Search

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-1β, 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.

Abstract Opencast coal mining has a large impact on the land surface, both at the mining pits themselves and at waste sites. After artificial management is stopped, a reclaimed opencast coal mine dump is affected by wind and water erosion from natural processes, resulting in land degradation and even safety incidents. In this paper, the soil erosion and land degradation after 5 years of such natural processes, at the Xilinhot opencast coal mine dump in Inner Mongolia, were investigated. A multi-source data acquisition method was applied: the vegetation fraction coverage (VFC) was extracted from GF-1 satellite imagery, high-precision terrain characteristics and the location and degree of soil erosion were obtained using a drone, and the physical properties of the topsoil were obtained by field sampling. On this basis, the degree and spatial distribution of erosion cracks were identified, and the causes of soil erosion and land degradation were analyzed using the geographical detector. The results show that (1) multi-source data acquisition method can provide effective basic data for the quantitative evaluation of the ecological environment at dumps, and (2) slope aspect and VFC are the main factors affecting the degree of degradation and soil erosion. Based on above analysis, several countermeasures are proposed to mitigate land degradation: (1) The windward slope be designed to imitate the natural landform. (2) Reasonable engineering measures should be applied at the slope to restrain soil erosion. (3) The Pioneer plants should be widely planted on the platform at the early stage of reclamation.

Objective: To explore the method of eliminating donor-specific anti-HLA antibodies (DSA) in haploidentical stem cell transplantation (haplo-SCT). Methods: We present a refractory B-cell acute lymphoblastic leukemia (ALL) patient who had strongly positive DSA, but had no human leukocyte antigen–matched donor. Although CD38 expression on leukemia cells was negative, daratumumab combined with etoposide and venetoclax therapy was chosen for her. Results: She achieved a significant decrease in DSA levels and complete remission on the combination therapy with daratumumab. She then received a haplo-SCT from a daughter as a donor and had a successful engraftment of donor stem cell. In haplo-SCT, strongly positive DSA levels, directed against donor HLA antigens, could be significantly reduced by daratumumab therapy before transplantation and successfully bridge subsequent haplo-SCT. Conclusion: Although CD38 expression is negative in leukemia cells, refractory B-ALL patients may still benefit from combination therapy with daratumumab. We need further clinical observation.

Mangrove wetlands are under increasing pollution pressure from human activities due to rapid industrialization and urbanization of coastal regions. Many pollutants such as heavy metals may be accumulated via food chains to hazardous levels which will thus bring potential health issues to humans. In the present study, three species of crabs (Sesarma dehaani, Sesarma plicata, Macrophthalmus japonicus) and associated sediments from three mangrove habitats with different vegetation were collected from the mangrove wetlands in Qi'ao Island, South China to investigate the levels, bioaccumulation and dietary exposure of heavy metals including copper (Cu), zinc (Zn), manganese (Mn), cadmium (Cd) and chromium (Cr). Metal concentrations in sediment samples were 65–91, 212–247, 506–1256, 0.6–1.3, and 8.8–14 mg/kg dry weight for Cu, Zn, Mn, Cd and Cr, respectively. The spatial heterogeneity of these metals in mangrove sediments was observed with a descendant order of metal concentrations as Mn > Zn > Cu > Cr > Cd at each site. Species-specific and tissue-specific accumulation of metals was also found in mangrove crabs, both in the degree of accumulation of particulate metals and the tissues in which they were most abundant. All biota-sediment accumulation factors (BSAF) values >1 for Cd in each crab species suggested that the native mangrove crabs tended to be good tools for the monitoring of Cd pollution in mangrove forests. Results of the estimated daily intake (EDI) and target hazard quotient (THQ) suggested that consumption of the mangrove crabs in Qi'ao Island might subject local residents to potential health risks as far as the metals are concerned. Keywords: Heavy metal, Sediment, Crab, Mangrove wetland, Qi'ao Island

The recovery of lower-urinary-tract activity is a top priority for patients with spinal-cord injury. Historically, locomotor training improved micturition function in both patients with spinal cord injury and animal models. We explore whether training augments such as the supraspinal control of the external urethral sphincter results in enhanced coordination in detrusor-sphincter activity. We implemented a clinically relevant contusive spinal-cord injury at the 12th thoracic level in rats and administered forced wheel running exercise for 11 weeks. Awake rats then underwent bladder cystometrogram and sphincter electromyography recordings to examine the micturition reflex. Subsequently, pseudorabies-virus-encoding red fluorescent protein was injected into the sphincter to trans-synaptically trace the supraspinal innervation of Onuf’s motoneurons. Training in the injury group reduced the occurrence of bladder nonvoiding contractions, decreased the voiding threshold and peak intravesical pressure, and shortened the latency of sphincter bursting during voiding, leading to enhanced voiding efficiency. Histological analysis demonstrated that the training increased the extent of spared spinal-cord tissue around the epicenter of lesions. Compared to the group of injury without exercise, training elicited denser 5-hydroxytryptamine-positive axon terminals in the vicinity of Onuf’s motoneurons in the cord; more pseudorabies virus-labeled or c-fos expressing neurons were detected in the brainstem, suggesting the enhanced supraspinal control of sphincter activity. Thus, locomotor training promotes tissue sparing and axon innervation of spinal motoneurons to improve voiding function following contusive spinal-cord injury.

Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C (1, 5, 10, 20, 40 μg/mL) for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner. Mitomycin C upregulated the expression levels of Fas, DR4, DR5, cleaved caspase-8/9, Bax, Bim and cleaved caspase-3 proteins, and it downregulated Bcl-2 and Bcl-xL expression. In addition, inhibitors of caspase-8 and caspase-9 (Z-IETD-FMK and Z-LEHD-FMK, respectively) did not fully inhibit mitomycin C-induced apoptosis. Furthermore, mitomycin C induced endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78, CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-4 in a dose-dependent manner. Salubrinal significantly inhibited the mitomycin C-induced cell viability loss and apoptosis, and these effects were accompanied by a reduction in CHOP expression. Our results support the hypothesis that mitomycin C induces human epidural scar fibroblast apoptosis, at least in part, via the endoplasmic reticulum stress pathway.

Background/Aims: Hypertrophic scars (HS) formation results from reduced apoptosis and increased proliferation of fibroblasts. Therefore, apoptosis of fibroblasts is a key target for the development of novel therapeutic strategies for HS. Previous reports demonstrated that FK506 could attenuate scar formation in vivo and FK506 could also induce endoplasmic reticulum stress (ER stress). However, the effects of FK506 on ER stress-mediated apoptosis in fibroblasts remain unclear. Methods: Rat skin fibroblasts were used in the study. Cell viability was examined using cell counting Kit-8. Apoptosis was detected by Annexin V/Propidium Iodide Double Staining. Gene silencing was performed using Small Interfering RNAs (siRNAs) or via lentiviral infection. The expression of apoptosis-related proteins was determined via Western blot. Interaction between proteins was explored by co-immunoprecipitation. Results: FK506 significantly reduced cell viability and induced apoptosis in fibroblasts. Interestingly, ER stress was also activated after FK506 treatment. We further demonstrated that FK506-induced apoptosis was mediated by ER stress via activating CHOP, evidenced by decreased apoptosis after inhibition of ER stress using TUDCA or silencing expression of CHOP. Furthermore, Co-immunoprecipitation results indicated that treatment of FK506 induced disassociation of FKBP12.6 from RyR2 and its translocation from ER membrane to cytosol, consequently promoting ER stress-mediated apoptosis. Conclusion: FK506-induced fibroblasts apoptosis was mediated by ER stress via CHOP signaling pathway.

Background/Aims: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. Methods: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. Results: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-β/Smad pathway, evidenced by no change in the expression of TGF-β and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-β-induced fibrosis. Conclusions: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy.

Coal production in opencast mining generates substantial waste materials, which are typically delivered to an on-site waste dump. As a large artificial loose pile, such dumps have a special multi-berm structure accompanied by some security issues due to wind and water erosion. Highly accurate digital surface models (DSMs) provide the basic information for detection and analysis of elevation change. Low-cost unmanned aerial vehicle systems (UAS) equipped with a digital camera have become a useful tool for DSM reconstruction. To achieve high-quality UAS products, consideration of the number and configuration of ground control points (GCPs) is required. Although increasing of GCPs will improve the accuracy of UAS products, the workload of placing GCPs is difficult and laborious, especially in a multi-berm structure such as a waste dump. Thus, the aim of this study is to propose an improved GCPs configuration to generate accurate DSMs of a waste dump to obtain accurate elevation information, with less time and fewer resources. The results of this study suggest that: (1) the vertical accuracy of DSMs is affected by the number of GCPs and their configuration. (2) Under a set number of GCPs, a difference of accuracy is obtained when the GCPs are located on different berms. (3) For the same number of GCPs, the type 4 (GCPs located on the 1st and 4th berms) in the study is the best configuration for higher vertical accuracy compared with other types. The principal objective of this study provides an effective GCP configuration for DSM construction of coal waste dumps with four berms, and also a reference for engineering piles using multiple berms.

Idiopathic hypereosinophilic syndrome (HES) is a disease characterized by persistent hypereosinophilia (>1.5×109/L) for more than 6 months in the absence of other causes of reactive eosinophilia. Patients with HES presenting with multiorgan thromboses are rare. Herein we report a 57-year-old man with HES who presented with deep venous thrombosis of the lower extremities, portal thrombosis, pulmonary embolism, and mesenteric venous thrombosis, which led to intestinal obstruction.

Identification of motor and sensory nerves is important in applications such as nerve injury repair. Conventional practice relies on time consuming staining methods for this purpose. Here, we use laser scanning infrared differential interference contrast (IR-DIC) microscopy for label-free observation of the two types of nerve. Ventral and dorsal nerve roots of adult beagle dogs were collected and sections of different thicknesses were imaged with an IR-DIC microscope. Different texture patterns of the IR-DIC images of the motor and sensory nerve can be distinguished when the section thickness increases to 40μm. This suggests that nerve fibers in motor and sensory nerves have different distribution patterns. The result hints a potential new way for more rapid identification of nerve type in peripheral nerve repair surgery.

To study the main molecular mechanisms responsible for itraconazole resistance in clinical isolates of Candida krusei.The 14α-demethylases encoded by ERG11 gene in the 16 C.krusei clinical isolates were amplified by polymerase chain reaction (PCR), and their nucleotide sequences were determined to detect point mutations. Meanwhile, ERG11 and efflux transporters (ABC1 and ABC2) genes were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) for their expression in itraconazole-resistant (R), itraconazole-susceptible dose dependent (SDD) and itraconazole-susceptible (S) C.krusei at the mRNA level.We found 7-point mutations in ERG11 gene of all the C.krusei clinical isolates, including 6 synonymous mutations and 1 missense mutation (C44T). However, the missense mutation was found in the three groups. The mRNA levels of ERG11 gene in itraconazole-resistant isolates showed higher expression compared with itraconazole-susceptible dose dependent and itraconazole-susceptible ones (P = 0.015 and P = 0.002 respectively). ABC2 gene mRNA levels in itraconazole-resistant group was significantly higher than the other two groups, and the levels of their expression in the isolates appeared to increase with the decrease of susceptibility to itraconazole (P = 0.007 in SDD compared with S, P = 0.016 in SDD with R, and P

Differences in the levels of acetylcholinesterase (AChE) in ventral and dorsal spinal roots can be used to differentiate the spinal nerves. Although many methods are available to assay AChE, a rapid and sensitive method has not been previously developed. Here, we describe an antibody-based quartz crystal microbalance (QCM) assay and its application for the quantification of AChE in the solutions of ventral and dorsal spinal roots. The frequency variation of the QCM device corresponds to the level of AChE over a wide dynamic range (0.5-10 µg/ml), which is comparable to the response range of the ELISA method. The frequency shift caused by the ventral roots is 3-fold greater than that caused by the dorsal roots. The antibody-based QCM sensor was stable across many successive replicate samples, and the method required less than 10 min, including the AChE extraction and analysis steps. This method is a rapid and convenient means for the quantification of AChE in biological samples and may be applicable for distinguishing the ventral and dorsal roots during surgical operations.

Copyright of Journal of Planning Education & Research is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The editorial discusses recent advances in deep learning for traffic probabilistic prediction, emphasizing the importance of probabilistic models in handling uncertainties in traffic systems. Deep learning methods such as Bayesian Deep Learning, Deep Gaussian Processes, Quantile Regression, and diffusion models are explored for their effectiveness in providing a range of possible traffic states and their corresponding probabilities. The practical implications of probabilistic traffic prediction include proactive congestion control, refined passenger information systems, improved risk assessment for autonomous driving, and enhanced public transport planning. Future research directions focus on developing efficient and scalable deep Bayesian inference techniques, integrating various data sources for more precise predictions, and incorporating uncertainty estimates into decision-making frameworks for robust traffic management solutions. [Extracted from the article]

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 13 414.20 (± 2 890.30) and 10 613.20 (± 2 135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm2 and 1.08 (± 0.26) mm2, 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. [ABSTRACT FROM AUTHOR]