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Two-dimensional (2D) cell culture methods dominate the current research. However, the inherent responsiveness of cells to their native three-dimensional (3D) microenvironment necessitates a paradigm shift toward the development of advanced hydrogels that faithfully mimic the intricacies of the extracellular matrix (ECM) and enable continuous cell-ECM interactions. To address the constraints of traditional static hydrogel networks that impede effective cell-matrix and cell-cell interactions, and to tackle the inherent stability issues associated with dynamically cross-linked hydrogels, which have become a pressing concern. Herein, we present an interpenetrating polymer network (IPN) hydrogel (HA/Alg-RGD hydrogel) that combines a physically cross-linked network between alginate and calcium ions (Alg-Ca2+) for the enhanced cell growth adaptability with a chemically cross-linked hyaluronic acid (HA) network to ensure macroscopic stability during cell culture. The incorporation of arginine-glycine-aspartic peptide modified alginate (Alg-RGD) further facilitates cell adhesion and improves the cell-hydrogel interaction. Notably, this IPN hydrogel demonstrates mechanical stability and enables cell spreading and growth within its structural framework. Leveraging the reversible characteristics of the ionically cross-linked Alg-Ca2+ network within IPN hydrogels, we demonstrate the feasibility of the gelatin sacrificial solution for 3D printing purposes within the hydrogel matrix. Subsequent UV-induced covalent cross-linking enables the fabrication of vascularized microfluidic channels within the resulting construct. Our results demonstrate endothelial cell spreading and spontaneous cell sprouting within the hydrogel matrix, thus highlighting the efficacy of this IPN hydrogel system in facilitating 3D cell growth. Additionally, our study emphasizes the potential of 3D printed constructs as a promising approach for vascularization in tissue engineering. The importance of RGD peptides in promoting favorable cell-hydrogel scaffold interactions is also highlighted, emphasizing their critical role in optimizing biomaterial-cell interfaces.
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Ácido Hialurônico , Polímeros , Ácido Hialurônico/química , Hidrogéis/farmacologia , Hidrogéis/química , Engenharia Tecidual/métodos , Alginatos/química , Impressão Tridimensional , Oligopeptídeos , Alicerces TeciduaisRESUMO
Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.
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Quitosana , Curcumina , Nanopartículas , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Adesivos , Aderências Teciduais , Bandagens , Curcumina/farmacologia , Curcumina/química , Quitosana/química , Colágeno , Íons , AntibacterianosRESUMO
Granulocyte colony-stimulating factor (G-CSF) is widely used in clinical settings to mobilize hematopoietic stem cells (HSCs) into the circulation for HSC harvesting and transplantation. However, whether G-CSF directly stimulates HSCs to change their cell cycle state and fate is controversial. HSCs are a heterogeneous population consisting of different types of HSCs, such as myeloid-biased HSCs and lymphoid-biased HSCs. We hypothesized that G-CSF has different effects on different types of HSCs. To verify this, we performed serum-free single-cell culture and competitive repopulation with cultured cells. Single highly purified HSCs and hematopoietic progenitor cells (HPCs) were cultured with stem cell factor (SCF), SCF + G-CSF, SCF + granulocyte/macrophage (GM)-CSF, or SCF + thrombopoietin (TPO) for 7 days. Compared with SCF alone, SCF + G-CSF increased the number of divisions of cells from the lymphoid-biased HSC-enriched population but not that of cells from the My-bi HSC-enriched population. SCF + G-CSF enhanced the level of reconstitution of lymphoid-biased HSCs but not that of myeloid-biased HSCs. Clonal transplantation assay also showed that SCF + G-CSF did not increase the frequency of myeloid-biased HSCs. These data showed that G-CSF directly acted on lymphoid-biased HSCs but not myeloid-biased HSCs. Our study also revised the cytokine network at early stages of hematopoiesis: SCF directly acted on myeloid-biased HSCs; TPO directly acted on myeloid-biased HSCs and lymphoid-biased HSCs; and GM-CSF acted only on HPCs. Early hematopoiesis is controlled differentially and sequentially by a number of cytokines.
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Fator Estimulador de Colônias de Granulócitos , Células-Tronco Hematopoéticas , Animais , Células Cultivadas , Fator Estimulador de Colônias de Granulócitos/farmacologia , Hematopoese , Camundongos , Fator de Células-Tronco/farmacologia , Trombopoetina/farmacologiaRESUMO
Visual browse and exploration in motion capture data take resource acquisition as a human-computer interaction problem, and it is an essential approach for target motion search. This paper presents a progressive schema which starts from pose browse, then locates the interesting region and then switches to online relevant motion exploration. It mainly addresses three core issues. First, to alleviate the contradiction between the limited visual space and ever-increasing size of real-world database, it applies affinity propagation to numerical similarity measure of pose to perform data abstraction and obtains representative poses of clusters. Second, to construct a meaningful neighborhood for user browsing, it further merges logical similarity measures of pose with the weight quartets and casts the isolated representative poses into a structure of phylogenetic tree. Third, to support online motion exploration including motion ranking and clustering, a biLSTM-based auto-encoder is proposed to encode the high-dimensional pose context into compact latent space. Experimental results on CMU's motion capture data verify the effectiveness of the proposed method.
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Algoritmos , Filogenia , Análise por Conglomerados , Bases de Dados Factuais , Humanos , Movimento (Física)RESUMO
Given that current Internet of Things (IoT) applications employ many different sensors to provide information, a large number of the Bluetooth low energy (BLE) devices will be developed for IoT systems. Developing low-power and low-cost BLE advertisers is one of most challenging tasks for supporting the neighbor discovery process (NDP) of such a large number of BLE devices. Since the parameter setting is essential to achieve the required performance for the NDP, an energy model of neighbor discovery in BLE networks can provide beneficial guidance when determining some significant parameter metrics, such as the advertising interval, scan interval, and scan window. In this paper, we propose a new analytical model to characterize the energy consumption using all possible parameter settings during the NDP in BLE networks. In this model, the energy consumption is derived based on the Chinese remainder theorem (CRT) for an advertising event and a scanning event during the BLE NDP. In addition, a real testbed is set up to measure the energy consumption. The measurement and experimental results reveal the relationship between the average energy consumption and the key parameters. On the basis of this model, beneficial guidelines for BLE network configuration are presented to help choose the proper parameters to optimize the power consumption for a given IoT application.
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RATIONALE: Airway stents have been developed rapidly to treat airway stenosis and fistula caused by various reasons. Malignant conditions that lead to central airway obstruction, especially the invasion of trachea carina and formation of esophageal fistula, are still a challenge for clinicians. PATIENT CONCERNS: A 61-year-old man presented with malignant airway obstruction and fistula between trachea carina and esophagus accompanied by severe respiratory failure. DIAGNOSIS: The patient was clinically diagnosed with esophageal squamous cell cancer of stage IV, carina esophageal fistula, severe pneumonia, hypoproteinemia. INTERVENTIONS: Y-shaped covered metallic stent and Y-type silicone stent (hybrid stent) were placed in the airway to increase tracheal patency, block the fistula and perform carinal plasty. OUTCOMES: The clinical symptoms of the patient improved rapidly and the lung infection was controlled effectively. This patient was followed up for more than 2 month, and the quality of life was better than before. LESSONS: Hybrid stent can be used as 1 of options for airway reconstruction and palliative treatment for patients with complex airway diseases caused by malignant tumors.
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Obstrução das Vias Respiratórias , Fístula Esofágica , Neoplasias Esofágicas , Masculino , Humanos , Pessoa de Meia-Idade , Traqueia/cirurgia , Qualidade de Vida , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Fístula Esofágica/cirurgia , Fístula Esofágica/complicações , Stents/efeitos adversos , Resultado do Tratamento , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgiaRESUMO
Spinal cord injury (SCI) often causes severe and permanent disabilities due to the complexity of injury progression. The promising methods are generally based on tissue engineering technology using biocompatible hydrogels to achieve SCI repair. However, hydrogels are commonly incapable of close contact with the damaged spinal cord stumps and fail to support neural regeneration in SCI. Therefore, it is still a challenge to achieve stable contact with the transected nerve stumps and accelerate neural regeneration in the lesion microenvironment. Here, an in situ forming glycidyl methacrylated silk fibroin/ laminin-acrylate (SF-GMA/LM-AC) hydrogel was fabricated for SCI repair. The polymer chains formed a network quickly after ultraviolet (UV)-light trigger, in topological entanglement with the spinal cord, stitching the hydrogel and wet tissues together like a suture at the molecular scale. The SF-GMA/LM-AC hydrogel also provided a favorable environment for the growth of cells due to the incorporation of LM-AC. Compared with physical entrapment of LM, LM-AC immobilized in the hydrogel by covalent technology provided better microenvironments for neural stem cells (NSCs) growth. The repair of complete transection SCI in rats demonstrated that this hydrogel guided and promoted neural regeneration over 8 weeks, leading to hind limb locomotion recovery. This adhesive and bioactive SF-GMA/LM-AC hydrogel may open many opportunities in various therapeutic indications, including SCI. STATEMENT OF SIGNIFICANCE: Many materials have been developed for building transplanted scaffolds, but it is still a challenge to fabricate bioactive scaffolds and adhesion to wet tissues. In this study, we successfully developed an in situ forming SF-GMA/LM-AC hydrogel for SCI repair. This in situ forming hydrogel formed significant adhesion to the native spinal cord, stitching hydrogel and tissue together like a suture at the molecular scale. In addition, covalent immobilized LM-AC was used as the contact guidance biochemical cues for axonal outgrowth and had much better bioactive effects than physically entangled LM. Moreover, this universal strategy would open an avenue to fabricate adhesive and bioactive hydrogel for various disease treatments including SCI.
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Fibroínas , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Ratos , Animais , Fibroínas/farmacologia , Alicerces Teciduais/química , Hidrogéis/farmacologia , Hidrogéis/química , Adesivos , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologiaRESUMO
Endobronchial ultrasound bronchoscopy (EBUS) and needle confocal laser endomicroscopy (nCLE) are techniques for screening benign and malignant lesions of the hilar and mediastinal lymph node (HMLN). This study investigated the diagnostic potential of EBUS, nCLE, and combined EBUS and nCLE in HMLN lesions. We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS-nCLE approach was analyzed according to the results. Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS-nCLE examination. The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively). The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11). No serious complications occurred in patients with HMLN lesions. To summarize, the diagnostic efficacy of nCLE was better than EBUS. The EBUS-nCLE combination is a suitable approach for diagnosing HMLN lesions.
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Broncoscopia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Mediastino/diagnóstico por imagem , Mediastino/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pulmão/patologia , Sensibilidade e Especificidade , Estudos RetrospectivosRESUMO
This study was designed to investigate the feasibility of genetic testing using circulating tumor cells (CTCs) instead of tumor tissues in lung adenocarcinoma to break through its limitation. Separation system for epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and Vimentin expressing CTCs was constructed and used to capture CTCs in the blood samples of 57 patients with lung adenocarcinoma. Genetic mutations of genes involved in targeted therapies were detected by next-generation sequencing (NGS) in tissues from these patients. Blood CTC samples with the gene mutations identified by tissue-NGS were selected and corresponding gene mutations were detected by Sanger sequencing. The specificity of the CTC separation system was 95.48% and the sensitivity was 90.85%. The average number of CTCs in the blood of patients with lung adenocarcinoma was 12.47/7.5 mL. Comparison of the tissue-NGS with the CTC-Sanger sequencing showed that the consistencies of genetic mutations of EGFR (n = 24), KRAS (n = 9), TP53 (n = 19), BRAF (n = 1), ERBB2 (n = 2), and PIK3CA (n = 3) were 92.31%, 75.00%, 86.36%, 50.00%, 66.67%, and 75.00%, with an overall consistency of 84.06%. The CTC separation system established in this study shows high specificity and sensitivity. CTCs can be used as a suitable alternative to tumor tissues that are difficult to obtain in clinical practice and overcome the difficulties in tumor tissue collection, which is of significance in guiding clinical medication and individualized treatment with significant clinical application value in terms of genetic testing for targeted therapies in tumor treatment.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Adenocarcinoma de Pulmão/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Células Neoplásicas Circulantes/metabolismoRESUMO
Object: In this study, we aimed to explore the influences of stress responses and psychological resilience on depression of vocational middle school students during the initial COVID-19 outbreak in China. Methods: An online questionnaire survey on the students of a medical school in Jiangxi Province, China, and obtained 3,532 valid questionnaires. A self-compiled general situation questionnaire, Stress Response of COVID-19 Questionnaire, the Resilience Scale for Chinese Adolescents and Center for Epidemiological Studies Depression Scale (CES-D) were used. Hierarchical regression analysis was used to explore the regulatory role of psychological resilience between stress response and depression. Results: (1) There were significant differences in gender between vocational middle school students' evaluation (t = 3.07, P = 0.002) and defense (t = 3.28, P = 0.001) of the pandemic. Males had higher cognitive evaluation of the pandemic than females, and females had more defense against the pandemic than males. (2) There is a significant difference between vocational middle school students from different grades in depression level (F = 3.62, P = 0.03), pneumonia defense (F = 13.65, P < 0.001) and pneumonia panic (F = 3.10, P = 0.045). (3) Depression level (F = 7.17, P < 0.001), pneumonia evaluation (F = 2.78, P = 0.04) and pneumonia panic (F = 3.32, P = 0.02) of the students concerning the spatial distance of the pandemic. (4) The severity of urban pandemic affects the evaluation of pneumonia among vocational middle school students. (5) Depression was negatively correlated with psychological resilience and pneumonia evaluation, and positively correlated with pneumonia panic. Psychological resilience was positively correlated with pneumonia evaluation and pneumonia defense, and negatively correlated with pneumonia panic. (6) Psychological resilience could reduce the level of depression caused by pneumonia evaluation and pneumonia panic. Conclusion: There were significant differences in depression level and stress responses in grades, gender and spatial distance of pandemic. Resilience has a significant negative moderator effect on the relationship between pandemic panic and depression. Resilience has a significant positive moderator effect on the relationship between pandemic evaluation and depression.
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Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.
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Little is known regarding whether the cell of origin differs among different leukemia types. To address this fundamental issue, we determined the cell of origin in five distinct types of acute leukemia induced by N-Myc overexpression in mice. CD150+CD48-CD41-CD34-c-Kit+Sca-1+Lin- (KSL) (HSC1) cells, CD150-CD48-CD41-CD34-KSL (HSC2) cells, CD150+CD41+CD34-KSL (HPC1) cells, CD150+CD41+CD34+KSL (HPC2) cells, and CD150-CD41-CD34+KSL (HPC3) cells were purified from the bone marrow of adult C57BL/6 mice, transduced with the N-Myc retrovirus vector, and transplanted into lethally irradiated mice. B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and mixed phenotype acute leukemia (MPAL) developed from five populations. RNA sequencing data supported the phenotypical diagnoses of leukemia, except that AUL appeared transcriptionally close to T-ALL. Whole-genome sequencing revealed that retroviral integration sites were irrelevant to the leukemia types and that T-ALL and AML of MPAL shared the same integration site and many gene mutations, suggesting their common origin. Additionally, leukemic stem cells were identified in the KSL cell population, suggesting that the phenotypes of leukemic stem cells are irrelevant to leukemia types. This study provides experimental evidence for the similar and multiple cells of origin in acute leukemia.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Animais , Antígenos CD34 , Humanos , Leucemia Mieloide Aguda/genética , Camundongos , Camundongos Endogâmicos C57BL , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
Myelodysplastic syndromes (MDS) are generally considered as a group of clonal diseases derived from hematopoietic stem cells, but a number of studies have suggested that they are derived from myeloid progenitor cells. We aimed to identify the cell of origin in MDS by single-cell analyses. Targeted single-cell RNA sequencing, covering six frequently mutated genes (U2AF1, SF3B1, TET2, ASXL1, TP53, and DNMT3A) in MDS, was developed and performed on individual cells isolated from the CD34+ and six lineage populations in the bone marrow of healthy donors (HDs) and patients with MDS. The detected mutations were used as clonal markers to define clones. By dissecting the distribution of clones in six lineages, the clonal origin was determined. We identified three mutations both in HDs and patients with MDS, termed clonal hematopoiesis (CH) mutations. We also identified fifteen mutations only detected in patients with MDS, termed MDS mutations. Clonal analysis showed that CH clones marked by CH mutations and MDS clones marked by MDS mutations were derived from hematopoietic stem cells as well as various hematopoietic progenitor cells. Most patients with MDS showed the chimeric state with CH clones and MDS clones. Clone size analysis suggested that CH mutations may not contribute to clonal expansion of MDS. In conclusion, MDS comprise multiple clones derived from hematopoietic stem and progenitor cells.
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Micro-light-emitting diodes (µ-LEDs) are regarded as the cornerstone of next-generation display technology to meet the personalised demands of advanced applications, such as mobile phones, wearable watches, virtual/augmented reality, micro-projectors and ultrahigh-definition TVs. However, as the LED chip size shrinks to below 20 µm, conventional phosphor colour conversion cannot present sufficient luminance and yield to support high-resolution displays due to the low absorption cross-section. The emergence of quantum dot (QD) materials is expected to fill this gap due to their remarkable photoluminescence, narrow bandwidth emission, colour tuneability, high quantum yield and nanoscale size, providing a powerful full-colour solution for µ-LED displays. Here, we comprehensively review the latest progress concerning the implementation of µ-LEDs and QDs in display technology, including µ-LED design and fabrication, large-scale µ-LED transfer and QD full-colour strategy. Outlooks on QD stability, patterning and deposition and challenges of µ-LED displays are also provided. Finally, we discuss the advanced applications of QD-based µ-LED displays, showing the bright future of this technology.
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Thermoplastic polymer micro- and nanostructures suffer pattern decay when heated to a temperature close to or above the polymer's glass transition temperature. In this work, we report enhanced thermal stability of polycarbonate nanostructures at temperatures well above their glass transition temperatures. Based on this observation, we develop a unique technique for high-resolution polymer patterning by polymer reflows. This technique is characterized as the precise control of polymer reflows regardless of the annealing time, which avoids the time-domain nonlinear reflow of the polymer melt. We also implement thermal nanoimprinting in a step-and-repeat fashion, which dramatically increases the throughput of the thermal nanoimprint. The enhanced pattern stability against thermal reflow also allows for multiple imprinting at the same location to generate complex resist patterns from a simple mold structure. Since modern lithography often uses thin resist films (sub-100 nm) due to the restraint from the pattern aspect ratio, the unusual annealing behavior of thin polymer films is highly relevant in sub-100 nm lithographic processing.
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The brown planthopper (BPH) Nilaparvata lugens is an economically important pest on rice plants. In this study, the higher population density and yellow-ripe stage of rice plants were used to construct adverse survival conditions (ASC) against BPH nymphs. Simultaneously, the low population density and tillering stage of rice plants were used to establish a suitable survival condition (SSC) as a control. Solexa/Illumina sequencing was used to identify genes of BPH nymphs responding to ASC. Significantly longer duration development of BPH nymphs and significantly lower brachypterous ratio of BPH adults were observed by ASC compared with SSC. A total of 2 544 differentially expressed genes (DEGs) were obtained and analyzed by BLASTx, Gene Ontology and KEGG Orthology. Gene ontology analysis revealed that the DEGs were mainly involved in categories of cell, cell part, cellular process, binding, catalytic, organelle and metabolic processes. 1 138 DEGs having enzyme commission numbers were assigned to different metabolic pathways. The largest clusters were neurodegenerative diseases (137, 12.0%), followed by carbohydrate metabolism (113, 9.9%), amino acid metabolism (94, 8.3%), nucleotide metabolism (76, 6.7%), energy metabolism (64, 5.6%), translation (60, 5.3%), lipid metabolism (58, 5.1%), and folding, sorting and degradation (52, 4.6%). Expressing profile of 11 DEGs during eight nymphal developmental stages of BPH were analyzed by quantitative real-time polymerase chain reaction. The 11 genes exhibited differential expression between ASC and SSC during at least one developmental stage. The DEGs identified in this study provide molecular proof of how BPH reconfigures its gene expression profile to adapt to overcrowding and low-quality hosts.