Local Well-Posedness of the Skew Mean Curvature Flow for Small Data in d≧2 Dimensions.

The skew mean curvature flow is an evolution equation for d dimensional manifolds embedded in Rd+2 (or more generally, in a Riemannian manifold). It can be viewed as a Schrödinger analogue of the mean curvature flow, or alternatively as a quasilinear version of the Schrödinger Map equation. In an earlier paper, the authors introduced a harmonic/Coulomb gauge formulation of the problem, and used it to prove small data local well-posedness in dimensions d≧4. In this article, we prove small data local well-posedness in low-regularity Sobolev spaces for the skew mean curvature flow in dimension d≧2. This is achieved by introducing a new, heat gauge formulation of the equations, which turns out to be more robust in low dimensions.

A midterm follow-up study of the application of a confluent aortic valve neocuspidization technique with pericardium in children.

Background: The treatment of aortic valve diseases in children remains a great challenge. We aim to report outcomes and midterm follow-up data of our confluent neocuspidization technique with pericardium for aortic valve replacement (AVR) in children. Methods: A retrospective analysis was performed on all 20 children who underwent the confluent neocuspidization technique with pericardium at Children's Hospital of Fudan University from March 2017 to May 2022. Outcome measures included echocardiographic measurements, surgical intervention, and mortality. Results: A total of 20 patients (17 males vs. 3 females), with a median age of 7.5 years [min-max, 0.3-12 years; interquartile range (IQR), 4.4-9.7 years], a median body weight of 24.0 kg (min-max, 6.0-52.3 kg; IQR, 15.6-31.0 kg), and median aortic valve annulus size before surgery of 19.0 mm (min-max, 11.0-25.0 mm; IQR, 17.1-21.5 mm), underwent the neocuspidization technique with pericardium (17 autologous pericardia and 3 bovine patch). With 50% of bicuspid aortic valve and 50% of tricuspid, they were respectively diagnosed as aortic stenosis (AS) (7/20, 35%), aortic regurgitation (AR) (8/20, 40%) and mixed AS and AR (AS & AR) (5/20, 25%). The median postoperative follow-up time was 19 months (min-max, 5-61 months; IQR, 16.3-35 months). The peak pressure gradient across the aortic valve decreased from 81.0±37.0 mmHg in AS group and AS & AR group before surgery to 25.9±15.8 mmHg within 24 hours after surgery (P<0.001) and was mostly around 25 mmHg during follow-up. All patients presented mild or less than mild regurgitation within 24 hours after surgery. There were no hospital mortalities. Three patients needed reintervention during follow-up. There was one late death related to mitral valve stenosis. Conclusions: Though the confluent neocuspidization technique with pericardium provided immediate relief of significant AS or regurgitation, the midterm outcome was suboptimal. More research is needed to find the optimal material for AVR.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.

Attention bias modification for depression: A systematic review and meta-analysis.

Background: Depression is a mental health disorder characterized by affective, somatic, and cognitive symptoms. Attention bias modification (ABM) has been widely used to treat depression. However, the results seem inconsistent. We conducted a systematic review and meta-analysis to investigate the efficacy of ABM for depression and to explore the optimal protocol of ABM. Methods: Seven databases were systematically searched from their inceptions to 5 October 2022 to include randomized controlled trials (RCTs) of ABM for depression. Two independent reviewers selected the eligible articles, extracted data, and evaluated the risk of bias using version 2 of the Cochrane risk-of-bias tool (ROB 2.0) for randomized trials. The primary outcome was the evaluation of depressive symptoms using widely accepted and validated scales. The secondary outcomes included rumination and attentional control. Meta-analysis was conducted by using RevMan (version 5.4) and Stata (version 12.0). Subgroup analyses and meta-regressions were performed to identify the source of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 19 trials involving 20 datasets (1,262 participants) were included. The overall risk of bias in one study was rated as low risk of bias, three studies were considered as high, and the remaining studies were some concerns. Compared with attention control training (ACT), ABM had a greater effect in the improvement of depression (SMD = -0.48, 95% CI -0.80 to -0.17, I2 = 82%) and rumination (MD = -3.46, 95% CI -6.06 to -0.87, I2 = 0%). No significant differences were observed in the attentional control outcome between ABM and ACT (MD = 3.07, 95% CI -0.52 to 6.65, I 2 = 0%). Subgroup analysis demonstrated that adults exhibited a greater decrease in depression scores than adolescents. ABM using the dot-probe task, training target stimulus presented by face, and training directions by left-right were associated with better antidepressant effects. ABM training delivered in the laboratory tended to yield a better effect than those conducted at home. Sensitivity analysis indicated that the results were robust. The certainty of the evidence for all outcomes was low or very low, and publication bias may exist. Conclusion: Due to high heterogeneity and limited studies, not enough current evidence supported that ABM could be an effective intervention to relieve depressive symptoms. More rigorous RCTs are required to verify the benefits and to explore the optimal protocol of ABM training for depression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42021279163].

Diagnosis and intervention of severe tricuspid regurgitation secondary to rupture of the chordae tendineae: A case report and literature review.

Unguarded severe tricuspid regurgitation caused by rupture of papillary muscle or chordae tendineae is rare but fatal in neonates. The experience in the management of these patients is still limited. A newborn presenting severe cyanosis after delivery was diagnosed with severe tricuspid regurgitation secondary to rupture of chordae tendineae by echocardiography (Echo), then treated by surgical reconstruction of chordae/papillary muscle connection without artificial materials. A takeaway lesson from this case is that Echo is an important method to diagnose a rupture of chordae tendineae or papillary muscle and that prompt diagnosis and timely surgery can be life-saving.

Advances in the development of phosphodiesterase 7 inhibitors.

Phosphodiesterase 7 (PDE7) specifically hydrolyzes cyclic adenosine monophosphate (cAMP), a second messenger that plays essential roles in cell signaling and physiological processes. Many PDE7 inhibitors used to investigate the role of PDE7 have displayed efficacy in the treatment of a wide range of diseases, such as asthma and central nervous system (CNS) disorders. Although PDE7 inhibitors are developed more slowly than PDE4 inhibitors, there is increasing recognition of PDE7 inhibitors as potential therapeutics for no nausea and vomiting secondary. Herein, we summarized the advances in PDE7 inhibitors over the past decade, focusing on their crystal structures, key pharmacophores, subfamily selectivity, and therapeutic potential. Hopefully, this summary will lead to a better understanding of PDE7 inhibitors and provide strategies for developing novel therapies targeting PDE7.

Retrospective cohort study on the correlation analysis among peri-procedural factors, complications, and local tumor progression of lung tumors treated with CT-guided microwave ablation.

Background: Despite adherence to guidelines, recurrence of lesions remains possible in lung tumor microwave ablation (MWA) even when termination is enabled by 5-10 mm ground glass changes. Limited evidence exists regarding the correlation between timely management of perioperative complications (including pneumothorax, pleural effusion, hemorrhage, cavity formation, and infection) and local tumor progression. This retrospective study aimed to investigate the relationship among peri-procedural factors, complications, and local tumor progression in 164 cases of lung tumors treated with computed tomography-guided MWA (CT-MWA), and improve the local prognosis and reduce the complication rate of CT-guided lung tumor ablation. Methods: We reviewed 164 consecutive patients who underwent CT-MWA at Fudan University Shanghai Cancer Center's Minimally Invasive Therapy Center for lung cancer from September 2019 to May 2020. Correlative analysis was performed between peri-procedural factors, complications and outcomes (local tumor progression rates). Patients who have had prior surgery or previous MWA were excluded. Ablation was the first treatment of choice, and all patients who have had other treatments were excluded. Patients were followed every 3 months with CT. Outcomes of ablation including complications and local tumor progression were evaluated. Peri-procedural factors included demographical factors, tumor features, ablation parameters, management of intra-procedural pneumothorax, and CT features. Complications included pneumothorax, post-procedural refractory infection, and pleural effusion. Results: The study included 98 males and 68 females, with an average age of 56.1 years. Local tumor progression rate was negatively correlated with intra-procedural management of pneumothorax (R=-0.550, P=0.0003) and Hounsfield unit (HU) difference between HU before and after procedure (R=-0.855, P=0.006), and positively correlated with the average HU value of immediate post-procedural CT at the measurement points (R=0.857, P=0.00002). The correlation analysis results also showed a positive correlation between infection after procedure and pneumothorax (R=0.340, P=0.0001). Conclusions: A greater difference between HU before and after the procedure or a decrease in CT values immediately after ablation may predict a higher rate of local complete ablation. Prompt management of intraoperative pneumothorax may lower local tumor progression rates and decrease incidence of post-procedural infection.

The Connection of Early Life Adversity and Post Traumatic Stress Disorder: an Updated Review.

Human beings develop a highly coordinated and flexible system of social behavior and threat evaluation. In this review we focus on the unique role of early life adversity (ELA) in programming deficits in social behavior and threat processing, and provides guidance on future investigations in the areas of stress reactivity and mental health. We propose that neuroendocrine perturbations of hypothalamus-pituitary-adrenal (HPA) axis and gene activity by epigenetic mechanisms may explain how early adverse circumstances may lead to post traumatic stress disorder (PTSD). The detailed exploration of the interaction of stress as environmental factor and epigenetic and genetic regulation in HPA axis may improve targeted interventions among vulnerable individuals. We are convinced that further studies following these directions will contribute to effective prevention and treatment of PTSD in early traumatized patients.

The effectiveness and safety of repetitive transcranial magnetic stimulation on spasticity after upper motor neuron injury: A systematic review and meta-analysis.

To systematically evaluate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) on spasticity after upper motor neuron (UMN) injury. Eight electronic databases were searched from inception to August 6, 2022. Randomized controlled trials (RCTs) investigating the effectiveness and safety of rTMS on spasticity after UMN injury were retrieved. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Review Manager 5.3 and Stata 14.0 software were used to synthesize data. The certainty of the evidence was appraised with the Grade of Recommendation, Assessment, Development and Evaluation tool. Forty-two studies with a total of 2,108 patients were included. The results of meta-analysis revealed that, compared with control group, rTMS could significantly decrease scores of the Modified Ashworth Scale (MAS) in patients with UMN injury. The subgroup analysis discovered that rTMS effectively decreased the MAS scores in patients with stroke. Meanwhile, rTMS treatment > 10 sessions has better effect and rTMS could decrease the MAS scores of upper limb. Thirty-three patients complained of twitching facial muscles, headache and dizziness, etc. In summary, rTMS could be recommended as an effective and safe therapy to relieve spasticity in patients with UMN injury. However, due to high heterogeneity and limited RCTs, this conclusion should be treated with caution.

Human-computer interaction emotional design and innovative cultural and creative product design.

To make the interface design of computer application system better, meet the psychological and emotional needs of users, and be more humanized, the emotional factor is increasingly valued by interface designers. In the design of human-computer interaction graphical interfaces, the designer attaches great importance to the emotional design of the interface, and enhances the humanized design of the interface, which cannot only improve the comfort of the interface, but also improve the fun of the interface, to ensure the psychological and emotional needs of users can be better satisfied. It may acquire information that is favorable to innovative design by utilizing cluster analysis algorithm to tackle the problem of complicated cultural information, and then utilize cellular genetic algorithm to carry out creative design of cultural items. It increases the availability of cultural and creative goods. The classic cluster analysis technique offers the maximum data clustering effect of 53.3%, according to the findings of this paper's experiments. While the improved cluster analysis algorithm has the highest data clustering effect of 90%. It can be seen that the improved cluster analysis algorithm can effectively perform cluster analysis on a large amount of data in cultural and creative products. It thus finds out the most suitable designer's creative information, which helps designers create better products.

Heparin/Collagen-REDV Modification of Expanded Polytetrafluoroethylene Improves Regional Anti-thrombosis and Reduces Foreign Body Reactions in Local Tissues.

Prosthetic implants of expanded polytetrafluoroethylene (ePTFE) in the cardiovascular system have a high failure rate over the long term because of thrombosis and intimal hyperplasia. Although multiple surface modification methods have been applied to improve the anti-thrombotic and in situ endothelialization abilities of ePTFE, none have delivered outstanding results in vivo. Our previous study combined heparin/collagen multilayers and REDV peptides to modify ePTFE, and the in-vitro results showed that modification ePTFE with heparin/collagen-REDV can promote the cytocompatibility and antiplatelet property. This study illustrated the physical change, selective endothelial cells capture ability, and in vivo performance in further. The physical test demonstrated that this modification improved the hydrophilicity, flexibility and strength of ePTFE. A competition experiment of co-cultured endothelial cells and vascular smooth muscle cells verified that the heparin/collagen-REDV modification had high specificity for endothelial cell capture. A rabbit animal model was constructed to evaluate the in vivo performance of modified ePTFE implanted in the right ventricular outflow tract. The results showed that heparin/collagen-REDV modification was safe, promoted endothelialization, and successfully achieved regional anti-thrombosis without influencing body-wide coagulation function. The pathologic manifestations and mRNA expression pattern in tissues in contact with modified ePTFE indicated that this modification method may reduce M2-type macrophage infiltration and the expression of genes related to immune and inflammatory responses. The heparin/collagen-REDV modification may lower the incidence of complications related to ePTFE implantation and has good prospects for clinical use.

Increased Prefrontal Activation During Verbal Fluency Task After Repetitive Transcranial Magnetic Stimulation Treatment in Depression: A Functional Near-Infrared Spectroscopy Study.

Background: Previous studies have shown the clinical effect of 2 Hz repetitive transcranial magnetic stimulation (rTMS) for depression; however, its underlying neural mechanisms are poorly understood. The aim of this study was to examine the effects of rTMS on the activity of the prefrontal cortex in patients with depression, using functional near-infrared spectroscopy (fNIRS). Methods: Forty patients with major depressive disorder (MDD) and 40 healthy controls were enrolled in this study. Patients underwent 4 weeks of 2 Hz TMS delivered to the right dorsolateral prefrontal cortex (DLPFC). fNIRS was used to measure the changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex during a verbal fluency task (VFT) in depressed patients before and after rTMS treatment. The severity of depression was assessed using the Hamilton Rating Scale for Depression-24 item (HAMD-24). Results: Prior to rTMS, depressed patients exhibited significantly smaller [oxy-Hb] values in the bilateral prefrontal cortex during the VFT compared with the healthy controls. After 4 weeks of 2 Hz right DLPFC rTMS treatment, increased [oxy-Hb] values in the bilateral frontopolar prefrontal cortex (FPPFC), ventrolateral prefrontal cortex (VLPFC) and left DLPFC during the VFT were observed in depressed patients. The increased [oxy-Hb] values from baseline to post-treatment in the right VLPFC in depressed patients were positively related to the reduction of HAMD score following rTMS. Conclusion: These findings suggest that the function of the prefrontal cortex in depressed patients was impaired and could be recovered by 2 Hz rTMS. The fNIRS-measured prefrontal activation during a cognitive task is a potential biomarker for monitoring depressed patients' treatment response to rTMS.

Local Well-Posedness of Skew Mean Curvature Flow for Small Data in d ≥ 4 Dimensions.

The skew mean curvature flow is an evolution equation for d dimensional manifolds embedded in R d + 2 (or more generally, in a Riemannian manifold). It can be viewed as a Schrödinger analogue of the mean curvature flow, or alternatively as a quasilinear version of the Schrödinger Map equation. In this article, we prove small data local well-posedness in low-regularity Sobolev spaces for the skew mean curvature flow in dimension d ≥ 4 .

Neural Activation via Acupuncture in Patients With Major Depressive Disorder: A Functional Near-Infrared Spectroscopy Study.

Background and Objective: Acupuncture is used as an alternative treatment for patients with major depressive disorder (MDD). The associated therapeutic effect of acupuncture is often attributed to its modulatory effect on the activity of the pre-frontal cortex (PFC), although the mechanism is not well-studied. We employed a repeated measures design to investigate the brain modulatory effect of acupuncture on the PFC in a group of patients with MDD and investigated whether the modulatory effect is influenced by the severity of the disease. Methods: A total of 47 patients diagnosed with MDD were enrolled in this functional near-infrared spectroscopy experiment. The severity of depressive symptoms was measured at baseline using the Hamilton Depression Rating Scale-24 (HAMD). The cortical activation in the bilateral PFC areas during a verbal fluency task (VFT) was measured before and after a single session of acupuncture in the Baihui acupoint. We further explored the potential correlation between the severity of MDD and task-related activation before and after acupuncture. Results: A single session of acupuncture significantly tended to enhance the activation level of the left frontopolar cortex in patients with severe depression during VFT, but a null effect was found in those with mild to moderate depression. Among patients with severe depression, a strong correlation was observed between HAMD scores and the change in VFT-related activation after acupuncture in the left dorsolateral PFC (DLPFC). Conclusion: A single session of acupuncture did not significantly modulate the activation of the left PFC in patients with mild to moderate depression; however, it demonstrated a tendency to enhance the activation of the frontopolar area in patients with severe depression. Among patients with severe depression, there is a correlation between the activation by acupuncture of left DLPFC during executive functioning and the severity of depressive symptoms, suggesting that the brain activity induced by acupuncture is likely to be influenced by the baseline disease severity in patients with MDD.

Evaluation of abnormal iron distribution in specific regions in the brains of patients with Parkinson's disease using quantitative susceptibility mapping and R2* mapping.

The primary aim of the present study was to evaluate abnormal iron distribution in specific regions of the brains in patients with Parkinson's disease (PD) using quantitative susceptibility mapping (QSM) and R2* mapping, and to compare the diagnostic performances of QSM and R2* mapping in differentiating patients with PD with that in normal controls. A total of 25 patients with idiopathic PD and 28 sex-and age-matched normal controls were included in the present study and their brains investigated using a 3T scanner. Magnetic resonance imaging techniques, namely, QSM and R2* mapping, were applied to generate susceptibility and R2* values. The differences in susceptibility and R2* values in deep grey matter nuclei between patients with PD and the normal controls were compared using independent samples t-tests. The abilities of QSM and R2* mapping to classify patients with PD and normal controls were analyzed using receiver operating characteristic curves. Correlation analyses between imaging parameters (e.g. susceptibility and R2* values) and clinical feature (disease severity assessed using the Hoehn and Yahr score) were performed. The intra-class correlation coefficient (ICC) for susceptibility (ICC=0.977; P<0.001) and R2* (ICC=0.945; P<0.001) values between two neuro-radiologists were >0.81, showing excellent inter-rater agreement. The susceptibility values were significantly increased in the substantia nigra (SN) and red nucleus, but were decreased in the putamen of patients with PD compared with that in the corresponding brain regions of normal controls. However, increased R2* values were observed only in the SN in patients with PD. QSM showed higher sensitivity and specificity compared with R2* mapping to separate the patients with PD from the normal controls. There were no significant correlations between the susceptibility/R2* values and clinical features in all targeted regions of the brains in patients with PD. In conclusion, both QSM and R2* mapping are feasible to calculate the iron levels in human brains, and QSM provides a more sensitive and accurate method to assess regional abnormal iron distribution in patients with PD.

A double-network hydrogel for the dynamic compression of the lumbar nerve root.

Current animal models of nerve root compression due to lumbar disc herniation only assess the mechanical compression of nerve roots and the inflammatory response. Moreover, the pressure applied in these models is static, meaning that the nerve root cannot be dynamically compressed. This is very different from the pathogenesis of lumbar disc herniation. In this study, a chitosan/polyacrylamide double-network hydrogel was prepared by a simple two-step method. The swelling ratio of the double-network hydrogel increased with prolonged time, reaching 140. The compressive strength and compressive modulus of the hydrogel reached 53.6 and 0.34 MPa, respectively. Scanning electron microscopy revealed the hydrogel's crosslinked structure with many interconnecting pores. An MTT assay demonstrated that the number of viable cells in contact with the hydrogel extracts did not significantly change relative to the control surface. Thus, the hydrogel had good biocompatibility. Finally, the double-network hydrogel was used to compress the L4 nerve root of male sand rats to simulate lumbar disc herniation nerve root compression. The hydrogel remained in its original position after compression, and swelled with increasing time. Edema appeared around the nerve root and disappeared 3 weeks after operation. This chitosan/polyacrylamide double-network hydrogel has potential as a new implant material for animal models of lumbar nerve root compression. All animal experiments were approved by the Animal Ethics Committee of Neurosurgical Institute of Beijing, Capital Medical University, China (approval No. 201601006) on July 29, 2016.

The Diagnostic Performance of DCE-MRI in Evaluating the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer: A Meta-Analysis.

Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in preoperative treatment for local breast cancer, and it gives high clinical response rates and can result in pathologic complete response (pCR) in 6-25% of patients. In recent years, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been increasingly used to assess the pathological response of breast cancer to NAC. In present analysis, we assess the diagnostic performance of DCE-MRI in evaluating the pathological response of breast cancer to NAC. Materials and Methods: A systematic search in PubMed, the Cochrane Library, and Web of Science for original studies was performed. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the methodological quality of the included studies. Patient, study, and imaging characteristics were extracted, and sufficient data to reconstruct 2 × 2 tables were obtained. Data pooling, heterogeneity testing, forest plot construction, meta-regression analysis and sensitivity analysis were performed using Stata version 12.0 (StataCorp LP, College Station, TX). Results: Eighteen studies (969 patients with breast cancer) were included in the present meta-analysis. The pooled sensitivity and specificity of DCE-MRI were 0.80 (95% confidence interval [CI]: 0.70, 0.88) and 0.84 (95% [CI]: 0.79, 0.88), respectively. Meta-regression analysis found no significant factors affecting heterogeneity. Sensitivity analysis showed that studies that set pathological complete response (pCR) (n = 14) as a responder showed a tendency for higher sensitivity compared with those that set pCR and near pCR together (n = 5) as a responder (0.83 vs. 0.72), and studies (n = 14) that used DCE-MRI to early predict the pathological response of breast cancer had a higher sensitivity (0.83 vs. 0.71) and equivalent specificity (0.80 vs. 0.86) compared to studies (n = 5) that assessed the response after NAC completion. Conclusion: Our results indicated that DCE-MRI could be considered an important auxiliary method for evaluating the pathological response of breast cancer to NAC and used as an effective method for dynamically monitoring the efficacy during NAC. DCE-MRI also performed well in predicting the pCR of breast cancer to NAC. However, due to the heterogeneity of the included studies, caution should be exercised in applying our results.

Molecular Mechanism for Selective Cytotoxicity towards Cancer Cells of Diselenide-Containing Paclitaxel Nanoparticles.

Diselenide-containing paclitaxel nanoparticles (SePTX NPs) indicated selectivity of cytotoxicity between cancerous and normal cells in our previous work. Herein, the mechanism is revealed by molecular biology in detail. Cancer cells and normal cells were treated with the SePTX NPs and cell proliferation was measured using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell morphology. Measurement of reactive oxygen species (ROS) levels and biochemical parameters were employed to monitor oxidative stress of the cells. JC-1 assay was used to detect the mitochondrial dysfunction of the cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect apoptosis of the cells. Immunofluorescence analysis and western blotting were employed to monitor changes in signaling pathway-related proteins. Compared with PTX, SePTX NPs has a good selectivity to cancer cells and can obviously induce the proliferation damage of cancer cells, but has no significant toxicity to normal cells, indicating that SePTX NPs has a specific killing effect on cancer cells. The results of mechanism research show that SePTX NPs can successfully inhibit the depolymerization of microtubules and induce cell cycle arrest, which is related to the upregulation of p53 and CyclinB1. Simultaneously, SePTX NPs can successfully induce oxidative stress, cause mitochondrial dysfunction, resulting in mitochondrial pathway-mediated apoptosis, which is related to the upregulation of autophagy-related protein LC3-II. On the other hand, lewis lung cancer C57BL/6 mice were used to evaluate the anti-tumor effects of SePTX NPs in vivo. Our data show that SePTX NPs exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects. Collectively, these data indicate that the high antitumor effect and selective cytotoxicities of SePTX NPs is promising in future cancer therapy.