Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.

Apoptotic vesicles (apoVs) play a vital role in various physiological and pathological conditions. However, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs). Here, we proved that systemic infusion of MSCs derived from wild-type (WT) mice rather than from ovariectomized (OVX) mice effectively improved the osteopenia phenotype and rescued the impaired recipient MSCs in osteoporotic mice. Meanwhile, apoVs derived from WT MSCs (WT apoVs) instead of OVX apoVs efficiently restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-ß/Smad 2/3-Wnt/ß-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. The differential expression of miR-145a-5p is responsible for the distinct efficacy between the two types of apoVs. Overall, our findings unveil the remarkable potential of apoVs, as a novel nongenetic engineering approach, in rescuing the biological function and therapeutic capability of MSCs derived from patients. This discovery offers a new avenue for exploring apoVs-based stem cell engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.

Functional Insights in PLS3-Mediated Osteogenic Regulation.

Plastin-3 (PLS3) encodes T-plastin, an actin-bundling protein mediating the formation of actin filaments by which numerous cellular processes are regulated. Loss-of-function genetic defects in PLS3 are reported to cause X-linked osteoporosis and childhood-onset fractures. However, the molecular etiology of PLS3 remains elusive. Functional compensation by actin-bundling proteins ACTN1, ACTN4, and FSCN1 was investigated in zebrafish following morpholino-mediated pls3 knockdown. Primary dermal fibroblasts from six patients with a PLS3 variant were also used to examine expression of these proteins during osteogenic differentiation. In addition, Pls3 knockdown in the murine MLO-Y4 cell line was employed to provide insights in global gene expression. Our results showed that ACTN1 and ACTN4 can rescue the skeletal deformities in zebrafish after pls3 knockdown, but this was inadequate for FSCN1. Patients' fibroblasts showed the same osteogenic transdifferentiation ability as healthy donors. RNA-seq results showed differential expression in Wnt1, Nos1ap, and Myh3 after Pls3 knockdown in MLO-Y4 cells, which were also associated with the Wnt and Th17 cell differentiation pathways. Moreover, WNT2 was significantly increased in patient osteoblast-like cells compared to healthy donors. Altogether, our findings in different bone cell types indicate that the mechanism of PLS3-related pathology extends beyond actin-bundling proteins, implicating broader pathways of bone metabolism.

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. CASE PRESENTATION: This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. CONCLUSIONS: These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Therapeutic Effects of PEG-Modified Polyamide Amine Dendrimer for Cell Free DNA Adsorption in Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.

Evaluation of clinical impact of two types of Temporomandibular joint disc reduction and fixation.

OBJECTIVE: To evaluate the clinical effectiveness and stability of open suture versus micro-screw anchored disc reduction and fixation in treating disc displacement without reduction in the anterior temporomandibular joint. METHODS: A total of 38 patients (51 sides) with anterior disc displacement without reduction (ADDwR) of the TMJ treated in our hospital from August 2021 to January 2023 were selected, including 19 cases in group A (23 sides) treated with open temporomandibular joint disc reduction and anchorage, and 19 cases in group B (28 sides) treated with temporomandibular joint disc reduction and suture. The Magnetic Resonance Imaging (MRI) data of the two groups before and after operation were compared to evaluate the effective rate of articular disc reduction, the change of articular disc length, The Maximal Interincisal Opening (MIO) and Numeric Rating Scale (NRS) were measured before and after operation. RESULTS: In group A, the MRI effective rate 6 months after disc reduction was 95.65 % (22/23), the disc length gain was 1.74 mm, MIO was 40.32±5.067 mm, and NRS was 0.47±0.697. The MRI effective rate 6 months after disc reduction in group B was 100 % (28/28). The disc length gain was 1.78 mm, MIO was 41.58±3.746 mm, and NRS was 0.00. There was no significant difference between the two groups (P > 0.05). CONCLUSIONS: TMJ disc reduction and suture and open TMJ disc anchorage can effectively reduce the TMJ disc. The TMJ disc stability is high at 6 months after operation, and the pain and mouth opening can be improved, which is worthy of further promotion in clinical practice.

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.

Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs) and regulating tissue homeostasis. Here, we proved that systemic infusion of bone marrow MSCs derived from wild-type (WT) mice effectively improved the osteopenia phenotype and hyperimmune state in ovariectomized (OVX) mice. Importantly, the WT MSCs rescued the impairment of OVX MSCs both in vivo and in vitro, whereas OVX MSCs did not show the same efficacy. Interestingly, treatment with apoVs derived from WT MSCs (WT apoVs) restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. This effect was not observed with OVX MSCs-derived apoVs (OVX apoVs) treatment. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-ß/Smad 2/3-Wnt/ß-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. Conversely, treatment with OVX apoVs did not produce significant effects due to their limited expression of miR-145a-5p. Overall, our findings unveil the remarkable potential of apoVs in rescuing the biological function and therapeutic capability of MSCs derived from individuals with diseases. This discovery offers a new avenue for exploring apoVs-based MSC engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.

Digital measurement of deciduous tooth dimensions in China: A cross-sectional survey.

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.

Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration.

Comparative study of clinical and MRI features of TMD patients with or without joint effusion: a retrospective study.

BACKGROUND: The relationship between joint effusion and temporomandibular disorders (TMD) remains unclear. The purpose of this study was to investigate the correlation among joint effusion, clinical features and MRI imaging features of TMD. METHODS: A total of 1532 temporomandibular joints (TMJs) from 766 patients (605 females and 161 males) with the mean age of 31.68 ± 13.71 years from January 2022 to June 2023 were included in the study. Clinical and MRI features were collected and analyzed. Chi-Square test, Spearman correlation coefficient and binary logistic regression analysis were performed. RESULTS: Patients with joint effusion were significantly older and had smaller value of MIO (p < 0.001). There were significant differences in the distribution of joint sounds (with or without), joint pain (with or without), disc morphology (biconcave, contracture, irregular and lengthened) and disc position between joint effusion group (JE) and non-joint effusion group (NA) (P < 0.05).The odds of having joint effusion were 1.726 higher in patients with joint sounds when compared to those without joint sounds. The odds of having joint effusion were 8.463 higher in patients with joint pain when compared to those without joint pain. The odds of having joint effusion were 2.277 higher in patients with contracture when compared to those with biconcave. The odds of having joint effusion were 1.740 higher in patients with anterior disc displacement with reduction (ADDWR) when compared to those with normal disc position. The prediction accuracy of this model is 74.9%, and the area under curve (AUC) is 79.5%, indicating that it can be used for the prediction and the judgment effect is average. CONCLUSIONS: The results demonstrated that joint sounds, joint pain, contracture, and ADDWR are high risk factors for joint effusion, especially joint pain. TRIAL REGISTRATION: This study was retrospectively registered on 28/03/2022 and endorsed by the Ethics Committee of Affiliated Stomatology Hospital of Guangzhou Medical University (LCYJ2022014).

260 fs, 403 W coherently combined fiber laser with precise high-order dispersion management.

An ultrafast fiber laser system comprising two coherently combined amplifier channels is reported. Within this system, each channel incorporates a rod-type fiber power amplifier, with individual operations reaching approximately 233 W. The active-locking of these coherently combined channels, followed by compression using gratings, yields an output with a pulse energy of 504 µJ and an average power of 403 W. Exceptional stability is maintained, with a 0.3% root mean square (RMS) deviation and a beam quality factor M2 < 1.2. Notably, precise dispersion management of the front-end seed light effectively compensates for the accumulated high-order dispersion in subsequent amplification stages. This strategic approach results in a significant reduction in the final output pulse duration for the coherently combined laser beam, reducing it from 488 to 260 fs after the gratings compressor, while concurrently enhancing the energy of the primary peak from 65% to 92%.

Clean hundred-µJ-level sub-6-fs blue pulses generated with helium-assisted solid thin plates.

In this work, 85 µJ, 5.5 fs pulses spanning 350-500 nm with 96% energy concentrated on the main pulse are generated by pulse compression using a helium-assisted, two-stage solid thin plate apparatus. To the best of our knowledge, these are the highest energy sub-6 fs blue pulses obtained to date. Furthermore, during the spectral broadening process, we observe that solid thin plates are much more easily damaged by blue pulses in a vacuum than in a gas-filled environment at the same field intensity. Helium, with the highest ionization energy and extremely low material dispersion, is adopted to create a gas-filled environment. Thus, the damage to solid thin plates is eliminated, and high-energy, clean pulses can be obtained with only two commercially available chirped mirrors in a chamber. Furthermore, the excellent output power stability of 0.39% root mean square (rms) fluctuations over 1 h is maintained. We believe that few-cycle blue pulses at the hundred-µJ level can open the door to numerous new ultrafast and strong-field applications in this spectral region.

Human Salivary Histatin-1 Attenuates Osteoarthritis through Promoting M1/M2 Macrophage Transition.

Osteoarthritis (OA) is an inflammation-driven degenerative joint disease. Human salivary peptide histatin-1 (Hst1) shows pro-healing and immunomodulatory properties. but its role in OA treatment is not fully understood. In this study, we investigated the efficacy of Hst1 in the inflammation modulation-mediated attenuation of bone and cartilage damage in OA. Hst1 was intra-articularly injected into a rat knee joint in a monosodium iodoacetate (MIA)-induced OA model. Micro-CT, histological, and immunohistochemical analyses showed that Hst1 significantly attenuates cartilage and bone deconstruction as well as macrophage infiltration. In the lipopolysaccharide-induced air pouch model, Hst1 significantly reduced inflammatory cell infiltration and inflammation. Enzyme-linked immunosorbent assay (ELISA), RT-qPCR, Western blot, immunofluorescence staining, flow cytometry (FCM), metabolic energy analysis, and high-throughput gene sequencing showed that Hst1 significantly triggers M1-to-M2 macrophage phenotype switching, during which it significantly downregulated nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways. Furthermore, cell migration assay, Alcian blue, Safranin O staining, RT-qPCR, Western blot, and FCM showed that Hst1 not only attenuates M1-macrophage-CM-induced apoptosis and matrix metalloproteinase expression in chondrogenic cells, but it also restores their metabolic activity, migration, and chondrogenic differentiation. These findings show the promising potential of Hst1 in treating OA.

Extracellular vesicles in osteoarthritis of peripheral joint and temporomandibular joint.

Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and temporomandibular joint (TMJ). As a representative of peripheral joint OA, knee OA shares similar symptoms with TMJ OA. However, these two joints also display differences based on their distinct development, anatomy, and physiology. Extracellular vesicles (EVs) are phospholipid bilayer nanoparticles, including exosomes, microvesicles, and apoptotic bodies. EVs contain proteins, lipids, DNA, micro-RNA, and mRNA that regulate tissue homeostasis and cell-to-cell communication, which play an essential role in the progression and treatment of OA. They are likely to partake in mechanical response, extracellular matrix degradation, and inflammatory regulation during OA. More evidence has shown that synovial fluid and synovium-derived EVs may serve as OA biomarkers. More importantly, mesenchymal stem cell-derived EV shows a therapeutic effect on OA. However, the different function of EVs in these two joints is largely unknown based on their distinct biological characteristic. Here, we reviewed the effects of EVs in OA progression and compared the difference between the knee joint and TMJ, and summarized their potential therapeutic role in the treatment of OA.

The contribution of subliminal perceptions, dietary habits, and psychological traits to the perception of oral tingling and burning sensations.

The tingling evoked by Sichuan pepper and the burning elicited by chili pepper constitutes the typical flavor of Sichuan cuisine and is a component of leisure food. Although factors affecting the burning sensation have extensively been studied, few studies have examined the factors of individual sensitivity, personality traits, and dietary habits that contribute to the perception of oral tingling sensation, which hinders the formulation of tingling products and the development of new products. In contrast, many studies have examined the factors influencing the burning sensation. In this web-based survey, 68 participants disclosed their dietary habits, liking for tingling and hot foods, and psychological traits. Individual sensitivity to the tingling and burning sensation produced by a range of Sichuan pepper oleoresin and capsaicin solutions was determined using rated differences from control, generalized labeled magnitude scale method and ranking test. The consistency score indicated the accuracy of individual ranking results while also providing an indirect response to the sensitivity of the participant to supra-threshold for burning or tingling. Individual ratings for medium Sichuan pepper oleoresin concentrations significantly correlated with the just noticeable difference (p < 0.01), and ratings for medium and high capsaicin concentrations correlated significantly with 6-n-propylthiouracil ratings (p < 0.01). Notably, the power exponent of burning was significantly correlated with the burning recognition threshold (p < 0.01), and the power exponent of tingling and burning were significantly correlated (r = 0.340, p < 0.05). There was a negative correlation between supra-threshold tingling and burning sensation perceptions and life satisfaction ratings. Further, intensity ratings for oral tingling and burning sensation did not always correspond with individual sensitivity indicators (e.g., recognition threshold, 6-n-propylthiouracil, just noticeable difference, and consistency score). Thus, this study provides new insight into establishing a sensory selection method for chemesthetic sensation panelists and theoretical guidelines for formulation design and in-depth analysis of popular tingling dishes and foods.

Comparison of imaging findings of 714 symptomatic and asymptomatic temporomandibular joints: a retrospective study.

BACKGROUND: The correlation between temporomandibular disorders (TMD) and imaging features remains unclear. This study compared the cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI) features in the temporomandibular joints (TMJs) with and without TMD symptoms. METHODS: The participants were recruited from the TMJ Diagnosis and Treatment Center from March 2022 to September 2022. Condylar morphology and condylar position were evaluated by CBCT. Disc morphology, disc position, and joint effusion were evaluated by T2-weighted image of MRI. The Chi-Square test and binary logistic regression analysis were carried out. RESULTS: Eighty-two patients with bilateral symptoms, 196 patients with unilateral symptoms, and 79 asymptomatic participants received MRI and CBCT examination. There were significant differences in the distribution of sex, age, condylar morphology, condylar position, disc morphology, disc position, and joint effusion in symptomatic and asymptomatic TMJs (P < 0.05), which showed a positive correlation with symptoms (P < 0.05). In multiple logistic regression, 19-30-year-age group, > 30-year-age group, abnormal condylar morphology, posterior condylar position, disc displacement with reduction (DDWR), and disc displacement without reduction (DDWoR) were found to be statistically significant (P < 0.05). The odds of having symptomatic TMJ were 1.952 higher in the 19-30-year-age group and 1.814 higher in the > 30-year-age group when compared to those aged ≤ 18-year-age group. The odds of having symptomatic TMJ were 2.360 higher in persons with abnormal condylar morphology when compared to those with normal condylar morphology. The odds of having symptomatic TMJ were 2.591 higher in persons with posterior condylar position when compared to those with the normal condylar position. The odds of having symptomatic TMJ were 2.764 higher in persons with DDWR and 4.189 higher in persons with DDWoR when compared to those with normal disc position. The area under the curve of the model was 0.736 ± 0.019 (95% CI 0.700-0.773, P = 0.000), which indicated that the model has a good fitting effect. CONCLUSIONS: The imaging findings of TMJs were significantly different between symptomatic and asymptomatic TMJs. TMD is affected by multiple factors including > 19-year-age, abnormal condylar morphology, posterior condylar position, DDWR, and DDWoR, which could be risk factors for the development of TMD symptoms. Trial registration This study was retrospectively registered on 28/03/2022 and endorsed by the Ethics Committee of Affiliated Stomatology Hospital of Guangzhou Medical University (LCYJ2022014).

Correlation of patients' demographics and clinical symptoms with temporomandibular disorders.

OBJECTIVE: To investigate the correlation between basic characteristics and clinical features of patients with temporomandibular disorders (TMD). METHODS: The R language statistical tool was used to analyze the clinical information of 500 TMD patients, i.e., age, sex, joint noises, mouth opening pattern, and pain symptoms, as well as the results of the mandibular push-back test. A pairwise correlation analysis of each clinical feature was carried out. RESULTS: The highest incidence of TMD was observed in the age group of 20 to 30 years (240/500). Around 2/3 of the patients showed pain symptoms. Abnormal mouth opening patterns, joint noises, and temporomandibular joint synovitis (TMJS) were observed in 48.4, 65.4, and 34% of patients, respectively. CONCLUSION: Joint click and the corrected deviation of the mouth opening pattern are signs of early-stage TMD, whereas limited mouth opening and TMJS are indicators of progressive stage and complicated TMD.

Comparison of magnetic resonance imaging findings in 880 temporomandibular disorder patients of different age groups: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) in temporomandibular disorder (TMD) patients of different ages are still unclear. The aim of this study was to analyze and compare the characteristics of MRI features of TMJs in different age groups. METHODS: A total of 1760 TMJs from 880 patients were included in the study and divided into three groups: ≤ 18Y (n = 195, 14.89 ± 2.35Y); 19-30Y (n = 475, 24.09 ± 3.23Y); and > 30Y (n = 210, 41.73 ± 10.45Y). T2-weighted image (T2WI) of MRI was obtained to evaluate the relationship between age and disc morphology, the degree of disc displacement, joint effusion, joint movement and changes of condylar bone morphology. Data were analyzed by Pearson Chi square test and Spearman correlation coefficient. RESULTS: There was no statistical difference between left and right sides in all age groups. Except condylar morphology (χ2 = 0.943, P = 0.624), there were significant differences in the distribution of disc morphology, disc position, joint effusion and joint motion among different age groups (χ2 = 24.450, χ2 = 24.829, χ2 = 19.855, χ2 = 39.259, respectively). There were significant differences in the distribution of the degree of anterior disc displacement, condyle morphology and joint effusion in different types of disc morphology among the different age groups (except for joint effusion in > 30Y), among which the first two were significantly correlated with the disc morphology. CONCLUSIONS: The morphology and position of the articular disc changed significantly with age, but the proportion of abnormal condylar bone remained about 50%. The greater the degree of disc folding, the more prone to bone abnormalities. Trial registration This study was retrospectively registered on 28/03/2022 and endorsed by the Ethics committee (LCYJ2022014).

Differential Proteomic Profiles of Coronary Serum Exosomes in Acute Myocardial Infarction Patients with or Without Diabetes Mellitus: ANGPTL6 Accelerates Regeneration of Endothelial Cells Treated with Rapamycin via MAPK Pathways.

PURPOSE: Delayed re-endothelialization after coronary drug-eluting stent implantation is associated with an increased incidence of late in-stent thrombosis. Serum exosomes exhibit controversial effects on promoting endothelialization. This study aimed to compare the angiogenic effects of serum exosomes derived from patients with acute myocardial infarction (AMI) and AMI plus diabetes mellitus (DM) and to explore the underlying mechanisms. METHODS: Serum exosomes derived from patients in the control (Con-Exos), AMI (AMI-Exos), and AMI plus DM (AMI+DM-Exos) groups were isolated and identified using standard assays. CCK-8, wound healing, and tube formation assays were performed to detect the angiogenic abilities of serum exosomes on rapamycin-conditioned human umbilical vein endothelial cells (HUVECs). Differential proteomic profiles between AMI-Exos and AMI+DM-Exos were analyzed by mass spectrometry. The effects and potential mechanisms of exosomal angiopoietin-like 6 (ANGPTL6) were investigated. RESULTS: Functional assays indicated that compared with Con-Exos, AMI-Exos enhanced, whereas AMI+DM-Exos inhibited the cell proliferation, migration, and tube formation of rapamycin-conditioned HUVECs. Subsequently, 28 differentially expressed proteins between AMI-Exos and AMI+DM-Exos were identified, which were correlated with material transportation, immunity, and inflammatory reaction. Moreover, ANGPTL6 was highly enriched in AMI-Exos. Overexpression and knockdown of ANGPTL6 enhanced and inhibited angiogenesis, respectively. Furthermore, the effect of ANGPTL6 on angiogenesis was mediated via the activation of ERK 1/2, JNK, and p38 pathways. The inhibition of ERK 1/2 signaling markedly attenuated the migration abilities of overexpressing ANGPTL6. CONCLUSION: Diabetes impairs the regenerative capacities of serum exosomes. Exosomal ANGPTL6 contributes to endothelial repair and is a novel therapeutic target for enhanced stent endothelization.

Full experimental determination of tunneling time with attosecond-scale streaking method.

Tunneling is one of the most fundamental and ubiquitous processes in the quantum world. The question of how long a particle takes to tunnel through a potential barrier has sparked a long-standing debate since the early days of quantum mechanics. Here, we propose and demonstrate a novel scheme to accurately determine the tunneling time of an electron. In this scheme, a weak laser field is used to streak the tunneling current produced by a strong elliptically polarized laser field in an attoclock configuration, allowing us to retrieve the tunneling ionization time relative to the field maximum with a precision of a few attoseconds. This overcomes the difficulties in previous attoclock measurements wherein the Coulomb effect on the photoelectron momentum distribution has to be removed with theoretical models and it requires accurate information of the driving laser fields. We demonstrate that the tunneling time of an electron from an atom is close to zero within our experimental accuracy. Our study represents a straightforward approach toward attosecond time-resolved imaging of electron motion in atoms and molecules.

Temporomandibular joint synovial chondromatosis: An analysis of 7 cases and literature review.

OBJECTIVE: To investigate the diagnosis and treatment procedure of synovial chondromatosis (SC) of the temporomandibular joint (TMJ). METHODS: Clinical features, imaging features, surgical methods, and prognosis of 7 patients with SC of the TMJ were analyzed. We also reviewed and analyzed surgery-relevant literature included in the Pubmed database in the past decade using the search terms "synovial chondromatosis" and "temporomandibular joint", and found 181 cases. RESULTS: There was no specific difference in the symptoms of SC in the TMJ in different Milgram's stages in our cases and the cases mentioned in the literature. The main symptoms of SC in the TMJ were pain (100%, 7/7; 64.64%, 117/181), limited mouth opening (57.14%, 4/7; 53.59%, 97/181), swelling (14.29%, 1/7; 28.18%, 51/181), crepitus (28.57%, 2/7; 19.34%, 35/181), and clicking (14.29%, 1/7; 9.94%, 18/181) in our cases and cases from literature separately. The imaging features of SC were occupying lesions (including loose bodies or masses) (71.42%, 5/7; 37.57%, 68/181), bone change in condyle or glenoid fossa (1/7, 14.29%; 34.81%, 63/181), effusion (42.86%, 3/7; 20.99%, 38/181), joint space changes (42.86%, 3/7; 11.05%, 20/181) in our cases and cases from literature separately. The surgical procedures seem to depend mainly on the involved structures and the extension of the lesion rather than the Milgram's stage. CONCLUSIONS: The clinical features of SC in the TMJ are nonspecific and easy to be misdiagnosed. MRI is helpful in the diagnosis of SC in the TMJ. The surgical procedures mainly depend on the involved structures and the extension of the lesion.