Outcomes of prophylactic lauromacrogol injection versus non-injection in patients with endogenous cesarean scar pregnancy treated by hysteroscopic surgery: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy of hysteroscopic surgery for endogenous cesarean scar pregnancy (CSP) and the value of prophylactic ultrasound-guided local injection of lauromacrogol. METHODS: This retrospective study included 131 patients diagnosed with endogenous CSP who underwent hysteroscopic surgery at the Hangzhou Fuyang Women and Children Hospital between January 2018 and May 2022. Lauromacrogol (10-20 mL) was administered within 24 h preoperatively using an ultrasound-guided vaginal injection to 78 patients (L group) versus not administered to 53 patients (non-L group). Their clinical data and outcomes were analyzed. RESULTS: Mean gestational age, gestational mass size, and uterine scar thickness and median preoperative blood ß-human chorionic gonadotropin levels of the non-L versus L groups were 46.26 versus 45.01 days, 2.05 versus 2.39 cm, 0.35 versus 0.32 cm, and 19850.0 versus 26790.0 U/L, respectively (P > 0.05 for each). The non-L and L groups had similar success rates (98.1% vs. 98.7%, P = 1.0). Complications related to lauromacrogol administration, including abdominal pain, massive bleeding, and bradycardia, were experienced by 46.2% (36/78; P < 0.001) of L group patients. The non-L had a significantly shorter mean hospital stay (4.85 ± 1.12 vs 5.44 ± 1.08 days) and lower total cost (6148.75 ± 1028.71 vs 9016.61 ± 1181.19) (P < 0.01). CONCLUSIONS: Hysteroscopic surgery is effective and safe for patients with endogenous CSP. Prophylactic lauromacrogol injection increases the incidence of complications and costs. Direct hysteroscopic surgery can reduce pain and financial burden in patients with endogenous CSP and save medical resources for other patients.

Long-term effect of bilateral anterior elevation of occlusion on the temporomandibular joints.

OBJECTIVE: Incisors tubed prosthesis with bilateral anterior elevation (BAE) relation had been reported to stimulate the proliferative response in the mandibular condylar cartilage of mice, thus the prosthetic occlusion elevation had been proposed to treat cartilage degeneration. Currently, we aimed to detect the long-term effect of BAE on temporomandibular joints (TMJs). MATERIALS AND METHODS: Twelve 6-week-old female mice were assigned to age-matched control and BAE groups (n = 6). Micro-CT images and the macro- and micro-morphology of the mandibular condyles were analyzed at 29 weeks. RESULTS: Compared with the age-matched controls, in BAE group, there were loss of subchondral cortical bone and heavy loss of the subchondral trabecular bone at the superior sites of the TMJ condyles, but hyperostosis at the inferior sites as revealed by micro-CT images and histological slices. In BAE group, cartilage thickness and matrix area were increased with upregulated expression of type II, type X collagen, and Ki67, but the expression of cleaved caspase-3 was downregulated (all, p < 0.05). CONCLUSION: In addition to cartilage thickening, long-term BAE induces loss of the subchondral cortical bone and heavy loss of the underneath subchondral trabecular bone, but hyperostosis further underneath. Using BAE as a treatment remains double-edged.

Development of hydrophilic magnetic molecularly imprinted polymers for the dispersive solid-phase extraction of sulfonamides from animal-derived samples before HPLC detection.

Highly hydrophilic magnetic molecularly imprinted polymers were prepared through a surface imprinting technique for dispersive solid-phase extraction coupled with high-performance liquid chromatography to detect trace levels of ten sulfonamides in animal-derived samples. The obtained imprinted polymers were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and adsorption experiments, which exhibited excellent specific adsorption for template sulfamethazine in aqueous solution. Moreover, the adsorption process could be completed within 25 min. Under the optimum conditions, the method exhibits good linear performance in the range of 5-to 10 mg/L, limits of detection ranging from 0.57 to 1.50 µg/L, and good recoveries of 85.09-110.93% in the spiked samples (chicken, cow milk, and goat milk). The proposed detection method not only avoids the use of organic solvents but also simplifies the pretreatment procedure via excellent magnetic properties. Furthermore, the method shows great potential for the rapid detection of drug residues.

Preparation of hydrophilic molecularly imprinted solid-phase microextraction fiber for the selective removal and extraction of trace tetracyclines residues in animal derived foods.

The present work reported a novel hydrophilic and selective solid-phase microextraction fiber by improved multiple co-polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high-performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid-phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross-linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid-phase microextraction conditions, satisfactory linearity (5-1000 µg/L) and detection limits (0.38-0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3-104.4%.

The therapeutic role of bone marrow stem cell local injection in rat experimental periodontitis.

Mesenchymal stem cell therapy brings hope for regenerating damaged periodontal tissues. The present study aimed to investigate the therapeutic role of local bone marrow stem cell (BMSC) injection in ligation-induced periodontitis and the underlying mechanisms. Alveolar bone lesion was induced by placing ligatures subgingivally around the bilateral maxillary second molars for 28 days. The alveolar bone lesion was confirmed by micro-CT analysis and bone histomorphometry. Allogeneic BMSC transplantation was carried out at 28 day after ligation. The survival state of the transplanted BMSC was observed by bioluminescent imaging. The implantation of the BMSC into the gingival tissues and periodontal ligament was confirmed by green fluorescent protein (GFP) immunohistochemical staining. The expression level of pro-inflammatory, tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), and receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues were evaluated by immunohistochemical staining and real-time PCR. Significant reverse of alveolar bone lesion was observed after BMSC transplantation. The expression of TNF-α and IL-1ß was down-regulated by BMSC transplantation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the periodontal ligament was reduced, and the increased RANKL expression and decreased OPG expression were also reversed after BMSC transplantation. It is concluded that allogeneic BMSC local injection could inhibit the inflammation of the periodontitis tissue and promote periodontal tissue regeneration.

Bilateral anterior elevation prosthesis boosts chondrocytes proliferation in mice mandibular condyle.

OBJECTIVE: We aimed to develop a mouse model predominating in a proliferative response in the articular cartilage of the temporomandibular joints. MATERIALS AND METHODS: Bilateral anterior elevation of occlusion was developed by installing metal tubes onto the incisors of mice with edge-to-edge relation to prevent tooth wear, leading to an increase in the vertical height of the dental occlusion with time. Morphological changes and expression changes in Cyclin D1, Aggrecan, and type II and type X collagen in the mandibular condylar cartilage were detected. In addition, cells were isolated from the mandibular condylar cartilage and exposed to cyclic tensile strain (CTS). RESULTS: Compared with age-matched controls, the tooth length was longer at 3 weeks, 7 weeks, and 11 weeks in BAE mice (p < 0.05), with increased condylar cartilage thickness, matrix amount, and cell number (p < 0.05). Compared with the deep zone cells, CTS stimulated the superficial zone cells to express a higher level of proliferating cell nuclear antigen, Cyclin D1, Aggrecan, and type II collagen but a lower level of type X collagen and alkaline phosphatase. CONCLUSION: Bilateral anterior elevation stimulated the proliferative response in the mandibular condylar cartilage, offering a new therapeutic strategy for cartilage degeneration.

Catabolic changes of rat temporomandibular joint discs induced by unilateral anterior crossbite.

BACKGROUND: The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown. OBJECTIVE: To describe changes in the TMJ discs of UAC rats. METHODS: The discs of fifty-four Sprague-Dawley rats, equally distributed into a UAC group and an age-matched sham-operated control group at 4, 12 and 20 weeks (n = 9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements. RESULTS: No macro- or micro-morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P < 0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt-related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N-terminal fragment, which can induce cartilage degradation, were accumulated (P < 0.05). CONCLUSION: TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time.

Molecular changes in peripheral blood involving osteoarthritic joint remodelling.

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty-four six-week-old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene-fold changes in PBLs were detected by a microarray analysis comparing rats that received 20-week unilateral anterior crossbite (UAC) treatment with age-matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA-like lesions. The other twenty-four rats were randomly placed in the UAC and control groups at 12- and 20-week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real-time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1-positive, EXPH1-positive and IL10-positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.

Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism.

The temporomandibular joint (TMJ), which is biomechanically related to dental occlusion, is often insulted by osteoarthritis (OA). This study was conducted to clarify the relationship between Indian hedgehog (Ihh) and parathyroid hormone receptor 1 (PTH1R) signaling in modulating the enhanced chondrocyte terminal differentiation in dental stimulated TMJ osteoarthritic cartilage. A gain- and loss-of-function strategy was used in an in vitro model in which fluid flow shear stress (FFSS) was applied, and in an in vivo model in which the unilateral anterior cross-bite (UAC) stimulation was adopted. Ihh and PTH1R signaling was modulated through treating the isolated chondrocytes with inhibitor/activator and via deleting Smoothened (Smo) and/or Pth1r genes in mice with the promoter gene of type 2 collagen (Col2-CreER) in the tamoxifen-inducible pattern. We found that both FFSS and UAC stimulation promoted the deep zone chondrocytes to undergo terminal differentiation, while cells in the superficial zone were robust. We demonstrated that the terminal differentiation process in deep zone chondrocytes promoted by FFSS and UAC was mediated by the enhanced Ihh signaling and declined PTH1R expression. The FFSS-promoted terminal differentiation was suppressed by administration of the Ihh inhibitor or PTH1R activator. The UAC-promoted chondrocytes terminal differentiation and OA-like lesions were rescued in Smo knockout, but were enhanced in Pth1r knockout mice. Importantly, the relieving effect of Smo knockout mice was attenuated when Pth1r knockout was also applied. Our data suggest a chondrocyte protective effect of suppressing Ihh signaling in TMJ OA cartilage which is dependent on PTH1R signaling.

Long-Term Detection of Glycemic Glucose/Hypoglycemia by Microfluidic Sweat Monitoring Patch.

A microfluidic sweat monitoring patch that collects human sweat for a long time is designed to achieve the effect of detecting the rise and fall of human sweat glucose over a long period of time by increasing the use time of a single patch. Five collection pools, four serpentine channels, and two different valves are provided. Among them, the three-dimensional valve has a large burst pressure as a balance between the internal and external air pressures of the patch. The bursting pressure of the two-dimensional diverter valve is smaller than that of the three-dimensional gas valve, and its role is to control the flow direction of the liquid. Through plasma hydrophilic treatment of different durations, the optimal hydrophilic duration is obtained. The embedded chromogenic disc detects the sweat glucose value at two adjacent time intervals and compares the information of the human body to increase or reduce glucose. The patch has good flexibility and can fit well with human skin, and because polydimethylsiloxane (PDMS) has good light transmission, it reduces the measurement error caused by the color-taking process and makes the detection results more accurate.

Mussel byssus-inspired dual-functionalization of zirconia dental implants for improved bone integration.

Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.

Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation.

Autophagy is a cell protective mechanism for maintaining cellular homeostasis. The present study aimed to investigate whether autophagy is enhanced in the biomechanically induced degenerative cartilage of the temporomandibular joint (TMJ) and the potential role of mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) and mammalian Target of rapamycin (mTOR) in this observation. To induce degenerative changes in the TMJs, rats were subjected to biomechanical dental stimulation by moving 4 molars away from their original position as we previously reported. The ultrastructure of autophagosome was observed by transmission electron microscopy. The number of lysosomes was analyzed by flow cytometry. The expression levels of Beclin1 and LC3 and the involvement of MAP4K3 activity were detected by immunohistochemistry, real-time PCR and western blot. The activity of the mTOR pathway indicated by p-mTOR and p-p70S6 K was assayed by western blot. TMJ degeneration, characterized by irregular cell arrangement and cell-free area, was induced in the experimental groups. Under transmission electron microscopy, we observed the presence of autophagosomes, small patches of condensed chromatin, abundant rough endoplasmic reticulum and Golgi apparatus. The number of lysosomes and the expression levels of Beclin1 and LC3 increased, while the activity of mTOR and the expression level of MAP4K3 decreased in the experimental groups. Cartilage in TMJ which was induced to be degenerative biomechanically exhibited autophagy accompanied by reduced mTOR and MAP4K3 activity.

Encoding CsPbX3 perovskite quantum dots with different colors in molecularly imprinted polymers as fluorescent probes for the quantitative detection of Sudan I in food matrices.

All-inorganic cesium lead halides (CsPbX3, X  = Cl, Br, I) perovskite quantum dots (PQDs) have attracted extensive research attention due to their unique optical properties. However, their instability and sensitivity to air and moisture hinder further use in fluorescent sensing applications. In this work, the construction and application of PQDs encoded molecularly imprinted polymers (MIPs-CsPbX3) for Sudan I detection were proposed. After being encoded the PQDs, the obtained MIPs-CsPbX3 microspheres exhibited high stability for the external environment, remarkable bright fluorescence, and specific recognition for Sudan I. The fluorescent intensity of the MIPs-CsPbX3 microspheres was obviously quenched upon loading Sudan I, and good linear responses in the range of 0.5-150 µg L-1, limit of detection of 0.3 µg L-1, and good recoveries of 95.27 % to 105.96 % in spiked samples were obtained. The developed fluorescent probe provided a selective and sensitive quantified method for Sudan I detection in food matrices.

Changes of myelinated nerve and myelin basic protein expression in rats' periodontal ligaments after experimental tooth movement.

INTRODUCTION: Information about the effect of tooth movement on the myelinated nerve in the periodontal ligament is limited. In this study, we aimed to investigate what responses of the periodontal myelinated nerve can be evoked during experimental tooth movement. METHODS: In experimental-I group, the maxillary left and mandibular right third molars were moved distally. In experimental-II group, the maxillary left third molar but not the right one was moved, and the bilateral mandibular third molars were extracted. The ultrastructures of the myelinated nerve in the periodontal ligament of the bilateral maxillary third molars were observed under a transmission electron microscope. The expression of myelin basic protein was evaluated by immunohistochemistry. RESULTS: Degenerative ultrastructural changes of the myelinated nerve in the periodontal ligament were noticed mainly in the myelin sheath; these were observed earlier and were recoverable in the experimental-I group. In contrast, the ultrastructural changes of the myelinated nerve occurred mainly in the axons, were observed later, and were unrecoverable in the experimental-II group. A concomitant decrease of myelin basic protein expression was observed in both groups. CONCLUSIONS: Both experimental tooth movement and occlusal changes accompanying it caused changes of the myelinated nerve in the periodontal ligament.

Effect of CaCO3 particles and suspended bacteria on biofilm components and activity in the model recirculating cooling water system.

Biofilms are a serious problem in industrial recirculating cooling water systems. Biofilm formation and properties are affected by many factors, such as inorganic particles and suspended bacteria. In this research a laboratory model recirculating cooling water system was applied to investigate the effects of CaCO(3) concentration and suspended bacterial count on extracellular polymeric substances (EPS) content and dehydrogenase activity (DHA) in the attached biofilms. In addition, nutrient level was also the key factor when investigating the effect of suspended bacterial count. The results showed that EPS content and DHA first increased and then decreased with the increase of CaCO(3) concentration from 0 to 200 mg/l. At the low nutrient level, with the increase of suspended bacterial count from 4.04 to 5.78 log(10) c.f.u./ml, biofilm EPS content decreased firstly and then increased. However, biofilm DHA always gradually increased. At the medium nutrient level, biofilm EPS content increased firstly and then decreased and DHA always gradually decreased when suspended bacterial count ranged from 4.04 to 5.78 log(10) c.f.u./ml. At the high nutrient level, biofilm EPS content and DHA both showed the increasing trend with the increase of suspended bacterial count. This work provides the basis and reference for management strategies in actual recirculating cooling water systems.

Sequential oxygen supply system promotes peripheral nerve regeneration by enhancing Schwann cells survival and angiogenesis.

Local hypoxia in cellular grafts remains a challenge during the repair of peripheral nerve injury. Oxygen carriers (perfluorotributylamine, PFTBA) have been shown to provide oxygen to Schwann cells (SCs) for a short period. However, the limited oxygen supply from oxygen-carrying materials hinders the ability of such systems to counteract hypoxia over an extended period and limits their therapeutic potential. In this study, PFTBA/VEGF core-shell fibers were fabricated through coaxial electrospinning to construct an oxygen supply system that can sequentially provide oxygen, first via the oxygen carrier and subsequently by promoting angiogenesis via VEGF. Then, the oxygen release and proangiogenic effects of the PFTBA/VEGF core-shell fibers were examined in vitro. Furthermore, sequential oxygen supply conduits prepared using the fibers and filled with SCs were used to bridge 15-mm-long sciatic nerve defects in rats. The PFTBA-VEGF system was confirmed to protect SCs from hypoxia and promote angiogenesis in vitro. Subsequent in vivo studies showed that after the oxygen carried by PFTBA was exhausted, the VEGF could induce neovascularization, and the nascent blood vessels acted as sequential oxygen suppliers for SCs during nerve regeneration. In addition, rats transplanted with the sequential oxygen supply system showed significant morphological and functional improvements in axonal regeneration, the sciatic function index, and the muscle wet weight ratio. The final functional outcomes were similar after treatment with the sequential oxygen supply conduits and autografts. Western blots revealed that the VEGF in the system could upregulate p-AMPK, contributing to axon regeneration after sciatic nerve injury. The sequential oxygen supply system offers essential insights into the oxygen regulation of biomaterials and highlights the potential of oxygen supply strategies as therapeutic approaches for repairing defects in peripheral nerves and other aerobic tissues.

Cell-friendly photo-functionalized TiO2 nano-micro-honeycombs for selectively preventing bacteria and platelet adhesion.

Titanium dioxide (TiO2) is a widely used biomaterial. It is a great challenge to confer antibacterial and antithrombotic properties to TiO2 while maintaining its cell affinity. Here, we developed a new strategy to achieve the above goal by comprehensively controlling the chemical cues and geometrical cues of the surface of TiO2. Using colloidal etching technology and UV irradiation treatment, we obtained the photofunctionalized nano-micro-honeycomb structured TiO2. The honeycomb structured increased the photocatalytic activity of TiO2, which endowed TiO2 with photo-induced superhydrophilicity to inhibit bacterial adhesion. The high photocatalytic activity also induced the strong photocatalytic oxidation of TiO2 surface organic adsorbates to suppress fibrinogen and platelet attachment. In addition, owing to the micropore trapping-isolation effect on the bacteria and the nano-frames' contact guidance effect on the growth and spreading of platelet pseudopods, the honeycomb structure also shows a considerable inhibiting effect on bacterial and platelet adhesion. Therefore, due to the controlled chemical and geometrical cues' synergistic effect, the photo-functionalized TiO2 honeycomb structure shows excellent bacterial-adhesion resistance and antithrombotic properties. More importantly, the photo-functionalized TiO2 honeycomb did not inhibit the adhesion and growth of endothelial cells (ECs) after culturing for 3 d, indicating a good cell affinity that the traditional antifouling surfaces do not possess.

A controlled nucleation and formation rate of self-assembled peptide nanofibers.

Self-assembling peptide matrixes are powerful platforms for encouraging tissue regeneration, but are usually formed within seconds and remain relatively static in both structure and function throughout their application. For the first time, we have shown that it is possible to extend the time it takes for peptide self-assembly so as to allow for the dynamic building of a self-assembled system over days, in the presence of an enzyme. Specifically, K5 and K10 sequences were conjugated, via a thrombin-specific cleavage domain NleTPR/SFL, to prevent the nanofiber formation and form stable nanoparticles composed of (RADA)4-GG-NleTPR/SFL-K5 and (RADA)4-GG-NleTPR/SFL-K10 that act as nucleation sites for reassembling. Upon introduction of thrombin, a model enzyme, this system showed an extremely slow rate of nanofiber formation in a parallel direction that is in sharp contrast to the well-known rapid assembly of (RADA)4 systems with random networks. These bioresponsive materials may provide a novel platform for utilizing long-term enzymatic profiles to form new nanofibers within an existing matrix over long therapeutic timeframes.

Mussel-inspired "built-up" surface chemistry for combining nitric oxide catalytic and vascular cell selective properties.

Specific selectivity of vascular cells and antithrombogenicity are crucial factors for the long-term success of vascular implants. In this work, a novel concept of mussel-inspired "built-up" surface chemistry realized by sequential stacking of a copper-dopamine network basement, followed by a polydopamine layer is introduced to facilitate the combination of nitric oxide (NO) catalysis and vascular cell selectivity. The resultant "built-up" film allowed easy manipulation of the content of copper ions and the density of catechol/quinone groups, facilitating the multifunctional surface engineering of vascular devices. For example, the chelated copper ions in the copper-dopamine network endow a functionalized vascular stent with a durable release of NO via catalytic decomposition of endogenous S-nitrosothiol. Meanwhile, the catechol/quinone groups on the film surface allow the facile, secondary grafting of the REDV peptide to develop a selectivity for vascular cells, as a supplement to the functions of NO. As a result, the functionalized vascular stent perfectly combines the functions of NO and REDV, showing excellent antithrombotic properties and competitive selectivity toward the endothelial cells over the smooth muscle cells, hence impressively promotes re-endothelialization and improves anti-restenosis in vivo. Therefore, the first mussel-inspired "built-up" surface chemistry can be a promising candidate for the engineering of multifunctional surfaces.

MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint.

A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA.Abbreviations : ACTB: actin beta; ATF6: activating transcription factor 6; BECN1: beclin 1; BFL: bafilomycin A1; CASP12: caspase 12; CASP3: caspase 3; DAPI: 4',6-diamidino-2-phenylindole; DDIT3: DNA-damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; FFSS: flow fluid shear stress; HSPA5/GRP78/BiP: heat shock protein 5; LAMP2: lysosome-associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; OA: osteoarthritis; PRKAA1/2/AMPK1/2: protein kinase, AMP-activated, alpha 1/2 catalytic subunit; RPS6: ribosomal protein S6; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TG: thapsigargin; TMJ: temporomandibular joints; TSC1/2: tuberous sclerosis complex 1/2; UAC: unilateral anterior crossbite; UPR: unfolded protein response; XBP1: x-box binding protein 1.