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1.
Front Public Health ; 12: 1413772, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171305

RESUMEN

Background: The older adult migrant population in China is on the rise, which presents challenges for the national public health service system. However, the heterogeneity of public health service utilization and its relationship with social integration among the older adult migrant population remains unclear. This study aims to explore the heterogeneity the public health service utilization and how it relates to their social integration. Methods: A total of 6,178 older adult migrants from the China Migrants Dynamic Survey (CMDS) in 2017 were included in this study. Exploratory factor analysis was used to categorize social integration into four dimensions. Latent class analysis (LCA) was used to identify different sub-groups of public health service utilization. ANOVA and multivariate logistic regression were used to determine the characteristics of different sub-groups. Results: Three potential classes of public health service utilization were identified: low utilization of basic public health services class (N = 3,264,52.756%), medium utilization of basic public health services class (N = 1,743,28.172%), and high utilization of basic public health services class (N = 1,180,19.072%). Gender, education, extent of mobility, and move alone or not, flow time were all predictors of the class of public health service utilization. There were significant differences in social integration across potential categories (p<0.0001). Conclusion: The utilization of public health services of the older adult migrants is affected by many aspects. Social integration deserves attention as a significant influencing factor in the utilization of public health services. The government should pay attention to the characteristics of the older adult migrants and formulate relevant policies in a targeted manner in order to improve the utilization of public health services of the older adult migrants.


Asunto(s)
Análisis de Clases Latentes , Integración Social , Migrantes , Humanos , China , Femenino , Masculino , Migrantes/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Encuestas y Cuestionarios
2.
Mol Cell ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39173640

RESUMEN

Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein-coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of Sec61 (BOS) complex, a component of the multipass translocon, was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC⋅BOS holocomplex showed that characteristics of a GPCR's soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, the multipass translocon, and Sec61 for the biogenesis of diverse membrane proteins in human cells.

3.
Transl Pediatr ; 13(7): 1219-1230, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39144426

RESUMEN

Background: This study aimed to analyze the clinical features of children with lobar pneumonia caused by Mycoplasma pneumoniae (MP) infection, to explore the independent risk factors for bronchoscopic intervention in children with lobar pneumonia caused by MP infection. There is a lack of objective assessment tools to guide the use of bronchoscopy in clinical practice. For children with lobar pneumonia caused by MP infection, whether line shall be actively bronchoscope intervention therapy remains to be further defined. We also aimed to construct an early warning model of bronchoscopic intervention to provide an objective evaluation tool for clinicians. Methods: We collected the clinical data of 533 children with lobar pneumonia caused by MP infection. The patients were divided into three groups according to the interventional indications for bronchoscopy and whether they were treated with bronchoscopic intervention, and the clinical features and prognosis of the three groups were compared. A binary logistic regression analysis was performed on the indicators with a significance value of P<0.05, which we retrieved from the comparative analysis between the first two groups to uncover the independent risk factors and regression equations concerning bronchoscopic intervention. The regression coefficient (ß) of our regression model was then used to score related values in the model to construct a predictive scoring model of bronchoscopic intervention for the treatment of children with lobar pneumonia caused by MP infection. Results: Children with lobar pneumonia caused by MP infection who demonstrated absolute indications for bronchoscopy exhibited more severe clinical manifestations, and children without absolute indications for bronchoscopy had a better prognosis even without bronchoscopic intervention. To establish our early warning model of bronchoscopic intervention for children with lobar pneumonia caused by MP infection, we used the following indices: C-reactive protein ≥20.94 mg/L (ß1=2.253) received 3 points, while a fever duration before bronchoscopy ≥6.5 d (ß2=1.424), lactate dehydrogenase ≥461.5 U/L (ß3=1.246), or fever (ß4=1.223) each received 2 points, and the complication of pleural effusion (ß5=0.841) received 1 point, for a total possible score of 10 points. Conclusions: When the score for the children with lobar pneumonia caused by MP infection was ≥6, the possibility of bronchoscopic intervention for treatment was >80%. The higher the score, the greater the possibility of bronchoscopic intervention.

4.
Adv Mater ; : e2406636, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148152

RESUMEN

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.

5.
Front Chem ; 12: 1400886, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39176072

RESUMEN

Introduction: In clinical practice, phosphodiesterase 5 (PDE5) inhibitors are commonly used to treat erectile dysfunction and pulmonary arterial hypertension. However, due to the high structural similarity between PDE5 and Phosphodiesterase 6 (PDE6), there is a risk that existing drugs will cause off-target effects on PDE6 resulting in visual disorders such as low visual acuity and color blindness. Previous research on the selectivity of PDE5 inhibitors focused on marketed drugs such as sildenafil and tadalafil. Methods: In this study, a highly selective PDE5 inhibitor, ligand3, was used as the subject, and molecular docking, molecular dynamics simulations, MM-GBSA, alanine scanning, and independent gradient model analysis were employed to investigate the biological mechanism underlying the selectivity of PDE5 inhibitors. Results and Discussion: The present work revealed that the binding mode of ligand3 to the PDE5A and PDE6C targets was distinctly different. Ligand3 exhibited stronger coulombic forces when binding to PDE5A, while showing stronger van der waals forces when binding to PDE6C. Ligand3 binds more deeply at the active site of PDE5A than at PDE6C, allowing its side chains to effectively bind to the critical TYR612, whereas in the case of the shallow binding to PDE6C, ligand3 lacks a similar effect. Mechanism investigations of highly selective inhibitors through computational simulation might provide an insight into potent treatment of drugs.

6.
Front Psychiatry ; 15: 1432792, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39176225

RESUMEN

Background: Depression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field. Methods: We retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps. Results: A total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as "Default Mode Network," "Functional Connectivity," and "Theta Burst" have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels. Conclusion: In recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

7.
Biosens Bioelectron ; 263: 116636, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39116631

RESUMEN

The clinical diagnosis of pathogen infectious diseases increasingly requires sensitive and rapid RNA detection technologies. The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system has shown immense potential in molecular diagnostics due to its trans-cleavage activity. However, most Cas13a-based detection methods require an amplicon transcription step, and the multi-step open-tube operations are prone to contamination, limiting their widespread application. Here, we propose an ultrasensitive (single-copy range, ∼aM) and rapid (within 40 min) isothermal one-pot RNA detection platform, termed SATCAS (Simultaneous Amplification and Testing platform based on Cas13a). This method effectively distinguishes viable bacteria (0%-100%) under constant total bacterial conditions, demonstrating its robustness and universality. SATCAS excels in identifying single nucleotide polymorphisms (SNPs), particularly detecting 0.5% drug-resistant mutations. We validated SATCAS by detecting infections in biological samples from 68 HBV, 23 EBV, and 48 SARS-CoV-2 patients, achieving 100% sensitivity, 92.86% specificity, and 97.06% accuracy in HBV infection testing. We anticipate that SATCAS has broad application potential in the early diagnosis, subtyping, drug resistance detection, and point-of-care monitoring of pathogen infectious diseases.


Asunto(s)
Técnicas Biosensibles , Sistemas CRISPR-Cas , Técnicas de Amplificación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , Técnicas Biosensibles/métodos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , COVID-19/diagnóstico , COVID-19/virología , ARN Viral/genética , Técnicas de Diagnóstico Molecular/métodos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación
9.
Cell Biol Int ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164961

RESUMEN

The soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) is an α/ß hydrolase fold protein that is, widely distributed throughout the body. Recent studies have highlighted that sEH, in the metabolism of polyunsaturated fatty acids, plays a part in the pathogenesis of various diseases, including cardiovascular disease, Alzheimer's disease and intestine-associated disease. This review discusses the current findings on the role of sEH in the development of intestine- and intestine-associated diseases, including colitis, colorectal cancer, and other intestinal diseases, as well as the potential underlying mechanisms involved.

10.
Microbiol Spectr ; : e0114924, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120142

RESUMEN

Sugarcane yellow leaf virus (SCYLV) can reduce sugarcane productivity. A novel detection system based on reverse transcription-multienzyme isothermal rapid amplification (RT-MIRA) combined with CRISPR-Cas12a, named RT-MIRA-CRISPR-Cas12a, was developed. This innovative approach employs crude leaf extract directly as the reaction template, streamlining the extraction process for simplicity and speed. Combining RT-MIRA and CRISPR-Cas12a in one reaction tube increases the ease of operation while reducing the risk of aerosol contamination. In addition, it exhibits sensitivity equivalent to qPCR, boasting a lower detection limit of 25 copies. Remarkably, the entire process, from sample extraction to reaction completion, requires only 52-57 minutes, just a thermostat water bath. The result can be observed and judged by the naked eye.IMPORTANCESugarcane yellow leaf disease (SCYLD) is an important viral disease that affects sugarcane yield. There is an urgent need for rapid, sensitive, and stable detection methods. The reverse transcription-multienzyme isothermal rapid amplification combined with CRISPR-Cas12a (RT-MIRA-CRISPR-Cas12a) method established in this study has good specificity and high sensitivity. In addition, the system showed good compatibility and stability with the crude leaf extract, as shown by the fact that the crude extract of the positive sample could still be stably detected after 1 week when placed at 4°C. RT-MIRA-CRISPR-Cas12a, reverse transcription polymerase chain reaction (RT-PCR), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect SCYLV on 33 sugarcane leaf samples collected from the field, and it was found that the three methods reached consistent conclusions. This Cas12a-based detection method proves highly suitable for the rapid on-site detection of the SCYLV.

11.
Cell Rep ; 43(8): 114558, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39088321

RESUMEN

Chromatin priming promotes cell-type-specific gene expression, lineage differentiation, and development. The mechanism of chromatin priming has not been fully understood. Here, we report that mouse hematopoietic stem and progenitor cells (HSPCs) lacking the Baf155 subunit of the BAF (BRG1/BRM-associated factor) chromatin remodeling complex produce a significantly reduced number of mature blood cells, leading to a failure of hematopoietic regeneration upon transplantation and 5-fluorouracil (5-FU) injury. Baf155-deficient HSPCs generate particularly fewer neutrophils, B cells, and CD8+ T cells at homeostasis, supporting a more immune-suppressive tumor microenvironment and enhanced tumor growth. Single-nucleus multiomics analysis reveals that Baf155-deficient HSPCs fail to establish accessible chromatin in selected regions that are enriched for putative enhancers and binding motifs of hematopoietic lineage transcription factors. Our study provides a fundamental mechanistic understanding of the role of Baf155 in hematopoietic lineage chromatin priming and the functional consequences of Baf155 deficiency in regeneration and tumor immunity.

12.
Cancer ; 130(S17): 3054-3066, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39092590

RESUMEN

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.


Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados
13.
Nanomicro Lett ; 16(1): 273, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39147921

RESUMEN

Defect engineering in transition metal oxides semiconductors (TMOs) is attracting considerable interest due to its potential to enhance conductivity by intentionally introducing defects that modulate the electronic structures of the materials. However, achieving a comprehensive understanding of the relationship between micro-structures and electromagnetic wave absorption capabilities remains elusive, posing a substantial challenge to the advancement of TMOs absorbers. The current research describes a process for the deposition of a MoO3 layer onto SiC nanowires, achieved via electro-deposition followed by high-temperature calcination. Subsequently, intentional creation of oxygen vacancies within the MoO3 layer was carried out, facilitating the precise adjustment of electromagnetic properties to enhance the microwave absorption performance of the material. Remarkably, the SiC@MO-t4 sample exhibited an excellent minimum reflection loss of - 50.49 dB at a matching thickness of 1.27 mm. Furthermore, the SiC@MO-t6 sample exhibited an effective absorption bandwidth of 8.72 GHz with a thickness of 2.81 mm, comprehensively covering the entire Ku band. These results not only highlight the pivotal role of defect engineering in the nuanced adjustment of electromagnetic properties but also provide valuable insight for the application of defect engineering methods in broadening the spectrum of electromagnetic wave absor ption effectiveness. SiC@MO-t samples with varying concentrations of oxygen vacancies were prepared through in-situ etching of the SiC@MoO3 nanocomposite. The presence of oxygen vacancies plays a crucial role in adjusting the band gap and local electron distribution, which in turn enhances conductivity loss and induced polarization loss capacity. This finding reveals a novel strategy for improving the absorption properties of electromagnetic waves through defect engineering.

14.
J Glob Health ; 14: 04127, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149826

RESUMEN

Background: The increasing prevalence of depressive symptoms has emerged as a critical public health issue globally, highlighting the need for analyses of the factors contributing to depressive symptoms within the Chinese population and the development of targeted recommendations for improving mental well-being. We aimed to explore the correlation between internet use and depressive symptoms and the role of socioeconomic inequalities in this association. Methods: We included data on 8019 residents aged 18 years and above, which we retrieved from the 2018 and 2020 waves of the China Family Panel Studies. We used latent profile analysis to categorise individuals' internet usage patterns and multiple linear regression to determine their association with depressive symptoms. Results: Higher socioeconomic status (SES) was associated with fewer depressive symptoms (τ = -0.08; 95% confidence interval (CI) = -0.36, -0.18). Individuals in the high-dependence group presented a greater likelihood of developing depressive symptoms (τ = 0.04; 95% CI = 0.007, 0.66). We observed no significant difference in the interaction effect between individual-level SES and the four patterns of internet usage. However, compared with urban-dwelling respondents, those in rural areas had a stronger association between internet usage patterns and depressive symptoms, especially those in the high-dependence group (τ = -0.07; 95% CI = -1.47, -0.20). Conclusions: Our findings indicate a significant association between depressive symptoms and internet usage patterns, indicating a need for interventions related to internet use, especially those targeted at reducing the risk of depressive symptoms in individuals of lower SES.


Asunto(s)
Depresión , Uso de Internet , Factores Socioeconómicos , Humanos , Masculino , Femenino , China/epidemiología , Depresión/epidemiología , Adulto , Persona de Mediana Edad , Estudios Longitudinales , Adulto Joven , Uso de Internet/estadística & datos numéricos , Adolescente , Clase Social , Internet/estadística & datos numéricos , Anciano , Pueblos del Este de Asia
15.
J Food Sci ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150698

RESUMEN

Roasting is essential for developing the characteristic aroma of flaxseed oil (FSO), yet its impact on oil quality remains underexplored. This study employed headspace-gas chromatography-mass spectrometry coupled with multivariate analysis to elucidate the dynamic changes in volatile compounds and quality characteristics of FSO subjected to varying roasting temperatures. Our findings revealed that seven key aroma compounds, identified through the variable importance in the projection scores of partial least square-discrimination analysis models and relative aroma activity value, served as molecular markers indicative of distinct roasting temperatures. These compounds included 2,5-dimethylpyrazine, 2-pentylfuran, (E)-2-pentenal, 2-ethyl-3,6-dimethylpyrazine, heptanal, octanal, and 2-hexenal. Notably, roasting at 200°C was found to enhance oil stability and antioxidant capacity, with phenolic compounds and Maillard reaction products playing synergistic roles in bolstering these qualities. Network analysis further uncovered significant correlations between these key aroma compounds and quality characteristics, offering novel perspectives for assessing FSO quality under diverse roasting conditions. This research not only enriched our understanding of the roasting process's impact on FSO but also provided valuable guidance for the optimization of industrial roasting practices. This study would provide important practical applications in aroma regulation and process optimization of flaxseed oil. .

16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(8): 957-961, 2024 Aug 10.
Artículo en Chino | MEDLINE | ID: mdl-39097279

RESUMEN

OBJECTIVE: To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome. METHODS: A pregnant woman who had visited Suzhou Municipal Hospital on February 26, 2021 was selected as the study subject. The fetus and her parents were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. cDNA analysis of her father and RNA sequencing of her sister were also carried out. RESULTS: The fetus was found to harbor compound heterozygous variants of the TCTN1 gene, namely c.624G>A and c.96dupA (p.Glu33Argfs*49), which were inherited from her father and mother, respectively. Her sister also carried the paternal c.624G>A variant, and mRNA transcripts with the c.624G>A variant of the TCTN1 gene were not detected by cDNA analysis of her father and RNA sequencing of her sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.624G>A and c.96dupA variants were both classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The compound heterozygous variants of the TCTN1 gene probably underlay the pathogenesis in this fetus. Above finding has also expanded the mutational spectrum of the TCTN1 gene.


Asunto(s)
Anomalías Múltiples , Cerebelo , Anomalías del Ojo , Feto , Enfermedades Renales Quísticas , Adulto , Femenino , Humanos , Masculino , Embarazo , Anomalías Múltiples/genética , Cerebelo/anomalías , Secuenciación del Exoma , Anomalías del Ojo/genética , Feto/anomalías , Heterocigoto , Enfermedades Renales Quísticas/genética , Proteínas de la Membrana/genética , Mutación , Retina/anomalías , Diagnóstico Prenatal
17.
Chem Sci ; 15(32): 13082-13089, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39148792

RESUMEN

Abnormal copper ion (Cu2+) levels are considered to be one of the pathological factors of Parkinson's disease (PD), but the internal relationship between Cu2+ and PD progression remains elusive. Visualizing Cu2+ in the brain will be pivotal for comprehending the underlying pathophysiological processes of PD. In this work, a near-infrared (NIR) fluorescent probe, DDAO-Cu, capable of detecting Cu2+ with exceptional sensitivity (about 1.8 nM of detection limit) and selectivity, rapid response (<3 min), and deep tissue penetration, was designed for quantification and visualization of the Cu2+ level. It could detect not only Cu2+ in cells but also the changes in the Cu2+ level in the rotenone-induced cell and zebrafish PD models. Moreover, DDAO-Cu can cross the blood-brain barrier to image Cu2+ in the brain of PD model mice. The imaging result showed a significant increase in Cu2+ levels in brain regions of PD model mice, including the cerebral cortex, hippocampus, and striatum. Meanwhile, Cu2+ levels in the substantia nigra region were significantly reduced in PD model mice. It revealed the nuanced relationship of Cu2+ levels in different brain regions in the disease and indicated the pathological complexity of PD. Overall, DDAO-Cu represents a novel and practical tool for investigating Cu2+-related physiological and pathological processes underlying Parkinson's disease.

18.
Adv Sci (Weinh) ; : e2309754, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162106

RESUMEN

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast-specific knock-in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK-49F cells suppresses the pro-fibrotic response induced by transforming growth factor-ß1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer-aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.

19.
Langmuir ; 40(33): 17786-17795, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39120944

RESUMEN

Exploring nucleation pathways has been a research hot spot in the fields of crystal engineering. In this work, vanillin as a model compound was utilized to explore the factors influencing different nucleation pathways with or without liquid-liquid phase separation (LLPS). A thermodynamic phase diagram of vanillin in the mixed solvent system of water and acetone from 10 to 55 °C was determined. It was found that the occurrence of LLPS might be related to different nucleation pathways. Under the guidance of a thermodynamic phase diagram, Raman spectroscopy and molecular simulation were applied to investigate the influencing factors of different nucleation paths. It was found that the degree of solvation is a key factor determining the nucleation path, and strong solvation could lead to LLPS. Additionally, the molecular self-assembly evolution during the crystallization process was further investigated by using small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The findings indicate that larger clusters with a diffuse transition layer may lead to LLPS during the nucleation process.

20.
Vet Microbiol ; 298: 110225, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154555

RESUMEN

Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that can cause diarrhea in pigs of all ages with varying severity. Host-virus protein interactions are critical for intracellular viral replication. Elucidating the interactions between cellular and viral proteins can help us to design antiviral strategies. PDCoV N protein is the most abundant and vital regulator in virus replication. In this study, 604 host proteins were identified to interact with PDCoV N protein by Co-IP combined with LC-MS, of which 243 proteins were specifically bound to N protein. PPI analysis revealed that the N-interacting host proteins are categorized into three groups: ribonucleoprotein complex biogenesis modulation, cellular nitrogen compound metabolism, and nucleic acid binding. GO and KEGG analyses showed that the host proteins are primarily involved in mRNA splicing, stress granule assembly, spliceosomal snRNP assembly. Additionally, four host proteins-TRIM25, HNRNPUL1, RPS27A, and SLC3A2-were selected to validate the interactome data through Co-IP and Confocal assays. This study can help in designing anti-PDCoV strategies and understanding the replication mechanism of PDCoV.

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