How Do the Position and Number of Methyl Substituents Affect the Photochemical Process of Criegee Intermediate? Trajectory Surface-Hopping Dynamics of Four-Carbon CIs.

Electronic-structure calculations combined with nonadiabatic trajectory surface-hopping (TSH) dynamic simulations were carried out on two alkenyl-substituted Criegee intermediates (CIs), i.e., propenyl-substituted CI (PCI) and 1-methyl-propenyl substituted CI (MPCI), in order to investigate the influence of the position and number of substituents on the photochemical process of CI in S1 states. It is found that they play critical roles in the reactivity, dominant product channel, and mechanism of the CIs. More specifically, introducing a methyl group on either C1 (α-C) or C3 (γ-C) position of a vinyl-substituted CI (VCI) skeleton facilitates the rotation of the C1═O1 bond and leads to the formation of a three-membered dioxirane ring; meanwhile, it evidently enhances the reactively of the S1-state molecule. Meanwhile, methyl substitution on the vinyl moiety [i.e., C2 (ß-C) and C3 (γ-C) positions] is beneficial for the rotation of the C2═C3 bond and thus facilitates the formation of the five-membered 1,2-dioxole ring, and the substitution on C2 site decreases the reactivity. The cosubstitution of C2 and C3 atoms by methyl groups well balances the features of VCI in the sense of high reactivity, consistently predominant channel, and possible dioxole side-product. The findings here not only deepen the knowledge on the photochemical processes of the CI but also inspire the rethinking of the "old" concept of substitution effect.

Chitosan nanomedicines-engineered bifidobacteria complexes for effective colorectal tumor-targeted delivery of SN-38.

The clinical application of 7-ethyl hydroxy-camptothecin (SN-38) maintains challenges not only due to its poor solubility and stability but also the lack of effective carriers to actively deliver SN-38 to deep tumor sites. Although SN-38-based nanomedicines could improve the solubility and stability from different aspects, the tumor targeting efficiency remains very low. Leveraging the hypoxic taxis of bifidobacteria bifidum (B. bifi) to the deep tumor area, we report SN-38-based nanomedicines-engineered bifidobacterial complexes for effective tumor-targeted delivery. Firstly, SN-38 was covalently coupled with poly-L-glutamic acid (L-PGA) and obtained soluble polymeric prodrug L-PGA-SN38 to improve its solubility and stability. To prolong the drug release, L-PGA-SN38 was mildly complexed with chitosan to form nanomedicines, and nanomedicines engineered B. bifi were further elaborated via electrostatic interaction of the excess of cationic chitosan shell from nanomedicines and anionic teichoic acid from B. bifi. The engineered B. bifi complexes inherited the bioactivity of native B. bifi and exhibited distinctly enhanced accumulation at the tumor site. More importantly, significantly elevated anti-tumor efficacy was achieved after the treatment of CS-L-PGA-SN38 NPs/B. bifi complexes, with favorable tumor suppression up to 80%. Such a B. bifi-mediated delivery system offers a promising platform for effective drug delivery and enhanced drug accumulation in the hypoxia deep tumor with superior anti-tumor efficacy.

Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression.

Most nanomedicines with suitable sizes (normally 100-200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) -triggered size-shrinkable micelle system (Fe3O4@AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe3O4@AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe3O4@AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe3O4@Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe3O4@AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe3O4@AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration.

Imperatorin ameliorates pulmonary fibrosis via GDF15 expression.

Background: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to myofibroblasts, and accumulation of matrix proteins. Hypothesis/purpose: Imperatorin shows anti-inflammatory effects on alveolar macrophages against acute lung injury. We attempt to evaluate the properties of imperatorin on the basis of fibroblasts. Methods: In in vitro, zymosan was introduced to provoke pro-fibrotic responses in NIH/3T3 or MRC-5 pulmonary fibroblasts. Imperatorin was given for examining its effects against fibrosis. The mice were stimulated by bleomycin, and imperatorin was administered to evaluate the prophylactic potential in vivo. Results: The upregulated expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen protein due to zymosan introduction was decreased by imperatorin in fibroblasts. Zymosan induced the activity of transglutaminase 2 (TGase2) and lysyl oxidase (LOX), which was also inhibited by the administration of imperatorin. Imperatorin alone enhanced sirtuin 1 (SIRT1) activity and growth differentiation factor 15 (GDF15) secretion in fibroblasts via LKB1/AMPK/CREB pathways. In addition, GDF15 exerted a beneficial effect by reducing the protein expression of CTGF, α-SMA, and collagen and the activities of TGase and LOX. Moreover, orally administered imperatorin showed prophylactic effects on bleomycin-induced pulmonary fibrosis in mice. Conclusion: Imperatorin reduces fibrotic marker expression in fibroblasts and also increases GDF15 secretion via the LKB1/AMPK/CREB pathway, attenuating pro-fibrotic responses in vitro. Imperatorin also alleviates pulmonary fibrosis induced by bleomycin in vivo.

Escherichia coli Nissle 1917-driven microrobots for effective tumor targeted drug delivery and tumor regression.

Potent tumor regression remains challenging due to the lack of effective targeted drug delivery into deep tumors as well as the reduced susceptibility of cancer cells to anticancer agents in hypoxic environments. Bacteria-driven drug-delivery systems are promising carriers in overcoming targeting and diffusion limits that are inaccessible for conventional antitumor drugs. In this study, probiotic facultative anaerobe Escherichia coli Nissle 1917 (EcN) was functionalized and formed self-propelled microrobots to actively deliver therapeutic drug and photosensitizer to the deep hypoxic regions of tumors. Doxorubicin (Dox) was firstly modified with cis-aconityl anhydride (CA) and terminal thiol-decorated hydrazone derivative (Hyd-SH) through dual pH-sensitive amide and imine bonds, respectively. The functionalized CA-Dox-Hyd-SH was further coordinated with photosensitizer gold nanorods (AuNRs) and then conjugated to the surface of EcN. The resulting microrobots (EcN-Dox-Au) inherited the mobility characteristics and bioactivity of native EcN. Upon the irradiation of NIR laser, the microrobots exhibited enhanced tumor accumulation and penetration into the deep hypoxia tumor site. Strikingly, after 21 days of treatment with EcN-Dox-Au formulations, complete tumor regression was achieved without relapse for at least 53 days. This self-propelled strategy utilizing bacteria-driven microrobots provides a promising paradigm for enhancing drug penetration and elevating chemosensitivity, resulting in a superior antitumor effect. STATEMENT OF SIGNIFICANCE: Self-propelled Escherichia coli Nissle 1917 (EcN) - mediated microrobots are functionalized to co-deliver therapeutic drugs and photosensitizers to the deep tumor site. Anti-tumor drug doxorubicin (Dox) was modified through dual pH-sensitive bonds on both terminals and then linked with EcN and photosensitizer gold nanorods (AuNRs) to realize tumor microenvironment acidic pH-responsive drug release. Upon irradiation with a NIR laser near the tumor site, AuNRs produced a photothermal effect which realized the superficial tumor thermal ablation and increased the permeability of the tumor cell membrane to facilitate the penetration of microrobots. Moreover, the deep penetration of microrobots also enhanced the susceptibility of the cancer cells to Dox, and realized the complete tumor regression in the established breast cancer-bearing mice without recurrence using a lower dose of drug regimen.

Theoretical Insights into Aggregation-Induced Emission with the Ionic π Fluorophore: The Importance of Choosing the Dimer QM Model in the ONIOM Study.

In understanding the mechanism of aggregation-induced emission (AIE), the multilevel ONIOM framework has been demonstrated as one of the efficient tools that can capture the essential mechanistic information by choosing a single fluorophore as the quantum mechanics (QM) model and putting all surrounding molecules in the low-level region. Recently, the ionic styryl-pyridine salt (namely, SPH) has been reported as a new class of AIEgen with a high fluorescence yield. In the SPH crystal, a pair of ionic SPH molecules are closely stacked with each other in an antiparallel, head-to-tail pattern, thus the choice of QM models (an individual or dimeric structure) becomes critical in the ONIOM study. Herein we report the AIE mechanism of the ionic SPH at the QM ((TD)-CAM-B3LYP) and ONIOM(QM:MM) levels. As usual, the fluorescence quenching of SPH in tetrahydrofuran (THF) solution is attributed to a nonradiative relaxation via the central C═C bond rotation, with a rather low barrier of 2.7 kcal/mol. In crystals, either with a monomer or dimer model, the fluorescence quenching channel is found to be restricted due to the obvious C═C rotation barriers. Compared with the monomer model, the dimer model, by treating the orbital interaction of the two SPH molecules at the QM level, provides significantly increased barriers and a red-shifted emission wavelength that better matches the experimental value. In addition, the calculated exciton coupling in the fluorescence emission state can be discovered only by a dimer model. The findings here emphasize not only the importance of choosing a proper model in the ONIOM study of AIE but also expanding our understanding of novel AIE systems.

Revisiting photocyclization of the donor-acceptor stenhouse adduct: missing pieces in the mechanistic jigsaw discovered.

Donor-acceptor Stenhouse adducts (DASA) have recently emerged as a class of visible-light-induced photochromic molecular switches, but their photocyclization mechanism remains puzzling and incomplete. In this work, we carried out MS-CASPT2//SA-CASSCF calculations to reveal the complete mechanism of the dominant channels and possible side reactions. We found that a new thermal-then-photo isomerization channel, i.e., EEZ → EZZ → EZE, other than the commonly accepted EEZ → EEE → EZE channel, is dominant in the initial step. Besides, our calculations rationalized why the expected byproducts ZEZ and ZEE are unobserved and proposed a competitive stepwise channel for the final ring-closure step. The findings here redraw the mechanistic picture of the DASA reaction by better accounting for experimental observations, and more importantly, provide critical physical insight in understanding the interplay between thermal- and photo-induced processes widely present in photochemical synthesis and reactions.

Tuning Water-Resistant Networks in Mussel-Inspired Hydrogels for Robust Wet Tissue and Bioelectronic Adhesion.

Hydrogels with robust wet adhesion are desirable for applications in aqueous environments. Wet adhesion arising from synergy between hydrophobic and catechol components in mussel foot proteins has been highlighted. However, optimizing hydrogels with multiple components is challenging because of their complex structure-property relationships. Herein, high-throughput screening of a series of hydrophobic alkyl monomers and adhesive catechol derivatives was used to systematically develop wet adhesive hydrogels. Short alkyl chains promote wet adhesion by repelling water at the adhesive interface, whereas long alkyl chains form strong hydrophobic interactions inside the hydrogel network that impede or dissipate energy for wet adhesion. The optimized wet adhesive hydrogel, containing short alkyl chain, was applied for rapid hemostasis and wound healing because of the synergistic effect of catechol and alkyl groups and its immunomodulation ability, which is revealed through a transcriptomic analysis. Conductive nanocomponents were incorporated into the optimized hydrogel to produce a wearable device, which was used for continuous monitoring human electrocardiogram (ECG) during swimming, and in situ epicardial ECG on a porcine living and beating heart. This study demonstrated an efficient and generalized molecular design strategy for multifunctional wet adhesive hydrogels.

The diagnostic potential of plasma SCUBE-1 concentration for pulmonary embolism: A pilot study.

INTRODUCTION: This study aimed to investigate the potential application of plasma signal peptide-complement C1r/C1s, Uegf and Bmp1-epidermal growth factor domain-containing protein 1 (SCUBE-1) as a biomarker in the diagnosis of pulmonary embolism (PE). METHODS: This cross-sectional study enrolled 177 patients who underwent PE diagnostic test and 87 healthy controls. The results of CT pulmonary angiogram (CTPA) were used as reference standards for PE diagnosis. The levels of SCUBE-1 and D-dimer in participants' plasma were detected with enzyme-linked immunosorbent assay and compared among patients with confirmed PE, suspicious PE and healthy controls. The diagnostic values were analysed using receiver operating characteristic (ROC) curve analysis. In addition, differences in plasma SCUBE-1 levels were compared among patients with different risk stratifications. RESULTS: The plasma SCUBE-1 concentration levels in patients with CTPA confirmed PE (14.28 ± 7.74 ng/ml) was significantly higher than those in the suspicious patients (11.11 ± 4.48 ng/ml) and in healthy control (4.40 ± 3.23 ng/ml) (P < 0.01). ROC curve analysis showed that at the cut-off of 7.789 ng/ml, SCUBE-1 has significant diagnostic value in differentiating PE patients from healthy control (AUC = 0.919, sensitivity = 81.25%, specificity = 92.13%), and the performance is more accurate than D-dimer (cut-off 273.4 ng/ml, AUC = 0.648, sensitivity = 65.75%, specificity = 67.42%). The combination of D-dimer with SCUBE-1 did not further improve the diagnostic value. However, SCUBE-1 did not show significant diagnostic value in identifying PE among suspicious patients There was no significant difference in SCUBE-1 level among different risk groups (P > 0.05). CONCLUSION: We believe that SCUBE-1 could be a potential coagulation-related marker for the diagnosis of PE.

Clinical and radiographic outcomes of customized allogeneic bone block versus autogenous bone block for ridge augmentation: 6 Month results of a randomized controlled clinical trial.

AIM: To evaluate the efficacy of customized allogeneic bone block (CABB) for ridge augmentation compared with autogenous bone block. MATERIALS AND METHODS: Patients (N = 24) in need of ridge augmentation were randomly assigned to one of two treatment modalities: CABBs (CABB group) and autogenous bone blocks (ABB group). The primary outcome of the present study was the horizontal bone gain at 1 mm below the alveolar ridge crest (HBG1 ). Secondary outcomes were the bone gain at other levels, bone resorption rate, ridge width, operative time, postoperative pain score, and histological results. The data obtained from the current study were analysed using a generalized linear mixed effects model, two-sample t-test, or a Mann-Whitney U-test. RESULTS: Twenty-four patients completed a 6-month follow-up. One patient in the CABB group exhibited block exposure. The CABB group had significantly more horizontal bone gain (HBG1 ) and less horizontal bone resorption (HBRR1 ) at 1 mm below the alveolar ridge crest when compared with those in the ABB group (HBG1 : CABB group [4.29 ± 1.48 mm] and ABB group [1.12 ± 3.25 mm]; HBRR0 : CABB group [42.15 ± 14.03%] and ABB group [92.52 ± 55.78%], p < .05). In addition, a longer operative time was reported in the ABB group compared with the CABB group (p < .05). The histological observation indicated a new bone formation in both groups. CONCLUSIONS: The use of CABBs resulted in more horizontal bone gain and less horizontal bone resorption at 1 mm below the alveolar ridge crest at 6 months post-surgery compared with ABBs while reducing the operative time in the treatment of ridge augmentation.

The photoisomerization mechanism of methacrolein oxide (MACR-OO): the cyclic dioxole formation pathway revealed.

Methacrolein oxide (MACR-OO), the isopropenyl substituted Criegee intermediate (CI), is one product of isoprene ozonolysis. In this work, we report MACR-OO's photo-isomerization paths with electronic structure calculation at the CASSCF and MS-CASPT2 levels and trajectory surface-hopping (TSH) nonadiabatic dynamics simulation at the CASSCF level. Our calculated results show that the ring-closure is the dominant photo-induced unimolecular isomerization of MACR-OO in the S1 state. In addition, a new photo-induced ring-closure to heterocyclopentane dioxole in syn_syn-MACR-OO is found. The findings of MACR-OO are expected to deepen the understanding of the substituted CIs and their photochemistry.

Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes.

Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge. Here, a polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment. PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold. The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+ channels. Moreover, the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity. It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages. The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive, ROS-scavenging, anti-inflammatory, and immunomodulatory abilities. This study provides fundamental insights into the synergistical effects of conductivity, osteoinductivity, and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.

Artificial intelligence for caries and periapical periodontitis detection.

OBJECTIVES: Periapical periodontitis and caries are common chronic oral diseases affecting most teenagers and adults worldwide. The purpose of this study was to develop an evaluation tool to automatically detect dental caries and periapical periodontitis on periapical radiographs using deep learning. METHODS: A modified deep learning model was developed using a large dataset (4129 images) with high-quality annotations to support the automatic detection of both dental caries and periapical periodontitis. The performance of the model was compared to the classification performance of dentists. RESULTS: The deep learning model automatically distinguished dental caries with an F1-score of 0.829 and periapical periodontitis with an F1-score of 0.828. The comparison of model-only and expert-only detection performance showed that the accuracy of the fully automatic method was significantly higher than that of the young dentists. With deep learning assistance, the experts not only reached a higher diagnostic accuracy with an average F1-score of 0.7844 for dental caries and 0.8208 for periapical periodontitis compared to expert-only scenarios, but also increased inter-observer agreement from 0.585/0.590 to 0.726/0.713 for dental caries and from 0.623/0.563 to 0.752/0.740 for periapical periodontitis. CONCLUSIONS: Based on these experimental results, deep learning can improve the accuracy and consistency of evaluating dental caries and periapical periodontitis on periapical radiographs. CLINICAL SIGNIFICANCE: Deep learning models can improve accuracy and consistency and reduce the workload of dentists, making artificial intelligence a powerful tool for clinical practice.

Epidemiological Characteristics of COVID-19 Resurgence in Areas Initially Under Control.

Objectives: To investigate the epidemiological characteristics and infection routes of new cases in order to provide information for preventing COVID-19 resurgence in areas initially under control. Methods: The information of new symptomatic and asymptomatic patients in Chinese mainland was collected. The location distribution, epidemic course, infection routes and patients' characteristics of outbreaks were described and analyzed. Results: There were 43 new outbreaks with 3,795 symptomatic patients in Chinese mainland from March 21, 2020 to June 13, 2021. These outbreaks mainly occurred in central, border and coastal port cities. The main infection route of first generation indigenous patients was contact with imported cases and contaminated goods or environments. The infection routes of secondary generation patients mainly included family transmission, indoor social gathering infection, nosocomial infection and other infection routes. Family transmission was the most common infection route, and indoor social gathering was the most important reason for the large-scale outbreaks. Conclusions: Strengthen the management of imported patients and staff in high-risk posts was the key point to avoid the first generation indigenous patients. Adequate family isolation, prompt management policies for indoor public place and monitor of population at risk of infection were key strategies for preventing COVID-19 resurgence in areas initially under control.

Lateral Ridge Augmentation with Guided Bone Regeneration Using Particulate Bone Substitutes and Injectable Platelet-Rich Fibrin in a Digital Workflow: 6 Month Results of a Prospective Cohort Study Based on Cone-Beam Computed Tomography Data.

This study aimed to test whether or not a digital workflow for GBR with particulate bone substitutes and injectable platelet-rich fibrin improved the thickness of the hard tissue compared to the conventional workflow. 26 patients in need of lateral bone augmentation were enrolled. GBR with particulate bone substitutes and injectable platelet-rich fibrin was performed in all patients. Patients were divided into two groups: control (conventional workflow; n = 14) and test (digital workflow; n = 12). CBCT scans were performed before surgery, immediately after wound closure, and 6 months post-surgery, and the labial thickness of the hard tissue (LT) was assessed at 0-5 mm apical to the implant shoulder (LT0-LT5) at each time point. A total of 26 patients were included in this study. After wound closure, the test group showed significantly greater thickness in LT0-LT2 than the control group (LT0: test: 4.31 ± 0.73 mm, control: 2.99 ± 1.02 mm; LT1: test: 4.55 ± 0.69 mm, control: 3.60 ± 0.96 mm; LT2: test: 4.76 ± 0.54 mm, control: 4.05 ± 1.01 mm; p < 0.05). At 6 months, significant differences in LT0-LT1 were detected between the groups (LT0: test: 1.88 ± 0.57 mm, control: 1.08 ± 0.60 mm; LT1: test: 2.36 ± 0.66 mm, control: 1.69 ± 0.58 mm; p < 0.05). Within the limitations of this study, the use of digital workflow in GBR with particulate bone substitutes and i-PRF exerted a positive effect on the labial thickness of hard tissue in the coronal portion of the implant after wound closure and at 6 months.

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds.

Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.

Inhibition of mTORC1 in the rat condyle subchondral bone aggravates osteoarthritis induced by the overly forward extension of the mandible.

The present study aimed to investigate the role of mammalian target of rapamycin complex 1 (mTORC1) in the remodeling of the condyle subchondral bone in rats with temporomandibular joint osteoarthritis (TMJ OA) and explore the mechanisms involved. In this study, we used rats fitted with appliances to overly extend the mandible forward as an animal model of TMJ OA. Bone samples were collected 2, 4, and 8 weeks after appliance fixation. Histological changes in the condyle subchondral bone were assessed by staining with hematoxylin and eosin, safranin O, and tartrate-resistant acid phosphatase. Real-time polymerase chain reaction and immunohistochemical analyses were performed to evaluate the expression levels of osterix, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and mTORC1 in the condyle subchondral bone. The dissected condyles were analyzed using a micro-CT scanner. We also investigated changes in the condyle subchondral bone after mTORC1 pathway inhibition. In the early stages of TMJ OA, preosteoblasts, osteoblasts, and osteoclasts of the condyle subchondral bone were activated, which stimulated subchondral bone loss. MTORC1 was activated in subchondral bone preosteoblasts in rats with TMJ OA. The mTORC1 pathway was inhibited by a local injection of rapamycin, and the number of osteoblasts and mRNA levels of osteogenic markers in the condyle subchondral bone decreased, but the number of osteoclasts was basically unchanged. As a result, in the early stages of TMJ OA, subchondral bone loss and aggravation of OA were observed. These findings suggest that the mTORC1 signaling pathway plays an important role in subchondral bone remodeling during early stages of TMJ OA.

The Influence of Different Guided Bone Regeneration Procedures on the Contour of Bone Graft after Wound Closure: A Retrospective Cohort Study.

The aim of this study was to evaluate the impact of different guided bone regeneration (GBR) procedures on bone graft contour after wound closure in lateral ridge augmentation. A total of 48 patients with 63 augmented sites were included in this study. Participants were divided into 4 groups (n = 12 in each group) based on different surgical procedures: group 1: particulate bone substitute + collagen membrane; group 2: particulate bone substitute + collagen membrane + healing cap, group 3: particulate bone substitute + injectable platelet-rich fibrin (i-PRF) + collagen membrane; group 4: particulate bone substitute + i-PRF + surgical template + collagen membrane. After wound closure, the thickness of labial graft was measured at 0-5 mm apical to the implant shoulder (T0-T5). At T0-T2, the thickness of labial graft in group 4 was significantly higher than the other three groups (p < 0.05). And group 4 showed significantly more labial graft thickness than group 1 and group 2 at T3-T5 (p < 0.05). Within the limitations of this study, the use of i-PRF in combination with the surgical template in GBR may contribute to achieving an appropriate bone graft contour after wound closure.

Role of the SDF-1/CXCR4 signaling pathway in cartilage and subchondral bone in temporomandibular joint osteoarthritis induced by overloaded functional orthopedics in rats.

OBJECTIVES: To (i) use a mandibular advancement appliance in rats to investigate the role of the stromal cell-derived factor/CXC receptor 4 (SDF-1/CXCR4) signaling pathway in temporomandibular joint osteoarthritis (TMJ OA) induced by overloaded functional orthopedics (OFO) and (ii) provide a cellular and molecular basis for efficacious treatment of skeletal class-II malocclusion and avoidance of TMJ OA. METHOD: Male Sprague-Dawley rats (6 weeks) were divided randomly into control + normal saline (NS), EXP + ADM3100 (SDF-1 antagonist), EXP + NS, and control + ADM3100 groups. Changes in articular cartilage and subchondral bone after TMJ OA in these four groups were observed by hematoxylin and eosin (H&E), immunofluorescence double staining (IDS), Safranin-O staining, immunohistochemical (IHC) staining, real-time polymerase chain reaction, and micro-computed tomography at 2, 4, and 8 weeks. RESULTS: OFO led to increased expression of SDF-1, CXCR4, and matrix metalloproteinase (MMP) 13 and decreased expression of collagen II. The thickness of the hypertrophic cartilage layer was reduced at 4 weeks in the EXP + NS group, and damage to subchondral bone was observed at 2 weeks. Using ADM3100 to inhibit SDF-1 signaling could attenuate expression of MMP13, cartilage damage, and osteoblast differentiation. IDS showed that the areas of expression of SDF-1 and OSX in subchondral bone overlapped. CONCLUSIONS: Overloaded functional orthopedics (OFO) induced TMJ OA. The destruction of subchondral bone in TMJ OA caused by OFO occurred before damage to cartilage. SDF-1/CXCR4 may induce the osteogenic differentiation and cause cartilage degradation in TMJ OA caused by OFO.