Machine learning-based prediction model of lower extremity deep vein thrombosis after stroke.

This study aimed to apply machine learning (ML) techniques to develop and validate a risk prediction model for post-stroke lower extremity deep vein thrombosis (DVT) based on patients' limb function, activities of daily living (ADL), clinical laboratory indicators, and DVT preventive measures. We retrospectively analyzed 620 stroke patients. Eight ML models-logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), neural network (NN), extreme gradient boosting (XGBoost), Bayesian (NB), and K-nearest neighbor (KNN)-were used to build the model. These models were extensively evaluated using ROC curves, AUC, PR curves, PRAUC, accuracy, sensitivity, specificity, and clinical decision curves (DCA). Shapley's additive explanation (SHAP) was used to determine feature importance. Finally, based on the optimal ML algorithm, different functional feature set models were compared with the Padua scale to select the best feature set model. Our results indicated that the RF algorithm demonstrated superior performance in various evaluation metrics, including AUC (0.74/0.73), PRAUC (0.58/0.58), accuracy (0.75/0.77), and sensitivity (0.78/0.80) in both the training set and test set. DCA analysis revealed that the RF model had the highest clinical net benefit. SHAP analysis showed that D-dimer had the most significant influence on DVT, followed by age, Brunnstrom stage (lower limb), prothrombin time (PT), and mobility ability. The RF algorithm can predict post-stroke DVT to guide clinical practice.

Unveiling the Nature of Superior Sodium Storage in the CoSe2/rGO Nanocomposite.

Sodium-ion batteries (SIBs) are considered the most promising alternatives to lithium-ion batteries (LIBs) due to the abundant availability of sodium and their cost-effectiveness. Transition metal selenides (TMSes) are considered promising anodes for SIBs due to their economic efficiency and high theoretical capacity. Nevertheless, overcoming the challenges of sluggish reaction kinetics and severe structural damage is crucial to improving cycle life and rate capability. Herein, a simple microwave hydrothermal process was used to synthesize a nanocomposite of CoSe2 nanoparticles uniformly anchored on reduced graphene oxide nanosheets (CoSe2/rGO). The influences of rGO on the structure and electrochemical performance and Na+ diffusion kinetics are investigated through a series of characterization and electrochemical tests. The resulting CoSe2/rGO nanocomposite exhibits a remarkable initial specific capacity of 544 mAh g-1 at 0.5 A g-1, impressive rate capability (368 mAh g-1 at 20 A g-1), and excellent cycle life and maintains 348 mAh g-1 at 5 A g-1 over 1200 cycles. In addition, the in situ electrochemical impedance spectroscopy (EIS), ex situ X-ray diffraction (XRD), and transmission electron microscopy (TEM) tests are selected to further investigate the sodium storage mechanism.

Orlistat exerts anti-obesity and anti-tumorigenic effects in a transgenic mouse model of endometrial cancer.

Introduction: Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models. Methods: In this study, the Lkb1fl/flp53fl/fl mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo. Results: The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer. Discussion: Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity in vivo and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer.

Comparative efficacy of different noninvasive brain stimulation therapies for recovery of global cognitive function, attention, memory, and executive function after stroke: a network meta-analysis of randomized controlled trials.

Background: Which noninvasive brain stimulation (NIBS) treatment - transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) - is more beneficial for stroke patients' cognitive rehabilitation is still up for debate. Objectives: Our goal is to provide an overview of the research on the effectiveness and safety of various NIBS protocols. Design: Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). Methods: This NMA compared any active NIBS versus sham stimulation in adult stroke survivors to enhance cognitive function, with a focus on global cognitive function (GCF), attention, memory, and executive function (EF) using the databases MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. The NMA statistical approach was built on a frequency framework. The effect size was estimated by the standardized mean difference (SMD) and a 95% confidence interval (CI). We compiled a relative ranking of the competing interventions based on their surface under the cumulative ranking curve (SUCRA). Results: NMA showed that high-frequency repeated TMS (HF-rTMS) improved GCF compared with sham stimulation (SMD = 1.95; 95% CI: 0.47-3.43), while dual-tDCS improved memory performance versus sham stimulation significantly (SMD = 6.38; 95% CI: 3.51-9.25). However, various NIBS stimulation protocols revealed no significant impact on enhancing attention, executive function, or activities of daily living. There was no significant difference between the active stimulation protocols for TMS and tDCS and sham stimulation in terms of safety. Subgroup analysis demonstrated an effect favoring activation site of the left dorsolateral prefrontal cortex (DLPFC) (SUCRA = 89.1) for enhancing GCF and bilateral DLPFC (SUCRA = 99.9) stimulation for enhancing memory performance. Conclusion: The HF-rTMS over the left DLPFC appears to be the most promising NIBS therapeutic option for improving global cognitive performance after stroke, according to a comparison of numerous NIBS protocols. Furthermore, for patients with post-stroke memory impairment, dual-tDCS over bilateral DLPFC may be more advantageous than other NIBS protocols. Both tDCS and TMS are reasonably safe. Registration: PROSPERO ID: CRD42022304865.

NF-κB-Inducing Kinase Provokes Insulin Resistance in Skeletal Muscle of Obese Mice.

Skeletal muscle is crucial for preserving glucose homeostasis. Insulin resistance and abnormalities in glucose metabolism result from a range of pathogenic factors attacking skeletal muscle in obese individuals. To relieve insulin resistance and restore glucose homeostasis, blocking the cell signaling pathways induced by those pathogenic factors seems an attractive strategy. It has been discovered that insulin sensitivity in obese people is inversely linked with the activity of NF-κB inducing kinase (NIK) in skeletal muscle. In order to evaluate NIK's pathological consequences, mechanism of action, and therapeutic values, an obese mouse model reproduced by feeding a high-fat diet was treated with a NIK inhibitor, B022. C2C12 myoblasts overexpressing NIK were utilized to assess insulin signaling and glucose uptake. B022 thus prevented high-fat diet-induced NIK activation and insulin desensitization in skeletal muscle. The insulin signaling in C2C12 myoblasts was compromised by the upregulation of NIK brought on by oxidative stress, lipid deposition, inflammation, or adenoviral vector. This inhibition of insulin action is mostly due to an inhibitory serine phosphorylation of IRS1 caused by ERK, JNK, and PKC that were activated by NIK. In summary, NIK integrates signals from several pathogenic factors to impair insulin signaling by igniting a number of IRS1-inhibiting kinases, and it also has significant therapeutic potential for treating insulin resistance.

A Facile Microwave Hydrothermal Synthesis of ZnFe2O4/rGO Nanocomposites for Supercapacitor Electrodes.

As a typical binary transition metal oxide, ZnFe2O4 has attracted considerable attention for supercapacitor electrodes due to its high theoretical specific capacitance. However, the reported synthesis processes of ZnFe2O4 are complicated and ZnFe2O4 nanoparticles are easily agglomerated, leading to poor cycle life and unfavorable capacity. Herein, a facile microwave hydrothermal process was used to prepare ZnFe2O4/reduced graphene oxide (rGO) nanocomposites in this work. The influence of rGO content on the morphology, structure, and electrochemical performance of ZnFe2O4/rGO nanocomposites was systematically investigated. Due to the uniform distribution of ZnFe2O4 nanoparticles on the rGO surface and the high specific surface area and rich pore structures, the as-prepared ZnFe2O4/rGO electrode with 44.3 wt.% rGO content exhibits a high specific capacitance of 628 F g-1 and long cycle life of 89% retention over 2500 cycles at 1 A g-1. This work provides a new process for synthesizing binary transition metal oxide and developing a new strategy for realizing high-performance composites for supercapacitor electrodes.

Environmental barriers and participation restrictions in community-dwelling individuals with spinal cord injury in Jiangsu and Sichuan Provinces of China: Results from a cross-sectional survey.

OBJECTIVE: (1) to describe environmental barriers and participation restrictions experienced by people with spinal cord injury (SCI) from China, (2) to examine associations between lesion characteristics and participation restrictions, considering a mediating role of environmental barriers, (3) to identify those environmental barriers that have the largest influence on participation. DESIGN: Cross-sectional study. This study is part of the International Spinal Cord Injury Survey (InSCI). SETTING: Community, Jiangsu and Sichuan Province, China. PARTICIPANTS: 1355 persons with SCI. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Participation restrictions were measured with items from the Model Disability Survey, Environmental Barriers were measured with the Nottwil Environmental Factors Inventory-Short Form. RESULTS: Participants experienced a median of five (IQR 1-9) environmental barriers and five (IQR 0-9) participation restrictions. Environmental barriers were mainly reported in relation to climate, insufficient resources and accessibility, and participation restrictions mainly occurred in using public transportation, taking care of others, and getting to places. In an adjusted zero-inflated Poisson model, people with more severe injuries reported a greater number of environmental barriers (complete injury: IRR = 1.31, 95%CI = [1.24,1.38]) and participation restrictions (tetraplegia: IRR = 1.15, 95%CI = [1.10,1.21]; complete injury: IRR = 1.25, 95%CI = [1.18,1.31]). Moreover, environmental barriers (IRR = 1.07, 95%CI = [1.06,1.08]) were a significant predictor of participation restrictions and partially mediated the association of lesion completeness with participation restrictions. Barriers related to accessibility of public places (IRR = 1.47, 95%CI = [1.33,1.62]), accessing homes (IRR = 1.32, 95%CI = [1.21,1.44]), long distance transportation (IRR = 1.11, 95%CI = [1.04,1.20]), communication devices (IRR = 1.07, 95%CI = [1.01,1.15]) and state services (IRR = 1.10, 95%CI = [1.02,1.19]) had the greatest negative impact on participation. CONCLUSION: Social participation of people with SCI is seriously restricted in China. Removing environmental barriers will be an important element of programs to address this problem.

Achieving High-Energy-Density Graphene/Single-Walled Carbon Nanotube Lithium-Ion Capacitors from Organic-Based Electrolytes.

Developing electrode materials with high voltage and high specific capacity has always been an important strategy for increasing the energy density of lithium-ion capacitors (LICs). However, organic-based electrolytes with lithium salts limit their potential for application in LICs to voltages below 3.8 V in terms of polarization reactions. In this work, we introduce Li[N(C2F5SO2)2] (lithium Bis (pentafluoroethanesulfonyl)imide or LiBETI), an electrolyte with high conductivity and superior electrochemical and mechanical stability, to construct a three-electrode LIC system. After graphite anode pre-lithiation, the anode potential was stabilized in the three-electrode LIC system, and a stable solid electrolyte interface (SEI) film formed on the anode surface as expected. Meanwhile, the LIC device using LiBETI as the electrolyte, and a self-synthesized graphene/single-walled carbon nanotube (SWCNT) composite as the cathode, showed a high voltage window, allowing the LIC to achieve an operating voltage of 4.5 V. As a result, the LIC device has a high energy density of up to 182 Wh kg-1 and a 2678 W kg-1 power density at 4.5 V. At a current density of 2 A g-1, the capacity retention rate is 72.7% after 10,000 cycles.

Effects of Gaze Stabilization Exercises on Gait, Plantar Pressure, and Balance Function in Post-Stroke Patients: A Randomized Controlled Trial.

This study aims to explore the effects of gaze stabilization exercises (GSEs) on gait, plantar pressure, and balance function in post-stroke patients (≤6 months). Forty post-stroke patients were randomly divided into an experimental group (n = 20) and a control group (n = 20). The experimental group performed GSEs combined with physical therapy, while the control group only performed physical therapy, once a day, 5 days a week, for 4 weeks. The Berg Balance Scale (BBS) was used to test the balance function and the risk of falling, which was the primary outcome. The Timed Up and Go test (TUGT) evaluated the walking ability and the fall risk. The envelope ellipse area and the plantar pressure proportion of the affected side were used to measure the patient's supporting capacity and stability in static standing. The anterior−posterior center of pressure displacement velocity was used to test the weight-shifting capacity. Compared to the control group, the swing phase of the affected side, swing phase's absolute symmetric index, envelope ellipse area when eyes closed, and TUGT of the experimental group had significantly decreased after GSEs (p < 0.05); the BBS scores, TUGT, the anterior−posterior COP displacement velocity, and the plantar pressure proportion of the affected side had significantly increased after 4 weeks of training (p < 0.05). In conclusion, GSEs combined with physical therapy can improve the gait and balance function of people following stroke. Furthermore, it can enhance the weight-shifting and one-leg standing capacity of the affected side, thus reducing the risk of falling.

A nomogram for individualized prediction of lower extremity deep venous thrombosis in stroke patients: A retrospective study.

To develop and validate a nomogram for individualized prediction of lower extremity deep venous thrombosis (DVT) in stroke patients based on extremity function and daily living ability of stroke patients. In this study, 423 stroke patients admitted to the Rehabilitation Medical Center of the First Affiliated Hospital of Nanjing Medical University from December 2015 to February 2019 were taken as the subjects, who were divided into the DVT group (110) and No-DVT group (313) based on the existence of DVT. Inter-group comparison of baseline data was performed by 1-way Analysis of Variance, Kruskal-Wallis rank-sum test, or Pearson chi-square test. Data dimensions and predictive variables were selected by least absolute shrinkage and selection operator (LASSO); the prediction model was developed and the nomogram was prepared by binary logistics regression analysis; the performance of the nomogram was identified by the area under the receiver operating characteristic curve (AUC), Harrell's concordance index, and calibration curve; and the clinical effectiveness of the model was analyzed by clinical decision curve analysis. Age, Brunnstrom stage (lower extremity), and D-dimer were determined to be the independent predictors affecting DVT. The independent predictors mentioned above were developed and presented as a nomogram, with AUC and concordance index of 0.724 (95% confidence interval [CI]: 0.670-0.777), indicating the satisfactory discrimination ability of the nomogram. The P value of the results of the Hosmer-Lemeshow test was 0.732, indicating good fitting of the prediction model. Decision curve analysis showed that the clinical net benefit of this model was 6% to 50%. We developed a nomogram to predict lower extremity deep venous thrombosis in stroke patients, and the results showed that the nomogram had satisfactory prediction performance and clinical efficacy.

Altered cerebellar functional connectivity in chronic subcortical stroke patients.

Background: Previous studies demonstrated that cerebellar subregions are involved in different functions. Especially the cerebellar anterior lobe (CAL) and cerebellar posterior lobe (CPL) have been postulated to primarily account for sensorimotor and cognitive function, respectively. However, the functional connectivity (FC) alterations of CAL and CPL, and their relationships with behavior performance in chronic stroke participants are unclear so far. Materials and methods: The present study collected resting-state fMRI data from thirty-six subcortical chronic stroke participants and thirty-eight well-matched healthy controls (HCs). We performed the FC analysis with bilateral CAL and CPL as seeds for each participant. Then, we detected the FC difference between the two groups by using a two-sample t-test and evaluated the relationship between the FC and scores of motor and cognitive assessments across all post-stroke participants by using partial correlation analysis. Results: The CAL showed increased FCs in the prefrontal cortex, superior/inferior temporal gyrus, and lingual gyrus, while the CPL showed increased FCs in the inferior parietal lobule, precuneus, and cingulum gyrus in the stroke participants compared with HCs. Moreover, the FC alteration in the right CAL and the right CPL were negatively correlated with executive and memory functions across stroke participants, respectively. Conclusion: These findings shed light on the different increased FC alteration patterns of CAL and CPL that help understand the neuro-mechanisms underlying behavior performance in chronic stroke survivors.

Development and Validation of a Nomogram to Predict Hemiplegic Shoulder Pain in Patients With Stroke: A Retrospective Cohort Study.

Objective: The development and validation of a nomogram for the individualized prediction of hemiplegic shoulder pain (HSP) during the inpatient rehabilitation of patients with stroke. Design: Retrospective cohort study. Setting: The rehabilitation department at a tertiary hospital. Participants: A total of 376 patients (N=376) with stroke admitted to inpatient rehabilitation from January 2018 to April 2021 were included in this study. Interventions: Not applicable. Main Outcome Measures: The outcome measure was shoulder pain on the patients' hemiplegic side occurring at rest or with movement during hospitalization. Results: Among the 376 patients with stroke, 113 (30.05%) developed HSP. Five independent predictors were included in the nomogram: subluxation, Brunnstrom stage, hand edema, spasticity, and sensory disturbance. The nomogram was a good predictor, with a C-index of 0.85 (95% confidence interval, 0.81-0.89) and corrected C-index of 0.84. The Homer-Lemeshow test (χ2=13.854, P=.086) and calibration plot suggested good calibration ability of the nomogram. The optimal cutoff value for the predicted probability of HSP was 0.30 (sensitivity, 0.73; specificity, 0.83). Moreover, the decision curve analysis revealed that the nomogram would add net clinical benefits if the threshold possibility of HSP risk was from 5%-88%. Conclusions: Our nomogram could accurately predict HSP, which may help clinicians accurately quantify the HSP risk in individuals and implement early interventions.

A Nomogram for Individualized Prediction of Calf Muscular Vein Thrombosis in Stroke Patients During Rehabilitation: A Retrospective Study.

Objectives: To develop a nomogram for predicting calf muscle veins thrombosis (CMVT) in stroke patients during rehabilitation. Methods: We enrolled 360 stroke patients from the Rehabilitation Medicine Center from December 2015 to February 2019. Of the participants, 123 were included in the CMVT group and 237 in the no CMVT group. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. Performance and clinical utility of the nomogram were generated using the Harrell's concordance index, calibration curve, and decision curve analysis (DCA). Results: Age, Brunnstrom stage (lower extremity), D-dimer, and antiplatelet therapy were associated with the occurrence of CMVT. The prediction nomogram showed satisfactory performance with a concordance index of 0.718 (95% CI: 0.663-0.773) in internal verification. The Hosmer-Lemeshow test, P = .217, suggested that the model was of goodness-of-fit. In addition, the DCA demonstrated that the CMVT nomogram had a good clinical net benefit. Conclusions: We developed a nomogram that could help clinicians identify high-risk groups of CMVT in stroke patients during rehabilitation for early intervention.

Ultra-Fine Ruthenium Oxide Quantum Dots/Reduced Graphene Oxide Composite as Electrodes for High-Performance Supercapacitors.

This study synthesized ultra-fine nanometer-scaled ruthenium oxide (RuO2) quantum dots (QDs) on reduced graphene oxide (rGO) surface by a facile and rapid microwave-assisted hydrothermal approach. Benefiting from the synergistic effect of RuO2 and rGO, RuO2/rGO nanocomposite electrodes showed ultra-high capacitive performance. The impact of different RuO2 loadings in RuO2/rGO nanocomposite on their electrochemical performance was investigated by various characterizations. The composite RG-2 with 38 wt.% RuO2 loadings exhibited a specific capacitance of 1120 F g-1 at 1 A g-1. In addition, it has an excellent capacity retention rate of 84 % from 1A g-1 to 10 A g-1, and excellent cycling stability of 89% retention after 10,000 cycles, indicating fast ion-involved redox reactions on the nanocomposite surfaces. These results illustrate that RuO2/rGO composites prepared by this facile process can be an ideal candidate electrode for high-performance supercapacitors.

Combination of repetitive transcranial magnetic stimulation and treadmill training reduces hyperreflexia by rebalancing motoneuron excitability in rats after spinal cord contusion.

Spasticity commonly emerges during the process of recovery after spinal cord injury (SCI) and critically exacerbates motor dysfunction. Given insufficient effects of individual therapies, we combined repetitive transcranial magnetic stimulation (rTMS) with treadmill training (Tr) in rats with SCI to investigate potential synergistic effects on alleviating spasticity and motor dysfunction. Animals were randomized into four groups: SCI only, rTMS, Tr, and rTMS plus Tr. At the study endpoint eight weeks after the start of interventions, the rTMS plus Tr group exhibited the largest decrease in maximal H-reflex amplitude/maximal M-wave amplitude ratio (effect size (ES): -0.082, 95% confidence interval (CI): -0.118 to -0.046, p < 0.001) as well as the greatest improvement in motor function measured with the Basso, Beattie, and Bresnahan locomotor scale (ES: 1.811, 95% CI: 1.018 to 2.603, p < 0.001; significantly different from all other groups at p < 0.01) and grid-walking test (ES: -5.1, 95% CI: -7.784 to -2.416, p < 0.001, significantly different from rTMS alone at p < 0.01). Pathological analyses demonstrated that the combined treatment facilitated the growth of serotonergic axons around the lesion site, and the upregulation of 5-hydroxytryptamine, potassium-chloride cotransporter-2, and glutamic acid decarboxylases 67 in the lumbar spinal cord distal to the injury site. All effects of combined treatment of rTMS and treadmill training were enhanced compared to treadmill training or rTMS alone. Treadmill training and rTMS intervention appear to have synergistic effects on hyperreflexia and locomotion likely related to a restored balance between facilitatory and inhibitory inputs to motoneurons.

Remotely monitored Baduanjin exercise in moderate-to-severe chronic obstructive pulmonary disease patients (BROCADE): A study protocol.

BACKGROUND: Baduanjin is a traditional Chinese exercise regimen used to treat various chronic illnesses and is associated with both psychological and physical benefits. However, its benefits for patients suffering from chronic obstructive pulmonary disease (COPD) are unclear. This study aims to assess the efficacy, safety, and underlying mechanisms of Baduanjin exercise in patients with moderate-to-severe COPD (BROCADE) by remote monitoring. METHODS: This study protocol describes a multicenter, open-label, prospective randomized computed tomography. A total of 150 individuals who meet the inclusion criteria after the screening and consent processes will take part in the study. All participants will be provided routine medication and lifestyle interventions. They will be randomly assigned to a control group, a classical pulmonary rehabilitation group, or a Baduanjin group, which will undergo remotely monitored Baduanjin exercises for a cumulative duration of 1 hour per day, three times per week for 12 weeks. The participants will be followed for 24 weeks. The primary outcomes will be a 6-minutes walking distance and St. George's Respiratory Questionnaire index. The secondary outcomes will be lung function, cross-sectional area of the pectoralis major and subcutaneous fat, modified Medical Research Council score, COPD assessment test questionnaire results, extremity muscle strength, and quality of life. Any adverse events that may occur will be monitored and recorded. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for publication once completed. CONCLUSION: A novel neutrophil-related inflammatory mechanism will potentially be identified. In addition, the study results will provide a safe, effective, simple and operational Baduanjin exercise protocol for moderate-to-severe COPD patients aimed at improving prognosis and quality of life.

Melatonin attenuates repeated mild traumatic brain injury-induced cognitive deficits by inhibiting astrocyte reactivation.

Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.

Asparagus officinalis Exhibits Anti-Tumorigenic and Anti-Metastatic Effects in Ovarian Cancer.

Ovarian cancer is one of the leading causes of female cancer death. Emerging evidence suggests that many dietary natural products have anti-tumorigenic activity, including that of asparagus officinalis. The current study aimed to assess the anti-tumorigenic and anti-metastatic effects of asparagus officinalis on serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer. Asparagus officinalis decreased cellular viability, caused cell cycle G1 phase arrest and induced apoptosis in the OVCAR5 and SKOV3 cells. Induction of apoptosis and inhibition of cell proliferation was rescued by the pan-caspase inhibitor, Z-VAD-FMK, implying that its cytotoxic effects were mainly dependent on caspase pathways. Asparagus officinalis increased levels of ROS and decreased mitochondrial membrane potential with corresponding increases in PERK, Bip, Calnexin PDI and ATF4 in both cell lines. Treatment with asparagus officinalis also reduced ability of adhesion and invasion through epithelial-mesenchymal transition and reduction of VEGF expression. The combination of Asparagus officinalis with paclitaxel had synergistic anti-proliferative activity. Furthermore, Asparagus officinalis significantly inhibited tumor growth and reduced serum VEGF in a genetically engineered mouse model of ovarian cancer under obese and lean conditions, accompanied with a decrease in the expression of Ki67, VEGF and phosphorylated S6, and in an increase in phosphorylation of AMPK in the ovarian tumor tissues. Overall, our data provide a pre-clinical rationale for asparagus officinalis in the prevention and treatment of ovarian cancer as a novel natural product.

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury.

BACKGROUND This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) on motor function recovery in rats with partial spinal cord injury (SCI). MATERIAL AND METHODS Sixty rats with moderate partial SCI at the 9th thoracic vertebral level induced by a Louisville Injury System Apparatus impactor were randomly allocated to 5 groups: Sham surgery (Intact); Sham rTMS without TT (S-rTMS/Non-TT); Sham rTMS with TT (S-rTMS/TT); rTMS without TT (rTMS/Non-TT); and rTMS with TT (rTMS/TT). Interventions commenced 8 days after SCI and continued for 8 weeks. Outcomes studied were Basso, Beattie, and Bresnahan locomotor scale scores, grid walking test, and biochemical analysis of the brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in the motor cortex and spinal cord. RESULTS The rTMS/TT contributed to greater Basso, Beattie, and Bresnahan scores compared with the S-rTMS/Non-TT (P<0.01), S-rTMS/TT (P<0.05), and rTMS/Non-TT (P<0.05), and showed obviously reduced numbers of foot drops compared with the S-rTMS/Non-TT (P<0.05). The rTMS/TT significantly increased the expressions of BDNF, SYN, and PSD-95 compared with the S-rTMS/Non-TT, both in the motor cortex (P<0.01, P<0.01, P<0.001, respectively) and spinal cord (P<0.001, P<0.01, P<0.05, respectively). CONCLUSIONS In a modified rat model of SCI, combined rTMS with TT improved motor function, indicating that this combined approach promoted adaptive neuroplasticity between the motor cortex and the spinal cord. A combined app roach to improving motor function following SCI requires further evaluation to determine the possible clinical applications.

Association between circular RNA expression content and severity of coronary atherosclerosis in human coronary artery.

BACKGROUND: Circular RNAs (circRNAs) may act as biomarkers of coronary artery disease (CAD). However, the relationship between expression characteristics of circRNAs and coronary atherosclerosis has not been fully explored. The aim of this study was to determine and characterize the circRNAs from human coronary artery. METHODS: The coronary artery segments were obtained from an 81-year-old male patient with sudden death of myocardial infarction at autopsy. The coronary stenosis and atherosclerosis were evaluated by hematoxylin and eosin (H&E) staining, and the circRNAs expression profile was characterized by RNA sequencing (RNA-seq). The differentially expressed circRNAs were validated by qRT-PCR. RESULTS: The analysis of H&E staining indicated that coronary atherosclerosis grade and extent in the LM was more serious than that in other coronary arteries. Twenty-seven circRNAs were selected for expression validation in coronary artery. CircRNAs corresponding cyclization sites of 3 circRNAs (hsa_circ_0016868, hsa_circ_0001364, hsa_circ_0006731) have been verified by Sanger sequencing. CONCLUSION: The 3 circRNAs are suggested to play a pathological role underlying the coronary arteries atherosclerosis and may serve as a valuable resource as diagnostic or therapeutic targets against CAD.