Ruxolitinib improves the inflammatory microenvironment, restores glutamate homeostasis, and promotes functional recovery after spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

Simulation-guided development of advanced PID control algorithm for skin cooling in radiofrequency lipolysis.

BACKGROUND: The clinical outcomes of bipolar radiofrequency (RF) lipolysis, a prevalent non-invasive fat reduction procedure, hinge on the delicate balance between effective lipolysis and patient safety, with skin overheating and subsequent tissue damage as primary concerns. OBJECTIVE: This study aimed to investigate a novel bipolar radiofrequency lipolysis technique, safeguarding the skin through an innovative PID temperature control algorithm. METHODS: Utilizing COMSOL Multiphysics simulation software, a two-dimensional fat and skin tissue model was established, simulating various PID temperature control schemes. The crux of the simulation involved a comparative analysis of different PID temperatures at 45 °C, 50 °C, and 55 °C and constant power strategies, assessing their implications on skin temperature. Concurrently, a custom bipolar radiofrequency lipolysis device was developed, with ex vivo experiments conducted using porcine tissue for empirical validation. RESULTS: The findings indicated that with PID settings of Kp = 7, Ki = 2, and Kd = 0, and skin temperature control at 45 °C or 50 °C, the innovative PID-based epidermal temperature control strategy successfully maintained the epidermal temperature within a safe range. This maintenance was achieved without compromising the effectiveness of RF lipolysis, significantly reducing the risk of thermal damage to the skin layers. CONCLUSION: Our research confirms the substantial practical utility of this advanced PID-based bipolar RF lipolysis technique in clinical aesthetic procedures, enhancing patient safety during adipose tissue ablation therapies.

Comparison Between Drug-Coated Balloon and Stents in Large De Novo Coronary Artery Disease: A Systematic Review and Meta-Analysis of RCT Data.

PURPOSE: Although a number of studies involving small-vessel de novo coronary disease showed clinical benefits of drug-coated balloons (DCB), the role of DCB in large vessel lesions is still unclear. METHODS: We searched main electronic databases for randomized controlled trials (RCTs) comparing DCB with stents for large vessel de novo coronary artery disease. The primary endpoint was major cardiovascular adverse events (MACE), composite cardiovascular death (CD), myocardial infarction (MI), or target lesion revascularization (TLR). RESULTS: This study included 7 RCTs with 770 participants. DCB were associated with a marked risk reduction in MACE [Risk Ratio (RR): 0.48; 95% confidence interval [CI]: 0.24 to 0.97; P = 0.04], TLR (RR: 0.53; 95% CI: 0.25 to 1.14; P = 0.10), and late lumen loss [standard mean difference (SMD): -0.57; 95% CI: -1.09 to -0.05; P = 0.03] as compared with stents. There is no significant difference in MI (RR: 0.58; 95% CI: 0.21 to 1.54; P = 0.27), CD (RR: 0.33; 95% CI: 0.06 to 1.78; P = 0.19), and minimal lumen diameter (SMD: -0.34; 95% CI: -0.72 to 0.05; P = 0.08) between groups. In subgroup analyses, the risk reduction of MACE persisted in patients with chronic coronary syndrome (RR: 0.25; 95% CI: 0.07 to 0.89; P = 0.03), and patients receiving DCB vs. bare metal stent (RR: 0.19; 95% CI: 0.05 to 0.73; P = 0.01). In addition, there was no significant difference between the DCB group and the drug eluting stent group for MACE (RR: 0.69; 95% CI: 0.30 to 1.60; P = 0.38). CONCLUSION: DCB may be an effective therapeutic option in patients with large vessel de novo coronary artery disease.

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.

OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

A Dynamic Path-Planning Method for Obstacle Avoidance Based on the Driving Safety Field.

Establishing an accurate and computationally efficient model for driving risk assessment, considering the influence of vehicle motion state and kinematic characteristics on path planning, is crucial for generating safe, comfortable, and easily trackable obstacle avoidance paths. To address this topic, this paper proposes a novel dual-layered dynamic path-planning method for obstacle avoidance based on the driving safety field (DSF). The contributions of the proposed approach lie in its ability to address the challenges of accurately modeling driving risk, efficient path smoothing and adaptability to vehicle kinematic characteristics, and providing collision-free, curvature-continuous, and adaptable obstacle avoidance paths. In the upper layer, a comprehensive driving safety field is constructed, composed of a potential field generated by static obstacles, a kinetic field generated by dynamic obstacles, a potential field generated by lane boundaries, and a driving field generated by the target position. By analyzing the virtual field forces exerted on the ego vehicle within the comprehensive driving safety field, the resultant force direction is utilized as guidance for the vehicle's forward motion. This generates an initial obstacle avoidance path that satisfies the vehicle's kinematic and dynamic constraints. In the lower layer, the problem of path smoothing is transformed into a standard quadratic programming (QP) form. By optimizing discrete waypoints and fitting polynomial curves, a curvature-continuous and smooth path is obtained. Simulation results demonstrate that our proposed path-planning algorithm outperforms the method based on the improved artificial potential field (APF). It not only generates collision-free and curvature-continuous paths but also significantly reduces parameters such as path curvature (reduced by 62.29% to 87.32%), curvature variation rate, and heading angle (reduced by 34.11% to 72.06%). Furthermore, our algorithm dynamically adjusts the starting position of the obstacle avoidance maneuver based on the vehicle's motion state. As the relative velocity between the ego vehicle and the obstacle vehicle increases, the starting position of the obstacle avoidance path is adjusted accordingly, enabling the proactive avoidance of stationary or moving single and multiple obstacles. The proposed method satisfies the requirements of obstacle avoidance safety, comfort, and stability for intelligent vehicles in complex environments.

[Identification of ecological functional zoning and its influencing factors in the Sihu Lake Basin, China]. / å››æ¹–æµåŸŸç”Ÿæ€åŠŸèƒ½åˆ†åŒºåŠå ¶å½±å“å› ç´ è¯†åˆ«.

Rational delineation of ecological functional areas and clarification of their driving factors are of significance for maintaining regional ecosystem stability. We assessed six ecosystem services of Sihu Lake Basin located in Jianghan Plain using InVEST and RUSLE models and recreational scoring methods. By using K-means clustering, we identified the ecosystem service bundles, and delineated the ecological functional areas in combination with ecological sensitivity and ecosystem service bundles. The dominant driving factors of different ecological functional areas were analyzed by Geodetector. The results showed that the spatial distributions of habitat quality and carbon sequestration services were similar, with high values being mainly concentrated in Changhu Lake Basin and Honghu Lake Basin. However, the spatial distributions of crop production and soil conservation services were different, with high-value areas concentrated in the northwest area with mountains. The high values of water production service were mainly concentrated in the eastern part of Honghu Lake Basin, while the high-value areas of ecological recreation service were mainly concentrated in the northwest area and the southern part of Honghu Lake Basin. The Sihu Lake Basin could be classified into crop production bundle, habitat quality bundle, and urban living bundle according to cluster analysis. The low ecological sensitivity areas accounted for 59.0% of the Sihu Lake Basin. We classified the study area into ecological restoration areas, ecological conservation areas, ecological transition areas, ecological development areas, and comprehensive use areas by combination of ecological sensitivity and ecosystem service bundles. The geodetector results indicated that the driving factors of each ecological function zone were significantly different. The natural factors significantly influenced the ecological restoration zone, while the normalized vegetation index and population density were the main influencing factors in the ecological conservation zone and the ecological development zone, respectively. Land use type was the main influencing factor in the ecological transition zone and the comprehensive use zone. The results could provide important support for coordinated regional social development and environmental protection.

Extradural contralateral S1 nerve root transfer for spastic lower limb paralysis.

The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root (VR) to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis. Six formalin-fixed (three males and three females) cadavers were used. The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5. The sural nerve was selected as a bridge between the donor and recipient nerve. The number of axons, the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured. The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion. The gross distance between the S1 nerve root and L5 nerve root was 31.31 (± 3.23) mm in the six cadavers, while that on the diffusion tensor imaging was 47.51 (± 3.23) mm in 60 patients without spinal diseases, and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion. The numbers of axons in the S1 VRs and L5 VRs were 13414.20 (± 2890.30) and 10613.20 (± 2135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm 2 and 1.08 (± 0.26) mm 2, respectively. In conclusion, transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.

Deep removal of trace C2H2 and CO2 from C2H4 by using customized potassium-exchange mordenite.

Adsorptive separation using porous materials is a promising approach for separating alkynes/olefins due to its energy efficiency, while the deep removal of trace amounts of C2H2 and CO2 from C2H4 is still very challenging for a commercial adsorbent. Herein, we report a low-cost inorganic metal cation-mediated mordenite (MOR) zeolite with the specific location and distribution of K+ cations acting as a goalkeeper for accurately controlling diffusion channels, as evidence of the experimental and simulation results. Deep purification of C2H4 from ternary CO2/C2H2/C2H4 mixtures was first realized on K-MOR with exceptional results, achieving a remarkable polymer-grade C2H4 productivity of 1742 L kg-1 for the CO2/C2H2/C2H4 mixture. Our approach which only involves adjusting the equilibrium ions, is both promising and cost-effective, and opens up new possibilities for the use of zeolites in the industrial light hydrocarbon adsorption and purification process.

Advances in In Vitro Models of Neuromuscular Junction: Focusing on Organ-on-a-Chip, Organoids, and Biohybrid Robotics.

The neuromuscular junction (NMJ) is a peripheral synaptic connection between presynaptic motor neurons and postsynaptic skeletal muscle fibers that enables muscle contraction and voluntary motor movement. Many traumatic, neurodegenerative, and neuroimmunological diseases are classically believed to mainly affect either the neuronal or the muscle side of the NMJ, and treatment options are lacking. Recent advances in novel techniques have helped develop in vitro physiological and pathophysiological models of the NMJ as well as enable precise control and evaluation of its functions. This paper reviews the recent developments in in vitro NMJ models with 2D or 3D cultures, from organ-on-a-chip and organoids to biohybrid robotics. Related derivative techniques are introduced for functional analysis of the NMJ, such as the patch-clamp technique, microelectrode arrays, calcium imaging, and stimulus methods, particularly optogenetic-mediated light stimulation, microelectrode-mediated electrical stimulation, and biochemical stimulation. Finally, the applications of the in vitro NMJ models as disease models or for drug screening related to suitable neuromuscular diseases are summarized and their future development trends and challenges are discussed.

Transplantation of A2 type astrocytes promotes neural repair and remyelination after spinal cord injury.

BACKGROUND: Limited progress in terms of an effective treatment for spinal cord injury (SCI) emphasizes the urgent need for novel therapies. As a vital central nervous system component, the resident astrocytes play crucial roles in regulating recovery after SCI. In this study, recovery after SCI was compared following the transplantation of either A1 or A2 astrocytes. A1 astrocytes are harmful as they upregulate the neurotoxic classical complement cascade genes. Conversely, A2 astrocytes are characterized as neuroprotective as they upregulate the production of many neurotrophic factors. METHODS: We used different supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4 to generate A1 and A2 astrocytes. We detected the influence of astrocytes on neurons by co-culturing A1 and A2 astrocytes with neurons. We transplanted astrocytes into the lesion site of the spinal cord and assessed lesion progression, neural restoration, glia formation and locomotor recovery. RESULTS: Astrocytes were polarized into A1 and A2 phenotypes following culture in the supernatant obtained from microglia stimulated with lipopolysaccharide or interleukin-4, respectively. Furthermore, co-culturing A2 astrocytes with neurons significantly suppressed glutamate-induced neuronal apoptosis and promoted the degree of neuron arborization. Transplantation of these A2 astrocytes into the lesion site of the spinal cord of mice significantly improved motor function recovery, preserved spared supraspinal pathways, decreased glia scar deposition, and increased neurofilament formation at the site of injury compared to the transplantation of A1 astrocytes. Additionally, enhanced A2 astrocytes with potentially beneficial A2-like genes were also detected in the A2 group. Moreover, luxol fast blue staining and electron microscopy indicated increased preservation of myelin with organized structure after transplantation of A2 astrocytes than of A1 astrocytes. CONCLUSIONS: A2 astrocyte transplantation could be a promising potential therapy for SCI. Video abstract.

Simultaneous profiling of dust aerosol mass concentration and optical properties with polarized high-spectral-resolution lidar.

Dust particles originating from arid desert regions can be transported over long distances, presenting severe risks to climate, environment, social economics, and human health at the source and downwind regions. However, there has been a dearth of continuous diurnal observations of vertically resolved mass concentration and optical properties of dust aerosols, which hinders our understanding of aerosol mixing, stratification, aerosol-cloud interactions, and their impacts on the environment. To fill the gap of the insufficient observations, to the best of our knowledge, this work presents the first high-spectral-resolution lidar (HSRL) observation providing days of continuous profiles of the mass concentration, along with particle linear depolarization ratio (PLDR), backscattering coefficient, extinction coefficient and lidar ratio (LR), simultaneously. We present the results of two strong dust events observed by HSRL over Beijing in 2021. The maximum particle mass concentrations reached (1.52 ± 3.5) x103 µg/m3 and (19.48 ± 0.36) x103 µg/m3 for the two dust events, respectively. The retrieved particle mass concentrations and aerosol optical depth (AOD) agree well with the observation from the surface PM10 concentrations and sun photometer with correlation coefficients of 0.90 and 0.95, respectively. The intensive properties of PLDR and LR of the dust aerosols are 0.31 ± 0.02 and 39 ± 7 sr at 532 nm, respectively, which are generally close to those obtained from observations in the downwind areas. Moreover, inspired by the observations from HSRL, a universal analytical relationship is discovered to evaluate the proportion of dust aerosol backscattering, extinction, AOD, and mass concentration using PLDR. The universal analytical relationship reveals that PLDR can directly quantify dust aerosol contribution, which is expected to further expand the application of polarization technology in dust detection. These valuable observations and findings further our understanding of the contribution of dust aerosol to the environment and help supplement dust aerosol databases.

Ultrasensitive Acetylcholinesterase detection based on a surface-enhanced Raman scattering lever strategy for identifying nerve fibers.

Accurate discriminating nerve fibers is a prerequisite for right suturing nerves in nerve transfer operation. Various methods have been developed for identification of motor and sensory fibers, but no simple method meets the requirements in clinic. In this study, a surface-enhanced Raman scattering (SERS) lever strategy is designed and developed to detect Acetylcholinesterase (AchE) ultrasensitively, in which using produced thiocholine with weak intrinsic Raman activity (four ounces) to adjust absorbance of Rhodamine B with strong intrinsic Raman activity (thousand catties) on SERS-active substrates is to increase the sensitivity. Employing a miniaturized SERS substrate, SERS-active microneedles, is to decrease the volume of enzymolysis systems. Adopting an internal reference is to increase the repeatability of collected signal. The ultrasensitive AchE detection method discriminate samples with four times of difference in enzyme activity between 1-1 × 10-4 U/mL in about 10 min of enzymolysis time. AchE amounts in 2-mm-long segments of ventral and dorsal roots were about 0.00025-0.001 U and 0.01-0.02 U, respectively. The developed method would be a reliable method met the requirements of identifying motor and sensory fibers in clinic.

Experimental demonstration of spectral suppression effect improvement for multi-longitudinal mode high-spectral-resolution lidar.

The multi-longitudinal mode high-spectral-resolution lidar (MLM-HSRL) is an effective technique for detecting atmospheric optical characteristics of aerosols. Due to the excessive longitudinal mode numbers, the current MLM-HSRL cannot obtain a well spectral suppression effect, which seriously affects the retrieval accuracy of the optical characteristic parameters. In this paper, a new index called Longitudinal Mode Rejection Ratio (LMRR) has been proposed to evaluate the spectral suppression effect of the MLM-HSRL; a novel mismatch error and mode control (MEMC) technique is proposed to improve the spectral suppression effect of the MLM-HSRL, which contributes to developing the scientific potential of the MLM-HSRL for aerosol remote sensing. Based on our self-developed MLM laser, through controlling the longitudinal mode frequency-pulled shift of the MLM laser, adjusting the total mismatch error, and reducing the longitudinal mode numbers, we realize the LMRR index improved from about 5 to over 30, and the working stability of the system is also promoted by decreasing the longitudinal mode numbers. The experiment well improves the spectral suppression effect and verifies the effectiveness of the proposed MEMC technique. To the best of our knowledge, for the first time, the study addresses the conundrum of the lower spectral suppression effect for the MLM-HSRL. This work would help to provide a powerful support for the high-precision, long-term, and stable operation of the MLM-HSRL in the future.

High-spectral-resolution LIDAR based on a few-longitudinal mode laser for aerosol and cloud characteristics detection.

A novel implementation of high-spectral-resolution LIDAR based on a passively Q-switched few-longitudinal mode laser (PQFLM-HSRL) is proposed, and the prototype is built for detecting aerosol and cloud characteristics. The spatial-temporal distributions of the aerosol and cloud are continuously observed by the PQFLM-HSRL for the first time, to the best of our knowledge. Based on observation, we present the retrieval results of backscatter coefficient, particle linear depolarization ratio, and LIDAR ratio, and these intensive parameters are used to classify the aerosol and cloud into different types. Particularly, we have observed mix-phased clouds. The resulting aerosol optical depths (AODs) are highly consistent with CE-318, the Sun photometer measurements of the local National Meteorological Station (NMS), which verify the retrieval accuracy and the system stability. In addition, the retrieved AODs also characterize the ambient air quality, which show a high correlation with the measured PM2.5 concentrations. The implementation of the PQFLM-HSRL provides a new method for atmospheric feature detection, which shows superior scientific potential for further study on climate change and environmental health.

Shipborne oceanic high-spectral-resolution lidar for accurate estimation of seawater depth-resolved optical properties.

Lidar techniques present a distinctive ability to resolve vertical structure of optical properties within the upper water column at both day- and night-time. However, accuracy challenges remain for existing lidar instruments due to the ill-posed nature of elastic backscatter lidar retrievals and multiple scattering. Here we demonstrate the high performance of, to the best of our knowledge, the first shipborne oceanic high-spectral-resolution lidar (HSRL) and illustrate a multiple scattering correction algorithm to rigorously address the above challenges in estimating the depth-resolved diffuse attenuation coefficient Kd and the particulate backscattering coefficient bbp at 532 nm. HSRL data were collected during day- and night-time within the coastal areas of East China Sea and South China Sea, which are connected by the Taiwan Strait. Results include vertical profiles from open ocean waters to moderate turbid waters and first lidar continuous observation of diel vertical distribution of thin layers at a fixed station. The root-mean-square relative differences between the HSRL and coincident in situ measurements are 5.6% and 9.1% for Kd and bbp, respectively, corresponding to an improvement of 2.7-13.5 and 4.9-44.1 times, respectively, with respect to elastic backscatter lidar methods. Shipborne oceanic HSRLs with high performance are expected to be of paramount importance for the construction of 3D map of ocean ecosystem.

Extradural Contralateral Ventral Root Transfer to Treat Lower Limb Motor Dysfunction in Paraplegia.

STUDY DESIGN: Eight cadavers were included in this anatomical study. OBJECTIVE: This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia. SUMMARY OF BACKGROUND DATA: Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction. MATERIALS AND METHODS: Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. H&E staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves. RESULTS: After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured. CONCLUSION: Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia. LEVEL OF EVIDENCE: 5.

A Cadaver Feasibility Study of Extradural Contralateral C7 Ventral Root Transfer Technique for Treating Upper Extremity Paralysis.

STUDY DESIGN: A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study. OBJECTIVE: The aim was to ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior. SUMMARY OF BACKGROUND DATA: Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, the authors established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior. METHODS: In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical magnetic resonance imaging scans of 60 adults were used to measure the distance between the donor and recipient nerves. RESULTS: Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm ( P <0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root. CONCLUSION: Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function. LEVEL OF EVIDENCE: 5.

AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2.

Porcine reproductive and respiratory syndrome (PRRS) is a pig disease caused by the PRRS virus (PRRSV) that is characterized with diffuse interstitial pneumonia and lung edema. High expressions of chemokine CXCL10 and its receptor CXCR3 are reported in infected porcine lungs. Since CXCR3 is a key player in host inflammatory response, it might be a therapeutic target to treat lung damage caused by PRRSV infection. The size of pigs has long hampered research into molecular mechanisms of PRRS and validating the potential pharmaceutical targets. In this study, a porcine lung xenograft model with PRRSV infection was generated in immunodeficient mice to evaluate the therapeutic effects of the CXCR3 antagonist AMG487 on PRRSV infection-induced lung injury. The porcine lung tissues developed normally two weeks after xeno-transplantation in the mouse kidney capsule. Infection of PRRSV resulted in its efficient replication in the xenografts and histological damage to the porcine lung tissue structure, with no or little effects on mouse lungs. AMG487 administration dramatically reduced the number of PRRSV genome copies and significantly alleviated the porcine lung injury. Furthermore, treatment of AMG487 in cultured porcine macrophages consistently suppressed PRRSV replication with significant downregulation of Annexin A2 (ANXA2), a cellular protein facilitating viral replication. These findings provide a suitable model for evaluating new antiviral therapies as well as a possible therapeutic option for virus infection-induced lung injury.

Dihydromyricetin protects against Doxorubicin-induced cardiotoxicity through activation of AMPK/mTOR pathway.

BACKGROUND: Doxorubicin (DOX) is a highly effective broad-spectrum antitumor agent, but its clinical administration is limited by self-induced cardiotoxicity. Dihydromyricetin (DHM) is a flavonoid compound extracted from the Japanese raisin tree. Evidence that DHM has neovascular protective properties makes it a candidate for studying cardiotoxicity prevention strategy. However, it remains unknown if DHM can protect against cardiotoxicity caused by DOX. PURPOSE: The present study was performed to evaluate the protective effect of DHM on DOX-induced cardiotoxicity in vivo and in vitro. METHODS: C57BL/6 mice were intraperitoneally injected with DOX to construct cardiac injury model in vivo, and AC16 cells were exposed to DOX to induce cell injury in vitro. Left ventricular function of mice were detected by echocardiography, the apoptosis of mice cardiac tissue and AC16 cells were detected by TUNEL and Hoechst33342/PI double staining. The expression of apoptosis and autophagy related proteins were detected by western blotting, immunohistochemical staining and immunofluorescence staining. RESULTS: Echocardiographic results showed that DOX-induced cardiotoxicity were significantly alleviated by DHM pretreatment. DOX induced cardiotoxicity of mice by inhibiting AMPK activation, increasing apoptosis and decreasing autophagy. However, under the same conditions, the heart tissue of DHM-pretreated mice showed increased autophagy and decreased apoptosis via activation AMPK/mTOR pathway. The same results were observed in vitro, and it was also found that DHM can inhibit the production of intracellular ROS in vitro. CONCLUSION: DHM protects against cardiotoxicity by inhibiting apoptosis and oxidative stress and it can allevate theautophagy inhibition caused by DOX through AMPK/mTOR pathway. DHM preconditioning may be a breakthrough in protecting DOX-induced cardiotoxicity in the future clinical applications.

Activation of glucagon-like peptide-1 receptor in microglia attenuates neuroinflammation-induced glial scarring via rescuing Arf and Rho GAP adapter protein 3 expressions after nerve injury.

Rationale: The neuroinflammation is necessary for glial group initiation and clearance of damaged cell debris after nerve injury. However, the proinflammatory polarization of excessive microglia amplifies secondary injury via enhancing cross-talk with astrocytes and exacerbating neurological destruction after spinal cord injury (SCI). The glucagon-like peptide-1 receptor (GLP-1R) agonist has been previously shown to have a neuroprotective effect in neurodegeneration, whereas its potency in microglial inflammation after SCI is still unknown. Methods: The effect and mechanism of GLP-1R activation by exendin-4 (Ex-4) were investigated in in vitro cultured glial groups and in vivo in SCI mice. Alterations in the gene expression after GLP-1R activation in inflammatory microglia were measured using mRNA sequencing. The microglial polarization, neuroinflammatory level, and astrocyte reaction were detected by using western blotting, flow cytometry, and immunofluorescence. The recoveries of neurological histology and function were also observed using imaging and ethological examinations. Results: GLP-1R activation attenuated microglia-induced neuroinflammation by reversing M1 subtypes to M2 subtypes in vitro and in vivo. In addition, activation of GLP-1R in microglia blocked production of reactive astrocytes. We also found less neuroinflammation, reactive astrocytes, corrected myelin integrity, ameliorated histology, and improved locomotor function in SCI mice treated with Ex-4. Mechanistically, we found that Ex-4 rescued the RNA expression of Arf and Rho GAP adapter protein 3 (ARAP3). Knockdown of ARAP3 in microglia reversed activation of RhoA and the pharmacological effect of Ex-4 on anti-inflammation in vitro. Conclusion: Ex-4 exhibited a previously unidentified role in reducing reactive astrocyte activation by mediation of the PI3K/ARAP3/RhoA signaling pathway, by neuroinflammation targeting microglia, and exerted a neuroprotective effect post-SCI, implying that activation of GLP-1R in microglia was a therapeutical option for treatment of neurological injury.