Antibacterial-Antioxidative Thiolated Gelatin/Methacrylated Silk Fibroin Hydrogels with Nitric Oxide Release Catalyzed by Metal-Polyphenol Nanoparticles for MRSA-Infected Wound Healing.

Chronic wound infection often leads to irregular tissue closure and accompanies delayed healing and economy issues. Developing an ideal wound dressing that can control the occurrence of antibacterial infections and biological responses is highly desirable. In this study, a multifunctional hybrid hydrogel (GS@EG-Cu-CA NPs) containing synthesized thiolated gelatin, methacrylated silk fibroin, and (-)-epigallocatechin gallate-copper ionic-carrageenan nanoparticles (EG-Cu-CA NPs) was engineered by a thio-ene click reaction. The metal-polyphenol EG-Cu-CA NPs were encapsulated with kappa-carrageenan to enhance its aqueous-soluble, mechanical, and bioactive properties and endowed the hydrogel dressing with fascinating antibacterial, antioxidation, and nitric oxide (NO) generation by catalyzing. The hybrid hydrogels also illustrated a favorable cytocompatibility. Benefiting from the thio-ene click reaction, the hybrid hydrogels were injected and photocured rapidly in situ to cover an irregular wound. In an SD rat full-thickness skin-wound-infected model, the methicillin-resistant Staphylococcus aureus-infected wound covered with GS@EG-Cu-CA NPs was almost completely healed after 10 days. This study presents a facile design of hydrogel dressing incorporating metal-polyphenol nanoparticles, which demonstrates a promising potential way for dealing with effective wound infection management and other complicated wound healings.

Cyanoacrylate glue foreign body after CT-guided localization of a pulmonary nodule during video-assisted thoracoscopic surgery: a case report.

BACKGROUND: A tracheal foreign body is a common airway aspiration that creates an emergency, which often causes unobserved respiratory problems and requires management. Iatrogenic tracheal foreign bodies are rarely observed, which results in tracheal obstruction. If the foreign body were removed from the tracheobronchial system, it would save lives. A similar case of a tracheal foreign body was focused on, which was caused by medical glue used during preoperative computed tomography localization of pulmonary nodules. CASE PRESENTATION: The foreign body was deposited in the right upper bronchi, accidentally discovered after anesthesia when a double-lumen tube was located by fiber bronchoscopy. Following a video-assisted thoracoscopic surgery, the foreign body was removed using a respiratory endoscopy without subsequent adverse consequences for the patient. CONCLUSIONS: There is a risk of complications from iatrogenic airway foreign bodies for preoperative localization of pulmonary nodules by injecting cyanoacrylate glue.

Development and Internal Validation of a Prediction Model for Difficult Laryngoscopy Using Ultrasound-Derived Factor in Comatose Patients.

OBJECTIVES: The distance from skin to the hyoid bone (DSHB) and skin to the anterior commissure of vocal cords (DSAC) are reliable parameters for pre-operative airway ultrasound assessment in awake patients and can be assessed in comatose patients. This study aimed to inspect its feasibility and accuracy in predicting difficult laryngoscopy for comatose patients. METHODS: A prospective cohort study included patients with a Glasgow Coma Scale (GCS) of ≤8 who underwent emergency tracheal intubation between November 2019 and August 2020. The outcome was difficult laryngoscopy and classified according to the Cormack-Lehane grading. RESULTS: A total of 151 patients were included in the study. Fifty-two (34.4%) patients were categorized as having difficult laryngoscopy. The DSHB add DSAC (hereinafter referred to as the "DSBAC") was superior to either parameter alone in the predictive performance, and the optimal cut-off value was 1.90. To optimize the predictive value, DSBAC (adjusted odds ratio [OR]: 7.76; 95% confidence interval [CI]: 2.88-20.94; P < .001), GCS (adjusted OR: 1.39; 95% CI: 3.93-26.28; P = .039), mandibular retraction (adjusted OR: 8.20; 95% CI: 1.92-35.09; P = .005) and edentulous (adjusted OR: 4.23; 95% CI: 1.40-12.80; P = .011) were included in a multivariable model and constructed a nomogram. Discrimination and calibration statistics were satisfactory, with C-index above 0.80 from both model development and internal validation. CONCLUSIONS: Ultrasound-derived factor, DSBAC, can be easily assessed and help predict difficult laryngoscopy among comatose patients. A simple nomogram including only four clinical items exhibited excellent discrimination performance and was useful when comatose patients underwent emergency tracheal intubation.

Chemisorption-Induced Formation of Biphenylene Dimer on Ag(111).

We report an example that demonstrates the clear interdependence between surface-supported reactions and molecular-adsorption configurations. Two biphenyl-based molecules with two and four bromine substituents, i.e., 2,2'-dibromobiphenyl (DBBP) and 2,2',6,6'-tetrabromo-1,1'-biphenyl (TBBP), show completely different reaction pathways on a Ag(111) surface, leading to the selective formation of dibenzo[e,l]pyrene and biphenylene dimer, respectively. By combining low-temperature scanning tunneling microscopy, synchrotron radiation photoemission spectroscopy, and density functional theory calculations, we unravel the underlying reaction mechanism. After debromination, a biradical biphenyl can be stabilized by surface Ag adatoms, while a four-radical biphenyl undergoes spontaneous intramolecular annulation due to its extreme instability on Ag(111). Such different chemisorption-induced precursor states between DBBP and TBBP consequently lead to different reaction pathways after further annealing. In addition, using bond-resolving scanning tunneling microscopy and scanning tunneling spectroscopy, we determine with atomic precision the bond-length alternation of the biphenylene dimer product, which contains 4-, 6-, and 8-membered rings. The 4-membered ring units turn out to be radialene structures.

Mxene Reinforced Supramolecular Hydrogels with High Strength, Stretchability, and Reliable Conductivity for Sensitive Strain Sensors.

Conductive hydrogels used as electronics have received much attention due to their great flexibility and stretchability. However, the fabrication of ideal conductive hydrogels fulfilling the excellent mechanical properties and outstanding sensitivity remains a great challenge until now. Moreover, high sensitivity and broad linearity range are pivotal for the feasibility and accuracy of hydrogel sensors. In this study, a conductive supramolecular hydrogel is engineered by directly mixing the aqueous dispersion of MXene with the precursor of N-acryloyl glycinamide (NAGA) monomer and then rapidly photo cross-linked by UV irradiation. The resultant PNAGA/MXene hydrogel-sensors exhibit high mechanical strength (4.8 MPa), great stretchability (630%), and excellent durability. The conductive hydrogel-based sensor presents excellent conductivity (17.3 S m-1 ) and a wide scope of linear dependence of sensitivity on strain (0%-125%, gauge factor = 2.05). It displays reliable detection of various motions, including repeated subtle movements and large strain. It also shows good degradation in vitro and antifouling capability. This work may provide a simple and promising platform for engineering conductive supramolecular hydrogels with integrated high performance aiming for smart wearable electronics, electronic skin, soft robots, and human-machine interfacing.

Metformin protects PC12 cells and hippocampal neurons from H2 O 2 -induced oxidative damage through activation of AMPK pathway.

Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2 O2 -induced cell death. Metformin significantly ameliorated cell death due to H2 O2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H2 O2 . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H2 O2 . Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.

A randomized trial to evaluate a modified tracheal catheter with upper and lower balloons for anesthetic administration: effect on the cardiovascular, stress response, and comfort in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: We aimed to evaluate a modified endotracheal tube containing upper and lower balloons for anesthetic administration among patients undergoing laparoscopic cholecystectomy. METHODS: Ninety patients scheduled to undergo laparoscopic cholecystectomy were randomly allocated to 3 equal groups: group A (conventional tracheal intubation without endotracheal anesthesia); B (conventional tracheal intubation with endotracheal anesthesia); and C (tracheal intubation using a modified catheter under study). Blood pressure, heart rate, angiotensin II level, blood glucose level, airway pressure before anesthesia (T1) were measured immediately after intubation (T2), 5 min after intubation (T3), and immediately after extubation (T4). The post-extubation pain experienced was evaluated using the Wong-Baker Face Pain scale. Adverse reactions within 30 min after extubation were recorded. RESULTS: Systolic blood pressure, diastolic blood pressure, angiotensin II, and blood sugar level in group C at T2, T3 and T4, and heart rate at T2 and T4 were significantly lower than those in group A (P < 0.05); systolic blood pressure and blood sugar at T4, and angiotensin II levels at T2, T3, and T4 were significantly lower than those in group B (P < 0.05). Patients in group C reported the lowest post-extubation pain (P < 0.05 vs. Group A), and the lowest incidence of adverse events such as nausea, vomiting, and sore throat than that in groups A and B (P < 0.05). CONCLUSION: The modified endotracheal anesthesia tube under study is effective in reducing cardiovascular and tracheal stress response, and increasing patient comfort, without inducing an increase in airway resistance. TRIAL REGISTRATION: The clinical trial was retrospectively registered at the Chinese Clinical Trial Registry with the Registration Number ChiCTR1900020832 at January 20th 2019.

Adaptive Aggregation Routing to Reduce Delay for Multi-Layer Wireless Sensor Networks.

The quality of service (QoS) regarding delay, lifetime and reliability is the key to the application of wireless sensor networks (WSNs). Data aggregation is a method to effectively reduce the data transmission volume and improve the lifetime of a network. In the previous study, a common strategy required that data wait in the queue. When the length of the queue is greater than or equal to the predetermined aggregation threshold ( N t ) or the waiting time is equal to the aggregation timer ( T t ), data are forwarded at the expense of an increase in the delay. The primary contributions of the proposed Adaptive Aggregation Routing (AAR) scheme are the following: (a) the senders select the forwarding node dynamically according to the length of the data queue, which effectively reduces the delay. In the AAR scheme, the senders send data to the nodes with a long data queue. The advantages are that first, the nodes with a long data queue need a small amount of data to perform aggregation; therefore, the transmitted data can be fully utilized to make these nodes aggregate. Second, this scheme balances the aggregating and data sending load; thus, the lifetime increases. (b) An improved AAR scheme is proposed to improve the QoS. The aggregation deadline ( T t ) and the aggregation threshold ( N t ) are dynamically changed in the network. In WSNs, nodes far from the sink have residual energy because these nodes transmit less data than the other nodes. In the improved AAR scheme, the nodes far from the sink have a small value of T t and N t to reduce delay, and the nodes near the sink are set to a large value of T t and N t to reduce energy consumption. Thus, the end to end delay is reduced, a longer lifetime is achieved, and the residual energy is fully used. Simulation results demonstrate that compared with the previous scheme, the performance of the AAR scheme is improved. This scheme reduces the delay by 14.91%, improves the lifetime by 30.91%, and increases energy efficiency by 76.40%.

Caching Joint Shortcut Routing to Improve Quality of Service for Information-Centric Networking.

Hundreds of thousands of ubiquitous sensing (US) devices have provided an enormous number of data for Information-Centric Networking (ICN), which is an emerging network architecture that has the potential to solve a great variety of issues faced by the traditional network. A Caching Joint Shortcut Routing (CJSR) scheme is proposed in this paper to improve the Quality of service (QoS) for ICN. The CJSR scheme mainly has two innovations which are different from other in-network caching schemes: (1) Two routing shortcuts are set up to reduce the length of routing paths. Because of some inconvenient transmission processes, the routing paths of previous schemes are prolonged, and users can only request data from Data Centers (DCs) until the data have been uploaded from Data Producers (DPs) to DCs. Hence, the first kind of shortcut is built from DPs to users directly. This shortcut could release the burden of whole network and reduce delay. Moreover, in the second shortcut routing method, a Content Router (CR) which could yield shorter length of uploading routing path from DPs to DCs is chosen, and then data packets are uploaded through this chosen CR. In this method, the uploading path shares some segments with the pre-caching path, thus the overall length of routing paths is reduced. (2) The second innovation of the CJSR scheme is that a cooperative pre-caching mechanism is proposed so that QoS could have a further increase. Besides being used in downloading routing, the pre-caching mechanism can also be used when data packets are uploaded towards DCs. Combining uploading and downloading pre-caching, the cooperative pre-caching mechanism exhibits high performance in different situations. Furthermore, to address the scarcity of storage size, an algorithm that could make use of storage from idle CRs is proposed. After comparing the proposed scheme with five existing schemes via simulations, experiments results reveal that the CJSR scheme could reduce the total number of processed interest packets by 54.8%, enhance the cache hits of each CR and reduce the number of total hop counts by 51.6% and cut down the length of routing path for users to obtain their interested data by 28.6⁻85.7% compared with the traditional NDN scheme. Moreover, the length of uploading routing path could be decreased by 8.3⁻33.3%.

A Trust-Based Secure Routing Scheme Using the Traceback Approach for Energy-Harvesting Wireless Sensor Networks.

The Internet of things (IoT) is composed of billions of sensing devices that are subject to threats stemming from increasing reliance on communications technologies. A Trust-Based Secure Routing (TBSR) scheme using the traceback approach is proposed to improve the security of data routing and maximize the use of available energy in Energy-Harvesting Wireless Sensor Networks (EHWSNs). The main contributions of a TBSR are (a) the source nodes send data and notification to sinks through disjoint paths, separately; in such a mechanism, the data and notification can be verified independently to ensure their security. (b) Furthermore, the data and notification adopt a dynamic probability of marking and logging approach during the routing. Therefore, when attacked, the network will adopt the traceback approach to locate and clear malicious nodes to ensure security. The probability of marking is determined based on the level of battery remaining; when nodes harvest more energy, the probability of marking is higher, which can improve network security. Because if the probability of marking is higher, the number of marked nodes on the data packet routing path will be more, and the sink will be more likely to trace back the data packet routing path and find malicious nodes according to this notification. When data packets are routed again, they tend to bypass these malicious nodes, which make the success rate of routing higher and lead to improved network security. When the battery level is low, the probability of marking will be decreased, which is able to save energy. For logging, when the battery level is high, the network adopts a larger probability of marking and smaller probability of logging to transmit notification to the sink, which can reserve enough storage space to meet the storage demand for the period of the battery on low level; when the battery level is low, increasing the probability of logging can reduce energy consumption. After the level of battery remaining is high enough, nodes then send the notification which was logged before to the sink. Compared with past solutions, our results indicate that the performance of the TBSR scheme has been improved comprehensively; it can effectively increase the quantity of notification received by the sink by 20%, increase energy efficiency by 11%, reduce the maximum storage capacity needed by nodes by 33.3% and improve the success rate of routing by approximately 16.30%.

Adding Active Slot Joint Larger Broadcast Radius for Fast Code Dissemination in WSNs.

By using Software Defined Network (SDN) technology, senor nodes can get updated program code which can provide new features, so it has received extensive attention. How to effectively spread code to each node fast is a challenge issue in wireless sensor networks (WSNs). In this paper, an Adding Active Slot joint Larger Broadcast Radius (AAS-LBR) scheme is proposed for fast code dissemination. The AAS-LBR scheme combines the energy of data collection and code dissemination, making full use of the remaining energy in the far-sink area to increase the active slot and the broadcast radius to speed up the code dissemination. The main contributions of the proposed AAS-LBR scheme are the following: (1) Make full use of the remaining energy of the far sink area to expand the broadcast radius, so that the node broadcasts a longer distance. The wide range of broadcasts makes the number of nodes receiving code more, which speeds up the spread of code dissemination. (2) AAS-LBR uses two improved methods to further reduce the number of broadcasts and speed up the code dissemination: (a) When constructing the broadcast backbone whose nodes dominate all nodes in network and are responsible for broadcasting code, the active slot is added to the next hop node in a pipeline style on the diffusion path, which enables the code dissemination process to continue without pause. Thus, the code can quickly spread to the entire broadcast backbone. (b) For the nodes in the non-broadcast backbone whose nodes are dominated by the broadcast backbone and only for receiving code, an active slot is added coincident with its broadcast backbone' active slot, which can reduce the time required for code dissemination and reduce the number of broadcasts. A lot of performance analysis and simulation results show that compared to previous schemed, the AAS-LBR scheme can balance energy consumption, the transmission delay can be reduced 43.09⁻78.69%, the number of broadcasts can be reduced 44.51⁻86.18% and the energy efficiency is improved by about 24.5%.

Berberine Protects Human Retinal Pigment Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Damage through Activation of AMPK.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly with less effective treatment, especially for dry AMD (90% of AMD). Although the etiology of this disease is not well elucidated, increasing evidences indicate that excessive reactive oxygen species (ROS) impairing the physiological functions of retinal pigment epithelium (RPE) cells may be one of the main causes. Therefore, it could be a great strategy to find some drugs that can effectively protect RPE cells from oxidative damage which is desired to treat and slow the process of AMD. In the present study, a well-known traditional Chinese medicine berberine (BBR) was found to suppress hydrogen peroxide (H2O2)-induced oxidative damage in D407 cells, a human RPE cell line. Pre-treatment of D407 cells with BBR significantly suppressed H2O2-induced cell apoptosis by restoring abnormal changes in nuclear morphology, preventing the decline of mitochondrial membrane potential, reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities induced by H2O2. Western blot analysis showed that BBR was able to stimulate the phosphorylation/activation of AMPK in a time- and dose-dependent manner in D407 cells, while treatment of cells with AMPK pathway inhibitor Compound C, or knockdown of the AMPK by specific siRNA blocked the effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrated that BBR was able to protect RPE cells against oxidative stress via the activation of AMPK pathway. Our findings also indicate the potential application of BBR in AMD treatment.

A sparse autoencoder-based deep neural network for protein solvent accessibility and contact number prediction.

BACKGROUND: Direct prediction of the three-dimensional (3D) structures of proteins from one-dimensional (1D) sequences is a challenging problem. Significant structural characteristics such as solvent accessibility and contact number are essential for deriving restrains in modeling protein folding and protein 3D structure. Thus, accurately predicting these features is a critical step for 3D protein structure building. RESULTS: In this study, we present DeepSacon, a computational method that can effectively predict protein solvent accessibility and contact number by using a deep neural network, which is built based on stacked autoencoder and a dropout method. The results demonstrate that our proposed DeepSacon achieves a significant improvement in the prediction quality compared with the state-of-the-art methods. We obtain 0.70 three-state accuracy for solvent accessibility, 0.33 15-state accuracy and 0.74 Pearson Correlation Coefficient (PCC) for the contact number on the 5729 monomeric soluble globular protein dataset. We also evaluate the performance on the CASP11 benchmark dataset, DeepSacon achieves 0.68 three-state accuracy and 0.69 PCC for solvent accessibility and contact number, respectively. CONCLUSIONS: We have shown that DeepSacon can reliably predict solvent accessibility and contact number with stacked sparse autoencoder and a dropout approach.

Transplantation of bone marrow stromal stem cells overexpressing tropomyosin receptor kinase A for peripheral nerve repair.

BACKGROUND AIMS: Previously we reported that overexpression of tropomyosin receptor kinase A (TrkA) could improve the survival and Schwann-like cell differentiation of bone marrow stromal stem cells (BMSCs) in nerve grafts for bridging rat sciatic nerve defects. The aim of this study was to investigate how TrkA affects the efficacy of BMSCs transplantation on peripheral nerve regeneration and functional recovery. METHODS: Rat BMSCs were infected with recombinant lentiviruses to construct TrkA-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then seeded in acellular nerve allografts for bridging 10-mm rat sciatic nerve defects. RESULTS: At 8 weeks post-transplantation, compared with Vector and Control BMSCs-laden groups, TrkA-overexpressing BMSCs-laden group demonstrated obviously improved axon growth, such as significantly higher expression of myelin basic protein and superior results of myelinated fiber density, axon diameter and myelin sheaths thickness. In accordance with this increased nerve regeneration, the animals of TrkA-overexpressing BMSCs-laden group showed significantly better restoration of sciatic nerve function, manifested as greater sciatic function index value and superior electrophysiological parameters including shorter onset latency and higher peak amplitude of compound motor action potentials and faster nerve conduction velocity. However, these beneficial effects could be reversed in TrkA-shRNA-expressing BMSCs-laden group, which showed much fewer and smaller axons with thinner myelin sheaths and correspondingly poor functional recovery. CONCLUSIONS: These results demonstrated that TrkA may regulate the regenerative potential of BMSCs in nerve grafts, and TrkA overexpression can enhance the efficacy of BMSCs on peripheral nerve regeneration and functional recovery, which may help establish novel strategies for repairing peripheral nerve injuries.

Palmitic acid triggers cell apoptosis in RGC-5 retinal ganglion cells through the Akt/FoxO1 signaling pathway.

Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells (RGCs). Lipotoxicity, involving a series of pathological cellular responses after exposure to elevated levels of fatty acids, leads to oxidative stress and cell death in various cell types. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O1 (PI3K/Akt/FoxO1) pathway is crucial for cell survival and apoptosis. More importantly, FoxO1 gene has been reported to confer relatively higher risks for eye diseases including glaucoma. However, little information is available regarding the interaction between FoxO1 and RGC apoptosis, much less a precise mechanism. In the present study, immortalized rat retinal ganglion cell line 5 (RGC-5) was used as a model to study the toxicity of palmitic acid (PA), as well as underlying mechanisms. We found that PA exposure significantly decreased cell viability by enhancing apoptosis in RGC-5 cells, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. PA also induced a remarkable increase in reactive oxygen species and malondialdehyde. Moreover, PA significantly decreased the level of phospho-Akt and phospho-FoxO1 in cells. Finally, shRNA knockdown and plasmid overexpression studies displayed that downregulation of Akt protein or upregulation of FoxO1 protein augmented cell death, while knockdown of FoxO1 or overexpression of Akt1 abolished PA-induced cell death. Collectively, our results indicated that PA-induced cell death is mediated through modulation of Akt/FoxO1 pathway activity.

ß-arrestin1 promotes epithelial-mesenchymal transition via modulating GSK-3ß/ß-catenin pathway in prostate cancer cells.

Recently, ß-arrestin1 was indicated as a tumor promoter in prostate cancer, but its exact role in cancer metastasis still have not been well clarified. Here, our data revealed that ß-arrestin1 could promote the migration and invasion of prostate cancer cells via initiating epithelial-mesenchymal transition (EMT). Mechanically, ß-arrestin1 could increase the transcriptional activity and expression of ß-catenin, together with Akt activity, whereas decrease the activities of GSK-3ß and PP2A. In addition, ß-arrestin1 could function as a scaffold protein in modulating the interactions between PP2A, Akt, GSK-3ß and ß-catenin. These results reveal a novel mechanism of ß-arrestin1 in modulating EMT and GSK-3ß/ß-catenin signaling in prostate cancer, thereby suggest that assessment of ß-arrestin1 may provide a potential therapeutic target for prostate cancer.

Overexpression of tropomyosin receptor kinase A improves the survival and Schwann-like cell differentiation of bone marrow stromal cells in nerve grafts for bridging rat sciatic nerve defects.

BACKGROUND AIMS: Bone marrow stromal cells (BMSCs) can differentiate into Schwann-like cells in vivo and effectively promote nerve regeneration and functional recovery as the seed cells for peripheral nerve repair. However, the survival rate and neural differentiation rate of the transplanted BMSCs are very low, which would limit their efficacy. METHODS: In this work, rat BMSCs were infected by recombinant lentiviruses to construct tropomyosin receptor kinase A (TrkA)-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then used in transplantation for rat sciatic nerve defects. RESULTS: We showed that lentivirus-mediated overexpression of TrkA in BMSCs can promote cell survival and protect against serum-starve-induced apoptosis in vitro. At 8 weeks after transplantation, the Schwann-like differentiated ratio of the existing implanted cells had reached 74.8 ± 1.6% in TrkA-overexpressing BMSCs-laden nerve grafts, while 40.7 ± 2.3% and 42.3 ± 1.5% in vector and control BMSCs-laden nerve grafts, but only 8.2 ± 1.8% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. The cell apoptosis ratio of the existing implanted cells in TrkA-overexpressing BMSCs-laden nerve grafts was 16.5 ± 1.2%, while 33.9 ± 1.9% and 42.6 ± 2.9% in vector and control BMSCs-laden nerve grafts, but 87.2 ± 2.5% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. CONCLUSIONS: These results demonstrate that TrkA overexpression can improve the survival and Schwann-like cell differentiation of BMSCs and prevent cell death in nerve grafts, which may have potential implication in advancing cell transplantation for peripheral nerve repair.

ß-Arrestin2 Contributes to Cell Viability and Proliferation via the Down-Regulation of FOXO1 in Castration-Resistant Prostate Cancer.

ß-Arrestin2 has been identified to act as a corepressor of androgen receptor (AR) signaling by binding to AR and serving as a scaffold to affect the activity and expression of AR in androgen-dependent prostate cancer cells; however, little is known regarding its role in castration-resistant prostate cancer (CRPC) progression. Here, our data demonstrated that ß-arrestin2 contributes to the cell viability and proliferation of CRPC via the downregulation of FOXO1 activity and expression. Mechanistically, in addition to its requirement for FOXO1 phosphorylation induced by IGF-1, ß-arrestin2 could inhibit FOXO1 activity in an Akt-independent manner and delay FOXO1 dephosphorylation through the inhibition of PP2A phosphatase activity and the attenuation of the interaction between FOXO1 and PP2A. Furthermore, ß-arrestin2 could downregulate FOXO1 expression via ubiquitylation and proteasomal degradation. Together, our results identified a novel role for ß-arrestin2 in the modulation of the CRPC progress through FOXO1. Thus, the characterization of ß-arrestin2 may represent an alternative therapeutic target for CRPC treatment.

[Protective effect and mechanisms of dihydromyricetin on PC12 cells induced by oxidative injury].

OBJECTIVE: To study the protective effect and possible mechanisms of Dihydromyricetin(DMY)on PC12 cells injury in- duced by sodium nitroprusside( SNP). METHODS: SNP toxicity cellular model was established using PC12 cells treated with SNP. Cell via- bility was determined by MTT assay. The apoptosis of treated cells was detected by Hoechst Staining. Effect of DMY on accumulation of ROS in PC12 cells induced by SNP was detected by fluorometric analysis. The pathways involved were studied by kinase specific inhibi- tors; The level of phosphorylated Akt and ERK1/2 was detected by Western blot with specific phosphor-antibodies. RESULTS: SNP in- duced the apoptosis of PC12 cells in a dose-dependent manner. DMY dose-dependently protected PC12 cells from injury induced by SNP. Hoechst staining indicated that SNP decreased the number of viable cells and induced shrinkage and aggregation of the nucleus, whereas DMY attenuiated the toxic effects of SNP. The level of ROS induced by SNP in PC12 cells was decreased gradually by DMY. PI3K specific inhibitor LY294002 and the MAPK pathway specific inhibitor PD98059 attenuated the protective effect of DMY on SNP-induced injury of PC12 cells. However, the effect of DMY could be blocked by LY294002 and PD98059 respectively. CONCLUSION: DMY possesses protective effect against apoptosis induced by SNP in PC12 cells,and its mechanisms may be partially related with Akt and ERK1/2 signaling.