AD. Sensitivity analyses, including MR-Egger and weighted median analyses, also supported this causal association. Conclusion: The present MR study provides evidence to support a plausible causal connection between PM2.5 exposure and AD. The results emphasize the importance of contemplating air quality interventions as a public health strategy for reducing AD risk.


Assuntos
Doença de Alzheimer , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Material Particulado , Material Particulado/efeitos adversos , Humanos , Doença de Alzheimer/genética , Fatores de Risco , Exposição Ambiental/efeitos adversos , Causalidade , Poluição do Ar/efeitos adversos
18.
J Biol Chem ; : 107468, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876301

RESUMO

The nucleosome remodeling and deacetylase (NuRD) complex plays a pivotal role in chromatin regulation and transcriptional repression. In mice, methyl-CpG binding domain 3 isoform C (MBD3C) interacts specifically with the histone H3 binding protein WD repeat-containing protein 5 (WDR5) and forms the WDR5-MBD3C/NuRD complex. Despite the functional significance of this interaction on embryonic stem cells gene regulation, the molecular mechanism underlying MBD3C recognition by WDR5 remains elusive. Here, we determined the crystal structure of WDR5 in complex with the peptide (residues 40-51) derived from the MBD3C protein at a resolution of 1.9 Å. Structural analysis revealed that MBD3C utilizes a unique binding mode to interact with WDR5, wherein MBD3C Arg43 and Phe47 are involved in recognizing the WDR5-interacting (WIN) site and Tyr191-related B site on the small surface of WDR5, respectively. Notably, the binding induces a ∼91° rotation of WDR5 Tyr191, generating the hydrophobic B site. Furthermore, mutation experiments combined with isothermal titration calorimetry (ITC) assays confirmed the importance of both Arg43 and Phe47 in mediating WDR5 binding affinity. By determining structures of various peptides bound to WDR5, we demonstrated that the WDR5 WIN site and B site can be concurrently recognized by WIN motif peptides containing ''Arg-Cys/Ser-Arg-Val-Phe'' consensus sequence. Overall, this study reveals the structural basis for the formation of the WDR5-MBD3C subcomplex and provides new insights into the recognition mode of WDR5 for the WIN motif. Moreover, these findings shed light on structural-based designs of WDR5-targeted anti-cancer small molecule inhibitors or peptide-mimic drugs.

19.
Carbohydr Polym ; 341: 122320, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38876713

RESUMO

In an oil exploitation process, hydrogel plugging agents can effectively reduce the water-oil intermixing, decrease water extraction volume, and enhance oil recovery rate. The practical applications of traditional polyacrylamide (PAM) hydrogel plugging agents in oilfield are limited by their non-biodegradability, poor mechanical performance, and inferior temperature-resistance. This work developed a mechanically stable and high-temperature-resistant composite hydrogel (STP) by incorporating biodegradable scleroglucan (Slg) and TEMPO-oxidized cellulose nanofibers (TOCN) in the PAM hydrogel. The addition of Slg conferred heat resistance to the PAM hydrogel, while TOCN reinforced the mechanical strength. Anti-aging analyses revealed that the STP endured for 108 h in a saline environment at 140 °C. In the water flooding characterization, the STP displayed a breakthrough pressure of 42.10 psi/ft. at a flow rate of 0.75 cm3/min. Under these extreme conditions, the plugging pressure reached 14.74 psi/ft., meeting the essential criteria for oilfield water plugging. This research demonstrates the potential of polysaccharides in the preparation of sustainable, tough, and heat-resistant water plugging materials.

20.
Cell Rep ; 43(6): 114341, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878290

RESUMO

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when confronting reward uncertainty. However, it has been unclear whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider these attributes to make a choice. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes, and this population tended to integrate the attributes in a manner that reflected monkeys' preferences for amount, delay, and uncertainty. After decision-making, in response to post-decision feedback, these same neurons signaled signed reward prediction errors, suggesting a broader role in tracking value across task epochs and behavioral contexts. Our data illustrate how the DRN participates in value computations, guiding theories about the role of the DRN in decision-making and psychiatric disease.

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