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The mechanisms of trypsin hydrolysis time on the structure of soy protein hydrolysate fibril aggregates (SPHFAs) and the stability of SPHFAs-high internal phase Pickering emulsions (HIPPEs) were investigated. SPHFAs were prepared using soy protein hydrolysate (SPH) with different trypsin hydrolysis time (0 min-120 min) to stabilize SPHFAs-HIPPEs. The results showed that moderate trypsin hydrolysis (30 min, hydrolysis degree of 2.31 %) induced SPH unfolding and increased the surface hydrophobicity of SPH, thereby promoting the formation of flexible SPHFAs with maximal thioflavin T intensity and ζ-potential. Moreover, moderate trypsin hydrolysis improved the viscoelasticity of SPHFAs-HIPPEs, and SPHFAs-HIPPEs remained stable after storage at 25 °C for 80 d and heating at 100 °C for 1 h. Excessive trypsin hydrolysis (> 30 min) decreased the stability of SPHFAs-HIPPEs. In conclusion, moderate trypsin hydrolysis promoted the formation of flexible SPHFAs with high surface charge by inducing SPH unfolding, thereby promoting the stability of SPHFAs-HIPPEs.
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Emulsões , Interações Hidrofóbicas e Hidrofílicas , Hidrolisados de Proteína , Proteínas de Soja , Tripsina , Tripsina/química , Hidrólise , Emulsões/química , Proteínas de Soja/química , Hidrolisados de Proteína/química , Agregados ProteicosRESUMO
JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
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JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
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Ambient mass spectrometry allows direct analysis of various sample types with minimal or no pretreatment. However, due to the influence of matrix effects, there are sensitivity and issues in analyzing trace analytes in complex food samples. In this work, we developed a spray mass spectrometry platform based on SSS@TPBD-TPA@MIPs (Stainless steel substrate (SSS), terephthalaldehyde (TPA), N, N, N', N'-tetrakis(p-aminophenyl)-p-phenylenediamine (TPBD), molecularly imprinted polymer (MIP)), for rapid, in situ, high-throughput, highly enrichment efficiency and highly selective trace analysis of aflatoxins. By simplifying the sample pretreatment and directly applying high voltage for ESI-MS, the analysis can be completed within 1 min. The established method base on SSS@TPBD-TPA@MIPs exhibited high sensitivity and accuracy when determine trace level AFs in maize and peanuts. The results demonstrated a good linear relationship within the range of 0.01-10 µg/L, with the determination coefficient (R2) ≥ 0.9956. The limits of detection (LODs) was 0.035-0.3 ng/mL and limits of quantitation (LOQs) was 0.12-0.99 ng/mL, with acceptable recovery rate of 82.09-115.66 % and good repeatability represented by the relative standard deviation (RSD) less than 17.43 %. Furthermore, SSS@TPBD-TPA@MIPs exhibited excellent reusability, with more than 8 repeated uses, and showed good adsorption performance.
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BACKGROUND: The UDP-glucuronosyltransferase 91D2 (SrUGT91D2) gene is a crucial element in the biosynthetic pathway of steviol glycosides (SGs) and is responsible for creating 1,2-ß-D glucosidic bonds at the C19 and C13 positions. This process plays a vital role in the synthesis of rebaudioside M (RM) and rebaudioside D (RD). The promoter, which regulates gene expression, requires functional analysis to understand gene expression regulation. However, investigations into the function of the promoter of SrUGT91D2 (pSrUGT91D2) have not been reported. RESULTS: The pSrUGT91D2 was isolated from six S. rebaudiana lines, and subsequent multiple sequence comparisons revealed the presence of a 26 bp inDel fragment (pSrUGT91D2-B1188 type) in lines GP, GX, 110, 1114, and B1188 but not in the pSrUGT91D2 of line 023 (pSrUGT91D2-023 type). Bioinformatics analysis revealed a prevalence of significant cis-regulatory elements (CREs) within the promoter sequences, including those responsive to abscisic acid, light, anaerobic conditions, auxin, drought, low temperature, and MeJA. To verify the activity of pSrUGT91D2, the full-length promoter and a series of 5' deletion fragments (P1-P7) and a 3' deletion fragment (P8) from various lines were fused with the reporter ß-glucuronidase (GUS) gene to construct the plant expression vector, pCAMBIA1300-proâ·GUS. The transcriptional activity of these genes was examined in tobacco leaves through transient transformation. GUS tissue staining analysis and enzyme activity assays demonstrated that both the full-length promoter and truncated pSrUGT91D2 were capable of initiating GUS expression in tobacco leaves. Interestingly, P8-pSrUGT91D2-B1188 (containing the inDel segment, 301 bp) exhibited enhanced activity in driving GUS gene expression. Transient expression studies of P8-pSrUGT91D2-B1188 and P8-pSrUGT91D2-023 in response to exogenous hormones (abscisic acid and indole-3-acetic acid) and light indicated the necessity of the inDel region for P8 to exhibit transcriptional activity, as it displayed strong responsiveness to abscisic acid (ABA), indole-3-acetic acid (IAA), and light induction. CONCLUSIONS: These findings contribute to a deeper understanding of the regulatory mechanism of the upstream region of the SrUGT91D2 gene and provide a theoretical basis for future studies on the interaction between CREs of pSrUGT91D2 and related transcription factors.
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Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas , Regiões Promotoras Genéticas , Stevia , Estresse Fisiológico , Regiões Promotoras Genéticas/genética , Stevia/genética , Stevia/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Diterpenos do Tipo Caurano/metabolismoRESUMO
Navigating space and forming memories based on spatial experience are crucial for survival, including storing memories in an allocentric (map-like) framework and conversion into body-centered action. The hippocampus and parietal cortex (PC) comprise a network for coordinating these reference frames, though the mechanism remains unclear. We used a task requiring remembering previous spatial locations to make correct future action and observed that hippocampus can encode the allocentric place, while PC encodes upcoming actions and relays this to hippocampus. Transformation from location to action unfolds gradually, with 'Came From' signals diminishing and future action representations strengthening. PC sometimes encodes previous spatial locations in a route-based reference frame and conveys this to hippocampus. The signal for the future location appears first in PC, and then in hippocampus, in the form of an egocentric direction of future goal locations, suggesting egocentric encoding recently observed in hippocampus may originate in PC (or another "upstream" structure). Bidirectional signaling suggests a coordinated mechanism for integrating map-like, route-centered, and person-centered spatial reference frames at the network level during navigation.
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This study investigates the incidence of Class B respiratory infectious diseases (RIDs) in China under the Coronavirus disease 2019 (COVID-19) epidemic and examines variations post-epidemic, following the relaxation of non-pharmaceutical interventions (NPIs). Two-stage evaluation was used in our study. In the first stage evaluation, we established counterfactual models for the pre-COVID-19 period to estimate expected incidences of Class B RIDs without the onset of the epidemic. In the second stage evaluation, we constructed seasonal autoregressive integrated moving average intervention (SARIMA-Intervention) models to evaluate the impact on the Class B RIDs after NPIs aimed at COVID-19 pandemic were relaxed. The counterfactual model in the first stage evaluation suggested average annual increases of 10.015%, 78.019%, 70.439%, and 67.799% for tuberculosis, scarlet fever, measles, and pertussis respectively, had the epidemic not occurred. In the second stage evaluation, the total relative reduction in 2023 of tuberculosis, scarlet fever, measles and pertussis were - 35.209%, - 59.184%, - 4.481%, and - 9.943% respectively. The actual incidence declined significantly in the first stage evaluation. However, the results of the second stage evaluation indicated that a rebound occurred in four Class B RIDs after the relaxation of NPIs; all of these showed a negative total relative reduction rate.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/prevenção & controle , China/epidemiologia , Incidência , SARS-CoV-2/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/transmissão , Infecções Respiratórias/virologia , Infecções Respiratórias/prevenção & controle , Escarlatina/epidemiologia , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Coqueluche/transmissão , Sarampo/epidemiologia , Sarampo/transmissão , Sarampo/prevenção & controle , Pandemias/prevenção & controle , Tuberculose/epidemiologia , Tuberculose/transmissão , Tuberculose/prevenção & controleRESUMO
Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs.
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Lipídeos , Nanopartículas , Tamanho da Partícula , Polietilenoglicóis , RNA Mensageiro , Transfecção , Nanopartículas/química , Animais , Polietilenoglicóis/química , Injeções Intramusculares , Lipídeos/química , Transfecção/métodos , Camundongos , Técnicas de Transferência de Genes , Humanos , Luciferases/metabolismo , Luciferases/genética , Propriedades de Superfície , LipossomosRESUMO
East Asian herbivorous waterfowl intensively use farmland in spring, next to their natural habitat. Accordingly, they might have expanded their migration strategy from merely tracking the green wave of newly emerging vegetation to also incorporating the availability of post-harvest agricultural seeds (here dubbed the seed wave). However, if and how waterfowl use multiple food resources to time their seasonal migration is still unknown. We test this migration strategy using 167 spring migration tracks of five East Asian herbivorous waterfowl species and mixed-effect resource selection function models. We found that all study species arrived at their core stopover sites in the Northeast China Plain after agricultural seeds became available, extended their stay after spring vegetation emerged and arrived at their breeding sites around the emergence of vegetation. At the core stopover sites, all study species used snowmelt as a cue to track seed availability, although smaller-bodied species tended to arrive later. At the breeding sites, swans tracked the onset of vegetation emergence and geese tracked the mid- or end phases of snowmelt. Our findings suggest that waterfowl track multiple resource waves to fine-tune their migration, highlighting new opportunities for conservation.
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Migração Animal , Anseriformes , Herbivoria , Estações do Ano , Animais , Anseriformes/fisiologia , China , Gansos/fisiologia , EcossistemaRESUMO
BACKGROUND: To assess the distribution characteristics of immune infiltration and lymphovascular invasion in breast cancer skin recurrence patients. METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent radical surgery for primary breast cancer and experienced skin recurrence between January 2001 and April 2019. Immune and lymphovascular biomarkers were quantified in primary breast cancers, skin lesions and visceral metastatic lesions. Differences in biomarkers distribution between matched tissues were statistically analyzed using the Wilcoxon signed-rank test and Kruskal-Wallis one-way ANOVA. RESULTS: A total of 71 female breast cancer patients were reviewed in this study. Our study found that the expression levels of various lymphocyte immune markers in primary tumor specimens were higher than those in skin recurrences. The expression of CD8, CD57 and CD31 in primary breast cancer was higher than those in the skin. Compared to visceral metastatic lesions, D2-40 was highly expressed in the skin, while CD8 tended to decrease. In the skin specimens, the expression of CD8 (P < 0.001), FOXP3 (P = 0.006) and CD68 (P < 0.001) in the intratumoral area was higher, while the expression of CD57 (P < 0.001) was higher in the peritumoral area. Analyzing specimens from the same patient at different time points of skin progression, it was found that the expression of peritumoral CD4 decreased (P = 0.044) as the disease progressed. The low expression of D2-40 and CD163 in the skin lesions suggested a decrease in DFS. CONCLUSION: The immune microenvironment of breast cancer skin recurrence may be in a state of suppression, and this suppression may intensify with disease progression. The pattern of skin recurrence may be more inclined toward lymphatic invasion. Our study provides new insights into the biological behaviors of this disease and its response to immunotherapy.
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Neoplasias da Mama , Linfócitos do Interstício Tumoral , Recidiva Local de Neoplasia , Neoplasias Cutâneas , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/metabolismo , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Metástase Linfática/patologia , Metástase Linfática/imunologia , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral/imunologia , Invasividade Neoplásica , PrognósticoRESUMO
A major scientific drive is to characterize the protein-coding genome as it provides the primary basis for the study of human health. But the fundamental question remains: what has been missed in prior genomic analyses? Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states, with major implications for proteomics, genomics, and clinical science. However, the impact of ncORFs has been limited by the absence of a large-scale understanding of their contribution to the human proteome. Here, we report the collaborative efforts of stakeholders in proteomics, immunopeptidomics, Ribo-seq ORF discovery, and gene annotation, to produce a consensus landscape of protein-level evidence for ncORFs. We show that at least 25% of a set of 7,264 ncORFs give rise to translated gene products, yielding over 3,000 peptides in a pan-proteome analysis encompassing 3.8 billion mass spectra from 95,520 experiments. With these data, we developed an annotation framework for ncORFs and created public tools for researchers through GENCODE and PeptideAtlas. This work will provide a platform to advance ncORF-derived proteins in biomedical discovery and, beyond humans, diverse animals and plants where ncORFs are similarly observed.
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Mealworms (Tenebrio molitor) larvae can degrade both plastics and lignocellulose through synergistic biological activities of their gut microbiota because they share similarities in chemical and physical properties. Here, a total of 428 genes encoding lignocellulose-degrading enzymes were screened from the gut microbiome of T. molitor larvae to identify poly(ethylene terephthalate) (PET)-degrading activities. Five genes were successfully expressed in E. coli, among which a feruloyl esterase-like enzyme named TmFae-PETase demonstrated the highest PET degradation activity, converting PET into MHET (0.7 mgMHETeq ·h-1·mgenzyme-1) and TPA (0.2 mgTPAeq ·h-1·mgenzyme-1) at 50 °C. TmFae-PETase showed a preference for the hydrolysis of ferulic acid methyl ester (MFA) in the presence of both PET and MFA. Site-directed mutagenesis and molecular dynamics simulations of TmFae-PETase revealed similar catalytic mechanisms for both PET and MFA. TmFae-PETase effectively depolymerized commercial PET, making it a promising candidate for application. Additionally, the known PET hydrolases IsPETase, FsC, and LCC also hydrolyzed MFA, indicating a potential origin of PET hydrolytic activity from its lignocellulosic-degrading abilities. This study provides an innovative strategy for screening PET-degrading enzymes identified from lignocellulose degradation-related enzymes within the gut microbiome of plastic-degrading mealworms. This discovery expands the existing pool of plastic-degrading enzymes available for resource recovery and bioremediation applications.
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We are writing to you in response to the article published in BMC Nephrology titled "Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study". The study provided valuable information on the use of nafamostat mesylate (NM) during continuous renal replacement therapy (CRRT) in critically ill patients. We noticed in this study that a higher dose of NM resulted in a decrease in ICU and hospital mortality. However, the underlying mechanism behind this phenomenon remains unclear. We believe exploring this further is warranted.
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Benzamidinas , Estado Terminal , Guanidinas , Humanos , Estado Terminal/terapia , Guanidinas/uso terapêutico , Terapia de Substituição Renal Contínua , Membranas Artificiais , Adsorção , Injúria Renal Aguda/terapia , Terapia de Substituição RenalRESUMO
Comprehensive site investigation techniques, including Electrical Resistivity Tomography (ERT), Induced Polarization (IP), Multichannel Analysis of Surface Waves (MASW), and Microtremor Array Method (MAM), were integrated with geotechnical and geochemical tests of retrieved waste samples from Singapore's operational offshore landfill. The properties of landfill wastes vary widely, including shear-wave velocities 127-248 m/s, densities 1.2-2.1 Mg/m3, resistivity 3.0-25.3 Ωâm, and chargeability 48-82 mV/V. The natural clay layer underneath was clearly delineated and effectively mitigated leachate leakage. K-means clustering of the geophysical data facilitates precise mapping of waste distribution and quantities of recoverable metals based on quantitative criteria. This study illustrates a thorough case study adopting the new site investigation and characterization paradigm for an offshore landfill, which provides insights into leachate leakage detection and evaluations of landfill mining and resource recovery.
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The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with Mn of 20.3 kDa and Mw of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13C isotopic shift of the residual PS in feces versus pristine PS (Δ Î´13C of 2.28 ), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics.
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Biodegradação Ambiental , Baratas , Microbioma Gastrointestinal , Poliestirenos , Animais , Poliestirenos/química , Baratas/microbiologia , Baratas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Microplásticos/toxicidadeRESUMO
Weeds are undesired plants competing with crops for light, nutrients, and water, negatively impacting crop growth. Identifying weeds in wheat fields accurately is important for precise pesticide spraying and targeted weed control. Grass weeds in their early growth stages look very similar to wheat seedlings, making them difficult to identify. In this study, we focused on wheat fields with varying levels of grass weed infestation and used unmanned aerial vehicles (UAVs) to obtain images. By utilizing deep learning algorithms and spectral analysis technology, the weeds were identified and extracted accurately from wheat fields. Our results showed that the precision of weed detection in scattered wheat fields was 91.27% and 87.51% in drilled wheat fields. Compared to areas without weeds, the increase in weed density led to a decrease in wheat biomass, with the maximum biomass decreasing by 71%. The effect of weed density on yield was similar, with the maximum yield decreasing by 4320 kg·ha- 1, a drop of 60%. In this study, a method for monitoring weed occurrence in wheat fields was established, and the effects of weeds on wheat growth in different growth periods and weed densities were studied by accurately extracting weeds from wheat fields. The results can provide a reference for weed control and hazard assessment research.
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OBJECTIVE: To create a deep-learning automatic segmentation model for esophageal cancer (EC), metastatic lymph nodes (MLNs) and their adjacent structures using the UperNet Swin network and computed tomography angiography (CTA) images and to improve the effectiveness and precision of EC automatic segmentation and TN stage diagnosis. METHODS: Attention U-Net, UperNet Swin, UNet++ and UNet were used to train the EC segmentation model to automatically segment the EC, esophagus, pericardium, aorta and MLN from CTA images of 182 patients with postoperative pathologically proven EC. The Dice similarity coefficient (DSC), sensitivity, and positive predictive value (PPV) were used to assess their segmentation effectiveness. The volume of EC was calculated using the segmentation results, and the outcomes and times of automatic and human segmentation were compared. All statistical analyses were completed using SPSS 25.0 software. RESULTS: Among the four EC autosegmentation models, the UperNet Swin had the best autosegmentation results with a DSC of 0.7820 and the highest values of EC sensitivity and PPV. The esophagus, pericardium, aorta and MLN had DSCs of 0.7298, 0.9664, 0.9496 and 0.5091. The DSCs of the UperNet Swin were 0.6164, 0.7842, 0.8190, and 0.7259 for T1-4 EC. The volume of EC and its adjacent structures between the ground truth and UperNet Swin model were not significantly different. CONCLUSIONS: The UperNet Swin showed excellent efficiency in autosegmentation and volume measurement of EC, MLN and its adjacent structures in different T stage, which can help to T and N stage diagnose EC and will save clinicians time and energy.
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Angiografia por Tomografia Computadorizada , Aprendizado Profundo , Neoplasias Esofágicas , Linfonodos , Metástase Linfática , Humanos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Masculino , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Feminino , Pessoa de Meia-Idade , Angiografia por Tomografia Computadorizada/métodos , Idoso , Adulto , Processamento de Imagem Assistida por Computador/métodos , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: This study aims to elucidate the role of Fe2+ overload in kainic acid (KA)-induced excitotoxicity, investigate the involvement of ferritinophagy selective cargo receptor NCOA4 in the pathogenesis of excitotoxicity. METHODS: Western blotting was used to detect the expression of FTH1, NCOA4, Lamp2, TfR, FPN, and DMT1 after KA stereotaxic injection into the unilateral striatum of mice. Colocalization of Fe2+ with lysosomes in KA-treated primary cortical neurons was observed by using confocal microscopy. Desferrioxamine (DFO) was added to chelate free iron, a CCK8 kit was used to measure cell viability, and the Fe2+ levels were detected by FerroOrange. BODIPY C11 was used to determine intracellular lipid reactive oxygen species (ROS) levels, and the mRNA levels of PTGS2, a biomarker of ferroptosis, were measured by fluorescent quantitative PCR. 3-Methyladenine (3-MA) was employed to inhibit KA-induced activation of autophagy, and changes in ferritinophagy-related protein expression and the indicated biomarkers of ferroptosis were detected. Endogenous NCOA4 was knocked down by lentivirus transfection, and cell viability and intracellular Fe2+ levels were observed after KA treatment. RESULTS: Western blot results showed that the expression of NCOA4, DMT1, and Lamp2 was significantly upregulated, while FTH1 was downregulated, but there were no significant changes in TfR and FPN. The fluorescence results indicated that KA enhanced the colocalization of free Fe2+ with lysosomes in neurons. DFO intervention could effectively rescue cell damage, reduce intracellular lipid peroxidation, and decrease the increased transcript levels of PTGS2 caused by KA. Pretreatment with 3-MA effectively reversed KA-induced ferritinophagy and ferroptosis. Endogenous interference with NCOA4 significantly improved cell viability and reduced intracellular free Fe2+ levels in KA-treated cells. CONCLUSION: KA-induced excitotoxicity activates ferritinophagy, and targeting ferritinophagy effectively inhibits downstream ferroptosis. Interference with NCOA4 effectively attenuates KA-induced neuronal damage. This study provides a potential therapeutic target for excitotoxicity related disease conditions.