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1.
Heliyon ; 10(12): e32695, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39183826

RESUMEN

This paper uses panel data of 260 prefecture-level cities from 2000 to 2019 to explore spatial characteristics such as spatiotemporal divergence and dynamic convergence based on measuring the level of human capital misallocation in Chinese cities and empirically tests the green development effect of human capital misallocation. The study finds that: ① the human capital misallocation levels of the country and the eight major urban agglomerations show a fluctuating downward trend. ② Divergences in human capital misallocation continue to narrow across the country and urban agglomerations, and the difference between inter-urban agglomerations is the primary source of regional difference. ③ The YRD, PRD, MYR, HC, and CP have significant σ-convergence characteristics of human capital misallocation. Meanwhile, the country and each urban agglomeration show significant spatial absolute ß-convergence and conditional ß-convergence trends. ④ Human capital misallocation significantly negatively affects green economic efficiency, inhibiting green economy efficiency. Therefore, in the future, it is necessary to improve the match between regional industrial structure and human capital allocation through a combination of targeted policy guidance and market mechanisms tailored to local conditions to enhance the efficiency of the green economy. The significance of the study lies in accelerating the accumulation of human capital while realizing the appropriate matching of human capital, releasing the human capital dividend to the maximum extent, and boosting the structural reform of the labor market to realize the transformation of the green economy.

2.
Nutr Res Pract ; 18(4): 511-522, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109204

RESUMEN

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the 'H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project' among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 µmol/L, which was significantly higher than the non-diabetic patients (18.18 µmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01-1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22-6.69) in the highest quintile (tHcy ≥ 20.60 µmol/L) compared to the reference group (tHcy < 12.04 µmol/L). When tHcy was grouped by 15 µmol/L and 20 µmol/L, patients with tHcy ≥ 20 µmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04-3.96) than in those with tHcy < 15 µmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION: In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

3.
Front Psychol ; 15: 1448827, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144605

RESUMEN

Introduction: This study aims to investigate whether exercise adherence and positive mental character significantly affect subjective well-being among Chinese college students during the COVID-19 pandemic and whether positive mental character plays a mediating role. Methods: The study employed questionnaires, including the Exercise Adherence Scale, the Positive Mental Character Scale, and the Subjective Well-Being Scale, which were administered to students across seven universities in Henan Province, China. A total of 1,001 participants were analyzed in the final sample. Data were analyzed using SPSS 21.0 for descriptive statistics, independent samples T-test, correlation, and regression analyses. Furthermore, structural equation model with AMOS was conducted to examine the potential mediating effect of positive mental characteristics on the relationship between exercise adherence and subjective well-being. Results: The results indicated significant differences in exercise adherence, positive mental character, and subjective well-being between male and female participants, with males scoring higher in all three domains. Among Chinese university students during the COVID-19 pandemic, there was a significant correlation among exercise adherence, positive mental character, and subjective well-being. Exercise adherence was found to have a significant and positive impact on both positive mental character and subjective well-being. Additionally, it was found that positive mental character had a significant positive association with subjective well-being. The mediating role of positive mental character in the relationship between exercise adherence and subjective well-being was partially supported. Discussion: Exercise adherence among Chinese college students had a significant positive association on both positive mental character and subjective well-being throughout the COVID-19 pandemic. The exercise adherence can directly or indirectly enhance subjective well-being through its association with positive mental character. Therefore, positive mental and subjective well-being can be enhanced by consistent physical activity even during a pandemic.

4.
Emerg Microbes Infect ; 13(1): 2369193, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38873898

RESUMEN

The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after COVID-19. The mRNA cap N7 methyltransferase (RNMT) of MPXV methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs and plays a vital role in evading host antiviral immunity. MPXV RNMT is composed of the large subunit E1 and the small subunit E12. How E1 and E12 of MPXV assembly remains unclear. Here, we report the crystal structures of E12, the MTase domain of E1 with E12 (E1CTD-E12) complex, and the E1CTD-E12-SAM ternary complex, revealing the detailed conformations of critical residues and the structural changes upon E12 binding to E1. Functional studies suggest that E1CTD N-terminal extension (Asp545-Arg562) and the small subunit E12 play an essential role in the binding process of SAM. Structural comparison of the AlphaFold2-predicted E1, E1CTD-E12 complex, and the homologous D1-D12 complex of vaccinia virus (VACV) indicates an allosteric activating effect of E1 in MPXV. Our findings provide the structural basis for the MTase activity stimulation of the E1-E12 complex and suggest a potential interface for screening the anti-poxvirus inhibitors.


Asunto(s)
Metiltransferasas , Monkeypox virus , Metiltransferasas/química , Metiltransferasas/metabolismo , Metiltransferasas/genética , Monkeypox virus/genética , Monkeypox virus/enzimología , Monkeypox virus/química , Proteínas Virales/química , Proteínas Virales/genética , Proteínas Virales/metabolismo , Cristalografía por Rayos X , Caperuzas de ARN/metabolismo , Caperuzas de ARN/química , Modelos Moleculares , Humanos , Conformación Proteica , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/química
5.
Front Immunol ; 15: 1380982, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915416

RESUMEN

Introduction: Viral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach. Methods: We utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry. We applied inverse variance weighting, MR Egger, and weighted median methods to infer causality. We performed sensitivity analysis using the "leave-one-out" method to verify robustness. Results: We found no evidence of a causal association between gene-predicted COVID-19 and laryngeal cancer [Odds ratio (OR)=0.24 (95% Confidence intervals (CI), 0.05-1.26), P=0.09]. However, we observed significant inverse associations between gene-predicted COVID-19 hospitalization [OR=0.51 (95% CI, 0.28-0.95), P=0.03] and severe patients [OR=0.62 (95% CI, 0.43-0.90), P=0.01] and laryngeal cancer. Notably, the study detected important genetic variants, such as rs13050728, that modulate the expression of interferon alpha receptor 2 (IFNAR2), indicating possible roles for immune response pathways in both COVID-19 and cancer. Discussion: This study reveals a potential interaction between COVID-19 severity, genetic factors, and laryngeal cancer, underscoring the importance of investigating the immune response mechanisms in both conditions. These findings contribute to the understanding of the complex interactions between COVID-19 and laryngeal cancer and may guide future research on the role of immune response, particularly involving IFNAR2.


Asunto(s)
COVID-19 , Estudio de Asociación del Genoma Completo , Neoplasias Laríngeas , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/inmunología , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/virología , Neoplasias Laríngeas/inmunología , SARS-CoV-2/fisiología , Predisposición Genética a la Enfermedad , Factores de Riesgo
6.
Molecules ; 29(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38731549

RESUMEN

Targeting translation factor proteins holds promise for developing innovative anti-tuberculosis drugs. During protein translation, many factors cause ribosomes to stall at messenger RNA (mRNA). To maintain protein homeostasis, bacteria have evolved various ribosome rescue mechanisms, including the predominant trans-translation process, to release stalled ribosomes and remove aberrant mRNAs. The rescue systems require the participation of translation elongation factor proteins (EFs) and are essential for bacterial physiology and reproduction. However, they disappear during eukaryotic evolution, which makes the essential proteins and translation elongation factors promising antimicrobial drug targets. Here, we review the structural and molecular mechanisms of the translation elongation factors EF-Tu, EF-Ts, and EF-G, which play essential roles in the normal translation and ribosome rescue mechanisms of Mycobacterium tuberculosis (Mtb). We also briefly describe the structure-based, computer-assisted study of anti-tuberculosis drugs.


Asunto(s)
Proteínas Bacterianas , Mycobacterium tuberculosis , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Biosíntesis de Proteínas , Factores de Elongación de Péptidos/metabolismo , Factores de Elongación de Péptidos/química , Factores de Elongación de Péptidos/genética , Antituberculosos/farmacología , Antituberculosos/química , Ribosomas/metabolismo , Modelos Moleculares , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/metabolismo , Conformación Proteica
7.
Talanta ; 275: 126151, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38678927

RESUMEN

This article discusses the importance of early tumor detection, particularly in liver cancer, and the role of leucine aminopeptidase (LAP) as a potential marker for liver cancer diagnosis and prognosis assessment. The article highlights the limitations of current tumor markers and the need for new markers and multi-marker approaches to improve accuracy. The authors introduce a novel near-infrared fluorescent probe, NTAP, designed for LAP detection. They describe the synthesis of the probe and evaluate its spectral properties, including the LOD was 0.0038 U/mL, and QY was 0.32 %. The kinetic properties of NTAP, such as the relationship between LAP concentration (0-0.08 U/mL), reaction time (3 min), and fluorescence excitation spectra (475 nm) and emission spectra (715 nm) are investigated. The article also discusses the stability and selectivity of the probe and its ability to detect LAP in complex samples. Cellular imaging experiments demonstrate the NATP specificity and selectivity in detecting LAP activity and its inhibition. Animal models of liver and lung metastasis are used to evaluate the probe's imaging capabilities, showing its ability to accurately locate and detect metastatic lesions. The article concludes by emphasizing the potential applications of the NTAP probe in early tumor diagnosis, treatment monitoring, and the study of tumor metastasis mechanisms.


Asunto(s)
Colorantes Fluorescentes , Leucil Aminopeptidasa , Metástasis de la Neoplasia , Animales , Humanos , Ratones , Progresión de la Enfermedad , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Rayos Infrarrojos , Leucil Aminopeptidasa/metabolismo , Leucil Aminopeptidasa/análisis , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Imagen Óptica
8.
ACS Nano ; 18(12): 8600-8625, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38469753

RESUMEN

Accurately controlling magnetic and spin states presents a significant challenge in spintronics, especially as demands for higher data storage density and increased processing speeds grow. Approaches such as light control are gradually supplanting traditional magnetic field methods. Traditionally, the modulation of magnetism was predominantly achieved through polarized light with the help of ultrafast light technologies. With the growing demand for energy efficiency and multifunctionality in spintronic devices, integrating photovoltaic materials into magnetoelectric systems has introduced more physical effects. This development suggests that sunlight will play an increasingly pivotal role in manipulating spin orientation in the future. This review introduces and concludes the influence of various light types on magnetism, exploring mechanisms such as magneto-optical (MO) effects, light-induced magnetic phase transitions, and spin photovoltaic effects. This review briefly summarizes recent advancements in the light control of magnetism, especially sunlight, and their potential applications, providing an optimistic perspective on future research directions in this area.

9.
Sci Total Environ ; 926: 172106, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38556015

RESUMEN

Sewage sludge land application is recognized as a strategy for recycling resource and replenishing soil nutrients. However, the subsequent greenhouse gas emissions following this practice are not yet fully understood, and the lack of quantitative research and field experiments monitoring these emissions hampers the establishment of reliable emission factors. This study investigated the greenhouse gas emission characteristics of sewage sludge land application through a field experiment that monitoring soil greenhouse gas fluxes. Seven nitrogen input treatments were implemented in a typical Bermuda grassland in China, with D and C representing the amendment of digested and composted sludge, respectively, at the nitrogen input rate of 0, 100, 200, and 300 kg N ha-1. Soil CH4, CO2, and N2O fluxes were measured throughout the entire experimental period, and soil samples from different treatments at various growth stages were analyzed. The results revealed that sewage sludge land application significantly increased soil N2O and CO2 emissions while slightly reducing soil CH4 uptake. The increased CO2 emissions were biogenic and carbon-neutral, mainly due to enhanced plant root respiration. The N2O emissions were the primary greenhouse gas emissions of sewage sludge land application, which were mainly concentrated in two 50-day periods following base and topdressing fertilization, respectively. N2O emissions following base fertilization by rotary tillage were substantially lower than those following topdressing fertilization. A logarithmic response relationship between N input rates and increased soil N2O emissions was observed, suggesting lower N2O emissions from sewage sludge land application compared to conventional N fertilizers at the same N input level. Future field experiments and meta-analysis are necessary to develop reliable greenhouse gas emission factors for sewage sludge land application.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38414718

RESUMEN

Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.


Asunto(s)
Neutrófilos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Monocitos , Eosinófilos , Estudios Retrospectivos , Linfocitos , Biomarcadores , Pronóstico , Proteína C-Reactiva/análisis
11.
Nano Lett ; 24(10): 3082-3088, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38416583

RESUMEN

The translational and rotational dynamics of anisotropic optical nanoprobes revealed in single particle tracking (SPT) experiments offer molecular-level information about cellular activities. Here, we report an automated high-speed multidimensional SPT system integrated with a deep learning algorithm for tracking the 3D orientation of anisotropic gold nanoparticle probes in living cells with high localization precision (<10 nm) and temporal resolution (0.9 ms), overcoming the limitations of rotational tracking under low signal-to-noise ratio (S/N) conditions. This method can resolve the azimuth (0°-360°) and polar angles (0°-90°) with errors of less than 2° on the experimental and simulated data under S/N of ∼4. Even when the S/N approaches the limit of 1, this method still maintains better robustness and noise resistance than the conventional pattern matching methods. The usefulness of this multidimensional SPT system has been demonstrated with a study of the motions of cargos transported along the microtubules within living cells.


Asunto(s)
Aprendizaje Profundo , Nanopartículas del Metal , Imagen Individual de Molécula , Oro , Transporte Biológico
12.
iScience ; 27(2): 108926, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38357670

RESUMEN

The molecular mechanism of ibrutinib-induced atrial fibrillation (AF) remains unclear. We here demonstrate that treating rats with ibrutinib for 4 weeks resulted in the development of inducible AF, left atrial enlargement, atrial fibrosis, and downregulation of connexin expression, which were associated with C-terminal Src kinase (CSK) inhibition and Src activation. Ibrutinib upregulated angiotensin-converting enzyme (ACE) protein expression in human pulmonary microvascular endothelial cells (HPMECs) by inhibiting the PI3K-AKT pathway, subsequently increasing circulating angiotensin II (Ang II) levels. However, the expression of ACE and Ang II in the left atria was not affected. Importantly, we observed that perindopril significantly mitigated ibrutinib-induced left atrial remodeling and AF promotion by inhibiting the activation of the ACE and its downstream CSK-Src signaling pathway. These findings indicate that the Ibrutinib-induced activation of the ACE contributes to AF development and could serve as a novel target for potential prevention strategies.

13.
Sci Total Environ ; 918: 170653, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38331294

RESUMEN

The capacity of microplastics to harbor and propagate bacteria has been the focus of attention over the last decade. Such microplastic-supported bacterial colonization behavior in the municipal sewer system could be a critical ecological link influencing the biogeochemical activities and risks in receiving waters in urban areas, given the alarming microplastic loads discharged there. This study conducted a large-scale survey covering a wide range of residential and industrial catchments in Shanghai, China. We aimed to assess the microplastic prevalence and bacterial colonization patterns in different sewer habitats and to explore the role of land use, stratified wastewater and sediment, and microplastic attributes in shaping the patterns. We found that the sewer system formed a temporal but pronounced microplastic pool, with land use playing a significant role in the variability of microplastic prevalence. Industrial sewers contained a high abundance of microplastics with large particle sizes, diverse polymer compositions, and shapes. However, while there was a spatial discrepancy between urban and suburban areas in the abundance of microplastics in residential sewers, their predominant polymer and shape types were simple, i.e., polyethylene terephthalate (PET) and fibers. Sewer habitat characteristics, particularly the stratified wastewater and sediment determined microbial colonization patterns. The latter acted as a long-term sink for microplastics and supported the high growth of colonizers. In contrast, the wastewater plastisphere presented novel niches, hosting communities with a marked proportion of unique bacterial genera after colonization. Besides, statistics showed a highly positive and dense co-occurrence network of the plastisphere communities, especially those from the industrial sewer sediment, with enhanced metabolic activity, cellular processes and systems, and increased human pathogenic potential. Findings indicated a coarse and uncertain effect of the selective pressure of microplastic attributes on plastisphere community structure differentiation.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Humanos , Plásticos , Aguas Residuales , Prevalencia , Contaminantes Químicos del Agua/análisis , China , Ecosistema , Bacterias , Monitoreo del Ambiente
14.
Sci Rep ; 14(1): 153, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168479

RESUMEN

Mycoplasma pneumoniae pneumonia (MPP) often overlaps with the clinical manifestations and chest imaging manifestations of other types of community-acquired pneumonia (CAP). We retrospectively analyzed the clinical and imaging data of a group of patients with CAP, summarized their clinical and imaging characteristics, and discussed the diagnostic significance of their certain HRCT findings. The HRCT findings of CAP researched in our study included tree-in-bud sign (TIB), ground-glass opacity (GGO), tree fog sign (TIB + GGO), bronchial wall thickening, air-bronchogram, pleural effusion and cavity. The HRCT findings of all cases were analyzed. Among the 200 cases of MPP, 174 cases showed the TIB, 193 showed the GGO, 175 showed the tree fog sign, 181 lacked air-bronchogram. In case taking the tree fog sign and lack of air-bronchogram simultaneously as an index to distinguish MPP from OCAP, the sensitivity was 87.5%, the specificity was 97.5%, the accuracy was 92.5%. This study showed that that specific HRCT findings could be used to distinguish MPP from OCAP. The combined HRCT findings including the tree fog sign and lacked air-bronchogram simultaneously would contribute to a more accurate diagnosis of MPP.


Asunto(s)
Infecciones Comunitarias Adquiridas , Derrame Pleural , Neumonía por Mycoplasma , Adulto , Humanos , Neumonía por Mycoplasma/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Pandemias , Pulmón
15.
Chem Res Toxicol ; 37(1): 57-71, 2024 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-38177062

RESUMEN

Epimedii Folium (EF) is a botanical dietary supplement to benefit immunity. Baohuoside I (BI), a prenylated flavonoid derived from EF, has exhibited the cholestatic risk before. Here, the mechanism of BI on the stability and membrane localization of liver MRP2, a bile acid exporter in the canalicular membrane of hepatocytes, was investigated. The fluorescent substrate of MRP2, CMFDA was accumulated in sandwich-cultured primary mouse hepatocytes (SCH) under BI stimulation, followed by reduced membrane MRP2 expression. BI triggered MRP2 endocytosis associated with oxidative stress via inhibition of the NRF2 signaling pathway. Meanwhile, BI promoted the degradation of MRP2 by reducing its SUMOylation and enhancing its ubiquitination level. Co-IP and fluorescence colocalization experiments all proved that MRP2 was a substrate protein for SUMOylation for SUMO proteins. CHX assays showed that SUMO1 prolonged the half-life of MRP2 and further increased its membrane expression, which could be reversed by UBC9 knockdown. Correspondingly, MRP2 accumulated in the cytoplasm by GP78 knockdown or under MG132 treatment. Additionally, the SUMOylation sites of MRP2 were predicted by the algorithm, and a conversion of lysines to arginines at positions 940 and 953 of human MRP2 caused its decreased stability and membrane location. K940 was further identified as the essential ubiquitination site for MRP2 by an in vitro ubiquitination assay. Moreover, the decreased ubiquitination of MRP2 enhanced the SUMOylation MRP2 and vice versa, and the crosstalk of these two modifiers could be disrupted by BI. Collectively, our findings indicated the process of MRP2 turnover from the membrane to cytoplasm at the post-translational level and further elucidated the novel toxicological mechanism of BI.


Asunto(s)
Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Sumoilación , Ratones , Animales , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Hepatocitos/metabolismo , Flavonoides/metabolismo , Ubiquitinación
16.
Anal Chem ; 96(6): 2500-2505, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38252963

RESUMEN

Understanding the host-guest interactions in porous materials is of great importance in the field of separation science. Probing it at the single-molecule level uncovers the inter- and intraparticle inhomogeneity and establishes structure-property relationships for guiding the design of porous materials for better separation performance. In this work, we investigated the dynamics of host-guest interactions in core-shell mesoporous silica particles under in situ conditions by using a fluorogenic reaction-initiated single-molecule tracking (riSMT) approach. Taking advantage of the low fluorescence background, three-dimensional (3D) tracking of the dynamics of the molecules inside the mesoporous silica pore was achieved with high spatial precision. Compared to the commonly used two-dimensional (2D) tracking method, the 3D tracking results show that the diffusion coefficients of the molecules are three times larger on average. Using riSMT, we quantitatively analyzed the mass transfer of probe molecules in the mesoporous silica pore, including the fraction of adsorption versus diffusion, diffusion coefficients, and residence time. Large interparticle inhomogeneity was revealed and is expected to contribute to the peak broadening for separation application at the ensemble level. We further investigated the impact of electrostatic interaction on the mass transfer of molecules in the mesoporous silica pore and discovered that the primary effect is on the fraction rather than their diffusion rates of resorufin molecules undergoing diffusion.

17.
Chinese Journal of Analytical Chemistry ; (12): 45-53,中插5-中插13, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1017628

RESUMEN

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

18.
NPJ Precis Oncol ; 7(1): 134, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38081998

RESUMEN

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1045-1052, 2023 Dec 18.
Artículo en Chino | MEDLINE | ID: mdl-38101787

RESUMEN

OBJECTIVE: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). METHODS: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. RESULTS: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. CONCLUSION: Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.


Asunto(s)
Aborto Espontáneo , Enfermedades del Tejido Conjuntivo , Leucopenia , Lupus Eritematoso Sistémico , Preeclampsia , Complicaciones del Embarazo , Enfermedades Indiferenciadas del Tejido Conectivo , Embarazo , Recién Nacido , Femenino , Humanos , Resultado del Embarazo , Estudios Retrospectivos , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Preeclampsia/epidemiología , Factores de Riesgo , Complicaciones del Embarazo/epidemiología , Progresión de la Enfermedad , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/epidemiología
20.
ArXiv ; 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37808093

RESUMEN

Cell shape has long been used to discern cell phenotypes and states, but the underlying premise has not been quantitatively tested. Here, we show that a single cell image can be used to discriminate its migration behavior by analyzing a large number of cell migration data in vitro. We analyzed a large number of two-dimensional cell migration images over time and found that the cell shape variation space has only six dimensions, and migration behavior can be determined by the coordinates of a single cell image in this 6-dimensional shape-space. We further show that this is possible because persistent cell migration is characterized by spatial-temporally coordinated protrusion and contraction, and a distribution signature in the shape-space. Our findings provide a quantitative underpinning for using cell morphology to differentiate cell dynamical behavior.

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