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Despite the corona-virus pandemic, Korean cosmetics maintain brand attachment in the Chinese market. This study identifies critical influencing and outcome factors of brand attachment within this consumer phenomenon. Specifically, it investigates the relationship between Chinese consumers' perceived brand authenticity and brand attachment, brand loyalty, willingness to pay a premium, and forgiveness. To this end, it uses AMOS 21.0 to analyze data collected through a questionnaire, testing the research model. The study reveals several key findings. Firstly, it assesses brand authenticity based on the following five sub-factors: consistency, naturalness, originality, advertisement truthfulness, and reliability. According to the assessment results, originality shows the most significant impact, followed by reliability, consistency, and naturalness. Furthermore, brand attachment significantly enhances brand loyalty, willingness to pay a premium, and forgiveness toward the brand. Higher levels of brand attachment lead to increased brand loyalty. In addition, greater brand attachment correlates with consumers' increased willingness to pay more for products and greater forgiveness towards the brand.
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BACKGROUND: Research is increasingly highlighting the intricate relationship between mental and physical health. However, longitudinal studies investigating the interplay between chronic diseases (CDs), depression and anxiety are still relatively scarce. This study aimed to delve into the longitudinal connections among these variables. METHODS: This study conducted a 4-year prospective survey involving 486 participants from rural communities in Shandong Province, China. The relationships among these variables were analyzed using multiple linear regression, cross-lagged path analysis, and multiple-group analysis. RESULTS: Our analysis revealed that the number of CDs reported at wave 1 significantly predicted anxiety levels (ß = 0.126, p < .01) at wave 2, while depression symptoms also predicted anxiety (ß = 0.220, p < .01) at wave 2. Furthermore, anxiety levels at wave 1 significantly predicted both the number of CDs (ß = 0.219, p < .01) and depression symptoms (ß = 0.160, p < .05) at wave 2. However, the study did not find support for a relationship between CDs and depression. CONCLUSION: The study uncovered a bidirectional association between CDs and anxiety, depression and anxiety, but found no direct longitudinal relationship between CDs and depression. Research has indicated that CDs indirectly affect depression through anxiety.
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Purpose: The present study aimed to revise the Reckless Driving Behaviour Scale (RDBS) and examined its reliability and validity among young Chinese drivers. Methods: The RDBS, the Safe Driving Climate among Friends Scale (SDCaF), the Family Climate for Road Safety Scale (FCRSS) and a social desirability scale were administrated to 560 young drivers. Exploratory factor analysis (EFA, n = 250) and confirmatory factor analysis (CFA, n = 250) were conducted to examine the factorial structure of the RDBS. Results: The Chinese version of the RDBS has 18 items that are divided into 4 factors: distraction, substance use, extreme behaviour and positioning. Both the results of EFA and CFA confirmed its factorial structure. The reliability of the RDBS was acceptable and the concurrent validity of the scale was supported by its significant associations with the SDCaF and FCRSS factors. Finally, drivers who had violation involvement scored higher on all four factors than their peers who did not have violation involvement, providing evidence for its known-group validity. Conclusion: The revised RDBS has similar structure with the original version and its reliability and validity were satisfactory. It is an effective tool to measure the reckless driving behaviour of young drivers in China and interventions that incorporated joint efforts of family and peers should be developed.
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AIM: Negative life events have been reported as a risk factor for depression. However, the mechanism between negative life events and depression is still unclear. This study aimed to explore the mediating role of sleep quality and the moderating role of economic income in the association between negative life events and depression among older adults aged 60 years and over. METHODS: A multi-stage stratified sampling method was used to select elderly individuals over 60 years old in Shandong, China, making use of the Household Health Interview Survey (2020). In total, 3868 older adults completed the measures of negative life events, sleep quality, depression, and economic income. RESULTS: Negative life events positively predicted depression among the elderly (proportion of direct effect, 55.12%), and poor sleep quality could mediate this association (proportion of indirect effect, 44.87%). Economic income played a moderating role in the relationship between negative life events, sleep quality, and depression (the first and second half of the mediating effect, the direct effect of negative life events on depression). Both effects were weaker among the elderly with higher economic incomes. CONCLUSIONS: Negative life events had positive effects on depression in older adults. Economic income moderated the direct effect of negative life events and the mediating effect (first and second half) of sleep quality on depression. When the elderly experience negative life events, interventions for improving their sleep quality and financial support could effectively prevent depression. Geriatr Gerontol Int 2024; 24: 751-757.
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Depresión , Renta , Acontecimientos que Cambian la Vida , Calidad del Sueño , Humanos , Anciano , Masculino , China/epidemiología , Femenino , Renta/estadística & datos numéricos , Persona de Mediana Edad , Depresión/epidemiología , Depresión/psicología , Factores de Riesgo , Anciano de 80 o más Años , Factores Socioeconómicos , Encuestas EpidemiológicasRESUMEN
The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 µg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 µg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.
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Biochar is widely used in integrated soil management, and can directly alter the soil environment and drastically affect the soil microbial community. Given the important role of soil microorganisms in the carbon cycling of soils, it is important to understand how biochar alters the stability of soil organic carbon (SOC) pools in Dahurian larch (Larix gmelinii) forests through microbial pathways unburned and high-severity burned soils to guide comprehensive soil management and restore ecological functions in postfire soils. This study employed the r/K ecological strategy theory to quantify the ecological strategy propensities of soil microbial communities. The ratio of oligotrophic species to copiotrophic species was used to measure these propensities. The study aimed to establish a link between the ecological strategy choices of microbial communities and SOC pools. We found: that (1) biochar increases the mass of SOC regardless of whether the soil has experienced fire, (2) biochar addition to unburned stands makes the K-strategy dominant in microbial communities, significantly decreasing the mineral-associated organic carbon (MAOC) to SOC ratio and weakening the of SOC pool stability; (3) biochar addition to high-severity burned stands shifts the dominant microbial strategy to r-strategy, restoring the damaged microbial community to its preburned state. The MAOC/SOC ratio significantly increased, contributing to the restoration of the SOC pool stability and enhancing the soil carbon sequestration capacity. This study elucidates the effects of biochar addition on the dominant ecological strategy of microbial communities and alterations in the structure and stability of SOC pools, which is important for understanding how biochar affects SOC pools through biochemical pathways, and provides important references for unraveling the relation between microbial ecological strategies and soil carbon pools.
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Carbono , Carbón Orgánico , Bosques , Larix , Microbiología del Suelo , Suelo , Carbón Orgánico/química , Suelo/química , China , Microbiota , Ciclo del CarbonoRESUMEN
BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. CONCLUSION: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
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Enterococcus faecium , Infecciones por Bacterias Grampositivas , Linezolid , Pruebas de Sensibilidad Microbiana , Linezolid/farmacología , Humanos , China/epidemiología , Enterococcus faecium/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Enterococcus faecalis/genética , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/aislamiento & purificación , Femenino , Vancomicina/farmacología , Antibacterianos/farmacología , Epidemiología Molecular , Adulto , Resistencia a la Vancomicina/genética , Anciano , Estudios Retrospectivos , Enterococos Resistentes a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Adulto Joven , Enterococcus/genética , Enterococcus/efectos de los fármacos , Enterococcus/aislamiento & purificaciónRESUMEN
Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.
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Adamantano , Aminobenzoatos , Aminofenoles , Anilidas , Compuestos Policíclicos , Aminofenoles/química , Aminofenoles/farmacología , Aminofenoles/síntesis química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/síntesis química , Adamantano/química , Adamantano/farmacología , Adamantano/síntesis química , Adamantano/análogos & derivados , Anilidas/farmacología , Anilidas/química , Anilidas/síntesis química , Aminobenzoatos/farmacología , Aminobenzoatos/química , Aminobenzoatos/síntesis química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Estructura Molecular , Reacción de Cicloadición , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/químicaRESUMEN
Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.
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Radioisótopos de Galio , Ratones Endogámicos C57BL , Tomografía de Emisión de Positrones , Radiofármacos , Receptores de Somatostatina , Animales , Ratones , Receptores de Somatostatina/metabolismo , Humanos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Radiofármacos/química , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/inducido químicamente , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/metabolismo , Masculino , Bleomicina , Endopeptidasas/metabolismo , Modelos Animales de Enfermedad , Femenino , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , QuinolinasRESUMEN
Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.
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Inhibidores de Puntos de Control Inmunológico , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Endopeptidasas/genética , Células 3T3 NIH , Radiofármacos/uso terapéutico , Serina Endopeptidasas/genética , Serina Endopeptidasas/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Inmunoterapia , Gelatinasas/genética , Gelatinasas/inmunología , Lutecio/farmacología , Línea Celular TumoralRESUMEN
Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors.
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Proteínas de la Membrana , Neoplasias , Investigación Biomédica Traslacional , Animales , Humanos , China , Endopeptidasas , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Tomografía de Emisión de Positrones , Trazadores RadiactivosRESUMEN
Circular RNA Ribonuclease P RNA Component H1 (circ_RPPH1) and microRNA (miRNA) miR-1296-5p play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that miR-1296-5p can activate tripartite motif-containing 14 (TRIM14). Clinical indications of eighty BC patients were collected and the circ_RPPH1 expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of circ_RPPH1, miR-1296-5p, or TRIM14. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with circ_RPPH1 overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of miR-1296-5 and TRIM14 mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. Circ_RPPH1 levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. Circ_RPPH1 altered cell cycle and hindered apoptosis. Circ_RPPH1 knockdown or miR-1296-5p overexpression inhibited the malignant phenotype of BC. Furthermore, miR-1296-5p knockdown reversed circ_RPPH1's promotion effects on BC. Interestingly, TRIM14 overexpression counteracts the inhibitory effects of miR-1296-5p overexpression and circ_RPPH1 silencing on BC. Moreover, in BC tumor-bearing mice, circ_RPPH1 overexpression led to increased TRIM14 expression and facilitated tumor growth. Circ_RPPH1 enhanced BC progression through miR-1296-5p/TRIM14 axis, indicating its potential as a biomarker and therapeutic target in BC.
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Neoplasias de la Mama , Proliferación Celular , Progresión de la Enfermedad , MicroARNs , ARN Circular , Proteínas de Motivos Tripartitos , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Animales , Ratones , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Apoptosis , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Línea Celular Tumoral , Ratones DesnudosRESUMEN
BACKGROUND: Childhood sexual abuse (CSA) is a severe global problem associated with alcohol use disorder (AUD). Previous studies have confirmed this relationship; however, there is a lack of research on the disease burden of AUD attributable to CSA. OBJECTIVE: To analyze global spatiotemporal trends and differences in the disease burden of AUD attributable to CSA and its relationship with age, sex, and the sociodemographic index (SDI). PARTICIPANTS AND SETTING: Data from the Global Burden of Disease 2019 Public Database. METHODS: Summary exposure value (SEV) was used to evaluate CSA. Disability-adjusted life year (DALY), years lived with disability (YLD), years of life lost (YLL), and their annual rates of change were used to evaluate disease burden. Cluster analysis based on Ward's method was used to examine the global burden associated with age, sex, and SDI. A 95 % uncertainty intervals (UI), excluding 0, was considered statistically significant. RESULTS: In 2019, 1.63 million (95 % UI 0.23-3.90 million) DALYs of AUD were caused by CSA and the age-standardized rates (ASRs) of DALY was 19.77 (95 % UI 2.78-47.46) globally. Annual rates of change in DALY of people over 65 years of age increased from 1990 to 2019 in all regions except the High-middle SDI regions. The ASRs of DALY of females in High SDI regions, were always at a much higher level than other SDI regions, and showed an upward trend from 1990 to 2019 (DALY 1990: 20.38 [95 % UI 2.87-47.77], 2019: 23.61 [95 % UI 3.55-54.94]). CONCLUSIONS: Substantial geographical differences were observed in the burden of AUD attributable to CSA. The level of CSA exposure was inconsistent with the related burden of AUD in different regions according to the sociodemographic index. The burden of disease increased in the elderly population and in females in high sociodemographic index regions.
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Alcoholismo , Abuso Sexual Infantil , Carga Global de Enfermedades , Salud Global , Humanos , Femenino , Carga Global de Enfermedades/tendencias , Masculino , Adulto , Adulto Joven , Persona de Mediana Edad , Adolescente , Niño , Alcoholismo/epidemiología , Salud Global/estadística & datos numéricos , Abuso Sexual Infantil/estadística & datos numéricos , Anciano , Factores Sexuales , Factores Socioeconómicos , Factores Sociodemográficos , Años de Vida Ajustados por Discapacidad/tendencias , Costo de Enfermedad , Factores de EdadRESUMEN
As common pollutants, Cu2+ and glyphosate pose a serious threat to human health and the ecosystem. Herein, a fluorescent probe (E)-7-(diethylamino)-N'(4-(diethylamino)-2-hydroxybenzyl)-2-oxo-2H chromophore-3-carbazide (DDHC) was designed and synthesised for the sequential recognition of Cu2+ and glyphosate. DDHC has the advantages of a short synthesis path, easy-to-obtain raw materials, good anti-interference ability, and strong stability. The interaction of the DDHC-Cu2+ complexes with glyphosate allows the amino and carboxyl groups in glyphosate molecules to coordinate with Cu2+ strongly, competing for the Cu2+ in the DDHC-Cu2+ complexes and releasing the DDHC, leading to the recovery of fluorescence. The recognition was further validated through Job's plot, HRMS, and DFT calculations. In addition, the successful recovery of Cu2+ and glyphosate in different environmental water samples fully demonstrates the practical application potential of DDHC. Especially, DDHC has low cytotoxicity and can enter zebrafish and HeLa cells, rapidly reacting with Cu2+ and glyphosate in the body, generating visible fluorescence quenching and recovery phenomena, achieving real-time visual monitoring of exogenous Cu2+ and glyphosate in zebrafish and HeLa cells. The targeting and dual selectivity of DDHC greatly enhance its potential application value in the field of detection, providing important theoretical support for studying the fate of multiple pollutants in the environment.
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Cobre , Colorantes Fluorescentes , Glicina , Glifosato , Pez Cebra , Glicina/análogos & derivados , Glicina/análisis , Glicina/química , Cobre/análisis , Cobre/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Animales , Células HeLa , Espectrometría de Fluorescencia/métodos , Contaminantes Químicos del Agua/análisis , Herbicidas/análisis , Teoría Funcional de la DensidadRESUMEN
Standard energy-consumption testing, providing the only publicly available quantifiable measure of battery electric vehicle (BEV) energy consumption, is crucial for promoting transparency and accountability in the electrified automotive industry; however, significant discrepancies between standard testing and real-world driving have hindered energy and environmental assessments of BEVs and their broader adoption. In this study, we propose a data-driven evaluation method for standard testing to characterize BEV energy consumption. By decoupling the impact of the driving profile, our evaluation approach is generalizable to various driving conditions. In experiments with our approach for estimating energy consumption, we achieve a 3.84% estimation error for 13 different multiregional standardized test cycles and a 7.12% estimation error for 106 diverse real-world trips. Our results highlight the great potential of the proposed approach for promoting public awareness of BEV energy consumption through standard testing while also providing a reliable fundamental model of BEVs.
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Introduction: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. Purpose: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. Methods: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort. Conducting differential analysis resulted in the identification of differentially expressed miRNA (DE-miRNAs) and differentially expressed genes (DEGs) between the TNBC and Control samples. Screening for prognostic miRNAs and biomarkers involved employing univariate Cox analysis and least absolute shrinkage and selection operator regression analyses. These methods were utilized to construct risk models aimed at predicting the survival of patients with TNBC. Based on the median value of risk scores, patients were then stratified into low- and high-risk groups. Functional enrichment analysis was employed to explore the potential function and pathways of prognostic genes. Additionally, independent prognostic analysis was performed through univariate and multivariate Cox regression. Immune infiltration analysis was performed to examine disparities in the infiltration of immune cells between the two risk groups. Finally, the prognostic gene expression was mined in key cell types of TNBC. Results: We obtained 5213 DEGs and 204 DE-miRNAs related to cuproptosis between TNBC and Control samples. Five prognostic miRNAs (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were closely associated with TNBC. Significant differences in the functions of prognostic genes between the two risk groups were observed, encompassing adipogenesis, inflammatory response, and hormone metabolic process. The prognostic gene regulatory network revealed that miR200C-3p regulated ZFPM2 and CFL2, and miR-1277-3p regulated BMP2 and RORA. A nomogram was created based on riskScore, cancer status, and pathologic stage to predict 1/3/5-year survival of patients with TNBC. Immune infiltration analysis indicated that the immune microenvironment may be associated with the progression of TNBC. Interestingly, prognostic genes exhibited higher expression levels in T cells, fibroblasts, endothelial cells, and monocytes compared to other cells. Conclusions: Five prognostic miRNA (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were significantly associated with TNBC, it provides new therapeutic targets for the treatment and prognosis of TNBC.
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Ni60-WC coatings with different WC contents on the bucket tooth substrates were pre- pared using laser cladding technology. Their abrasive wear properties were assessed using the dry sand rubber wheel test system. The substrate and the hard-facing layer were tested for comparison. The results showed that the hardness of the Ni60-WC coatings increased with the increase in WC content. The wear resistance of the bucket tooth substrate was greatly improved by hard-facing and laser cladding Ni60-WC coatings. The wear rate of the hard-facing layer was reduced to 1/6 of that of the tooth substrate. The wear rate of the laser cladding coatings with 20-40 wt.% WC was similar to that of the hard-facing layer. It is worth mentioning that the wear rate of the coatings with 60-80 wt.% WC was only 1/4 of that of the hard-facing layer. Micro-cutting with surface plastic deformation was the main wear mechanism of the substrate to form narrow and deep furrows. The wear mechanism of the hard-facing layer was mainly plastic deformation with a wide groove, and the surface cracks promoted the removal of the material. The removal of the binder phase caused by micro-cutting was the main wear mechanism of the laser cladding Ni60-WC coatings. However, the hard phase of WC hinders micro-cutting and plastic deformation, which improves the wear resistance of the coating.
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BACKGROUND: To analyze the clinical characteristics of ureteropelvic junction obstruction (UPJO) caused by crossing vessels (CV) in infants and young children. METHODS: A retrospective analysis was performed on children with UPJO who underwent primary surgery. Patients were classified into laparoscopic pyeloplasty (LP) and open pyeloplasty (OP) groups and classified as ≤3 or >3 (years old) groups. Children with CV-caused UPJO were identified. RESULTS: A total of 747 patients were included. Ninety cases of CV were identified. The CV discovery rate was higher in the LP group (78/457, 17.1%) than in the OP group (12/290, 4.1%) (P < 0.001). In the ≤3 group, the CV discovery rate in the LP group (27/144, 18.8%) was higher than that in the OP group (11/274, 4.0%) (P < 0.001). In the LP group, there was no significant difference between ≤3 (27/144, 18.8%) and >3 (51/313, 16.3%) groups in the CV discovery rate. The rate in children with UPJO was not significantly different at any age (P > 0.05). Progressive aggravation of hydronephrosis (21/27, 77.8%) and symptomatic hydronephrosis (44/51, 86.3%) were the main surgical indications in the ≤3 and > 3 groups, respectively. There were no preoperatively confirmed cases of CV in the ≤3 group. In the OP group, five patients underwent reoperation, three of whom were due to failure to detect CV during the initial operation. CONCLUSIONS: The CV distribution is similar in children with UPJO across all ages; CV in infants and young children are not rare. LP should be considered as CV are prone to being missed during OP. LEVELS OF EVIDENCE: III.
Asunto(s)
Pelvis Renal , Obstrucción Ureteral , Humanos , Obstrucción Ureteral/cirugía , Obstrucción Ureteral/etiología , Estudios Retrospectivos , Lactante , Femenino , Masculino , Pelvis Renal/cirugía , Preescolar , Laparoscopía/métodos , Hidronefrosis/etiología , Hidronefrosis/cirugía , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.
Asunto(s)
Medicamentos Herbarios Chinos , Hiperuricemia , Riñón , Ratas Sprague-Dawley , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ácido Úrico/sangre , Ratas , Modelos Animales de Enfermedad , Farmacología en Red/métodos , Creatinina/sangre , Nitrógeno de la Urea SanguíneaRESUMEN
We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including the COVID-19 pandemic caused by SARS-CoV-2. Main protease (MPro), a highly conserved protease among various CoVs, is essential for viral replication and pathogenesis, making it a prime target for antiviral drug development. Here, we leverage proteolysis targeting chimera (PROTAC) technology to develop a new class of small-molecule antivirals that induce the degradation of SARS-CoV-2 MPro. Among them, MPD2 was demonstrated to effectively reduce MPro protein levels in 293T cells, relying on a time-dependent, CRBN-mediated, and proteasome-driven mechanism. Furthermore, MPD2 exhibited remarkable efficacy in diminishing MPro protein levels in SARS-CoV-2-infected A549-ACE2 cells. MPD2 also displayed potent antiviral activity against various SARS-CoV-2 strains and exhibited enhanced potency against nirmatrelvir-resistant viruses. Overall, this proof-of-concept study highlights the potential of targeted protein degradation of MPro as an innovative approach for developing antivirals that could fight against drug-resistant viral variants.