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Summary Aims The objective of this study was to analyze the efficacy of polypyrrole/polylactic acid (PPy/PLA) nanofibrous scaffold cotransplanted with bone marrow stromal cells (BMSCs) in promoting the functional recovery in a rat spinal cord injury (SCI). Methods Female Sprague‐Dawley rats were randomly divided into three groups (n = 18/group): control group, PPy/PLA group, and PPy/PLA/BMSCs group. The SCI was induced in all rats. Consequently, rats in PPy/PLA/BMSCs group were transplanted with 1 × 105 BMSCs after implantation of PPy/PLA, while those in the PPy/PLA group were implanted with PPy/PLA only; no implantation was performed in the control group. Six weeks after surgery, immunofluorescence microscopy, electron microscope, and polymerase chain reaction (PCR) techniques were performed to assess the changes in the injured spinal cord tissues. Results Electrophysiology and locomotor function testing suggested that PPy/PLA nanofibrous scaffold cotransplanted with BMSCs could promote the functional recovery of the spinal cord. Six weeks after the operation, lower amount of scar tissue was found in the PPy/PLA group compared with the control group. Abundant neurofilament (NF) and neuron‐specific marker (NeuN) positive staining, and myelin formations were detected in the injured area. In addition, the transplantation of BMSCs not only improved the efficacy of PPy/PLA but also managed to survive well and was differentiated into neural and neuroglial cells. Conclusions The implantation of PPy/PLA nanofibrous scaffold and BMSCs has a great potential to restore the electrical conduction and to promote functional recovery by inhibiting the scar tissue formation, promoting axon regeneration, and bridging the gap lesion.

Polypyrrole (PPy) is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly(lactic acid) (PLA) nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topography. There was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration.

Patients with non-small cell lung cancer (NSCLC) who develop brain metastases (BM) have a poor prognosis. This study aimed to construct a clinical prediction model to determine the overall survival (OS) of NSCLC patients with BM. A total of 300 NSCLC patients with BM at the Yunnan Cancer Centre were retrospectively analysed. The prediction model was constructed using the least absolute shrinkage and selection operator-Cox regression. The bootstrap sampling method was employed for internal validation. The performance of our prediction model was compared using recursive partitioning analysis (RPA), graded prognostic assessment (GPA), the update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA), the basic score for BM (BSBM), and tumour-lymph node-metastasis (TNM) staging. The prediction models comprising 15 predictors were constructed. The area under the curve (AUC) values for the 1-year, 3-year, and 5-year time-dependent receiver operating characteristic (curves) were 0.746 (0.678-0.814), 0.819 (0.761-0.877), and 0.865 (0.774-0.957), respectively. The bootstrap-corrected AUC values and Brier scores for the prediction model were 0.811 (0.638-0.950) and 0.123 (0.066-0.188), respectively. The time-dependent C-index indicated that our model exhibited significantly greater discrimination compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging. Similarly, the decision curve analysis demonstrated that our model displayed the widest range of thresholds and yielded the highest net benefit. Furthermore, the net reclassification improvement and integrated discrimination improvement analyses confirmed the enhanced predictive power of our prediction model. Finally, the risk subgroups identified by our prognostic model exhibited superior differentiation of patients' OS. The clinical prediction model constructed by us shows promise in predicting OS for NSCLC patients with BM. Its predictability is superior compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging.

Backgroud It is important to expound the opposite clinical outcomes between children and adulthood for eradicate malaria. There remains unknown about the correlation between adaptive immune response and age-related in malaria. Methods 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. Results The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4 + T-bet + IFN-γ + Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4 + GATA3 + IL-4 + Th2 cells and CD4 + CXCR5 + Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4 + or activated CD4 + T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusions Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4 + T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

Edge detection is essential to comprehend and analyze high-resolution remote sensing images. The Gaussian filter is widely used for image preprocessing prior to edge detection. However, some weak edge points in the images with low gradient values are more likely to be missed during edge detection following Gaussian filtering. Moreover, balancing the demands of denoising and sharpening edges is challenging in the Gaussian filter. An edge detection algorithm based on the adaptive multi-directional anisotropic Gaussian filter (AMDAGF) is proposed in this article to address these issues. Meanwhile, this article proposes an effective solution for the adaptive setting of the key parameters of the proposed algorithm, which provides assistance for the application and promotion of the proposed algorithm. Finally, by using ROC curve analysis technology, comparative edge detection experiments about two experimental areas were performed, and the superiority and viability of the proposed algorithm have been demonstrated.

Purpose To investigate the risk factors of second primary malignant tumor (SPMT) in patients with differentiated thyroid cancer (DTC) and establish a competing risk nomogram to predict the probability of SPMT occurrence. Methods We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with DTC between 2000 and 2019. The Fine and Gray subdistribution hazard model was employed to identify SPMT risk factors in the training set and develop a competing risk nomogram. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results A total of 112,257 eligible patients were included in the study and randomized into a training set ( n  = 112,256) and a validation set ( n  = 33,678). The cumulative incidence rate of SPMT was 15% ( n  = 9528). Age, sex, race, tumor multifocality, and TNM stage were independent risk factors of SPMT. The calibration plots showed good agreement between the predicted and observed SPMT risks. The 10-year AUCs of the calibration plots were 70.2 (68.7–71.6) in the training set and 70.2 (68.7–71.5) in the validation set. Moreover, DCA showed that our proposed model resulted in higher net benefits within a defined range of risk thresholds. The cumulative incidence rate of SPMT differed among risk groups, classified according to nomogram risk scores. Conclusion The competing risk nomogram developed in this study exhibits high performance in predicting the occurrence of SPMT in patients with DTC. These findings may help clinicians identify patients at distinct levels of risk of SPMT and develop corresponding clinical management strategies.

The frequency and extent of debris flows have increased tremendously due to the extreme weather and the Wenchuan earthquake on May 12, 2008. Previous studies focused on the debris flow from gullies damming the mountain streams. In this paper, an equation for the run-out distance of debris flow in the main river is proposed based on the dynamic equation of debris flow at different slopes given by Takahashi. By undertaking field investigations and flume experiments, a new calculation method of the volume of debris flow damming large river is obtained. Using the percolation theory and the renormalization group theory it was deduced that the large particles should comprise more than 50% for forming a stable debris flow dam. Hence, the criteria of damming large river by debris flow is presented in terms of run-out distance and grain composition which was then validated through the event of damming river by debris flow at Gaojia gully, the upper reaches of the Minjiang River, Sichuan, China, on July 3, 2011.

Rib segment, as one of the most widely used autologous boneresources for bone repair, is commonly isolated with an empty left in the defect. Although defective rib repair is thought to be unnecessary traditionally, it’s of vital importance actually to promote rib regeneration for patients with better postoperative recovery and higher life quality. Comparative investigations on rabbit rib bone regeneration with and without graft were reported in this article. A segmental defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The mineralized collagen bone graft (MC) was implanted into the defect and evaluated for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8 and 12 weeks and histological examinations at 12 weeks after surgery, which showed a higher bone remodeling activity in the groups with MC implantation in comparison with blank control group, especially at the early stage of remodeling.

Background：Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells （RGCs）.High intraocular pressure （HIOP）,the main risk factor,causes the optic nerve damage.However,the precise mechanism of HIOP-induced RGC death is not yet completely understood.This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures,explore whether laminin is associated with apoptosis under pressure,whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.Methods：RGC-5 cells were exposed to 0,20,40,and 60 mmHg in a pressurized incubator for 6,12,and 24 h,respectively.The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining,3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay,and Western blotting of cleaved caspase-3 protein.Location and expression oflaminin were detected by immunofluorescence.The expression of β 1-integrin,phosphorylation of focal adhesion kinase （FAK） and protein kinase B （PKB,or AKT） were investigated with real-time polymerase chain reaction and Western blotting analysis.Results：Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells.Pressure with 40 mmHg for 24 h induced a maximum apoptosis.Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h.After pretreating with laminin,RGC-5 cells survived from elevated pressure.Furthermore,β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.Conclusions：The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure.Laminin can protect RGC-5 cells against high pressure via β 1-integrin/FAK/AKT signaling pathway.These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure,and laminin or activating β1-integrin/FAK/AKT pathway might be potential treatments to prevent RGC loss in glaucomatous optic neuropathy.

Alzheimer＇s disease （AD） is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress （OS） and tauopathy is believed to be one of the major players in AD development. Here, we demonstrated the capability of the small molecule N-（1,3-benzodioxol-5-yl）-2-[5-chloro-2- methoxy（phenylsulfonyl）anilino]acetamide （LX2343） to ameliorate the cognitive dysfunction of AD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin （STZ） was used to induce OS in neuronal cells in vitro and in AD model rats that were made by intracerebroventricular injection of STZ （3 mg/kg, bilaterally）, and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 （5-20 pmol/L） significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase ATP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3β inhibitor with ICso of 1.84＋0.07 pmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 （7, 21 mg·kg^-1·d^-1, ip, for 5 weeks） efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of AD.