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1.
Cereb Cortex ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38584086

RESUMEN

Machine learning is an emerging tool in clinical psychology and neuroscience for the individualized prediction of psychiatric symptoms. However, its application in non-clinical populations is still in its infancy. Given the widespread morphological changes observed in psychiatric disorders, our study applies five supervised machine learning regression algorithms-ridge regression, support vector regression, partial least squares regression, least absolute shrinkage and selection operator regression, and Elastic-Net regression-to predict anxiety and depressive symptom scores. We base these predictions on the whole-brain gray matter volume in a large non-clinical sample (n = 425). Our results demonstrate that machine learning algorithms can effectively predict individual variability in anxiety and depressive symptoms, as measured by the Mood and Anxiety Symptoms Questionnaire. The most discriminative features contributing to the prediction models were primarily located in the prefrontal-parietal, temporal, visual, and sub-cortical regions (e.g. amygdala, hippocampus, and putamen). These regions showed distinct patterns for anxious arousal and high positive affect in three of the five models (partial least squares regression, support vector regression, and ridge regression). Importantly, these predictions were consistent across genders and robust to demographic variability (e.g. age, parental education, etc.). Our findings offer critical insights into the distinct brain morphological patterns underlying specific components of anxiety and depressive symptoms, supporting the existing tripartite theory from a neuroimaging perspective.


Asunto(s)
Depresión , Sustancia Gris , Humanos , Masculino , Femenino , Sustancia Gris/diagnóstico por imagen , Depresión/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ansiedad/diagnóstico por imagen , Ansiedad/psicología , Afecto
2.
BMC Biotechnol ; 24(1): 77, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385151

RESUMEN

BACKGROUND: Homocysteine (HCY) is a sulfur-containing amino acid that is an independent or important risk factor for the occurrence of many chronic diseases and is one of the most important indicators for determining health risks. However, existing HCY detection methods do not meet the requirements of clinical diagnosis. Therefore, there is an urgent need to establish new detection methods to meet the needs of clinical detection. RESULTS: In this study, we used the principle of competitive method to establish a new method for the determination of HCY in human serum using a chemiluminescent enzyme immunoassay in conjunction with a chemiluminescent assay instrument that uses magnetic microparticles as the solid phase of the immunoreaction. The established method achieved satisfactory results in terms of minimum detection limit, specificity, accuracy, and clinical application. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 1.94-5.05%, the inter-assay CV was 2.29-6.88%, and the recovery rate was 88.60-93.27%. Cross-reactivity with L-cysteine ranged from 0.0100 to 0.0200 µmol/L, and cross-reactivity with glutathione ranged from 0.0100 to 0.200 µmol/L, all of which were less than the limit of detection (LoD) of this method. The linear factor R of this method was greater than 0.99. CONCLUSIONS: In summary, the developed method showed a good correlation with the product from Abbott. A total of 996 clinical patients with cardiovascular diseases were evaluated using the method developed in this study.


Asunto(s)
Homocisteína , Límite de Detección , Mediciones Luminiscentes , Humanos , Homocisteína/sangre , Mediciones Luminiscentes/métodos , Inmunoensayo/métodos , Femenino , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto
3.
J Transl Med ; 22(1): 290, 2024 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500157

RESUMEN

Lipid metabolism is widely reprogrammed in tumor cells. Lipid droplet is a common organelle existing in most mammal cells, and its complex and dynamic functions in maintaining redox and metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, and providing essential biomolecules and ATP have been well established in tumor cells. The balance between lipid droplet formation and catabolism is critical to maintaining energy metabolism in tumor cells, while the process of energy metabolism affects various functions essential for tumor growth. The imbalance of synthesis and catabolism of fatty acids in tumor cells leads to the alteration of lipid droplet content in tumor cells. Diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2, the enzymes that catalyze the final step of triglyceride synthesis, participate in the formation of lipid droplets in tumor cells and in the regulation of cell proliferation, migration and invasion, chemoresistance, and prognosis in tumor. Several diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 inhibitors have been developed over the past decade and have shown anti-tumor effects in preclinical tumor models and improvement of metabolism in clinical trials. In this review, we highlight key features of fatty acid metabolism and different paradigms of diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 activities on cell proliferation, migration, chemoresistance, and prognosis in tumor, with the hope that these scientific findings will have potential clinical implications.


Asunto(s)
Diacilglicerol O-Acetiltransferasa , Neoplasias , Animales , Humanos , Diacilglicerol O-Acetiltransferasa/genética , Diacilglicerol O-Acetiltransferasa/metabolismo , Triglicéridos/metabolismo , Metabolismo de los Lípidos , Lipogénesis , Proliferación Celular , Mamíferos/metabolismo
4.
Gynecol Oncol ; 191: 116-123, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39388742

RESUMEN

OBJECTIVE: Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC. METHODS: Starting at 4 weeks of age, Lkb1fl/flp53fl/fl mice were fed a low-fat diet vs a high-fat diet to generate a lean or obese phenotype. Nine weeks after induction of EC, obese and lean mice were randomized to receive tirzepatide for 4 weeks. Body and tumor weights, tumor transcriptomic and metabolomic profiles, and serum metabolic markers and chemokines were assessed. RESULTS: Both obese and lean mice began to lose body weight after 2 weeks of tirzepatide treatment, ultimately achieving a significant weight loss of 20.1 % in obese mice and 16.8 % in lean mice. Tirzepatide improved obesity-induced serum adiponectin, leptin, GIP, and C-reactive protein levels. Furthermore, tirzepatide relative to vehicle, effectively reduced tumor growth in obese and lean mice, inhibited the ErbB signaling and glycolysis/gluconeogenesis in tumors of obese mice, and increased O-linked glycosylation biosynthesis and phospholipase D signaling in tumors of lean mice. CONCLUSION: Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC.

5.
Gynecol Oncol ; 183: 93-102, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38555710

RESUMEN

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.


Asunto(s)
Apoptosis , Ácido Ascórbico , Carboplatino , Cistadenocarcinoma Seroso , Sinergismo Farmacológico , Neoplasias Uterinas , Ácido Ascórbico/farmacología , Ácido Ascórbico/administración & dosificación , Humanos , Carboplatino/farmacología , Carboplatino/administración & dosificación , Femenino , Línea Celular Tumoral , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Neoplasias Uterinas/metabolismo , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Especies Reactivas de Oxígeno/metabolismo , Daño del ADN/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/administración & dosificación
6.
Cereb Cortex ; 33(9): 5323-5335, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36320161

RESUMEN

When anticipating future losses, people respond by exhibiting 1 of 2 starkly distinct behavioral decision patterns: the dread of future losses (DFL) and the preference of future losses (vs. immediate losses). Yet, how to accurately discriminate between those who exhibit dread vs. preference and uncover the potential neurobiological substrates underlying these 2 groups remain understudied. To address this, we designed a novel experimental task in which the DFL group was defined as selecting immediate-loss options >50% in the trials with approximate subjective value in immediate and delayed options (n = 16), otherwise coding as the preference of future losses (PFL). At the behavioral level, DFL exhibited higher weight for delayed losses than immediate losses via the logistic regression model. At the neural level, DFL manifested hypoactivations on subjective valuations of delayed losses, atypical brain pattern when choosing immediate-loss options, and decreased functional coupling between the valuation and choice-systems when making decisions related to immediate-loss alternatives compared with PFL. Moreover, both these brain activations subserving distinct decision processes and their interactions predicted individual decisions and behavioral preferences. Furthermore, morphological analysis also revealed decreased right precuneus volume in DFL compared with PFL, and brain activations related to valuation and choice process mediated the associations between this region volume and behavioral performances. Taken together, these findings help to clarify potential cognitive and neural mechanisms underlying the DFL and provide a clear discrimination strategy.


Asunto(s)
Encéfalo , Toma de Decisiones , Humanos , Mapeo Encefálico , Recompensa
7.
Neurobiol Dis ; 179: 106066, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36889483

RESUMEN

Although both are myeloid cells located surrounding cerebral vasculature, vessel-associated microglia (VAM) and perivascular macrophages (PVMs) can be distinguished by their distinct morphologies, signatures and microscopic location. As key component of neuro-glia-vascular unit (NGVU), they play prominent roles in neurovasculature development and pathological process of various central nervous system (CNS) diseases, including phagocytosis, angiogenesis, vessel damage/protection and blood flow regulation, therefore serving as potential targets for therapeutics of a broad array of CNS diseases. Herein, we will provide a comprehensive overview of heterogeneity of VAM/PVMs, highlight limitations of current understanding in this field, and discuss possible directions of future investigations.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Microglía , Humanos , Microglía/fisiología , Encéfalo/patología , Macrófagos , Fagocitosis , Enfermedades del Sistema Nervioso Central/patología
8.
Hum Brain Mapp ; 44(17): 5693-5711, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37614216

RESUMEN

Several studies have examined the neural substrates of probabilistic decision-making, but few have systematically investigated the neural representations of the two objective attributes of probabilistic rewards, that is, the reward amount and the probability. Specifically, whether there are common or distinct neural activity patterns to represent the objective attributes and their association with the neural representation of the subjective valuation remains largely underexplored. We conducted two studies (nStudy1 = 34, nStudy2 = 41) to uncover distributed neural representations of the objective attributes and subjective value as well as their association with individual probability discounting rates. The amount and probability were independently manipulated to better capture brain signals sensitive to these two attributes and were presented simultaneously in Study 1 and successively in Study 2. Both univariate and multivariate pattern analyses showed that the brain activities in the superior parietal lobule (SPL), including the postcentral gyrus, were modulated by the amount of rewards and probability in both studies. Further, representational similarity analysis revealed a similar neural representation between these two objective attributes and between the attribute and valuation. Moreover, the SPL tracked the subjective value integrated by the hyperbolic function. Probability-related brain activations in the inferior parietal lobule were associated with the variability in individual discounting rates. These findings provide novel insights into a similar neural representation of the two attributes during probabilistic decision-making and perhaps support the common neural coding of stimulus objective properties and subjective value in the field of probabilistic discounting.


Asunto(s)
Encéfalo , Recompensa , Humanos , Encéfalo/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Mapeo Encefálico , Sistema Límbico , Imagen por Resonancia Magnética
9.
J Neuroinflammation ; 20(1): 244, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875988

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) is a significant worldwide public health concern that necessitates attention. Apoptosis signal-regulating kinase 1 (ASK1), a key player in various central nervous system (CNS) diseases, has garnered interest for its potential neuroprotective effects against ischemic stroke and epilepsy when deleted. Nonetheless, the specific impact of ASK1 on TBI and its underlying mechanisms remain elusive. Notably, mutation of ATP-binding sites, such as lysine residues, can lead to catalytic inactivation of ASK1. To address these knowledge gaps, we generated transgenic mice harboring a site-specific mutant ASK1 Map3k5-e (K716R), enabling us to assess its effects and elucidate potential underlying mechanisms following TBI. METHODS: We employed the CRIPR/Cas9 system to generate a transgenic mouse model carrying the ASK1-K716R mutation, aming to investigate the functional implications of this specific mutant. The controlled cortical impact method was utilized to induce TBI. Expression and distribution of ASK1 were detected through Western blotting and immunofluorescence staining, respectively. The ASK1 kinase activity after TBI was detected by a specific ASK1 kinase activity kit. Cerebral microvessels were isolated by gradient centrifugation using dextran. Immunofluorescence staining was performed to evaluate blood-brain barrier (BBB) damage. BBB ultrastructure was visualized using transmission electron microscopy, while the expression levels of endothelial tight junction proteins and ASK1 signaling pathway proteins was detected by Western blotting. To investigate TBI-induced neuroinflammation, we conducted immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analyses. Additionally, immunofluorescence staining and electrophysiological compound action potentials were conducted to evaluate gray and white matter injury. Finally, sensorimotor function and cognitive function were assessed by a battery of behavioral tests. RESULTS: The activity of ASK1-K716R was significantly decreased following TBI. Western blotting confirmed that ASK1-K716R effectively inhibited the phosphorylation of ASK1, JNKs, and p38 in response to TBI. Additionally, ASK1-K716R demonstrated a protective function in maintaining BBB integrity by suppressing ASK1/JNKs activity in endothelial cells, thereby reducing the degradation of tight junction proteins following TBI. Besides, ASK1-K716R effectively suppressed the infiltration of peripheral immune cells into the brain parenchyma, decreased the number of proinflammatory-like microglia/macrophages, increased the number of anti-inflammatory-like microglia/macrophages, and downregulated expression of several proinflammatory factors. Furthermore, ASK1-K716R attenuated white matter injury and improved the nerve conduction function of both myelinated and unmyelinated fibers after TBI. Finally, our findings demonstrated that ASK1-K716R exhibited favorable long-term functional and histological outcomes in the aftermath of TBI. CONCLUSION: ASK1-K716R preserves BBB integrity by inhibiting ASK1/JNKs pathway in endothelial cells, consequently reducing the degradation of tight junction proteins. Additionally, it alleviates early neuroinflammation by inhibiting the infiltration of peripheral immune cells into the brain parenchyma and modulating the polarization of microglia/macrophages. These beneficial effects of ASK1-K716R subsequently result in a reduction in white matter injury and promote the long-term recovery of neurological function following TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Sustancia Blanca , Ratones , Animales , Barrera Hematoencefálica/metabolismo , Enfermedades Neuroinflamatorias , Sustancia Blanca/patología , Células Endoteliales/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Lesiones Encefálicas/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Ratones Endogámicos C57BL
10.
Behav Brain Funct ; 19(1): 21, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38041182

RESUMEN

This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (ntotal = 452). In Cohort 1 (n = 83), task-based functional magnetic resonance imaging (t-fMRI) results from a region-of-interest (ROI) analysis revealed no direct correlation between amygdala reactivity to fearful and angry faces and GPT. Instead, whole-brain analyses revealed GPT to robustly negatively vary with activations in the right ventromedial prefrontal cortex (vmPFC), supramarginal gyrus, and angular gyrus in the contrast of fearful + angry faces > shapes. Moreover, task-based psychophysiological interaction (PPI) analyses showed that the high GPT group showed weaker functional connectivity of the vmPFC seed with a top-down control network and visual pathways when processing fearful or angry faces compared to their lower GPT counterparts. In Cohort 2, resting-state functional connectivity (rs-FC) analyses indicated stronger connectivity between the vmPFC seed and the top-down control network and visual pathways in individuals with higher GPT. Comparing the two cohorts, bilateral amygdala seeds showed weaker associations with the top-down control network in the high group via PPI analyses in Cohort 1. Yet, they exhibited distinct rs-FC patterns in Cohort 2 (e.g., positive associations of GPT with the left amygdala-top-down network FC but negative associations with the right amygdala-visual pathway FC). The study underscores the role of the vmPFC and its functional connectivity in understanding GPT, rather than amygdala reactivity.


Asunto(s)
Mapeo Encefálico , Emociones , Humanos , Emociones/fisiología , Mapeo Encefálico/métodos , Corteza Prefrontal/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiología , Imagen por Resonancia Magnética , Personalidad , Vías Nerviosas/diagnóstico por imagen
11.
Environ Sci Technol ; 57(9): 3623-3633, 2023 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-36790324

RESUMEN

Nonradical oxidation has been determined to be a promising pathway for the degradation of organic pollutants in heterogeneous catalytic ozonation (HCO). However, the bottlenecks are the rational design of catalysts to selectively induce nonradicals and the interpretation of detailed nonradical generation mechanisms. Herein, we propose a new HCO process based on single-atom iron catalysts, in which Fe-N4 sites anchored on the carbon skeleton exhibited outstanding catalytic ozonation activity and stability for the degradation of oxalic acid (OA) and p-hydroxybenzoic acid (pHBA) as well as the advanced treatment of a landfill leachate secondary effluent. Unlike traditional radical oxidation, nonradical pathways based on surface-adsorbed atomic oxygen (*Oad) and singlet oxygen (1O2) were identified. A substrate-dependent behavior was also observed. OA was adsorbed on the catalyst surface and mainly degraded by *Oad, while pHBA was mostly removed by O3 and 1O2 in the bulk solution. Density functional theory calculations and molecular dynamics simulations revealed that one terminal oxygen atom of ozone preferred bonding with the central iron atom of Fe-N4, subsequently inducing the cleavage of the O-O bond near the catalyst surface to produce *Oad and 1O2. These findings highlight the structural design of an ozone catalyst and an atomic-level understanding of the nonradical HCO process.


Asunto(s)
Ozono , Contaminantes Químicos del Agua , Purificación del Agua , Carbono , Oxidación-Reducción , Hierro/química , Catálisis , Ácido Oxálico , Contaminantes Químicos del Agua/análisis
12.
Int J Med Sci ; 20(3): 415-428, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36860677

RESUMEN

Endometriosis is a hormone-dependent disease in women of reproductive age and seriously affects women's health. To analyze the involvement of sex hormone receptors in endometriosis development, we performed bioinformatics analysis using four datasets derived from the Gene Expression Omnibus (GEO) database, which may help us understand the mechanisms by which the sex hormones act in vivo in endometriosis patients. The enrichment analysis and protein-protein interaction (PPI) analysis of the differentially expressed genes (DEGs) revealed that there are different key genes and pathways involved in eutopic endometrium aberrations of endometriosis patients and endometriotic lesions, and sex hormone receptors, including androgen receptor (AR), progesterone receptor (PGR) and estrogen receptor 1 (ESR1), may play important roles in endometriosis development. Androgen receptor (AR), as the hub gene of endometrial aberrations in endometriotic patients, showed positive expression in the main cell types for endometriosis development, and its decreased expression in the endometrium of endometriotic patients was also confirmed by immunohistochemistry (IHC). The nomogram model established based on it displayed good predictive value.


Asunto(s)
Endometriosis , Humanos , Femenino , Endometriosis/genética , Receptores Androgénicos/genética , Biología Computacional , Bases de Datos Factuales , Hormonas Esteroides Gonadales
13.
Int J Mol Sci ; 24(15)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37569896

RESUMEN

To better understand the potential toxicity risks of isoflucypram in humans, The interaction between isoflucypram and HSA (human serum albumin) was studied through molecular docking, molecular dynamics simulations, ultraviolet-visible absorption, fluorescence, synchronous fluorescence, three-dimensional fluorescence, Fourier transform infrared spectroscopies, and circular dichroism spectroscopies. The interaction details were studied using the molecular docking method and molecular dynamics simulation method. The results revealed that the effect of isoflucypram on human serum albumin was mixed (static and dynamic) quenching. Additionally, we were able to obtain important information on the number of binding sites, binding constants, and binding distance. The interaction between isoflucypram and human serum albumin occurred mainly through hydrogen bonds and van der Waals forces. Spectroscopic results showed that isoflucypram caused conformational changes in HSA (human serum albumin), in which the α-helix was transformed into a ß-turn, ß-sheet, and random coil, causing the HSA structure to loosen. By providing new insights into the mechanism of binding between isoflucypram and human serum albumin, our study has important implications for assessing the potential toxicity risks associated with isoflucypram exposure.


Asunto(s)
Fungicidas Industriales , Albúmina Sérica Humana , Humanos , Sitios de Unión , Dicroismo Circular , Fungicidas Industriales/toxicidad , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica , Albúmina Sérica Humana/química , Espectrometría de Fluorescencia/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Termodinámica
14.
J Nanobiotechnology ; 20(1): 468, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36329515

RESUMEN

The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from "cold tumor" to "hot tumor" that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias Ováricas , Humanos , Femenino , Ratones , Animales , Fototerapia/métodos , Nanopartículas/uso terapéutico , Hidróxido de Aluminio , Línea Celular Tumoral , Verde de Indocianina , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Inmunoterapia , Antígenos de Neoplasias , Microambiente Tumoral
15.
Plant Dis ; 2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-36324200

RESUMEN

Tea-oil tree (Camellia oleifera Abel) is an important economic woody plant in southern China. The buds, fruits, and leaves of tea oil tree are all susceptible to the disease, causing the wilt or even fall of the plant. Every year, the disease incidence of anthracnose reached 20%-40% in diseased fields. In 2020, leaves with anthracnose were collected from the main producing areas of tea-oil tree in Yunnan Province and Guizhou Province, China. To isolate the pathogen, several fragments of diseased tissues (5×5mm) were disinfected in 75% alcohol for 40 s, and rinsed 3 times in sterilized water. Then, tissues were placed on PDA medium and incubated at 26℃ for 5 days. Fungal isolates with morphology characteristics similar to Colletotrichum spp. were consistently recovered from diseased tissues. Eighteen fungal isolates were obtained. Among them, 3 representative single-spore isolates (C2, gy15, Ch) were picked for further analysis. The isolates C2 and gy15 on the PDA were gray-white in the initial stage, and later became olive green and spread to the edge. Abundant orange-red conidial masses were present in the colony surface. Conidia were cylindrical and with blunt circles at both ends, with a size of 9.9 µm ~ 21.8 µm × 4.0 µm ~ 6.8 µm (n=50). The hyphae of isolate Ch on PDA were thin, cotton-like, gray to gray-black; the center of the back of the colony was brown, and the color of the colony became darker, and concentric rings could be produced. The conidia were cylindrical , with blunt circles at both ends, with a size of 6.3 µm ~15.0 µm × 3.2 µm ~ 7.0µm (n=50). In order to further identify the pathogens, the internal transcribed spacer (ITS) region of ribosomal DNA, actin (ACT), chitin synthase (CHS), ß-tubulin (TUB2), calmodulin (CAL) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were amplified (Weir et al. 2012; Yang et al. 2009). The resulting sequences were deposited under the GenBank accession numbers OK148894, OM397909, OM249943, OL422149, OM184266 and OM718003 for C2,OK148975, OM397910, OM249944, OL422150, OM184267, OM718004 for gy15, OK148976, OM397911, OM249945, OL422151, OM184268 and OM718005 for Ch. A BLAST search showed that the sequences of isolates C2 and gy15 had 99.57% to 100% similarity to the type strain of Colletotrichum kahawae ICMP12952. The sequences of isolate Ch had 99.03% to 100% similarity to the type strain of Colletotrichum horri ICMP 17968. Further, a phylogenetic tree based on the combined ITS, ACT, CHS, TUB, CAL, and GAPDH sequence using the neighbor-joining algorithm revealed that the isolates were C. kahawae and C. horri (Fig. 1). Pathogenicity assays were conducted on healthy leaves collected from 1-year-old tea-oil tree. The experiments were repeated twice. The leaves were surface-sterilized with 75% ethanol. After drying, they were placed in a plastic box pre-laid with sterilized absorbent paper. The leaf surface was slightly pierced with a sterile needle, and each stab wound was inoculated with 10 µL of conidial suspension (1×106 conidia/ml). All inoculated leaves were placed in a moist chamber at 25℃ with 80% relative humidity. After 10 days, inoculated leaves showed similar symptoms as observed in the field, whereas controls remained symptomless. C. kahawae and C. horri were re-isolated from the diseased leaves, and identifed by sequencing. C. kahawae is widespread on coffee in Africa (Waller et al. 1993). C. horri has been associated with fruit and stem diseases of Diospyros kaki from China, Japan, and New Zealand (Weir et al. 2010). To our knowledge, this is the first report of C. kahawa and C. horri causing anthracnose of tea-oil tree.

16.
Plant Dis ; 2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35869583

RESUMEN

Root rot of peanut, caused by Fusarium spp., is a devastating disease in most peanut cultivation regions. In this reported outbreak, Fusarium root rot of peanut has been observed in Henan province, China in July 2021. About 20% of peanuts in a field (0.66 ha) were affected. Early symptoms comprised the wilt of the lower leaves, and the darkening of the vascular tissue of roots, which turned brown. Progressively, the whole plant wilted, the roots rotted, and the plant ultimately died. Pathogenic species were isolated from plants showing symptoms of root rot in the field. A total of 206 Fusarium isolates were generated, and 16 isolates were preliminarily identified as Fusarium fujikuroi based on morphological characteristics. Isolates were obtained and grown on PDA plates. Isolates developed floccose white aerial mycelia with reddish-pink coloration in the medium in 2 weeks on the benchtop. Macroconidia were 3-5 septate, measuring 27.5 to 48.8 × 2.6 to 3.8 µm (avg. 36.7 × 3.6 µm, n=50). Microconidia were abundant in chains, mainly asepatate, oval to kidney-shaped, 4.0 to 11.6 × 2.5 to 4.1 µm (avg. 5.8 ×3.1 µm, n=50). DNA was extracted from mycelium and the following genes were amplified and sequenced: the internal transcribed spacer (ITS) region using ITS1/ITS4 primers (White et al.1990) (Genbank assessions MZ831304 to MZ831308), the partial calmodulin gene (CAM, primer CL1/CL2A, O'Donnell.)(Genbank assession MZ856333 to MZ856337) and the partial translation elongation factor (EF-1α) using primer EF1/EF2 (Geiser et al.)(Genbank assession MZ856338 to MZ8564342). FUSARIUM-ID analysis showed 98.18% to 100% similarity with sequences of the F. fujikuroi species complex. The phylogenetic analysis was conducted using a neighbor-joining algorithm based on the ITS, CAM, and EF-1α gene sequences. The isolates were clustered with F. fujikuroi clade (Supplementary Fig.1). Koch's postulates were conducted using a sand-cornmeal-inoculum-layer method (Bilgi et al.). Briefly, 400 ml plastic boxes were filled with 15g of sterilized premium-grade coarse vermiculite, followed by a 15 g of inoculum prepared as sand-cornmeal mixture inoculum. The inoculum for each F. fujikuroi isolates was prepared by infesting a pre-sterilized sand-cornmeal mixture with three 5 mm plugs of cultures. Three F. fujikuroi isolates and PDA plugs were inoculated to serve as positive control and non-inoculated control treatments, respectively. The completed colonization of the sand-cornmeal mixture was finished by incubating at 25 ℃ for 7-10 days. Eight pre-germinated seeds of cv. Luhua No.1 was then covered with another 8 g of vermiculite. Peanuts were grown at 25 °C with 85% relative humidity under a light/dark cycle of 14h/10h. After 14 days of incubation, the inoculated plants showed typical symptoms of root rot similar to those in the field: pre-emergence damping-off, reddish-brown lesions on the tap, and lateral roots. F. fujikuroi was successfully re-isolated from inoculated plants but not from the controls and identified as described above. F. fujikuroi was reported to cause bakanae disease of rice (Amatulli et. al.), and root rot of soybeans (Zhao et. al.). To the best of our knowledge, this is the first record of F. fujikuroi causing root rot of peanut in China.

17.
Plant Dis ; 106(4): 1134-1142, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34752126

RESUMEN

Microbial communities are essential for soil health, but fungicide application may have significant effects on their structure. It is difficult to predict whether nontarget pathogens of applied fungicides in the soil will cause crop damage. Tebuconazole is a triazole fungicide that can be used as a seed treatment and, thereby, introduced to the soil. However, seed-applied tebuconazole has a potential risk of causing poor emergence of corn (Zea mays) seedlings. Using soil with a history of poor corn seedling emergence, we demonstrate through TA cloning and isolation that the poor emergence of corn seedlings from tebuconazole-coated corn seeds was primarily because of infection by surviving soil pathogens, specifically Pythium species that are not targeted by tebuconazole, rather than the phytotoxic effects of tebuconazole. Bioassay tests on tebuconazole-amended media showed that tebuconazole can suppress soil fungi while allowing Pythium to grow. Pythium species primarily contributing to the corn seed rot were more pathogenic at cooler temperatures. Furthermore, the nontarget biocontrol agent of Trichoderma spp. was strongly inhibited by tebuconazole. Taken together, the nontarget effects of tebuconazole are likely not significant under favorable plant growing conditions but are considerable because of low-temperature stress.


Asunto(s)
Fungicidas Industriales , Pythium , Fungicidas Industriales/farmacología , Prevalencia , Plantones , Semillas/microbiología , Suelo , Triazoles/farmacología , Zea mays
18.
Int J Mol Sci ; 23(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35163447

RESUMEN

Botrytis cinerea is considered an important plant pathogen and is responsible for significant crop yield losses. With the frequent application of commercial fungicides, B. cinerea has developed resistance to many frequently used fungicides. Therefore, it is necessary to develop new kinds of fungicides with high activity and new modes of action to solve the increasingly serious problem of resistance. During our screening of fungicide candidates, one novel sulfonamide compound, N-(2-trifluoromethyl-4-chlorphenyl)-2-oxocyclohexyl sulfonamide (L13), has been found to exhibit good fungicidal activity against B. cinerea. In this work, the mode of action of L13 against B. cinerea and the field control effect on tomato gray mold was studied. L13 had good control against B. cinerea resistant to carbendazim, diethofencarb, and iprodione commercial fungicides in the pot culture experiments. SEM and TEM observations revealed that L13 could cause obvious morphological and cytological changes to B. cinerea, including excessive branching, irregular ramification or abnormal configuration, and the decomposition of cell wall and vacuole. L13 induced more significant electrolyte leakage from hyphae than procymidone as a positive control. L13 had only a minor effect on the oxygen consumption of intact mycelia, with 2.15% inhibition at 50 µg/mL. In two locations over 2 years, the field control effect of L13 against tomato gray mold reached 83% at a rate of 450 g ai ha-1, better than the commercial fungicide of iprodione. Moreover, toxicological tests demonstrated the low toxicological effect of L13. This research seeks to provide technical support and theoretical guidance for L13 to become a real commercial fungicide.


Asunto(s)
Botrytis/crecimiento & desarrollo , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/prevención & control , Solanum lycopersicum/crecimiento & desarrollo , Sulfonamidas/farmacología , Administración Cutánea , Administración Oral , Animales , Botrytis/efectos de los fármacos , Botrytis/metabolismo , Pared Celular/efectos de los fármacos , Farmacorresistencia Fúngica , Fungicidas Industriales/administración & dosificación , Fungicidas Industriales/efectos adversos , Solanum lycopersicum/microbiología , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Estructura Molecular , Conejos , Ratas , Piel/efectos de los fármacos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Vacuolas/efectos de los fármacos , Vacuolas/metabolismo
19.
Entropy (Basel) ; 23(6)2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34070385

RESUMEN

In this paper, we present order invariance theoretical results for weighted quasi-arithmetic means of a monotonic series of numbers. The quasi-arithmetic mean, or Kolmogorov-Nagumo mean, generalizes the classical mean and appears in many disciplines, from information theory to physics, from economics to traffic flow. Stochastic orders are defined on weights (or equivalently, discrete probability distributions). They were introduced to study risk in economics and decision theory, and recently have found utility in Monte Carlo techniques and in image processing. We show in this paper that, if two distributions of weights are ordered under first stochastic order, then for any monotonic series of numbers their weighted quasi-arithmetic means share the same order. This means for instance that arithmetic and harmonic mean for two different distributions of weights always have to be aligned if the weights are stochastically ordered, this is, either both means increase or both decrease. We explore the invariance properties when convex (concave) functions define both the quasi-arithmetic mean and the series of numbers, we show its relationship with increasing concave order and increasing convex order, and we observe the important role played by a new defined mirror property of stochastic orders. We also give some applications to entropy and cross-entropy and present an example of multiple importance sampling Monte Carlo technique that illustrates the usefulness and transversality of our approach. Invariance theorems are useful when a system is represented by a set of quasi-arithmetic means and we want to change the distribution of weights so that all means evolve in the same direction.

20.
Small ; 16(15): e1902860, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31468709

RESUMEN

In situ monitoring of hydrogen peroxide (H2 O2 ) during its production process is needed. Here, an electrochemical H2 O2 sensor with a wide linear current response range (concentration: 5 × 10-8 to 5 × 10-2 m), a low detection limit (32.4 × 10-9 m), and a high sensitivity (568.47 µA mm-1 cm-2 ) is developed. The electrocatalyst of the sensor consists of cobalt nanoparticles and atomic Co-Nx moieties anchored on nitrogen doped carbon nanotube arrays (Co-N/CNT), which is obtained through the pyrolysis of the sandwich-like urea@ZIF-67 complex. More cobalt nanoparticles and atomic Co-Nx as active sites are exposed during pyrolysis, contributing to higher electrocatalytic activity. Moreover, a portable screen-printed electrode sensor is constructed and demonstrated for rapidly detecting (cost ≈40 s) H2 O2 produced in microbial fuel cells with only 50 µL solution. Both the synthesis strategy and sensor design can be applied to other energy and environmental fields.

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