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Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.
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Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch's permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0-8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections.
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Beef is a major global source of protein, playing an essential role in the human diet. The worldwide production and consumption of beef continue to rise, reflecting a significant trend. However, despite the critical importance of beef cattle resources in agriculture, the diversity of cattle breeds faces severe challenges, with many breeds at risk of extinction. The initiation of the Beef Cattle Genome Project is crucial. By constructing a high-precision functional annotation map of their genome, it becomes possible to analyze the genetic mechanisms underlying important traits in beef cattle, laying a solid foundation for breeding more efficient and productive cattle breeds. This review details advances in genome sequencing and assembly technologies, iterative upgrades of the beef cattle reference genome, and its application in pan-genome research. Additionally, it summarizes relevant studies on the discovery of functional genes associated with key traits in beef cattle, such as growth, meat quality, reproduction, polled traits, disease resistance, and environmental adaptability. Finally, the review explores the potential of telomere-to-telomere (T2T) genome assembly, structural variations (SVs), and multi-omics techniques in future beef cattle genetic breeding. These advancements collectively offer promising avenues for enhancing beef cattle breeding and improving genetic traits.
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Genoma , Animais , Bovinos/genética , Genômica/métodos , Cruzamento/métodos , Sequenciamento Completo do Genoma/métodos , Carne Vermelha , Locos de Características QuantitativasRESUMO
Objectives: This study aimed to explore the value of radiomics nomogram based on computed tomography (CT) on the diagnosis of benign and malignant solitary indeterminate smoothly marginated solid pulmonary nodules (SMSPNs). Methods: This study retrospectively reviewed 205 cases with solitary indeterminate SMSPNs on CT, including 112 cases of benign nodules and 93 cases of malignant nodules. They were divided into training (n=143) and validation (n=62) cohorts based on different CT scanners. Radiomics features of the nodules were extracted from the lung window CT images. The variance threshold method, SelectKBest, and least absolute shrinkage and selection operator were used to select the key radiomics features to construct the rad-score. Through multivariate logistic regression analysis, a nomogram was built by combining rad-score, clinical factors, and CT features. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 19 radiomics features were selected to construct the rad-score, and the nomogram was constructed by the rad-score, one clinical factor (history of malignant tumor), and three CT features (including calcification, pleural retraction, and lobulation). The nomogram performed better than the radiomics model, clinical model, and experienced radiologists who specialized in thoracic radiology for nodule diagnosis. The AUC values of the nomogram were 0.942 in the training cohort and 0.933 in the validation cohort. The calibration curve and decision curve showed that the nomogram demonstrated good consistency and clinical applicability. Conclusion: The CT-based radiomics nomogram achieved high efficiency in the preoperative diagnosis of solitary indeterminate SMSPNs, and it is of great significance in guiding clinical decision-making.
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The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.
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Serina Endopeptidases , Glicoproteína da Espícula de Coronavírus , Internalização do Vírus , Humanos , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Polissacarídeos/metabolismo , Polissacarídeos/química , Células HEK293 , Ligação Proteica , Receptores Virais/metabolismo , Receptores Virais/química , Coronavirus/metabolismo , Modelos MolecularesRESUMO
Introduction: The ban on antibiotics in animal husbandry underscores the crucial need for safe, natural feed additives. This study investigates the effects of Ampelopsis grossedentata flavonoids (AGF) and Tween 80 on the growth performance, blood indexes, and rumen microbiota of Nubian goats, evaluating their potential as alternative feed additives in livestock management. Methods: Thirty-two goats were randomly divided into four groups. The control group (CON group) was provided with a basal diet, while the experimental groups received diets supplemented with various dietary additives for a duration of 100 days: either a basal diet supplemented with 25 mg/kg of monensin (MN group), a basal diet containing 2.0 g/kg of Ampelopsis grossedentata flavonoids (AGF group), or a basal diet containing 7.5 mL/kg of Tween 80 (TW group). Blood and rumen fluid samples were collected for analysis at the end of the feeding period. Growth performance was monitored through regular weighing and feed intake measurements. Blood indexes were analyzed using standard biochemical techniques, while the microbial composition of the rumen fluid was determined through high throughput 16S rRNA gene sequencing to assess microbial diversity and function. The effects of the dietary treatments on growth performance, blood indexes, and rumen microbial composition were then evaluated. Results: The AGF group exhibited significantly increased average daily gain, and decreased feed-to-gain ratio (p < 0.05). Blood indexes analysis revealed no differences between the CON and AGF groups, with both showing higher concentrations of triglyceride, low-density lipoprotein cholesterol, glutamic-pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase compared to the monensin group (p < 0.05). The TW group had significantly higher glucose, glutamic-oxaloacetic transaminase, and glutamic-pyruvic transaminase levels than the MN group (p < 0.05). Microbial diversity analysis revealed that the TW group had significantly greater alpha-diversity than other groups, while beta-diversity analysis showed closer similarity between the rumen microbiota of the AGF and CON groups. LEfSe analysis identified Proteobacteria, Deferribacteres, Ehryarchaeoia, and Elusimicrobia as biomarkers distinguishing the rumen microbiota among the groups. In conclusion, AGF supplementation increased the relative abundance of beneficial bacteria in the rumen of Nubian goats, and thus enhanced the growth performance. TW supplementation significantly increased rumen microbial diversity and abundance, suggesting benefits for rumen health despite poor palatability. These findings highlight the potential of AGF as a new green additive with important implications for the efficiency and development of animal husbandry.
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The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic sequencing. This investigation used tissues from five distinct organs (heart, liver, spleen, kidney, and brain) of the Chungtien schizothoracin for PacBio Iso-seq and RNA-seq analyses, yielding a repertoire of 16,598 full-length transcripts spanning lengths from 363 bp to 7,157 bp. Gene family clustering and phylogenetic analysis encompassed a comprehensive set of 13 fish species, all of which were cyprinids, including the zebrafish and the examined species Ptychobarbus chungtienensis. Moreover, the identification of long non-coding RNAs (lncRNAs) and coding sequences was accomplished across all five tissues. Comprehensive analyses of gene expression profiles and differentially expressed genes among the above five tissues were performed. In summary, the obtained full-length transcripts and detailed gene expression profiles of the Chungtien schizothoracin tissues furnish crucial expression data and genetic sequences, laying the groundwork for future investigations and fostering a holistic comprehension of the adaptive mechanisms inherent in the Chungtien schizothoracin under various conditions.
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Cyprinidae , Filogenia , Transcriptoma , Animais , Cyprinidae/genética , RNA-Seq , RNA Longo não Codificante/genética , Espécies em Perigo de ExtinçãoRESUMO
Peganum harmala L. is a perennial herbaceous plant that plays critical roles in protecting the ecological environment in arid, semi-arid, and desert areas. Although the seed germination characteristics of P. harmala in response to environmental factors (i.e., drought, temperature, and salt) have been investigated, the response mechanism of seed germination to drought conditions has not yet been revealed. In this study, the changes in the physiological characteristics and transcriptional profiles in seed germination were examined under different polyethylene glycol (PEG) concentrations (0-25%). The results show that the seed germination rate was significantly inhibited with an increase in the PEG concentration. Totals of 3726 and 10,481 differentially expressed genes (DEGs) were, respectively, generated at 5% and 25% PEG vs. the control (C), with 1642 co-expressed DEGs, such as drought stress (15), stress response (175), and primary metabolism (261). The relative expression levels (RELs) of the key genes regulating seed germination in response to drought stress were in accordance with the physiological changes. These findings will pave the way to increase the seed germination rate of P. harmala in drought conditions.
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Plants generally enhance their root growth in the form of greater biomass and/or root length to boost nutrient uptake in response to short-term low nitrogen (LN). However, the underlying mechanisms of short-term LN-mediated root growth remain largely elusive. Our genome-wide association study, haplotype analysis, and phenotyping of transgenic plants showed that the crucial nitrate signaling component NIN-LIKE PROTEIN3.2 (ZmNLP3.2), a positive regulator of root biomass, is associated with natural variations in root biomass of maize (Zea mays L.) seedlings under LN. The monocot-specific gene AUXIN/INDOLE-3-ACETIC ACID14 (ZmAux/IAA14) exhibited opposite expression patterns to ZmNLP3.2 in ZmNLP3.2 knockout and overexpression lines, suggesting that ZmNLP3.2 hampers ZmAux/IAA14 transcription. Importantly, ZmAux/IAA14 knockout seedlings showed a greater root dry weight (RDW), whereas ZmAux/IAA14 overexpression reduced RDW under LN compared with wild-type plants, indicating that ZmAux/IAA14 negatively regulates the RDW of LN-grown seedlings. Moreover, in vitro and vivo assays indicated that AUXIN RESPONSE FACTOR19 (ZmARF19) binds to and transcriptionally activates ZmAux/IAA14, which was weakened by the ZmNLP3.2-ZmARF19 interaction. The zmnlp3.2 ZmAux/IAA14-OE seedlings exhibited further reduced RDW compared to ZmAux/IAA14 overexpression lines when subjected to LN treatment, corroborating the ZmNLP3.2-ZmAux/IAA14 interaction. Thus, our study reveals a ZmNLP3.2-ZmARF19-ZmAux/IAA14 module regulating root biomass in response to nitrogen limitation in maize.
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Sinopodophylli Fructus is a traditional medicine used by the Tibetan people. It is known for its ability to regulate menstruation and promote blood circulation. Presently, bioactive constituents that have been isolated and identified from Sinopodophylli Fructus mainly include 15 lignans(e.g., podophyllotoxin, deoxypodophyllotoxin, and 4'-demethylpodophyllotoxin) and 20 flavonoids(e.g., quercetin, kaempferol, and rutin). These components exhibit pharmacological effects such as anticancer, antibacterial, and lipid-lowering activities. Additionally, Sinopodophylli Fructus contains other components such as proteins, fatty acids, polysaccharides, vitamins, amino acids, and trace elements. According to the relevant literature reports in China and abroad, this article reviewed the chemical constituents and pharmacological effects of Sinopodophylli Fructus, aiming to provide references for the development and rational clinical application of this medicinal resource.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Tibetana , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Animais , Flavonoides/química , Flavonoides/farmacologia , Frutas/químicaRESUMO
Purpose: To determine the efficacy and safety of a neuromodulation intervention regimen in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Patients and Methods: Systematic searches were conducted in seven English databases. Randomized controlled trials of all neuromodulation interventions (both invasive and non-invasive) for the treatment of CIPN were selected. Group comparisons of differences between interventions and controls were also made. We divided the outcomes into immediate-term effect (≤3 weeks), short-term effect (3 weeks to ≤3 months), and long-term effect (>3 months). Results: Sixteen studies and 946 patients with CIPN were included. Among immediate-term effects, neuromodulation interventions were superior to usual care for improving pain (SMD=-0.77, 95% CI -1.07~ 0.47), FACT-Ntx (MD = 5.35, 95% CI 2.84~ 7.87), and QOL (SMD = 0.44, 95% CI 0.09~ 0.79) (moderate certainty); neuromodulation loaded with usual care was superior to usual care for improving pain (SMD=-0.47, 95% CI -0.71 ~ -0.23), and QOL (SMD = 0.40, 95% CI 0.12 ~ 0.69) (moderate certainty). There were no statistically significant differences between the neuromodulation interventions regimen vs usual care in short- and long-term outcomes and neuromodulation vs sham stimulation from any outcome measure. There were mild adverse events such as pain at the site of stimulation and bruising, and no serious adverse events were reported. Conclusion: Neuromodulation interventions had significant immediate-term efficacy in CIPN but had not been shown to be superior to sham stimulation; short-term and long-term efficacy could not be determined because there were too few original RCTs. Moreover, there are no serious adverse effects of this therapy.
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The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia-reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia-reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.
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Sistema Glinfático , Traumatismo por Reperfusão , Animais , Sistema Glinfático/metabolismo , Camundongos , Traumatismo por Reperfusão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Dexmedetomidina/farmacologia , Acidente Vascular Cerebral , Anestesia , Isoflurano/farmacologia , Nanopartículas/química , Líquido Cefalorraquidiano/metabolismo , Líquido Cefalorraquidiano/químicaRESUMO
Papain-like cysteine proteases (PLCPs) play pivotal roles in plant defense against pathogen invasions. While pathogens can secrete effectors to target and inhibit PLCP activities, the roles of PLCPs in plant-virus interactions and the mechanisms through which viruses neutralize PLCP activities remain largely uncharted. Here, we demonstrate that the expression and activity of a maize PLCP CCP1 (Corn Cysteine Protease), is upregulated following sugarcane mosaic virus (SCMV) infection. Transient silencing of CCP1 led to a reduction in PLCP activities, thereby promoting SCMV infection in maize. Furthermore, the knockdown of CCP1 resulted in diminished salicylic acid (SA) levels and suppressed expression of SA-responsive pathogenesis-related genes. This suggests that CCP1 plays a role in modulating the SA signaling pathway. Interestingly, NIa-Pro, the primary protease of SCMV, was found to interact with CCP1, subsequently inhibiting its protease activity. A specific motif within NIa-Pro termed the inhibitor motif was identified as essential for its interaction with CCP1 and the suppression of its activity. We have also discovered that the key amino acids responsible for the interaction between NIa-Pro and CCP1 are crucial for the virulence of SCMV. In conclusion, our findings offer compelling evidence that SCMV undermines maize defense mechanisms through the interaction of NIa-Pro with CCP1. Together, these findings shed a new light on the mechanism(s) controlling the arms races between virus and plant.
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Cisteína Proteases , Vírus do Mosaico , Potyvirus , Zea mays/genética , Cisteína Proteases/genética , Ácido Salicílico/metabolismo , Vírus do Mosaico/metabolismo , Doenças das PlantasRESUMO
ChinaMu is the largest sequence-indexed Mutator (Mu) transposon insertional library in maize (Zea mays). In this study, we made significant improvements to the size and quality of the ChinaMu library. We developed a new Mu-tag isolation method Mu-Tn5-seq (MuT-seq). Compared to the previous method used by ChinaMu, MuT-seq recovered 1/3 more germinal insertions, while requiring only about 1/14 of the sequencing volume and 1/5 of the experimental time. Using MuT-seq, we identified 113,879 germinal insertions from 3,168 Mu-active F1 families. We also assembled a high-quality genome for the Mu-active line Mu-starter, which harbors the initial active MuDR element and was used as the pollen donor for the mutation population. Using the Mu-starter genome, we recovered 33,662 (15.6%) additional germinal insertions in 3,244 (7.4%) genes in the Mu-starter line. The Mu-starter genome also improved the assignment of 117,689 (54.5%) germinal insertions. The newly upgraded ChinaMu dataset currently contains 215,889 high-quality germinal insertions. These insertions cover 32,224 pan-genes in the Mu-starter and B73Ref5 genomes, including 23,006 (80.4%) core genes shared by the two genomes. As a test model, we investigated Mu insertions in the pentatricopeptide repeat (PPR) superfamily, discovering insertions for 92% (449/487) of PPR genes in ChinaMu, demonstrating the usefulness of ChinaMu as a functional genomics resource for maize.
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Cromossomos , Elementos de DNA Transponíveis , Humanos , Elementos de DNA Transponíveis/genética , Mutagênese Insercional/genética , Sequência de Bases , Mutação , Zea mays/genéticaRESUMO
Accurately determining the metastatic status of sentinel lymph nodes (SLNs) through noninvasive imaging with high imaging resolution and sensitivity is crucial for cancer therapy. Herein, we report a dual-tracer-based NIR-II ratiometric fluorescence nanoplatform combining targeted and nontargeted moieties to determine the metastatic status of SLNs through the recording of ratio signals. Ratiometric fluorescence imaging revealed approximately 2-fold increases in signals in tumor-draining SLNs compared to inflamed and normal SLNs. Additionally, inflamed SLNs were diagnosed by combining the ratio value with the enlarged size outputted by NIR-II fluorescence imaging. The metastatic status diagnostic results obtained through NIR-II ratiometric fluorescence signals were further confirmed by standard H&E staining, indicating that the ratiometric fluorescence strategy could achieve distant metastases detection. Furthermore, the superior imaging quality of ratiometric probes enables visualization of the detailed change in the lymphatic network accompanying tumor growth. Compared to clinically available and state-of-the-art NIR contrast agents, our dual-tracer-based NIR-II ratiometric fluorescence probes provide significantly improved performance, allowing for the quick assessment of lymphatic function and guiding the removal of tumor-infiltrating SLNs during cancer surgery.
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Linfonodo Sentinela , Humanos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Corantes Fluorescentes , Metástase Linfática/patologia , Verde de Indocianina , Imagem ÓpticaRESUMO
PURPOSE: The purpose of this study was to assess the predictive performance of multiparametric magnetic resonance imaging (MRI) for molecular subtypes and interpret features using SHapley Additive exPlanations (SHAP) analysis. MATERIAL AND METHODS: Patients with breast cancer who underwent pre-treatment MRI (including ultrafast dynamic contrast-enhanced MRI, magnetic resonance spectroscopy, diffusion kurtosis imaging and intravoxel incoherent motion) were recruited between February 2019 and January 2022. Thirteen semantic and thirteen multiparametric features were collected and the key features were selected to develop machine-learning models for predicting molecular subtypes of breast cancers (luminal A, luminal B, triple-negative and HER2-enriched) by using stepwise logistic regression. Semantic model and multiparametric model were built and compared based on five machine-learning classifiers. Model decision-making was interpreted using SHAP analysis. RESULTS: A total of 188 women (mean age, 53 ± 11 [standard deviation] years; age range: 25-75 years) were enrolled and further divided into training cohort (131 women) and validation cohort (57 women). XGBoost demonstrated good predictive performance among five machine-learning classifiers. Within the validation cohort, the areas under the receiver operating characteristic curves (AUCs) for the semantic models ranged from 0.693 (95% confidence interval [CI]: 0.478-0.839) for HER2-enriched subtype to 0.764 (95% CI: 0.681-0.908) for luminal A subtype, inferior to multiparametric models that yielded AUCs ranging from 0.771 (95% CI: 0.630-0.888) for HER2-enriched subtype to 0.857 (95% CI: 0.717-0.957) for triple-negative subtype. The AUCs between the semantic and the multiparametric models did not show significant differences (P range: 0.217-0.640). SHAP analysis revealed that lower iAUC, higher kurtosis, lower D*, and lower kurtosis were distinctive features for luminal A, luminal B, triple-negative breast cancer, and HER2-enriched subtypes, respectively. CONCLUSION: Multiparametric MRI is superior to semantic models to effectively predict the molecular subtypes of breast cancer.
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Neoplasias da Mama , Aprendizado de Máquina , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Adulto , Idoso , Valor Preditivo dos TestesRESUMO
Multi-omics-integrated analysis, known as panomics, represents an advanced methodology that harnesses various high-throughput technologies encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Sheep, playing a pivotal role in agricultural sectors due to their substantial economic importance, have witnessed remarkable advancements in genetic breeding through the amalgamation of multiomics analyses, particularly with the evolution of high-throughput technologies. This integrative approach has established a robust theoretical foundation, enabling a deeper understanding of sheep genetics and fostering improvements in breeding strategies. The comprehensive insights obtained through this approach shed light on diverse facets of sheep development, including growth, reproduction, disease resistance, and the quality of livestock products. This review primarily focuses on the application of principal omics analysis technologies in sheep, emphasizing correlation studies between multiomics data and specific traits such as meat quality, wool characteristics, and reproductive features. Additionally, this paper anticipates forthcoming trends and potential developments in this field.
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The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.
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Técnicas Biossensoriais , Melanoma , Humanos , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Melanoma/diagnóstico , Peptídeos/química , Limite de DetecçãoRESUMO
Objective.Automatic radiology report generation is booming due to its huge application potential for the healthcare industry. However, existing computer vision and natural language processing approaches to tackle this problem are limited in two aspects. First, when extracting image features, most of them neglect multi-view reasoning in vision and model single-view structure of medical images, such as space-view or channel-view. However, clinicians rely on multi-view imaging information for comprehensive judgment in daily clinical diagnosis. Second, when generating reports, they overlook context reasoning with multi-modal information and focus on pure textual optimization utilizing retrieval-based methods. We aim to address these two issues by proposing a model that better simulates clinicians perspectives and generates more accurate reports.Approach.Given the above limitation in feature extraction, we propose a globally-intensive attention (GIA) module in the medical image encoder to simulate and integrate multi-view vision perception. GIA aims to learn three types of vision perception: depth view, space view, and pixel view. On the other hand, to address the above problem in report generation, we explore how to involve multi-modal signals to generate precisely matched reports, i.e. how to integrate previously predicted words with region-aware visual content in next word prediction. Specifically, we design a visual knowledge-guided decoder (VKGD), which can adaptively consider how much the model needs to rely on visual information and previously predicted text to assist next word prediction. Hence, our final intensive vision-guided network framework includes a GIA-guided visual encoder and the VKGD.Main results.Experiments on two commonly-used datasets IU X-RAY and MIMIC-CXR demonstrate the superior ability of our method compared with other state-of-the-art approaches.Significance.Our model explores the potential of simulating clinicians perspectives and automatically generates more accurate reports, which promotes the exploration of medical automation and intelligence.
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Radiologia , Radiografia , Percepção Visual , AutomaçãoRESUMO
Currently, studies of ancient faunal community networks have been based mostly on uniformitarian and functional morphological evidence. As an important source of data, taphonomic evidence offers the opportunity to provide a broader scope for understanding palaeoecology. However, palaeoecological research methods based on taphonomic evidence are relatively rare, especially for body fossils in lacustrine sediments. Such fossil communities are not only affected by complex transportation and selective destruction in the sedimentation process, they also are strongly affected by time averaging. Historically, it has been believed that it is difficult to study lacustrine entombed fauna by a small-scale quadrat survey. Herein, we developed a software, the TaphonomeAnalyst, to study the associational network of lacustrine entombed fauna, or taphocoenosis. TaphonomeAnalyst allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. The dataset for these investigations resulted from fieldwork of the latest Middle Jurassic Jiulongshan Formation near Daohugou Village, in Ningcheng County of Inner Mongolia, China, spotlighting the core assemblage of the Yanliao Fauna. Our data included 27,000 fossil specimens of animals from this deposit, the Yanliao Fauna, whose analyses reveal sedimentary environments, taphonomic conditions, and co-occurrence networks of this highly studied assemblage, providing empirically robust and statistically significant evidence for multiple Yanliao habitats.