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Objective:To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion(PSM)with that designed by average-value virtual articulator(AVA).Methods:The study had recruited 12 participants with complete dentition and stable incisal guidance.An intraoral scanner was used to scan digital casts and record two types of patient-specific mo-tion(data only including protrusive movement,and data including protrusive movement and lateral pro-trusive movement).The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast.A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast.The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method.The incisal guidance was designed by different methods.The incisal guidance in control group was designed by the average-value virtual articulator.The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement(PSM1)and with the patient-specific motion including protru-sive movement and lateral protrusive movement(PSM2).The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015(3DSystem,America).The measurements included:Average of positive values,ratio of positive area and maximum value reflecting supra-occlusion;average of negative values,ratio of negative area and minimum value re-flecting over-correction;and root mean square reflecting overall deviation.Results:Statistical data were collected using the median(interquartile range)method.The average of positive values,ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group[8.0(18.8)μm vs.37.5(47.5)μm;0vs.7.2％(38.1％);-109.0(63.8)μm vs.-66.5(64.5)μm],and the ratio of negative area of PSM2 group was larger than those of the control group[52.9％(47.8％)vs.17.3％(45.3％)],with significant differences(P all＜0.05).The ratio of positive area[0.1％(7.0％)]and average of negative values[-97.0(61.5)μm]of PSM1 group,were smaller than those of the control group,and the ratio of negative area[40.7％(39.2％)]of the PSM1 group was larger than that of the control group,with significant differences(P＜0.05).The average of positive values[20.0(42.0)μm]and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences(P＜0.05).Conclusion:To establish the incisor guidance of implant-supported single crowns,compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement,the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

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Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.

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Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.

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Objective:To compare the genetic spectrums of esophageal squamous cell carcinoma (ESCC) patients with different prognosis after postoperative radiotherapy and to screen the genetic variants associated with radiotherapy resistance.Methods:A total of 32 ESCC patients who received radical surgery and postoperative adjuvant radiotherapy in Affiliated Hospital of Nantong University from January 2015 to December 2019 were selected as the study objects. According to whether there was any recurrence in the radiation field within 1 year, they were divided into a recurrence group (radiotherapy resistance group, n=16) and a stable group (radiotherapy sensitive group, n=16). Genomic DNA was extracted from patients and high-throughput sequencing was performed using whole exome sequencing (WES) technology. Biological information analysis software Trimmomatic, BWA and Picard were used to process the data and the alignment files were obtained by GATK comparison, then Vardict software was used to screen out various genetic variants from the sequencing data. The disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method. Cox proportional hazard regression model was used to analyze the independent risk factors of DFS and OS of ESCC patients. Results:After quality control of the sample data, 26 patients were finally included in this study for follow-up analysis, 13 in each of the recurrence and stable groups. The median tumor mutation burden of non-silent tumors in the whole group was 0.95 mutations/Mb. The substitution types of mutant bases were mainly C>T conversion, followed by C>G transmutation. The genetic variants with the highest frequency were single nucleotide polymorphism (SNP) (75.1%), deletion mutation (13.7%) and insertion mutation (10.5%). The number of tumor-specific mutations in the recurrence group was slightly higher than that in the stable group (median mutation number was 36 and 34, respectively), and the top ten gene profiles of mutation frequency were significantly different between the two groups. In the recurrence group, 392 unique mutated genes were detected, and the top five were MUC19, NPIPA5, EPPK1, FLG and FOXG1. In the stable group, 192 unique mutation genes were detected, and the top five were TCHH, WNK1, AIM1L, COL6A5 and DPCR1. The median DFS and OS were 15.0 months (95% CI: 10.1 months-not reached) and 26.2 months (95% CI: 19.8 months-not reached) in the recurrence group respectively, and no recurrence or metastasis occurred in the stable group. Univariate analysis showed that GRIK2 ( χ2=6.81, P=0.009), MUC4 ( χ2=4.25, P=0.039), MUC5B ( χ2=4.03, P=0.045), PRRG1 ( χ2=5.15, P=0.023) gene mutations, 3p deletion ( χ2=4.16, P=0.041) and 14q deletion ( χ2=7.09, P=0.008) were correlated with DFS. FLG ( χ2=6.41, P=0.011), NPIPA5 ( χ2=4.57, P=0.033), PKD1L2 ( χ2=6.41, P=0.011), FOXG1 ( χ2=4.57, P=0.033) gene mutations, 3p deletion ( χ2=3.88, P=0.049), 14q deletion ( χ2=5.66, P=0.017) and 18p deletion ( χ2=3.85, P=0.050) were associated with OS. Multivariate analysis showed that 14q deletion ( HR=3.65, 95% CI: 1.18-11.32, P=0.025) was an independent risk factor for DFS of ESCC patients with postoperative adjuvant radiotherapy, and FLG ( HR=8.94, 95% CI: 1.52-52.74, P=0.016), NPIPA5 ( HR=6.36, 95% CI: 1.23-33.03, P=0.028) gene mutation and 14q deletion ( HR=3.82, 95% CI: 1.18-12.31, P=0.025) were independent risk factors for OS of ESCC patients with postoperative adjuvant radiotherapy. Conclusion:The WES results suggest that the types and rates of gene mutations of the ESCC patients with postoperative adjuvant radiotherapy in the recurrence and stable groups are basically the same, but the mutation spectrum of the two groups is significantly different. FLG, NPIPA5 gene mutations and 14q deletion can be used as molecular markers to predict the prognosis of ESCC patients treated with postoperative adjuvant radiotherapy.

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Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

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11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues, resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with a variety of ailments including metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a 3-point pharmacophore for 11ß-HSD1 that was utilized to design a 2-spiroproline derivative as a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of several leads, such as compounds 39 and 51. Importantly, deleterious hERG inhibition and pregnane X receptor induction were mitigated by the introduction of a 4-hydroxyl group to the proline ring system.

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11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a three-point pharmacophore for 11ß-HSD1 that was utilized to design a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of INCB13739. Clinical evaluation of INCB13739 confirmed for the first time that tissue-specific inhibition of 11ß-HSD1 in patients with type 2 diabetes mellitus was efficacious in controlling glucose levels and reducing cardiovascular risk factors.

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OBJECTIVE@#To investigate the effect of porous surface morphology of zirconia on the proliferation and differentiation of osteoblasts.@*METHODS@#According to different manufacturing and pore-forming methods, the zirconia specimens were divided into 4 groups, including milled sintering group (M-Ctrl), milled porous group (M-Porous), 3D printed sintering group (3D-Ctrl) and 3D printed porous group (3D-Porous). The surface micromorphology, surface roughness, contact angle and surface elements of specimens in each group were detected by scanning electron microscope (SEM), 3D laser microscope, contact angle measuring device and energy-dispersion X-ray analysis, respectively. MC3T3-E1 cells were cultured on 4 groups of zirconia discs. The cell morphology of MC3T3-E1 cells on zirconia discs was eva-luated on 1 and 7 days by SEM. The cell proliferation was detected on 1, 3 and 5 days by cell counting kit-8 (CCK-8). After osteogenic induction for 14 days, the relative mRNA expression of alkaline phosphatase (ALP), type Ⅰ collagen (Colla1), Runt-related transcription factor-2 (Runx2) and osteocalcin (OCN) in MC3T3-E1 cells were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#The pore size [(419.72±6.99) μm] and pore depth [(560.38±8.55) μm] of 3D-Porous group were significantly larger than the pore size [(300.55±155.65) μm] and pore depth [(69.97±31.38) μm] of M-Porous group (P < 0.05). The surface of 3D-Porous group appeared with more regular round pores than that of M-Porous group. The contact angles of all the groups were less than 90°. The contact angles of 3D-Ctrl (73.83°±5.34°) and M-Porous group (72.7°±2.72°) were the largest, with no significant difference between them (P>0.05). Cells adhered inside the pores in M-Porous and 3D-Porous groups, and the proliferation activities of them were significantly higher than those of M-Ctrl and 3D-Ctrl groups after 3 and 5 days' culture (P < 0.05). After 14 days' incubation, ALP, Colla1, Runx2 and OCN mRNA expression in 3D-Porous groups were significantly lower than those of M-Ctrl and 3D-Ctrl groups (P < 0.05). Colla1, Runx2 and OCN mRNA expressions in M-Porous group were higher than those of 3D-Porous group (P < 0.05).@*CONCLUSION@#The porous surface morphology of zirconia can promote the proliferation and adhesion but inhibit the differentiation of MC3T3-E1 cells.

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Smallanthus sonchifolius， a plant resource with both medicinal and edible values， has been taken as fruit for a long history. Studies have proved that phenolic acids， flavonoids， sesquiterpene lactones， and fructooligosaccharides are the major compounds in S. sonchifolius. The extract of S. sonchifolius demonstrates noticeable antioxidant， anti-inflammatory， antimicrobial， and anti-cancer effects， as well as the activities of lowering blood glucose level， regulating intestinal function and so on. The rhizomes and leaves of S. sonchifolius contain abundant phenolic acids， mainly caffeic acid and its derivatives， which endow S. sonchifolius with remarkable antioxidant effect. Moreover， these substances can reduce blood glucose by improving insulin sensitivity. Fructooligosaccharides are abundant in the tuber of this plant， which can improve intestinal function by regulating intestinal flora. The sesquiterpene lactones in glandular trichomes on the leaf surface can inhibit the proliferation of cancer cells， among which uvedafolin and enhydrofolin have particularly strong activities. Furthermore， the sesquiterpene lactones have obvious inhibitory effect on Gram-positive bacteria. In terms of structure， the number of epoxy groups is linked to the strength of anticancer and antimicrobial effects. In addition， S. sonchifolius contains other compounds such as volatile oils， fatty acids， sterols， diterpenes， p-hydroxyacetophenone derivatives， and octulosonic acid derivatives， thereby exhibiting the pharmacological effects of treating Alzheimer's disease， protecting kidney， and lowering blood lipids. However， the isolation and identification of the main compounds in S. sonchifolius need further exploration， and the mechanism of action remains to be studied. Here we summarized the principal chemical components and pharmacological activities of S. sonchifolius， aiming to give a clue for the comprehensive development and utilization of this plant.

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Uronic acid in extracellular polymeric substances is a primary but often ignored factor related to the difficult hydrolysis of waste-activated sludge (WAS), with alginate as a typical polymer. Previously, we enriched alginate-degrading consortia (ADC) in batch reactors that can enhance methane production from WAS, but the enzymes and metabolic pathway are not well documented. In this work, two chemostats in series were operated to enrich ADC, in which 10 g/L alginate was wholly consumed. Based on it, the extracellular alginate lyase (∼130 kD, EC 4.2.2.3) in the cultures was identified by metaproteomic analysis. This enzyme offers a high specificity to convert alginate to disaccharides over other mentioned hydrolases. Genus Bacteroides (>60%) was revealed as the key bacterium for alginate conversion. A new Entner-Doudoroff pathway of alginate via 5-dehydro-4-deoxy-d-glucuronate (DDG) and 3-deoxy-d-glycerol-2,5-hexdiulosonate (DGH) as the intermediates to 2-keto-3-deoxy-gluconate (KDG) was constructed based on the metagenomic and metaproteomic analysis. In summary, this work documented the core enzymes and metabolic pathway for alginate degradation, which provides a good paradigm when analyzing the degrading mechanism of unacquainted substrates. The outcome will further contribute to the application of Bacteroides-dominated ADC on WAS methanogenesis in the future.

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OBJECTIVE@#To evaluate the effects of femtosecond laser treated microgrooved surface on microscopic topography, phase transformation, and three-points flexural strength of zirconia, and to provide reference for surface microstructure optimization of zirconia implant.@*METHODS@#According to different surface treatment methods, 57 computer aided design/computer aided manufacture (CAD/CAM) zirconia bars (20.0 mm×4.0 mm×1.4 mm) were evenly divided into three groups: sintered group, no treatment after sintering, taken as control; sandblasted group, sandblasted with 110 μm aluminium oxide (Al2O3) after sintering; microgrooved group, femtosecond laser fabricated microgrooves with 50 μm width, 30 μm depth, and 100 μm pitch. Surface microscopic topography was observed with scanning electron microscope (SEM) and 3D laser microscope. Further, surface roughness in each group and microgroove size were measured. Crystal phase was analyzed with X-ray diffraction. Specimens were subjected to three- points flexural strength test, and Weibull distribution was used to analyze their strength characteristics.@*RESULTS@#SEM showed that sintered surface was flat with clear grain structure; sandblasted surface exihibited bumps and holes with sharp margins and irregular shape; microgrooves were regularly aligned without evident defect, and nano-scale particles were observed on the surface inside of the microgrooves. Ra value of microgrooved group [(9.42±0.28)] μm was significantly higher than that of sandblasted group [(1.04±0.03) μm] and sintered group [(0.60±0.04) μm], and there was statistical difference between sandblasted group and sintered group (P < 0.001). The microgroove size was precise with (49.75±1.24) μm width, (30.85±1.02) μm depth, and (100.58±1.94) μm pitch. Crystal phase analysis showed that monoclinic volume fraction of sandblasted group (18.17%) was much higher than that of sintered group (1.55%), while microgrooved group (2.21%) was similar with sintered group. The flexural strength of sandblasted group (986.22±163.25) MPa had no statistical difference with that of sintered group (946.46±134.15) MPa (P=0.847), but the strength in microgrooved group (547.92±30.89) MPa dropped significantly compared with the other two groups (P < 0.001). Weibull modulus of sintered, sandblasted, microgrooved groups were 7.89, 6.98, and 23.46, respectively.@*CONCLUSION@#Femtosecond laser was able to form micro/nanostructured microgrooves on zirconia surface, which deleteriously affected the flexural strength of zirconia.

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【Objective】 To explore the establishment of individualized prediction model of recurrence after percutaneous endoscopic lumbar discectomy （PELD） in patients with lumbar disc herniation （LDH）. 【Methods】 We selected 124 LDH patients treated with PELD in Department of Orthopedics， The First Affiliated Hospital of Xi’an Jiaotong University， from January 2017 to January 2020 as the research subjects. Their clinical data were retrospectively analyzed， and the independent risk factors affecting PELD recurrence in the LDH patients were screened by univariate analysis and Logistic regression analysis， respectively； the correlation histogram prediction model was established. 【Results】 Age， history of diabetes， course of disease， work intensity and IDDG were the risk factors for the recurrence of PELD in LDH patients （P<0.05）. Based on the risk factors screened out， the prediction model of the histogram was established， and the model was verified. The results showed that the C-index of the modeling set and the validation set was 0.944 （95% CI： 0.902-0.963） and 0.969 （95% CI： 0.911-0.978）， respectively. The correction curves of both groups were well fitted with the standard curves. The areas under the ROC curve （AUC） in the two groups were 0.944 and 0.969， respectively， which proved that the model had good prediction accuracy. 【Conclusion】 LDH patients have many independent risk factors for recurrence after PELD， and the model based on risk factors with good predictive ability can be useful in preoperative evaluation， appropriate patient selection， and decrease of recurrence rate after PELD.

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Microbial fuel cell (MFC) is a bioelectrochemical device, that enables simultaneous wastewater treatment and energy generation. However, a few issues such as low output power, high ohmic internal resistance, and long start-up time greatly limit MFCs' applications. MFC anode is the carrier of microbial attachment, and plays a key role in the generation and transmission of electrons. High-quality bioelectrodes have developed into an effective way to improve MFC performance. Conjugated polymers have advantages of low cost, high conductivity, chemical stability and good biocompatibility. The use of conjugated polymers to modify bioelectrodes can achieve a large specific surface area and shorten the charge transfer path, thereby achieving efficient biological electrochemical performance. In addition, bacteria can be coated with nano-scale conjugated polymer and effectively transfer the electrons generated by cells to electrodes. This article reviews the recently reported applications of conjugated polymers in microbial fuel cells, focusing on the MFC anode materials modified by conjugated polymers. This review also systematically analyzes the advantages and limitations of conjugated polymers, and how these composite hybrid bioelectrodes solve practical issues such as low energy output, high inner resistance, and long starting time.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Psychrophilic microbial fuel cell (PMFC) offers an alternative method for low temperature wastewater treatment, but is seldom reported. In this study, the two-chamber PMFC was constructed at 10 °C using acetate as an electron donor. The maximum voltage under external resistance of 1000 Ω was around 550 mV. The columbic efficiency (CE) was 82.4% under external resistance of 100 Ω and the max power density was 582.4 mW/m2. After temperature decreasing to 4 °C, the maximum voltage also reached 530 mV and CE was 38.4%. The direct electron transfer was proposed in PMFC according to cyclic voltammetry curves. The short enriching time (~30 days) of biofilm in the anodic electrode may be due to the high activity of enriched novel exoelectrogens of M. fermentans (46.2%) and E. lemanii (15.4%). The development of PMFC involved biotechnologies in low temperature regions shall benefit for valuable chemicals production and energy generation in the future.

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Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G-protein-coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1ß (IL1ß) production, more M1-like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti-oxidation, IL1ß production alleviation, and glycolysis control. Although GIT1 has been recognized as a scaffold protein, our data clarified that GIT1-mediated extracellular-signal-regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid-derived 2)-like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1-activated ERK/NRF2 negatively regulates the 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that macrophage GIT1 could be a potential target to improve bone regeneration. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..

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Caproate production by mixed culture fermentation (MCF) is economically attractive. Xylose is known as the second most abundant sugar in nature, however, producing caproate from xylose is never reported. In this study, caproate production from xylose by mesophilic MCF was firstly investigated. The results showed that as pH decreasing to 5.0, the caproate concentration was 2.06 g/L in a batch reactor and was between 0.45 and 1.07 g/L in a continuously stirred reactor. Microbial analysis illustrated that Caproiciproducens and Clostridium_sensu_stricto_12, as two main identified caproate producers, occupied over 50% and around 10% of mixed culture, respectively. Thus, caproate production from xylose was proposed via the fatty acid biosynthesis pathway, not the well-known reverse ß-oxidation pathway. These unexpected differences from literatures gains more understanding about caproate production from organic substrates via MCF.

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Huge amounts of wastewater that contain aromatic compounds such as benzene and phenols are discharged worldwide. Benzoate is a typical intermediate in the anaerobic transformation of those aromatic compounds. In this study, electrically conductive carbon-based materials of granulated activated carbon (GAC), multiwalled carbon nanotubes (MwCNTs), and graphite were evaluated for the ability to promote the benzoate degradation. The results showed that 82-93% of the electrons were recovered in CH4 production from benzoate. The carbon materials stimulated benzoate degradation in the sequence of GAC (5 g/L) > MwCNTs (1 g/L) ~ Graphite (0.1 g/L) > Control. Acetate was the only detected intermediate in the process of benzoate degradation. Taxonomic analyses revealed that benzoate was degraded by Syntrophus to acetate and H2, which were subsequently converted to methane by Methanosarcina (both acetoclastic methanogens and hydrogenotrophic methanogens) and Methanoculleus (hydrogenotrophic methanogens), and direct interspecies electron transfer (DIET) of Desulfovibrio and Methanosarcina. Thus, these results suggest a method to effectively enhance the removal of aromatic compounds and methane recovery.

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BACKGROUND: A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. METHODS: The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. RESULTS: In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. CONCLUSIONS: Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.

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In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.

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