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Prussian blue analogs (PBAs) show great promise as anode materials for potassium-ion batteries (PIBs) due to their high specific capacity. However, PBAs still suffer from the drawbacks of low electronic conductivity and poor structural stability, leading to inadequate rate and cyclic performance. To address these limitations, CoFe PBA nanocubes wrapped with N/S doped carbon network (CoFe PBA@NSC) as anode for PIBs is designed by using thermal-induced in situ conversion strategy. As expected, the structural advantages of nanosized PBA cubes, such as abundant interfaces and large surface area, enable the CoFe PBA@NSC electrode to demonstrate superior rate properties (557 and 131 mAh g-1 at 0.05 and 10 A g-1) and low capacity degradation (0.093% per cycle over 1000 cycles at 0.5 A g-1). Furthermore, several ex situ characterizations revealed the K-ion storage mechanism. Fe+ and Co0 are generated during potassicization, followed by a completely reversible chemical state of iron while some cobalt monomers remained during depotassication. Additionally, the as-built potassium-ion hybrid capacitor based on CoFe PBA@NSC anode exhibits a high energy density of 118 Wh kg-1. This work presents an alternative but promising synthesis route for Prussian blue analogs, which is significant for the advancement of PIBs and other related energy storage devices.
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BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.
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Broncoscopia , Pulmão , Biópsia/efeitos adversos , Broncoscopia/efeitos adversos , Congelamento , Hemorragia , Humanos , Incidência , Pulmão/patologia , Estudos ProspectivosRESUMO
We present a case study for developing clinical trial scenarios in a complex progressive disease with multiple events of interest. The idea is to first capture the course of the disease in a multistate Markov model, and then to simulate clinical trials from this model, including a variety of hypothesized drug effects. This case study focuses on the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). The patient trajectory after HSCT is characterized by a complex interplay of various events of interest, and there is no established best method of measuring and/or analyzing treatment benefits. We characterized patient trajectories by means of multistate models that we fitted to a subset of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Events of interest included acute GvHD of grade III or IV, severe chronic GvHD, relapse of the underlying disease, and death. The transition probability matrix was estimated using the Aalen-Johansen estimator, and patient characteristics were identified that were associated with different transition rates. In a second step, clinical trial scenarios were simulated from the model assuming various drug effects on the background transition rates, and the operating characteristics of different endpoints and analysis strategies were compared in these scenarios. This helped devise a drug development strategy in GvHD prevention after allogeneic HSCT. More generally, multistate models provide a rich framework for exploring complex progressive diseases, and the availability of a corresponding simulation machinery provides great flexibility for clinical trial planning.
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Biometria , Ensaios Clínicos como Assunto , Descoberta de Drogas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Modelos Estatísticos , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Cadeias de Markov , Transplante Homólogo/efeitos adversosRESUMO
BACKGROUND: Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. METHODS: The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. RESULTS: In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25- T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. CONCLUSIONS: The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression.
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Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias Laríngeas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/fisiologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Progressão da Doença , Retroalimentação Fisiológica , Humanos , Tolerância Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C3H , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Ankylosing spondylitis is a chronic immune-mediated inflammatory disease characterised by spinal inflammation, progressive spinal rigidity, and peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key inflammatory cytokine in the development of ankylosing spondylitis, the prototypical form of spondyloarthritis. We assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis. METHODS: We did a randomised double-blind proof-of-concept study at eight centres in Europe (four in Germany, two in the Netherlands, and two in the UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either intravenous secukinumab (2×10 mg/kg) or placebo, given 3 weeks apart. Randomisation was done with a computer-generated block randomisation list without a stratification process. The primary efficacy endpoint was the percentage of patients with a 20% response according to the Assessment of SpondyloArthritis international Society criteria for improvement (ASAS20) at week 6 (Bayesian analysis). Safety was assessed up to week 28. This study is registered with ClinicalTrials.gov, number NCT00809159. FINDINGS: 37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The final efficacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99·8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group. INTERPRETATION: Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated. It is the first targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial. FUNDING: Novartis.
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Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Abscesso/induzido quimicamente , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/efeitos adversos , Biomarcadores/metabolismo , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/complicações , Infecções Cutâneas Estafilocócicas/induzido quimicamente , Staphylococcus aureus , Resultado do Tratamento , Adulto JovemRESUMO
Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.
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Durapatita , Células-Tronco Mesenquimais , Nylons , Impressão Tridimensional , Alicerces Teciduais , Durapatita/química , Alicerces Teciduais/química , Nylons/química , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Temperatura , Adesão CelularRESUMO
With the increasing application of lithium-ion batteries, the demand for high energy density, high-rate performance and high stability lithium-ion batteries is becoming more and more urgent. Ti2CO2 MXene, as a two-dimensional material with multilayer atomic structure and multiple active sites, has great advantages in lithium-ion battery electrode materials. However, the original Ti2CO2 MXene has been unable to meet the requirements of lithium-ion batteries due to its semiconductor properties. Doping is an effective means to regulate the conductivity and electrochemical properties of Ti2CO2 and improve the capacity of lithium-ion batteries and other energy storage devices. Hence, we use first-principles calculations to study the effect of V atom doping on the adsorption and diffusion of Li on the MXene surface. The density of states (DOS) and partial density of states (PDOS) of TiVCO2 and Ti2CO2 MXene indicated the transition of their conductive types from semiconductors to conductors. In addition, we observed that TiVCO2 has higher electrical conductivity and ion transport speed than the original Ti2CO2 MXene, and at the same time, Li atoms can be adsorbed well on the surface of MXene and show a lower diffusion energy barrier. Therefore, TiVCO2 is expected to become the anode material for the next generation of lithium-ion batteries and has good lithium storage performance.
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Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core's slow degradation and the shell's gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.
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Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds.
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Durapatita , Osteogênese , Poliésteres , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Alicerces Teciduais , Alicerces Teciduais/química , Osteogênese/efeitos dos fármacos , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Poliésteres/química , Durapatita/química , Regeneração Óssea/efeitos dos fármacos , Polímeros/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Ácido Poliglicólico/química , Engenharia Tecidual/métodos , Ácido Láctico/químicaRESUMO
Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.
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Immune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms of immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one of the best characterized RNA-binding proteins controlling the stability of targeted mRNAs, mediates innate immune evasion of mycobacteria. We found that TTP knockout mice displayed reduced bacterial burden in the early stage after Mtb aerosol challenge. Macrophages deficient in TTP also showed an inhibition in intracellular mycobacterial growth. Live mycobacteria induced TTP protein expression in macrophages, which was blocked by the mTOR inhibitor rapamycin. Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG-132 blocked rapamycin function and thus stabilized TTP protein. TTP induction suppressed the expression of iNOS/TNF-α/IL-12/IL-23, and weakened protective immune responses in macrophages, whereas rapamycin enhanced the bactericidal effects through TTP inhibition. Moreover, blocking TTP binding increased the expression of TNF-α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA-binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host-directed therapy against tuberculosis (TB).
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The combined design of scaffold structure and multi-biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein-2 (BMP-2) and a poly(DL-lactic-co-glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell-derived factor-1α (SDF-1α) is adsorbed on a scaffold surface to achieve the sequential release of the dual-biofactors. The results indicate that the rapid release of SDF-1α chemokine on the scaffold surface effectively recruits bone marrow-derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long-term sustained release of BMP-2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF-1α or BMP-2 biofactor alone, and the scaffold with surface SDF-1α and BMP-2 dual-biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high-performance bone repairing scaffolds.
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Durapatita , Osteogênese , Durapatita/farmacologia , Durapatita/química , Microesferas , Alicerces Teciduais/química , Quimiocina CXCL12/farmacologia , Ácido Láctico/química , Regeneração ÓsseaRESUMO
Scientists in the fields of nutrition and other biological sciences often design factorial studies to test the hypotheses of interest and importance. In the case of two-factorial studies, it is widely recognized that the analysis of factor effects is generally based on treatment means when the interaction of the factors is statistically significant, and involves multiple comparisons of treatment means. However, when the two factors do not interact, a common understanding among biologists is that comparisons among treatment means cannot or should not be made. Here, we bring this misconception into the attention of researchers. Additionally, we indicate what kind of comparisons among the treatment means can be performed when there is a nonsignificant interaction among two factors. Such information should be useful in analyzing the experimental data and drawing meaningful conclusions.
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Pesquisa Biomédica , Interpretação Estatística de Dados , Modelos Teóricos , Algoritmos , HumanosRESUMO
With the global outbreak of coronavirus disease 2019 (COVID-19), public health has received unprecedented attention. The cultivation of emergency and compound professionals is the general trend through public health education. However, current public health education is limited to traditional teaching models that struggle to balance theory and practice. Fortunately, the development of artificial intelligence (AI) has entered the stage of intelligent cognition. The introduction of AI in education has opened a new era of computer-assisted education, which brought new possibilities for teaching and learning in public health education. AI-based on big data not only provides abundant resources for public health research and management but also brings convenience for students to obtain public health data and information, which is conducive to the construction of introductory professional courses for students. In this review, we elaborated on the current status and limitations of public health education, summarized the application of AI in public health practice, and further proposed a framework for how to integrate AI into public health education curriculum. With the rapid technological advancements, we believe that AI will revolutionize the education paradigm of public health and help respond to public health emergencies.
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COVID-19 , Humanos , COVID-19/epidemiologia , Inteligência Artificial , Currículo , Educação em SaúdeRESUMO
Bone tissue engineering scaffolds with similar composition, structure, and mechanical properties to natural bone are conducive to bone regeneration. The objective of this study was to prepare hydroxyapatite/poly (lactic-co-glycolic acid) (HA/PLGA) three-dimensional porous scaffolds with HA content close to natural bone and strong mechanical strength to promote osteogenesis. To achieve this, we modified HA microspheres with polyvinyl alcohol to create an inorganic filler to endow the HA/PLGA printing ink with higher HA content and excellent printing fluidity for 3D printing. We successfully printed a series of HA/PLGA scaffolds with different HA contents. The highest HA content reached 60 wt%, which is close to the mineral percentage in natural bone. The composition, structure, mechanical properties, and in vitro degradability of the fabricated scaffolds were systematically characterized. The cytocompatibility and osteogenic activity of the fabricated HA/PLGA scaffolds were evaluated by in vitro cell culture and rabbit femoral defect repair experiments in vivo. The results indicated that the HA/PLGA composite scaffold with 45 wt% HA had the highest compressive strength of more than 40 MPa, which was six times higher than that of the pure PLGA scaffold. The incorporation of HA microspheres into the PLGA matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs) cultured on the surface of the scaffolds. Animal experiments showed that the HA/PLGA composite with 45 wt% HA exhibited the best structure maintenance and osteogenic performance in vivo. The prepared HA/PLGA composite 3D scaffold with HA microsphere reinforcement has considerable application potential in the field of large bone defect repair.
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Durapatita , Osteogênese , Animais , Regeneração Óssea , Durapatita/farmacologia , Microesferas , Impressão Tridimensional , CoelhosRESUMO
We have demonstrated that fish oil- and pectin-containing (FO/P) diets protect against colon cancer compared with corn oil and cellulose (CO/C) by upregulating apoptosis and suppressing proliferation. To elucidate the mechanisms whereby FO/P diets induce apoptosis and suppress proliferation during the tumorigenic process, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. Rats consumed diets containing FO/P or CO/C and were injected with azoxymethane (AOM; 2 times, 15 mg/kg body weight, subcutaneously). Feces collected at initiation (24 h after AOM injection) and at aberrant crypt foci (ACF) (7 wk postinjection) and tumor (28 wk postinjection) stages of colon cancer were used for poly (A)+ RNA extraction. Gene expression signatures were determined using Codelink arrays. Changes in phenotypes (ACF, apoptosis, proliferation, and tumor incidence) were measured to establish the regulatory controls contributing to the chemoprotective effects of FO/P. At initiation, FO/P downregulated the expression of 3 genes involved with cell adhesion and enhanced apoptosis compared with CO/C. At the ACF stage, the expression of genes involved in cell cycle regulation was modulated by FO/P and the zone of proliferation was reduced in FO/P rats compared with CO/C rats. FO/P also increased apoptosis and the expression of genes that promote apoptosis at the tumor endpoint compared with CO/C. We conclude that the effects of chemotherapeutic diets on epithelial cell gene expression can be monitored noninvasively throughout the tumorigenic process and that a FO/P diet is chemoprotective in part due to its ability to affect expression of genes involved in apoptosis and cell cycle regulation throughout all stages of tumorigenesis.
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Neoplasias do Colo/genética , Neoplasias do Colo/prevenção & controle , Enterócitos/metabolismo , Óleos de Peixe/administração & dosagem , Pectinas/administração & dosagem , Animais , Azoximetano/toxicidade , Ciclo Celular/genética , Proliferação de Células , Neoplasias do Colo/patologia , Dieta , Gorduras Insaturadas na Dieta/administração & dosagem , Sacarose Alimentar/administração & dosagem , Enterócitos/citologia , Enterócitos/efeitos dos fármacos , Fezes/química , Fezes/citologia , Perfilação da Expressão Gênica , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
We consider the problem of testing for a constant nonparametric effect in a general semi-parametric regression model when there is the potential for interaction between the parametrically and nonparametrically modeled variables. The work was originally motivated by a unique testing problem in genetic epidemiology (Chatterjee, et al., 2006) that involved a typical generalized linear model but with an additional term reminiscent of the Tukey one-degree-of-freedom formulation, and their interest was in testing for main effects of the genetic variables, while gaining statistical power by allowing for a possible interaction between genes and the environment. Later work (Maity, et al., 2009) involved the possibility of modeling the environmental variable nonparametrically, but they focused on whether there was a parametric main effect for the genetic variables. In this paper, we consider the complementary problem, where the interest is in testing for the main effect of the nonparametrically modeled environmental variable. We derive a generalized likelihood ratio test for this hypothesis, show how to implement it, and provide evidence that our method can improve statistical power when compared to standard partially linear models with main effects only. We use the method for the primary purpose of analyzing data from a case-control study of colorectal adenoma.
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The ideal scaffold for bone repair should have a hierarchical pore structure and gradient degradation performance to satisfy the uniform adhesion and proliferation of cells in the scaffold at the early stage of implantation, as well as providing space for the subsequent regeneration of bone tissue. To this end, we developed a hierarchical polylactic acid glycolic acid copolymer (PLGA)/nano-hydroxyapatite (n-HA)/gelatin (Gel) (PHG) scaffold with a printed PLGA/n-HA (PH) framework and a Gel network filler for bone regeneration by the combination of 3D printing and freeze-drying technologies. The fabricated PHG scaffold features large front hole size (>1100 µm × 1100 µm) and side hole size (>500 µm) to provide sufficient open space and reliable integrated support for cell and tissue ingrowth. The gelatin network filled in the PH framework played the role of a cell holder just like an extracellular matrix (ECM) in the early stage. In vitro degradation experiments revealed that the gelatin network completely degraded within 5 weeks while the structural integrity of the framework still remained at the 32nd week. The results of cell culture confirmed that the PHG scaffold was more conducive to cell attachment. In vivo assessments in a rat femoral defect model showed that PHG scaffolds were more favored for new bone formation and achieving a tighter bond between the scaffold and the original tissues. The hierarchical PHG scaffold has great application potential in bone tissue engineering and will provide a reference for the model design of bone scaffolds.
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Regeneração Óssea , Durapatita/química , Matriz Extracelular/metabolismo , Impressão Tridimensional , Alicerces Teciduais , Adesão Celular , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
The deformation shrinkage of a poly(lactide-co-glycolide) (PLGA) fibrous material seriously affects its biomedical application. To demonstrate the underlying shrinking mechanism and to find a method to prevent the shrinkage of an electrospun PLGA membrane, we investigated the shrinking behavior of PLGA electrospun membranes under various test conditions and discussed the underlying shrinking mechanism. The results indicated that the shrinkage of the electrospun PLGA membrane was mainly regulated by the glass transition of its polymer fiber; the temperature and liquid environment were found to be the two main factors leading to the shrinkage of the electrospun PLGA membrane through affecting its glass transition. Then a heat stretching (HS) technique was proposed by us to stabilize the electrospun PLGA membrane. After HS treatment, the glass transition temperature (Tg) of the electrospun PLGA membrane could increase from 48.38 °C to 54.55 °C. Our results indicated that the HS-treated membranes could maintain a high area percentage of 90.89 ± 2.27% and 84.78 ± 3.36% after immersion respectively in PBS and blood at 37 °C for 2 hours. Further experiments confirmed that the HS technique could also stabilize the dimensional structure of the electrospun PDLLA membrane in PBS and blood at 37 °C. This study provides an effective strategy for preventing the shrinkage of electrospun polyester biomaterials in a physiological environment that may benefit both the material structural stability and the in vivo biological performance.