Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Quantifying Imaging Agent Binding and Dissociation in 3-D Cancer Spheroid Tissue Culture Using Paired-Agent Principles.

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k3 (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

The Role of T Cells in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory decline and cognitive impairment, which is related to hallmark protein aggregates, amyloid-ß (Аß) plaques and neurofibrillary tangles; the latter are accumulated with hyperphosphorylated Tau protein. Immune cells play an important role in AD pathogenesis. Although the role of T cells in AD remains controversial, studies have shown that T cell deficiency is associated with increased AD pathology. In contrast, transplantation of T cells reduces AD pathology. T cells can help B cells generate anti-Ðß antibody to neutralize the toxin of Ðß and hyperphosphorylated Tau. T cells also activate macrophages to phagocytose misfolded proteins including Ðß and Tau. Recent data have also shown that AD animals have a damaged thymic microenvironment, especially thymic epithelial cells (TECs), resulting in decreased T cell numbers, which contribute to AD pathology. Therefore, regulation of T cell regeneration, for example by rejuvenating the thymic microenvironment, has the potential to be used in the treatment of AD.

miR-100a-5p-enriched exosomes derived from mesenchymal stem cells enhance the anti-oxidant effect in a Parkinson's disease model via regulation of Nox4/ROS/Nrf2 signaling.

BACKGROUND: The pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available. METHODS: Here, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.g., western blotting, immunofluorescence and immunohistochemistry staining). RESULTS: We assessed the levels of DA neuron injury and oxidative stress in MPTP-induced PD mice and MPP+-induced MN9D cells after treating them with T-MSCs or T-MSCs-Exo. Furthermore, T-MSCs-Exo miRNA sequencing analysis revealed that miR-100-5p-enriched T-MSCs-Exo directly targeted the 3' UTR of NOX4, which could protect against the loss of DA neurons, maintain nigro-striatal system function, ameliorate motor deficits, and reduce oxidative stress via the Nox4-ROS-Nrf2 axis in PD models. CONCLUSIONS: The study suggests that miR-100-5p-enriched T-MSCs-Exo may be a promising biological agent for the treatment of PD. Schematic summary of the mechanism underlying the neuroprotective actions of T-MSCs-Exo in PD. T-MSCs Exo may inhibit the expression level of the target gene NOX4 by delivering miR-100-5p, thereby reducing ROS production and alleviating oxidative stress via the Nox4-ROS-Nrf2 axis, thus improving DA neuron damage in PD.

Quantifying imaging agent binding and dissociation in 3D cancer spheroid tissue culture using paired-agent principles.

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody-mimetic) and IRDye 700DX-carboxylate in 3D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR targeted ABY-029 agent. A linear correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r=0.99, p<0.05). Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3D tumor spheroid models, can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

Comparative analysis of sensitivity and specificity of computer-aided cognitive test in screening mild cognitive impairment patients and test of reliability and validity.

OBJECTIVES: To evaluate the reliability and validity of the computer-aided cognitive test (CACT). METHODS: 219 Subjects of Tongji Hospital's Brain Health cohort (115 cases of Mild Cognitive Impairment (MCI) patients and 104 cases of normal controls) were enrolled, of which 24 cases received a retest after 2 weeks. Finally, the reliability and validity of the scale were tested and analyzed. RESULTS: (1) Reliability: (a) the internal consistency reliability of the total score of the scale was 0.645; (b) the retest reliability correlation coefficient of the total score of the scale was 0.900; (c) the Guttman Split-Half coefficient was 0.631; (2) Validity: (a) construct validity analysis showed that the correlation coefficient between each section score was between 0.036 and 0.408, and the correlation coefficient between each section score and the total score was between 0.468 and 0.781; (b) criterion validity analysis showed that the correlation coefficient between the total score of CACT and that of the Mini Mental State Examination (MMSE) was 0.733, and the coefficient between the total score of CACT and that of the basic version of the Montreal Cognitive Assessment (MoCA) was 0.763; (c) the area under the ROC curve of the CACT to distinguish between MCI patients and controls was 0.920, with an optimal diagnostic threshold of 20, a sensitivity of 88.5%, and a specificity of 80.9%. CONCLUSION: The CACT is little influenced by education level. It has good reliability and validity, which can be used for early clinical screening of cognitive dysfunction.

A robust CD8+ T cell-related classifier for predicting the prognosis and efficacy of immunotherapy in stage III lung adenocarcinoma.

Patients with stage III lung adenocarcinoma (LUAD) have significant survival heterogeneity, meanwhile, CD8+ T cell has a remarkable function in immunotherapy. Therefore, developing novel biomarkers based on CD8+ T cell can help evaluate the prognosis and guide the strategy of immunotherapy for patients with stage III LUAD. Thus, we abstracted twelve datasets from multiple online databases and grouped the stage III LUAD patients into training and validation sets. We then used WGCNA and CIBERSORT, while univariate Cox analysis, LASSO analysis, and multivariate Cox analysis were performed. Subsequently, a novel CD8+ T cell-related classifier including HDFRP3, ARIH1, SMAD2, and UPB1 was developed, which could divide stage III LUAD patients into high- and low-risk groups with distinct survival probability in multiple cohorts (all P < 0.05). Moreover, a robust nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its powerful predictive capacity. Besides, we detected the difference in immune cell subpopulations and evaluated the potential benefits of immunotherapy between the two risk subsets. Finally, we verified the correlation between the gene expression and CD8+ T cells included in the model by immunohistochemistry and validated the validity of the model in a real-world cohort. Overall, we constructed a robust CD8+ T cell-related risk model originally which could predict the survival rates in stage III LUAD. What's more, this model suggested that patients in the high-risk group could benefit from immunotherapy, which has significant implications for accurately predicting the effect of immunotherapy and evaluating the prognosis for patients with stage III LUAD.

Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model.

Objective: Many patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals. Methods: In the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis. Results: No kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft. Conclusions: Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.

Adipose-Derived Stromal Cell-Sheets Sandwiched, Book-Shaped Acellular Dermal Matrix Capable of Sustained Release of Basic Fibroblast Growth Factor Promote Diabetic Wound Healing.

The management of diabetic wounds is a therapeutic challenge in clinical settings. Current tissue engineering strategies for diabetic wound healing are insufficient, owing to the lack of an appropriate scaffold that can load a large number of stem cells and induce the interaction of stem cells to form granulation tissue. Herein we fabricated a book-shaped decellularized dermal matrix (BDDM), which shows a high resemblance to native dermal tissue in terms of its histology, microstructure, and ingredients, is non-cytotoxic and low-immunogenic, and allows adipose-derived stromal cell (ASC) attachment and proliferation. Then, a collagen-binding domain (CBD) capable of binding collagen was fused into basic fibroblast growth factor (bFGF) to synthetize a recombinant growth factor (termed as CBD-bFGF). After that, CBD-bFGF was tethered onto the collagen fibers of BDDM to improve its endothelial inducibility. Finally, a functional scaffold (CBD-bFGF/BDDM) was fabricated. In vitro and in vivo experiments demonstrated that CBD-bFGF/BDDM can release tethered bFGF with a sustained release profile, steadily inducing the interaction of stem cells down to endothelial differentiation. ASCs were cultured to form a cell sheet and then sandwiched by CBD-bFGF/BDDM, thus enlarging the number of stem cells loaded into the scaffold. Using a rat model, the ASC sheets sandwiched with CBD-bFGF/BDDM (ASCs/CBD-bFGF/BDDM) were capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition and remodeling. Therefore, the findings of this study demonstrate that ASCs/CBD-bFGF/BDDM could be applicable for diabetic wound healing.

Bronchoscopy for diagnosis of COVID-19 with respiratory failure: A case report.

BACKGROUND: Although the imaging features of coronavirus disease 2019 (COVID-19) are starting to be well determined, what actually occurs within the bronchi is poorly known. Here, we report the processes and findings of bronchoscopy in a patient with COVID-19 accompanied by respiratory failure. CASE SUMMARY: A 65-year-old male patient was admitted to the Hainan General Hospital on February 3, 2020 for fever and shortness of breath for 13 d that worsened for the last 2 d. The severe acute respiratory syndrome coronavirus 2 nucleic acid test was positive. Routine blood examination on February 28 showed a white blood cell count of 11.02 × 109/L, 86.9% of neutrophils, 6.4% of lymphocytes, absolute lymphocyte count of 0.71 × 109/L, procalcitonin of 2.260 ng/mL, and C-reactive protein of 142.61 mg/L. Oxygen saturation was 46% at baseline and turned to 94% after ventilation. The patient underwent video bronchoscopy. The tracheal cartilage ring was clear, and no deformity was found in the lumen. The trachea and bilateral bronchi were patent, while the mucosa was with slight hyperemia; no neoplasm or ulcer was found. Moderate amounts of white gelatinous secretions were found in the dorsal segment of the left inferior lobe, and the bronchial lumen was patent after sputum aspiration. The right inferior lobe was found with hyperemia and mucosal erosion, with white gelatinous secretion attachment. The patient's condition did not improve after the application of therapeutic bronchoscopy. CONCLUSION: For patients with COVID-19 and respiratory failure, bronchoscopy can be performed under mechanical ventilation to clarify the airway conditions. Protection should be worn during the process. Considering the risk of infection, it is not necessary to perform bronchoscopy in the mild to moderate COVID-19 patients.

Fast-Degrading Tissue-Engineered Vascular Grafts Lead to Increased Extracellular Matrix Cross-Linking Enzyme Expression.

Tissue-engineered vascular grafts (TEVGs) require adequate extracellular matrix (ECM) to withstand arterial pressure. Tissue transglutaminase (TG2) and lysyl oxidase (LOX) are enzymes that cross-link ECM proteins and play a pivotal role in the development of vascular stiffness associated with aging. The purpose of this study is to investigate the expression of ECM cross-linking enzymes and mechanisms of scaffold degeneration leading to vascular stiffness in TEVG remodeling. Fast- and slow-degrading electrospun TEVGs were fabricated using polydioxanone (PDO) and poly(L-lactide-co-caprolactone) (PLCL) copolymer, with a PDO/PLCL ratio of 9:1 for fast-degrading and 1:1 for slow-degrading graft. These grafts were implanted in rats (n = 5/group) as abdominal aortic interposition conduits. The grafts were harvested at 1 month to evaluate patency, mechanical properties, vascular neotissue formation, and the expression of ECM cross-linking enzymes. All TEVGs were patent without any aneurysmal formation at 1 month. ECM area, TG2-positive area, and LOX-positive area were significantly greater in fast-degrading TEVGs compared to slow-degrading TEVGs, with significantly less remaining scaffold. The mechanical properties of fast-degrading TEVGs were similar to that of native aorta, as demonstrated by strain-stress curve. In conclusion, at 1 month, fast-degrading TEVGs had rapid and well-organized ECM with greater TG2 and LOX expression and native-like mechanical properties, compared to slow-degrading TEVGs. Impact statement Around 1.4 million patients in the United States require arterial prostheses each year due to cardiovascular diseases. Current synthetic vascular grafts suffer from increased risk of infection, thrombosis, a lack of endothelialization, and compliance mismatch to the native vasculature. Tissue-engineered vascular graft (TEVGs) presented in this study exhibited tunable biodegradation profiles by controlling the polymer ratio of polydioxanone/poly(L-lactide-co-caprolactone). One month after implantation, the fast-degrading TEVGs exhibited mechanical properties similar to that of native aorta, formation of endothelium, and well-organized extracellular matrix (ECM) with increased expression of tissue transglutaminase and lysyl oxidases, which are critical to the ECM remodeling process.

Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol.

PURPOSE: Correctly identifying nodal status is recognized as a critical prognostic factor in many cancer types and is essential to guide adjuvant treatment. Currently, surgical removal of lymph nodes followed by pathological examination is commonly performed as a standard-of-care to detect node metastases. However, conventional pathology protocols are time-consuming, yet less than 1 % of lymph node volumes are examined, resulting in a 30-60 % rate of missed micrometastases (0.2-2 mm in size). PROCEDURES: This study presents a method to fluorescently stain excised lymph nodes using paired-agent molecular imaging principles, which entail co-administration of a molecular-targeted imaging agent with a suitable control (untargeted) agent, whereby any nonspecific retention of the targeted agent is accounted for by the signal from the control agent. Specifically, it was demonstrated that by dual-needle continuous infusion of either an antibody-based imaging agent pair (epidermal growth factor receptor (EGFR) targeted agent: IRDye-800CW labeled Cetuximab; control agent: IRDye-700DX-IgG) or an Affibody-based pair (EGFR targeted Affibody® agent: ABY-029; control agent IRDYe-700DX carboxylate) at 0.3 ml/min. RESULTS: The results demonstrated the possibility to achieve >99 % sensitivity and > 95 % specificity for detection of a single micrometastasis (~0.2 mm diameter) in a whole lymph node within 22 min of tissue processing time. CONCLUSION: The detection capabilities offer substantial improvements over existing intraoperative lymph node biopsy methods (e.g., frozen pathology has a micrometastasis sensitivity <20 %).

Cell-Laden Gradient Hydrogel Scaffolds for Neovascularization of Engineered Tissues.

Gradients in mechanical properties, physical architecture and biochemical composition exist in a variety of complex tissues, yet 3D in vitro models that enable investigation of these cues on cellular processes, especially those contributing to vascularization of engineered tissues are limited. Here, a photopolymerization approach to create cell-laden hydrogel biomaterials with decoupled and combined gradients in modulus, immobilized cell adhesive peptide (RGD) concentration, and proteolytic degradation enabling spatial encapsulation of vascular spheroids is reported to elucidate their impact on vascular sprouting in 3D culture. Vascular spheroids encapsulated in these gradient scaffolds exhibit spatial variations in total sprout length. Scaffolds presenting an immobilized RGD gradient promote biased vascular sprouting toward increasing RGD concentration. Importantly, biased sprouting is found to be dependent on immobilized RGD gradient characteristics, including magnitude and slope, with increases in these factors contributing to significant enhancements in biased sprouting responses. Conversely, reduction in biased sprouting responses is observed in combined gradient scaffolds possessing opposing gradients in RGD and modulus. The presented work is the first to demonstrate the use of a cell-laden biomaterial platform to systematically investigate the role of multiple scaffold gradients as well as gradient slope, magnitude and orientation on vascular sprouting responses in 3D culture.

Development of an immune-related prognostic index associated with osteosarcoma.

Tumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.

An in vitro tissue model for screening sustained release of phosphate-based therapeutic attenuation of pathogen-induced proteolytic matrix degradation.

Tissue response to intestinal injury or disease releases pro-inflammatory host stress signals triggering microbial shift to pathogenic phenotypes. One such phenotype is increased protease production resulting in collagen degradation and activation of host matrix metalloproteinases contributing to tissue breakdown. We have shown that surgical injury depletes local intestinal phosphate concentration triggering bacterial virulence and that polyphosphate replenishment attenuates virulence and collagenolytic activity. Mechanistic studies of bacterial and host protease expression contributing to tissue breakdown are difficult to achieve in vivo necessitating the development of novel in vitro tissue models. Common techniques for screening in vitro protease activity, including gelatin zymography or fluorogenic protease-sensitive substrate kits, do not readily translate to 3D matrix degradation. Here, we report the application of an in vitro assay in which collagenolytic pathogens are cultured in the presence of a proteolytically degradable poly(ethylene) glycol scaffold and a non-degradable phosphate and/or polyphosphate nanocomposite hydrogel matrix. This in vitro platform enables quantification of pathogen-induced matrix degradation and screening of sustained release of phosphate-based therapeutic efficacy in attenuating protease expression. To evaluate matrix degradation as a function of bacterial enzyme levels secreted, we also present a novel method to quantify hydrogel degradation. This method involves staining protease-sensitive hydrogels with Sirius red dye to correlate absorbance of the degraded gel solution with hydrogel weight. This assay enables continuous monitoring and greater accuracy of hydrogel degradation kinetics compared to gravimetric measurements. Combined, the proposed in vitro platform and the presented degradation assay provide a novel strategy for screening efficacy of therapeutics in attenuating bacterial protease-induced matrix degradation.

Immobilized RGD concentration and proteolytic degradation synergistically enhance vascular sprouting within hydrogel scaffolds of varying modulus.

Insufficient vascularization limits the volume and complexity of engineered tissue. The formation of new blood vessels (neovascularization) is regulated by a complex interplay of cellular interactions with biochemical and biophysical signals provided by the extracellular matrix (ECM) necessitating the development of biomaterial approaches that enable systematic modulation in matrix properties. To address this need poly(ethylene) glycol-based hydrogel scaffolds were engineered with a range of decoupled and combined variations in integrin-binding peptide (RGD) ligand concentration, elastic modulus and proteolytic degradation rate using free-radical polymerization chemistry. The modularity of this system enabled a full factorial experimental design to simultaneously investigate the individual and interaction effects of these matrix cues on vascular sprout formation in 3 D culture. Enhancements in scaffold proteolytic degradation rate promoted significant increases in vascular sprout length and junction number while increases in modulus significantly and negatively impacted vascular sprouting. We also observed that individual variations in immobilized RGD concentration did not significantly impact 3 D vascular sprouting. Our findings revealed a previously unidentified and optimized combination whereby increases in both immobilized RGD concentration and proteolytic degradation rate resulted in significant and synergistic enhancements in 3 D vascular spouting. The above-mentioned findings would have been challenging to uncover using one-factor-at-time experimental analyses.

Angular restriction fluorescence optical projection tomography to localize micrometastases in lymph nodes.

Lymph node biopsy is a primary means of staging breast cancer, yet standard pathological techniques are time-consuming and typically sample less than 1% of the total node volume. A low-cost fluorescence optical projection tomography (OPT) protocol is demonstrated for rapid imaging of whole lymph nodes in three dimensions. The relatively low scattering properties of lymph node tissue can be leveraged to significantly improve spatial resolution of lymph node OPT by employing angular restriction of photon detection. It is demonstrated through porcine lymph node metastases models that simple filtered-backprojection reconstruction is sufficient to detect and localize 200-µm-diameter metastases (the smallest clinically significant) in 1-cm-diameter lymph nodes.

Analysis of correlation between cerebral perfusion and KIM score of white matter lesions in patients with Alzheimer's disease.

PURPOSE: This study aimed to characterize white matter lesions (WMLs) and regional cerebral perfusion, and evaluate their correlations with cognitive deficits in Alzheimer's disease (AD) patients. PATIENT AND METHODS: One hundred and twenty-eight patients with AD (AD group) and 75 subjects without AD (control group) were recruited. The medical information was collected from each subject. Montreal cognitive assessment (MoCA) was employed for the assessment of cognition. Cranial MRI was performed, and the KIM scoring system was used to evaluate the white matter hyperintensity. The CT perfusion (CTP) imaging was employed to assess the whole cerebral perfusion, and the region of interest (ROI) was selected to determine the blood perfusion at different parts. RESULTS: The education level and MoCA score in AD group were significantly lower than in control group (P<0.001). The KIM score of juxtaventricular WML (JVWMLs) was significantly different between two groups (P<0.05) and AD group showed a higher incidence of severe JVWML and periventricular WML (PVWMLs); in AD group, the total KIM score and KIM scores of JVWMLs, PVWMLs and deep WML (DWMLs) showed negative relationships with the MoCA score (P<0.001). As compared to control group, the blood perfusion of either whole brain or different parts in the AD group reduced significantly (P<0.05). In the AD group, there was a negative correlations of blood perfusion at JVWM and PVWM with corresponding KIM scores (P<0.05 or 0.01). In the AD group, the blood perfusions of the whole brain, JVWMLs, PVWMLs and deep WML were negatively related to MoCA score (P<0.05). CONCLUSION: In conclusion, the cognitive deficits in the AD patients are associated with the degree of WMLs, especially the JVWML, PVWML and DWML as well as with the reduced perfusion of JVWM, PVWM and deep WM.

A fluorometric aptasensor for bisphenol a based on the inner filter effect of gold nanoparticles on the fluorescence of nitrogen-doped carbon dots.

An aptamer-based fluorometric assay is described for the determination of bisphenol A (BPA). The aptamer against BPA is first attached to the surface of the red AuNPs, and this prevents the AuNPs from salt-induced formation of a blue-colored aggregate. Hence, the blue fluorescence of added nitrogen-doped carbon dots (NCDots) is quenched via an inner filter effect (IFE) caused by the red AuNPs. After addition of BPA, the BPA/aptamer complex is formed, and the AuNPs are no longer stabilized agains aggregation. This weakens the IFE and results in the recovery of the fluorescence of the NCDots which is measured best at excitation/emission wavelengths of 300/420 nm. The recovered fluorescence increases linearly in the 10 to 250 nM and 250 to 900 nM BPA concentration ranges, and the detection limit is 3.3 nM. The method was successfully applied to the determination of BPA in spiked environmental tap water samples. Graphical abstract Schematic presentation of a fluorometric aptamer based assay for bisphenol A (BPA). It is based on the inner filter effect of gold nanoparticles (AuNPs) on the fluorescence of nitrogen-doped carbon dots (NCDots).

Aptamer based electrochemiluminescent determination of bisphenol A by using carboxylated graphitic carbon nitride.

An electrochemiluminescence (ECL) based assay is described for the determination of the endocrine disruptor bisphenol A (BPA). The method is based on the use of carboxylated graphitic carbon nitride (C-g-C3N4) carrying an immobilized aptamer against BPA. In the presence of BPA, the ECL signal decreases due to ECL energy transfer from excited-state C-g-C3N4 to the BPA oxidation product. Under the optimal conditions, ECL intensity increases linearly in the 0.1 pM to 1 nM BPA concentration range. The detection limit is as low as 30 fM. The assay has excellent sensitivity, outstanding stability and high selectivity. It was applied to the determination of BPA in spiked water samples. Graphical abstract Aptamer modified carboxylated graphitic carbon nitride was synthesized and applied in an electrochemiluminescence-based aptasensor for bisphenol A.