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Naive pluripotent stem cells have the highest developmental potential but their in vivo existence in the blastocyst is transient. Here we report a blastocyst motif substrate for the in vitro reversion of mouse and human pluripotent stem cells to a naive state. The substrate features randomly varied microstructures, which we call motifs, mimicking the geometry of the blastocyst. Motifs representing mouse-blastocyst-scaled curvature ranging between 15 and 62 mm-1 were the most efficient in promoting reversion to naivety, as determined by time-resolved correlative analysis. In these substrates, apical constriction enhances E-cadherin/RAC1 signalling and activates the mechanosensitive nuclear transducer YAP, promoting the histone modification of pluripotency genes. This results in enhanced levels of pluripotency transcription factor NANOG, which persist even after cells are removed from the substrate. Pluripotent stem cells cultured in blastocyst motif substrates display a higher development potential in generating embryoid bodies and teratomas. These findings shed light on naivety-promoting substrate design and their large-scale implementation.
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BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.
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OBJECTIVES: Considering the escalating incidence of strabismus and its consequential jeopardy to binocular vision, there is an imperative demand for expeditious and precise screening methods. This study was to develop an artificial intelligence (AI) platform in the form of an applet that facilitates the screening and management of strabismus on any mobile device. METHODS: The Visual Transformer (VIT_16_224) was developed using primary gaze photos from two datasets covering different ages. The AI model was evaluated by 5-fold cross-validation set and tested on an independent test set. The diagnostic performance of the AI model was assessed by calculating the Accuracy, Precision, Specificity, Sensitivity, F1-Score and Area Under the Curve (AUC). RESULTS: A total of 6194 photos with corneal light-reflection (with 2938 Exotropia, 1415 Esotropia, 739 Vertical Deviation and 1562 Orthotropy) were included. In the internal validation set, the AI model achieved an Accuracy of 0.980, Precision of 0.941, Specificity of 0.979, Sensitivity of 0.958, F1-Score of 0.951 and AUC of 0.994. In the independent test set, the AI model achieved an Accuracy of 0.967, Precision of 0.980, Specificity of 0.970, Sensitivity of 0.960, F1-Score of 0.975 and AUC of 0.993. CONCLUSIONS: Our study presents an advanced AI model for strabismus screening which integrates electronic archives for comprehensive patient histories. Additionally, it includes a patient-physician interaction module for streamlined communication. This innovative platform offers a complete solution for strabismus care, from screening to long-term follow-up, advancing ophthalmology through AI technology for improved patient outcomes and eye care quality.
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Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.
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Because of its insensitivity to existing radiotherapy, namely chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to overcome. Increasing evidence has indicated abnormal Wnt/ß-catenin pathway activation in TNBC but not luminal or HER2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between activated and inactivated wnt/ß-catenin pathway of TNBC tissues, lnc-WAL (wnt/ß-catenin associated lncRNA; WAL) was selected as the top upregulated lncRNA in wnt/ß-catenin pathway activation compared with the inactivation group. RIP-seq was used to compare the ß-catenin and IgG groups, where lnc-WAL could interact with ß-catenin. Clinically, increased lnc-WAL in TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted EMT, the proliferation, migration and invasion of breast cancer stem cells (BCSCs), and TNBC cells. Mechanistically, lnc-WAL inhibited ß-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, ß-catenin accumulated in the nucleus and activated the target genes. Importantly, wnt/ß-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/ß-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL may be a potential therapeutic target against TNBC. Implications: The positive feedback between lnc-WAL and the Wnt/ß-catenin pathway promotes TNBC progression, and lnc-WAL could be a potential prognostic marker for TNBC patients.
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Mixing native broadleaved tree species is a widely used method for renovating Pinus massoniana plantations. Soil microbial necromass carbon and organic carbon fractions are important parameters for evaluating the impacts of tree species mixing and soil organic carbon (SOC) stability. However, their responses to the mixing and renovation of P. massoniana plantation has not been understood yet. Here, we selected a pure P. massoniana plantation (PP) and a mixed P. massoniana and Castanopsis hystrix plantation, with ages of 16 (MP16) and 38 years (MP38), respectively, as the research objects. We quantified soil physical and chemical properties, microbial necromass carbon content, and organic carbon components at different soil layers to reveal whether and how the introduction of C. hystrix into P. massoniana plantation affected soil microbial necromass carbon and organic carbon components. The results showed that the mixed P. massoniana and C. hystrix plantation significantly reduced fungal necromass carbon content and the ratio of fungal/bacterial necromass carbon in the 0-20 cm and 20-40 cm soil layers. There were no significant differences in microbial necromass carbon contents, bacterial necromass carbon contents, and their contributions to SOC among the different plantations. The contribution of fungal necromass carbon to SOC was higher than that of bacterial necromass carbon in all plantation types. The contribution of soil mineral-associated organic carbon (MAOC) to SOC was higher than that of occluded particulate organic carbon (oPOC) and light-free particulate organic carbon (fPOC) for all plantation types. Mixing the precious broadleaved tree species (i.e., C. hystrix) with coniferous species (P. massoniana) significantly increased MAOC content and the contribution of MAOC, oPOC, and fPOC to SOC in the 0-20 cm and 20-40 cm soil layers. The MAOC of MP38 was significantly higher than that of PP in all soil layers and the MAOC of MP38 stands were significantly higher than MP16 stands in the 20-40 cm, 40-60 cm, and 60-100 cm soil layers, indicating that hybridization enhanced SOC stability and that the SOC of MP38 stands were more stable than MP16 stands. SOC and total nitrogen contents were the main environmental factors driving the changes in soil microbial necromass carbon, while soil total nitrogen and organically complexed Fe-Al oxides were the primary factors affecting organic carbon fraction. Therefore, SOC stability can be enhanced by introducing native broadleaved species, such as C. hystrix, during the management of the P. massoniana plantation.
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Pinus , Árboles , Carbono/análisis , Suelo/química , Microbiología del Suelo , Nitrógeno/análisis , Bacterias , China , BosquesRESUMEN
While the correlation between parental autonomy granting and adolescents' problematic Internet use (PIU) has been confirmed, the processes underlying this connection have not been thoroughly investigated. Drawing on the ecological systems theory, this study sought to investigate the mediating mechanism of peer attachment and the moderating mechanism of school climate that link parental autonomy granting to PIU. A two-wave longitudinal design was employed with a time interval of six months. The participants were 852 adolescents who attended three middle schools located in Guangdong Province, China. Self-report questionnaires were used to obtain data on demographics, parental autonomy granting, peer attachment, school climate, and PIU. The findings indicated that peer attachment significantly mediated the link between parental autonomy granting and adolescent PIU. A positive school climate significantly moderated the influence of parental autonomy granting on peer attachment and the influence of peer attachment on PIU. Specifically, the association between parental autonomy granting and peer attachment and the association between peer attachment and PIU were more pronounced when the school climate was perceived to be positive. This research underscores the possible significance of peer attachment in the association between parental autonomy granting and PIU and offers valuable insights for mitigating the negative outcomes of PIU.
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Basal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis. POU4F1 is necessary for the tumor growth and malignant phenotypes of BLBC through regulating G1/S transition by direct binding at the promoter of CDK2 and CCND1. More importantly, POU4F1 maintains BLBC identity by repressing ERα expression through CDK2-mediated EZH2 phosphorylation and subsequent H3K27me3 modification in ESR1 promoter. Knocking out POU4F1 in BLBC cells reactivates functional ERα expression, rendering BLBC sensitive to tamoxifen treatment. In-depth epigenetic analysis reveals that the subtype-specific re-configuration and activation of the bivalent chromatin in the POU4F1 promoter contributes to its unique expression in BLBC, which is maintained by DNA demethylase TET1. Together, these results reveal a subtype-specific epigenetically activated TF with critical role in promoting and maintaining BLBC, suggesting that POU4F1 is a potential therapeutic target for BLBC.
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Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Humanos , Femenino , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Ratones , Animales , Factor de Transcripción Brn-3A/genética , Factor de Transcripción Brn-3A/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Modelos Animales de Enfermedad , Regiones Promotoras Genéticas/genéticaRESUMEN
Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.
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Enfermedades Mitocondriales , Enfermedades de los Roedores , Ratones , Humanos , Femenino , Animales , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/prevención & control , Enfermedades Mitocondriales/veterinaria , Haplorrinos/genética , Mitocondrias/genética , ADN Mitocondrial/genética , Primates/genéticaRESUMEN
The introduction of dual carbon targets will significantly impact power system development. Despite this, there is currently limited research on achieving system evolution and transition while ensuring safety, low-carbon output, and efficiency, as well as quantitatively analyzing the resulting changes dual carbon targets will have on the power system. Co-evolution of the power system offers a solution to balance the impact of dual carbon goals and enhance interaction among system entities, thereby facilitating the achievement of these goals. Our study focuses on constructing an evolutionary topological network by analyzing the dynamic evolution rule of power systems. We investigate the co-evolution pattern of power systems by analyzing the relationship between the role of power system agents and their dynamic structures. Furthermore, we analyze the future structural changes of power systems, which can provide theoretical support for achieving dual carbon goals in the power system. Our findings highlight key measures to promote synergistic evolution, including increasing energy storage capabilities, stabilizing renewable energy supply, breaking inter-provincial barriers in electricity transmission, and developing a multi-level intelligent power system. Through link analysis, we discover that future power systems will maintain a mild coordination among agents rather than implementing large-scale realignment and reconfiguration. We posit that overcoming obstacles can be achieved by fostering cohesion between the network and agents through technological innovation and widespread market diffusion to drive co-evolution.
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Glioblastoma (GBM) is a common primary central nervous system tumor. Although the multimodal integrated treatment for GBM has made great progress in recent years, the overall survival time of GBM is still short. Thus, novel treatments for GBM are worth further investigation and exploration. This study aimed to investigate the effects of etomidate on GBM tumor growth and the underlying mechanism. A xenograft tumor model was established and treated with etomidate to assess tumor growth. Immunohistochemistry (IHC) assay evaluated the positive rate of Ki67 cells in tumor tissues. Cell counting kit (CCK)-8 and EdU assays accessed the cell viability and proliferation. Immunofluorescence (IF) staining detected the distribution of macrophage markers in tumor tissues. The percentages of M1- and M2-like macrophages in tumor-associated macrophages (TAMs) and co-culture system (macrophages and GBM cells) were detected using flow cytometry. Macrophage polarization-related genes were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Etomidate treatment inhibited the tumor growth, and increased the CD86+ cells but decreased the CD206+ cells in TAMs. The gene expression of M1 markers was increased in TAMs of etomidate-treated mice, whereas that of M2 markers was decreased. Moreover, etomidate treatment increased the number of CD86+ M1-like macrophages co-cultured with tumor cells but decreased that of CD206+ M2-like macrophages, with the upregulation of M1 markers and downregulation of M2 markers. Etomidate inhibited GBM tumor growth by promoting M1 macrophage polarization, suggesting a new insight into the clinical treatment of GBM.
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Neoplasias Encefálicas , Etomidato , Glioblastoma , Macrófagos , Etomidato/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Animales , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Ratones DesnudosRESUMEN
Despite abundant theoretical investigations on the dynamic behavior of functionally graded (FG) structures, the study on frequency analysis of FG bio-composite structures is limited. FG bio-composite materials due to their biocompatibility potentials and good material properties can be applied in biomedical applications, especially dental implants. In this investigation, a natural frequency response of the FG bio-composite plate is analyzed within the framework of the newly developed refined higher-order shear deformation plate theory. Additionally, the imperfection impact on frequency behavior is evaluated while three imperfection distribution patterns are taken into account. The constitutive materials of FG bio-composite plate are Hydroxyapatite and Titanium. The effective material properties of the structure are determined with the help of the upper Hashin-Shtrikman bounds homogenization model. In continuation, to solve the derived governing equations of imperfect FG bio-composite plate, Galerkin's analytical method is employed. Also, the precision of the used theory is validated, the obtained outcomes are compared and an acceptable matching is found. Later, the sensitivity of different considerable variables is comprehensively assessed and discussed.
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Placas Óseas , Durapatita , Durapatita/químicaRESUMEN
Emerging data have shown that previously defined noncoding genomes might encode peptides that bind human leukocyte antigen (HLA) as cryptic antigens to stimulate adaptive immunity1,2. However, the significance and mechanisms of action of cryptic antigens in anti-tumour immunity remain unclear. Here mass spectrometry of the HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human breast cancer samples identified HLA-I-binding cryptic antigenic peptides that were noncanonically translated by a tumour-specific circular RNA (circRNA): circFAM53B. The cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and induced anti-tumour immunity. Clinically, the expression of circFAM53B and its encoded peptides was associated with substantial infiltration of antigen-specific CD8+ T cells and better survival in patients with breast cancer and patients with melanoma. Mechanistically, circFAM53B-encoded peptides had strong binding affinity to both HLA-I and HLA-II molecules. In vivo, administration of vaccines consisting of tumour-specific circRNA or its encoded peptides in mice bearing breast cancer tumours or melanoma induced enhanced infiltration of tumour-antigen-specific cytotoxic T cells, which led to effective tumour control. Overall, our findings reveal that noncanonical translation of circRNAs can drive efficient anti-tumour immunity, which suggests that vaccination exploiting tumour-specific circRNAs may serve as an immunotherapeutic strategy against malignant tumours.
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Neoplasias de la Mama , Melanoma , Péptidos , Biosíntesis de Proteínas , ARN Circular , Animales , Femenino , Humanos , Ratones , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Espectrometría de Masas , Melanoma/genética , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/patología , Péptidos/genética , Péptidos/inmunología , Perfilado de Ribosomas , ARN Circular/genética , ARN Circular/metabolismo , Análisis de SupervivenciaRESUMEN
Platinum metal (PtM, M=Ni, Fe, Co) alloys catalysts show high oxygen reduction reaction (ORR) activity due to their well-known strain and ligand effects. However, these PtM alloys usually suffer from a deficient ORR durability in acidic environment as the alloyed metal is prone to be dissolved due to its high electronegativity. Herein, we report a new class of PtMn alloy nanodendrite catalyst with low-electronegativity Mn-contraction for boosting the oxygen reduction durability of fuel cells. The moderate strain in PtMn, induced by Mn contraction, yields optimal oxygen reduction activity at 0.53â A mg-1 at 0.9â V versus reversible hydrogen electrode (RHE). Most importantly, we show that relative to well-known high-electronegativity Ni-based Pt alloy counterpart, the PtMn nanodendrite catalyst experiences less transition metals' dissolution in acidic solution and achieves an outstanding mass activity retention of 96 % after 10,000 degradation cycles. Density functional theory calculation reveals that PtMn alloys are thermodynamically more stable than PtNi alloys in terms of formation enthalpy and cohesive energy. The PtMn nanodendrite-based membrane electrode assembly delivers an outstanding peak power density of 1.36â W cm-2 at a low Pt loading and high-performance retention over 50â h operations at 0.6â V in H2 -O2 hydrogen fuel cells.
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Phenazine compounds are widely used in agricultural control and the medicine industry due to their high inhibitory activity against pathogens and antitumor activity. The green and sustainable method of synthesizing phenazine compounds through microbial fermentation often requires a complex culture medium containing tryptone and yeast extract, and its cost is relatively high, which greatly limits the large-scale industrial production of phenazine compounds by fermentation. The aim of this study was to develop a cost-effective minimal medium for the efficient synthesis of phenazine compounds by Pseudomonas chlororaphis. Through testing the minimum medium commonly used by Pseudomonas, an ME medium for P. chlororaphis with a high production of phenazine compounds was obtained. Then, the components of the ME medium and the other medium were compared and replaced to verify the beneficial promoting effect of Fe2+ and NH4+ on phenazine compounds. A cost-effective general defined medium (GDM) using glycerol as the sole carbon source was obtained by optimizing the composition of the ME medium. Using the GDM, the production of phenazine compounds by P. chlororaphis reached 1073.5 mg/L, which was 1.3 times that achieved using a complex medium, while the cost of the GDM was only 10% that of a complex medium (e.g., the KB medium). Finally, by engineering the glycerol metabolic pathway, the titer of phenazine-1-carboxylic acid reached the highest level achieved using a minimum medium so far. This work demonstrates how we systematically analyzed and optimized the composition of the medium and integrated a metabolic engineering method to obtain the most cost-effective fermentation strategy.
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BACKGROUND: As a rapid-progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs. METHODS: The expression and prognostic significance of CD146 in PTs was detected through single-cell RNA-sequencing (scRNA-seq), immunostaining, real-time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti-CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient-derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co-immunoprecipitation, and pull-down assay was employed to identify the modulating pathway and additional molecular mechanism. RESULTS: In this study, the scRNA-seq analysis of PTs disclosed a CD146-positive characteristic in the α-SMA+ fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective "shield" to prevent the degradation of Discoidin, CUB, and LCCL domain-containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98. CONCLUSIONS: These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146-DCBLD2/PI3K/AKT axis in the malignant progression of PTs.
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Neoplasias de la Mama , Tumor Filoide , Animales , Femenino , Humanos , Neoplasias de la Mama/patología , Antígeno CD146/genética , Modelos Animales de Enfermedad , Proteínas de la Membrana , Fosfatidilinositol 3-Quinasas , Tumor Filoide/genética , Tumor Filoide/metabolismo , Tumor Filoide/patología , Proteómica , Proteínas Proto-Oncogénicas c-aktRESUMEN
BACKGROUND: Artificial intelligence-based aided diagnostic systems for pulmonary nodules can be divided into subtasks such as nodule detection, segmentation, and benign and malignant differentiation. Most current studies are limited to single-target tasks. However, aided diagnosis aims to distinguish benign from malignant pulmonary nodules, which requires the fusion of multiple-scale features and comprehensive discrimination based on the results of multiple learning tasks. OBJECTIVE: This study focuses on the aspects of model design, network structure, and constraints and proposes a novel model that integrates the learning tasks of pulmonary nodule detection, segmentation, and classification under weakly supervised conditions. METHODS: The main innovations include the following three aspects: (1) a two-dimensional sequence detection model based on a ConvLSTM (Convolutional Long Short-Term Memory) network and U-shaped structure network is proposed to obtain the context space features of image slices fully; (2) a differential diagnosis of benign and malignant pulmonary nodules based on multitask learning is proposed, which uses the annotated data of different types of tasks to mine the potential common features among tasks; and (3) an optimization strategy incorporating prior knowledge of computed tomography images and dynamic weight adjustment of multiple tasks is proposed to ensure that each task can efficiently complete training and learning. RESULTS: Experiments on the LIDC-IDRI and LUNA16 datasets showed that our proposed method achieved a final competition performance metric score of 87.80% for nodule detection and a Dice similarity coefficient score of 83.95% for pulmonary nodule segmentation. CONCLUSION: The cross-validation results of the LIDC-IDRI and LUNA16 datasets show that our model achieved 87.80% of the final competition performance metric score for nodule detection and 83.95% of the DSC score for pulmonary nodule segmentation, representing the optimal result for that dataset.
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PURPOSE: Convolutional Neural Networks (ConvNets) have quickly become popular machine learning techniques in recent years, particularly in the classification and segmentation of medical images. One of the most prevalent types of brain cancers is glioma, and early, accurate diagnosis is essential for both treatment and survival. In this study, MRI scans were examined utilizing deep learning techniques to examine glioma diagnosis studies. METHODS: In this systematic review, keywords were used to obtain English-language studies from the Arxiv, IEEE, Springer, ScienceDirect, and PubMed databases for the years 2010-2022. The material needed for review was then collected from the articles once they had been chosen based on the entry and exit criteria and in accordance with the research's goal. RESULTS: Finally, 77 different academic articles were chosen. According to a study of published articles, glioma brain tumors were discovered, categorized, and segmented utilizing a coordinated approach that included image collecting, pre-processing, model design and execution, and model output evaluation. The majority of investigations have used publicly accessible photo databases and already-trained algorithms. The bulk of studies have employed Dice's classification accuracy and similarity coefficient metrics to assess model performance. CONCLUSION: The results of this study indicate that glioma segmentation has received more attention from researchers than glioma detection and classification. It is advised that more research be done in the areas of glioma detection and, particularly, grading in order to be included in systems that support medical diagnosis.
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Neoplasias Encefálicas , Aprendizaje Profundo , Glioma , Humanos , Glioma/diagnóstico por imagen , Glioma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Redes Neurales de la ComputaciónRESUMEN
Purpose: To comprehensively reassess the efficacy and safety of different concentrations of atropine for retarding myopia progression and seek the most appropriate therapeutic concentration for clinical practice. Methods: We searched PubMed, Cochrane Library, Embase, Chinese Science and Technology Periodicals (VIP) and China National Knowledege Infrastructure (CNKI) from their inception to 23 March 2023, to obtain eligible randomized controlled trials (RCTs) and cohort studies that had atropine in at least one treatment arm and placebo/no intervention in another arm. We evaluated the risk of bias of the RCTs according to the recommendations of the Cochrane Collaboration for RCTs and quality of cohort studies by the NewcastleâOttawa Scale. Weighted mean difference (WMD), 95% confidence interval were calculated for meta-analysis. All data analyses were performed using Review Manager 5.3, STATA 12.0 and SPSS 26.0 software. Results: A total of 44 studies were included in the meta-analysis. Weighted mean difference (WMD) were 0.73 diopters (D), 0.65 D, 0.35 D per year in refraction progression (χ 2 = 14.63, I 2 = 86.3%; p < 0.001) and -0.26 mm, -0.37 mm, -0.11 mm per year in axial length progression (χ 2 = 5.80, I 2 = 65.5%; p = 0.06) for high (0.5%-1%), moderate (0.1%-0.25%), and low (0.005%-0.05%) dose atropine groups, respectively. Logarithmic doseâresponse correlations were found between atropine and their effect on change of refraction, axial length, accommodation and photopic pupil diameter. Through these curves, we found that atropine with concentrations ≤0.05% atropine resulted in a residual value of accommodation of more than 5 D and an increase in pupil diameter no more than 3 mm. Higher doses of atropine resulted in a higher incidence of adverse effects, of which the incidence of photophobia was dose-dependent (r = 0.477, p = 0.029). Conclusion: Both the efficacy and risk of adverse events for atropine treatment of myopia were mostly dose dependent. Comprehensively considered the myopia control effect and safety of each dose, 0.05% may be the best concentration of atropine to control myopia progression at present, at which myopia is better controlled and the side effects are tolerable. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42022377705.
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Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.