Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT.

Radiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.

Association between homotopic connectivity and clinical symptoms in first-episode schizophrenia.

Background: Abnormal functional connectivity (FC) in the brain has been observed in schizophrenia patients. However, studies on FC between homotopic brain regions are limited, and the results of these studies are inconsistent. The aim of this study was to compare homotopic connectivity between first-episode schizophrenia (FES) patients and healthy subjects and assess its correlation with clinical symptoms. Methods: Thirty-one FES patients and thirty-three healthy controls (HC) were included in the study. The voxel-mirrored homotopic connectivity (VMHC) method of resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyse the changes in homotopic connectivity between the two groups. The 5-factor PANSS model was used to quantitatively evaluate the severity of symptoms in FES patients. Partial correlation analysis was used to assess the correlation between homotopic connectivity changes and clinical symptoms. Results: Compared to those in the HC group, VMHC values were decreased in the paracentral lobule (PL), thalamus, and superior temporal gyrus (STG) in the FES group (P < 0.05, FDR correction). No significant differences in white matter volume (WMV) within the subregion of the corpus callosum or in brain regions associated with reduced VMHC were observed between the two groups. Partial correlation analyses revealed that VMHC in the bilateral STG of FES patients was positively correlated with negative symptoms (rleft = 0.46, p < 0.05; rright = 0.47, p < 0.05), and VMHC in the right thalamus was negatively correlated with disorganized/concrete symptoms (rright = 0.45, p < 0.05). Conclusion: Our study revealed that homotopic connectivity is altered in the resting-state brain of FES patients and correlates with the severity of negative symptoms; this change may be independent of structural changes in white matter. These findings may contribute to the development of the abnormal connectivity hypothesis in schizophrenia patients.

Sparser spiking activity can be better: Feature Refine-and-Mask spiking neural network for event-based visual recognition.

Event-based visual, a new visual paradigm with bio-inspired dynamic perception and µs level temporal resolution, has prominent advantages in many specific visual scenarios and gained much research interest. Spiking neural network (SNN) is naturally suitable for dealing with event streams due to its temporal information processing capability and event-driven nature. However, existing works SNN neglect the fact that the input event streams are spatially sparse and temporally non-uniform, and just treat these variant inputs equally. This situation interferes with the effectiveness and efficiency of existing SNNs. In this paper, we propose the feature Refine-and-Mask SNN (RM-SNN), which has the ability of self-adaption to regulate the spiking response in a data-dependent way. We use the Refine-and-Mask (RM) module to refine all features and mask the unimportant features to optimize the membrane potential of spiking neurons, which in turn drops the spiking activity. Inspired by the fact that not all events in spatio-temporal streams are task-relevant, we execute the RM module in both temporal and channel dimensions. Extensive experiments on seven event-based benchmarks, DVS128 Gesture, DVS128 Gait, CIFAR10-DVS, N-Caltech101, DailyAction-DVS, UCF101-DVS, and HMDB51-DVS demonstrate that under the multi-scale constraints of input time window, RM-SNN can significantly reduce the network average spiking activity rate while improving the task performance. In addition, by visualizing spiking responses, we analyze why sparser spiking activity can be better. Code.

Attention Spiking Neural Networks.

Brain-inspired spiking neural networks (SNNs) are becoming a promising energy-efficient alternative to traditional artificial neural networks (ANNs). However, the performance gap between SNNs and ANNs has been a significant hindrance to deploying SNNs ubiquitously. To leverage the full potential of SNNs, in this paper we study the attention mechanisms, which can help human focus on important information. We present our idea of attention in SNNs with a multi-dimensional attention module, which infers attention weights along the temporal, channel, as well as spatial dimension separately or simultaneously. Based on the existing neuroscience theories, we exploit the attention weights to optimize membrane potentials, which in turn regulate the spiking response. Extensive experimental results on event-based action recognition and image classification datasets demonstrate that attention facilitates vanilla SNNs to achieve sparser spiking firing, better performance, and energy efficiency concurrently. In particular, we achieve top-1 accuracy of 75.92% and 77.08% on ImageNet-1 K with single/4-step Res-SNN-104, which are state-of-the-art results in SNNs. Compared with counterpart Res-ANN-104, the performance gap becomes -0.95/+0.21 percent and the energy efficiency is 31.8×/7.4×. To analyze the effectiveness of attention SNNs, we theoretically prove that the spiking degradation or the gradient vanishing, which usually holds in general SNNs, can be resolved by introducing the block dynamical isometry theory. We also analyze the efficiency of attention SNNs based on our proposed spiking response visualization method. Our work lights up SNN's potential as a general backbone to support various applications in the field of SNN research, with a great balance between effectiveness and energy efficiency.

Study on the correlation between B vitamins and breast cancer.

BACKGROUND: Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. METHODS: The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ2 test was used to evaluate the relationship between B vitamin level and age,BMI,TNM staging,Ki-67,Her-2,surgery and chemotherapy, and other baseline characteristics and through binary logistic regression analysis, calculating odds ratio and 95% confidence interval (CI) to evaluate the relationship between B vitamins and breast cancer risk. CONCLUSION: The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Prim-O-glucosycimifugin attenuates liver injury in septic mice by inhibiting NLRP3 inflammasome/caspase-1 signaling cascades in macrophages.

BACKGROUND: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear. PURPOSE: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway. METHOD: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1ß and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1ß and IL-18 were measured by ELISA assays. RESULTS: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1ß and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950. CONCLUSION: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate.

A Co-driven Functional Electrical Stimulation Control Strategy by Dynamic Surface Electromyography and Joint Angle.

Functional electrical stimulation (FES) is widely used in neurorehabilitation to improve patients' motion ability. It has been verified to promote neural remodeling and relearning, during which FES has to produce an accurate movement to obtain a good efficacy. Therefore, many studies have focused on the relationship between FES parameters and the generated movements. However, most of the relationships have been established in static contractions, which leads to an unsatisfactory result when applied to dynamic conditions. Therefore, this study proposed a FES control strategy based on the surface electromyography (sEMG) and kinematic information during dynamic contractions. The pulse width (PW) of FES was determined by a direct transfer function (DTF) with sEMG features and joint angles as the input. The DTF was established by combing the polynomial transfer functions of sEMG and joint torque and the polynomial transfer functions of joint torque and FES. Moreover, the PW of two FES channels was set based on the muscle synergy ratio obtained through sEMG. A total of six healthy right-handed subjects were recruited in this experiment to verify the validity of the strategy. The PW of FES applied to the left arm was evaluated based on the sEMG of the right extensor carpi radialis (ECR) and the right wrist angle. The coefficient of determination (R 2) and the normalized root mean square error (NRMSE) of FES-included and voluntary wrist angles and torques were used to verify the performance of the strategy. The result showed that this study achieved a high accuracy (R 2 = 0.965 and NRMSE = 0.047) of joint angle and a good accuracy (R 2 = 0.701 and NRMSE = 0.241) of joint torque reproduction during dynamic movements. Moreover, the DTF in real-time FES system also had a nice performance of joint angle fitting (R 2 = 0.940 and NRMSE = 0.071) and joint torque fitting (R 2 = 0.607 and NRMSE = 0.303). It is concluded that the proposed strategy is able to generate proper FES parameters based on sEMG and kinematic information for dynamic movement reproduction and can be used in a real-time FES system combined with bilateral movements for better rehabilitation.

Canonical transformation for multivariate mixed model association analyses.

KEY MESSAGE: In extension of Single-RunKing to analyze multiple correlated traits, mvRunKing not only enlarged number of the analyzed phenotypes with canonical transformation, but also improved statistical power to detect pleiotropic QTNs through joint association analysis. Based on genomic variance-covariance matrices, we simplified multivariate mixed model association analysis to multiple univariate ones by using canonical transformation, and then individually implemented univariate association tests in the Single-RunKing. which enlarged number of the analyzed phenotypes. With canonical transformation back to the original scale, the association results would be biologically interpretable. Especially, we rapidly estimated genomic variance-covariance matrices with multivariate GEMMA and optimized separately the polygenic variances (or heritabilities) for only the markers that had large effects or higher significance levels in univariate mixed models, greatly improving computing efficiency for multiple univariate association tests. Beyond one test at once, joint association analysis for quantitative trait nucleotide (QTN) candidates can significantly increase statistical powers to detect QTNs. A user-friendly mvRunKing software was developed to efficiently implement multivariate mixed model association analyses.

Passive Non-Line-of-Sight Imaging Using Optimal Transport.

Passive non-line-of-sight (NLOS) imaging has drawn great attention in recent years. However, all existing methods are in common limited to simple hidden scenes, low-quality reconstruction, and small-scale datasets. In this paper, we propose NLOS-OT, a novel passive NLOS imaging framework based on manifold embedding and optimal transport, to reconstruct high-quality complicated hidden scenes. NLOS-OT converts the high-dimensional reconstruction task to a low-dimensional manifold mapping through optimal transport, alleviating the ill-posedness in passive NLOS imaging. Besides, we create the first large-scale passive NLOS imaging dataset, NLOS-Passive, which includes 50 groups and more than 3,200,000 images. NLOS-Passive collects target images with different distributions and their corresponding observed projections under various conditions, which can be used to evaluate the performance of passive NLOS imaging algorithms. It is shown that the proposed NLOS-OT framework achieves much better performance than the state-of-the-art methods on NLOS-Passive. We believe that the NLOS-OT framework together with the NLOS-Passive dataset is a big step and can inspire many ideas towards the development of learning-based passive NLOS imaging. Codes and dataset are publicly available (https://github.com/ruixv/NLOS-OT).

The study of correlation between nomogram prediction of uric acid and different chemotherapy regimens in breast cancer patients.

Background: High levels of serum uric acid (SUA) are associated with a poor survival rate of breast cancer. Meanwhile, a sharp increase in SUA after chemotherapy may lead to tumor lysis syndrome (TLS). We created and validated a nomogram to help doctors better manage the patient's SUA level ahead of time in this study. Methods: From July 2012 to June 2021, 206 patients with breast cancer undergoing chemotherapy participated in the study. They are randomly divided into training set (n=137) and validation set (n=69). Univariate and multivariate logistic regression analysis was used to screen the independent predictors of the risk of elevated uric acid in the whole training set data. The receiver operating characteristic (ROC) curve and decision curve assessed the accuracy and clinical application value of nomogram. Results: We confirmed that body mass index (BMI), age, menopause, EC-T chemotherapy (epirubicin-cyclophosphamide followed by paclitaxel) and THP + C-T (pirarubicin-cyclophosphamide followed by paclitaxel) are independent risk factors for high SUA. We established a nomogram for high SUA risk prediction to help clinicians make individualized choice of chemotherapy regimen. In the training cohort, the area under the ROC curve (AUC) showed statistical accuracy (AUC =0.796). Decision curve analysis proved the clinical value of the nomogram. Conclusions: This nomogram can be used to calculate the specific likelihood of high SUA in patients with breast cancer undergoing chemotherapy with different chemotherapy options.

Intermedin Inhibits the Ox-LDL-Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid-Binding Protein 4 Through the PKA Pathway.

Objectives: Macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) play an important role in the occurrence and progression of atherosclerosis. Fatty acid-binding protein 4 (FABP4), mainly existing in macrophages and adipocytes, can influence lipid metabolism and inflammation regulated by macrophages. Herein, we first established the connection between intermedin (IMD: a new peptide that has versatile biological activities in the cardiovascular system) and FABP4 and then investigated the influence of IMD on ox-LDL-induced changes in RAW264.7 macrophages line. Methods: The bioinformatics analysis, such as gene ontology enrichment and protein-protein interactions, was performed. For ox-LDL-stimulated assays, RAW264.7 was first pretreated with IMD and then exposed to ox-LDL. To explore the cell signaling pathways of IMD on inflammatory inhibition, main signaling molecules were tested and then cells were co-incubated with relevant inhibitors, and then exposed/not exposed to IMD. Finally, cells were treated with ox-LDL. The protein and gene expression of FABP4, IL-6, and TNF-α were quantified by WB/ELISA and RT-qPCR. Results: In the ox-LDL-stimulated assays, exposure of the RAW264.7 macrophages line to ox-LDL reduced cell viability and increased the expression of FABP4, as well as induced the release of IL-6 and TNF-α (all p < 0.05). On the other hand, IMD prevented ox-LDL-induced cell toxicity, FABP4 expression, and the inflammatory level in RAW264.7 (all p < 0.05) in a dose-dependent manner. The inhibition of FABP4 and the anti-inflammatory effect of IMD were partially suppressed by the protein kinase A (PKA) inhibitor H-89. Conclusion: IMD can prevent ox-LDL-induced macrophage inflammation by inhibiting FABP4, whose signaling might partially occur via the PKA pathway.

Phase Synchronization of EEG in Bilateral, Cyclical Ankle Alternating Movements of Stroke.

Electroencephalogram (EEG) is a basic physiological signal of human body, which can effectively record the nervous system activities of the brain and contains rich information. The synchronization of EEG signals is not only the key to the exchange of information between different brain regions, but also reflects the neural activity of the brain, which in turn can infer people's cognitive activities. Therefore, studying the phase synchronization of EEG signals after stroke is of great significance for understanding the communication and neuroplasticity of neurons after brain injury. In this paper, the changes of EEG phase synchronization in bilateral, cyclical ankle movements alternately after stroke were studied by Hilbert transform. Ten stroke patients and six healthy adults participated in the test. The results showed that the inter-hemisphere phase synchronization index (inter-PSI) and the global PSI of patients were significantly lower than that of the healthy subjects during the task. The PSI between Cz and the affected sensory cortex associated with lower limb movements was also significantly lower than that in the control group. There was a significant negative correlation between National Institutes of Health Stroke Scale (NIHSS) and cortical synchronization. The above results indicated that PSI under ankle alternating movements may be used as a new biomarker to evaluate the recovery of patients' brain neurons.

Correlation Between Poststroke Balance Function and Brain Symmetry Index in Sitting and Standing Postures.

Balance problems are the main sequelae of stroke, which increases the risk of falling. The assessment of balance ability can guide doctors to formulate rehabilitation plans, thereby reducing the risk of falls. Studies have reported the role of resting-state EEG during sitting in the motor assessment of the upper extremity and prognosis of stroke patients. However, the above research in the sitting posture lacks specificity in evaluating the balance ability of the lower limbs. Herein, this article investigated whether EEG was different in sitting and standing positions with different difficulty levels and validated the feasibility of EEG in assessing body balance ability. The resting-state EEG signals were collected from 11 stroke patients. The pairwise-derived brain symmetry index (pdBSI) was used to identify the differences in EEG-quantified interhemispheric cortical power asymmetry observable in healthy versus cortical and subcortical stroke patients by calculating the absolute value of the difference in power at each pair of electrodes. Subsequently, we computed the pdBSI over different frequency bands. Balance function was assessed using the BBS (Berg Balance Scale). Stroke survivors showed higher pdBSI (1-25 Hz) values in standing posture compared to sitting (p <0.05) and the pdBSI was significantly negatively correlated with BBS (r = -0.671, p =0.034). Additionally, the pdBSI within beta band was also significantly negatively correlated with BBS (r = -0.711, p=0.017). In conclusion, stroke brain asymmetry in standing posture was significantly more severe and the pdBSIs in 1-25Hz and beta hand were related to balance function. BBS and NIHSS was significantly negatively correlated (r = -0.701, p = 0.024), and NIHSS was significantly correlated with age (r = 0.822, p = 0.004). The present study suggests that stroke can seriously affect the body's balance ability. Compared with the sitting posture, the asymmetry of cortical energy in the standing posture can better assess the patient's balance ability.

SlimConv: Reducing Channel Redundancy in Convolutional Neural Networks by Features Recombining.

The channel redundancy of convolutional neural networks (CNNs) results in the large consumption of memories and computational resources. In this work, we design a novel Slim Convolution (SlimConv) module to boost the performance of CNNs by reducing channel redundancies. Our SlimConv consists of three main steps: Reconstruct, Transform, and Fuse. It aims to reorganize and fuse the learned features more efficiently, such that the method can compress the model effectively. Our SlimConv is a plug-and-play architectural unit that can be used to replace convolutional layers in CNNs directly. We validate the effectiveness of SlimConv by conducting comprehensive experiments on various leading benchmarks, such as ImageNet, MS COCO2014, Pascal VOC2012 segmentation, and Pascal VOC2007 detection datasets. The experiments show that SlimConv-equipped models can achieve better performances consistently, less consumption of memory and computation resources than non-equipped counterparts. For example, the ResNet-101 fitted with SlimConv achieves 77.84% top-1 classification accuracy with 4.87 GFLOPs and 27.96M parameters on ImageNet, which shows almost 0.5% better performance with about 3 GFLOPs and 38% parameters reduced.

Assessment and validation of three spot urine assay methods for the estimation of 24-hour urinary sodium excretion in Chinese Tibetan adults living in the mountains.

Twenty-four-hour urine collection is the gold standard method for the evaluation of salt intake, but it is often impractical in large-scale investigations, especially in resource-poor areas. Methods for the estimation of 24-hour urinary sodium excretion (USE) using a spot urine sample have been established, but have not been validated in Chinese Tibetans. Therefore, the authors aimed to evaluate the Kawasaki, Tanaka, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) formulas for the prediction of 24-hour USE in Chinese Tibetan adults. The authors analyzed the bias, correlation, agreements between estimated values and measured values, and the relative and absolute differences and misclassification at the individual level for the three methods in 323 Tibetan participants from the Ganzi Tibetan Autonomous Prefecture of Sichuan Province, China. The mean biases between the measured values and the estimated 24-hour USE using the Kawasaki, Tanaka, and INTERSALT methods were 5.4 mmol/day (95% confidence interval [CI]: 0.8-10.1 mmol/day), -40.8 mmol/day (95% CI: -44.6 to -36.9 mmol/day), and -57.1 mmol/day (95% CI: -61.9 to -52.4 mmol/day), respectively. The Pearson correlation coefficients for the relationships between the measured values and the estimated 24-hour USE were 0.43 (Kawasaki), 0.38 (Tanaka), and 0.27 (INTERSALT), respectively (all p < .01). The intraclass correlation coefficients showed similar patterns to the correlation data: 0.47 for Kawasaki, 0.40 for Tanaka, and 0.27 for INTERSALT (all p < .01). The upper and lower limits of agreement between the measured values and the estimated 24-hour USE were -92.6 and 81.8 mmol/day for the Kawasaki method, -28.5 and 110.0 mmol/day for the Tanaka method, and -28.4 and 142.7 mmol/day for the INTERSALT method. Compared with the other two methods, the percentage of individuals that were misclassified by using the Kawasaki method was 48.2%, while those for the Tanaka and INTERSAL methods was 72.1% and 75.5%, respectively. However, when an individual's salt intake was higher than 12.8 g/day, the misclassification rates of the Kawasaki, Tanaka, and INTERSALT methods were 20%, 90%, and 97.5%, respectively. Thus, the authors found that the Kawasaki equation may have performed better than the other equations at Chinese Tibetan population level assessment, but none of these equations are suitable for use or perform well at the individual level. A more accurate method of using a spot urine sample to evaluate individual 24-hour USE for Tibetans is needed.

Synthesis of Icariin-Zinc and its Protective Effect on Exercise Fatigue and Reproductive System Related Glands in Male Rats.

Background: Icariin, a traditional Chinese medicine, plays a protective role in the treatment of exercise fatigue. Zinc, a trace element, plays an important role in the reproductive system. Therefore, we aimed to synthesize an Icariin-Zinc complex (by chemical means) and verify its protective effect on exercise fatigue and the reproductive system using animal experiments. Methods: The icariin-zinc complex was prepared by the reaction of icariin carbonyl and zinc ions (molar ratio 1:3). The molecular formula and structural formula of the complex were identified and tested. Fifty-six rats selected by swimming training were randomly divided into six groups: static control, exercise control, icariin, gluconate zinc (G-Zn group), icariin glucose zinc and icariin-zinc exercise ( low, high dose/L-E group, H-E group) groups. These groups respectively received the following doses: 1 ml/100 g, daily gavage with NS (for the first two groups), 45 mg/kg icariin, 110 mg/kg Gluconate Zinc, Icariin glucose zinc (45 mg/kg Icariin and 110 mg/kg Gluconate Zinc), 60 mg/kg icariin zinc and 180 mg/kg icariin zinc. After 3 weeks of gavage, we conducted 6 weeks of exhaustive swimming training. Test indices such as exhaustive swimming time of rats and body weight were evaluated after the last training exercise. The seminal vesicles, testes, and prostate gland were weighed, and their indices were calculated. The levels of testosterone (in the plasma) and glycogen (in the liver and muscle homogenates) were also evaluated using ELISA. Results: Compared with the static control group, the exhaustive swimming time of the rats in each group was prolonged. Compared with the other groups, the exhaustive swimming time of the L-E and H-E groups was significantly longer (p < 0.01); the Icariin-Zinc complex significantly increased the exhaustive swimming time of the rats. Compared with the static control group, the plasma testosterone content of the L-E and H-E groups increased significantly (p < 0.05). Compared with the exercise control group and G-Zn group, the plasma testosterone content of the H-E group also increased significantly (p < 0.01). The Icariin-Zinc complex significantly increased the serum levels of testosterone in rats. Compared with the control group, the muscle glycogen reserves of each group decreased, indicating that the muscle glycogen reserves of the rats decreased after swimming. Compared with other groups, the Icariin-Zinc complex can reduce the level of glycogen in the muscles, indicating that it can increase the utilization efficiency of glycogen in muscles. Compared with the static control and exercise control groups, the testicular weight of rats in the administration groups increased slightly. The Icariin-Zinc complex increased the testicular weight, indicating that the function of the reproductive system was improved to some extent. Conclusion: Icariin-Zinc can significantly prolong the exhaustive swimming time, improve exercise ability, and increase the plasma testosterone level (which is beneficial for improving the reproductive ability of male rats). Moreover, the beneficial effect of Icariin-Zinc on the glycogen content, testis index, and other reproductive system glands is dose-dependent.

Overexpression of ING3 is associated with attenuation of migration and invasion in breast cancer.

Inhibitor of growth 3 (ING3) has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate ING3 expression in breast cancer, its clinical value, and how ING3 influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein interaction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that ING3 expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of ING3 compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of ING3 significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/ß-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion in vitro. However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways.

Improved in vivo stability of silicon-containing polyurethane by fluorocarbon side chain modulation of the surface structure.

As a class of widely used biomedical materials, polyurethanes suffer from their insufficient stability in vivo. Although the commercialized silicone-polyetherurethanes (SiPEUs) have demonstrated excellent biostability compared with polyetherurethanes (PEUs) for long-term implantation, the usage of polydimethylsiloxane (PDMS) inevitably decreased the mechanical properties and unexpected breaches were observed. In this study, we introduced a fluorinated diol (FDO) into SiPEU to modulate the molecular interactions and micro-separated morphology. The fluorinated silicon-containing polyurethane (FSiPEU) was achieved with desirable silicone- and fluorine-enriched surfaces and mechanical properties at a low silicon content. As evidenced by in vitro culture of macrophages and in vivo hematoxylin-eosin (H&E) staining, FSiPEU demonstrated a minimized inflammatory response. After implantation in mice for 6 months, the material was devoid of significant surface degradation and had the least chain cleavage of soft segments. The results indicate that FSiPEU could be promising candidates for long-term implantation considering the combination of biostability, biocompatibility and mechanical performances.

Hierarchical mixed-model expedites genome-wide longitudinal association analysis.

A hierarchical random regression model (Hi-RRM) was extended into a genome-wide association analysis for longitudinal data, which significantly reduced the dimensionality of repeated measurements. The Hi-RRM first modeled the phenotypic trajectory of each individual using a RRM and then associated phenotypic regressions with genetic markers using a multivariate mixed model (mvLMM). By spectral decomposition of genomic relationship and regression covariance matrices, the mvLMM was transformed into a multiple linear regression, which improved computing efficiency while implementing mvLMM associations in efficient mixed-model association expedited (EMMAX). Compared with the existing RRM-based association analyses, the statistical utility of Hi-RRM was demonstrated by simulation experiments. The method proposed here was also applied to find the quantitative trait nucleotides controlling the growth pattern of egg weights in poultry data.

Finite-temperature density-functional-theory investigation on the nonequilibrium transient warm-dense-matter state created by laser excitation.

We present a finite-temperature density-functional-theory investigation of the nonequilibrium transient electronic structure of warm dense Li, Al, Cu, and Au created by laser excitation. Photons excite electrons either from the inner shell orbitals or from the valence bands according to the photon energy, and give rise to isochoric heating of the sample. Localized states related to the 3d orbital are observed for Cu when the hole lies in the inner shell 3s orbital. The electrical conductivity for these materials at nonequilibrium states is calculated using the Kubo-Greenwood formula. The change of the electrical conductivity, compared to the equilibrium state, is different for the case of holes in inner shell orbitals or the valence band. This is attributed to the competition of two factors: the shift of the orbital energies due to reduced screening of core electrons, and the increase of chemical potential due to the excitation of electrons. The finite-temperature effect of both the electrons and the ions on the electrical conductivity is discussed in detail. This work is helpful to better understand the physics of laser excitation experiments of warm dense matter.