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1.
Nat Methods ; 20(10): 1563-1572, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37723244

RESUMEN

Fluorescent RNAs, aptamers that bind and activate small fluorogenic dyes, have provided a particularly attractive approach to visualizing RNAs in live cells. However, the simultaneous imaging of multiple RNAs remains challenging due to a lack of bright and stable fluorescent RNAs with bio-orthogonality and suitable spectral properties. Here, we develop the Clivias, a series of small, monomeric and stable orange-to-red fluorescent RNAs with large Stokes shifts of up to 108 nm, enabling the simple and robust imaging of RNA with minimal perturbation of the target RNA's localization and functionality. In combination with Pepper fluorescent RNAs, the Clivias enable the single-excitation two-emission dual-color imaging of cellular RNAs and genomic loci. Clivias can also be used to detect RNA-protein interactions by bioluminescent imaging both in live cells and in vivo. We believe that these large Stokes shift fluorescent RNAs will be useful tools for the tracking and quantification of multiple RNAs in diverse biological processes.


Asunto(s)
Aptámeros de Nucleótidos , Colorantes Fluorescentes , ARN , Microscopía Fluorescente , Aptámeros de Nucleótidos/genética
2.
Nat Chem Biol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783134

RESUMEN

Fluorescent RNAs (FRs) provide an attractive approach to visualizing RNAs in live cells. Although the color palette of FRs has been greatly expanded recently, a green FR with high cellular brightness and photostability is still highly desired. Here we develop a fluorogenic RNA aptamer, termed Okra, that can bind and activate the fluorophore ligand ACE to emit bright green fluorescence. Okra has an order of magnitude enhanced cellular brightness than currently available green FRs, allowing the robust imaging of messenger RNA in both live bacterial and mammalian cells. We further demonstrate the usefulness of Okra for time-resolved measurements of ACTB mRNA trafficking to stress granules, as well as live-cell dual-color superresolution imaging of RNA in combination with Pepper620, revealing nonuniform and distinct distributions of different RNAs throughout the granules. The favorable properties of Okra make it a versatile tool for the study of RNA dynamics and subcellular localization.

3.
J Cell Sci ; 136(17)2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37622381

RESUMEN

Emerging pathogen infections, such as Zika virus (ZIKV), pose an increasing threat to human health, but the role of mechanobiological attributes of host cells during ZIKV infection is largely unknown. Here, we reveal that ZIKV infection leads to increased contractility of host cells. Importantly, we investigated whether host cell contractility contributes to ZIKV infection efficacy, from both the intracellular and extracellular perspective. By performing drug perturbation and gene editing experiments, we confirmed that disruption of contractile actomyosin compromises ZIKV infection efficiency, viral genome replication and viral particle production. By culturing on compliant matrix, we further demonstrate that a softer substrate, leading to less contractility of host cells, compromises ZIKV infection, which resembles the effects of disrupting intracellular actomyosin organization. Together, our work provides evidence to support a positive correlation between host cell contractility and ZIKV infection efficacy, thus unveiling an unprecedented layer of interplay between ZIKV and the host cell.


Asunto(s)
Infección por el Virus Zika , Virus Zika , Humanos , Actomiosina , Citoesqueleto de Actina , Biofisica
4.
Development ; 149(6)2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35237793

RESUMEN

The mitochondrial matrix AAA+ Lon protease (LONP1) degrades misfolded or unassembled proteins, which play a pivotal role in mitochondrial quality control. During heart development, a metabolic shift from anaerobic glycolysis to mitochondrial oxidative phosphorylation takes place, which relies strongly on functional mitochondria. However, the relationship between the mitochondrial quality control machinery and metabolic shifts is elusive. Here, we interfered with mitochondrial quality control by inactivating Lonp1 in murine embryonic cardiac tissue, resulting in severely impaired heart development, leading to embryonic lethality. Mitochondrial swelling, cristae loss and abnormal protein aggregates were evident in the mitochondria of Lonp1-deficient cardiomyocytes. Accordingly, the p-eIF2α-ATF4 pathway was triggered, and nuclear translocation of ATF4 was observed. We further demonstrated that ATF4 regulates the expression of Tfam negatively while promoting that of Glut1, which was responsible for the disruption of the metabolic shift to oxidative phosphorylation. In addition, elevated levels of reactive oxygen species were observed in Lonp1-deficient cardiomyocytes. This study revealed that LONP1 safeguards metabolic shifts in the developing heart by controlling mitochondrial protein quality, suggesting that disrupted mitochondrial quality control may cause prenatal cardiomyopathy.


Asunto(s)
Corazón , Mitocondrias Cardíacas , Proteasa La , Proteasas ATP-Dependientes/metabolismo , Animales , Corazón/crecimiento & desarrollo , Ratones , Mitocondrias Cardíacas/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Fosforilación Oxidativa , Proteasa La/genética , Proteasa La/metabolismo
5.
PLoS Pathog ; 19(11): e1011589, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37934791

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2, BA.2.75 and EG.5.1. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75 and EG.5.1) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Cricetinae , Humanos , SARS-CoV-2/genética , Virulencia , Aprendizaje Automático
6.
Bioessays ; 45(8): e2200225, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37254735

RESUMEN

During immune responses against invading pathogenic bacteria, the cytoskeleton network enables macrophages to implement multiple essential functions. To protect the host from infection, macrophages initially polarize to adopt different phenotypes in response to distinct signals from the microenvironment. The extracellular stimulus regulates the rearrangement of the cytoskeleton, thereby altering the morphology and migratory properties of macrophages. Subsequently, macrophages degrade the extracellular matrix (ECM) and migrate toward the sites of infection to directly contact invading pathogens, during which the involvement of cytoskeleton-based structures such as podosomes and lamellipodia is indispensable. Ultimately, macrophages execute the function of phagocytosis to engulf and eliminate the invading pathogens. Phagocytosis is a complex process that requires the cooperation of cytoskeleton-enriched super-structures, such as filopodia, lamellipodia, and phagocytic cup. This review presents an overview of cytoskeletal regulations in macrophage polarization, ECM degradation, migration, and phagocytosis, highlighting the pivotal role of the cytoskeleton in host defense against infection.


Asunto(s)
Citoesqueleto , Macrófagos , Macrófagos/metabolismo , Citoesqueleto/metabolismo , Fagocitosis/fisiología , Membrana Celular , Microtúbulos
7.
BMC Med ; 22(1): 215, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38807144

RESUMEN

BACKGROUND: Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. METHODS: The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494-0.957) and 51.6% (95% CI, 0.307-0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. CONCLUSIONS: Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. TRIAL REGISTRATION: ChiCTR2000031608.


Asunto(s)
Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Neoplasias de Cabeza y Cuello , Melanoma , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Masculino , Femenino , Persona de Mediana Edad , Anciano , Melanoma/tratamiento farmacológico , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Adulto , Animales , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Ratones , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Amplificación de Genes , Resultado del Tratamiento
8.
BMC Cancer ; 24(1): 580, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735973

RESUMEN

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.


Asunto(s)
Apoptosis , Neoplasias Óseas , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Osteosarcoma , Factores de Empalme Serina-Arginina , Humanos , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Apoptosis/genética , Movimiento Celular/genética , Regulación hacia Arriba , Empalme Alternativo
9.
Bioorg Med Chem ; 102: 117660, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38442524

RESUMEN

Werner (WRN) syndrome protein is a multifunctional enzyme with helicase, ATPase, and exonuclease activities that are necessary for numerous DNA-related transactions in the human cell. Recent studies identified WRN as a synthetic lethal target in cancers. In this study, a series of new N-arylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline. The structures of the thirty-two newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The anticancer activity in vitro against chronic myeloid leukemia cells (K562), non-small cell lung cancer cells (A549), human prostate cancer cells (PC3), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, the inhibition ratio of compounds 17d, 18a, 18b, 11 and 23a against four cancer cells at 5 µM concentration were more than 50 %. The IC50 values of compounds 18a and 18b were 0.3 ± 0.01 µM and 0.05 ± 0.02 µM in K562 cells respectively, compared with HeLa and A549 cells, 18a and 18b were more sensitive to K562 cells. In addition, the PC3 cells with WRN overexpression (PC3-WRN) was constructed, 18a and 18b and 23a were more sensitive to PC3-WRN cells compared with the control group cells (PC3-NC). Then, the cell viability of the novel WRN inhibitors were further assessed by colony formation assay. Compared with PC3-NC cells, 18b and 23a had obvious inhibitory effect on PC3-WRN cell at 1000 nM. In summary, these results indicated that the compounds 18b and 23a could be WRN protein inhibitor with potent anticancer properties in vitro.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , RecQ Helicasas , Exodesoxirribonucleasas/metabolismo , Células HeLa
10.
Pediatr Transplant ; 28(1): e14611, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37735900

RESUMEN

BACKGROUND: Published data on LCP-tacrolimus (LCPT) in the pediatric population are limited. METHODS: This single-center, retrospective, observational study describes LCPT doses needed to reach therapeutic ranges in pediatric and young adult kidney and liver transplant recipients in both de novo usage and conversion from immediate-release tacrolimus (IR-Tac). Adverse outcomes up to 12 months after LCPT initiation were also evaluated. RESULTS: Forty-one transplant recipients (30 kidney, 11 liver) were included. The median initial doses of LCPT were 0.034 mg/kg (IQR 0.019) de novo and 0.09 mg/kg (IQR = 0.076) converted. The median doses at first therapeutic level were 0.086 mg/kg (IQR 0.028) de novo and 0.1 mg/kg (IQR 0.066) converted. The median LCPT:IR-Tac conversion ratio initially was 0.7 and 0.75 at therapeutic levels. The rate of AKI per 100 days of exposure to IR-Tac was 0.546 and 0.439 on LCPT. The percentage of patients with rejection was not different before and after conversion (clinical rejection 8.6% [n = 3] vs 11.4% [n = 4], p = .6; biopsy-proven rejection 2.9% [n = 1] vs 11.4% [n = 4], p = .11). One patient had graft loss unrelated to rejection, and the graft was explanted. CONCLUSION: In this study, pediatric and young adult abdominal transplant recipients had therapeutic tacrolimus levels at LCPT doses below the adult-labeled dose; the conversion ratio from IR-Tac to LCPT at therapeutic level was similar. There were no identified safety concerns in de novo or converted LCPT use in pediatric and young adult patients.


Asunto(s)
Trasplante de Riñón , Tacrolimus , Humanos , Niño , Adulto Joven , Inmunosupresores/efectos adversos , Receptores de Trasplantes , Trasplante de Riñón/efectos adversos , Rechazo de Injerto/prevención & control , Rechazo de Injerto/tratamiento farmacológico , Esquema de Medicación , Estudios Prospectivos
11.
J Sep Sci ; 47(3): e2300768, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38356228

RESUMEN

Countercurrent chromatography (CCC) is a potent separation approach known for its remarkable efficiency and capacity in preparation. It's applied as a substitute or combined with different chromatographic techniques, resulting in its rebranding as multidimensional CCC (MDCCC). Numerous essential mixtures from natural products contain hundreds or thousands of distinct components of importance. These mix types are too complicated to separate in any reasonable time using a single CCC dimension. However, if a multidimensional technique is utilized, where a complex mixture is separated by an initial dimension, smaller fractions of that separation are gathered. Each fraction is studied individually; complex mixes can be resolved relatively quickly. Thus, several MDCCC separation features have been studied to demonstrate their advantages, limitations, and prospective capacity to separate exceedingly complex mixtures. In this review, MDCCC aspects, including principles, multiple columns system, multilayer coil J-type, on-line monitoring system, and applications, have been thoroughly_explored.

12.
J Sep Sci ; 47(12): e2400190, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38894562

RESUMEN

An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) as a chiral selector in high-speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two-phase solvent system consisting of n-hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE-ß-CD) (1.5:0.5:2, v/v/v). A fast and predictable scale-up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11-fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high-performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale-up process and attaining continuous separation of chiral drugs.


Asunto(s)
Distribución en Contracorriente , Voriconazol , Distribución en Contracorriente/métodos , Estereoisomerismo , Voriconazol/química , Voriconazol/aislamiento & purificación , Cromatografía Líquida de Alta Presión , beta-Ciclodextrinas/química
13.
BMC Anesthesiol ; 24(1): 25, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38218762

RESUMEN

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).


Asunto(s)
Dolor Postoperatorio , Náusea y Vómito Posoperatorios , Humanos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Anestesia General , Hiperalgesia , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/inducido químicamente , Náusea y Vómito Posoperatorios/inducido químicamente , Remifentanilo/administración & dosificación , Remifentanilo/efectos adversos , Remifentanilo/uso terapéutico
14.
J Behav Med ; 47(3): 531-536, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38393444

RESUMEN

Women with negative body image engage in less physical activity. The purpose of this study is to examine the relationship between body image and physical activity in Latinas participating in a lifestyle program. Participants (age 43.8 ± 10.1 years and BMI 30.4 ± 5.2 kg/m2) were enrolled in a 12-month culturally and linguistically adapted, individually tailored, intervention focused on increasing moderate-to-vigorous intensity physical activity (MVPA). Longitudinal assessments were conducted on body image dissatisfaction (BID) using the Figure Rating Scale, MVPA using the 7-day PAR interview, and objectively measured body weight. Pre-intervention BID did not significantly predict MVPA change. Participants experienced considerable reduction in BID. Greater MVPA engagement and weight loss were independently related to BID reduction. Acculturation did not moderate these relationships. Body image improved in Latinas participating in a cognitive and behavioral physical activity intervention regardless of weight loss and acculturation level.


Asunto(s)
Imagen Corporal , Promoción de la Salud , Humanos , Femenino , Adulto , Persona de Mediana Edad , Promoción de la Salud/métodos , Ejercicio Físico , Hispánicos o Latinos/psicología , Pérdida de Peso
15.
Ecotoxicol Environ Saf ; 277: 116342, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38657457

RESUMEN

Pyrethroids (PYs) are widely applied pesticides whose residues pose potential health risks. This review describes current knowledge on PY chemical properties, usage patterns, environmental and food contamination, and human exposure models. It evaluates life cycle assessment (LCA), chemical alternatives assessment (CAA), and high-throughput screening (HTS) as tools for pesticide policy. Despite efforts to mitigate PY presence, their pervasive residues in the environment and food persist. And the highest concentrations ranged from 54,360 to 80,500 ng/L in water samples from agricultural fields. Food processing techniques variably reduce PY levels, yet no method guarantees complete elimination. This review provides insights into the fates and exposure pathways of PY residues in agriculture and food, and highlights the necessity for improved PY management and alternative practices to safeguard health and environment.


Asunto(s)
Contaminación de Alimentos , Residuos de Plaguicidas , Piretrinas , Piretrinas/análisis , Piretrinas/toxicidad , Residuos de Plaguicidas/análisis , Humanos , Contaminación de Alimentos/análisis , Monitoreo del Ambiente/métodos , Exposición a Riesgos Ambientales/análisis , Agricultura , Medición de Riesgo , Contaminantes Químicos del Agua/análisis
16.
Ecotoxicol Environ Saf ; 272: 116041, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38350213

RESUMEN

Although PFOS has been banned as a persistent organic pollutant, it still exists in large quantities within the environment, thus impacting the health of aquatic ecosystems. Previous studies focused solely on high PFOS concentrations, disregarding the connection with environmental factors. To gain a more comprehensive understanding of the PFOS effects on aquatic ecosystems amidst changing environmental conditions, this study investigated the cellular responses of Microcystis aeruginosa to varying PFOS concentrations under heatwave and nutrient stress conditions. The results showed that PFOS concentrations exceeding 5.0 µg/L had obvious effects on multiple physiological responses of M. aeruginosa, resulting in the suppression of algal cell growth and the induction of oxidative damage. However, PFOS concentration at levels below 20.0 µg/L has been found to enhance the growth of algal cells and trigger significant oxidative damage under heatwave conditions. Heatwave conditions could enhance the uptake of PFOS in algal cells, potentially leading to heightened algal growth when PFOS concentration was equal to or less than 5.0 µg/L. Conversely, deficiency or limitation of nitrogen and phosphorus significantly decreased algal abundance and chlorophyll content, inducing severe oxidative stress that could be mitigated by exposure to PFOS. This study holds significance in managing the impact of PFOS on algal growth across diverse environmental conditions.


Asunto(s)
Microcystis , Ecosistema , Clorofila , Estrés Oxidativo , Fósforo/farmacología
17.
Chem Biodivers ; 21(4): e202400135, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38425248

RESUMEN

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.


Asunto(s)
Tiadiazoles , Humanos , Tiadiazoles/farmacología , Antifúngicos/farmacología , Antibacterianos/farmacología , Hongos , Piridinas/farmacología , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
18.
Sensors (Basel) ; 24(4)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38400482

RESUMEN

The common channel attention mechanism maps feature statistics to feature weights. However, the effectiveness of this mechanism may not be assured in remotely sensing images due to statistical differences across multiple bands. This paper proposes a novel channel attention mechanism based on feature information called the feature information entropy attention mechanism (FEM). The FEM constructs a relationship between features based on feature information entropy and then maps this relationship to their importance. The Vaihingen dataset and OpenEarthMap dataset are selected for experiments. The proposed method was compared with the squeeze-and-excitation mechanism (SEM), the convolutional block attention mechanism (CBAM), and the frequency channel attention mechanism (FCA). Compared with these three channel attention mechanisms, the mIoU of the FEM in the Vaihingen dataset is improved by 0.90%, 1.10%, and 0.40%, and in the OpenEarthMap dataset, it is improved by 2.30%, 2.20%, and 2.10%, respectively. The proposed channel attention mechanism in this paper shows better performance in remote sensing land use classification.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38536574

RESUMEN

While the correlation between parental autonomy granting and adolescents' problematic Internet use (PIU) has been confirmed, the processes underlying this connection have not been thoroughly investigated. Drawing on the ecological systems theory, this study sought to investigate the mediating mechanism of peer attachment and the moderating mechanism of school climate that link parental autonomy granting to PIU. A two-wave longitudinal design was employed with a time interval of six months. The participants were 852 adolescents who attended three middle schools located in Guangdong Province, China. Self-report questionnaires were used to obtain data on demographics, parental autonomy granting, peer attachment, school climate, and PIU. The findings indicated that peer attachment significantly mediated the link between parental autonomy granting and adolescent PIU. A positive school climate significantly moderated the influence of parental autonomy granting on peer attachment and the influence of peer attachment on PIU. Specifically, the association between parental autonomy granting and peer attachment and the association between peer attachment and PIU were more pronounced when the school climate was perceived to be positive. This research underscores the possible significance of peer attachment in the association between parental autonomy granting and PIU and offers valuable insights for mitigating the negative outcomes of PIU.

20.
Fetal Pediatr Pathol ; 43(2): 111-122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38213180

RESUMEN

Background: We evaluated CD30 and CD56 expression in lymphoblastic lymphoma (LBL) and correlated the results with clinicopathological features and prognosis. Methods: Immunohistochemical (IHC) staining was performed on 85 formalin-fixed paraffin-embedded LBL specimens using two CD30 clones and one CD56 antibody clone. Results: Weak and diffuse expression of CD30 was expressed in 4.7% (clone Ber-H2) or 14.1% (clone EPR4102) in LBL, while CD56 was expressed in 24.7%. CD30 and CD56 expression correlated with lactate dehydrogenase levels. CD56-positive expression was closely associated with an unfavorable prognosis. Although CD30 expression exhibited a trend toward poorer overall survival, it did not reach statistical significance. Conclusion: CD56 is a potential negative prognostic marker. These findings suggest that CD30 and CD56 targeted therapies could be potential therapeutic targets for LBL patients.


Asunto(s)
Relevancia Clínica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Inmunohistoquímica , Adhesión en Parafina , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Estudios Retrospectivos , Antígeno Ki-1
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