CDX2 alleviates hypoxia-induced apoptosis and oxidative stress in spermatogenic cells through suppression of reactive oxygen species-mediated Wnt/ß-catenin pathway.

Hypoxia-induced apoptosis and oxidative stress in spermatogenic cells are considered to be important factors leading to male infertility. It was reported that CDX2 expression was downregulated in hypoxia-stimulated spermatogenic cells. However, the effects of CDX2 on hypoxia-induced apoptosis and oxidative stress in spermatogenic cells are still unknown. This study aimed to explore the roles of CDX2 in hypoxia-induced injury of spermatogenic cells, as well as its mechanism of action. Spermatogenic cells were cultured under 1% oxygen for 48 h to established hypoxia damage model. Reactive oxygen species (ROS) generation was determined using 2',7'-dichlorofluorescein diacetate assay. Apoptosis was assessed using flow cytometry. Enzyme-linked immunosorbent assay was used to evaluate oxidative stress markers, including malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GSH-Px). Protein levels were detected using western blotting. Hypoxia exposure induced increase in ROS generation, apoptosis rate, and oxidative stress in spermatogenic cells. ROS scavenger inhibited hypoxia-induced apoptosis, oxidative stress, and Wnt/ß-catenin pathway activation. Hypoxia exposure induced CDX2 downregulation. CDX2 overexpression suppressed hypoxia-induced ROS generation, apoptosis rate, oxidative stress, and Wnt/ß-catenin pathway activation. Moreover, CDX2 knockdown restores the inhibitory effects of si-ß-catenin or NAC on hypoxia-induced activation of the Wnt/ß-catenin pathway, apoptosis, and oxidative stress. In conclusion, our study suggests that CDX2 overexpression alleviates hypoxia-induced apoptosis and oxidative stress by suppression of ROS-mediated Wnt/ß-catenin pathway in spermatogenic cells.

A long-term study comparing the quality of life and psychological status of patients with highly suspicious thyroid nodules ≤ 1 cm undergoing active surveillance with those undergoing immediate surgery.

BACKGROUND: Limited information is available on the long-term impact of active surveillance (AS) and immediate surgery (IS) on the quality of life (QoL) and psychological status of patients with highly suspicious sub-centimeter thyroid nodules. METHODS: A prospective study was conducted on 752 patients showing highly suspicious sub-centimeter thyroid nodules, among whom 584 chose AS and 168 chose IS. All patients underwent at least two assessments regarding their QoL and psychological status, using three questionnaires: THYCA-QoL, HADS and EORTC QLQ-C30. Propensity-score matching (PSM) at a ratio of 3:1 was utilized on patients in the AS and IS groups to mitigate selection bias (504 patients in the AS group and 168 in the IS group). Subsequently, the mixed linear model was used to analyze the QoL data. RESULTS: The median time from the initial evaluation to the last follow-up in the AS and IS groups was 24.0 months and 14.2 months, respectively. The AS group showed superior QoL outcomes compared to the IS group, mainly manifested in voice (p < 0.001), sympathetic (p = 0.008), throat/mouth (p < 0.001), and problems with scar (p < 0.001) domains, as per the THYCA-QoL questionnaire. Further, the EORTC QLQ-C30 questionnaire highlighted better outcomes in physical function (p = 0.029), role function (p < 0.001), social function (p < 0.001), global health status (p < 0.001), fatigue (p = 0.012), pain (p = 0.028), appetite loss (p = 0.017), and financial difficulties (p < 0.001). Compared to the initial assessment (one week after surgery), the IS group showed progressive improvements in QoL, especially in voice (p = 0.024), throat/mouth (p < 0.001), physical function (p = 0.004), social function (p = 0.014), nausea & vomiting (p < 0.001), pain (p = 0.006), and appetite loss (p = 0.048) domains as per both questionnaires. CONCLUSION: Patients with highly suspicious sub-centimeter thyroid nodules who choose IS tend to experience a poorer long-term QoL compared to those who choose AS. Although the situation may improve over time, certain issues might persist, making AS a favorable option for these patients.

Criteria to Evaluate Tumor Enlargement During the Active Surveillance of High-Risk Thyroid Nodules: Which is Better, Diameter or Volume?

INTRODUCTION: Tumor enlargement is the most common parameter identifying disease progression during active surveillance, but the value and significance of the changes in tumor diameter and volume in the evaluation of tumor growth have not been compared. METHODS: This cohort study included 468 patients with high-risk thyroid nodule, in whom nodule size change was monitored using ultrasound, to compare the changes in tumor diameter and volume in assessing tumor growth. RESULTS: A total of 569 high-risk thyroid nodules were found in the 468 patients. A total of 14 nodules (2.5%) showed a diameter increase ≥ 3 mm. The number of nodules with a peak volume change exceeding 50% and 100% was 185 (32.5%) and 86 (15.1%), respectively. Among the 555 stable nodules, the number of nodules with volume fluctuations exceeding 50% and 100% was 171 (30.8%) and 72 (13.0%), respectively. Among 212 stable nodules at the baseline and in the first three follow-up, the percentage of peak volume fluctuations exceeding 50% (48.5% vs. 28.5%, p = 0.004) and 100% (26.5% vs. 8.3%, p < 0.001) in the nodules with the sum of three diameters (SOTDs) ≤ 1 cm was significantly higher than that of nodules with SOTDs > 1 cm. A statistically significant difference was also found in the range distribution of SOTDs ≤ 1 cm and SOTDs > 1 cm (p = 0.007). CONCLUSIONS: Volume is not an appropriate method for determining tumor growth. Tumor diameter measurement alone serves as a better surrogate for disease progression in sonographically high-risk thyroid nodules than volume.

Anti­BCMA CAR­T cell immunotherapy for relapsed or refractory multiple myeloma.

The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x105 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x105 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects.

Experimental quantum simulation of a topologically protected Hadamard gate via braiding Fibonacci anyons.

Topological quantum computation (TQC) is one of the most striking architectures that can realize fault-tolerant quantum computers. In TQC, the logical space and the quantum gates are topologically protected, i.e., robust against local disturbances. The topological protection, however, requires complicated lattice models and hard-to-manipulate dynamics; even the simplest system that can realize universal TQC-the Fibonacci anyon system-lacks a physical realization, let alone braiding the non-Abelian anyons. Here, we propose a disk model that can simulate the Fibonacci anyon system and construct the topologically protected logical spaces with the Fibonacci anyons. Via braiding the Fibonacci anyons, we can implement universal quantum gates on the logical space. Our disk model merely requires two physical qubits to realize three Fibonacci anyons at the boundary. By 15 sequential braiding operations, we construct a topologically protected Hadamard gate, which is to date the least-resource requirement for TQC. To showcase, we implement a topological Hadamard gate with two nuclear spin qubits, which reaches 97.18% fidelity by randomized benchmarking. We further prove by experiment that the logical space and Hadamard gate are topologically protected: local disturbances due to thermal fluctuations result in a global phase only. As a platform-independent proposal, our work is a proof of principle of TQC and paves the way toward fault-tolerant quantum computation.

Effect of Non-Isothermal Aging on the Mechanical Properties and Corrosion Resistance of 2A12 Aluminum Alloy.

The effect of linear non-isothermal aging and composite non-isothermal aging on the mechanical properties and corrosion resistance of 2A12 aluminum alloy was investigated. Optical microscopy (OM) and scanning electron microscopy (SEM) equipped with energy-dispersive spectroscopy (EDS) were used to study the microstructure and intergranular corrosion morphology, and the precipitates were analyzed using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results showed that the mechanical properties of 2A12 aluminum alloy were improved by both non-isothermal aging techniques due to the formation of an S' phase and a point S″ phase in the alloy matrix. Linear non-isothermal aging resulted in better mechanical properties than composite non-isothermal aging. However, the corrosion resistance of the 2A12 aluminum alloy was reduced after non-isothermal aging due to the transformation of matrix precipitates and grain boundary precipitates. The corrosion resistance of the samples followed the order: annealed state > linear non-isothermal aging > composite non-isothermal aging.

Construction of a risk model and prediction of prognosis and immunotherapy based on cuproptosis-related LncRNAs in the urinary system pan-cancer.

BACKGROUND: Urinary pan-cancer system is a general term for tumors of the urinary system including renal cell carcinoma (RCC), prostate cancer (PRAD), and bladder cancer (BLCA). Their location, physiological functions, and metabolism are closely related, making the occurrence and outcome of these tumors highly similar. Cuproptosis is a new type of cell death that is different from apoptosis and plays an essential role in tumors. Therefore, it is necessary to study the molecular mechanism of cuproptosis-related lncRNAs to urinary system pan-cancer for the prognosis, clinical diagnosis, and treatment of urinary tumors. METHOD: In our study, we identified 35 co-expression cuproptosis-related lncRNAs (CRLs) from the urinary pan-cancer system. 28 CRLs were identified as prognostic-related CRLs by univariate Cox regression analysis. Then 12 CRLs were obtained using lasso regression and multivariate cox analysis to construct a prognostic model. We divided patients into high- and low-risk groups based on the median risk scores. Next, Kaplan-Meier analysis, principal component analysis (PCA), functional rich annotations, and nomogram were used to compare the differences between the high- and low-risk groups. Finally, the prediction of tumor immune dysfunction and rejection, gene mutation, and drug sensitivity were discussed. CONCLUSION: Finally, the candidate molecules of the urinary system pan-cancer were identified. This CRLs risk model may be promising for clinical prediction of prognosis and immunotherapy response in urinary system pan-cancer patients.

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China.

INTRODUCTION: Active surveillance (AS) is considered an alternative to immediate surgery (IS) for low-risk papillary thyroid microcarcinoma (PTMC) patients. However, it is difficult to decide between AS and IS due to limited evidence regarding risks and benefits for patients in China. METHODS: This study prospectively enrolled 485 patients with highly suspicious thyroid nodules

Mild hypothermia alleviates oxygen-glucose deprivation/reperfusion-induced apoptosis by inhibiting ROS generation, improving mitochondrial dysfunction and regulating DNA damage repair pathway in PC12 cells.

The brain ischemia/reperfusion (I/R) injury has a great impact on human life and property safety. As far as we know, mild hypothermia (MH) is an effective measure to reduce neuronal injury after I/R. However, the precise mechanism is not extremely clear. The purpose of this study was to investigate whether mild therapeutic hypothermia can play a protective role in nerve cells dealing with brain I/R injury and explore its specific mechanism in vitro. A flow cytometer, cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay were performed to detect apoptotic rate of cells, cell viability and cytotoxicity, respectively, reactive oxygen species (ROS) assay kit, JC-1 fluorescent methods, immunofluorescence and western blot were used to explore ROS, mitochondrial transmembrane potential (Δψm), mitochondrial permeability transition pore (MPTP) and protein expression, respectively. The result indicated that the cell activity was decreased, while the cytotoxicity and apoptosis rate were increased after treating with oxygen-glucose deprivation/reperfusion (OGD/R) in PC12 cells. However, MH could antagonize this phenomenon. Interestingly, treating with OGD/R increased the release of ROS and the transfer of Cytochrome C (Cyt-C) from mitochondria to cytoplasm. In addition, it up-regulated the expression of γH2AX, Bax and Clv-caspase3, down-regulated the expression of PCNA, Rad51 and Bcl-2, and inhibited the function of mitochondria in PC12 cells. Excitingly, the opposite trend was observed after MH treatment. Therefore, our results suggest that MH protects PC12 cells against OGD/R-induced injury with the mechanism of inhibiting cell apoptosis by reducing ROS production, improving mitochondrial function, reducing DNA damage, and enhancing DNA repair.

Brain Magnetic Resonance Imaging Features of Nicotine-Dependent Individuals and Its Correlation with Polymorphisms of Dopamine D Receptor Gene.

The aim of this research was developed to provide a scientific basis for individualized prevention, clinical diagnosis, and corrective treatment of nicotine addiction. The objects were 214 cases in the smoke group and 43 cases in the control group. According to the Fagerstrom Nicotine Dependence Test (FTND), the smokers were divided into mild nicotine dependence group (FTND < 6 points, 138 cases) and nicotine severe dependence group (≥6 points, 76 cases). The brain structure in long-term smokers was evaluated by using magnetic resonance imaging (MRI). The nicotine dependence was further analyzed by grouping the included individuals, and some candidate genes related to nicotine addiction were screened by combining with bioinformatics analysis. The family research strategy was adopted to detect nicotine addiction susceptibility genes and their polymorphisms. The MRI imaging results showed that the bilateral thalamus, right parietal, and left lens gram-molecule volume (GMV) were negatively correlated with smoking index and smoking years in the smoking group. The GMV of the posterior cingulate cortex in the severe nicotine dependence group was lower than that of the control group, and the GMVs of bilateral thalamus and bilateral superior limbic gyrus in the mild nicotine dependence group were lower than those of the control group. The gene polymorphism detection showed that rs6275 was highly polymorphic in the target population and the frequency of rs6275-C allele was 53.26%. Therefore, the MRI imaging characteristics suggested that the affected brain regions of smokers and people with varying degrees of nicotine dependence were mainly concentrated in response-related pathways and the limbic system and had cumulative effects on the central nervous system. In addition, the M6275 polymorphism of DRD2 gene was associated with susceptibility to nicotine addiction in Chinese population, and the M6275-C allele had a protective effect on susceptibility to nicotine addiction and smoking initiation.

Active surveillance of highly suspicious thyroid nodules cohort in China shows a worse psychological status in younger patients.

Background: Active surveillance has been considered a safe alternative to surgery for low-risk papillary thyroid microcarcinoma. This study aimed to assess the oncological outcomes and psychological status of active surveillance of highly suspicious thyroid nodules ≤10 mm in China. Methods: This prospective single-center cohort study enrolled 336 patients with highly suspicious thyroid nodules for active surveillance to assess oncological outcomes and psychological status. The psychological status of patients was assessed by two different questionnaires and compared among different patient groups. Results: During a median follow-up period of 28.5 months, eight patients underwent delayed surgery for tumor enlargement and one for lymph node metastases. The cumulative incidence of disease progression at 5 and 10 years was 6.0% and 12.8%, respectively. Patients who underwent delayed surgery had no permanent complications, and no patient had distant metastasis or death. Patients ≤30 years old had a higher baseline anxiety score (4.9 vs. 3.8, p=0.024), a higher proportion of baseline anxiety score, i.e., ≥8 points (24.0% vs. 12.6%, p=0.033), and a worse baseline emotional function (62.7 vs. 70.7, p=0.013) than patients >30. During AS, patients ≤30 years of age had higher overall anxiety levels (p=0.005) and a worse overall emotional function (p=0.001). Conclusions: Active surveillance in Chinese patients with highly suspicious subcentimetre thyroid nodules has good oncological outcomes and can be used as a safe alternative to surgery. Younger patients (≤30) show a worse psychological status; therefore, more attention should be paid to younger patients.

Entanglement-Enhanced Quantum Metrology in Colored Noise by Quantum Zeno Effect.

In open quantum systems, the precision of metrology inevitably suffers from the noise. In Markovian open quantum dynamics, the precision can not be improved by using entangled probes although the measurement time is effectively shortened. However, it was predicted over one decade ago that in a non-Markovian one, the error can be significantly reduced by the quantum Zeno effect (QZE) [Chin, Huelga, and Plenio, Phys. Rev. Lett. 109, 233601 (2012)PRLTAO0031-900710.1103/PhysRevLett.109.233601]. In this work, we apply a recently developed quantum simulation approach to experimentally verify that entangled probes can improve the precision of metrology by the QZE. Up to n=7 qubits, we demonstrate that the precision has been improved by a factor of n^{1/4}, which is consistent with the theoretical prediction. Our quantum simulation approach may provide an intriguing platform for experimental verification of various quantum metrology schemes.

An immediate postoperative response to therapy assessment can help avoid unnecessary RAI therapy.

Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

Construction of a Prognostic Model for Hypoxia-Related LncRNAs and Prediction of the Immune Landscape in the Digestive System Pan-Cancer.

Digestive system pan-cancer is a general term for digestive system tumors including colorectal carcinoma (CRC), esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and liver hepatocellular carcinoma (LIHC). Since the anatomical location, function and metabolism are closely related, there may be similarities in development and progression of these tumors. Hypoxia is the consequence of an imbalance between oxygen demand and supply, and intracellular hypoxia is associated with malignant progression, treatment resistance, and poor prognosis in tumors. Therefore, an urgent and challenging task is to investigate the molecular mechanisms associated with hypoxia in digestive system pan-cancer for the prognosis and treatment of digestive tract tumors. In this study, we identified 18 hypoxia-related lncRNAs (HRlncRNAs) by co-expression analysis between hypoxia genes and lncRNAs from digestive system pan-cancer. Six HRlncRNAs were then obtained using lasso regression and multivariate cox analysis to construct a prognostic model. Next, the Akaike information criterion (AIC) values for 3-year receiver operating curve (ROC) were counted to determine the cut-off point and establish an optimal model to distinguish between high- or low-risk groups among patients with digestive system pan-cancer. To evaluate the stability of the prognosis model, we validated it in terms of survival outcomes, clinicopathological stage, tumor-infiltrating immune cells, immune checkpoint inhibitors (ICIs) and anticancer drugs sensitivity. The results suggested that high- risk group had a worse prognosis and a more positive association with tumor-infiltrating immune cells such as B cells, cancer-associated fibroblasts, endothelial cells, monocytes, macrophages and bone marrow dendritic cells in digestive system pan-cancer. Immune checkpoint inhibitors (ICIs) related biomarkers discovered that high-risk group was positively correlated with high expression of HAVCR2 in digestive system pan-cancer. The anticancer drugs sensitivity analysis showed that the high-risk group was associated with the lower half-inhibitory centration (IC50) of Imatinib in digestive system pan-cancer. In conclusion, the prognostic model of HRlncRNAs showed a promising clinical prediction value and may provide a useful reference for the diagnosis and treatment of the digestive system tumors.

Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis.

Background: The prognostic factors for differentiated thyroid cancer (DTC) patients with pulmonary metastases (PM) remain scantly identified and analyzed. Therefore, this systematic review and meta-analysis were performed to identify and summarize the prognostic factors in adult DTC patients with PM to help distinguish patients with different prognoses and inform the rational treatment regimens. Method: We performed a comprehensive search of the relevant studies published in the Cochrane Library, PubMed, Scopus, Embase, Wanfang database, VIP database, China National Knowledge Infrastructure, and Google Scholar from their inception until February 2021. The pooled hazard ratios (HR) for overall survival and/or progression-free survival (PFS) with 95% confidence intervals were applied to evaluate and identify the potential prognostic factors. Pooled OS at different time points were also calculated for the available data. A random-effects model was used in the meta-analysis. Results: The review and meta-analysis included 21 studies comprising 2722 DTC patients with PM. The prognostic factors for poor OS were: age over 40 years (HR=7.21, 95% confidence interval [CI] 1.52-34.10, P=0.01, N=788), age over 45 years (HR=2.18, 95% CI 1.26-3.77, P<0.01, N=601), male gender (HR=1.01, 95% CI 1.01-1.19, P=0.03, N=1396), follicular subtype of thyroid cancer (HR=1.63, 95% CI 1.36-1.96, P<0.01, N=2110), iodine non-avidity (HR=3.10, 95% CI 1.79-5.37, P<0.01, N=646), and metastases to other organs (HR=3.18, 95% CI 2.43-4.16, P<0.01, N=1713). Factors associated with poor PFS included age over 45 years (HR=3.85, 95% CI 1.29-11.47, P<0.01, N=306), male gender (HR=1.36, 95% CI 1.06-1.75, P=0.02, N=546), iodine non-avidity (HR=2.93, 95% CI 2.18-3.95, P<0.01, N=395), pulmonary metastatic nodule size over 10mm (HR=2.56, 95% CI 2.02-3.24, P<0.01, N=513), and extra-thyroidal invasion (HR=2.05, 95% CI 1.15-3.67, P=0.02, N=271). The pooled 1, 3, 5, 10, 15, and 20-years OS were 95.24%, 88.46%, 78.36%, 64.86%, 56.57%, and 51.03%, respectively. Conclusions: This review and meta-analysis identified the prognostic factors of DTC patients with PM. Notably, FTC, metastases to other organs, and iodine non-avidity were particularly associated with poor prognosis. The identified prognostic factors will help guide the clinical management of DTC patients with PM. Systematic review registration: https://inplasy.com/inplasy-2022-2-0026/, identifier (INPLASY202220026).

Regulatory role of miR-129 and miR-384-5p on apoptosis induced by oxygen and glucose deprivation in PC12 cell.

This study aimed to establish the role of miR-129 and miR-384-5p in cerebral ischemia-induced apoptosis. Using PC12 cells transfected with miR-129 or miR-384-5p mimics or inhibitors, oxygen glucose deprivation (OGD) conditions were applied for 4 h to simulate transient cerebral ischemia. Apoptotic phenotypes were assessed via lactate dehydrogenase (LDH) assay, MTT cell metabolism assay, and fluorescence-activated cell sorting (FACS). The effect of miR overexpression and inhibition was evaluated by protein and mRNA detection of bcl-2 and caspase-3, critical apoptosis factors. Finally, the direct relationship of miR-129 and bcl-2 and miR-384-5p and caspase-3 was measured by luciferase reporter assay. The overexpression of miR-384-5p and miR-129 deficiency significantly enhanced cell viability, reduced LDH release, and inhibited apoptosis. By contrast, overexpression of miR-129 and miR-384-5p deficiency aggravated hypoxia-induced apoptosis and cell injury. miR-129 overexpression significantly reduced mRNA and protein levels of bcl-2 and miR-129 inhibition significantly increased mRNA and protein levels of bcl-2 in hypoxic cells.miR-384-5p overexpression significantly reduced protein levels of caspase-3 while miR-384-5p deficiency significantly increased protein levels of caspase-3. However, no changes were observed in caspase-3 mRNA in either transfection paradigm. Finally, luciferase reporter assay confirmed caspase-3 to be a direct target of miR-384-5p; however, no binding activity was detected between bcl-2 and miR-129.Transient cerebral ischemia induces differential expression of miR-129 and miR-384-5p which influences apoptosis by regulating apoptotic factors caspase-3 and bcl-2, thereby participating in the pathological mechanism of cerebral ischemia, and becoming potential targets for the treatment of ischemic cerebral injury in the future.

Predicting factors of tumor progression in adult patients with low-grade glioma within five years after surgery.

BACKGROUND: Glioma is the most common primary intracranial tumor with the worst prognosis whose 5-year mortality rate is second only to pancreatic cancer and lung cancer among systemic tumors. WHO divides gliomas into grades I to IV, with grades I and II as low grades. Low-grade gliomas tend to occur in people between the ages of 30 and 40, who usually have the characteristics of well-differentiated, slow growth, and low invasiveness. Timely diagnosis and surgery are the main treatment strategies for low-grade gliomas. The current ideal treatment represents the MST reaching average seven years. However, many patients relapse with adverse outcomes. It's important to identify high-risk patients by predicting factors in adult patients with low-grade glioma. METHODS: A total of 287 patients who were treated in our hospital from February 2011 to May 2015 were included in the final analysis according to the inclusion and exclusion criteria. The patients were divided into progression-free groups and progression groups according to the results of 5-year follow-up after surgery by information like patients' baseline data, surgical data, postoperative follow-up data. The ROC was used to analyze the greatest quantitative treatment boundary value and distinguish high and low risk. Kaplan-Meier survival curve was used to analyze risk factors' predictive value for patients' postoperative results. RESULTS: The results of 5-year follow-up showed 122 cases (42.5%) had no progression (progression-free group), 165 cases (57.5%) had progression (progression group). Univariate and multivariate analysis showed that age older than 50 (OR =1.42, P=0.013), partial resection of tumor (OR =1.86, P=0.027), tumor diameter larger than 5 cm (OR =1.85, P=0.022) and long-term statins treatment before surgery (OR =0.36, P=0.036) were closely associated with tumor progression. The Kaplan-Meier survival curve showed patients aged older than 50, partial resection of the tumor, a tumor diameter larger than 5 cm whose results were poor, while long-term statins treatment before surgery had a better prognosis within the 5-year follow-up. CONCLUSIONS: Patients aged older than 50, partial resection of the tumor, tumor diameter larger than 5 cm and long-term statins treatment before surgery were closely related to the prognosis after surgery.

Optical Scattering of Liquid Gallium Nanoparticles Coupled to Thin Metal Films.

We investigate experimentally and numerically the scattering properties of liquid gallium nanoparticles coupled to a thin gold or silver film. The gallium nanoparticles are excited either directly by using inclined white light or indirectly by surface plasmon polaritons generated on the surface of the gold/silver film. In the former case, the scattering spectrum is always dominated by a scattering peak at ∼540 nm with a long-wavelength shoulder which is redshifted with increasing diameter of the gallium nanoparticle. Under the excitation of the surface plasmon polaritons, optical resonances with much narrower linewidths, which are dependent on the incidence angle of the white light, appear in the scattering spectra. In this case, the scattering spectrum depends weakly on the diameter of the gallium nanoparticle but the radiation pattern exhibits a strong dependence. In addition, a significant enhancement of electric field is expected in the gap region between the gallium nanoparticles and the gold film based on numerical simulation. As compared with the gallium nanoparticle coupled to the gold film which exhibit mainly yellow and orange colors, vivid scattering light spanning the visible light spectrum can be achieved in the gallium nanoparticles coupled to the silver film by simply varying the incidence angle. Gallium nanoparticles coupled to thin metal films may find potential applications in light-matter interaction and color display.