ROS: Executioner of regulating cell death in spinal cord injury.

The damage to the central nervous system and dysfunction of the body caused by spinal cord injury (SCI) are extremely severe. The pathological process of SCI is accompanied by inflammation and injury to nerve cells. Current evidence suggests that oxidative stress, resulting from an increase in the production of reactive oxygen species (ROS) and an imbalance in its clearance, plays a significant role in the secondary damage during SCI. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulatory molecule for cellular redox. This review summarizes recent advancements in the regulation of ROS-Nrf2 signaling and focuses on the interaction between ROS and the regulation of different modes of neuronal cell death after SCI, such as apoptosis, autophagy, pyroptosis, and ferroptosis. Furthermore, we highlight the pathways through which materials science, including exosomes, hydrogels, and nanomaterials, can alleviate SCI by modulating ROS production and clearance. This review provides valuable insights and directions for reducing neuronal cell death and alleviating SCI through the regulation of ROS and oxidative stress.

Apelin-13 alleviates osteoclast formation and osteolysis through Nrf2-pyroptosis pathway.

Wear particle-induced periprosthetic osteolysis is the key to aseptic loosening after artificial joint replacement. Osteoclastogenesis plays a central role in this process. Apelin-13 is a member of the adipokine family with anti-inflammatory effects. Here, we report that apelin-13 alleviates RANKL-mediated osteoclast differentiation and titanium particle-induced osteolysis in mouse calvaria. Mechanistically, apelin-13 inhibits NLRP3 inflammasome-mediated pyroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In summary, apelin-13 is expected to be a potential drug for relieving aseptic osteolysis. RESEARCH HIGHLIGHTS: This study reveals the molecular mechanism by which apelin-13 inhibits NLRP3 inflammasome activation and pyroptosis by promoting Nrf2. This study confirms that apelin-13 alleviates osteoclast activation by inhibiting pyroptosis. In vivo studies further confirmed that apelin-13 alleviated mouse skull osteolysis by inhibiting the activation of NLRP3 inflammasome.

Influence of sarcopenia on surgical efficacy and mortality of percutaneous kyphoplasty in the treatment of older adults with osteoporotic thoracolumbar fracture.

BACKGROUND: Sarcopenia is an age-related condition that causes loss of skeletal muscle mass and disability. Sarcopenia is closely related to the prognosis of patients suffering osteoporotic thoraco-lumbar compression fractures (OTLCF). The purpose of this study was to investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty (PKP) in the treatment of older adults with OTLCF surgery and postoperative mortality. METHODS: From February 2016 to June 2019, 101 patients who met the inclusion and exclusion criteria were included in this study. The grip strength of the dominant hand was measured using an electronic grip tester. The diagnostic cutoff value of grip strength for sarcopenia was <27 kg for males and <16 kg for females. The cross-sectional area (cm2) of the musculature at the level of the pedicle of the thoracic 12th vertebra (T12) was measured by chest CT. The skeletal muscle index (SMI) was calculated by dividing the muscle cross-sectional area at the T12 pedicle level by the square of the height. The diagnostic cut-off value of SMI at T12 level is 42.6 cm2/m2 for males and 30.6 cm2/m2 for females. Sarcopenia was diagnosed when the grip strength and SMI values were both lower than the diagnostic cut-off value. All included patients received PKP treatment for OTLCF. The age, gender, operation time, bleeding volume, time to ground, length of hospital stay, visual analog scale (VAS) score before operation and one month after operation, Oswestry Disability Index (ODI) one month after operation and the incidence of refracture within 36 months after operation were compared between the two groups. The survival curves of the two groups were analyzed by Kaplan Meier. Chi-square test was used to compare the differences in survival rates between the two groups at 12, 24, and 36 months after operation. Univariate and multivariate Cox regression analysis compared multivariate factors on OTLCF postoperative mortality. RESULTS: There was no significant difference in gender, operation time, blood loss and preoperative VAS score between the two groups (χ2 = 1.750, p = 0.186; t = 1.195, p = 0.235; t = -0.582, p = 0.562; t = -1.513, p = 0.133), respectively. The patients in the sarcopenia group were older (t = 3.708, p = 0.000), and had longer postoperative grounding time and hospitalization time (t = 4.360, p = 0.000; t = 6.458, p = 0.000). The VAS scores and ODI scores one month postoperatively were also higher in sarcopenia group (t = 5.900, p = 0.000; t = 7.294, p = 0.000), and there was a statistical difference between the two groups. Interestingly, there was no significant difference in the incidence of spinal refracture within 36 months between the two groups (χ2 = 1.510, p = 0.219). The sarcopenia group had a higher mortality rate at 36 months after operation, and the difference was statistically significant (p = 0.002). Sarcopenia is an independent risk factor for long-term mortality in OTLCF patients received PKP surgery. CONCLUSIONS: Patients with sarcopenia combined with OTLCF have poor postoperative recovery of limb function and a high risk of death in the long-term (36 months) after surgery. Active and effective intervention for sarcopenia is required during treatment.

Evolution of intrinsic defects and ring structures on the surface of fused silica optics after CO2 laser conditioning.

Recently and interestingly, experiments show that the CO2 laser conditioning can significantly increase the laser-induced damage threshold (LIDT) of fused silica optics, but its underlying mechanism has not been clearly revealed. This Letter reports the experimental studies on the evolution of the intrinsic point defects and intrinsic ring structures on the surface of fused silica optics under the CO2 laser irradiation. The laser conditioning can effectively reduce the intrinsic defect contents in the surface layer of mechanically processed fused silica. However, the suppression effect of defects can be affected by the initial surface state. If there are micro-cracks on the component surface, the effect of the laser conditioning would be limited. The evolution of the intrinsic ring structures indicate that most of the intrinsic defects tend to recombine as short (Si-O)n ring structures during the laser healing of the micro-fractures. The observed recombination behavior and suppression of the intrinsic defects can help find out the reason for the increase of the LIDT of the fused silica optics.

Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis.

Joint replacement surgery is the most effective treatment for end-stage arthritis. Aseptic loosening caused by periprosthetic osteolysis is a common complication after joint replacement. Inflammation induced by wear particles derived from prosthetic biomaterials is a major cause of osteolysis. We emphasize that bone marrow-derived macrophages and their fusion-derived osteoclasts play a key role in this pathological process. Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. Aiming at wear particle-induced periprosthetic aseptic osteolysis, this review separately discusses the molecular mechanism of regulation of ROS formation and inflammatory response through intervention of macrophage/osteoclast RANKL-MAPKs-NF-κB pathway. These molecular mechanisms regulate osteoclast activation in different ways, but they are not isolated from each other. There is also a lot of crosstalk among the different mechanisms. In addition, other bone and joint diseases related to osteoclast activation are also briefly introduced. Therefore, we discuss these new findings in the context of existing work with a view to developing new strategies for wear particle-associated osteolysis based on the regulation of macrophages/osteoclasts.

From Tetranitromethane to Gem-Dinitro-Bridged Nitrogen-Rich Heterocyclic Compound: Achieving High Heat of Detonation.

Improving the detonation performance of tetranitromethane (TNM) by introducing energetic moieties is an intriguing area in the field of energetic materials. Incorporation of a mono nitrogen-rich skeleton into TNM usually results in unsatisfactory detonation performance. Now, we reported the design and synthesis of an advanced TNM-like molecule (3) containing nitrogen-rich triazole and nitro-triazinane moieties. In addition, two of its analogues (4 and 5) were also obtained. Taking advantage of the positive heat of formation brought by triazole and triazinane rings and high-density properties donated by many nitro groups, 3 shows promising heat of detonation (Q = 5859 kJ kg-1), which is 2.8 times of TNM and higher than most of its mono ring-modified derivatives (Q: 2076 to 5594 kJ kg-1). The detonation velocity and detonation pressure of 3 (Dv = 8964 m s-1 and P = 35.7 GPa) are competitive with those of RDX (Q = 5763 kJ kg-1, Dv = 8782 m s-1, and P = 34.7 GPa). Structural modification by using triazole and nitro-triazinane rings may be helpful in exploring more TNM derivatives and other types of high-performance explosives.

Triazole-induced planarization of a twisted tetrazole-based molecule towards energetic materials with improved thermostability and insensitivity.

Pursuing the structural planarization of energetic materials is an efficient method for achieving improved performance. Although many planar energetic molecules have been prepared so far, the innovation of advanced planar explosives still relies on the scientific intuition, experience and trial-and-error of researchers. Now, a triazole-induced planarization strategy is proposed based on the regulation of aromaticity, charge distribution, and hydrogen bonds. The incorporation of a triazole ring into the non-planar molecule 5-amino-1-nitriminotetrazole (VII) results in a planar energetic material named N-[5-amino-1-(1H-tetrazol-5-yl)-1H-1,2,4-triazol-3-yl]nitramide (3). Compared with VII (Td = 85 °C; IS < 0.25 J; FS < 5 N), 3 shows remarkably improved thermal stability (Td = 145 °C) and reduced sensitivities (IS = 20 J; FS > 360 N). The variation of thermal stability and mechanical sensitivity from VII to 3 reflects the effectiveness and superiority of the planarization strategy. Benefiting from the properties of 3, its energetic salt 5 exhibits excellent overall performance (Dv = 9342 m s-1; P = 31.6 GPa; Td = 201 °C; IS = 20 J; FS = 360 N), which is comparable to that of HMX. Moreover, the triazole-induced planarization strategy may serve as a guide for exploring advanced energetic materials.

The dual role of autophagy in periprosthetic osteolysis.

Periprosthetic osteolysis (PPO) induced by wear particles is an important cause of aseptic loosening after artificial joint replacement, among which the imbalance of osteogenesis and osteoclastic processes occupies a central position. The cells involved in PPO mainly include osteoclasts (macrophages), osteoblasts, osteocytes, and fibroblasts. RANKL/RANK/OGP axis is a typical way for osteolysis. Autophagy, a mode of regulatory cell death and maintenance of cellular homeostasis, has a dual role in PPO. Although autophagy is activated in various periprosthetic cells and regulates the release of inflammatory cytokines, osteoclast activation, and osteoblast differentiation, its beneficial or detrimental role remains controversy. In particular, differences in the temporal control and intensity of autophagy may have different effects. This article focuses on the role of autophagy in PPO, and expects the regulation of autophagy to become a powerful target for clinical treatment of PPO.

Olfactory-auditory sensory integration in the lateral entorhinal cortex.

Multisensory integration plays an important role in animal cognition. Although many studies have focused on visual-auditory integration, studies on olfactory-auditory integration are rare. Here, we investigated neural activity patterns and odor decoding in the lateral entorhinal cortex (LEC) under uni-sensory and multisensory stimuli in awake, head-fixed mice. Using specific retrograde tracing, we verified that the LEC receives direct inputs from the primary auditory cortex (AC) and the medial geniculate body (MGB). Strikingly, we found that mitral/tufted cells (M/Ts) in the olfactory bulb (OB) and neurons in the LEC respond to both olfactory and auditory stimuli. Sound decreased the neural responses evoked by odors in both the OB and LEC, for both excitatory and inhibitory responses. Interestingly, significant changes in odor decoding performance and modulation of odor-evoked local field potentials (LFPs) were observed only in the LEC. These data indicate that the LEC is a critical center for olfactory-auditory multisensory integration, with direct projections from both olfactory and auditory centers.

Pyroptosis in Periprosthetic Osteolysis.

Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting in the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts may be the decisive factor. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by gasdermins (GSDMs) family, among which GSDMD is the best characterized. Recent evidence indicates that activation of NLRP3 inflammasomes and pyroptosis play a pivotal role in the pathological process of PPO. Here, we review the pathological process of PPO, the molecular mechanism of pyroptosis and the interventions to inhibit the inflammation and pyroptosis of different cells during the PPO. Conclusively, this review provides theoretical support for the search for new strategies and new targets for the treatment of PPO by inhibiting pyroptosis and inflammation.

Effect of long noncoding RNA NONHSAT070806 on the apoptosis, proliferation, migration, invasion and tumorigenesis of bladder cancer.

Background: Bladder cancer (BC) is the most common malignancy of the urinary tract in China, and the extent of tumor invasion negatively correlates with prognosis. The mechanism of tumor invasion in BC has been unclear until recent studies revealed the critical role of long noncoding RNAs (lncRNAs) in the proliferation and invasion of tumors. Several lncRNAs have been reported to be associated with pathogenesis in BC, but not specifically. Methods: We used a microarray to screen the candidate lncRNAs with different expressions in BC. The expression of the lncRNAs in BC tissues or cells was identified by reverse transcription polymerase chain reaction (RT-PCR) or quantitative real-time PCR (qRT-PCR), and their ectopic expressions were measured via transfection experiment. The function of the lncRNAs was investigated by flow cytometry, caspase-3 enzyme linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8), wound healing, transwell and colony formation experiments in vitro and xenograft experiments in vivo. Results: We identified a novel sense lncRNA, NONHSAT070806, that was downregulated in BC tissues and cells and negatively correlated with level of tumor invasion in patients. Furthermore, overexpression of NONHSAT070806 induced apoptosis of T24 and 5637 cells, inhibited the proliferation, migration and invasion of BC cells, and attenuated the tumorigenesis of BC cells both in vitro and in vivo. Conclusions: NONHSAT070806 may act as a suppressor of BC and is a potential indicator of the invasiveness of BC.

Fucoidan Improves Growth, Digestive Tract Maturation, and Gut Microbiota in Large Yellow Croaker (Larimichthys crocea) Larvae.

The early life period is considered an essential period for gut microbial colonization. Manipulating gut microbiota interventions during early life periods has been proven to be a promising method to boost healthy growth. Therefore, the aim of the present study was to investigate the effects of dietary fucoidan (Fuc) on the growth, digestive tract maturation, and gut microbiota of large yellow croaker (Larimichthys crocea) larvae. Four diets were formulated with different levels of Fuc (0.00%, 0.50%, 1.00%, and 2.00%). Results showed that dietary Fuc significantly improved the growth performance of larvae. Meanwhile, dietary Fuc promoted digestive tract maturation. Dietary 1.00% Fuc significantly improved intestinal morphology. Dietary Fuc upregulated the expression of intestinal cell proliferation and differentiation related-genes and intestinal barrier related-genes. Dietary 2.00% Fuc significantly increased the activities of brush border membranes enzymes and lipase while inhibiting α-amylase. Furthermore, dietary Fuc maintained healthy intestinal micro-ecology. In detail, dietary 1.00% and 2.00% Fuc altered the overall structure of the gut microbiota and increased the relative abundance of Bacteroidetes while decreasing the relative abundance of opportunistic pathogens and facultative anaerobe. In conclusion, appropriate dietary Fuc (1.00-2.00%) could improve the growth of large yellow croaker larvae by promoting digestive tract maturation and maintaining an ideal intestinal micro-ecology.

KCC2 overexpressed exosomes meditated spinal cord injury recovery in mice.

Exosomes show great potential in treating diseases of the central nervous system including spinal cord injury (SCI), still better engineered exosomes have more advantages. In this study, we purified exosomes from K+-Cl-co-transporter (KCC2) overexpressed bone marrow mesenchymal stem cells (ExoKCC2), to investigate the effect of ExoKCC2on neural differentiationin vitroand the repairing function of ExoKCC2in SCI micein vivo. Compared to bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exo), ExoKCC2could better promote neural stem cell differentiated into neurons, ameliorate the function recovery of SCI mice, and accelerate the neural regeneration at the lesion site. Altogether, engineered ExoKCC2may prove to be an advantageous strategy for SCI treatment.

Toward Advanced High-Performance Insensitive FOX-7-like Energetic Materials via Positional Isomerization.

For an energetic molecule with a definite elemental composition, the substituent type and position are the most important factors to influence its detonation performance and mechanical sensitivities. In this work, two pairs of FOX-7-like energetic isomers based on (2 and HTz-FOX; 5 and 6) were synthesized and characterized. Through positional isomerization, advanced high-performance insensitive explosives were obtained. Compounds 2 and 5 with an amino group adjacent to the electron-withdrawing side of the ethene bridge show both higher thermal stability and lower mechanical sensitivities (2: Td = 258 °C, impact sensitivity (IS) = 25 J, and friction sensitivity (FS) = 300 N; 5: Td = 264 °C, IS = 30 J, and FS = 320 N). In addition, 2 shows ultrahigh detonation performance (Dv = 9224 m s-1 and P = 31.1 GPa). These promising physicochemical properties are comparable to those of HMX (Dv = 9193 m s-1, P = 37.8 GPa, Td = 275 °C, IS = 7.4 J, and FS = 120 N), which suggests that 2 may be a promising energetic material in future applications.

Effects of supplemental ferulic acid (FA) on survival, growth performance, digestive enzyme activities, antioxidant capacity and lipid metabolism of large yellow croaker (Larimichthys crocea) larvae.

A 30-day feeding trial was conducted to investigate the effects of supplemental ferulic acid (FA) on survival, growth performance, digestive enzyme activities, antioxidant capacity and lipid metabolism of the large yellow croaker larvae (initial weight: 2.58 ± 0.30 mg). Four isonitrogenous and isolipidic micro-diets were formulated with graded levels of FA (0, 20, 40, and 80 mg/kg) and fed to the experimental larvae seven times daily. Results showed that larvae fed the diet with 40 mg/kg FA had significantly higher survival rate, while the specific growth rate was higher in larvae fed diets with 40 and 80 mg/kg FA than the control group (P < 0.05). Activities of trypsin in pancreatic segments (PS) and intestinal segments, lipase in PS and alkaline phosphatase in brush border membrane were significantly increased by supplementation of FA compared to the control group (P < 0.05). Supplementation of FA significantly increased activities of total superoxide dismutase and catalase, and reduced the malondialdehyde content compared to the control group (P < 0.05). Meanwhile, activities of lysozyme, total nitric oxide synthase and nitric oxide content were significantly improved by supplemental FA in diets. Furthermore, supplementation of 40 mg/kg FA reduced the triglyceride content in larval visceral mass probably through down-regulating expression of lipogenesis-related genes (scd1, fas and dgat2) and up-regulating expression of lipid catabolism-related genes (aco, cpt-1 and hl). In conclusion, appropriate supplementation of 40 mg/kg FA could improve the survival and growth performance of large yellow croaker larvae through increasing digestive function, antioxidant capacity and promoting lipid metabolism.

Effect of Comprehensive Nursing on Traumatic Paraplegia Patients by Evaluation of Magnetic Resonance Imaging Features.

This research aimed to discuss the comprehensive nursing under the Omaha system in the treatment of patients with traumatic paraplegia (TP) and the changes in magnetic resonance imaging (MRI) features of patients. In total, 60 patients with TP were included as the research objects, and they were randomly divided into the experimental group (Omaha system-based comprehensive nursing) and the control group (routine nursing). All the objects underwent parallel MRI multisequence scanning. The scores of the quality of life, role change, mental health, care, oral hygiene, skin, neuromusculoskeletal (NMS) system, defecation function, urination function, contagion/infection, nutrition, healthcare supervision, and rest/sleep pattern in the experimental group were all significantly higher than those in the control group 3 months and 6 months after discharge (P < 0.05). The caregiving burden scores in the experimental group 3 months and 6 months after discharge from the hospital were 48.67 ± 6.97 and 43.40 ± 4.97, respectively, statistically lower than those in the control group (52.83 ± 6.37; 50.07 ± 7.14) (P < 0.05). On admission, MRI showed that the white lines disappeared from the compression of the dural sac, the spinal cord was compressed, and the intramedullary signal was abnormal. Then, six months after discharge, MRI showed that the compression of the dural sac was relieved, and the double white lines recovered. The apparent diffusion coefficient (ADC) of patients in the experimental group 6 months after discharge (1.063 ± 0.148) was highly lower than that in the control group (1.325 ± 0.245), with a difference of statistical significance (P < 0.05). In conclusion, comprehensive nursing under the Omaha system could improve the clinical treatment effect of patients with spinal cord injury (SCI) effectively, reduce the incidence of complications, and improve the quality of life and nursing outcomes of patients.

Effect of the degree of displacement of the third fragment on healing of femoral shaft fracture treated by intramedullary nailing.

OBJECTIVE: To investigate the effect of the degree of displacement of a femoral shaft fracture with the third fragment on fracture healing after intramedullary nailing. METHODS: In total, 216 patients with closed comminuted femoral fracture admitted to Lianyungang Hospital affiliated to Xuzhou Medical University from February 2010 to February 2016 were analyzed retrospectively. Among these patients, 142 were males and 74 were females, the mean age was 38 years (range 17-64 years), and 95 cases were on the right, while 121 cases were on the left. All patients were treated with a femoral interlocking intramedullary nail. Referring to the femoral shaft diameter, the degree of displacement of the third fragment was classified into four grades: grade I (displacement was less than a third of the diameter of the shaft): 121 cases; grade II (greater than a third of the diameter and less than two thirds): 52 cases; grade III (greater than two thirds of the diameter): 28 cases; and grade IV (fracture fragment turnover): 15 cases. According to the modified Radiological Union Scale for Femur (mRUSF), the fracture union rate and the mean union time of the fracture, the effect of the degree of displacement of the third fragment on fracture healing was evaluated. RESULTS: In total, 216 patients with a mean follow-up of 15.9 months (range 6-31 months) met the inclusion criteria. The best fracture healing was the grade I displacement, with a union rate of 89.2% and a mean union time of 7.7 months. The poorest fracture healing was for the grade IV displacement, with a union rate of 13.3% and a mean union time of 16.5 months. The healing was moderate in the grade II and III displacements, with a union rate of 46.2% and 28.6%, respectively, and a mean union time of 8.6 months and 13.5 months, respectively (P < 0.05). CONCLUSIONS: The third fragment with grade I displacement requires no intervention, whereas fractures with grade IV displacement should be reduced to as near as possible to the diaphyseal bone defect to avoid nonunion. The third fragments with the grade II or III displacement should be treated with closed reduction whenever possible to achieve a displacement within the range of grade I to minimize the incidence of nonunion.

Nutritional programming of large yellow croaker (Larimichthys crocea) larvae by dietary vegetable oil: effects on growth performance, lipid metabolism and antioxidant capacity.

The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.