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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. -k_-1M1wXF49hQ9JfigvAZ Video abstract [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The computational fluid dynamics (CFD) combined with radial basis function (RBF) method were adopted to obtain the response surface of the Muszynska nonlinear seal force model coefficient with two variables: eccentricity and rotation speed. During the implementation of the simulation, three coefficients of the seal force model were calculated in each sub-step according to the current state of the rotor-bearing seal system; following which the rotor dynamics analysis with varying parameters was realized. As with the traditional constant coefficient method, the first-order critical speed of the system was obtained, and the bifurcation point and oil film whirl of the system response were identified. The difference is that the coefficients of the traditional method ordinarily do not change with the state of the system. Comparing the results of the varying parameter method with those of the traditional method, it can be seen that the speeds of the system corresponding to the bifurcation and oil film whirl are different. The varying parameter rotor dynamics simulation method proposed in this paper provides a new way of analyzing the nonlinear characteristics of rotor-bearing-seal systems. [ABSTRACT FROM AUTHOR]

This paper mainly numerically investigates the ultimate compression strength of un-strengthened and CFRP-strengthened steel tubes with random pitting corrosion damage. First, a developed numerical method for steel tubes with random corroded pits is introduced in detail. The accuracy of a similar numerical method is verified through the corresponding experimental measurement and numerical prediction. Then, the ultimate axial compression behavior of steel tubes with random elliptical corroded pits is numerically investigated. Several influencing factors on the ultimate strength of corroded steel tubes under axial compression load are simulated and compared, including different random distributions, region size of corroded pits, number of pits, and depth of pits. Subsequently, the method for strengthening steel tubes by using CFRPs is studied and conducted on the corroded regions of steel tubes. The reliability of steel tubes strengthened by FRP is validated through experimental and numerical results. Finally, the residual compression performance and progressive damage mechanisms of CFRP-strengthened steel tubes are researched. The different parametric influences on the strengthened performance of FRPs are simulated, including layer direction, number of composite layers, and composite materials. The results demonstrate that FRP can improve the axial compression resistance of corroded steel tubes. [ABSTRACT FROM AUTHOR]

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. Here the authors delineate the dynamic changes in 3D genome and epigenome of differentiating macrophages and during infection with Mycobacterium tuberculosis. They reveal a role for NF-κB upon infection and identify SNPs in disease-susceptible loci, including rs1873613 that is located in the anchor of a dynamic chromatin loop. [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]

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). [ABSTRACT FROM AUTHOR]

Foams are substances widely used the foam flooding technology, which aim to greatly improve the residual oil recovery. In the present study, we perform a comprehensive investigation on the oil removal process driven by the foam embedded with magnetic particles, under the action of the magnetic force. The experiment shows that the addition of magnetic particles has little effect on the stability of the foam. During the motion of the foam, its maximum displacement and maximum acceleration are fully explored. Such factors as the volume of the foam, the volume of the oil droplet, the mass concentration of magnetic particles, and the Young's contact angle of surfactant on solid are surveyed in detail. The function curves of the maximum displacement and the maximum acceleration with respect to these variables are obtained in the experiment, and the selection of some optimal parameters is advised. Moreover, the dimensional analysis has been conducted and several scaling laws are given, which are in agreement with the experimental results. These findings are beneficial to understand the oil displacement with the aid of magnetic field, which also provide some inspirations on drug delivery, robots and micro-fluidics. [ABSTRACT FROM AUTHOR]

Carbon fibers were surface treated with supercritical water/nitrate system to improve the interfacial adhesion of the carbon fiber/epoxy composite. The surface chemistry analysis showed that oxygen functional groups on the surface of the carbon fibers increased after treatment, which were mainly carbonyl and carboxyl groups. The surface microstructure observation indicated that the treatment obviously increased the surface roughness of the carbon fibers. Surface energy of the treated carbon fibers also increased. The increased functional groups, surface roughness and surface energy were beneficial to enhance the interfacial adhesion of the carbon fiber/epoxy composite. Compared with the untreated carbon fibers, the strength loss of the treated carbon fibers was less than 3% and the other mechanical properties were almost unchanged. The caclulated interfacial fracture energy and the interfacial shear strength of the treated carbon fiber/epoxy composite were enhanced by 19% and 29%, respectively, compared with the untreated carbon fiber/epoxy composite. In summary, supercritical water/nitrate treatment is a potential method for changing the inert surface of carbon fibers to improve the interfacial adhesion between carbon fibers and matrix. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a debilitating infectious disease responsible for more than one million deaths per year. The emergence of drug-resistant TB poses an urgent need for the development of new anti-TB drugs. In this study, we screened a library of over 4,000 small molecules and found that orbifloxacin and the peptide AK15 possess significant bactericidal activity against Mycobacterium tuberculosis (Mtb) in vitro. Orbifloxacin also showed an effective ability on the clearance of intracellular Mtb and protect mice from a strong inflammatory response but not AK15. Moreover, we identified 17 nucleotide mutations responsible for orbifloxacin resistance by whole-genome sequencing. A critical point mutation (D94G) of the DNA gyrase (gyrA) gene was found to be the key role of resistance to orbifloxacin. The computational docking revealed that GyrA D94G point mutation can disrupt the orbifloxacin–protein gyrase interactions mediated by magnesium ion bridge. Overall, this study indicated the potential ability of orbifloxacin as an anti-tuberculosis drug, which can be used either alone or in combination with first-line antibiotics to achieve more effective therapy on TB. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival. [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]

Background: MiR-1297 is reported to function as a tumor suppressor of various cancers. However, the role of miR-1297 in the development of osteosarcoma (OS) has not been elaborated. The purpose of this study was to investigate the functional effects of miR-1297 on OS progression and the underlying mechanism. Methods: The expression of protein and mRNA in OS cells was evaluated by Western blotting and quantitative real-time polymerase chain reaction. Cellular proliferation was investigated by cell counting kit-8, colony formation and apoptosis assays. Bioinformatics methods were used to predict target genes. The relationship between PFKFB2 and miR-1297 was demonstrated by dual-luciferase reporter assay. Metabolic changes in OS cells were monitored using an XF96 metabolic flux analyzer. Results: We found that miR-1297 was downregulated in OS and that lower expression of miR-1297 promoted proliferation and contributed to the Warburg effect in OS cells. Furthermore, we showed that silencing PFKFB2 inhibited proliferation and reduced aerobic glycolysis while overexpression of PFKFB2 reduced the anti-tumor function of miR-1297 in OS cells. Mechanistically, miR-1297 acted as a tumor suppressor in OS and reduced the expression of PFKFB2 by directly targeting its 3ʹUTR. Conclusion: The miR-1297/PFKFB2 axis regulated OS proliferation by controlling the Warburg effect. Our results revealed a previously undiscovered function of miR-1297 in OS, which strongly linked metabolic alterations with cancer progression. Targeting miR-1297 may become a promising therapeutic approach for OS. [ABSTRACT FROM AUTHOR]

Circumferentially grooved seals have been widely used in pumps to eliminate outward leakage of rotating liquid. On many occasions, the turbulent flow enhances the drag force on the interface between the liquid and the stator as well as the interface between the liquid and the rotor, creating much higher heat exchange than the conventional thermal conduction in laminar flows. Attention must be paid in the seal design to prevent rapid heating by the seal liquid to the ambient stator. In this study, the geometry of a circumferentially grooved seal is optimized for a better design of thermal insulation as well as reduction in drag force of the seal fluid. For the forward problem, i.e., the hydraulic and thermal analysis of the seal, the theory of bulk flow is used to simplify the thin-film liquid to a two-dimensional field which preserves the average characteristics of the original flow. The method of three-control volume is adopted to partition the liquid into three types of cavity flows. The governing equations of continuity, momentum, and energy transportation are presented for each control volume, and are approximated by the perturbation method and the Fourier expansion. The fluid and thermal solutions by the present perturbation method are validated by a CFD simulation. For the seal optimization, the multi-objective optimization for thermal insulation and drag reduction is converted into an integrated optimization problem with key geometrical parameters of the seal. Response surfaces are generated through radial basis functions to make the constraint functions explicit for the efficiency of the optimization process. The method of moving asymptotes (MMA) is adopted to find the optimized design of the seal geometry with the best performance of thermal insulation and drag reduction of liquid. Examples are presented to demonstrate the effectiveness of the present optimization method. [ABSTRACT FROM AUTHOR]

From the theory of damage mechanics, based on the Hoek-Brown strength criterion and Weibull distribution law of rock microelement strength, a statistical constitutive model of rock thermal damage is established by using equivalent strain hypothesis, and the theoretical model is modified by considering the compression coefficient and residual strength correction coefficient. The rationality of the modified model is verified by experimental data. The results show that the stress-strain curves of rock can be divided into four stages: initial compaction, stable damage propagation, damage strengthening expansion, and damage failure according to the characteristics of rock damage evolution. The peak stress of rock increases exponentially with the increase of confining pressure, and the maximum damage evolution rate decreases exponentially with the increase of confining pressure, which indicates that confining pressure delays the development of cumulative damage. The peak stress and maximum damage evolution rate of rock decrease exponentially with the increase of temperature, which accelerates the damage of rock. The initial damage of rock is thermal damage caused by temperature, and the damage value increases with the increase of temperature. The revised theoretical curve reflects the characteristics of rock compaction stage and residual strength and improves the coincidence with the experimental curve. The research results provide a reference for the establishment of thermal damage constitutive model of rock in deep engineering. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to identify the key long non-coding (lnc)RNAs in the occurrence and development of osteoporosis (OP) and to explore the associated molecular mechanism. First, the Gene Expression Omnibus (GEO) datasets, with key words 'osteoporosis' and 'HG-133A', were screened. RankProd R package was used to calculate the dysregulated lncRNAs in OP. Following this, bone marrow mesenchymal stem cells (BM-MSCs) harvested from 3-week-old Sprague Dawley rats were employed for detection of osteoblast differentiation. Following overexpression or interference with X-inactive specific transcript (XIST), osteogenesis-associated genes and proteins in BM-MSCs were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Alkaline phosphatase (ALP) and Alizarin Red S staining were also performed to measure the osteogenic ability of BM-MSCs. Results from the two datasets indicated that 6 lncRNAs were dysregulated in OP. Notably, XIST is key lncRNA in diverse diseases, and was subsequently selected for analysis. It was revealed that XIST was significantly upregulated in plasma and monocytes from patients with OP compared with the normal controls. Furthermore, results indicated that overexpression of XIST significantly inhibited osteoblast differentiation in BM-MSCs, as evidenced by the decreased expression of ALP, bone γ-carboxyglutamic acid-containing protein and runt related transcription factor 2, reduced ALP activity and a decreased number of calcium deposits. However, interference of XIST exhibited the opposite biological effects in BM-MSCs. Taken together, XIST was highly expressed in the serum and monocytes of patients with OP. In addition, the findings suggested that XIST could inhibit osteogenic differentiation of BM-MSCs. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate whether the application of tacrolimus (FK506) could improve functional recovery in spinal cord injury (SCI) rat models by activating astrocytes, and to further investigate the underlying mechanisms of this action. Male Sprague-Dawley rats (n=56) were used to establish moderate SCI models, which were induced at the T10 spinal segment by dropping a 10-g weight from a height of 25 mm using a New York University Impactor device. The rats were randomly separated into the FK506 or control group (n=28 per group). Rats were treated with FK506 (0.5 mg/kg) or saline intravenously 30 min after sustaining the injury. Functional recovery was evaluated over 42 days following the injury, and epidermal growth factor (EGF) levels were detected. The astrocytes were treated with FK506 in vitro, and the EGF mRNA and protein expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and ELISA, respectively. DNA microarray analysis was also performed to evaluate the genes in astrocytes. Rats in the FK506 group had improved locomotor functional recovery compared with those of control group. Furthermore, FK506 upregulated EGF expression of astrocytes both in vivo and in vitro. Subsequent to treatment with FK506-conditioned medium (CM), the length of neuronal cells increased 61.06% on the first day, and increased 56.4% on the third day compared with those of C-CM group. Furthermore, addition of anti-EGF neutralizing antibodies could interrupt the promotion of neurite outgrowth by FK506-CM. The present study indicates that astrocytes have an important role as mediators of FK506-improved spinal cord function recovery, and this partially clarifies the role of cell-cell interaction through modulating EGF in this process. [ABSTRACT FROM AUTHOR]

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

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

Topology optimization to minimize the bottom-layer temperature and the structure compliance of the multi-layered thin-walled structure is carried out in this paper. A multi-layered thin-walled structure with improved performances in load-carrying and heat insulation inspired by a species of oceanic gastropods found on a hot and highly pressurized deep-sea floor is proposed. Using genetic algorithm to perform the optimization process, it is proved that the optimal topology under integrated thermal and load conditions is a sandwich structure of three layers similar to the original bionic structure of the oceanic gastropods. Soft layer with good heat insulation is placed as the middle layer, whereas hard layers with fast heat transmission are placed as the top and bottom layers to carry load. The concept of bionic three-layered structure is then applied to the skin design of an airfoil. The analysis for aerodynamic heating of the airfoil with different skin structures shows that the bionic multi-layered structure is an optimal design in both layer thickness and layer sequence. [ABSTRACT FROM AUTHOR]

Background/Aims: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. Methods: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. Results: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. Conclusions: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis. © 2016 The Author(s) Published by S. Karger AG, Basel [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]

Background/Aims: Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI. Methods: Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library, Medline databases and analyzed by Review Manager 5.2.5. Results: Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemisected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding. Conclusion: SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) solid or hollow graphene beads (GBs) with an obvious crumpled surface are fabricated by using a microfluidic emulsification device and with a post-treatment process. In the emulsification process, graphene oxide (GO)/polyvinylpyrrolidone (PVP) solution is cut off by flowing dimethyl silicone oil in a T-shape microfluidic channel and forms composite droplets with a uniform size. PVP is used as the binder for GO sheets during solidification and annealing procedures. The morphologies and structures of the solidified GBs are optimized by tailoring the concentration of GO/PVP solution, the size of droplets and the way of solidification. The as-prepared GBs are employed as electrode materials for supercapacitor application in this work. As three-step pre-oxidation and calcination processes are carried out in the post-treatment process, the ring structure of PVP is retained and this leads to the coexistence of electric double-layer capacitance (EDLC) and pseudocapacitance properties. The results show that the GBs have a specific capacitance of 243 F g−1 at a current density of 1 A g−1, and retain 97.5% of the initial capacitance after 3000 cycles in 6 M KOH aqueous solution. Thus, the 3D crumpled GBs present a great specific capacitance value, reduce the internal electrical resistance and enhance the durability of the electrode. [ABSTRACT FROM AUTHOR]

Background/Aims: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Methods: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Results: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Conclusion: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Mechanical stress has detrimental effects on cartilaginous endplate chondrocytes due to apoptosis in vivo and in vitro. In this study, we investigated the possible apoptosis signaling pathways induced by mechanical stress in cultured rat cervical endplate chondrocytes. Static mechanical load significantly reduced cell viability in a time- and load-dependent manner, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Chondrocyte apoptosis induced by mechanical stress was confirmed by annexin V/propidium iodide (PI) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Western blot analysis revealed that static load-induced chondrocyte apoptosis was accompanied by increased phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). The loss of mitochondrial membrane potential (ΔΨm), increased Cytochrome c release, and activated Caspase-9 and Caspase-3, indicating that the mitochondrial pathway is involved in mechanical stress-induced chondrocyte apoptosis. Treatment with inhibitors of JNK (SP600125), p38 MAPK (SB203580), and ERK (PD98059) prior to mechanical stimulation reversed both the static load-induced chondrocyte apoptosis and the activation of JNK, p38 MAPK, and ERK. Taken together, the data presented in this study demonstrate that mechanical stress induces apoptosis in rat cervical endplate chondrocytes through the MAPK-mediated mitochondrial apoptotic pathway. [ABSTRACT FROM AUTHOR]

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

Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation. [ABSTRACT FROM AUTHOR]

We explored the nature of chromosome 13 loss in cultured human vascular endothelial cells (HUVECs). Chromosome 13 loss detected by metaphase and interphase analysis was noted in earlier passages of HUVEC strains with no relation to telomere length or replicative senescence. Ectopic expression of telomerase did not influence the loss of chromosome 13. HUVECs losing chromosome 13 demonstrated increased migratory potential and loss of heterozygosity. Collectively, these observations suggest that the loss of chromosome 13 gives cultured HUVECs a replicative advantage. [ABSTRACT FROM AUTHOR]

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]

The effect of nano grain surface layer generated by ultrasonic impact on the fatigue behaviors of a titanium alloy Ti3Zr2Sn3Mo25Nb (TLM) was investigated. Three vibration strike-numbers of 24,000 times, 36,000 times and 48,000 times per unit are chosen to treat the surface of TLM specimens. Nanocrystals with an average size of 30 nm are generated. The dislocation motion plays an important role in the transformation of nanograins. Ultrasonic surface impact improves the mechanical properties of TLM, such as hardness, surface residual stress, tensile strength and fatigue strength. More vibration strike numbers will cause a higher enhancement. With a vibration strike number of 48,000 times per square millimeter the rotating-bending fatigue strength of TLM at 107 cycles is improved by 23.7%. All the fatigue cracks initiate from the surface of untreated specimens, while inner cracks appear after the fatigue life of 106 cycles with the ultrasonic surface impact. The crystal slip in the crack initiation zone is the main way of growth for microcracks. Crack cores are usually formed at the junction of crystals. The stress intensity factor of TLM titanium alloy is approximately 7.0 MPa·m1/2. [ABSTRACT FROM AUTHOR]