55 research outputs found

    Label-Free Spectral Imaging Unveils Biochemical Mechanisms of Low-Level Laser Therapy on Spinal Cord Injury

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    Background/Aims: Low-level laser therapy (LLLT) leads to complex photochemical responses during the healing process of spinal cord injury (SCI). Confocal Raman Microspectral Imaging (in combination with multivariate analysis) was adopted to illustrate the underlying biochemical mechanisms of LLLT treatment on a SCI rat model. Methods: Using transversal tissue sections, the Raman spectra can identify areas neighboring the injury site, glial scar, cavity, and unharmed white matter, as well as their correlated cellular alterations, such as demyelination and up-regulation of chondroitin sulfate proteoglycans (CSPGs). Multivariate data analysis methods are used to depict the underlying therapeutic effects by highlighting the detailed content and distribution variations of the biochemical constituents. Results: It is confirmed that photon-tissue interactions might lead to a decay of the inhibitory response to remyelination by suppressing CSPG expression, as also morphologically demonstrated by reduced glial scar and cavity areas. An inter-group comparison semi-quantitatively confirms changes in lipids, phosphatidic acid, CSPGs, and cholesterol during SCI and its LLLT treatment, paving the way for in vitro and in vivo understanding of the biochemical changes accompanying pathobiological SCI events. Conclusion: The achieved results in this work not only have once again proved the well-known cellular mechanisms of SCI, but further illustrate the underlying biochemical variability during LLLT treatment, which provide a sound basis for developing real-time Raman methodologies to monitor the efficacy of the SCI LLLT treatment

    A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575)

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    PURPOSE: To establish the recommended phase II dose of the oral Ξ³-secretase inhibitor RO4929097 (RO) in combination with gemcitabine; secondary objectives include the evaluation of safety, tolerability, pharmacokinetics, biomarkers of Notch signaling and preliminary anti-tumor activity. METHODS: Patients with advanced solid tumors were enrolled in cohorts of escalating RO dose levels (DLs). Tested RO DLs were 20 mg, 30 mg, 45 mg and 90 mg. RO was administered orally, once daily on days 1-3, 8-10, 15-17, 22-24. Gemcitabine was administered at 1,000 mg/m(2) on d1, 8, and 15 in 28 d cycles. Dose limiting toxicities (DLTs) were assessed by CTCAE v4. Serial plasma was collected for RO (total and unbound) and gemcitabine pharmacokinetic analysis. Biomarkers of Notch signaling were assessed by immunohistochemistry in archival tissue. Antitumor activity was evaluated (RECIST 1.1). RESULTS: A total of 18 patients were enrolled to establish the recommended phase II dose. Of these, 3 patients received 20 mg RO, 7 patients received 30 mg RO, 6 patients received 45 mg RO and 2 patients received 90 mg RO. DLTs were grade 3 transaminitis (30 mg RO), grade 3 transaminitis and maculopapular rash (45 mg RO), and grade 3 transaminitis and failure to receive 75 % of planned RO doses secondary to prolonged neutropenia (90 mg); all were reversible. The maximum tolerated dose was exceeded at 90 mg RO. Pharmacokinetic analysis of both total and free RO confirmed the presence of autoinduction at 45 and 90 mg. Median levels of Notch3 staining were higher in individuals who received fewer than 4 cycles (p = 0.029). Circulating angiogenic factor levels did not correlate with time to progression or β‰₯ grade 3 adverse events. Best response (RECIST 1.1) was partial response (nasopharyngeal cancer) and stable disease > 4 months was observed in 3 patients (pancreas, tracheal, and breast primary cancers). CONCLUSIONS: RO and gemcitabine can be safely combined. The recommended phase II dose of RO was 30 mg in combination with gemcitabine 1,000 mg/m(2). Although RO exposure was limited by the presence of autoinduction, RO levels achieved exceeded the area under the concentration-time curve for 0-24 h (AUC(0-24)) predicted for efficacy in preclinical models using daily dosing. Evidence of clinical antitumor activity and prolonged stable disease were identified

    An evaluation method of supercritical CO2 thickening result for particle transporting

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    This paper aims to propose an evaluation method for measuring the supercritical CO2 thickening result for particle transporting. By analyzing the particle transporting trajectory in supercritical CO2, the cotangent of particle landing angle (ratio of particle horizontal velocity to vertical velocity) was proposed as a new criterion of thickening result. Previous studies of supercritical CO2 thickening were evaluated and drawn in three dimensions using this new criterion. Moreover, the effects of CO2 density and viscosity on particle vertical and horizontal velocities and the cotangent of particle landing angle were analyzed. The cotangent of particle landing angle is more sensitive to supercritical CO2 density than viscosity. Therefore, supercritical CO2 density should be considered for the evaluation of supercritical CO2 thickening for particle transporting. The particle settling velocity was found to determine the particle transporting distance and also the transporting capability of supercritical CO2. According to this conclusion, the apparatus for experimental evaluation of supercritical CO2 thickening will be miniaturized significantly by the simplification from two-dimensional velocities measurement into one direction, particle settling velocity in vertical direction. Additionally, the supercritical CO2 viscosity was found to have an optimum value, exceeding which the effect of viscosity on particle transporting levels off

    An Improved Sparrow Search Algorithm for Global Optimization with Customization-Based Mechanism

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    To solve the problems of the original sparrow search algorithm’s poor ability to jump out of local extremes and its insufficient ability to achieve global optimization, this paper simulates the different learning forms of students in each ranking segment in the class and proposes a customized learning method (CLSSA) based on multi-role thinking. Firstly, cube chaos mapping is introduced in the initialization stage to increase the inherent randomness and rationality of the distribution. Then, an improved spiral predation mechanism is proposed for acquiring better exploitation. Moreover, a customized learning strategy is designed after the follower phase to balance exploration and exploitation. A boundary processing mechanism based on the full utilization of important location information is used to improve the rationality of boundary processing. The CLSSA is tested on 21 benchmark optimization problems, and its robustness is verified on 12 high-dimensional functions. In addition, comprehensive search capability is further proven on the CEC2017 test functions, and an intuitive ranking is given by Friedman's statistical results. Finally, three benchmark engineering optimization problems are utilized to verify the effectiveness of the CLSSA in solving practical problems. The comparative analysis shows that the CLSSA can significantly improve the quality of the solution and can be considered an excellent SSA variant

    Construction and validation of acuproptosis-related prognostic model in neuroblastoma based on TARGET, ArrayExpress and GEO databases

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    Objective To construct a prognostic model for neuroblastoma (NB) based on cuproptosis-related genes (CRGs) and improve individualized management of neuroblastoma patients. Methods CRGs expression data with complete clinical information were collected from publicly available databases. A total of 3 independent datasets were obtained, including the GSE49711 cohort from Gene Expression Omnibus (GEO) database, the TARGET-NB cohort from Therapeutically Applicable Research to Generate Effective Treatments(TARGET) database, and the E-MTAB-8248 cohort from ArrayExpress database. 968 patients were finally included for follow-up data analysis after excluding patients with incomplete follow-up information. The GSE49711 cohort was selected as the training set to construct the prognositic model, and the other two data sets were used as the validation set to verify the accuracy. Log-rank tests were used to screen prognostically significant variables, and the best multi-gene prognostic model was contructed using LASSO-Cox regression. ROC curves, column plots, calibration curves, and DCA curves were used to assess the accuracy of the prognostic models. RT-qPCR was used to validate the expression levels of risk genes in NB cell lines, and the key risk gene PDHA1 was selected for functional analysis. Results A prognostic model was first constructed in the training cohort with a risk score formula of (1.573)Γ—PDHA1+(-0.561)Γ—GLS+(0.320)Γ—LIAS+(0.088)Γ—MTF1+(0.301)Γ—PDHB. According to the risk scores calculated based on the formula, patients were classified into the high- and low-risk subgroups based on the median values. Survival analysis showed that NB patients in the high-risk subgroup had a significantly lower survival rate than that in the low-risk subgroup (P < 0.001). The time-dependent ROC curve predicted the area under curve (AUC) of 3-year, 5-year and 7-year survival rate was 0.80, 0.80, and 0.81, respectively. Survival analysis showed that in the TARGET-NB and E-MTAB-8248 cohorts, the high-risk subgroup was associated with a worse prognosis compared with the low-risk subgroup(P=0.011, P=0.008 7). The calibration curve and DCA curve (C-index: 0.736) of nomagram showed the good clinical value of nomagram. The expression levels of genes in the risk model and the function of the key gene PDHA1 were verified by RT-qPCR and loss-of-function experiments. Conclusion A prognostic model to predict the survival rate of patients with neuroblastoma is constructed based on cuproptosis-related genes and validated in two external datasets

    Effects of the Strain Rate Sensitivity and Strain Hardening on the Saturated Impulse of Plates

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    Abstract This paper studies the stiffening effects of the material strain rate sensitivity and strain hardening on the saturated impulse of elastic, perfectly plastic plates. Finite element (FE) code ABAQUS is employed to simulate the elastoplastic response of square plates under rectangular pressure pulse. Rigid-plastic analyses for saturated impulse, which consider strain rate sensitivity and strain hardening, are conducted. Satisfactory agreement between the finite element models (FEM) and predictions of the rigid-plastic analysis is obtained, which verifies that the proposed rigid-plastic methods are effective to solve the problem including strain rate sensitivity and strain hardening. The quantitative results for the scale effect of the strain rate sensitivity are given. The results for the stiffening effects suggest that two general stiffening factors n 1 and n 2, which characterizes the strain rate sensitivity and strain hardening effect, respectively can be defined. The saturated displacement is inversely proportional to the stiffening factors (i.e. n 1 and n 2) and saturated impulse is inversely proportional to the square roots of the stiffening factors (i.e. n 1 and n 2). Formulae for displacement and saturated impulse are proposed based on the empirical analysis

    A pathway study of factors influencing quality of fertility life

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    Abstract Backgroud To investigate the factors influencing fertility quality of life in infertile men, constructing a structural equation model of the factors influencing fertility quality of life in infertile men, and to provide suggested measures for improving fertility quality of life in infertile men. Methods It is a Observational study. Infertile men (n = 250) attending a fertility centre in a hospital in Xinjiang, matched 1:2 men with no obvious male factor in the control group (n = 500).The Quality of Fertility Life Scale, the Social Support Scale, the Fertility Stress Scale and the Positive Attention Awareness Scale were used to conduct the survey. The model was constructed by applying the maximum likelihood estimation method in Mplus 8.3 software, to explore the factors influencing the quality of reproductive life of infertile men through path analyses. Differences between the case and control groups were statistically significant (P < 0.05) in terms of total fertility quality of life scores, core entry dimensions, affective responses, physical and mental relationships, selective treatment dimensions, and treatment tolerance. Results Past medical history, history of exposure to hazardous environments, health insurance reimbursement, social support, fertility stress, and mindfulness are important factors affecting the quality of fertility life of infertile men. Conclusion The quality of fertility life of infertile men is not optimistic. By improving the level of mindfulness, fertility stress, and social support, we propose appropriate measures to improve the quality of fertility life of infertile men. These measures can improve their confidence in clinical diagnosis and infertility treatment, enabling them to cope positively with these challenges
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