Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study.

BACKGROUND: Although fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort. METHODS: 390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk. RESULTS: Fish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40-0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures. CONCLUSIONS: No significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.

Accuracy of dynamic navigation compared to static surgical guides and the freehand approach in implant placement: a prospective clinical study.

BACKGROUND: Computer-guided implant surgery has improved the quality of implant treatment by facilitating the placement of implants in a more accurate manner. This study aimed to assess the accuracy of implant placement in a clinical setting using three techniques: dynamic navigation, static surgical guides, and freehand placement. We also investigated potential factors influencing accuracy to provide a comprehensive evaluation of each technique's advantages and disadvantages. MATERIALS AND METHODS: Ninety-four implants in 65 patients were included in this prospective study. Patients were randomly assigned to one of three groups: dynamic navigation, static surgical guides, or freehand placement. Implants were placed using a prosthetically oriented digital implant planning approach, and postoperative CBCT scans were superimposed on preoperative plans to measure accuracy. Seven deviation values were calculated, including angular, platform, and apical deviations. Demographic and consistency analyses were performed, along with one-way ANOVA and post-hoc tests for deviation values. RESULTS: The mean global platform, global apical, and angular deviations were 0.99 mm (SD 0.52), 1.14 mm (SD 0.56), and 3.66° (SD 1.64°) for the dynamic navigation group; 0.92 mm (SD 0.36), 1.06 mm (SD 0.47), and 2.52° (SD 1.18°) for the surgical guide group; and 1.36 mm (SD 0.62), 1.73 mm (SD 0.66), and 5.82° (SD 2.79°) for the freehand group. Both the dynamic navigation and surgical guide groups exhibited statistically significant differences in all values except depth deviations compared to the freehand group (p < 0.05), whereas only the angular deviation showed a significant difference between the dynamic navigation and surgical guide groups (p = 0.002). CONCLUSION: Our findings highlight the superior accuracy and consistency of dynamic navigation and static surgical guides compared to freehand placement in implant surgery. Dynamic navigation offers precision and flexibility. However, it comes with cost and convenience considerations. Future research should focus on improving its practicality. TRIAL REGISTRATION: This study was retrospectively registered at the Thai Clinical Trials Register-Medical Research Foundation of Thailand (MRF) with the TCTR identification number TCTR20230804001 on 04/08/2023. It was also conducted in accordance with the Declaration of Helsinki and approved by the institutional ethics committee at the Xian Jiaotong University Hospital of Stomatology, Xian, China (xjkqII[2021] No: 043). Written informed consent was obtained from all participants.

Effects of chronic cold stress on tissue structure, antioxidant response, and key gene expression in the warm-water bivalve Chlamys nobilis.

As ectothermic invertebrates, mollusks are regarded as good environmental indicator species for determining the adverse effects of climate change on marine organisms. In the present study, the effects of cold stress on the tissue structure, antioxidant activity, and expression levels of genes were evaluated in the warm-water noble scallop Chlamys nobilis by simulating natural seawater cooled down during winter from 17 °C to 14 °C, 12 °C, 10 °C, and 9 °C. Firstly, the gill was severely damaged at 10 °C and 9 °C, indicating that it could be used as a visually indicative organ for monitoring cold stress. The methylenedioxyamphetamine (MDA) content significantly increased with the temperatures decreasing, meanwhile, the antioxidant enzyme activities superoxide dismutase (SOD) and catalase (CAT) showed a similar pattern, suggesting that the scallop made a positive response. More importantly, 6179 genes related to low temperatures were constructed in a module-gene clustering heat map including 10 modules. Furthermore, three gene modules about membrane lipid metabolism, amino acid metabolism, and molecular defense were identified. Finally, six key genes were verified, and HEATR1, HSP70B2, PI3K, and ATP6V1B were significantly upregulated, while WNT6 and SHMT were significantly downregulated under cold stress. This study provides a dynamic demonstration of the major gene pathways' response to various low-temperature stresses from a transcriptomic perspective. The findings shed light on how warm-water bivalves can tolerate cold stress and can help in breeding new strains of aquatic organisms with low-temperature resistance.

Association Between Serum Homocysteine Concentration, Aneurysm Wall Inflammation, and Aneurysm Symptoms in Intracranial Fusiform Aneurysm.

RATIONALE AND OBJECTIVES: The pathophysiology of fusiform intracranial aneurysm (FIA) involves inflammatory processes, and homocysteine plays a role in the inflammatory processes in the vessel wall. Moreover, aneurysm wall enhancement (AWE) has emerged as a new imaging biomarker of aneurysm wall inflammatory pathologies. To investigate the pathophysiological mechanisms of aneurysm wall inflammation and FIA instability, we aimed to determine the associations between the homocysteine concentration, AWE, and FIAs' related symptoms. MATERIALS AND METHODS: We retrospectively reviewed the data of 53 patients with FIA who underwent both high-resolution magnetic resonance imaging and serum homocysteine concentration measurement. FIAs' related symptoms were defined as ischemic stroke or transient ischemic attack, cranial nerve compression, brainstem compression, and acute headache. The contrast ratio of the signal intensity of the aneurysm wall to the pituitary stalk (CRstalk) was used to indicate AWE. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine how well the independent factors could predict FIAs' related symptoms. Predictors of CRstalk were also investigated. Spearman's correlation coefficient was used to identify the potential associations between these predictors. RESULTS: Fifty-three patients were included, of whom 23 (43.4%) presented with FIAs' related symptoms. After adjusting for baseline differences in the multivariate logistic regression analysis, the CRstalk (odds ratio [OR]=3.207, P = .023) and homocysteine concentration (OR=1.344, P = .015) independently predicted FIAs' related symptoms. The CRstalk was able to differentiate between FIAs with and without symptoms (area under the ROC curve [AUC]=0.805), with an optimal cutoff value of 0.76. The homocysteine concentration could also differentiate between FIAs with and without symptoms (AUC=0.788), with an optimal cutoff value of 13.13. The combination of the CRstalk and homocysteine concentration had a better ability to identify symptomatic FIAs (AUC=0.857). Male sex (OR=0.536, P = .018), FIAs' related symptoms (OR=1.292, P = .038), and homocysteine concentration (OR=1.254, P = .045) independently predicted the CRstalk. CONCLUSION: A higher serum homocysteine concentration and greater AWE indicate FIA instability. Serum homocysteine concentration may be a useful biomarker of FIA instability; however, this needs to be verified in future studies.

Developing the Limosilactobacillus reuteri Chassis through an Endogenous Programmable Endonuclease-Based Genome Editing Tool.

Using genetically tractable probiotics to engineer live biotherapeutic products (LBPs) for disease treatment is urgently needed. Limosilactobacillus reuteri is an important vertebrate gut symbiont, which has great potential for developing LBPs. However, in L. reuteri, synthetic biology work is largely limited by the long editing cycle. In this study, we identified a subtype II-A CRISPR-Cas9 system in L. reuteri 03 and found the endogenous Cas9 (LrCas9) recognizing a broad protospacer-adjacent motif (PAM) sequence (3'-NDR; N = A, G, T, C; D = A, G, T; R = A, G). We reprogrammed the LrCas9 for efficient gene deletion (95.46%), point mutation (86.36%), large fragment deletion (40 kb), and gene integration (1743 bp, 73.9%), which uncovered the function of the repeated conserved domains in mucus-binding protein. Moreover, we analyzed the distribution of endogenous endonucleases in 304 strains of L. reuteri and found the existence of programmable endonucleases in 98.36% of L. reuteri strains suggesting the potential to reprogram endogenous endonucleases for genetic manipulation in the majority of L. reuteri strains. In conclusion, this study highlights the development of a new probiotic chassis based on endogenous endonucleases in L. reuteri 03, which paves the way for the development of genome editing tools for functional genetic studies in other L. reuteri. We believe that the development of an endogenous endonuclease-based genetic tool will greatly facilitate the construction of LBPs.

A deep learning framework for intracranial aneurysms automatic segmentation and detection on magnetic resonance T1 images.

OBJECTIVES: To design a deep learning-based framework for automatic segmentation and detection of intracranial aneurysms (IAs) on magnetic resonance T1 images and test the robustness and performance of framework. METHODS: A retrospective diagnostic study was conducted based on 159 IAs from 136 patients who underwent the T1 images. Among them, 127 cases were randomly selected for training and validation, and 32 cases were used to assess the accuracy and consistency of our algorithm. We developed and assembled three convolutional neural networks for the segmentation and detection of IAs. The segmentation and detection performance of the model were compared with the ground truth, and various metrics were calculated at the voxel level, IAs level, and patient level to show the performance of our framework. RESULTS: Our assembled model achieved overall Dice, voxel-level sensitivity, specificity, balanced accuracy, and F1 score of 0.802, 0.874, 0.9998, 0.937, and 0.802, respectively. A coincidence greater than 0.7 between the aneurysms predicted by the model and the ground truth was considered as a true positive. For IAs detection, the sensitivity reached 90.63% with 0.58 false positives per case. The volume of IAs segmented by our model showed a high agreement and consistency with the volume of IAs labeled by experts. CONCLUSION: The deep learning framework is achievable and robust for IAs segmentation and detection. Our model offers more clinical application opportunities compared to digital subtraction angiography (DSA)-based, CTA-based, and MRA-based methods. CLINICAL RELEVANCE STATEMENT: Our deep learning framework effectively detects and segments intracranial aneurysms using clinical routine T1 sequences, showing remarkable effectiveness and offering great potential for improving the detection of latent intracranial aneurysms and enabling early identification. KEY POINTS: •There is no segmentation method based on clinical routine T1 images. Our study shows that the proper deep learning framework can effectively localize the intracranial aneurysms. •The T1-based segmentation and detection method is more universal than other angiography-based detection methods, which can potentially reduce missed diagnoses caused by the absence of angiography images. •The deep learning framework is robust and has the potential to be applied in a clinical setting.

Statins may Decrease Aneurysm wall Enhancement of Unruptured Fusiform Intracranial Aneurysms: A high-resolution 3T MRI Study.

Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms. Aneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) has emerged as a surrogate biomarker of vessel wall inflammation and unruptured intracranial aneurysm instability. We investigated the correlation between anti-inflammatory drug use and three-dimensional AWE of fusiform intracranial aneurysms (FIAs). We retrospectively analyzed consecutive patients with FIAs in our database who underwent 3T HR-MRI at three Chinese centers. FIAs were classified as fusiform-type, dolichoectatic-type, or transitional-type. AWE was objectively defined using the aneurysm-to-pituitary stalk contrast ratio in three-dimensional space by determining the contrast ratio of the average signal intensity in the aneurysmal wall and pituitary stalk on post-contrast T1-weighted images. Data on aneurysm size, morphology, and location, as well as patient demographics and comorbidities, were collected. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with AWE of FIAs on HR-MRI. In total, 127 FIAs were included. In multivariate analysis, statin use (ß = -0.236, P = 0.007) was the only independent factor significantly associated with decreased AWE. In the analysis of three FIA subtypes, the fusiform and transitional types were significantly associated with statin use (rs = -0.230, P = 0.035; and rs = -0.551, P = 0.010; respectively). It establishes an incidental correlation between the use of statins daily for ≥ 6 months and decreased AWE of FIAs. The findings also indicate that the pathophysiology may differ among the three FIA subtypes.

Three-dimensional aneurysm wall enhancement in fusiform intracranial aneurysms is associated with aneurysmal symptoms.

Background and purpose: Aneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) is a potential biomarker for evaluating unstable aneurysms. Fusiform intracranial aneurysms (FIAs) frequently have a complex and curved structure. We aimed to develop a new three-dimensional (3D) aneurysmal wall enhancement (AWE) characterization method to enable comprehensive FIA evaluation and to investigate the ability of 3D-AWE to predict symptomatic FIA. Methods: We prospectively recruited patients with unruptured FIAs and received 3 T HR-MRI imaging from September 2017 to January 2019. 3D models of aneurysms and parent arteries were generated. Boundaries of the FIA were determined using 3D vessel diameter measurements. Dmax was the greatest diameter in the cross-section, while Lmax was the length of the centerline of the aneurysm. Signal intensity of the FIA was normalized to the pituitary stalk and then mapped onto the 3D model, then the average enhancement (3D-AWEavg), maximum enhancement (3D-AWEmax), enhancement area (AWEarea), and enhancement ratio (AWEratio) were calculated as AWE indicators, and the surface area of the entire aneurysm (Aarea) was also calculated. Areas with high AWE were defined as those with a value >0.9 times the signal intensity of the pituitary stalk. Multivariable logistic regression analyses were performed to determine independent predictors of aneurysm-related symptoms. FIA subtypes were defined as fusiform, dolichoectasia, and transitional. Differences between the three FIA subtypes were also examined. Results: Forty-seven patients with 47 FIAs were included. Mean patient age was 55 ± 12.62 years and 74.5% were male. Twenty-nine patients (38.3%) were symptomatic. After adjusting for baseline differences in age, hypertension, Lmax, and FIA subtype, the multivariate logistics regression models showed that 3D-AWEavg (odds ratio [OR], 4.029; p = 0.019), 3D-AWEmax (OR, 3.437; p = 0.022), AWEarea (OR, 1.019; p = 0.008), and AWEratio (OR, 2.490; p = 0.045) were independent predictors of aneurysm-related symptoms. Dmax and Aarea were larger and 3D-AWEavg, 3D-AWEmax, AWEarea, and AWEratio were higher with the transitional subtype than the other two subtypes. Conclusion: The new 3D AWE method, which enables the use of numerous new metrics, can predict symptomatic FIAs. Different 3D-AWE between the three FIA subtypes may be helpful in understanding the pathophysiology of FIAs.

The reciprocal relations among self-compassion, posttraumatic stress disorder, and posttraumatic growth among adolescents after the Jiuzhaigou earthquake: a three-wave cross-lagged study.

BACKGROUND: Previous cross-sectional studies have examined the relationship between self-compassion, post-traumatic stress disorder (PTSD), and post-traumatic growth (PTG). But no study has tested whether self-compassion is a cause or a consequence of PTSD, PTG, or both. AIMS: The cross-lag analysis was used to examine the reciprocal effects among self-compassion, PTSD, and PTG. METHOD: We used data from 244 adolescents who had experienced earthquakes. We assessed self-compassion, PTSD, and PTG via self-report measures after the earthquake in Jiuzhaigou, as well as 6 and 12 months later. RESULTS: Cross-lagged analyses indicated that positive self-compassion could significantly predict subsequent PTSD and PTG. Meanwhile, PTSD and PTG also predicted later positive self-compassion. Negative self-compassion at T1 increased PTSD at T2, and neither PTSD nor PTG significantly predicted subsequent negative self-compassion. In addition, negative self-compassion at T1 significantly predicted positive self-compassion at T2, while positive self-compassion at T2 significantly predicted negative self-compassion at T3. CONCLUSIONS: Positive self-compassion is a protective factor of post-traumatic psychological response, and it is maintained for a long time, while negative self-compassion may aggravate the negative psychological outcomes of adolescents in the early stage of experiencing traumatic events. In addition, positive and negative self-compassion can influence each other over time.

Gender differences in symptom structure of adolescent problematic internet use: A network analysis.

BACKGROUND: Gender differences in problematic Internet use (PIU) have long been discussed. However, whether and how female and male adolescents differ in central symptoms and symptom associations are not fully understood. METHODS: As a national survey in the Chinese mainland, 4884 adolescents (51.6% females; Mage = 13.83 ± 2.41) participated in the present study. This study applies network analysis to identify central symptoms of PIU networks in female and male adolescents and compares whether and how global and local connectivity of PIU networks differ by gender. RESULTS: Female and male network structures of PIU were different and global strength was stronger in males than females, indicating a higher risk of chronicity of PIU among male adolescents. Specifically, "Reluctant to turn off Internet" exerted the largest effect on both genders. "Increase time online to achieve satisfaction" and "Feel depressed once not online for a while" were particularly critical to female and male adolescents, respectively. Moreover, females scored higher centralities in social withdrawal symptoms and males did so in interpersonal conflicts owing to PIU. CONCLUSIONS: These findings provide novel insights into gender differential risks and features of adolescent PIU. Differences in the core symptoms of PIU suggest that gender-specific interventions focusing on core symptoms might effectively relieve PIU and maximize treatment effects.

The reciprocal relations among self-compassion, and depression among adolescents after the Jiuzhaigou earthquake: A three-wave cross-lagged study.

BACKGROUND: Previous cross-sectional studies have examined the relationship between self-compassion and depression. Although it is often implicitly assumed that self-compassion may increase the vulnerability of an individual to depression, only a few studies have assessed whether self-compassion is a cause or a consequence of depression or both. METHOD: To examine such reciprocal effects, we assessed self-compassion and depression via self-report measures. At the baseline assessment (Time 1, T1), 450 students (M = 13.72, SD = 0.83, 54.2% females) participated 10 months after the Jiuzhaigou earthquake. We reassessed the T1 sample after 6- and 12-month intervals. At Time 2 (T2) assessment, 398 (56.0% female participants) of the Wave 1 participants were retained, and at Time 3 (T3) assessment, 235 (52.5% female participants) of the T1 and T2 participants were retained. RESULTS: Cross-lagged analyses indicated that positive self-compassion could significantly reduce subsequent depression. However, depression did not significantly predict later positive self-compassion. Negative self-compassion at T1 increased depression at T2, but negative self-compassion at T2 did not significantly predict depression at T3. In addition, positive self-compassion significantly reduced subsequent negative self-compassion. CONCLUSIONS: Positive self-compassion appears to protect adolescents against depression and maintain this protection over time, whereas negative self-compassion may worsen depression in adolescents during the initial stages of traumatic events. Additionally, positive self-compassion may decrease the level of negative self-compassion.

Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms.

Introduction: Inflammation plays a key role in the progression of intracranial aneurysms. Aneurysmal wall enhancement (AWE) correlates well with inflammatory processes in the aneurysmal wall. Understanding the potential associations between blood inflammatory indices and AWE may aid in the further understanding of intracranial aneurysm pathophysiology. Methods: We retrospectively reviewed 122 patients with intracranial fusiform aneurysms (IFAs) who underwent both high-resolution magnetic resonance imaging and blood laboratory tests. AWE was defined as a contrast ratio of the signal intensity of the aneurysmal wall to that of the pituitary stalk ≥ 0.90. The systemic immune-inflammation (SII) index (neutrophils × platelets/lymphocytes) was calculated from laboratory data and dichotomized based on whether or not the IFA had AWE. Aneurysmal symptoms were defined as sentinel headache or oculomotor nerve palsy. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to determine how well the SII index was able to predict AWE and aneurysmal symptoms. Spearman's correlation coefficients were used to explore the potential associations between variables. Results: This study included 95 patients, of whom 24 (25.3%) presented with AWE. After adjusting for baseline differences in neutrophil to lymphocyte ratios, leukocytes, and neutrophils in the multivariable logistic regression analysis, smoking history (P = 0.002), aneurysmal symptoms (P = 0.047), maximum diameter (P = 0.048), and SII index (P = 0.022) all predicted AWE. The SII index (P = 0.038) was the only independent predictor of aneurysmal symptoms. The receiver operating characteristic curve analysis revealed that the SII index was able to accurately distinguish IFAs with AWE (area under the curve = 0.746) and aneurysmal symptoms (area under the curve = 0.739). Discussion: An early elevation in the SII index can independently predict AWE in IFAs and is a potential new biomarker for predicting IFA instability.

Aneurysm wall enhancement, atherosclerotic proteins, and aneurysm size may be related in unruptured intracranial fusiform aneurysms.

OBJECTIVE: This cross-sectional study aimed to investigate the associations between aneurysm wall enhancement (AWE), atherosclerotic protein levels, and aneurysm size in unruptured intracranial fusiform aneurysms (IFAs). METHODS: Patients with IFAs underwent high-resolution magnetic resonance imaging (HR-MRI) and atherosclerotic protein examinations from May 2015 to December 2021 were collected. A CRstalk (signal intensity [SI] of IFA wall/SI of pituitary stalk) > 0.60 was considered to indicate AWE. Atherosclerotic protein data was obtained from the peripheral blood. Aneurysmal characteristics included the maximal diameter of the cross-section (Dmax), location, type of IFA, presence of mural thrombus, and mural clots. Statistical analyses were performed with univariate analysis, logistic regression analysis, and Spearman's correlation coefficient. RESULTS: Seventy-one IFAs from 71 patients were included in the study. Multivariate analysis revealed statin use (OR = 0.189, p = 0.026) and apolipoprotein B (Apo-B) level (OR = 6.019, p = 0.026) were the independent predictors of AWE in IFAs. In addition, statin use (OR = 0.813, p = 0.036) and Apo-B level (OR = 1.610, p = 0.003) were also the independent predictors of CRstalk. Additionally, we found that CRstalk and AWE were significantly positively associated with Dmax (rs = 0.409 and 0.349, respectively; p < 0.001 and p = 0.003, respectively). CONCLUSIONS: There may be correlations between AWE, atherosclerotic protein levels, and aneurysm size in patients with IFAs. Apo-B and statin use were independent predictors of AWE in IFAs, which have the potential to be new therapeutic targets for IFAs. KEY POINTS: • There may be correlations between aneurysm wall enhancement, atherosclerotic protein levels in the peripheral blood, and aneurysm size in patients with intracranial fusiform aneurysms. • Apolipoprotein B and statin use were independent predictors of aneurysm wall enhancement in intracranial fusiform aneurysms.

Relationship between self-compassion and nonsuicidal self-injury in middle school students after earthquake: Gender differences in the mediating effects of gratitude and posttraumatic growth.

OBJECTIVE: The present study examined the mediating roles of gratitude and posttraumatic growth (PTG) in the association between self-compassion and nonsuicidal self-injury (NSSI). It also analyzed the gender differences in the mediating effect among Chinese adolescents after an earthquake. METHOD: This study assessed self-compassion, gratitude, PTG, and NSSI via self-report measures among 597 adolescents after earthquake. RESULTS: In the entire sample, positive self-compassion (PSC) had a negative effect on NSSI, whereas negative self-compassion (NSC) had a positive effect on it. In addition, gratitude and PTG played significant mediating roles between self-compassion and NSSI. In the male group, the mediating roles of gratitude and PTG in the correlation between self-compassion and NSSI were significant. In the female group, only gratitude had a significant mediating effect between PSC and NSSI. CONCLUSIONS: PSC was associated with low NSSI levels in adolescents, whereas NSC was associated with high NSSI levels. The mediating effects of gratitude and PTG on the relationship between self-compassion and NSSI were also different by gender. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

Inflow Angle Impacts Morphology, Hemodynamics, and Inflammation of Side-wall Intracranial Aneurysms.

BACKGROUND: Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. PURPOSE: To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. STUDY TYPE: Prospective. POPULATION: A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. FIELD STRENGTH/SEQUENCE: A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. STATISTICAL TESTS: Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. RESULTS: The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs  = 0.31), WSSavg-IA (rs  = -0.45), and AWE grades (rs  = 0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P = 0.901), Vavg-IA (P = 0.699), Vmax-IA (P = 0.482), Flowavg-IA (P = 0.550), Flowmax-IA (P = 0.689), WSSavg-IA (P = 0.573), and AWE grades (P = 0.872). DATA CONCLUSION: A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

In Situ Growth of Tunable Gold Nanoparticles by Titania Nanotubes Templated Electrodeposition for Improving Osteogenesis through Modulating Macrophages Polarization.

Driving macrophages M2 polarization has attracted growing attention for improving osteogenesis. Here, the in situ growth of tunable gold nanoparticles (AuNPs) on titania nanotubes (TiNTs) array was realized by electrodeposition, with the guidance of TiNTs. The fabricated Au layer showed excellent biocompatibility with different osteoimmune effects. Briefly, the Au deposition on 5 and 10 V anodized TiNTs surface could induce RAW264.7 cells to M2 polarization, whereas the Au deposition on 20 V anodized TiNTs surface showed M1 polarization, as indicated by various markers determination through immunofluorescence staining, qPCR, Western blot, and ELISA. Furthermore, the osteogenic differentiation of MC3T3-E1 was significantly enhanced by the macrophages conditioned medium from the Au@10VNTs surface. The in vivo tests also confirmed denser and thicker new trabecula bone formation and more M2 macrophages infiltration both on and adjacent to the Au@10VNTs implant surface. In mechanism, the cytokine array analysis of macrophages conditioned medium from the Au@10VNTs surface revealed the upregulation of pro-healing cytokines such as IL-10 and VEGF and downregulation of pro-inflammatory cytokines such as IL-1ß and MCSF. In addition, the NF-κB pathway was significantly inhibited. In conclusion, the electrodeposition of a Au layer guided by TiNTs is a promising strategy for reducing postoperative inflammatory reactions and improving osseointegration through modulating macrophages polarization.

Gut microbiota is associated with differential metabolic characteristics: A study on a defined cohort of Africans and Chinese.

Objective: This study intended to determine the associations between gut microbiota and glucose response in healthy individuals and analyze the connection between the gut microbiome and glucose-metabolism-related parameters. Methods: Fecal bacterial composition and anthropometric, body composition, body fat distribution, and biochemical measures were analyzed. A 75-g oral glucose tolerance test (OGTT) was given to each participant to investigate changes in glucagon-like peptide 1 (GLP-1), insulin, and glucose. The whole body fat and the regions of interest of local body composition were analyzed using dual-energy X-ray absorptiometry (DEXA), and gut microbiota composition was assessed through variable regions (V3-V4) of the bacterial 16s ribosomal RNA gene using high-throughput sequencing techniques. Spearman correlation analysis was used to evaluate the association between gut microbiota and clinical and metabolic changes. Results: The number of operational taxonomic units (OTUs) demonstrated a reduction in the diversity and composition of gut microbiota associated with enhanced adiposity, dyslipidemia, insulin resistance, and hyperglycemia. The alpha diversity revealed that microbiota diversity, richness, and composition were higher in the African group and lower in the Chinese group. Principal coordinates analysis (PCoA) plots of beta diversity showed significant variability in gut microbial community structure between the two groups (p = 0.0009). LEfSe analysis showed that phylum Bacteroidetes was significantly more abundant in the Chinese group, and this group also harbored members of the order Bacteroidales, family Bacteroidaceae, and genus Bacteroides. In contrast, the phylum Verrucomicrobia was significantly more prevalent in the African group (all p < 0.05). Concerning species, metastats analysis revealed 8 species in the Chinese group and 18 species in the African group that were significantly abundant. Spearman's correlation analysis demonstrated that gut microbiota correlated with the factors that related to glucose metabolism. Conclusion: Our data suggest that there is an interaction between gut microbiota, host physiology, and glucometabolic pathways, and this could contribute to adiposity and pathophysiology of hyperlipidemia, insulin resistance, and hyperglycemia. These findings provide an important basis for determining the relation between the gut microbiota and the pathogenesis of various metabolic disorders.

Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing.

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes (HDs) with integrin α6ß4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6ß4, which can promote adhesion, migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules, including integrin α6ß4, LN332 and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.

Independent predictors and risk score for intraprocedural rupture during endovascular treatment of small ruptured intracranial aneurysms (<5 mm).

Background and purpose: Intraprocedural rupture (IPR) is a devastating complication of endovascular treatment (EVT). Small-sized and ruptured aneurysms are independent predictors of IPR, which presents a technical challenge during EVT. We aimed to develop a score to quantify the individual patient risk of IPR in the EVT of small (<5 mm) ruptured aneurysms (SRAs). Methods: A retrospective review was conducted to interrogate databases prospectively maintained at two academic institutions in China from January 2009 to October 2016. We collected intraoperative angiograms and medical records to identify independent predictors of IPR using univariate and multivariable analyses. A risk score for IPR was derived using multivariable logistic regression analyses. Results: Of the 290 enrolled patients, IPR occurred in 16 patients (5.5%). The univariate analysis showed that the rate of IPR was significantly higher in patients having aneurysms with a small basal outpouching (SBO), in patients having aneurysms concomitant with adjacent moderate atherosclerotic stenosis (ACAMAS), and in former or current smokers. Multivariate analyses showed that SBO [odds ratio (OR): 3.573; 95% confidence interval (CI): 1.078-11.840; p = 0.037], vascular eloquence (VE; OR: 3.780; 95% CI: 1.080-13.224; p = 0.037), and ACAMAS (OR: 6.086; 95% CI: 1.768-20.955; p = 0.004) were significantly and independently associated with IPR. A three-point risk score (S-V-A) was derived to predict IPR [SBO (yes = 1), VE (yes = 1), and ACAMAS (yes = 1)]. Conclusions: Intraprocedural rupture occurred in 5.5% of the patients during EVT of SRA. SBO, VE, and ACAMAS were independent risk factors of IPR in the EVT of SRA. Based on these variables, the S-V-A score may be useful in predicting IPR daily, but more confirmation studies are required.