Cholecystokinin-expressing superficial tufted cells modulate odour representation in the olfactory bulb and olfactory behaviours.

In mammals, odour information within the olfactory bulb (OB) is processed by complex neural circuits before being ultimately represented in the action potential activity of mitral/tufted cells (M/Ts). Cholecystokinin-expressing (CCK+) superficial tufted cells (sTCs) are a subset of tufted cells that potentially contribute to olfactory processing in the OB by orchestrating M/T activity. However, the exact role of CCK+ sTCs in modulating odour processing and olfactory function in vivo is largely unknown. Here, we demonstrate that manipulating CCK+ sTCs can generate perception and induce place avoidance. Optogenetic activation/inactivation of CCK+ sTCs exerted strong but differing effects on spontaneous and odour-evoked M/T firing. Furthermore, inactivation of CCK+ sTCs disrupted M/T odour encoding and impaired olfactory detection and odour discrimination. These results establish the role of CCK+ sTCs in odour representation and olfactory behaviours. KEY POINTS: Mice could perceive the activity of CCK+ sTCs and show place avoidance to CCK+ sTC inactivation. Optical activation of CCK+ sTCs increased the percentage of cells with odour response but reduced the odour-evoked response in M/Ts in awake mice. Optical inactivation of CCK+ sTCs greatly decreased spontaneous firing and odour-evoked response in M/Ts. Inactivation of CCK+ sTCs impairs the odour decoding performance of M/Ts and disrupts odour detection and discrimination behaviours in mice. These results indicate that CCK+ sTCs participate in modulating the odour representation and maintaining normal olfactory-related behaviours.

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.

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.

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.

Effects of dietary eucommia ulmoides leaf extract on growth performance, expression of feeding-related genes, activities of digestive enzymes, antioxidant capacity, immunity and cytokines expression of large yellow croaker (Larimichthys crocea) larvae.

A 30-d feeding trial was conducted to investigate effects of dietary eucommia ulmoides leaf extract (ELE) on growth performance, activities of digestive enzymes, antioxidant capacity, immunity, expression of inflammatory factors and feeding-related genes of large yellow croaker larvae. Five micro-diets were formulated with supplementation of 0 g kg-1 (the control), 5 g kg-1 (0·5 %), 10 g kg-1 (1·0 %) and 20 g kg-1 (2·0 %) of ELE, respectively. Results showed that the best growth performance was found in larvae fed the diet with 1·0 % ELE. Furthermore, ELE supplementation significantly increased the npy expression at 1·0 % dosage, while increased ghrelin in larvae at 0·5 % dosages. The activity of leucine aminopeptidase in larvae fed the diet with 1·0 % ELE was significantly higher than the control, while alkaline phosphatase was significantly upregulated in larvae fed the diet with 2·0 % ELE. A clear increase in total antioxidant capacity in larvae fed the diet with 1·0 % ELE was observed, whereas catalase activity was significantly higher in 1·0 % and 2·0 % ELE supplementation compared with the control. Larvae fed the diet with 1·0 % ELE had a significantly higher activities of lysozyme, total nitric oxide synthase and nitric oxide content than the control. Moreover, transcriptional levels of cox-2, il-1ß and il-6 were remarkably downregulated by the supplementation of 0·5-1·0 % ELE. This study demonstrated that the supplementation of 1·0 % ELE in diet could increase the growth performance of large yellow croaker larvae probably by promoting expression of feeding-related genes, enhancing antioxidant capacity and immunity and inhibiting expression of inflammatory factors.

Threshold Uniformity Improvement in 1b Quanta Image Sensor Readout Circuit.

A new readout architecture for single-bit quanta image sensor (QIS) consisting of a capacitive transimpedance amplifier (CTIA) before a 1-bit quantizer to improve the threshold uniformity of the readout cluster is proposed in this paper. The 1-bit quantizer in the previous single-bit QIS had significant threshold non-uniformity likely caused by the fluctuation of the common-mode voltage of the jot output. To guarantee the stability of the common-mode voltage of input signals fed to the 1-bit quantizer, the CTIA is added before the 1-bit quantizer. A pipeline operation mode is also proposed so the CTIA and 1-bit ADC can work at the same time, thereby reducing the CTIA power consumption. A 2048 × 1024 high-speed test chip was implemented with 45 nm/65 nm stacked backside illuminated (BSI) CMOS image sensor (CIS) process and tested. According to the measured D-log-H results, a good threshold uniformity in the range of 0.3 to 0.8 e- for all readout clusters is demonstrated at 500 frame per second (fps) equivalent timing with 68 mW power consumption.

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.

A Duo and a Trio of Triazoles as Very Thermostable and Insensitive Energetic Materials.

The triazole moiety with a high heat of formation and a high nitrogen content has been investigated for decades in combination with other nitrogen-rich heterocyclic rings in the field of energetic materials. A novel strategy for the construction of both thermally stable and mechanically insensitive energetic materials using a multi-aminotriazole system is now described. Using this methodology, two series of energetic materials were created on the basis of a duo of triazoles, 5-amino-3-(3,4-diamino-1,2,4-triazol-5-yl)-1H-1,2,4-triazole (TT), and a trio of triazoles, 4,5-di(3,4-diamino-1,2,4-triazol-5-yl)-2H-1,2,3-triazole (TTT). Their nitrogen-rich salts were also synthesized. Compound TT exhibits an excellent onset decomposition temperature (Td = 341 °C), which is superior to that of the conventional heat-resistant explosive hexanitrostilbene (HNS) (Td = 318 °C). The nitrogen-rich salt 4,5-di(3,4-diamino-1,2,4-triazol-5-yl)-2H-1,2,3-triazolium 3,4,5-trinitropyrazol-1-ide (TTT-1) exhibits both remarkable detonation properties and low sensitivities (Dv = 8715 m s-1; P = 32.6 GPa; IS > 40 J; FS > 360 N), which are superior to those of the traditional explosive LLM-105 (Dv = 8639 m s-1; P = 31.7 GPa; IS = 20 J; FS = 360 N). Therefore, this methodology of building a multi-aminotriazole system could effectively assist in the design of thermally stable and mechanically insensitive energetic materials in future exploration.

MYC upregulated LINC00319 promotes human acute myeloid leukemia (AML) cells growth through stabilizing SIRT6.

Long non-coding RNAs (lncRNAs) have been identified by accumulating studies as critical regulator in tumorigenesis and tumor development in human cancers, including in acute myeloid leukemia (AML). This study investigated the function and the underlying mechanism of LINC00319 in AML progression. Firstly, the low expression level of LINC00319 in whole blood of healthy individuals was obtained from UCSC, and its upregulation was detected in AML patients as well as AML cell lines. Besides, the prognostic significance of LINC00319 was revealed in AML patients. Functionally, the loss-of-function assays revealed that LINC00319 silence restrained proliferation but stimulated apoptosis in AML cells. Furthermore, LINC00319 expression was demonstrated proportional to MYC level in AML samples and transcriptionally regulated by MYC. Mechanistically, we identified FUS as a shared RNA binding protein (RBP) interacting with both LINC00319 and SIRT6. And LINC00319 regulated SIRT6 expression at post-transcriptional level through FUS-dependent pathway. Last but not least, SIRT6 overexpression rescued the suppressive effect of LINC00319 knockdown on AML cells growth. Overall, our findings unveiled that LINC00319 contributed to AML leukemogenesis via elevating SIRT6 expression, indicating a possible molecular target of LINC00319 for AML treatment.

Angiopoietin-1 Protects Spinal Cord Ischemia and Reperfusion Injury by Inhibiting Autophagy in Rats.

Spinal cord ischemia and reperfusion (SCIR) injury can induce autophagy, which is involved in the survival of neurons. However, whether autophagy plays a neuroprotective or a detrimental role in SCIR injury remains controversial. Angiopoietin-1 (Ang-1), an endothelial growth factor, has been shown to have neuroprotective effects. The present study aimed to explore the neuroprotective mechanisms of Ang-1 in neuronal cells in a rat model of SCIR injury in vivo. Ang-1 protein and rapamycin were injected intrathecally. Basso Beattie Bresnahan (BBB) scoring and hematoxylin and eosin staining were used to assess the degree of SCIR injury. Proteins that reflected the level of autophagy expression, such as Beclin-1 and LC3, were evaluated by western blotting. The results indicated that SCIR injury resulted in loss in lower limb motor function. Ang-1 protein inhibited the expression of Beclin-1 and LC3, which improved the BBB score and alleviated spinal cord injury. In contrast, rapamycin, an autophagy activator, caused the opposite effect. This study provides evidence that Ang-1 plays a neuroprotective role by inhibiting of autophagy expression in SCIR injury. Overall, findings could be useful for the treatment of SCIR injury.

Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1ß, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The ß-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The ß1-AR/ß2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the ß1-AR/ß2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.

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.

Comparison of the surgical efficacy of robot-assisted and freehand nail placement in the treatment of sarcopenia combined with femoral neck fractures younger than 65 years.

OBJECTIVE: There is limited research on the effectiveness of orthopedic robot-assisted treatment for sarcopenia combined with femoral neck fractures (FNF) in clinical settings. This study aimed to compare the clinical outcomes of orthopedic robot-assisted screw placement with traditional manual screw placement for treating sarcopenia combined with FNF. METHODS: The retrospective study included patients with FNF under the age of 65 who were admitted to the Department of Orthopedics at XX Hospital Affiliated to XX University between January 2019 and March 2022 and underwent internal fixation with cannulated screws. Grip strength of the dominant hand was measured, and the skeletal muscle index (SMI) was calculated based on the muscle tissue area at the level of the 12th thoracic vertebrae on chest CT divided by height squared. Sarcopenia was diagnosed when SMI was below 42.6 cm2/m2 for men or 30.6 cm2/m2 for women. Patients were then grouped based on whether they underwent orthopedic robot-assisted surgery, as the robot-assisted (RA) group or the freehand (FH) group. Follow-up evaluations over 24-36 months included various parameters such as operation time, blood loss, X-ray shots, number of needle drilling, cannulated nail parallelism, C-reactive protein (CRP) levels, time to weight-bearing, perioperative infection, VAS (visual analogue scale) scores at 1 and 6 months post-surgery, Harris hip score at 6 months post-surgery, and incidence of nonunions and femoral head necrosis within 24 months post-surgery. RESULTS: A total of 127 participants were enrolled in this study, with 46 individuals in the RG group and 81 in the FG group. Across both groups, factors such as gender, age, SMI, injury sides, Garden classifications, intraoperative blood loss, preoperative CRP, and VAS scores at 6 months post-surgery did not show statistically significant differences (p > 0.05). The RA group exhibited shorter operation time, fewer intraoperative X-ray shots, less needle drilling, and lower postoperative CRP levels compared to the FH group. The VAS score of the RA group was lower one month after surgery, whereas the Harris score was higher six months post-surgery (p < 0.05). The parallel angle of the hollow screws in the RA group was superior to that in the FH screw placement group, with an earlier time to bear weight on the ground post-surgery (p < 0.05). There were no statistically significant differences in incision infection, femoral neck nonunion (within 9 months after surgery), and patient satisfaction between the two groups (p > 0.05). Furthermore, the rate of femoral head necrosis after fracture within 2 years in the RA group was lower compared to the FH screw placement group, with statistically significant differences (p < 0.05).

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.

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.

Analysis of the influence of circumference and displacement of the third fracture fragment on the healing of femoral shaft fractures treated with intramedullary nailing.

The effect of circumference and displacement of the third fracture fragment on fracture healing after intramedullary nailing of femoral shaft fractures with a third fracture fragment was investigated. A retrospective cohort study was conducted to analyze the data of 142 patients who suffered femoral shaft fractures with a third fracture fragment and were admitted to the First People's Hospital of Lianyungang from February 2016 to December 2021. According to the circumference of the third fracture fragments, these were divided into three types of type 1: 71 cases; type 2: 52 cases; and type 3: 19 cases. On the basis of the diaphyseal diameter, the degree of displacement of the third fracture fragment was classified into three degrees of degree I: 95 cases; degree II: 31 cases; and degree III: 16 cases. Postoperative follow-up was performed to compare the fracture healing rate, healing time, and the modified Radiographic Union Scale for Tibia (mRUST) at 9th month after surgery in each group. All 142 patients were followed up after operation, with an average of (14.7 ± 4.1) months, and the overall healing rate was 73.4%. When the third fracture fragments were displaced in degree II and III, the mRUST score at 9th month in the type 1 group was higher than that in the type 2 and 3 groups (P = 0.017). Logistic regression analysis showed that greater displacement of third fracture fragments and greater circumference were associated with lower fracture healing rates (P < 0.05). After intramedullary nailing of femoral fractures, the degree of third fragment displacement and circumference affect fracture healing, and the former has a greater impact. When the third fracture fragment is displaced to degree II or III and its circumference is type 2 or type 3, it significantly affects the fracture healing. Intraoperative intervention to reduce the distance of third displacement of the fragment is required to reduce the incidence of non-union.

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.

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.