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A solid-state electrochemiluminescence (ECL) sensor was fabricated by immobilizing luminol, a classical luminescent reagent, on a Zn-Co-ZIF carbon fiber-modified electrode for the rapid and sensitive detection of procymidone (PCM) in vegetable samples. The sensor was created by sequentially modifying the glassy carbon electrode with Zn-Co-ZIF carbon fiber (Zn-Co-ZIF CNFs), Pt@Au NPs, and luminol. Zn-Co-ZIF CNFs, prepared through electrospinning and high-temperature pyrolysis, possessed a large specific surface area and porosity, making it suitable as carrier and electron transfer accelerator in the system. Pt@Au NPs demonstrated excellent catalytic activity, effectively enhancing the generation of active substances. The ECL signal was significantly amplified by the combination of Zn-Co-ZIF CNFs and Pt@Au NPs, which can subsequently be diminished by procymidone. The ECL intensity decreased proportionally with the addition of procymidone, displaying a linear relationship within the concentration range 1.0 × 10-13 to 1.0 × 10-6 mol L-1 (R2 = 0.993). The sensor exhibited a detection limit of 3.3 × 10-14 mol L-1 (S/N = 3) and demonstrated outstanding reproducibility and stability, making it well-suited for the detection of procymidone in vegetable samples.
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Cobalto , Técnicas Electroquímicas , Oro , Límite de Detección , Mediciones Luminiscentes , Luminol , Verduras , Zinc , Luminol/química , Verduras/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Mediciones Luminiscentes/métodos , Zinc/química , Oro/química , Cobalto/química , Nanopartículas del Metal/química , Platino (Metal)/química , Carbono/química , Electrodos , Sustancias Luminiscentes/química , Contaminación de Alimentos/análisis , Reproducibilidad de los ResultadosRESUMEN
Development of fresh solid phase extractant is critical for selective separation and purification of special proteins. Herein, we demonstrated a recombinant Staphylococcal Protein G (rSPG) with a His-tag modified the novel single-metal organic framework (rSPG@Ni-MOF-74). The proposed solid-phase extraction material possessed a uniform spindle-shaped structure, large surface area (709.60 m2 g-1) and pore volume (0.08 m3 g-1), high metal content (22.57 wt%), which facilitated the interaction between host and guest. As results, the composite displayed outstanding selective recognition and adsorption of IgG, due to synergistic effect of the binding ability of rSPG with the Fc region of IgG, maintained through hydrogen bonding and electrostatic attraction, as well as hydrophobic interaction. The adsorption performance and mechanism of rSPG@Ni-MOF-74 have been fully investigated. Additionally, the rSPG@Ni-MOF-74 composite could effectively separate IgG from serum obtained from healthy humans, with the purity of the separated IgG verified through SDS-PAGE analysis. Furthermore, LC-MS/MS analysis identified a high content of IgG (55.3 %) in the eluate from rSPG@Ni-MOF-74, suggesting the great potential of rSPG@Ni-MOF-74 in IgG separation and enrichment from complex matrix.
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Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.
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Antozoos , Colitis Ulcerosa , Sulfato de Dextran , Diterpenos , Animales , Colitis Ulcerosa/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/química , Diterpenos/uso terapéutico , Diterpenos/aislamiento & purificación , Ratones , Relación Estructura-Actividad , Antozoos/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/aislamiento & purificación , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismoRESUMEN
Background: Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory. Methods: We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings. Results: In whole-brain regression, we identified ß estimates of dorsolateral prefrontal cortex response (DLPFC ß) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 â DLPFC ß â differences in reaction time (2- minus 0-back; RT2-0) of correct trials â differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC ß's, and CSI2-0 in women. Conclusions: Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.
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Within the current process of large-scale dairy-cattle breeding, to address the problems of low recognition-accuracy and significant recognition-error associated with existing visual methods, we propose a method for recognizing the feeding behavior of dairy cows, one based on an improved RefineMask instance-segmentation model, and using high-quality detection and segmentation results to realize the recognition of the feeding behavior of dairy cows. Firstly, the input features are better extracted by incorporating the convolutional block attention module into the residual module of the feature extraction network. Secondly, an efficient channel attention module is incorporated into the neck design to achieve efficient integration of feature extraction while avoiding the surge of parameter volume computation. Subsequently, the GIoU loss function is used to increase the area of the prediction frame to optimize the convergence speed of the loss function, thus improving the regression accuracy. Finally, the logic of using mask information to recognize foraging behavior was designed, and the accurate recognition of foraging behavior was achieved according to the segmentation results of the model. We constructed, trained, and tested a cow dataset consisting of 1000 images from 50 different individual cows at peak feeding times. The method's effectiveness, robustness, and accuracy were verified by comparing it with example segmentation algorithms such as MSRCNN, Point_Rend, Cascade_Mask, and ConvNet_V2. The experimental results show that the accuracy of the improved RefineMask algorithm in recognizing the bounding box and accurately determining the segmentation mask is 98.3%, which is higher than that of the benchmark model by 0.7 percentage points; for this, the model parameter count size was 49.96 M, which meets the practical needs of local deployment. In addition, the technologies under study performed well in a variety of scenarios and adapted to various light environments; this research can provide technical support for the analysis of the relationship between cow feeding behavior and feed intake during peak feeding periods.
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Algoritmos , Conducta Alimentaria , Bovinos , Animales , Conducta Alimentaria/fisiología , Femenino , Redes Neurales de la Computación , Industria Lechera/métodosRESUMEN
INTRODUCTION: Kamebakaurin is an active constituent of both Rabdosia japonica and Rabdosia excisa, which are utilized in Chinese traditional medicine for improving symptoms in patients with allergies. We investigated the molecular mechanisms of the anti-allergic effects of kamebakaurin using BMMCs. METHODS: The degranulation ratio, histamine release, and the interleukin (IL)-4, leukotriene B4 (LTB4), and cysteinyl leukotriene productions on antigen-triggered BMMC were investigated. Additionally, the effects of kamebakaurin on signal transduction proteins were examined by Western blot and binding to the Syk and Lyn kinase domain was calculated. The effects of kamebakaurin on antigen-induced hyperpermeability were investigated using mouse model. RESULTS: At 10 µ
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Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.
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Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC50 value of 5.57â µM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.
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BACKGROUND: Staphylococcus aureus is one of the most prevalent pathogens in bovine mastitis, which leads to substantial financial losses for the dairy industry. RESULTS: In this study, S. aureus (n = 72) was isolated from 18 dairy farms in 15 provinces across China in 2021. The identification of these isolates at the species level was achieved by employing 16S rRNA sequencing. An isothermal amplification method for auxiliary detection of S. aureus was established, which can be employed not only for laboratory detection but also for point-of-care testing (POCT). Molecular characteristics of S. aureus mastitis in Chinese dairy cows were determined through MLST and spa typing. Finally, methicillin-resistant Staphylococcus aureus (MRSA) and MRSA resistance genes were detected using MIC and PCR amplification techniques. 72 isolates were identified as 12 sequence types (STs) and 7 clonal complexes (CC). ST1/CC1 was the dominant prevalent accounting for 33.3 % of the total, and exhibiting a wide distribution range. In terms of spa types, t114 was the dominant type, accounting for 31.9 % of the total, followed by t529 as the second major type. Four S. aureus strains were classified as MRSA according to their levels of oxacillin resistance (MIC ≥4 µg/mL). Among these four MRSA strains, one of them was found to be mecA positive. However, the presence of drug-resistance genes mecA and mecC was not detected in the remaining three MRSA strains, indicating the possible existence of new resistance genes. CONCLUSIONS: Our study investigated the prevalence of S. aureus mastitis in dairy cows in China, while also examined the molecular characteristics and MRSA strains. This information will help with the clinical monitoring, prevention, and control of S. aureus mastitis in dairy cattle.
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Antibacterianos , Mastitis Bovina , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , ARN Ribosómico 16S , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Bovinos , Mastitis Bovina/microbiología , Mastitis Bovina/epidemiología , China/epidemiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Femenino , Staphylococcus aureus/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , ARN Ribosómico 16S/genética , Antibacterianos/farmacología , Industria LecheraRESUMEN
Targeting the competitive-cooperative relationships among tumor cells and various immune cells can efficiently reverse the immune-dysfunction microenvironment to boost the immunotherapies for the triple-negative breast cancer treatment. Hence, a bacterial outer membrane vesicle-based nanocomplex is designed for specifically targeting malignant cells and immune cells to reconcile the relationships based on metabolic-immune crosstalk. By uniquely utilizing the property of charge-reversal polymers to realize function separation, the nanocomplexes could synergistically regulate tumor cells and immune cells. This approach could reshape the immunosuppressive competition-cooperation pattern into one that is immune-responsive, showcasing significant potential for inducing tumor remission in TNBC models.
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Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Humanos , Animales , Línea Celular Tumoral , Ratones , Microambiente Tumoral/efectos de los fármacos , Femenino , Inmunoterapia , Nanopartículas/químicaRESUMEN
In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.
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Perfilación de la Expresión Génica , ARN , Humanos , ARN/genética , Hibridación in Situ , Perfilación de la Expresión Génica/métodos , Transcriptoma , CitosolRESUMEN
Cancer metabolism plays multifaceted roles in the initiation and progression of tumors, and interventions in metabolism are considered fundamental approaches for cancer control. Within the vast metabolic networks of tumors, there exist numerous potential therapeutic targets, intricately interconnected with each other and with signaling networks related to immunity, metastasis, drug resistance, and more. Based on the characteristics of the tumor microenvironment, constructing drug delivery systems for multi-level modulation of the tumor microenvironment is proven as an effective strategy for achieving multidimensional control of cancer. Consequently, this article summarizes several features of tumor metabolism to provide insights into recent advancements in intelligent drug delivery systems for achieving multi-level regulation of the metabolic microenvironment in cancer, with the aim of offering a novel paradigm for cancer treatment.
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Neoplasias , Humanos , Neoplasias/terapia , Sistemas de Liberación de Medicamentos/métodos , Microambiente Tumoral , Nanomedicina/métodosRESUMEN
PURPOSE: To investigate prognostic values of prostatic urethra involvement (PUI) and construct a prognostic model that estimates the probability of cancer-specific survival for T1 bladder cancer patients. METHOD AND MATERIALS: We investigated the national Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to get patients diagnosed with T1 bladder cancer. An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Kaplan-Meier method with the log-rank test was applied to assess cancer-specific survival (CSS) and overall survival (OS). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were performed. All patients were randomly divided into the development cohort and validation group at the ratio of 7:3. The performance of the model was internally validated by calibration curves and the concordance index (C-index). RESULTS: The PUI group had a lower survival rate of both CSS and overall survival OS before and after PSM when compared to non-involved patients (All P < 0.05). Multivariate analysis revealed a poor prognosis in the PUI group for cancer-specific mortality (CSM) and all-cause mortality (ACM) analyses before and after PSM (All P < 0.05). Seven variables, including age, surgery, radiotherapy, tumour size, PUI, and marital status, were incorporated in the final nomogram. The C-index in the development cohort was 0.715 (0.711-0.719), while it was 0.672 (0.667-0.677) in the validation group. Calibration plots for 3- and 5-year cancer-specific survival showed good concordance in the development and validation cohorts. CONCLUSIONS: PUI was an independent risk factor of ACM and CSM in T1 bladder cancer patients. In addition, a highly discriminative and precise nomogram that predicted the individualized probability of cancer-specific survival for patients with T1 bladder cancer was constructed.
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Neoplasias , Nomogramas , Humanos , Pronóstico , Uretra , Bases de Datos FactualesRESUMEN
Much is known about the generation, removal, and roles of 5-methylcytosine (5mC) in eukaryote DNA, and there is a growing body of evidence regarding N6-methyladenine, but very little is known about N4-methylcytosine (4mC) in the DNA of eukaryotes. The gene for the first metazoan DNA methyltransferase generating 4mC (N4CMT) was reported and characterized recently by others, in tiny freshwater invertebrates called bdelloid rotifers. Bdelloid rotifers are ancient, apparently asexual animals, and lack canonical 5mC DNA methyltransferases. Here, we characterize the kinetic properties and structural features of the catalytic domain of the N4CMT protein from the bdelloid rotifer Adineta vaga. We find that N4CMT generates high-level methylation at preferred sites, (a/c)CG(t/c/a), and low-level methylation at disfavored sites, exemplified by ACGG. Like the mammalian de novo 5mC DNA methyltransferase 3A/3B (DNMT3A/3B), N4CMT methylates CpG dinucleotides on both DNA strands, generating hemimethylated intermediates and eventually fully methylated CpG sites, particularly in the context of favored symmetric sites. In addition, like DNMT3A/3B, N4CMT methylates non-CpG sites, mainly CpA/TpG, though at a lower rate. Both N4CMT and DNMT3A/3B even prefer similar CpG-flanking sequences. Structurally, the catalytic domain of N4CMT closely resembles the Caulobacter crescentus cell cycle-regulated DNA methyltransferase. The symmetric methylation of CpG, and similarity to a cell cycle-regulated DNA methyltransferase, together suggest that N4CMT might also carry out DNA synthesis-dependent methylation following DNA replication.
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ADN-Citosina Metilasas , Rotíferos , Animales , Metilación de ADN , ADN-Citosina Metilasas/química , ADN-Citosina Metilasas/aislamiento & purificación , Mamíferos/metabolismo , Rotíferos/clasificación , Rotíferos/enzimologíaRESUMEN
The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is the main block for the penetration of chemotherapy. In the tumor microenvironment, a dense matrix composed of fibrin is formed on the exterior, while the interior is featured by high reduction, hypoxia and low pH. How to match the special microenvironment to on-demand drug release is the key to improve chemotherapeutic efficacy. Herein, a microenvironment-responsive micellar system is developed to deepen tumoral penetration. Briefly, the conjugation of a fibrin-targeting peptide to PEG-poly amino acid has been utilized to achieve accumulation of micelles in the tumor stroma. By modification of micelles with hypoxia-reducible nitroimidazole which becomes protonated under acidic conditions, their surface charge is more positive, facilitating deeper penetration into tumors. Paclitaxel was loaded onto the micelles via a disulfide bond to enable glutathione (GSH)-responsive release. Therefore, the immunosuppressive microenvironment is relived through the alleviation of hypoxia and depletion of GSH. Hopefully, this work could establish paradigms by designing sophisticated drug-delivery systems to tactfully employ and retroact the tamed tumoral microenvironment to improve the therapeutic efficacy based on understanding the multiple hallmarks and learning the mutual regulation. STATEMENT OF SIGNIFICANCE: Tumor microenvironment(TME) is an unique pathological feature of pancreatic cancer and an inherent barrier to chemotherapy. Numerous studies regard TME as the targets for drug delivery. In this work, we propose a hypoxia-responsive nanomicellar drug delivery system that aiming hypoxia TME of pancreatic cancer. The nanodrug delivery system could respond to the hypoxic microenvironment and enhance the penetration of the inner tumor at the same time preserving the outer tumor stroma, thus achieving targeted treatment of PDAC by preserving the integrity of the outer stroma. Simultaneously, the responsive group can reverse the degree of hypoxia in TME by disrupting the redox balance in the tumor region, thus achieving precise treatment of PDAC by matching the pathological characteristics of TME. We believe our article would provide new design ideas for the future treatments for pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Micelas , Microambiente Tumoral , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Hipoxia , Glutatión , Terapia de Inmunosupresión , Línea Celular Tumoral , Neoplasias PancreáticasRESUMEN
Two new glycerolipids, syngaculipids A and B (1 and 2), one first naturally occurring metabolite (8), together with five known compounds (3-7) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116â cell lines. Compound 8 exhibited moderate cytotoxicity with IC50 values of 34.5 and 38.9â µM on the A549 and HCT-116â cell lines, respectively.
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Medicina Tradicional China , Humanos , Estructura Molecular , Células HCT116RESUMEN
A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients. Here, we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials (SIL@T). SIL@T modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells, releasing silybin and oxaliplatin responsively in the cells. SIL@T preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals. Mechanistic studies have shown that SIL@T can effectively induce immunogenic cell death of metastatic cells, activate immune responses and increase infiltration of CD8+ T cells. Meanwhile, the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed. This study demonstrates that SIL@T with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.
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Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex differences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and identified 981 (473 men) subjects evaluated by the Achenbach Adult Self-Report Syndrome Scales. We processed the imaging data with published routines and extracted VS response (ß) to win and to loss vs. baseline in a gambling task for correlation with externalizing and internalizing symptom severity. Men vs. women showed more severe externalizing symptoms and higher VS response to monetary losses (VS-loss ß) but not to wins. Men but not women showed a significant, positive correlation between VS-loss ß and externalizing traits, and the sex difference was confirmed by a slope test. The correlations of VS-loss vs. externalizing and of VS-win vs. externalizing and those of VS-loss vs. externalizing and of VS-loss vs. internalizing traits both differed significantly in slope, confirming its specificity, in men. Further, the sex-specific relationship between VS-loss ß and externalizing trait did not extend to activities during exposure to negative emotion in the face matching task. To conclude, VS responses to loss but not to win and their correlation with externalizing rather than internalizing symptom severity showed sex differences in young adults. The findings highlight the relationship of externalizing traits and VS response to monetary loss and may have implications for psychological models of externalizing behaviors in men.
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Caracteres Sexuales , Estriado Ventral , Adulto Joven , Humanos , Masculino , Femenino , Estriado Ventral/diagnóstico por imagenRESUMEN
Five undescribed dolabellane-type diterpenoids (1-5), together with three related known ones (6-8), were isolated from the soft coral Clavularia viridis. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis and NMR calculation with DP4+ probability analysis. The absolute configurations of 1 and 5 were unambiguously determined by X-ray crystallographic analysis. A plausible biosynthetic connection between undescribed compounds 1-5 was proposed.
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Antozoos , Diterpenos , Animales , Antozoos/química , Estructura Molecular , Diterpenos/química , Espectroscopía de Resonancia MagnéticaRESUMEN
The total synthesis of the marine natural product naamidine J and a rapid structure modification toward its derivatives were achieved on the basis of several rounds of structure-relationship analyses of their tumor immunological activities. These compounds were tested for programmed death-ligand 1 (PD-L1) protein expression in human colorectal adenocarcinoma RKO cells. Among them, compound 11c was found to efficiently suppress constitutive PD-L1 expression in RKO cells with low toxicity and further exerted its antitumor effect in MC38 tumor-bearing C57BL/6 mice by reducing PD-L1 expression and enhancing tumor-infiltrating T-cell immunity. This research work may provide insight for the discovery of new marine natural product-derived tumor immunological drug leads.