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By means of the ultrasonic surface impact (amplitude of 30 μm, strike number of 48,000 times/mm2), nanograins have been achieved in the surfaces of both Ti6Al4V(TC4) and Ti3Zr2Sn3Mo25Nb(TLM) titanium alloys, mainly because of the dislocation motion. Many mechanical properties are improved, such as hardness, residual stress, and roughness. The rotating–bending fatigue limits of TC4 and TLM subjected to ultrasonic impact are improved by 13.1% and 23.7%, separately. Because of the bending fatigue behavior, which is sensitive to the surface condition, cracks usually initiate from the surface defects under high stress amplitude. By means of an ultrasonic impact tip with the size of 8 mm, most of the inner cracks present at the zone with a depth range of 100~250 μm in the high life region. The inner crack core to TC4 usually appears as a deformed long and narrow α-phase, while the cracks in TLM specimens prefer to initiate at the triple grain boundary junctions. This zone crosses the grain refined layer and the deformed coarse grain layer. With the gradient change of elastic parameters, the model shows an increase of normal stress at this zone. Combined with the loss of plasticity and toughness, it is easy to understand these fatigue behaviors. [ABSTRACT FROM AUTHOR]

Objective: To explore the molecular mechanism of the protective effect of nerve growth factor (NGF) on injured spinal cord.Methods: The posterior T(8) (the 8th thoracic segment) spinal cords of 60 Wistar rats were injured by impacts caused by objects (weighing 10 g) falling from a height of 2.5 cm with Allen's way. Solution with nerve growth factors (NGF) was given to 30 rats (the NGF group) through a microtubule inserted into the subarachnoid cavity immediately, and at 2, 4, 8, 12 and 24 hours after spinal cord injury (SCI) respectively. Normal saline (NS) with same volume was given to the other 30 rats (the NS group) with the same method. And 5 normal rats were taken as the normal controls. The expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining.Results: The positive expression of bcl-2 protein was strong in the normal controls, but decreased in the NS group, and increased significantly in the NGF group as compared with that of the NS group (P<0.01). The positive expression of bax protein was also strong in the normal controls, but increased in the NS group, and decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Apoptotic neurons were found in the NS group, and they decreased significantly in the NGF group as compared with that of the NS group (P<0.01).Conclusions: NGF can protect the injured nerve tissues through stimulating the expression of bcl-2 protein, inhibiting the expression of bax protein and inhibiting the neuronal apoptosis after SCI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper mainly investigates the tensile behavior of fiber metal laminates (FMLs) under various temperatures ranged from 25 ℃ to 175 ℃ combined experimental measurement, theoretical model and numerical technique. Firstly, based on numerous tensile tests under various temperatures, different tensile load–displacement response and damage modes for FMLs can be obtained and compared. And in virtue of the scanning electron microscopy (SEM), microscopic damage modes are identified through the fracture surface scanning of FMLs subjected to different temperatures. Subsequently, in order to analyze the discreteness of experimental results and evaluate the theoretical tensile strength of FMLs under different temperatures, the two-parameter Weibull statistics model is established for engineering application of FMLs. Finally, the effect of layer direction on damage modes and progressive damage evolution process of FMLs is characterized numerically. These results indicate that the tensile strength of FMLs represents a nonlinear downward trend with the increase of temperature. The complex failure mechanisms under different temperatures can be captured from SEM observation, including fiber/matrix debonding, fiber pull-out, matrix microcrack, delamination damage and so on. The deeper understanding of tensile behavior and failure mechanisms of FMLs under thermal conditions can be provided for the design and utilization of FML structures. [ABSTRACT FROM AUTHOR]

In most cases, welding processes promote the application of structural materials at the expense of strength and ductility. Post-weld treatment is proposed to regain mechanical properties of weldment, which necessitates that microstructural and the associated mechanical behavior evolutions being clearly understood. In this study, post-weld heat treatment was conducted to enhance the mechanical properties of the electron beam welded Ti–5Al–2Sn–2Zr–4Mo–4Cr alloy joint. Microstructural evolutions and monotonic mechanical properties were characterized to optimize the post-weld heat treatment parameters. It was found that direct aging at 630 °C for 2 h can upraise the strength and ductility of the joint by ∼31% and ∼511% respectively. Metastable needle-shaped martensite α′ within rapidly solidified fusion zone had been completely decomposed, and thin recrystallized α lamella precipitated in the prior β phase without forming consecutive coarse grain boundary α after above direct aging treatment. Such microstructural characteristics enable the direct-aged joint to exhibit a higher fatigue strength from high to very high cycle region than the as-welded joint. Moreover, the fatigue crack nucleation resistance was enhanced significantly through direct aged treatment. • Post weld heat treatment was carried out to optimize the parameter on regaining mechanical properties of electron beam welded TC17 alloy joint. • The optimized parameter was obtained by precipitating recrystallized nano α lamella in FZ without coarsening in grain boundary α phase. • Fatigue strength and fatigue crack nucleation resistance were enhanced significantly by direct aging treatment. [ABSTRACT FROM AUTHOR]

This study explored diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to assess the prognosis of thoracolumbar spinal cord injury (SCI). Twenty patients with acute traumatic thoracolumbar complete SCI (T1-L1, American Spinal Injury Association Impairment Scale [AIS] grade A) underwent conventional magnetic resonance imaging and DTI examinations. DTI measured the fractional anisotropy (FA) and apparent diffusion coefficient adjacent to the lesion epicenter. DTT was used to detect the white matter fiber morphology and measure the imaginary white matter fiber volume and connection rates of fiber tractography (CRFT). The patients' neurological functions were evaluated by the AIS grades. At the final-follow-up, among the 20 patients with AIS grade A, 15 maintained the AIS grade (group A), and 5 patients showed improvement of AIS grade (group B). Group A's mean FA value was significantly lower than that of group B, whereas the mean apparent diffusion coefficient value among the 2 groups showed no significant difference. The white matter fibers of most patients in group A were completely ruptured (11/15), but the white matter fibers of all patients in group B were retained in different number (5/5). The mean CRFT of group B was significantly higher than that of group A (P < 0.05). The improvement of AIS grade was slightly positively correlated with FA values and highly positively correlated with CRFT. The prognosis of complete thoracolumbar SCI may be related to the FA value and the CRFT. The application of DTI and DTT may optimize the diagnosis of thoracolumbar SCI. [ABSTRACT FROM AUTHOR]

Background: Bilateral decompression via unilateral approach (BDUA) is an effective surgical approach for treating lumbar degenerative diseases. However, no studies of prognosis, especially the recovery of the soft tissue, have reported using BDUA in an elderly population. The aims of these research were to investigate the early efficacy of the bilateral decompression via unilateral approach versus conventional approach transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degenerative disc disease in the patients over 65 years of age, especially in the perioperative factors and the recovery of the soft tissue.Methods: The clinical data from 61 aging patients with lumbar degenerative disease who received surgical treatment were retrospectively analyzed. 31 cases who received the lumbar interbody fusion surgery with bilateral decompression via unilateral approach (BDUA) were compared with 30 cases who received conventional approach transforaminal lumbar interbody fusion. The radiographic parameters were measured using X-ray including lumbar lordosis angle and fusion rate. Japanese Orthopedic Association (JOA), Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were used to evaluate the clinical outcomes at different time points. Fatty degeneration ratio and area of muscle/vertebral body were used to detect recovery of soft tissue.Results: The BDUA approach group was found to have significantly less intraoperative blood loss(p < 0.05) and postoperative drainage(p < 0.05) compared to conventional approach transforaminal lumbar interbody fusion group. Symptoms of spinal canal stenosis and nerve compression were significantly relieved postoperatively, as compared with the preoperative state. However, the opposite side had a lower rate of fatty degeneration (9.42 ± 3.17%) comparing to decompression side (11.68 ± 3.08%) (P < 0.05) six months after surgery in the BDUA group. While there were no significant differences (P > 0.05) in two sides of conventional transforaminal lumbar interbody fusion approach group six months after surgery.Conclusions: Bilateral decompression via unilateral approach (BDUA) is able to reduce the intraoperative and postoperative body fluid loss in the elderly. The opposite side of decompression in BDUA shows less fatty degeneration in 6 months, which indicates better recovery of the soft tissue of the aging patients. [ABSTRACT FROM AUTHOR]

Background: Percutaneous kyphoplasty is the main method in the treatment of thoracolumbar osteoporotic compression fractures. However, much radiation exposure during the operation harms the health of surgeons and patients. In addition, the accuracy of this surgery still needs to be improved. This study aimed to assess the radiation exposure and clinical efficacy of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture. Methods: Included in this retrospective cohort study were 60 patients (60–90 years) who had undergone unilateral vertebroplasty for thoracolumbar osteoporotic compression fracture at our hospital between June 2019 and June 2020. All showed no systemic diseases and were assigned to Tirobot group (treated with Tirobot-assisted approach) and control group (treated with traditional approach). Fluoroscopic frequency, operative duration, length of stay (LOS), post-operative complications (cement leakage, infection, and thrombosis), and pre-operative and pre-discharge indexes (VAS score, JOA score, and Cobb's angle) were compared. Results: The fluoroscopic frequency (P < 0.001) and post-operative complications (P = 0.035) in Tirobot group were significantly lower than those in control group. The operative duration and LOS in the Tirobot group were shorter than those in the control group, but the differences were not statistically significant (P = 0.183). Pre-discharge VAS score and Cobb's angle decreased, and JOA increased after surgeries in both groups. These three indexes showed a significant difference after surgery in each group (P < 0.001), but not between groups (PVAS = 0.175, PCobb's = 0.585, PJOA = 0.448). Conclusion: The Tirobot-assisted vertebroplasty can reduce surgery-related trauma, post-operative complications, and patients' and operators' exposure to radiation. As a safe and effective strategy, this surgery can realize the quick recovery from thoracolumbar osteoporotic compression fracture. [ABSTRACT FROM AUTHOR]

• P38 serves as a direct target of miR-340-5p. • miR-340-5p overexpression attenuates neuroinflammation both in vitro and in vivo SCI models. • miR-340-5p mimics prevent inflammation-mediated oxidative stress and apoptosis via reducing P38 level. • miR-340-5p mimics improve locomotor recovery by alleviating P38/MAPK pathway-induced neuroinflammation. Spinal cord injury (SCI) is a destructive polyneuropathy that can result in loss of sensorimotor function and sphincter dysfunction, and even death in critical situations. MicroRNAs (miRs) are a series of non-coding RNA molecules that are involved in transcriptional regulation. Previous studies have demonstrated that modulation of multiple miRs is involved in neurological recovery after SCI. However, the functions of miR-340-5p in SCI remain uncertain. Therefore, we probed the therapeutic effect and mechanism of miR-340-5p in microglia in vitro and in vivo in SCI rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to examine the alterations in miR-340-5p and P38 levels in SCI rats. miR-340-5p targets in microglia were ascertained using luciferase reporter assays, immunofluorescence analyses, and western blotting. We also established an SCI model and administered miR-340-5p. The effects of miR-340-5p on the amelioration of inflammation, oxidative stress, and apoptosis following SCI were assessed using immunofluorescence, immunohistochemistry, and histological analyses. Finally, locomotor function recovery was determined using the Basso, Beattie, Bresnahan rating scale. In our study, the expression profiles and luciferase assay results clarified that P38 was a target of miR-340-5p, which was associated with activation of the P38-MAPK signaling pathway. Elevation of miR-340-5p decreased P38 expression, subsequently inhibiting the inflammatory reaction. SCI-induced secondary neuroinflammation was relieved under miR-340-5p treatment. Moreover, by controlling neuroinflammation, the increased levels of miR-340-5p might counter oxidative stress and reduce the degree of apoptosis. We also observed decreasing gliosis and glial scar formation and increasing neurotrophin expression at the chronic stage of SCI. Together, these potential effects of miR-340-5p treatment ultimately improved locomotor function recovery in SCI rats. [ABSTRACT FROM AUTHOR]

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. Ultrasensitive AchE detection based on a SERS lever strategy for identifying nerve fibers. 4-MBA absorbed on a miniaturized SERS substrate first as an internal reference. In an enzymolysis system containing ATCh, RB and AchE, ATCh and RB absorb on the SERS substrate equally by their quaternary amine groups, and the produced TCh with a thiol group would more dominantly absorb on the SERS substrate than ATCh and RB. The SERS intensity ratio of RB and 4-MBA can be used as an indicator of AchE amounts. [Display omitted] • The strategy of four ounces yields a thousand pounds was used to increase the sensitivity. • The strategy of an internal reference is to increase the repeatability of signal. • A miniaturized SERS substrate was used to detect AchE in small volume of samples. [ABSTRACT FROM AUTHOR]

Purpose: To ascertain the anatomic and radiological parameters of the atlas (C1) pedicle and to explore a preferable method of C1 pedicle screw insertion.Methods: Thirty-four conserved human cadaveric cervical spines (20 males, 14 females) underwent computed tomography (CT) scanning. Trajectories P (perpendicular to the coronal plane) and I (with medial inclination) were designed for each C1 pedicle on CT images. External pedicle wall width, medullary cavity width, transverse angle, and optimal entry point along each trajectory were measured. Cortical screws of 3.5 mm in diameter were inserted into C1 pedicles along trajectory P and I, respectively, and wall perforation was assessed (post-operative CT scanning).Results: The external pedicle wall width and medullary cavity width along trajectory I were significantly wider than trajectory P (P < 0.01). Although external pedicle wall widths were all greater than 3.5 mm, medullary cavity width <3.5 mm was found in 16.1 % pedicles along trajectory P and only 2.9 % along trajectory I. Transverse angle was 21.8° along trajectory I and 0° along trajectory P. Optimal entry point of trajectory I was 4.1 mm lateral from that of trajectory P. The lateral wall perforation rate was significantly lower along trajectory I than trajectory P (P < 0.05).Conclusions: C1 pedicle screw trajectory with medial inclination and more lateral entry points yielded wider medullary cavity width than that perpendicular to the coronal plane, and might minimize lateral wall perforation. [ABSTRACT FROM AUTHOR]

The nervous and immune systems are closely entwined to maintain the immune balance in health and disease. Here, we showed that LPS can activate suprarenal and celiac ganglia (SrG-CG) neurons and upregulate NPY expression in rats. Single-cell sequencing analysis revealed that knockdown of the NPY gene in SrG-CG altered the proliferation and activation of splenic lymphocytes. In a neuron and splenocyte coculture system and in vivo experiments, neuronal NPY in SrG-CG attenuated the splenic immune response. Notably, we demonstrated that neuronal NPF in Drosophila exerted a conservative immunomodulatory effect. Moreover, numerous SNPs in NPY and its receptors were significantly associated with human autoimmune diseases, which was further supported by the autoimmune disease patients and mouse model experiments. Together, we demonstrated that NPY is an ancient language for nervous-immune system crosstalk and might be utilized to alleviate inflammatory storms during infection and to modulate immune balance in autoimmune diseases. • LPS activates SrG-CG neurons and dramatically upregulates NPY gene expression in rats • SrG-CG neuronal NPY suppresses the bacteria or LPS-elicited inflammatory response • NPY/F has a conserved function in fine-tuning immune balance in different species • NPY and its receptors are associated with human autoimmune diseases Yu, Xiao, et al. identify NPY/F as an ancient language for the crosstalk between the nervous system and the immune system in different species. Neuronal NPY is dramatically elevated during infection and plays an important role in fine-tuning immune balance in inflammatory response and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Apoptosis of endothelial cells (ECs) is a crucial factor in blood-spinal cord barrier (BSCB) disruption post spinal cord injury (SCI). Insulin-like growth factor-1 (IGF-1) is a protective cytokine that plays an important role in multiple diseases, whereas the distinct role in SCI-induced remains critical questions to address. Here we designed to explore the role and underlying mechanism of IGF-1 in endothelial damage after SCI. In the current study, we established mouse microvascular endothelial cells (MVECs) injury model via LPS and cDNA of IGF-1 was transfected into MVECs. In vivo SCI mice, overexpression of IGF-1 (SCI-IGF-1) and its corresponding empty vehicle (SCI-NC) were conducted using lentivirus, then apoptosis degree, component of tight junction, and inflammatory damage were evaluated. IGF-1 treatment in MVECs displayed a milder apoptosis and cell damage under LPS insult. IGF-1 increased the level of PI3K/AKT pathway, which impeded the procedure of apoptosis. Blocking of PI3K/AKT pathway markedly neutralized the effect of IGF-1 treatment. Transfection of excess IGF-1 into SCI mice significantly corrected microenvironment of neural tissue repair, reduced area of injured core and improved functional recovery with greater activation of PI3K/AKT pathway. The results above argue that the promising roles played by IGF-1 is potentially vital for developing effective future therapies in SCI. Unlabelled Image [ABSTRACT FROM AUTHOR]

Osteosarcoma accounts for about 0.2% in human malignant solid tumors. The mortality and metastatic rates of osteosarcoma remain relatively high. MicroRNA (miRNA) is a kind of non-coding small-molecular RNA discovered in recent years. Various studies have identified the involvement of miRNA in the occurrence and development of tumor as an oncogene or tumor-suppressor gene. This study aims to investigate the effect of hsa-miR-889-3p on the progression of osteosarcoma and its underlying mechanism. Through the bioinformatics methods, we first found that hsa-miR-889-3p was upregulated in osteosarcoma, and it was a prognostic risk factor for osteosarcoma. Additionally, the gene set enrichment analysis (GSEA) revealed that hsa-miR-889-3p mainly affected cell cycle progression and proliferation of osteosarcoma. To verify the bioinformatics results, regulatory effects of hsa-miR-889-3p on osteosarcoma both in vitro and in vivo experiments were investigated. It is found that hsa-miR-889-3p could promote the proliferation of osteosarcoma cells though regulating cell cycle progression. Tumor size and growth rate of osteosarcoma were influenced by hsa-miR-889-3p in xenograft models. To further explore its potential mechanism, the target gene of hsa-miR-889-3p was predicted. Furthermore, hsa-miR-889-3p was confirmed to inhibit the expression of myeloid cell nuclear differentiation antigen (MNDA) in a targeted manner. In conclusion, hsa-miR-889-3p could promote the proliferation of osteosarcoma through inhibiting MNDA expression, which provides a potential therapeutic strategy in treatment for osteosarcoma. [ABSTRACT FROM AUTHOR]

Aims: To investigate the molecular mechanism of osteoclast-derived exosomes in osteoporosis., Main Methods: RANKL induced osteoclast model was screened for significantly differentially expressed lncRNAs and mRNAs by whole RNA sequencing. Exosomes were characterized using electron microscopy, western blotting and nanosight. Overexpression or knockdown of AW011738 was performed to explore its function. The degree of osteoporosis in an osteoporosis model was assessed by mirco-CT. The osteoclast model, osteoblast differentiation ability and the molecular mechanism of lncRNA AW011738/miR-24-2-5p/TREM1 axis in osteoporosis were assessed by dual luciferase reporter gene assay, Western blotting (WB), immunofluorescence and ALP staining. Bioinformatics was used to predict interactions of key osteoporosis-related genes with miRNAs, transcription factors, and potential drugs after upregulation of AW011738. To predict the protein-protein interaction (PPI) network associated with key genes, GO and KEGG analyses were performed on the key genes. The ssGSVA was used to predict changes in the immune microenvironment., Key Findings: Osteoclast-derived exosomes containing lncRNA AW011738 decreased the osteogenesis-related markers and accelerated bone loss in OVX mice. Osteoclast (si-AW011738)-derived exosomes showed a significant increase in biomarkers of osteoblast differentiation in vitro compared to the si-NC group. As analyzed by mirco-CT, tail vein injected si-AW011738 OVX mice were less osteoporotic than the control group. AW011738 inhibited osteoblast differentiation by regulating TREM1 expression through microRNA. Meanwhile, overexpression of miR-24-2-5p inhibited TREM1 expression to promote osteoblast differentiation., Significance: Osteoclast-derived exosomes containing lncRNA AW011738 inhibit osteogenesis in MC3T3-E1 cells through the lncRNA AW011738/miR-24-2-5p/TREM1 axis and exacerbate osteoporosis in OVX mice., Competing Interests: Declaration of Competing Interest The authors attest that they do not have any competing interests to report., (Copyright © 2024. Published by Elsevier Masson SAS.)

In the present study, effect of ultrasonic impact treatment (UIT) on the microstructural characterization and mechanical properties of 316L stainless steel (hereinafter referred to as 316L) was investigated experimentally. The fatigue fracture mechanism of 316L before and after UIT was revealed. The experimental results indicated that the martensitic grain size induced at the impact edge was about 2.00 Å. The surface modified 316L formed a gradient nanostructure and induced a martensitic phase transformation. The hardness of the surface layer of the modified 316L was twice the hardness of its matrix. The tensile strengths of 316L before and after UIT were 576 MPa and 703 MPa, respectively. The stretching stripes of 316L were more disordered after UIT. The fatigue strengths of 316L before and after UIT were 267 MPa and 327 MPa, respectively. The fatigue cracking of 316L started from the austenite grain boundaries. The fatigue fracture surface was relatively rough. The fatigue crack sources of the modified 316L came from internal inclusions. The inclusions were oxides dominated by SiO2. As the stress range increased, the crack initiation site migrated to the interior and the fatigue fracture surface became flatter., Competing Interests: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper., (Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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-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., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The human stress hormones catecholamines play a critical role in communication between human microbiota and their hosts and influence the outcomes of bacterial infections. However, it is unclear how M. tuberculosis senses and responds to certain types of human stress hormones. In this study, we screened several human catecholamine stress hormones (epinephrine, norepinephrine, and dopamine) for their effects on Mycobacterium growth. Our results showed that epinephrine significantly stimulated the growth of M. tuberculosis in the serum-based medium as well as macrophages. In silico analysis and molecular docking suggested that the extra-cytoplasmic domain of the MprB might be the putative adrenergic sensor. Furthermore, we showed that epinephrine significantly enhances M. tuberculosis biofilm formation, which has distinct texture composition, antibiotic resistance, and stress tolerance. Together, our data revealed the effect and mechanism of epinephrine on the growth and biofilm formation of M. tuberculosis , which contributes to the understanding of the environmental perception and antibiotic resistance of M. tuberculosis and provides important clues for the understanding of bacterial pathogenesis and the development of novel antibacterial therapeutics.

Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT-qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT-qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhu, Huang, Shi, Li, Lan, Cao, Wu, Ding and Chen.)

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.

Background: An increasing amount of research has speculated that necroptosis could be a therapeutic strategy for treating cancer. However, understanding the prognostic value of the necroptosis-related long non-coding RNAs (NRLs) in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains poor and needs to be developed. Our research aims to construct a model based on NRLs for the prognosis of patients with melanoma., Methods: We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) database and retrieved 86 necroptosis-related genes from the GeneCards database. The lncRNAs associated with necroptosis were identified via the Pearson correlation coefficient, and the prognostic model of melanoma was constructed using LASSO regression. Next, we employed multiple approaches to verify the accuracy of the model. Melanoma patients were categorized into two groups (high-risk and low-risk) according to the results of LASSO regression. The relationships between the risk score and survival status, clinicopathological correlation, functional enrichment, immune infiltration, somatic mutation, and drug sensitivity were further investigated. Finally, the functions of AL162457.2 on melanoma proliferation, invasion, and migration were validated by in vitro experiments., Results: The prognostic model consists of seven NRLs (EBLN3P, AC093010.2, LINC01871, IRF2-DT, AL162457.2, AC242842.1, HLA-DQB1-AS1) and shows high diagnostic efficiency. Overall survival in the high-risk group was significantly lower than in the low-risk group, and risk scores could be used to predict melanoma survival outcomes independently. Significant differences were evident between risk groups regarding the expression of immune checkpoint genes, immune infiltration, immunotherapeutic response and drug sensitivity analysis. A series of functional cell assays indicated that silencing AL162457.2 significantly inhibited cell proliferation, invasion, and migration in A375 cells., Conclusion: Our prognostic model can independently predict the survival of melanoma patients while providing a basis for the subsequent investigation of necroptosis in melanoma and a new perspective on the clinical diagnosis and treatment of melanoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Vaccination by inactivated vaccine is an effective strategy to prevent the COVID-19 pandemic. However, the detailed molecular immune response at single-cell level is poorly understood. In this study, we systematically delineated the landscape of the pre- and post-vaccination single-cell transcriptome, TCR (T cell antigen receptor) and BCR (B cell antigen receptor) expression profile of vaccinated candidates. The bulk TCR sequencing analysis of COVID-19 patients was also performed. Enrichment of a clonal CD8 + T cell cluster expressing specific TCR was identified in both vaccination candidates and COVID-19 patients. These clonal CD8 + T cells showed high expression of cytotoxicity, phagosome and antigen presentation related genes. The cell-cell interaction analysis revealed that monocytes and dendritic cells could interact with these cells and initiate phagocytosis via ICAM1-ITGAM and ITGB2 signaling. Together, our study systematically deciphered the detailed immunological response during SARS-CoV-2 vaccination and infection. It may facilitate understanding the immune response and the T-cell therapy against COVID-19., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

RNA N 6 -methyladenosine (m 6 A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m 6 A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3'-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo , YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m 6 A modification in SCI and might provide a potential therapy for SCI. SIGNIFICANCE STATEMENT Spinal cord injury is a devastating trauma of the CNS involving motor and sensory impairments. However, epigenetic modification in spinal cord injury is still unclear. Here, we propose an m 6 A regulation effect of astrocytic METTL3 following spinal cord injury, and we further characterize its underlying mechanism, which might provide promising strategies for spinal cord injury treatment., Competing Interests: The authors declared no competing financial interests., (Copyright © 2023 the authors.)

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., (© 2023. The Author(s).)

Background: Percutaneous kyphoplasty (PKP) has been demonstrated to be effective in the treatment of osteoporotic vertebral compression fractures (OVCF). However, bilateral puncture techniques take more time to accept more X-ray radiation; some spinal surgeons apply unilateral puncture PKP, but the cement cannot be symmetrically distributed in the vertebral body, so we apply a directional bone cement delivery device that undergoes PKP through the unilateral pedicle puncture. This research aims to compare the clinical and radiological results of PKP via unilateral pedicle approach using a traditional bone cement delivery device and a directional bone cement delivery device and determine the value of a directional delivery device for the therapy of thoracolumbar compression fracture in the elderly., Methods: We undertook a retrospective analysis of patients with single-level OVCF treated with unilateral pedicle puncture PKP from Jan 2018 to Jan 2020. Operation time, radiation exposure, bone cement injection volume, and the incidence of bone cement leakage were recorded for presentation, and the cement leakage and bone cement distribution were measured by X-ray and computed tomography scan. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes., Results: There was no significant difference in the operation time, radiation exposure time, and incidence of bone cement leakage between the two groups. A significant difference was observed in the volume of bone cement injection between the two groups. All patients in both groups had significantly less pain after the procedures, compared with their preoperative period pain. There were no significant differences in Visual Analogue Scale, the relative height of the vertebral body, Cobb angle, and Quality of Life Questionnaire of the European Foundation for Osteoporosis between the two groups at 1 week after PKP, significant difference was observed only 12 months after operation., Conclusion: Application of directional bone cement delivery device is safe and feasible, compared with the application of traditional bone cement delivery device, without prolonging the operative time, radiation exposure time, and the incidence of bone cement leakage. It has the advantages of good short- and medium-term effect, excellent bone cement distribution, and low incidence of kyphosis recurrence., (© 2023. The Author(s).)

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which is still the leading cause of mortality from a single infectious disease worldwide. The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M. tuberculosis. Here, we harnessed an endogenous type III-A CRISPR/Cas10 system of M. tuberculosis for efficient gene editing and RNA interference (RNAi). This simple and easy method only needs to transform a single mini-CRISPR array plasmid, thus avoiding the introduction of exogenous protein and minimizing proteotoxicity. We demonstrated that M. tuberculosis genes can be efficiently and specifically knocked in/out by this system as confirmed by DNA high-throughput sequencing. This system was further applied to single- and multiple-gene RNAi. Moreover, we successfully performed genome-wide RNAi screening to identify M. tuberculosis genes regulating in vitro and intracellular growth. This system can be extensively used for exploring the functional genomics of M. tuberculosis and facilitate the development of novel anti-TB drugs and vaccines., (Copyright © 2022. Published by Elsevier B.V.)

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.

Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose "degree of disorder" to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse., (© 2022. The Author(s).)

Magnetic fluid is a new type of smart material, which holds implications for highly enhancing the oil displacement efficiency. In the present study, we perform a comprehensive investigation to probe the influence of a magnetic fluid on the displacement efficiency in porous media under the action of magnetic force. First, the displacement efficiency is measured by a self-developed setup, where factors such as the magnet thicknesses, the volume of the fluid injected, the fluid injection speed, and the porosity of the sample are surveyed as controllable variables. Moreover, the experimental results are well verified by the scaling laws according to the principle of dimensional balance. Next, a numerical simulation is performed to explore the detailed displacement process. First, the magnetic force generated by the ring magnet is calculated. Then, the function curves of the displacement efficiency with respect to the controlling variables are validated by the numerical simulation. In addition, the numerical simulation also demonstrates the volume phase distribution, the pressure field, and the velocity field of the mixed fluid during the displacement process. The simulation results are in excellent agreement with the experimental data. These findings are beneficial for us to better understand the oil displacement with the aid of external fields, which also provide inspiration for the areas of microfluidics, diffusion of pollutants, microsensors, etc., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group ( P <0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group ( P <0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups ( P <0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.

Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3 + macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3 + macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Gao, Zhang, Xiong, Cao, Fu and Cui.)

Coronaviruses are a great source of threat to public health which could infect various species and cause diverse diseases. However, the epidemic's spreading among different species remains elusive. This study proposed an in silico infection analysis (iSFA) system that includes pathogen genome or transcript mining in transcriptome data of the potential host and performed a comprehensive analysis about the infection of 38 coronaviruses in wild animals, based on 2,257 transcriptome datasets from 89 mammals' lung and intestine, and revealed multiple potential coronavirus infections including porcine epidemic diarrhea virus (PEDV) infection in Equus burchellii . Then, through our transmission network analysis, potential intermediate hosts of five coronaviruses were identified. Notably, iSFA results suggested that the expression of coronavirus receptor genes tended to be downregulated after infection by another virus. Finally, binding affinity and interactive interface analysis of S1 protein and ACE2 from different species demonstrated the potential inter-species transmission barrier and cross-species transmission of SARS-CoV-2. Meanwhile, the iSFA system developed in this study could be further applied to conduct the source tracing and host prediction of other pathogen-induced diseases, thus contributing to the epidemic prevention and control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zou, Cao, Yang, Deng, Xu, Dong, Li, Wu and Cao.)

Under starvation conditions, bacteria tend to slow down their translation rate by reducing rRNA synthesis, but the way they accomplish that may vary in different bacteria. In Mycobacterium species, transcription of rRNA is activated by the RNA polymerase (RNAP) accessory transcription factor CarD, which interacts directly with RNAP to stabilize the RNAP-promoter open complex formed on rRNA genes. The functions of CarD have been extensively studied, but the mechanisms that control its expression remain obscure. Here, we report that the level of CarD was tightly regulated when mycobacterial cells switched from nutrient-rich to nutrient-deprived conditions. At the translational level, an antisense RNA of carD (AscarD) was induced in a SigF-dependent manner to bind with carD mRNA and inhibit CarD translation, while at the post-translational level, the residual intracellular CarD was quickly degraded by the Clp protease. AscarD thus worked synergistically with Clp protease to decrease the CarD level to help mycobacterial cells cope with the nutritional stress. Altogether, our work elucidates the regulation mode of CarD and delineates a new mechanism for the mycobacterial starvation response, which is important for the adaptation and persistence of mycobacterial pathogens in the host environment., Competing Interests: XL, FC, XL, JX, BA, QT, XC, SC, MG, JH No competing interests declared

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Study Design: Anatomic study in nine fresh-frozen cadavers., Objective: To confirm the anatomical feasibility of transferring the extradural ventral roots (VRs) and dorsal roots (DRs) of contralateral C7 nerves to those of the ipsilateral C7 nerves respectively through a cervical posterior approach., Summary of Background Data: The contralateral C7 nerve root transfer technique makes breakthrough for treating spastic limb paralysis. However, its limitations include large surgical trauma and limited indications., Methods: Nine fresh-frozen cadavers (four females and five males) were placed prone, and the feasibility of exposing the bilateral extradural C7 nerve roots, separation of the extradural C7 VR and DR, and transfer of the VR and DR of the contralateral C7 to those of the ipsilateral C7 on the dural mater were assessed. The pertinent distances and the myelography results of each specimen were analyzed. The acetylcholinesterase (AChE) and antineurofilament 200 (NF200) double immunofluorescent staining were preformed to determine the nerve fiber properties., Results: A cervical posterior midline approach was made and the laminectomy was performed to expose the bilateral extradural C7 nerve roots. After the extradural C7 VR and DR are separated, the VR and DR of the contralateral C7 have sufficient lengths to be transferred to those of the ipsilateral C7 on the dural mater. The myelography results showed that the spinal cord is not compressed after the nerve anastomosis. The AChE and NF200 double immunofluorescent staining showed the distal ends of the contralateral C7 VRs were mostly motor nerve fibers, and the distal ends of the contralateral C7 DRs were mostly sensory nerve fibers., Conclusion: Extradural contralateral C7 nerve root transfer in a cervical posterior approach for treating spastic limb paralysis is anatomically feasible., Level of Evidence: 5.

Epidural fibrosis causes serious complications in patients who have undergone laminectomy. Pirfenidone is an effective antifibrotic agent but its effect on epidural fibrosis remains unclear. In this study, we aimed to investigate the effect of pirfenidone on epidural fibrosis and to evaluate its mechanism of action on human epidural scar fibroblasts. In a rat model of laminectomy, the degree of epidural fibrosis was quantified via Rydell standard classification, histological analysis, and collagen density analyses. In cultured human epidural scar fibroblasts, cell proliferation was measured using a Cell Counting Kit-8 and EdU assay. Cell apoptosis was detected using Annexin V/propidium iodide staining, and cytotoxicity was evaluated via lactate dehydrogenase assay. Relative mRNA levels of α-smooth muscle actin (α-SMA) and collagen type I were analyzed using quantitative polymerase chain reaction. The protein expression of α-SMA and collagen type I and the phosphorylation status of Smad2, Smad3, protein kinase B (Akt), and p38 were determined via western blotting. Pirfenidone reduced epidural fibrosis by inhibiting fibroblast proliferation and suppressing collagen formation in rats. It also inhibited human epidural scar fibroblast proliferation with no cytotoxic or apoptotic effects. Pirfenidone inhibited fibroblast differentiation by decreasing TGF-β1-induced transcriptional and translational expression of α-SMA. It inhibited TGF-β1-induced phosphorylation of Smad2, Smad3, Akt, and p38. This study suggests that topical application of pirfenidone could reduce epidural scar adhesion after laminectomy, and that its mechanism of action may be the inhibition of TGF-β1-induced epidural scar fibroblast proliferation and differentiation into myofibroblasts through the attenuation of TGF-β1-induced Smad-dependent and -independent pathways., Competing Interests: None.

Study Design: Anatomic study in six formalin-fixed cadavers., Objective: To determine the anatomical feasibility of transferring the S2 and S3 ventral roots (VRs) to S1 VR as a method for restoring bladder dysfunction in spinal cord injury., Summary of Background Data: A large quantity of researches of neuroanastomosis methods have been used for treating the bladder dysfunction in spinal cord injury. However, some limitations retard the development of those studies., Methods: In this study, six formalin-fixed cadavers (four males, two females) were dissected. The feasibility of exposing the S1, S2, and S3 extradural nerve roots by the limited laminectomy, isolating the VR and dorsal roots from each extradural nerve root and transferring the S2,S3 VRs to the S1 VR were assessed. The pertinent distances and the nerve cross-sectional areas in each specimen were measured. The morphology of each nerve root was observed by hematoxylin-eosin staining., Results: The limited laminectomy was performed to expose the S1 to S3 extradural nerve roots. The VRs could be isolated from each extradural nerve root at the location of the dorsal root ganglion and the hematoxylin-eosin staining showed that there were some connective tissues separating the VRs from the corresponding dorsal root ganglion. The S2 and S3 VRs have sufficient lengths to be transferred to S1 VR without grafting. The mean cross-sectional area of the S1 VR was 2.60 ± 0.17 mm, and that was 1.02 ± 0.32 mm and 0.51 ± 0.21 mm of the S2 and S3 VRs, respectively., Conclusion: This study demonstrated that use of the S2 and S3 VRs for extradural transfer to S1 VR for restoring bladder dysfunction is surgically feasible., Level of Evidence: 5.