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1.
bioRxiv ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38746413

RESUMEN

The phosphoinositide-3 kinase (PI3K), a heterodimeric enzyme, plays a pivotal role in cellular metabolism and survival. Its deregulation is associated with major human diseases, particularly cancer. The p85 regulatory subunit of PI3K binds to the catalytic p110 subunit via its C-terminal domains, stabilising it in an inhibited state. Certain Src homology 3 (SH3) domains can activate p110 by binding to the proline-rich (PR) 1 motif located at the N-terminus of p85. However, the mechanism by which this N-terminal interaction activates the C-terminally bound p110 remains elusive. Moreover, the intrinsically poor ligand selectivity of SH3 domains raises the question of how they can control PI3K. Combining structural, biophysical, and functional methods, we demonstrate that the answers to both these unknown issues are linked: PI3K-activating SH3 domains engage in additional "tertiary" interactions with the C-terminal domains of p85, thereby relieving their inhibition of p110. SH3 domains lacking these tertiary interactions may still bind to p85 but cannot activate PI3K. Thus, p85 uses a functional selection mechanism that precludes nonspecific activation rather than nonspecific binding. This separation of binding and activation may provide a general mechanism for how biological activities can be controlled by promiscuous protein-protein interaction domains.

2.
Heliyon ; 10(9): e30380, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38737249

RESUMEN

Aim: To explore the abundance and diversity of the gut microbiota in patients with lung cancer accompanied by chronic obstructive pulmonary disease (LC-COPD). Methods: The study cohort comprised 15 patients with LC-COPD, 49 patients with lung cancer, and 18 healthy control individuals. ELISA was used to detect inflammatory factors in venous blood. 16S rDNA sequencing was performed to determine the abundance and diversity of the gut microbiota. Gas chromatography-mass spectrometry was used to determine the concentration of short-chain fatty acids (SCFAs) in feces samples. Results: The α-diversity index indicated that the richness and diversity of the gut microbiota were lower in patients with LC-COPD compared with patients with lung cancer and controls. Principal component analysis revealed significant differences among the three groups (P < 0.05). The linear discriminant analysis effect size algorithm indicated that the o_Lactobacillales, g_Lactobaccillus, f_Lactobaccillaceae, s_Lactobaccillus_oris, c_Bacilli, g_Anaerofustis, s_uncultured organism, and s_bacterium_P1C10 species were prevalent in patients with LC-COPD, while the g_Clostridium_XIVa and g_Butyricicoccus species were prevalent in patients with lung cancer. Furthermore, the concentrations of the SCFAs butyric acid, isobutyric acid, isovaleric acid, and valeric acid tended to be lower in patients with LC-COPD compared with patients with lung cancer and healthy controls, although these intergroup differences were not significant (P > 0.05). Patients with lung cancer had the lowest serum concentration of tumor necrosis factor (TNF)-a. There were no intergroup differences in the concentrations of other inflammatory factors. Conclusions: The present study indicated that the abundance and structure of the gut microbiota is altered, and the concentrations of SCFAs may be decreased in patients with LC-COPD. In addition, patients with lung cancer had the lowest serum concentration of TNF-a.

3.
Ecotoxicol Environ Saf ; 277: 116331, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38640801

RESUMEN

Polystyrene nanoparticles are emerging as contaminants in freshwater environments, posing potential risks to amphibians exposed to extended periods of water contamination. Using tadpoles as a model, this study aimed to evaluate the toxicity of PS NPs. Pyrolysis-gas chromatography-tandem mass spectrometry (Py-GCMS) analysis revealed a concentration-dependent increase in polystyrene nanoparticles (PS NPs) levels in tadpoles with escalating exposure concentrations. Following exposure to 100 nm fluorescent microspheres, fluorescence was observed in the intestines and gills, peaking at 48 hours. Histopathological analysis identified degenerative necrosis and inflammation in the liver, along with atrophic necrosis of glomeruli and tubules in the kidneys. These results indicate a discernible impact of PS NPs on antioxidant levels, including reduced superoxide dismutase and catalase activities, elevated glutathione content, and increased malondialdehyde levels. Electron microscopy observations revealed the infiltration of PS NPs into Kupffer's cells and hepatocytes, leading to visible lesions such as nuclear condensation and mitochondrial disruption. The primary objective of this research was to elucidate the adverse effects of prolonged PS NPs exposure on amphibians.


Asunto(s)
Larva , Hígado , Nanopartículas , Estrés Oxidativo , Poliestirenos , Contaminantes Químicos del Agua , Animales , Poliestirenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Nanopartículas/toxicidad , Hígado/efectos de los fármacos , Hígado/patología , Contaminantes Químicos del Agua/toxicidad , Larva/efectos de los fármacos , Glutatión/metabolismo , Superóxido Dismutasa/metabolismo , Malondialdehído/metabolismo , Catalasa/metabolismo
4.
Environ Sci Technol ; 58(15): 6519-6531, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38578272

RESUMEN

Paralytic shellfish toxins (PSTs) are widely distributed neurotoxins, and the PST metabolic detoxification mechanism in bivalves has received increasing attention. To reveal the effect of phase I (cytochrome P450)-II (GST)-III (ABC transport) metabolic systems on the PST metabolism in Azumapecten farreri, this study amplified stress on the target systems using rifampicin, dl-α-tocopherol, and colchicine; measured PST levels; and conducted transcriptomic analyses. The highest toxin content reached 1623.48 µg STX eq/kg in the hepatopancreas and only 8.8% of that in the gills. Inducer intervention significantly decreased hepatopancreatic PST accumulation. The proportional reductions in the rifampicin-, dl-α-tocopherol-, and colchicine-induced groups were 55.3%, 50.4%, and 36.1%, respectively. Transcriptome analysis showed that 11 modules were significantly correlated with PST metabolism (six positive/five negative), with phase I CYP450 and phase II glutathione metabolism significantly enriched in negatively correlated pathways. Twenty-three phase I-II-III core genes were further validated using qRT-PCR and correlated with PST metabolism, revealing that CYP46A1, CYP4F6, GSTM1, and ABCF2 were significantly correlated, while CYP4F11 and ABCB1 were indirectly correlated. In conclusion, phase I-II-III detoxification enzyme systems jointly participate in the metabolic detoxification of PSTs in A. farreri. This study provides key data support to profoundly elucidate the PST metabolic detoxification mechanism in bivalves.


Asunto(s)
Bivalvos , Dinoflagelados , Animales , Rifampin/metabolismo , alfa-Tocoferol/metabolismo , Mariscos/análisis , Colchicina/metabolismo , Dinoflagelados/metabolismo
5.
Int J Nanomedicine ; 19: 2995-3007, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559446

RESUMEN

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed. Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs. Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 µg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 µg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs. Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.


Asunto(s)
Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Otitis Media , Infecciones Estafilocócicas , Óxido de Zinc , Humanos , Staphylococcus aureus , Radical Hidroxilo , Óxido de Zinc/farmacología , Óxido de Zinc/química , Antibacterianos/farmacología , Antibacterianos/química , Otitis Media/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Nanopartículas del Metal/química
6.
Ann Noninvasive Electrocardiol ; 29(3): e13114, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38563240

RESUMEN

OBJECTIVE: To assess electrocardiogram (ECG) for risk stratification in inferior ST-elevation myocardial infarction (STEMI) patients within 24 h. METHODS: Three hundred thirty-four patients were divided into four ECG-based groups: Group A: R V1 <0.3 mV with ST-segment elevation (ST↑) V7-V9, Group B: R V1 <0.3 mV without ST↑ V7-V9, Group C: R V1 ≥0.3 mV with ST↑ V7-V9, and Group D: R V1 ≥0.3 mV without ST↑ V7-V9. RESULTS: Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK-MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT-proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post-onset. CONCLUSIONS: For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7-V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.


Asunto(s)
Infarto de la Pared Inferior del Miocardio , Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Infarto de la Pared Inferior del Miocardio/complicaciones , Infarto de la Pared Inferior del Miocardio/diagnóstico , Electrocardiografía , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Relevancia Clínica , Volumen Sistólico , Función Ventricular Izquierda , Arritmias Cardíacas
7.
iScience ; 27(4): 109550, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38595796

RESUMEN

During the evolution of large models, performance evaluation is necessary for assessing their capabilities. However, current model evaluations mainly rely on specific tasks and datasets, lacking a united framework for assessing the multidimensional intelligence of large models. In this perspective, we advocate for a comprehensive framework of cognitive science-inspired artificial general intelligence (AGI) tests, including crystallized, fluid, social, and embodied intelligence. The AGI tests consist of well-designed cognitive tests adopted from human intelligence tests, and then naturally encapsulates into an immersive virtual community. We propose increasing the complexity of AGI testing tasks commensurate with advancements in large models and emphasizing the necessity for the interpretation of test results to avoid false negatives and false positives. We believe that cognitive science-inspired AGI tests will effectively guide the targeted improvement of large models in specific dimensions of intelligence and accelerate the integration of large models into human society.

8.
Surgery ; 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38584073

RESUMEN

BACKGROUND: The indications for splenic hilar lymph node dissection in advanced proximal gastric cancer without invasion of the greater curvature are controversial. We aimed to develop a preoperative nomogram for individualized prediction of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer. METHODS: From January 2014 to December 2021, 558 patients with non-greater curvature advanced proximal gastric cancer who underwent D2 lymphadenectomy (including splenic hilar lymph node) were retrospectively analyzed and divided into a training cohort (n = 361) and validation cohort (n = 197), depending on the admission time. A preoperative predictive nomogram of splenic hilar lymph node metastasis was established based on independent predictors identified by multivariate analysis, and the performance and prognostic value were confirmed. RESULTS: In the training and validation cohorts, 48 (13.3%) and 24 patients (12.2%) had pathologically confirmed splenic hilar lymph node metastasis, respectively. Tumor located in the posterior wall, tumor size ≥5 cm, Borrmann type IV, and splenic hilar lymph node lymphadenectasis on computed tomography were preoperative factors independently associated with splenic hilar lymph node metastasis. The nomogram developed based on these four parameters had a high concordance index of 0.850 (95% confidence interval, 0.793-0.907) and 0.825 (95% confidence interval, 0.743-0.908) in the training and validation cohorts, respectively, with well-fitting calibration plots and better net benefits in the decision curve analysis. In addition, disease-free survival and overall survival were significantly shorter in the high-risk group, with hazard ratios of 3.660 (95% confidence interval, 2.228-6.011; log-rank P < .0001) and 3.769 (95% confidence interval, 2.279-6.231; log-rank P < .0001), respectively. CONCLUSION: The nomogram has good performance in predicting the risk of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer preoperatively, which can help surgeons make rational clinical decisions.

9.
Elife ; 122024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446535

RESUMEN

Cognitive control resolves conflicts between task-relevant and -irrelevant information to enable goal-directed behavior. As conflicts can arise from different sources (e.g., sensory input, internal representations), how a limited set of cognitive control processes can effectively address diverse conflicts remains a major challenge. Based on the cognitive space theory, different conflicts can be parameterized and represented as distinct points in a (low-dimensional) cognitive space, which can then be resolved by a limited set of cognitive control processes working along the dimensions. It leads to a hypothesis that conflicts similar in their sources are also represented similarly in the cognitive space. We designed a task with five types of conflicts that could be conceptually parameterized. Both human performance and fMRI activity patterns in the right dorsolateral prefrontal cortex support that different types of conflicts are organized based on their similarity, thus suggesting cognitive space as a principle for representing conflicts.


You are reading a book in your local coffeeshop, when your focus gets broken by the couple at the next table, passionately discussing mortgage rates. To minimise this interruption your brain engages in 'cognitive control', resolving conflicts between competing stimuli to prioritise one over another. Having finally regained your focus, another distraction emerges, this time of a different nature. Does your brain use the same mental mechanisms as before, and therefore a common brain circuit? Or does each kind of stimulus require a specific process? Tasks that involve successively presenting different distractors can help explore these questions by testing for a process known as generalization: if the same mental mechanism underpins the resolution of all conflicts, distractors should become easier to ignore after the first trial. Based on this paradigm, Yang et al. recorded brain activity during a modified version of a spatial Stroop-Simon task. Participants were asked to press a left or right button based on whether an arrow was pointing up or down, with both the vertical and horizontal position of the symbol potentially causing interference. For instance, accurate decision-making may be impaired when an arrow 'down' the bottom of the screen is pointing up (Stroop effect); or when participants must press the left button for an arrow shown on their right (Simon effect). Overall, the arrows could appear in 10 possible locations, giving rise to five types of conflicts with a unique blend of Stroop and Simon effects, with different levels of similarity. The results showed that the degree to which conflicts could generalize to each other depended on their similarity: the more similar the conflicts, the easier it was to resolve one after having faced another. This is contrary to previous views suggesting that different conflict types either entirely generalized or could not generalize at all. In addition, the analyses revealed that the neural networks involved in resolving each conflict type were organised in a continuous manner within a region called the prefrontal cortex. This pattern resembles how spatial information is arranged in the brain, prompting Yang et al. to suggest that cognitive control also falls under a set of principles known as cognitive space representations. Overall, the methodology employed in this work could prove useful to researchers from other fields who also investigate whether various stimuli are processed via the same or different neural networks.


Asunto(s)
Cognición , Corteza Prefontal Dorsolateral , Humanos
10.
Heliyon ; 10(6): e27988, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38509981

RESUMEN

Objective: Neuroblastoma (NB) is a prevalent pediatric tumor originating from primordial neural crest cells. As one of the latest epigenetics investigations focuses, RNA 5-methylcytosine (m5C) is closely related to cancer risk. TET methylcytosine dioxygenase 3 (TET3) is a demethylase for m5C modification. Whether there is an association between TET3 gene polymorphisms and neuroblastoma risk remains unclear. Methods: We conducted an epidemiological study in 402 patients and 473 controls to evaluate the relationship between TET3 gene SNPs (rs7560668 T > C, rs828867 G > A, and rs6546891 A > G) and NB susceptibility. Results: Our results showed that rs828867 G > A significantly reduced NB risk in Chinese children [GA vs. GG, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.52-0.98, P=0.040; GA/AA vs. GG, adjusted OR = 0.74, 95% CI = 0.55-0.998, P=0.048]. Individuals with 2-3 risk genotypes had a significantly higher NB risk than those with 0-1 risk genotypes (adjusted OR = 1.40, 95% CI = 1.04-1.88, P=0.027). The stratified analysis showed that the rs828867 G > A associated with decreased NB risk is remarkable among children aged >18 months (adjusted OR = 0.67, 95% CI = 0.46-0.96, P=0.029) and patients at clinical III + IV stages (adjusted OR = 0.67, 95% CI = 0.45-0.98, P=0.040). Compared with the 0-1 risk genotype, the concurrence of 2-3 risk genotypes significantly increased NB risk in the following subgroups: children aged >18 months and patients at clinical III + IV stages. GTEx analysis suggested that rs828867 G > A was significantly associated with RP11-287D1.4 and POLE4 mRNA expression. Conclusions: Overall, our results revealed that rs828867 G > A in the TET3 gene is significantly associated with predisposition to NB.

11.
Zhongguo Gu Shang ; 37(3): 306-10, 2024 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-38515420

RESUMEN

OBJECTIVE: To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome. METHODS: From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or orthopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old. Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal. The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored. RESULTS: The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients. Chest CT showed diffuse distribution of ground glass shadows in 13 patients,and severe symptoms were "snowstorm". Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion. Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and "starry sky sign" in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex. CONCLUSION: Fat embolism syndrome has a high mortality rate. Clinical manifestations of respiratory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation. The "blizzard" sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the "starry sky" sign is the typical manifestation of diffusion-weighted sequence of brain MRI examination of fat embolism.


Asunto(s)
Embolia Grasa , Exantema , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Imagen por Resonancia Magnética , Encéfalo , Embolia Grasa/diagnóstico por imagen , Embolia Grasa/etiología
12.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38517179

RESUMEN

The mechanisms of semantic conflict and response conflict in the Stroop task have mainly been investigated in the visual modality. However, the understanding of these mechanisms in cross-modal modalities remains limited. In this electroencephalography (EEG) study, an audiovisual 2-1 mapping Stroop task was utilized to investigate whether distinct and/or common neural mechanisms underlie cross-modal semantic conflict and response conflict. The response time data showed significant effects on both cross-modal semantic and response conflicts. Interestingly, the magnitude of semantic conflict was found to be smaller in the fast response time bins than in the slow response time bins, whereas no such difference was observed for response conflict. The EEG data demonstrated that cross-modal semantic conflict specifically increased the N450 amplitude. However, cross-modal response conflict specifically enhanced theta band power and theta phase synchronization between the medial frontal cortex (MFC) and lateral prefrontal electrodes as well as between the MFC and motor electrodes. In addition, both cross-modal semantic conflict and response conflict led to a decrease in P3 amplitude. Taken together, these findings provide cross-modal evidence for domain-specific mechanism in conflict detection and suggest both domain-specific and domain-general mechanisms exist in conflict resolution.


Asunto(s)
Electroencefalografía , Semántica , Mapeo Encefálico , Lóbulo Frontal/fisiología , Tiempo de Reacción/fisiología
13.
Elife ; 122024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526940

RESUMEN

Marburg virus (MARV) is one of the filovirus species that cause deadly hemorrhagic fever in humans, with mortality rates up to 90%. Neutralizing antibodies represent ideal candidates to prevent or treat virus disease. However, no antibody has been approved for MARV treatment to date. In this study, we identified a novel human antibody named AF-03 that targeted MARV glycoprotein (GP). AF-03 possessed a high binding affinity to MARV GP and showed neutralizing and protective activities against the pseudotyped MARV in vitro and in vivo. Epitope identification, including molecular docking and experiment-based analysis of mutated species, revealed that AF-03 recognized the Niemann-Pick C1 (NPC1) binding domain within GP1. Interestingly, we found the neutralizing activity of AF-03 to pseudotyped Ebola viruses (EBOV, SUDV, and BDBV) harboring cleaved GP instead of full-length GP. Furthermore, NPC2-fused AF-03 exhibited neutralizing activity to several filovirus species and EBOV mutants via binding to CI-MPR. In conclusion, this work demonstrates that AF-03 represents a promising therapeutic cargo for filovirus-caused disease.


Asunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Marburgvirus , Humanos , Anticuerpos Antivirales , Simulación del Acoplamiento Molecular , Glicoproteínas , Fiebre Hemorrágica Ebola/prevención & control , Ebolavirus/química
14.
J Obstet Gynaecol ; 44(1): 2321323, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38425023

RESUMEN

BACKGROUND: This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. METHODS: All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. RESULTS: Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. CONCLUSIONS: We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer.


Ferroptosis, hypoxia and immune regulation play important roles in cervical cancer progression. In this study, we developed a novel prognostic signature combining ferroptosis and hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer patients. The risk score established by ferroptosis and hypoxia-related gene as an independent prognostic factor of cervical cancer has a good survival prediction effect. High and low risk groups showed significant differences in TIME, prognosis, biological metabolic pathway and tumour mutation burden. In addition, we found drugs associated with signature genes. In short, this study has laid a theoretical foundation for exploring the related molecular mechanisms and prognosis of cervical cancer. It also contributes to the exploration of clinical management and treatment.


Asunto(s)
Ferroptosis , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Factor A de Crecimiento Endotelial Vascular , Ferroptosis/genética , Pronóstico , Hipoxia/genética , Hipoxia Fetal , Microambiente Tumoral/genética
15.
Pediatr Surg Int ; 40(1): 62, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38430253

RESUMEN

PURPOSE: Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. METHODS: We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. RESULTS: This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8 cm (range 0.5-10 cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. CONCLUSIONS: B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.


Asunto(s)
Quistes , Laparoscopía , Quiste Paraovárico , Femenino , Niño , Humanos , Adolescente , Estudios Retrospectivos , Quiste Paraovárico/patología , Quiste Paraovárico/cirugía , Quistes/cirugía , Ultrasonografía
16.
J Econ Entomol ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38482558

RESUMEN

Climate change involves changes in the pattern of temperature fluctuations and the frequency and magnitude of thermal extremes. It is essential to investigate how insects respond to increased temperature variations, especially for species that usually experience diel temperature variations extending to thermal performance limits. To explicitly elucidate the effects of sizes of amplitudes of temperature variations, we used daily alternating temperatures with an equivalent mean of 28 °C to investigate the impact of different fluctuation amplitudes (±â€…0 °C,  ±â€…2 °C,  ±â€…4 °C, and  ±â€…6 °C) across permissive temperature regimes on the performance of Spodoptera litura FabriciusFabricius, a highly destructive polyphagous pest of crops and vegetables in tropical and temperate climates. Amplitudes of temperature fluctuations significantly affected developmental durations, adult life spans, pupal weights, fecundity, and fertility of S. litura. The survival rates from the egg stage to the adult eclosion did not differ significantly across different temperature treatments. The developmental durations of individual life cycles significantly increased with larger amplitudes in 3 fluctuating temperature treatments. The pupal weight was significantly lower and the adult life span was significantly shorter in the ±â€…6 °C treatment in all treatments. Fecundity and fertility were significantly reduced in the ±â€…6 °C treatment, making the continuation of generations nearly impossible. The results should provide critical information for understanding the ecology of this widespread pest under diel, seasonal, and global climate changes.

17.
J Hazard Mater ; 469: 134075, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38508114

RESUMEN

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.


Asunto(s)
Bacillus , Desinfectantes , Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Cloro/química , Halogenación , Halógenos , Desinfección , Flavobacterium , Cloraminas/química
18.
Cereb Cortex ; 34(2)2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38372291

RESUMEN

The ecological validity of bilingual code-switching has garnered increasing attention in recent years. Contrary to traditional studies that have focused on forced language switching, emerging theories posit that voluntary switching may not incur such a cost. To test these claims and understand differences between forced and voluntary switching, the present study conducted a systematic comparison through both behavioral and neural perspectives. Utilizing fMRI alongside picture-naming tasks, our findings diverge from prior work. Voluntary language switching not only demonstrated switching costs at the behavioral level but also significantly activated brain regions associated with inhibitory control. Direct comparisons of voluntary and forced language switching revealed no significant behavioral differences in switching costs, and both shared several common brain regions that were activated. On the other hand, a nuanced difference between the two types of language switching was revealed by whole-brain analysis: voluntary switching engaged fewer language control regions than forced switching. These findings offer a comprehensive view of the neural and behavioral dynamics involved in bilingual language switching, challenging prior claims that voluntary switching imposes no behavioral or neural costs, and thus providing behavioral and neuroimaging evidence for the involvement of inhibitory control in voluntary language switching.


Asunto(s)
Imagen por Resonancia Magnética , Multilingüismo , Humanos , Lenguaje , Cognición , China
19.
Mar Drugs ; 22(2)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38393035

RESUMEN

Paralytic shellfish toxins (PSTs) are widely distributed in shellfish along the coast of China, causing a serious threat to consumer health; however, there is still a lack of large-scale systematic investigations and risk assessments. Herein, 641 shellfish samples were collected from March to November 2020, and the PSTs' toxicity was detected via liquid chromatography-tandem mass spectrometry. Furthermore, the contamination status and potential dietary risks of PSTs were discussed. PSTs were detected in 241 shellfish samples with a detection rate of 37.60%. The average PST toxicities in mussels and ark shells were considerably higher than those in other shellfish. The PSTs mainly included N-sulfonylcarbamoyl toxins (class C) and carbamoyl toxins (class GTX), and the highest PST toxicity was 546.09 µg STX eq. kg-1. The PST toxicity in spring was significantly higher than those in summer and autumn (p < 0.05). Hebei Province had the highest average PST toxicity in spring. An acute exposure assessment showed that consumers in Hebei Province had a higher dietary risk, with mussels posing a significantly higher dietary risk to consumers. This research provides reference for the green and sustainable development of the shellfish industry and the establishment of a shellfish toxin prevention and control system.


Asunto(s)
Bivalvos , Intoxicación por Mariscos , Animales , Toxinas Marinas/química , Intoxicación por Mariscos/etiología , Intoxicación por Mariscos/prevención & control , Intoxicación por Mariscos/diagnóstico , Espectrometría de Masas en Tándem/métodos , Mariscos/análisis , Bivalvos/química , Medición de Riesgo , China
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