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1.
Pediatr Res ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014239

RESUMEN

BACKGROUND: With the increase in the number of low birth weight infants, oxygen therapy is more widely used. However, chronic high-concentration oxygen environments lead to hyperoxic lung injury in children, which in turn leads to bronchopulmonary dysplasia (BPD). PGE1 is widely used in the clinic for its ability to inhibit inflammation and improve circulation. Therefore, we further investigated whether PGE-1 has a therapeutic effect on hyperoxic lung injury. METHODS: Hyperoxic lung injury model was adopted for investigating the interventional effects and underlying mechanisms of intraperitoneal injection of prostaglandin E1 (PGE-1) on hyperoxic lung injury in newborn rats via relevant experimental techniques, such as Diff-Quick staining, lung wet dry specific gravity measurements, HE staining, TUNEL staining, ELISA, and the Western blot method. RESULTS: Inflammatory and apoptotic cells in the PGE1-treated group were significantly lower than those in the hyperoxic lung injury group (p < 0.05); and the contents of IL-1ß, IL-6 and TNF-α in the treated group were significantly lower than those in the model group (p < 0.05). Caspase-3, CHOP, GRP78 and Bcl-2/Bax protein expression in the treatment group was significantly lower than that in the model group (p < 0.05). CONCLUSION: PGE-1 has a therapeutic effect on hyperoxic lung injury in neonatal rats. IMPACT: PGE1 treatment reduces levels of inflammatory cells and pro-inflammatory cytokines and decreases apoptosis. PGE1 has a therapeutic effect on BPD through the endoplasmic reticulum stress pathway. This study offers the possibility of PGE1 for the treatment of BPD.

2.
Environ Sci Technol ; 58(28): 12356-12367, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38953388

RESUMEN

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.


Asunto(s)
Hepatocitos , Metabolismo de los Lípidos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Desinfección , Hígado/metabolismo , Hígado/efectos de los fármacos , Acetaldehído/toxicidad , Línea Celular
3.
Nutrients ; 16(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892618

RESUMEN

It is crucial to provide adequate iodine nutrition to infants and toddlers for proper thyroid function and subsequent brain development. Infants are particularly vulnerable to iodine deficiency during the transition from a milk-based diet (breast milk and/or infant formula) to solid food. This study examines the current iodine levels of children during their first two years of life and investigates the association between these levels and feeding behaviors and the iodine status of their mothers in Shanghai, a city located in eastern China. A hospital-based cohort study was conducted to enroll mother-child pairs, where the child is aged 6-23 months, who visited community health service centers in the 16 districts of Shanghai, China. Data on socio-demographic factors and feeding behavior data were collected from the participants. The urinary iodine concentration (UIC) in both the young children and their mothers were analyzed. A total of 2282 mother-child pairs were included in this analysis. The median (p25-p75) UIC for lactating women, weaning women, and children were 121.3 µg/L (68.1-206.4 µg/L), 123.4 µg/L (58.4-227.2 µg/L), and 152.1 µg/L (75.8-268.3 µg/L), respectively. The UIC in children was found to be higher than that in their mothers (p < 0.001). Children who consumed less than 500 mL per day of formula milk in the last week had lower UICs compared with those who consumed 500 mL per day or more (p = 0.026). Furthermore, the children's UIC was positively correlated with the maternal UIC (rs = 0.285, p < 0.001). Multiple quantile regression analysis revealed a statistically significant positive association between maternal UIC and children's UIC between the 0.1 and 0.9 quantiles (all p < 0.001). We found that the iodine status of infants and toddlers, as well as of mothers, was sufficient. However, a large minority of children and mothers may be at risk of iodine deficiency. Furthermore, no associations between children's UIC and feeding behaviors were observed. Moreover, there was a positive correlation between the UIC of young children and their mothers.


Asunto(s)
Conducta Alimentaria , Yodo , Estado Nutricional , Humanos , Yodo/deficiencia , Yodo/orina , Yodo/administración & dosificación , Lactante , Femenino , China/epidemiología , Masculino , Madres , Adulto , Fenómenos Fisiológicos Nutricionales del Lactante , Análisis de Regresión , Estudios de Cohortes , Lactancia Materna/estadística & datos numéricos
4.
Anal Methods ; 16(26): 4291-4300, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38887095

RESUMEN

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers, which are of growing concern due to their endocrine-disrupting effects, developmental toxicity, and potential carcinogenicity. However, data on human exposure to OPEs is still scarce. In this study, a relatively simple and efficient method with less serum consumption for the detection of OPEs in human serum was developed and validated. Nine OPEs in 200 µL of human serum were extracted by an acetonitrile-formic acid system and analyzed using ultra-high-performance liquid chromatography-quadrupole tandem time-of-flight high-resolution mass spectrometry. Several experiments were conducted to optimize the chromatographic and mass spectrometric conditions as well as sample preparation to obtain a more sensitive and efficient analytical protocol. The proposed method was examined in terms of its linearity, accuracy, precision, detection limit, and matrix effect. The matrix-spiked recoveries of the target OPEs ranged from 83.3% to 111.1%, with relative standard deviations between 2.7% and 16.6%. The detection limits were within (0.002 to 0.029) ng mL-1, while the quantification limits were within (0.007 to 0.098) ng mL-1. The internal standard-corrected matrix effects varied from 82.7% to 113.9%. Finally, the method was applied to detect OPEs in actual human serum samples. All nine OPEs were detected in 269 serum samples to varying degrees, with the average concentrations ranging from (0.08 to 1.77) ng mL-1. After validation, the method was found to be simple in pretreatment, high in sensitivity, good in practicality, and suitable for exposure evaluation of OPEs in populations.


Asunto(s)
Ésteres , Organofosfatos , Humanos , Ésteres/sangre , Organofosfatos/sangre , Cromatografía Líquida de Alta Presión/métodos , Límite de Detección , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados , Cromatografía Liquida/métodos , Retardadores de Llama/análisis , Espectrometría de Masas/métodos , Cromatografía Líquida con Espectrometría de Masas
5.
Toxics ; 12(6)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922068

RESUMEN

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress-a pivotal mechanism behind its toxicity-is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications.

6.
Toxics ; 12(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38922072

RESUMEN

BACKGROUND: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in environmental media. Unfortunately, OPFRs have been associated with many adverse health outcomes. The issue of the health risks of OPFRs is attracting increasing attention. Therefore, there is a need to review the current state of research and trends in this field to help researchers and policymakers quickly understand the field, identify new research directions, and allocate appropriate resources for further development of the OPFR health risk research field. METHODS: This study statistically analyzed 1162 relevant publications included in the Web of Science Core Collection from 2003-2023. The internal and external features of the literature, such as publication trends, countries, authors, journals, and keywords, were quantitatively analyzed and visually presented to identify the research hotspots, compositions, and paradigms of the field and to horizontally and vertically analyze the development trends and structural evolution of the field. RESULTS: The development of the field can be divided into three stages, and the field entered a period of rapid development in 2016. China (649 papers) is the most prolific country, followed by the United States (188 papers). The authors STAPLETON HM and WANG Y have the highest combined impact. International collaboration between countries and researchers still needs to be strengthened. Science of The Total Environment is the most frequently published journal (162 papers), and Environmental Science and Technology is the most frequently cited journal (5285 citations). Endocrine disruption, developmental toxicity, and neurotoxicity are the health effects of greatest interest. CONCLUSIONS: Future research is expected to be multidisciplinary, and research hotspots may involve a comprehensive assessment of OPFR exposure in the population, exploration of the mechanisms of endocrine-disrupting effects and in vivo metabolic processes, and examination of the health effects of OPFR metabolites.

7.
Medicine (Baltimore) ; 103(24): e38423, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875425

RESUMEN

The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU.


Asunto(s)
Enfermedad Crítica , Tromboembolia Venosa , Humanos , Masculino , Femenino , Estudios Retrospectivos , Tromboembolia Venosa/epidemiología , Persona de Mediana Edad , Factores Sexuales , Anciano , Adulto , Factores de Riesgo , Unidades de Cuidados Intensivos/estadística & datos numéricos , APACHE
8.
Toxicol In Vitro ; 99: 105853, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38806067

RESUMEN

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women's test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.

9.
Sci Rep ; 14(1): 11670, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778047

RESUMEN

Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499-981 bp) and (1053-1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086-1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Ciclooxigenasa 2 , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Regiones Promotoras Genéticas , Regulación hacia Arriba , Humanos , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Movimiento Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Células HCT116
10.
Commun Med (Lond) ; 4(1): 90, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760506

RESUMEN

BACKGROUND: Though deep learning has consistently demonstrated advantages in the automatic interpretation of breast ultrasound images, its black-box nature hinders potential interactions with radiologists, posing obstacles for clinical deployment. METHODS: We proposed a domain knowledge-based interpretable deep learning system for improving breast cancer risk prediction via paired multimodal ultrasound images. The deep learning system was developed on 4320 multimodal breast ultrasound images of 1440 biopsy-confirmed lesions from 1348 prospectively enrolled patients across two hospitals between August 2019 and December 2022. The lesions were allocated to 70% training cohort, 10% validation cohort, and 20% test cohort based on case recruitment date. RESULTS: Here, we show that the interpretable deep learning system can predict breast cancer risk as accurately as experienced radiologists, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval = 0.882 - 0.921), sensitivity of 75.2%, and specificity of 91.8% on the test cohort. With the aid of the deep learning system, particularly its inherent explainable features, junior radiologists tend to achieve better clinical outcomes, while senior radiologists experience increased confidence levels. Multimodal ultrasound images augmented with domain knowledge-based reasoning cues enable an effective human-machine collaboration at a high level of prediction performance. CONCLUSIONS: Such a clinically applicable deep learning system may be incorporated into future breast cancer screening and support assisted or second-read workflows.


Breast cancer is one of the most common cancers, and finding it early can greatly improve patients' chances of survival and recovery. We create a tool based on artificial intelligence (AI)­whereby computer software learns to perform tasks that normally require human thinking­called MUP-Net. MUP-Net can analyze medical images to predict a patient's risk of having breast cancer. To make this AI tool usable in clinical practice, we enabled doctors to see the reasoning behind the AI's predictions by visualizing the key image features it analyzed. We showed that our AI tool not only makes doctors more confident in their diagnosis but also helps them make better decisions, especially for less experienced doctors. With further testing, our AI tool may help clinicians to diagnose breast cancer more accurately and quickly, potentially improving patient outcomes.

11.
Clinics (Sao Paulo) ; 79: 100372, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733688

RESUMEN

OBJECTIVE: This study aims to analyze the relationship between the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Epilepsy (EP), as well as its mechanism of action. METHODS: Thirty Wistar rats were divided into a control group (without treatment), a model group (EP modeling), and an inhibition group (EP modeling + intervention by Keap1/Nrf2 signaling pathway inhibitor ATRA) and subject to Morris water maze experiment. Then, the expression of Oxidative Stress (OS) markers, ferroptosis-associated proteins and Keap1/Nrf2 pathway in rat hippocampus was measured. In addition, rat hippocampal neuronal cell HT22 was purchased and treated accordingly based on the results of grouping, and cell proliferation and apoptosis in the three groups were determined. RESULTS: Compared with rats in the model group, those in the inhibition group showed shorter escape latency and an increased number of platform crossings (p < 0.05). Significant OS and neuron ferroptosis, increased apoptosis rate, elevated Keap1 expression, and decreased Nrf2 expression were observed in the model group compared to the control group (p < 0.05). The inhibition group exhibited notably improved OS and ferroptosis, as well as enhanced neuronal viability (p < 0.05). CONCLUSION: Inhibition of the Keap1/Nrf2 pathway can reverse the OS and neuron viability in EP rats.


Asunto(s)
Epilepsia , Ferroptosis , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Neuronas , Estrés Oxidativo , Ratas Wistar , Transducción de Señal , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/fisiología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología , Ferroptosis/fisiología , Ferroptosis/efectos de los fármacos , Neuronas/metabolismo , Epilepsia/metabolismo , Epilepsia/fisiopatología , Masculino , Hipocampo/metabolismo , Apoptosis/fisiología , Ratas , Progresión de la Enfermedad , Modelos Animales de Enfermedad
12.
Carbohydr Polym ; 335: 122079, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38616076

RESUMEN

The polysaccharides and triterpenes are important functional components of Ganoderma lucidum, but traditional preparation process of G. lucidum functional components can only realize the preparation of single functional component, which has poor targeting and low efficiency. In this study, the existence state of the functional components of G. lucidum was revealed. Then, the single step extraction process for functional components was established, and the precise structure evaluation of polysaccharide and triterpenes was conducted based on the process. The results showed that preparation time required for this strategy is only one-sixth of the traditional one, and 50 % of raw materials can be saved. Structural analysis of the functional components revealed that triterpenes were mainly Ganoderic acid and Lucidenic acid, and the polysaccharide structure was mainly 1,3-glucan and 1,3,6-glucan. The establishment of single step extraction strategy and the evaluation of the fine structure of functional components improved the efficiency of preparation and result determination, and provided an important basis for the development and utilization of green and low-carbon G. lucidum and even edible fungi resources and human nutritional dietary improvement strategies.


Asunto(s)
Reishi , Triterpenos , Humanos , Polisacáridos , Glucanos , China
14.
Int J Biol Macromol ; 263(Pt 1): 130607, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38447848

RESUMEN

Bactrocera dorsalis is a notorious pest widely distributed across most Asian countries. With the rapid development of pesticide resistance, new pest control methods are urgently needed. RNAi-based sterile insect technique (SIT) is a species-specific pest management strategy for B. dorsalis control. It is of great significance to identify more target genes from B. dorsalis, and improve the RNAi efficiency. In this study, microinjection-based RNAi results showed that six 20E response genes were necessary for male fertility of B. dorsalis, of which E75 was identified as the key target according to the lowest egg-laying number and hatching rate after E75 knockdown. Three nanoparticles chitosan (CS), chitosan­sodium tripolyphosphate (CS-TPP), and star polycation (SPc) were used to encapsulate dsE75 expressed by HT115 strain. Properties analysis of nanoparticle-dsRNA complexes showed that both CS-TPP-dsRNA and SPc-dsRNA exhibited better properties (smaller size and polydispersity index) than CS-dsRNA. Moreover, oral administration of CS-TPP-dsE75 and SPc-dsE75 by males resulted in more abnormal testis and significantly lower fertility than feeding naked dsE75. Semi-field trials further confirmed that the number of hatched larvae was dramatically reduced in these two groups. Our study not only provides more valuable targets for RNAi-based SIT, but also promotes the application of environment-friendly management against B. dorsalis in the field.


Asunto(s)
Quitosano , Infertilidad , Nanopartículas , Tephritidae , Animales , Masculino , Interferencia de ARN , Ecdisona , Insectos , Control de Plagas
15.
Protein Sci ; 33(4): e4944, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38501479

RESUMEN

Antibody (Ab)-based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab-based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag-X (S-X) to form the SpaCC-S-X complex, which binds non-covalently to an Ab to form the Ab-SpaCC-S-X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell-penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab-SpaCC-S-FITC(-TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab-SpaCC-SN3-MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab-DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab-SpaCC-SN3-Ap boosted the tumor-killing function of T-cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.


Asunto(s)
Péptidos de Penetración Celular , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Inmunoterapia , Anticuerpos , ADN , Línea Celular Tumoral
16.
Cell Mol Life Sci ; 81(1): 91, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38361078

RESUMEN

It is known that about 10 circular RNAs (circRNAs) can encode functional polypeptides in higher mammals. However, it is not clear whether the functional polypeptides that can be translated by circRNAs are only the products of the evolution of higher animals, or also widely exist in other lower organisms. In addition, it is also unclear whether the two ways of translating polypeptides using IRES and m6A in the one circRNA are exclusive or coexistent. Here, we discovered a novel circRNA derived from the 3'-5' RNA helicase Ythdc2 (Ythdc2) gene in lower vertebrate fish, namely circYthdc2, which can translate into a 170 amino acid polypeptide (Ythdc2-170aa) through IRES sequence or m6A modification, and is involved in antiviral immune of fish. Moreover, SCRV infection can promote circYthdc2 translate Ythdc2-170aa. Then, we found that both Ythdc2-170aa and Ythdc2 can promote the degradation of STING by promoting the ubiquitination modification of K11 and K48 link of STING, and weaken the host's antiviral innate immunity. Notably, when circYthdc2 is abundant, Ythdc2 preferentially degrades circYthdc2 and no longer promotes the degradation of STING. Further studies have shown that circYthdc2 is highly conserved from lower vertebrates to higher mammals, and human circYthdc2 can also encode the same polypeptide and play a similar function to that of fish circYthdc2. This discovery confirms for the first time that the ability of circRNA to encode functional proteins is evolutionarily conserved, and finds that the ways of polypeptide translation by the same circRNA were diverse, which is of great significance for further elucidating the function and evolution of circRNAs in vertebrates.


Asunto(s)
Péptidos , ARN Circular , Animales , Humanos , ARN Circular/genética , Péptidos/genética , Mamíferos/genética
17.
Adv Sci (Weinh) ; 11(12): e2305839, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38225713

RESUMEN

Durable superhydrophobic anti-erosion/anticorrosion coatings are highly demanded across various applications. However, achieving coatings with exceptional superhydrophobicity, mechanical strength, and corrosion resistance remains a grand challenge. Herein, a robust microstructure coating, inspired by the cylindrical structures situated on the surface of conch shell, for mitigating erosion and corrosion damages in gas transportation pipelines is reported. Specifically, citric acid monohydrate as a pore-forming agent is leveraged to create a porous structure between layers, effectively buffering the impact on the surface. As a result, the coating demonstrates remarkable wear resistance and water repellency. Importantly, even after abrasion by sandpaper and an erosion loop test, the resulting superhydrophobic surfaces retain the water repellency. The design strategy offers a promising route to manufacturing multifunctional materials with desired features and structural complexities, thereby enabling effective self-cleaning and antifouling abilities in harsh operating environments for an array of applications, including self-cleaning windows, antifouling coatings for medical devices, and anti-erosion/anticorrosion protection, among other areas.

18.
Sci Total Environ ; 914: 169731, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38163589

RESUMEN

Nitrogen (N) input has a significant impact on the availability of carbon (C), nitrogen (N), and phosphorus (P) in the rhizosphere, leading to an imbalanced stoichiometry in microbial demands. This imbalance can result in energy or nutrient limitations, which, in turn, affect C dynamics during plant growth. However, the precise influence of N addition on the C:N:P imbalance ratio and its subsequent effects on rhizosphere priming effects (RPEs) remain unclear. To address this gap, we conducted a 75-day microcosm experiment, varying N addition rates (0, 150, 300 kg N ha-1), to examine how microbes regulate RPE by adapting to stoichiometry and maintaining homeostasis in response to N addition, using the 13C natural method. Our result showed that N input induced a stoichiometric imbalance in C:N:P, leading to P or C limitation for microbes during plant growth. Microbes responded by adjusting enzymatic stoichiometry and functional taxa to preserve homeostasis, thereby modifying the threshold element ratios (TERs) to cope with the C:N:P imbalance. Microbes adapted to the stoichiometric imbalance by reducing TER, which was attributed to a reduction in carbon use efficiency. Consequently, we observed higher RPE under P limitation, whereas the opposite trend was observed under C or N limitation. These results offer novel insights into the microbial regulation of RPE variation under different soil nutrient conditions and contribute to a better understanding of soil C dynamics.


Asunto(s)
Nitrógeno , Rizosfera , Nitrógeno/análisis , Carbono , Suelo , Fósforo , Microbiología del Suelo
19.
J Am Chem Soc ; 146(5): 3200-3209, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38276958

RESUMEN

The introduction of lanthanide ions (Ln3+) into all-inorganic lead-free halide perovskites has captured significant attention in optoelectronic applications. However, doping Ln3+ ions into heterometallic halide layered double perovskite (LDP) nanocrystals (NCs) and their associated doping mechanisms remain unexplored. Herein, we report the first colloidal synthesis of Ln3+ (Yb3+, Er3+)-doped LDP NCs utilizing a modified hot-injection method. The resulting NCs exhibit efficient near-infrared (NIR) photoluminescence in both NIR-I and NIR-II regions, achieved through energy transfer down-conversion mechanisms. Density functional theory calculations reveal that Ln3+ dopants preferentially occupy the Sb3+ cation positions, resulting in a disruption of local site symmetry of the LDP lattices. By leveraging sensitizations of intermediate energy levels, we delved into a series of Ln3+-doped Cs4M(II)Sb2Cl12 (M(II): Cd2+ or Mn2+) LDP NCs via co-doping strategies. Remarkably, we observe a brightening effect of the predark states of Er3+ dopant in the Er3+-doped Cs4M(II)Sb2Cl12 LDP NCs owing to the Mn component acting as an intermediate energy bridge. This study not only advances our understanding of energy transfer mechanisms in doped NCs but also propels all-inorganic LDP NCs for a wider range of optoelectronic applications.

20.
Food Chem X ; 21: 101106, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38235345

RESUMEN

Cuticular wax is the first line of structural defense for plants against external stresses. This study investigated the effects of melatonin (MT) on chemical composition and accumulation profile of wax, as well as fruit quality of rabbiteye blueberry during storage. The results indicated a significant reduction in the overall wax content during storage. Nevertheless, MT effectively delayed the decline, with a higher amount of 9.8% and 15.17% in the treated 'Baldwin' and 'Garden Blue' compared to their respective controls at 21st day of storage. The wax composition significantly varied depending on storage time, MT treatment, and cultivars. Additionally, MT markedly improved the fruit quality of rabbiteye blueberries. Correlation analysis revealed water loss and decay rates were negatively correlated with triterpenoids and fatty acids. Taken together, this study highlights the positive effects of post-harvest MT application on shelf life and fruit quality of blueberry by modifying the wax profile during storage.

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