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1.
Comput Biol Med ; 182: 109152, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39298885

RESUMEN

BACKGROUND: Pilomatricoma, a benign childhood skin tumor, presents diagnostic challenges due to its manifestation variations and requires surgical excision upon histological confirmation of its characteristic cellular features. Recent artificial intelligence (AI) advancements in pathology promise enhanced diagnostic accuracy and treatment approaches for this neoplasm. METHODS: We employed a multiscale transfer learning model, initiating the training process at high resolutions and adapting to broader scales. For evaluation purposes, we applied metrics such as accuracy, precision, recall, the F1 score, and the area under the receiver operating characteristic curve (AUROC) to measure the performance of the model, with the statistical significance of the results assessed via two-sided P tests. Our novel approach also included a retrosynthetic saliency mapping technique to achieve enhanced lesion visualization in whole-slide images (WSIs), supporting pathologists' diagnostic processes. RESULTS: Our model effectively navigated the challenges of global-scale classification, achieving a high validation accuracy of up to 0.973 despite some initial fluctuations. This method displayed excellent accuracy in terms of identifying basaloid and ghost cells, especially at lower scales, with slight variability in its ghost cell accuracy and more noticeable changes in the 'Other' category at higher scales. The consistent performance attained for basaloid cells was clear across all scales, whereas areas for improvement were identified in the 'Other' category. The model also excelled at generating detailed and interpretable saliency maps for lesion visualization purposes, thereby enhancing its value in digital pathology diagnostics. CONCLUSION: Our pilomatricoma study demonstrates the efficacy of a deep learning-based histopathological diagnosis model, as validated by its high performance across various scales, and it is enhanced by an innovative retrosynthetic approach for saliency mapping.

2.
Nat Commun ; 15(1): 8081, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39278973

RESUMEN

The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention.


Asunto(s)
Envejecimiento , Bancos de Muestras Biológicas , Biomarcadores , Estudio de Asociación del Genoma Completo , Metabolómica , Humanos , Envejecimiento/genética , Envejecimiento/metabolismo , Reino Unido/epidemiología , Masculino , Femenino , Metabolómica/métodos , Anciano , Persona de Mediana Edad , Biomarcadores/metabolismo , Análisis de la Aleatorización Mendeliana , Espectroscopía de Resonancia Magnética , Metaboloma , Estudios Longitudinales , Secuenciación Completa del Genoma , Adulto , Anciano de 80 o más Años , Biobanco del Reino Unido
3.
World J Clin Cases ; 12(26): 5990-5997, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39286390

RESUMEN

BACKGROUND: Extragastrointestinal stromal tumors (EGIST) and gastrointestinal stromal tumors are of similar pathological type and form. Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity, the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors. CASE SUMMARY: The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days. Upon physical examination, the patient had flat and tough abdomen with mild pressing pain at lower abdomen, no obvious abdominal mass was touchable, and shifting dullness was positive. Positron emission tomography-computed tomography (CT) showed that in his peritoneal cavity, there were multiple nodules of various sizes, seroperitoneum, multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules. Plain CT scanning at epigastrium/hypogastrium/pelvic cavity + enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity, peritoneum and right groin. Tumor marker of carbohydrate antigen 125 was 808 U/mL, diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia, and postoperative pathological examination confirmed EGIST. Imatinib was administered with better therapeutic effect. CONCLUSION: Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation, and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.

4.
Heliyon ; 10(17): e36498, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296093

RESUMEN

Objective: To validate the predictive power of newly developed magnetic resonance (MR) morphological and clinicopathological risk models in predicting low anterior resection syndrome (LARS) 6 months after anterior resection of middle and low rectal cancer (MLRC). Methods: From May 2018 to January 2021, 236 patients with MLRC admitted to two hospitals (internal and external validation) were included. MR images, clinicopathological data, and LARS scores (LARSS) were collected. Tumor morphology data included longitudinal involvement length, maximum tumor diameter, proportion of tumor to circumference of the intestinal wall, tumor mesorectal infiltration depth, circumferential margin status, and distance between the tumor and anal margins. Pelvic measurements included anorectal angle, mesenterial volume (MRV), and pelvic volume. Univariate and multivariate logistic regression was used to obtain independent risk factors of LARS after anterior resection Then, the prediction model was constructed, expressed as a nomogram, and its internal and external validity was assessed using receiver operating characteristic curves. Results: The uni- and multivariate analysis revealed distance between the tumor and anal margins, MRV, pelvic volume, and body weight as significant independent risk factors for predicting LARS. From the nomogram, the area under the curve (AUC), sensitivity, and specificity were 0.835, 75.0 %, and 80.4 %, respectively. The AUC, sensitivity, and specificity in the external validation group were 0.874, 83.3 %, and 91.7 %, respectively. Conclusion: This study shows that MR imaging and clinicopathology presented by a nomogram can strongly predict LARSS, which can then individually predict LARS 6 months after anterior resection in patients with MLRC and facilitate clinical decision-making. Clinical relevance statement: We believe that our study makes a significant contribution to the literature. This method of predicting postoperative anorectal function by preoperative measurement of MRV provides a new tool for clinicians to study LARS.

5.
Front Microbiol ; 15: 1463144, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296290

RESUMEN

The microbial communities inhabiting polar ecosystems, particularly in Maxwell Bay, Antarctica, play a pivotal role in nutrient cycling and ecosystem dynamics. However, the diversity of these microbial communities remains underexplored. In this study, we aim to address this gap by investigating the distribution, environmental drivers, and metabolic potential of microorganisms in Maxwell Bay. We analyzed the prokaryotic and eukaryotic microbiota at 11 stations, revealing distinctive community structures and diverse phylum dominance by using high-throughput sequencing. Spatial analysis revealed a significant impact of longitude on microbial communities, with microeukaryotes exhibiting greater sensitivity to spatial factors than microprokaryotes. We constructed co-occurrence networks to explore the stability of microbial communities, indicating the complexity and stability of microprokaryotic communities compared with those of microeukaryotes. Our findings suggest that the microeukaryotic communities in Maxwell Bay are more susceptible to disturbances. Additionally, this study revealed the spatial correlations between microbial communities, diversity, and environmental variables. Redundancy analysis highlighted the significance of pH and dissolved oxygen in shaping microprokaryotic and microeukaryotic communities, indicating the anthropogenic influence near the scientific research stations. Functional predictions using Tax4Fun2 and FUNGuild revealed the metabolic potential and trophic modes of the microprokaryotic and microeukaryotic communities, respectively. Finally, this study provides novel insights into the microbial ecology of Maxwell Bay, expanding the understanding of polar microbiomes and their responses to environmental factors.

6.
IEEE Trans Image Process ; 33: 5159-5171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39264771

RESUMEN

Multi-human parsing is an image segmentation task necessitating both instance-level and fine-grained category-level information. However, prior research has typically processed these two types of information through distinct branch types and output formats, leading to inefficient and redundant frameworks. This paper introduces UniParser, which integrates instance-level and category-level representations in three key aspects: 1) we propose a unified correlation representation learning approach, allowing our network to learn instance and category features within the cosine space; 2) we unify the form of outputs of each modules as pixel-level results while supervising instance and category features using a homogeneous label accompanied by an auxiliary loss; and 3) we design a joint optimization procedure to fuse instance and category representations. By unifying instance-level and category-level output, UniParser circumvents manually designed post-processing techniques and surpasses state-of-the-art methods, achieving 49.3% AP on MHPv2.0 and 60.4% AP on CIHP. We have released our source code, pretrained models, and demos to facilitate future studies on https://github.com/cjm-sfw/Uniparser.

7.
BMC Med Educ ; 24(1): 1023, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294595

RESUMEN

OBJECTIVE: This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. METHODS: The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. RESULTS: The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P < 0.05). The post-class questionnaire survey of the experimental group showed that most students were satisfied with the virtual simulation experimental teaching model and believed that it represented the future teaching trend. CONCLUSIONS: In the teaching of debridement, virtual simulation experiment is an effective t teaching model, which not only helps to improve student performance, but also significantly reduces skill operation time and is recognized by students.


Asunto(s)
Desbridamiento , Entrenamiento Simulado , Estudiantes de Medicina , Humanos , Desbridamiento/educación , Educación de Pregrado en Medicina/métodos , Realidad Virtual , Masculino , Evaluación Educacional , Femenino , Educación a Distancia , Competencia Clínica , Heridas y Lesiones/terapia , Heridas y Lesiones/cirugía , Simulación por Computador
8.
Environ Res ; 262(Pt 2): 119922, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39237020

RESUMEN

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration. OBJECTIVE: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum. METHODS: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis. RESULTS: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 µg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (ß: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches. CONCLUSIONS: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific.

9.
Vet Microbiol ; 298: 110241, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39226763

RESUMEN

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65 nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40 µg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

10.
Parasit Vectors ; 17(1): 376, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232817

RESUMEN

BACKGROUND: Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. METHODS: This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. RESULTS: In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host's inflammatory reaction. CONCLUSIONS: XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis.


Asunto(s)
Toxoplasma , Toxoplasma/efectos de los fármacos , Animales , Ratones , Femenino , Péptidos/farmacología , Toxoplasmosis/parasitología , Antiprotozoarios/farmacología , Hemólisis/efectos de los fármacos , Humanos
11.
Cancer Med ; 13(17): e70197, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39233657

RESUMEN

BACKGROUD: Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. METHODS: A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. RESULTS: Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. CONCLUSION: These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Ácidos Nucleicos Libres de Células/genética , Mutación , Masculino , Femenino , Biomarcadores de Tumor/genética , Sensibilidad y Especificidad , Persona de Mediana Edad , Anciano , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas
12.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1695-1704, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39235029

RESUMEN

Ant nests can affect the process and seasonal dynamics of forest soil methane emissions through mediating methane oxidation/reduction microorganisms and physicochemical environments. To explore the process and mechanism by which ant nests affect soil methane emissions from Hevea brasiliensis plantation in Xishuangbanna, we measured the seasonal dynamics of methane emissions from ant nest and non-nest soils by using static chamber-gas chromatography method, and analyzed the effect of ant nesting on the changes in functional microbial diversity, microhabitats, and soil nutrients in the plantations. The results showed that: 1) Ant nests significantly affected the mean annual soil methane emissions in tropical plantation. Methane emissions in ant nest were decreased by 59.9% than the non-nest soil. In the dry season, ant nest soil was a methane sink (-1.770 µg·m-2·h-1), which decreased by 87.2% compared with the non-nest soil, while it was a methane source (0.703 µg·m-2·h-1) that increased by 152.7% in the wet season. 2) Ant nesting affected methane emissions via changing soil temperature, humidity, carbon and nitrogen concentrations. In contrast to the control, the mean annual temperature, humidity, and carbon and nitrogen content increased by 4.9%-138.5% in ant nest soils, which explained 90.1%, 97.3%, 27.3%-90.0% of the variation in methane emissions, respectively. 3) Ant nesting affected the emission dynamics through changing the diversity and community structure of methane functional microbe. Compared with the control, the average annual methanogen diversity (Ace, Chao1, Shannon, and Simpson indices) in the ant nest ranged from -9.9% to 61.2%, which were higher than those (-8.7%-31.2%) of the methane-oxidising bacterial communities. The relative abundance fluctuations of methanogens and methanotrophic bacteria were 46.76% and -6.33%, respectively. The explaining rate of methanogen diversity to methane emissions (78.4%) was higher than that of oxidizing bacterial diversity (54.5%), the relative abundance explained by the dominant genus of methanogens was 68.9%. 4) The structural equation model showed that methanogen diversity, methanotroph diversity, and soil moisture were the main factors controlling methane emissions, contributing 95.6%, 95.0%, and 91.2% to the variations of emissions, respectively. The contribution (73.1%-87.7%) of soil temperature and carbon and nitrogen components to the emission dynamics was ranked the second. Our results suggest that ant nesting mediates the seasonal dynamics of soil methane emissions, primarily through changing the diversity of methane-function microorganisms and soil water conditions. The research results deepen the understanding of the mechanism of biological regulation of methane emission in tropical forest soil.


Asunto(s)
Hormigas , Bosques , Metano , Comportamiento de Nidificación , Estaciones del Año , Suelo , Clima Tropical , Metano/análisis , Metano/metabolismo , Hormigas/fisiología , Suelo/química , Animales , China , Microbiología del Suelo , Hevea/crecimiento & desarrollo
13.
Sensors (Basel) ; 24(17)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39275604

RESUMEN

This work focuses on the improvement of the density peaks clustering (DPC) algorithm and its application to point cloud segmentation in LiDAR. The improvement of DPC focuses on avoiding the manual determination of the cut-off distance and the manual selection of cluster centers. And the clustering process of the improved DPC is automatic without manual intervention. The cut-off distance is avoided by forming a voxel structure and using the number of points in the voxel as the local density of the voxel. The automatic selection of cluster centers is realized by selecting the voxels whose gamma values are greater than the gamma value of the inflection point of the fitted γ curve as cluster centers. Finally, a new merging strategy is introduced to overcome the over-segmentation problem and obtain the final clustering result. To verify the effectiveness of the improved DPC, experiments on point cloud segmentation of LiDAR under different scenes were conducted. The basic DPC, K-means, and DBSCAN were introduced for comparison. The experimental results showed that the improved DPC is effective and its application to point cloud segmentation of LiDAR is successful. Compared with the basic DPC, K-means, the improved DPC has better clustering accuracy. And, compared with DBSCAN, the improved DPC has comparable or slightly better clustering accuracy without nontrivial parameters.

14.
Biomaterials ; 314: 122820, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39277948

RESUMEN

Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn2+) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. A SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn2+ compared to that of histidine and Zn2+, such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing the difficult-to-treat ovarian cancer.

15.
Chemosphere ; 365: 143308, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265735

RESUMEN

Anaerobic ammonium oxidation (anammox) is an efficient and economical nitrogen removal process for treating ammonium-rich industrial wastewaters. However, Cu(Ⅱ) and Ni(Ⅱ) present in industrial wastewaters are toxic to anaerobic ammonium-oxidizing bacteria (AnAOB). Unfortunately, the effects of Cu(Ⅱ) and Ni(Ⅱ) on anammox have not been thoroughly investigated, especially when Cu(Ⅱ) and Ni(Ⅱ) coexist. This work comprehensively investigated the individual and combined effects of Cu(Ⅱ) and Ni(Ⅱ) on anammox and revealed the inhibitory mechanisms. With the influent NH4+-N and NO2--N concentration of 230 and 250 mg L-1, the inhibition thresholds on anammox are 2.00 mg L-1 Cu(Ⅱ), 1.00 mg L-1 Ni(Ⅱ) and 1.00 mg L-1 Cu(Ⅱ) + 1.00 mg L-1 Ni(Ⅱ), and higher Cu(Ⅱ) or Ni(Ⅱ) concentrations resulted in sharp deteriorations of nitrogen removal performance. The inhibition of Ni(Ⅱ) on anammox was mainly attributed to the adverse effect on NiR activity, while the inhibition mechanism of Cu(Ⅱ) seemed to be unrelated to the four functional enzymes, but associated with disruption of cellular and organellar membranes. The behavior of extracellular polymeric substances (EPS) contributed to the antagonistic effect between Cu(Ⅱ) and Ni(Ⅱ) on anammox. In addition, the niche of Candidatus Brocadia and Candidatus Jettenia shifted under the Cu(II) and Ni(II) stress, and Candidatus Jettenia displayed greater tolerance to Cu(II) and Ni(II) stress. In conclusion, this research clarified the combined effect and the inhibitory mechanism of multiple heavy metals on anammox, and provide the guidances for anammox process application in treating high-ammonium industrial wastewaters containing heavy metals.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39287737

RESUMEN

The persistent reliance on coal has resulted in the accumulation of substantial coal gangue, a globally recognized problematic solid waste with environmental risks. Given the coal gangue properties and global land degradation severity, the resourceful utilization of coal gangue as soil conditioners is believed to be a universally applicable, cost-effective, high-demand and environment-friendly model with broad application prospect. The direct application of raw coal gangue faces challenges of low active beneficial ingredients, inadequate water and fertilizer retention, presence of potentially toxic elements, resulting in limited efficacy and environmental contamination. This paper provided a comprehensive review of various modification methods (including mechanical, chemical, microbiological, thermal, hydrothermal and composite modifications) employed to enhance the soil improvement performance and reduce the environmental pollution of coal gangue. Furthermore, an analysis was conducted on the potential application of modified coal gangue as a muti-function soil conditioner based on its altered properties. The modified coal gangue is anticipated to effectively enhance soil quality, exhibiting significant potential in mitigating carbon emissions and facilitating soil carbon sequestration. This paper provided innovative ideas for future research on the comprehensive treatment of coal gangue and restoration of degraded soil in order to achieve the dual goals of zero-coal gangue waste and sustainable agriculture.

17.
Materials (Basel) ; 17(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39274795

RESUMEN

This study employs a hybrid numerical-experimental calibration method based on phenomena to determine the fracture parameters of the Modified Mohr-Coulomb (MMC) model. Using a self-developed VUMAT subroutine and the element deletion technique, the fracture process of a wide plate pipeline is thoroughly analyzed. This study investigates the impact of various crack shapes on the fracture response under tensile loading and the influence of surface crack size on the initiation location of a wide plate. These results demonstrate the calibrated MMC fracture model's accurate prediction of the toughness fracture behavior of X80 pipeline steel. Under equal area conditions of the dangerous section, circular cracks exhibit lower bearing capacity compared to elliptical cracks. Elliptical cracks predominantly propagate in the thickness direction, whereas circular cracks show nearly uniform growth in all directions. Furthermore, when the crack depth is less than half of the wall thickness, the damage accumulation value at the midpoint of the crack front is maximized; conversely, when the crack front is closer to the internal measurement point of the wide plate, the damage accumulation value is maximized.

18.
Res Sq ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39281871

RESUMEN

Background Autistic individuals show deficits in sustained fine motor control which are associated with an over-reliance on visual feedback. Motor memory deficits also have been reported during sustained fine motor control in autism spectrum disorders (ASD). The development of motor memory and visuomotor feedback processes contributing to sustained motor control issues in ASD are not known. The present study aimed to characterize age-related changes in visual feedback and motor memory processes contributing to sustained fine motor control issues in ASD. Methods Fifty-four autistic participants and 31 neurotypical (NT) controls ages 10-25 years completed visually guided and memory guided sustained precision gripping tests by pressing on force sensors with their dominant hand index finger and thumb. For visually guided trials, participants viewed a stationary target bar and a force bar that moved upwards with increased force for 15s. During memory guided trials, the force bar was visible for 3s, after which participants attempted to maintain their force output without visual feedback for another 12s. To assess visual feedback processing, force accuracy, variability (standard deviation), and regularity (sample entropy) were examined. To assess motor memory, force decay latency, slope, and magnitude were examined during epochs without visual feedback. Results Relative to NT controls, autistic individuals showed a greater magnitude and steeper slope of force decay during memory guided trials. Across conditions, the ASD group showed reduced force accuracy (ß = .41, R 2 = 0.043, t 79.3 =2.36, p = 0.021) and greater force variability (ß=-2.16, R 2 = .143, t 77.1 =-4.04, p = 0.0001) and regularity (ß=-.52, R 2 = .021, t 77.4 =-2.21, p = 0.030) relative to controls at younger ages, but these differences normalized by adolescence (age x group interactions). Lower force accuracy and greater force variability during visually guided trials and steeper decay slope during memory guided trials were associated with overall autism severity. Conclusions Our findings that autistic individuals show a greater rate and magnitude of force decay than NT individuals following the removal of visual feedback indicate that motor memory deficits contribute to fine motor control issues in ASD. Findings that sensorimotor differences in ASD were specific to younger ages suggest delayed development across multiple motor control processes.

19.
Proc Natl Acad Sci U S A ; 121(38): e2402518121, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39254997

RESUMEN

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer-promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.


Asunto(s)
Axones , Cromatina , Cohesinas , Regeneración Nerviosa , Regiones Promotoras Genéticas , Células Receptoras Sensoriales , Animales , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Ratones , Regiones Promotoras Genéticas/genética , Cromatina/metabolismo , Regeneración Nerviosa/genética , Regeneración Nerviosa/fisiología , Axones/metabolismo , Axones/fisiología , Humanos , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Elementos de Facilitación Genéticos/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Nervio Ciático/metabolismo
20.
J Mol Biol ; 436(17): 168705, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39237194

RESUMEN

We introduce XGR-model (or XGRm), a web server made accessible at http://www.xgrm.pro, with the aim of meeting the increasing demand for effectively interpreting summary-level genomic data in model organisms. Currently, it hosts two enrichment analysers and two subnetwork analysers to support enrichment and subnetwork analyses for user-input mouse genomic data, whether gene-centric or genomic region-centric. The enrichment analysers identify ontology term enrichments for input genes (GElyser) or for genes linked from input genomic regions (RElyser). The subnetwork analysers rely on our previously established network algorithm to identify gene subnetworks from input gene-centric summary data (GSlyser) or from input region-centric summary data (RSlyser), leveraging network information about either functional interactions or pathway-derived interactions. Collectively, XGRm offers an all-in-one solution for gaining systems biology insights into summary-level genomic data in mice, underpinned by our commitment to regular updates as well as natural extensions to other model organisms.


Asunto(s)
Genómica , Internet , Programas Informáticos , Animales , Ratones , Genómica/métodos , Redes Reguladoras de Genes , Biología Computacional/métodos , Algoritmos , Genoma
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