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1.
Int J Biol Macromol ; 269(Pt 2): 131969, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697419

RESUMO

In this study, different concentrations of sodium alginate were compounded with pectin and phycocyanin to co-prepare composite hydrogel spheres (HP-PC-SA 0.2 %, 0.6 %, 1.0 %, 1.4 %) to evaluate the potential of the composite hydrogel spheres for the application as phycocyanin delivery carriers. The hydrogel spheres' physicochemical properties and bioaccessibility were assessed through scanning electron microscopy, textural analysis, drug-carrying properties evaluation, and in vitro and in vivo controlled release analysis in the gastrointestinal environment. Results indicated that higher sodium alginate concentrations led to smaller pore sizes and denser networks on the surface of hydrogel spheres. The textural properties of hydrogel spheres improved, and their water-holding capacity increased from 93.01 % to 97.97 %. The HP-PC-SA (1.0 %) formulation achieved the highest encapsulation rate and drug loading capacity, at 96.87 % and 6.22 %, respectively. Within the gastrointestinal tract, the composite hydrogel's structure significantly enhanced and protected the phycocyanin's digestibility, achieving a bioaccessibility of up to 88.03 %. In conclusion, our findings offer new insights into improving functionality and the effective use of phycocyanin via pectin-based hydrogel spheres.

2.
Int J Gen Med ; 17: 1729-1738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711824

RESUMO

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent ß-thalassemia (TDT). Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed. Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed. Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.

3.
ACS Nano ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717959

RESUMO

Since their introduction in 2004, high entropy alloys (HEAs) have attracted significant attention due to their exceptional mechanical and functional properties. Advances in our understanding of atomic-scale ordering and phase formation in HEAs have facilitated the development of fabrication techniques for synthesizing nanostructured HEAs. These materials hold immense potential for applications in various fields including automobile industries, aerospace engineering, microelectronics, and clean energy, where they serve as either structural or functional materials. In this comprehensive Review, we conduct an in-depth analysis of the mechanical and functional properties of nanostructured HEAs, with a particular emphasis on the roles of different nanostructures in modulating these properties. To begin, we explore the intrinsic and extrinsic factors that influence the formation and stability of nanostructures in HEAs. Subsequently, we delve into an examination of the mechanical and electrocatalytic properties exhibited by bulk or three-dimensional (3D) nanostructured HEAs, as well as nanosized HEAs in the form of zero-dimensional (0D) nanoparticles, one-dimensional (1D) nanowires, or two-dimensional (2D) nanosheets. Finally, we present an outlook on the current research landscape, highlighting the challenges and opportunities associated with nanostructure design and the understanding of structure-property relationships in nanostructured HEAs.

4.
Heliyon ; 10(9): e30006, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694075

RESUMO

Background: Wall shear stress (WSS) has been proved to be related to the formation, development and rupture of intracranial aneurysms. Aneurysm wall enhancement (AWE) on magnetic resonance imaging (MRI) can be caused by inflammation and have confirmed its relationship with low WSS. High WSS can also result in inflammation but the research of its correlation with AWE is lack because of the focus on large aneurysms limited by 3T MRI in most previous studies.This study aimed to assess the potential association between high or low WSS and AWE in different aneuryms. Especially the relationship between high WSS and AWE in small aneurysm. Methods: Forty-three unruptured intracranial aneurysms in 42 patients were prospectively included for analysis. 7.0 T MRI was used for imaging. Aneurysm size was measured on three-dimensional time-of-flight (TOF) images. Aneurysm-to-pituitary stalk contrast ratio (CRstalk) was calculated on post-contrast black-blood T1-weighted fast spin echo sequence images. Hemodynamics were assessed by four-dimensional flow MRI. Results: The small aneurysms group had more positive WSS-CRstalk correlation coefficient distribution (dome: 78.6 %, p = 0.009; body: 50.0 %, p = 0.025), and large group had more negative coefficient distribution (dome: 44.8 %, p = 0.001; body: 69.0 %, p = 0.002). Aneurysm size was positively correlated with the significant OSI-CRstalk correlation coefficient at the dome (p = 0.012) and body (p = 0.010) but negatively correlated with the significant WSS-CRstalk correlation coefficient at the dome (p < 0.001) and body (p = 0.017). Conclusion: AWE can be mediated by both high and low WSS, and translate from high WSS- to low WSS-mediated pathways as size increase. Additionally, AWE may serve as an indicator of the stage of aneurysm development via different correlations with hemodynamic factors.

5.
Front Oncol ; 14: 1376498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651151

RESUMO

Objectives: This study aimed to examine Ki-67's correlation with clinicopathological characteristics of head and neck squamous cell carcinoma (HNSCC), evaluate its prognostic significance, and develop a Ki-67 integrated prognostic model. Methods: The retrospective study included 764 HNSCC patients hospitalized from 2012 to 2022. Data were sourced from medical records and immunohistochemical analysis of surgical specimens. Results: Ki-67 expression was significantly associated with sex, pathological grade, clinical stage, and metastasis, but not with age or recurrence. Higher Ki-67 levels were linked to poorer prognosis, as indicated by Kaplan-Meier survival analysis. Utilizing a Cox proportional hazards model, four prognostic factors were identified: age, recurrence, metastasis, and Ki-67 expression. These factors were used to construct a prognostic model and a nomogram. The model's predictive accuracy was confirmed by a high concordance index and a reliable calibration curve. Conclusion: Ki-67 expression in HNSCC patients correlates with several clinicopathological features and serves as a negative prognostic marker. A prognostic model incorporating Ki-67 was successfully developed, offering a new tool for patient prognosis assessment in HNSCC.

6.
Front Bioeng Biotechnol ; 12: 1386534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655386

RESUMO

Extensive research on zeolitic imidazolate framework (ZIF-8) and its derivatives has highlighted their unique properties in nanomedicine. ZIF-8 exhibits advantages such as pH-responsive dissolution, easy surface functionalization, and efficient drug loading, making it an ideal nanosystem for intelligent drug delivery and phototherapy. These characteristics have sparked significant interest in its potential applications in tissue regeneration, particularly in bone, skin, and nerve regeneration. This review provides a comprehensive assessment of ZIF-8's feasibility in tissue engineering, encompassing material synthesis, performance testing, and the development of multifunctional nanosystems. Furthermore, the latest advancements in the field, as well as potential limitations and future prospects, are discussed. Overall, this review emphasizes the latest developments in ZIF-8 in tissue engineering and highlights the potential of its multifunctional nanoplatforms for effective complex tissue repair.

7.
J Cardiothorac Surg ; 19(1): 234, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627841

RESUMO

OBJECTIVES: The right lower sleeve lobectomy is a rarely performed major lung resection.This study aims to evaluate the safety and effectiveness of this procedure by comparing to right lower bilobectomy in non-small cell lung cancer patients. METHODS: We retrospectively reviewed a prospective database of non-small cell lung cancer patients who underwent right lower sleeve lobectomy (group S) or right lower bilobectomy (group B) from January 2014 to January 2020 in Shanghai Pulmonary Hospital. Propensity score matching method was applied to balance confounders between the two groups, resulting in 41 matched pairs.The analysis was performed to compare perioperative outcomes, long-term survival, and postoperative pulmonary volume between the two groups. RESULTS: No significant differences in the characteristics were observed between the two matched groups.Major postoperative complications developed in 31.7% of the patients in group B and 12.1% of the patients in group S (P = 0.032).Intervention rate for surgical residual cavity in group B is significantly higher than those patients in group S(21.9%vs7.3%,p = 0.037).The postoperative right lateral and overall lung volume in group S were both significantly larger than that in group B (P = 0.026,P = 0.001,respectively). CONCLUSIONS: Compared to bi-lobectomy, a middle lobe sparing sleeve resection obtains a less prevalence of major complications, smaller postoperative residual air space and similar long-term survival for selected central right lower NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Estudos de Coortes , China , Pulmão , Pneumonectomia/métodos
8.
Cell Stem Cell ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38663406

RESUMO

Due to the limitations of autologous chimeric antigen receptor (CAR)-T cells, alternative sources of cellular immunotherapy, including CAR macrophages, are emerging for solid tumors. Human induced pluripotent stem cells (iPSCs) offer an unlimited source for immune cell generation. Here, we develop human iPSC-derived CAR macrophages targeting prostate stem cell antigen (PSCA) (CAR-iMacs), which express membrane-bound interleukin (IL)-15 and truncated epidermal growth factor receptor (EGFR) for immune cell activation and a suicide switch, respectively. These allogeneic CAR-iMacs exhibit strong antitumor activity against human pancreatic solid tumors in vitro and in vivo, leading to reduced tumor burden and improved survival in a pancreatic cancer mouse model. CAR-iMacs appear safe and do not exhibit signs of cytokine release syndrome or other in vivo toxicities. We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer.

9.
Clin Transl Med ; 14(3): e1611, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38481388

RESUMO

BACKGROUND: Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs. METHODS: We applied single-cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data-independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining. RESULTS: Tumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer-associated fibroblast-like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter-patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading. CONCLUSIONS: Our study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.


Assuntos
Neoplasias da Mama , Tumor Filoide , Humanos , Feminino , Tumor Filoide/diagnóstico , Tumor Filoide/genética , Tumor Filoide/metabolismo , Transcriptoma/genética , Células Estromais/metabolismo , Diferenciação Celular/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo
10.
Transpl Immunol ; 84: 102042, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38527707

RESUMO

BACKGROUND: Exogenous neural cell transplantation may be therapeutic for stroke, cerebral ischemic injury. Among other mechanisms, increasing findings indicated circular RNAs (circRNAs) regulate the pathogenesis progression of cerebral ischemia. Mmu_circ_0015034 (circEfnb2) was upregulated in focal cortical infarction established by middle cerebral artery occlusion (MCAO) in mice. Our study was designed to probe the molecular mechanism of circEfnb2 in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage in cerebral ischemia. METHODS: We established an in vitro OGD/R cell model. CircEfnb2 and microRNA-202-5p (miR-202-5p) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were assessed using specific kits. Tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Flow cytometry analysis evaluated cell apoptosis. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved caspase 3, and Tumor necrosis factor receptor-associated factor 3 (TRAF3) were determined using Western blot assay. RESULTS: Overall, circEfnb2 was highly expressed whereas miR-202-5p was decreased in OGD/R-treated mouse hippocampal neuronal HT22 cells compared to normal controls (both p > 0.05). From an in vitro functional perspective, circEfnb2 knockdown attenuated an OGD/R-triggered neuronal injury compared to controls (p > 0.05). Mechanically, circEfnb2 acted as a sponge of miR-202-5p; downregulation of miR-202-5p annulled the inhibitory roles of circEfnb2 silencing in an OGD/R-caused neuronal injury model. Our analysis showed that miR-202-5p directly targeted TRAF3 as enhanced TRAF3 abolished the effects of miR-202-5p in the OGD/R-induced neuronal injury. In vivo, lentivirus with a short hairpin (sh)-circEfnb2 inhibited cerebral injury, when injected into cerebral cortex in MCAO mice (p > 0.05). CONCLUSION: Our results suggest that circEfnb2 deficiency may decrease OGD/R-induced HT22 cell damage by modulating the miR-202-5p/TRAF3 axis. This explanation may provide a new direction for cerebral infarction potential therapeutic targets.

11.
Neuroradiology ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38503986

RESUMO

PURPOSE: This study aimed to develop a multisequence MRI-based volumetric histogram metrics model for predicting pathological complete response (pCR) in advanced head and neck squamous cell carcinoma (HNSCC) patients undergoing neoadjuvant chemo-immunotherapy (NCIT) and compare its predictive performance with AJCC staging and RECIST 1.1 criteria. METHODS: Twenty-four patients with locally advanced HNSCC from a prospective phase II trial were enrolled for analysis. All patients underwent pre- and post-NCIT MRI examinations from which whole-tumor histogram features were extracted, including T1WI, T2WI, enhanced T1WI (T1Gd), diffusion-weighted imaging (DWI) sequences, and their corresponding apparent diffusion coefficient (ADC) maps. The pathological results divided the patients into pathological complete response (pCR) and non-pCR (N-pCR) groups. Delta features were calculated as the percentage change in histogram features from pre- to post-treatment. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Eleven of 24 patients achieved pCR. Pre_T2_original_firstorder_Minimum, Post_ADC_original_firstorder_MeanAbsoluteDeviation, and Delta_T1Gd_original_firstorder_Skewness were associated with achieving pCR after NCIT. The Combined_Model demonstrated the best predictive performance (AUC 0.95), outperforming AJCC staging (AUC 0.52) and RECIST 1.1 (AUC 0.72). The Pre_Model (AUC 0.83) or Post-Model (AUC 0.83) had a better predictive ability than AJCC staging. CONCLUSION: Multisequence MRI-based volumetric histogram analysis can non-invasively predict the pCR status of HNSCC patients undergoing NCIT. The use of histogram features extracted from pre- and post-treatment MRI exhibits promising predictive performance and offers a novel quantitative assessment method for evaluating pCR in HNSCC patients receiving NCIT.

12.
Nat Commun ; 15(1): 2230, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472198

RESUMO

Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominate SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency and required for in vivo growth of human CRC models. These studies highlight the utility of biologically designed endogenous reporter platforms to uncover regulators with therapeutic potential.


Assuntos
Neoplasias Colorretais , RNA Guia de Sistemas CRISPR-Cas , Humanos , Diferenciação Celular/genética , Células-Tronco/metabolismo , Neoplasias Colorretais/genética
13.
Vet Microbiol ; 292: 110038, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458047

RESUMO

In 2020, an H5N1 avian influenza virus of clade 2.3.4.4b was detected in Europe for the first time and was spread throughout the world by wild migratory birds, resulting in the culling of an unprecedented number of wild birds and poultry due to the epidemic. In February 2023, we isolated and identified a strain of H5N1 high pathogenicity avian influenza virus from a swab sample from a grey crane in Ningxia, China. Phylogenetic analysis of the Hemagglutinin (HA) gene showed that the virus belonged to clade 2.3.4.4b, and several gene segments were closely related to H5N1 viruses infecting humans in China. Analysis of key amino acid sites revealed that the virus contained multiple amino acid substitutions that facilitate enhanced viral replication and mammalian pathogenicity. The results of animal challenge experiments showed that the virus is highly pathogenic to chickens, moderately pathogenic to BALB/c mice, and highly infectious but not lethal to mallards. Moreover, the virus exhibited minor antigenic drift compared with the H5-Re14 vaccine strain. To this end, we need to pay more attention to the monitoring of wild birds to prevent further spread of viruses to poultry and mammals, including humans.


Assuntos
Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Doenças dos Roedores , Humanos , Camundongos , Animais , Aves Domésticas , Galinhas , Filogenia , Virulência , Patos , Animais Selvagens , Mamíferos
14.
Chin Med J (Engl) ; 137(5): 533-546, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38321811

RESUMO

ABSTRACT: Lung cancer remains the most common cause of cancer death. Given the continued research into new drugs and combination therapies, outcomes in lung cancer have been improved, and clinical benefits have been expanded to a broader patient population. However, the overall cure and survival rates for lung cancer patients remain low, especially in metastatic cases. Among the available lung cancer treatment options, such as surgery, radiation therapy, chemotherapy, targeted therapies, and alternative therapies, immunotherapy has shown to be the most promising. The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients. Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration (FDA)-approved drugs targeting the programmed cell death ligand-1 protein (e.g., durvalumab, atezolizumab), the programmed cell death-1 receptor (e.g., nivolumab, pembrolizumab), and cytotoxic T-lymphocyte-associated antigen 4 (e.g., tremelimumab, ipilimumab). Cytokines, cancer vaccines, adoptive T cell therapies, and Natural killer cell mono- and combinational therapies are rapidly being studied, yet to date, there are currently none that are FDA-approved for the treatment of lung cancer. In this review, we discuss the current lung cancer therapies with an emphasis on immunotherapy, including the challenges for future research and clinical applications.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Qualidade de Vida , Nivolumabe , Imunoterapia , Terapia Combinada , Antígeno B7-H1/metabolismo
15.
Lung ; 202(1): 53-61, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228883

RESUMO

BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic respiratory disease characterized by bronchial dilation. However, the significance of elevated eosinophil counts in acute exacerbations of bronchiectasis remains unclear. METHODS: This retrospective case-control study included 169 hospitalized patients with acute exacerbations of non-cystic fibrosis bronchiectasis. Based on blood eosinophil levels, patients were categorized into eosinophilic and non-eosinophilic bronchiectasis groups. Various clinical variables, including lung function, comorbidities and clinical features were collected for analysis. The study aimed to examine the differences between these groups and their clinical phenotypes. RESULTS: Eosinophilic bronchiectasis (EB) was present in approximately 22% of all hospitalized patients with bronchiectasis, and it was more prevalent among male smokers (P < 0.01). EB exhibited greater severity of bronchiectasis, including worse airway obstruction, higher scores in the E-FACED (FACED combined with exacerbations) and bronchiectasis severity index (BSI), a high glucocorticoids medication possession ratio, and increased hospitalization cost (P < 0.05 or P < 0.01). Furthermore, we observed a significant positive correlation between blood eosinophil count and both sputum eosinophils (r = 0.49, P < 0.01) and serum total immunoglobulin E levels (r = 0.21, P < 0.05). Additional analysis revealed that patients with EB had a higher frequency of shortness of breath (P < 0.05), were more likely to have comorbid sinusitis (P < 0.01), and exhibited a greater number of lung segments affected by bronchiectasis (P < 0.01). CONCLUSIONS: These findings suggest that EB presents a distinct pattern of bronchiectasis features, confirming the notion that it is a specific phenotype.


Assuntos
Bronquiectasia , Eosinófilos , Humanos , Masculino , Estudos Retrospectivos , Estudos de Casos e Controles , Fenótipo , Fibrose
16.
bioRxiv ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38293113

RESUMO

Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination. Using a focused-library CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs, we identified factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominated SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency in CRC and required for in vivo growth of human CRC models. These studies highlight the utility of a biologically designed endogenous reporter system to uncover novel therapeutic targets for drug development.

17.
Front Cardiovasc Med ; 11: 1330685, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283829

RESUMO

Objective: Early risk assessment of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is crucial to ensure timely treatment. We hypothesize that applying artificial intelligence (AI) to chest x-rays (CXRs) could identify the future risk of PAH in patients with ventricular septal defect (VSD). Methods: A total of 831 VSD patients (161 PAH-VSD, 670 nonPAH-VSD) was retrospectively included. A residual neural networks (ResNet) was trained for classify VSD patients with different outcomes based on chest radiographs. The endpoint of this study was the occurrence of PAH in VSD children before or after surgery. Results: In the validation set, the AI algorithm achieved an area under the curve (AUC) of 0.82. In an independent test set, the AI algorithm significantly outperformed human observers in terms of AUC (0.81 vs. 0.65). Class Activation Mapping (CAM) images demonstrated the model's attention focused on the pulmonary artery segment. Conclusion: The preliminary findings of this study suggest that the application of artificial intelligence to chest x-rays in VSD patients can effectively identify the risk of PAH.

18.
Mikrochim Acta ; 191(2): 101, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231363

RESUMO

Hyaluronidase (HAase) is an important endoglycosidase involved in numerous physiological and pathological processes, such as apoptosis, senescence, and cancer progression. Simple, convenient, and sensitive detection of HAase is important for clinical diagnosis. Herein, an easy-to-operate multicolor visual sensing strategy was developed for HAase determination. The proposed sensor was composed of an enzyme-responsive hydrogel and a nanochromogenic system (gold nanobipyramids (AuNBPs)). The enzyme-responsive hydrogel, formed by polyethyleneimine-hyaluronic acid (PEI-HA), was specifically hydrolyzed with HAase, leading to the release of platinum nanoparticles (PtNPs). Subsequently, PtNPs catalyzed the mixed system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 to produce TMB2+ under acidic conditions. Then, TMB2+ effectively etched the AuNBPs and resulted in morphological changes in the AuNBPs, accompanied by a blueshift in the localized surface plasmon resonance peak and vibrant colors. Therefore, HAase can be semiquantitatively determined by directly observing the color change of AuNBPs with the naked eye. On the basis of this, the method has a linear detection range of HAase concentrations between 0.6 and 40 U/mL, with a detection limit of 0.3 U/mL. In addition, our designed multicolor biosensor successfully detected the concentration of HAase in human serum samples. The results showed no obvious difference between this method and enzyme-linked immunosorbent assay, indicating the good accuracy and usability of the suggested method.


Assuntos
Benzidinas , Hialuronoglucosaminidase , Nanopartículas Metálicas , Humanos , Hidrogéis , Peróxido de Hidrogênio , Platina
19.
Plants (Basel) ; 13(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38256733

RESUMO

The morphological characteristics of the rice panicle play a pivotal role in influencing yield. In our research, we employed F2 and F2:3 populations derived from the high-yielding hybrid rice variety Chaoyou 1000. We screened 123 pairs of molecular markers, which were available, to construct the genetic linkage map. Subsequently, we assessed the panicle morphology traits of F2 populations in Lingshui County, Hainan Province, in 2017, and F2:3 populations in Hangzhou City, Zhejiang Province, in 2018. These two locations represent two types of ecology. Hangzhou's climate is characterized by high temperatures and humidity, while Lingshui's climate is characterized by a tropical monsoon climate. In total, 33 QTLs were identified, with eight of these being newly discovered, and two of them were consistently detected in two distinct environments. We identified fourteen QTL-by-environment interactions (QEs), which collectively explained 4.93% to 59.95% of the phenotypic variation. While most of the detected QTLs are consistent with the results of previous tests, the novel-detected QTLs will lay the foundation for rice yield increase and molecular breeding.

20.
Radiol Med ; 129(1): 48-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38082195

RESUMO

OBJECT: The purpose of this study was to explore a machine learning-based residual networks (ResNets) model to detect atrial septal defect (ASD) on chest radiographs. METHODS: This retrospective study included chest radiographs consecutively collected at our hospital from June 2017 to May 2022. Qualified chest radiographs were obtained from patients who had finished echocardiography. These chest radiographs were labeled as positive or negative for ASD based on the echocardiographic reports and were divided into training, validation, and test dataset. Six ResNets models were employed to examine and compare by using the training dataset and was tuned using the validation dataset. The area under the curve, recall, precision and F1-score were taken as the evaluation metrics for classification result in the test dataset. Visualizing regions of interest for the ResNets models using heat maps. RESULTS: This study included a total of 2105 chest radiographs of children with ASD (mean age 4.14 ± 2.73 years, 54% male), patients were randomly assigned to training, validation, and test dataset with an 8:1:1 ratio. Healthy children's images were supplemented to three datasets in a 1:1 ratio with ASD patients. Following the training, ResNet-10t and ResNet-18D have a better estimation performance, with precision, recall, accuracy, F1-score, and the area under the curve being (0.92, 0.93), (0.91, 0.91), (0.90, 0.90), (0.91, 0.91) and (0.97, 0.96), respectively. Compared to ResNet-18D, ResNet-10t was more focused on the distribution of the heat map of the interest region for most chest radiographs from ASD patients. CONCLUSION: The ResNets model is feasible for identifying ASD through children's chest radiographs. ResNet-10t stands out as the preferable estimation model, providing exceptional performance and clear interpretability.


Assuntos
Ecocardiografia , Comunicação Interatrial , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Comunicação Interatrial/diagnóstico por imagem , Aprendizado de Máquina , Radiografia , Estudos Retrospectivos
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