Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.

Peripheral Nerve Injury Induced by Japanese Encephalitis Virus in C57BL/6 Mouse.

Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barré syndrome caused by JEV infections is not frequent, a few cases have been reported in recent years. To date, no existing animal model for JEV-induced peripheral nerve injury (PNI) has been established, and thus the pathogenic mechanism is not clarified. Therefore, an animal model is urgently required to clarify the correlation between JEV infection and PNI. In the present study, we used JEV GIb strain of NX1889 to establish a mouse model of JEV infection. The general neurological signs emerged on day 3 of modeling. The motor function continued to deteriorate, reaching a maximum at 8 to 13 days postinfection (dpi) and gradually recovered after 16 dpi. The injuries of 105 PFU and 106 PFU groups were the most severe. Transmission electron microscopy and immunofluorescence staining showed varying degrees of demyelination and axonal degeneration in the sciatic nerves. The electrophysiological recordings demonstrated the presence of demyelinating peripheral neuropathy with reduced nerve conduction velocity. The decreased amplitudes and the prolonged end latency revealed axonal-type motor neuropathy. Demyelination is predominant in the early stage, followed by axonal injury. The expression level of JEV-E protein and viral RNA was elevated in the injured sciatic nerves, suggesting that it may cause PNI at the early stage. Inflammatory cell infiltration and increased inflammatory cytokines indicated that neuroinflammation is involved in JEV-induced PNI. IMPORTANCE JEV is a neurotropic flavivirus belonging to the Flaviviridae family and causes high mortality and disability rates. It invades the central nervous system and induces acute inflammatory injury and neuronal death. Thus, JEV infection is a major global public health concern. Previously, motor dysfunction was mainly attributed to central nervous system damage. Our knowledge regarding JEV-induced PNI is vague and neglected. Therefore, a laboratory animal model is essential. Herein, we showed that C57BL/6 mice can be used to study JEV-induced PNI through multiple approaches. We also demonstrated that viral loads might be positively correlated with lesion severity. Therefore, inflammation and direct virus infection may be the putative mechanisms underlying JEV-induced PNI. The results of this study laid the foundation for further elucidation of the pathogenesis mechanisms of PNI caused by JEV.

Quantifying the Importance of Non-Suicidal Self-Injury Characteristics in Predicting Different Clinical Outcomes: Using Random Forest Model.

Existing research on non-suicidal self-injury (NSSI) among adolescents has primarily concentrated on general risk factors, leaving a significant gap in understanding the specific NSSI characteristics that predict diverse psychopathological outcomes. This study aims to address this gap by using Random Forests to discern the significant predictors of different clinical outcomes. The study tracked 348 adolescents (64.7% girls; mean age = 13.31, SD = 0.91) over 6 months. Initially, 46 characteristics of NSSI were evaluated for their potential to predict the repetition of NSSI, as well as depression, anxiety, and suicidal risks at a follow-up (T2). The findings revealed distinct predictors for each psychopathology. Specifically, psychological pain was identified as a significant predictor for depression, anxiety, and suicidal risks, while the perceived effectiveness of NSSI was crucial in forecasting its repetition. These findings imply that it is feasible to identify high-risk individuals by assessing key NSSI characteristics, and also highlight the importance of considering diverse NSSI characteristics when working with self-injurers.

KLHL11 antibody-associated autoimmune encephalomyelitis in a middle-aged female patient: a case report and literature review.

HEADINGS: Kelch-like protein 11antibody is a recently identified biomarker for paraneoplastic neurological syndromes associated with germ-cell tumors that was first described as an onconeural antibody causing autoimmune encephalitis associated with seminoma in 2019. Ataxia is the most prevalent presenting symptom, with other neurological symptoms including vertigo, double vision, hearing loss, tinnitus and dysarthria. Magnetic resonance imaging scans reveal that the lesions are mostly located in the cerebellum and brainstem, particularly in the pontine region, and may also exhibit cerebellar atrophy. AIM OF THE STUDY: In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome. MATERIALS AND METHODS: We present a middle-aged female patient who presented with vertigo, cognitive decline, ataxia and limb weakness. A cell-based assay (CBA) showed positive IgG Kelch-like protein 11 in both her serum and CSF, as well as positive oligoclonal bands in her CSF. She was diagnosed with KLHL11 antibody-associated autoimmune encephalomyelitis and received high-dose intravenous methylprednisolone pulse therapy. RESULT AND CONCLUSIONS: Clinical outcomes suggest that patients with Kelch-like protein 11 antibody mostly have poor prognoses, excepting our case. We propose that early and appropriate treatments are critical for timely diagnosis and rapid improvement.

Y-Net: a dual-branch deep learning network for nonlinear absorption tomography with wavelength modulation spectroscopy.

This paper demonstrates a new method for solving nonlinear tomographic problems, combining calibration-free wavelength modulation spectroscopy (CF-WMS) with a dual-branch deep learning network (Y-Net). The principle of CF-WMS, as well as the architecture, training and performance of Y-Net have been investigated. 20000 samples are randomly generated, with each temperature or H2O concentration phantom featuring three randomly positioned Gaussian distributions. Non-uniformity coefficient (NUC) method provides quantitative characterizations of the non-uniformity (i.e., the complexity) of the reconstructed fields. Four projections, each with 24 parallel beams are assumed. The average reconstruction errors of temperature and H2O concentration for the testing dataset with 2000 samples are 1.55% and 2.47%, with standard deviations of 0.46% and 0.75%, respectively. The reconstruction errors for both temperature and species concentration distributions increase almost linearly with increasing NUC from 0.02 to 0.20. The proposed Y-Net shows great advantages over the state-of-the-art simulated annealing algorithm, such as better noise immunity and higher computational efficiency. This is the first time, to the best of our knowledge, that a dual-branch deep learning network (Y-Net) has been applied to WMS-based nonlinear tomography and it opens up opportunities for real-time, in situ monitoring of practical combustion environments.

Temperature-driven phase transition of Ti2CN from first-principles calculations.

First-principles evolutionary simulations are used to predict the stable compound of Ti2CN. Body-centered tetragonal I41/amd-Ti2CN is found to be more energetically favorable than the other Ti2CN compounds at 0 K. The phase stability as a function of temperature for all relevant competing Ti2CN phases is investigated by means of first-principles calculations and quasi-harmonic approximation. Our calculations predict that I41/amd-Ti2CN undergoes a phase transition to P42/mmc at 1698 K and then to R3̄m at 1872 K. The different effects from the harmonic, electronic and quasi-harmonic contributions to the Gibbs free energy for I41/amd, P42/mmc and R3̄m phases are compared and analyzed. It is found that both the electronic and quasi-harmonic contributions to the Gibbs free energies significantly affect the phase transition curve of Ti2CN. The calculated temperature-dependent lattice parameter is carefully compared with the previous experimental results. We also provide important thermodynamic quantities as the volumetric expansion coefficient and isothermal bulk modulus and discuss their temperature dependence.

A Robust Visual Tracking Method Based on Reconstruction Patch Transformer Tracking.

Recently, the transformer model has progressed from the field of visual classification to target tracking. Its primary method replaces the cross-correlation operation in the Siamese tracker. The backbone of the network is still a convolutional neural network (CNN). However, the existing transformer-based tracker simply deforms the features extracted by the CNN into patches and feeds them into the transformer encoder. Each patch contains a single element of the spatial dimension of the extracted features and inputs into the transformer structure to use cross-attention instead of cross-correlation operations. This paper proposes a reconstruction patch strategy which combines the extracted features with multiple elements of the spatial dimension into a new patch. The reconstruction operation has the following advantages: (1) the correlation between adjacent elements combines well, and the features extracted by the CNN are usable for classification and regression; (2) using the performer operation reduces the amount of network computation and the dimension of the patch sent to the transformer, thereby sharply reducing the network parameters and improving the model-tracking speed.

SD-36 promotes growth inhibition and induces apoptosis via suppression of Mcl-1 in glioma.

Glioma is one of the most commonly observed tumours, representing approximately 75% of brain tumours in the adult population. Generally, glioma therapy includes surgical resection followed by radiotherapy and chemotherapy. The transcription factor STAT3 (signal transducer and activator of transcription 3) is a promising target for the treatment of cancer and several other diseases. At nanomolar concentrations, SD-36 induces rapid cellular degradation of STAT3 but cannot degrade other STAT proteins. The current study demonstrates the therapeutic efficacies of the STAT3 degraders SD-36 against glioma, as well as understanding the elucidating mechanisms and identifying molecular markers that determine cell sensitivity to STAT3 degraders. Glioma cell lines possessed similar response patterns to SD-36 but different responses to the STAT3 inhibitor Stattic. SD-36 potently induced apoptosis in glioma cells along with a reduction in Mcl-1 levels, which are critical for mediating the induction of apoptosis and enhancing TMZ-induced apoptosis. Accordingly, SD-36 sensitizes the antitumour effect of TMZ in patient-derived xenograft. In addition, the downregulation of Mcl-1 expression-mediated antitumour effect of SD-36 was analysed in cell-derived xenograft. These observations need to be validated clinically to confirm the efficacy of STAT3 degraders in glioma.

Gaussian process regression for direct laser absorption spectroscopy in complex combustion environments.

Tunable diode laser absorption spectroscopy (TDLAS) has been proved to be a powerful diagnostic tool in combustion research. However, current methods for post-processing a large number of blended spectral lines are often inadequate both in terms of processing speed and accuracy. The present study verifies the application of Gaussian process regression (GPR) on processing direct absorption spectroscopy data in combustion environments to infer gas properties directly from the absorbance spectra. Parallelly-composed generic single-output GPR models and multi-output GPR models based on linear model of coregionalization (LMC) are trained using simulated spectral data at set test matrix to determine multiple unknown thermodynamic properties simultaneously from the absorbance spectra. The results indicate that compared to typical data processing methods by line profile fitting, the GPR models are proved to be feasible for accurate inference of multiple gas properties over a wide spectral range with a manifold of blended lines. While further validation and optimization work can be done, parallelly composed single-output GPR model demonstrates sufficient accuracy and efficiency for the demand of temperature and concentration inference.

Omp31 of Brucella Inhibits NF-κB p65 Signaling Pathway by Inducing Autophagy in BV-2 Microglia.

Neurobrucellosis is a serious central nervous system (CNS) inflammatory disorder caused by Brucella, and outer membrane protein-31 (Omp31) plays an important role in Brucella infection. This study aims to determine whether Omp31 can induce autophagy in BV-2 microglia. Another goal of the study is to further examine the effect of autophagy on the nuclear transcription factor κB (NF-κB) p65 signaling pathway. We observed that Omp31 stimulated autophagy by increasing microtubule-associated protein 1 light chain 3B (LC3B-II) levels and inducing autophagosome formation at 6 h and 12 h. Concomitantly, Omp31 induced tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression in a time-dependent manner but reduced the expression of TNF-α at 6 h. We utilized Omp31 with or without rapamycin or 3-methyladenine (3-MA) to treat BV-2 microglia, and it demonstrated further that Omp31 induced autophagy by promoting LC3B-II, Beclin-1 proteins expression and inhibiting the p62 protein levels. Furthermore, we explored the effects of autophagy on the NF-κB p65 pathway through western blot analysis, RT-qPCR assay, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. The data suggest that Omp31 as well as rapamycin, the autophagy inducer, can decrease TNF-α levels through the inhibition of the NF-κB p65 signaling pathway. Taken together, Omp31 can function as a catalyst in both autophagy induction and NF-κB p65 signal inhibition. Furthermore, Omp31-induced autophagy may inhibit the expression of TNF-α by negatively regulating NF-κB p65 signaling pathway.

A Micron-Sized Laser Photothermal Effect Evaluation System and Method.

The photothermal effects of lasers have played an important role in both medical laser applications and the development of cochlear implants with optical stimulation. However, there are few methods to evaluate the thermal effect of micron-sized laser spots interacting with other tissues. Here, we present a multi-wavelength micro-scale laser thermal effect measuring system that has high temporal, spatial and temperature resolutions, and can quantitatively realize evaluations in real time. In this system, with accurate 3D positioning and flexible pulsed laser parameter adjustments, groups of temperature changes are systematically measured when the micron-sized laser spots from six kinds of wavelengths individually irradiate the Pd/Cr thermocouple junction area, and reference data of laser spot thermal effects are obtained. This work develops a stable, reliable and universal tool for quantitatively exploring the thermal effect of micron-sized lasers, and provides basic reference data for research on light-stimulated neuron excitement in the future.

Prediction of Novel van der Waals Boron Oxides with Superior Deep-Ultraviolet Nonlinear Optical Performance.

Deep-ultraviolet nonlinear optical (DUV NLO) materials are attracting increasing attention because of their structural diversity and complexity. Using the two-dimensional (2D) crystal structure prediction method combined with the first-principles calculations, here we propose layered 18-membered-ring (18MR) boron oxide B2 O3 polymorphs as high-performance NLO materials. 18MR-B2 O3 with the AA and AB stackings are potential DUV NLO materials. The superior performing 18MR-B2 O3 AB has an unprecedentedly high second harmonic generation coefficient of 1.63 pm V-1 , the largest among the DUV NLO materials, three times larger than that of the advanced DUV NLO material KBe2 BO3 F2 and comparable to that of ß-BaB2 O4 . Its unusually large birefringence of 0.196 at 400 nm guarantees the phase-matching wavelength λPM to reach this material's extreme absorption edge of ≈154 nm.

Tibial Nail Combined with Vacuum Sealing Drainage for Gustilo Grade IIIB Open Tibial Fractures: A Patient Series.

Gustilo grade IIIB open tibial fractures are relatively difficult to treat. We investigated the treatment effects of tibial intramedullary nails combined with vacuum sealing drainage (VSD) for Gustilo grade IIIB open tibial fractures. From March 2015 to March 2017, 13 cases of Gustilo grade IIIB open tibial fractures were treated with Expert Tibial Nails combined with VSD. Causes of injury included falls from a height (n = 9, 69.2%) and road accidents (n = 4, 30.8%). The duration from time of injury to hospital intake was 7.3 hours (range 5 to 9.5), and the time between injury and operation was 6.7 days (range 3 to 11). Six months after the operation, overall patient general health was investigated via the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and the physical and mental health dimensions of the Short-Form Health Survey 36 (SF-36). Postoperative complications and infections also were recorded. The results indicated that the median AOFAS score was 93.7 (range 89 to 97), with all individuals having either excellent (90 to 100; n = 10, 76.9%) or good (80 to 89; n = 3, 23.1%) outcomes. The median physical SF-36 score was 83.1 (range 72.5 to 93.0), and the median mental SF-36 score was 80.6 (range 69.7 to 92.0). Moreover, there were no instances of tibial shortening, neurovascular injury, postoperative complications, implant failure, malunion, or serious infections. In conclusion, intramedullary tibial nail combined with VSD is a safe and effective method to treat type grade IIIB open tibial fractures.

Multifunctional Freestanding Microprobes for Potential Biological Applications.

Deep-level sensors for detecting the local temperatures of inner organs and tissues of an animal are rarely reported. In this paper, we present a method to fabricate multifunctional micro-probes with standard cleanroom procedures, using a piece of stainless-steel foil as the substrate. On each of the as-fabricated micro-probes, arrays of thermocouples made of Pd-Cr thin-film stripes with reliable thermal sensing functions were built, together with Pd electrode openings for detecting electrical signals. The as-fabricated sword-shaped freestanding microprobes with length up to 30 mm showed excellent mechanical strength and elastic properties when they were inserted into the brain and muscle tissues of live rats, as well as suitable electrochemical properties and, therefore, are promising for potential biological applications.

Water-Soluble Coenzyme Q10 Reduces Rotenone-Induced Mitochondrial Fission.

Parkinson's disease is a neurodegenerative disorder characterized by mitochondrial dysfunction and oxidative stress. It is usually accompanied by an imbalance in mitochondrial dynamics and changes in mitochondrial morphology that are associated with impaired function. The objectives of this study were to identify the effects of rotenone, a drug known to mimic the pathophysiology of Parkinson's disease, on mitochondrial dynamics. Additionally, this study explored the protective effects of water-soluble Coenzyme Q10 (CoQ10) against rotenone-induced cytotoxicity in murine neuronal HT22 cells. Our results demonstrate that rotenone elevates protein expression of mitochondrial fission markers, Drp1 and Fis1, and causes an increase in mitochondrial fragmentation as evidenced through mitochondrial staining and morphological analysis. Water-soluble CoQ10 prevented mitochondrial dynamic imbalance by reducing Drp1 and Fis1 protein expression to pre-rotenone levels, as well as reducing rotenone treatment-associated mitochondrial fragmentation. Hence, water-soluble CoQ10 may have therapeutic potential in treating patients with Parkinson's disease.

Expert Tibial Nails for Treating Distal Tibial Fractures With Soft Tissue Damage: A Patient Series.

Distal tibial fractures with soft tissue damage are relatively difficult to treat. We assessed the outcomes of patients with these fractures treated with the Expert Tibial Nail® (DePuy Synthes, Raynham, MA) from March 2012 to December 2014. At 6 months postoperatively, the general health quality of patients was assessed using operative time, interval to return to work, American Orthopaedic Foot and Ankle Society ankle scale score, pain measured using a visual analog scale, and short-form health outcomes 36-item survey physical functioning and mental health dimension scores. Of 11 cases, 7 (63.6%) were open fractures (3 [27.3%] Gustilo-Anderson type II, 3 [27.3%] type IIIA, and 1 [9.1%] type IIIB) and 4 (36.4%) were closed fractures with Tscherne-Oestern type II tissue damage. Their mean age was 52.2 (range 28 to 66) years. The mean operative time was 83 (range 65 to 105) minutes. The mean follow-up period was 16.3 (range 14 to 18) months. The median short-form 36-item survey scores were 79.1 (range 68.9 to 89.0) for the physical function dimension and 77.0 (range 64.3 to 90.0) for the mental health dimension. The mean postoperative ankle score was 88.6 (range 84 to 94). The mean pain score was 1.6 (range 0 to 4) mm. The mean interval to return to work was 14 (range 11 to 17) months. No patient showed evidence of neurovascular damage, malunion, nonunion, or shortening of the tibia. Taken together, we have confirmed that Expert Tibial Nails can effectively treat distal tibial fractures with soft tissue damage.

Band inversion and topological aspects in a TiNI monolayer.

To achieve a device application of the quantum spin Hall (QSH) effect, increasing the critical temperature is crucial. A two-dimensional topological insulator (2D-TI) with a sizeable bulk band gap is one of the most promising strategies to reach this goal. Using first-principles calculations, we propose a new 2D-TI, titanium nitride iodide (TiNI) monolayer, which can be exfoliated from a bulk TiNI crystal, thanks to the weak interlayer interaction. We demonstrate that the TiNI monolayer has an inverted band structure accompanied by topologically nontrivial states characterized by a topological invariant of Z2 = 1. The band gap (∼50 meV) opened due to spin-orbit coupling (SOC) is available for achieving the QSH effect at room temperature. The band inversion and topologically nontrivial states are robust under external strain, suggesting that the 2D TiNI monolayer lattice could be a versatile platform for hosting nontrivial topological states with potential applications in 2D spintronics and computer technology.

Real-Time Two-Dimensional Mapping of Relative Local Surface Temperatures with a Thin-Film Sensor Array.

Dynamic mapping of an object's local temperature distribution may offer valuable information for failure analysis, system control and improvement. In this letter we present a computerized measurement system which is equipped with a hybrid, low-noise mechanical-electrical multiplexer for real-time two-dimensional (2D) mapping of surface temperatures. We demonstrate the performance of the system on a device embedded with 32 pieces of built-in Cr-Pt thin-film thermocouples arranged in a 4 × 8 matrix. The system can display a continuous 2D mapping movie of relative temperatures with a time interval around 1 s. This technique may find applications in a variety of practical devices and systems.

Phagraphene: A Low-Energy Graphene Allotrope Composed of 5-6-7 Carbon Rings with Distorted Dirac Cones.

Using systematic evolutionary structure searching we propose a new carbon allotrope, phagraphene [fæ'græfi:n], standing for penta-hexa-hepta-graphene, because the structure is composed of 5-6-7 carbon rings. This two-dimensional (2D) carbon structure is lower in energy than most of the predicted 2D carbon allotropes due to its sp(2)-binding features and density of atomic packing comparable to graphene. More interestingly, the electronic structure of phagraphene has distorted Dirac cones. The direction-dependent cones are further proved to be robust against external strain with tunable Fermi velocities.