SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway.

SLFN11 is abnormally expressed and associated with survival outcomes in various human cancers. However, the role of SLFN11 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the clinical value and potential functions of SLFN11 in ccRCC. Comprehensive bioinformatics analyses were performed using online databases. Quantitative real-time PCR (qPCR) and western blotting were used to validate the expression data. CCK8, flow cytometry analysis, and EdU staining were performed to determine the level of cell proliferation. Flow cytometry analysis was also used to detect cell apoptosis. Wound-healing assay and Transwell assays were performed to assess cell migration and invasion capability, respectively. SLFN11 was overexpressed and was an independent prognostic factor in ccRCC. SLFN11 knockdown inhibited cell proliferation, migration, and invasion and promoted apoptosis. Functional and pathway enrichment analyses suggested that SLFN11 may have an impact on tumorigenesis in ccRCC through regulation of the inflammatory response, the PI3K/AKT signaling pathway and other effectors. Furthermore, SLFN11 knockdown inhibited the phosphorylation of the PI3K/AKT signaling pathway and could be activated by 740 Y-P. Finally, we demonstrated that miR-183 may specifically target SLFN11, and miR-183 expression was correlated with predicted survival. SLFN11 may play a critical role in ccRCC progression and may serve as a novel prognostic biomarker in ccRCC.

Approach to evaluate the sensory quality deterioration of chicken seasoning using characteristic oxidation indicators.

Sensory quality deterioration of chicken seasoning was investigated using physicochemical properties, gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis to approach an evaluation of the chicken seasoning deterioration. It was found that both peroxide value (POV) and total oxidation value (TOTOX) increased with the chicken seasoning deterioration, suggesting a dominant of the lipid oxidation in the sensory quality deterioration of chicken seasoning. Moreover, a continuously decreasing linoleic acid and contradictory increasing in volatile aldehydes (specifically for hexanal) indicated as characteristic oxidation indicators to evaluate the sensory quality deterioration. PLSR results further elucidated that the evolution of aldehydes was highly correlated with sensory quality deterioration. These results suggest the POV, TOTOX and hexanal as valuable indicators and provide a novel approach to quality and rapidly evaluate the sensory quality deterioration of chicken seasoning.

Multifunctional luminescent Zr(IV)-MOF for rapid and efficient detection of vanillin, CrO42- and Cr2O72- ions.

Fast and efficient detection of pollutants in the food or wastewater is an urgent need for protecting human health and ecological environment. Herein, a luminescent Zr(IV)-MOF (HBU-20) has been conveniently synthesized. It could be used as a fluorescent probe for detection of vanillin, CrO42-, and Cr2O72- in aqueous medium. All the fluorescence response time is less than 10 s and the detection limits of vanillin, CrO42- and Cr2O72- achieve 0.38 µM, 0.065 µM and 0.0089 µM, respectively. Interestingly, common anions, cations and amino acids in the solution can not affect the fluorescence detection. Meanwhile, the fluorescence detection process can be successfully implemented even under strong acid or strong alkaline conditions. Further research shows that the inner filter effect (IFE) plays a major role in the sensing process. The rapid and sensitive fluorescence responses indicate that the compound is a promising multifunctional probe for sensing toxic substance. The results can provide an important reference for the design of new fluorescent probes.

Electro-acupuncture and its combination with adult stem cell transplantation for spinal cord injury treatment: A summary of current laboratory findings and a review of literature.

The incidence and disability rate of spinal cord injury (SCI) worldwide are high, imposing a heavy burden on patients. Considerable research efforts have been directed toward identifying new strategies to effectively treat SCI. Governor Vessel electro-acupuncture (GV-EA), used in traditional Chinese medicine, combines acupuncture with modern electrical stimulation. It has been shown to improve the microenvironment of injured spinal cord (SC) by increasing levels of endogenous neurotrophic factors and reducing inflammation, thereby protecting injured neurons and promoting myelination. In addition, axons extending from transplanted stem cell-derived neurons can potentially bridge the two severed ends of tissues in a transected SC to rebuild neuronal circuits and restore motor and sensory functions. However, every single treatment approach to severe SCI has proven unsatisfactory. Combining different treatments-for example, electro-acupuncture (EA) with adult stem cell transplantation-appears to be a more promising strategy. In this review, we have summarized the recent progress over the past two decades by our team especially in the use of GV-EA for the repair of SCI. By this strategy, we have shown that EA can stimulate the nerve endings of the meningeal branch. This would elicit the dorsal root ganglion neurons to secrete excess amounts of calcitonin gene-related peptide centrally in the SC. The neuropeptide then activates the local cells to secrete neurotrophin-3 (NT-3), which mediates the survival and differentiation of donor stem cells overexpressing the NT-3 receptor, at the injury/graft site of the SC. Increased local production of NT-3 facilitates reconstruction of host neural tissue such as nerve fiber regeneration and myelination. All this events in sequence would ultimately strengthen the cortical motor-evoked potentials and restore the motor function of paralyzed limbs. The information presented herein provides a basis for future studies on the clinical application of GV-EA and adult stem cell transplantation for the treatment of SCI.

Electroacupuncture facilitates the integration of a grafted TrkC-modified mesenchymal stem cell-derived neural network into transected spinal cord in rats via increasing neurotrophin-3.

AIMS: This study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin-3 (NT-3) from injured spinal cord tissue, and, if so, whether the increased NT-3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)-modified mesenchymal stem cell (MSC)-derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord. METHODS: After NT-3-modified Schwann cells (SCs) and TrkC-modified MSCs were co-cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron-like cells that formed a MSC-derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks. RESULTS: Electroacupuncture application enhanced the production of endogenous NT-3 in damaged spinal cord tissues. The increase in local NT-3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT-3 high-affinity TrkC. The combination of MN implantation and EA application improved cortical motor-evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment. CONCLUSIONS: Electroacupuncture as an adjuvant therapy for TrkC-modified MSC-derived MN, acted by increasing the local production of NT-3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI.

4-Hydroxyphenyl Retinamide Preferentially Targets FLT3 Mutated Acute Myeloid Leukemia via ROS Induction and NF-κB Inhibition.

FMS-like tyrosine kinase 3 (FLT3) mutation is strongly associated with poor prognosis in acute myeloid leukemia (AML). Though many FLT3 inhibitors have been developed for clinical application with 34%-56% complete remission rate, patients would develop resistance sooner or later after initial response to tyrosine kinase inhibitors (TKIs), such as gilteritinib. And increasing studies have shown that several resistance related mutations of FLT3 emerged during the AML progression. Thus, further investigation is warranted for these FLT3mut AML patients to achieve a better treatment outcome. 4-Hydroxyphenyl retinamide (4-HPR) has been investigated extensively in animal models and clinical trials as an anticancer/chemopreventive agent and is currently used for protection against cancer development/recurrence, with minimal side effects. In this study, we performed gene-set enrichment analysis and found that down-regulated genes induced by 4-HPR were associated with FLT3-ITD gene sets. CD34+ AML stem/progenitor cells separated from 32 AML samples were treated with 4-HPR. Correlation analysis showed that AML cells with FLT3-ITD genetic alteration were more sensitive to 4-HPR treatment than those without FLT3-ITD. Next, we treated 22 primary AML cells with 4-HPR and found that 4-HPR was more toxic to AML cells with FLT3-ITD. These results indicated that 4-HPR was preferentially cytotoxic to all FLT3-ITD AML+ cells irrespective of stem/progenitor cells or blast cells. 4-HPR-induced reactive oxygen species (ROS) production and NF-κB inhibition might be the reason of 4-HPR selectivity on FLT3 mutated AML cells.

Decellularization optimizes the inhibitory microenvironment of the optic nerve to support neurite growth.

Allogeneic or homologous tissue transplantation is an effective strategy to repair tissue injury. However, the central nervous tissues like the brain, spinal cord, and optic nerve are not ideal materials for nervous tissue regeneration due to the excessive axonal inhibitor cues in their microenvironments. In the present study, we found that decellularization optimizes the function of the adult optic nerve in supporting the oriented outgrowth of dorsal root ganglion (DRG) neurites. The neurites growing on the decellularized optic nerve (DON) showed longer extension distances than those growing on the normal optic nerve (ON). Neurite branching was also significantly increased on the DON compared to on the ON. Decellularization selectively removed some axon-inhibitory molecules such as myelin-associated glycoprotein (basically not detected in DON) and chondroitin sulfate proteoglycans (detected in DON at a level less than 0.3 fold that in ON) and preserved some axon-promoted extracellular matrix (ECM) proteins, including collagen IV and laminin (detected at levels 6.0-fold higher in DON than in ON). Furthermore, collagen IV and laminin were shown to be preserved in DON, and their binding activities with integrin α1 were retained to promote the extension of DRG neurites. Together, the findings provide a feasible way to optimize the axon-inhibited microenvironment of central nervous tissues and establish a theoretical basis for the application of DON scaffolds in repairing central nervous injury.

A scoring system based on clinical features for the prediction of sporadic renal angiomyolipoma rupture and hemorrhage.

The purpose of this study is to analyze the risk factors of sporadic renal hamartoma and establish a risk scoring system, and to intervene in patients with high-risk sporadic renal hamartoma who are prone to rupture and bleeding as soon as possible.Retrospective univariate and multivariate logistic analyzes were conducted for clinical data of 332 sporadic renal hamartoma patients to screen out independent risk factors of tumor rupture. Score of each independent risk factor was calculated. (Calculation formula: the risk coefficient of each factor = the beta regression coefficient of each factor/the minimum value of the beta regression coefficient of all factors, the value of the smallest beta regression coefficient corresponding to all the factors was assigned 1 point. The score of each factor was equal to the risk coefficient of each variable was taken as an integer value by rounding.) The total score was equal to the sum of all factors. Then the area under the receiver operating characteristics (AUC) curve was compared between high risk factors and scoring system. Finally, the scoring system was evaluated by the area under the curve (AUC) and the Hosmer-Lemeshow method in an independent cohort of 130 patients.Factors such as symptoms at presentation, tumor size, tumor blood supply, and tumor growth pattern were significant predictors of sporadic renal angiomyolipoma rupture in both the univariate and multivariate analyses; these predictors were included in the scoring system to predict sporadic renal angiomyolipoma rupture. There were no significant differences in AUCs between high risk factors and scoring system (z = 0.6434, P = .583, AUC = 0.913, and 0.903 for high risk factors and scoring system, respectively). The sporadic renal angiomyolipoma patients who scored >6 points were prone to rupture. AUROC of the scoring system in the validation set was 0.854(95%CI:0.779, 0.928). Using the Hosmer-Lemeshow method, the value of X was 2.916, P = .893, suggesting the scoring system fitted well.A scoring system based on clinical features is simple and effective in predicting sporadic angiolipoma rupture and hemorrhage. When the score is higher than 6 points, the probability of hamartoma rupture and hemorrhage is significantly increased and early intervention is needed.

CD8+ T cells stimulated by exosomes derived from RenCa cells mediate specific immune responses through the FasL/Fas signaling pathway and, combined with GM­CSF and IL­12, enhance the anti­renal cortical adenocarcinoma effect.

A satisfactory cure rate for renal cell carcinoma (RCC) is difficult to achieve through traditional immunotherapy. RCC has a relatively high spontaneous regression rate due to tumor immune escape. However, tumor­derived exosomes (TEXs), which effectively carry tumor­associated antigens (TAAs) and trigger stronger antigen­specific tumor immunity against autologous tumors than against other tumors, have been widely viewed as attractive potential vaccines for tumor treatment, although improvements are needed. Therefore, in our study, we determined whether RenCa cell­derived exosome (RDE)­stimulated CD8+ T cells exert a stronger specific cytotoxic effect on autologous tumor cells than on other types of tumor cells through the Fas ligand (FasL)/Fas signaling pathway, and whether the combination of RDE­stimulated CD8+ T cells with GM­CSF and IL­12 enhances the anticancer effect. The results showed that RDEs were isolated, as expected, and promoted an increased percentage of CD8+/CD4+ T cells. RDE­stimulated CD8+ T cells also more effectively facilitated cytotoxicity against RenCa cells when combined with GM­CSF and IL­12 in vitro. Furthermore, immunization with RDEs restrained the growth of RenCa tumors in mouse models, and facilitated the stimulation of a stronger specific cytotoxic CD8+ T cell response via the FasL/Fas signaling pathway in vitro. However, these results were observed less frequently for other types of tumor cells after treatment with RDEs, suggesting that RDEs depend on their antigen specificity to trigger antitumor immune responses. These findings revealed that RDE­stimulated CD8+ T cells combined with GM­CSF and IL­12 can more effectively exert a stronger cytotoxic effect than RDEs alone and that RDEs can induce immunization more effectively against renal cortical adenocarcinoma than against other types of cancer. Therefore, according to our study, exosomes are promising potential vaccines, and the combination of exosome­stimulated CD8+ T cells with GM­CSF and IL­12 may be a novel strategy for the treatment of RCC.

Electroacupuncture Facilitates the Integration of Neural Stem Cell-Derived Neural Network with Transected Rat Spinal Cord.

The hostile environment of an injured spinal cord makes it challenging to achieve higher viability in a grafted tissue-engineered neural network used to reconstruct the spinal cord circuit. Here, we investigate whether cell survival and synaptic transmission within an NT-3 and TRKC gene-overexpressing neural stem cell-derived neural network scaffold (NN) transplanted into transected spinal cord could be promoted by electroacupuncture (EA) through improving the microenvironment. Our results showed that EA facilitated the cell survival, neuronal differentiation, and synapse formation of a transplanted NN. Pseudorabies virus tracing demonstrated that EA strengthened synaptic integration of the transplanted NN with the host neural circuit. The combination therapy also promoted axonal regeneration, spinal conductivity, and functional recovery. The findings highlight EA as a potential and safe supplementary therapeutic strategy to reinforce the survival and synaptogenesis of a transplanted NN as a neuronal relay to bridge the two severed ends of an injured spinal cord.

[Design and implementation of a long wavelength near infrared spectrometer based on MEMS scanning mirror].

Long Wavelength Near InfraRed (LW-NIR) spectrometer has wide applications. Miniaturization and low-cost are two major goals of the development of LW-NIR spectrometer in the industrial or research community. Under the background that having a trend of spectrometer miniaturization and integration, method and main problems involved in miniaturization of LW-NIR spectrometer through MEMS scanning mirror, such as the design strategy of the light-splitting optical system, selection considerations of the MEMS scanning mirror, design method of the preamplifier circuit, etc, have been presented in detail. A prototype of miniaturized LW-NIR spectrometer, with the spectrum range of detection of 900-2,055 nm, is designed and implemented using MEMS scanning mirror, InGaAs single detector unit with high sensitivity. Littrow optical layout is used for its light-splitting optical system, and the spectral resolution is between 9.4-16 nm at 1,000-1,965 nm detection wavelength range. The prototype is successfully applied in LW-NIR spectrum measurement on pure water and ethanol aqueous solution, and a forecast analysis on ethanol aqueous solution concentration is also demonstrated. Through adopting MEMS scanning mirror into the spectrometer system, the complexity of the mechanical scanning fixtures and its controlling mechanism is greatly reduced therefore the size of the spectrometer is reduced. Furthermore, due to MEMS scanning mirror technology, LW-NIR spectrometer with single InGaAs detector is achieved, thus the cost reduction of the NIR spectrometer system is also realized because the expensive InGaAs arrays are avoided.