Intrinsically disordered proteins SAID1/2 condensate on SERRATE for dual inhibition of miRNA biogenesis in Arabidopsis.

Intrinsically disordered proteins (IDPs) SAID1/2 are hypothetic dentin sialophosphoprotein-like proteins, but their true functions are unknown. Here, we identified SAID1/2 as negative regulators of SERRATE (SE), a core factor in miRNA biogenesis complex (microprocessor). Loss-of-function double mutants of said1; said2 caused pleiotropic developmental defects and thousands of differentially expressed genes that partially overlapped with those in se. said1; said2 also displayed increased assembly of microprocessor and elevated accumulation of microRNAs (miRNAs). Mechanistically, SAID1/2 promote pre-mRNA processing 4 kinase A-mediated phosphorylation of SE, causing its degradation in vivo. Unexpectedly, SAID1/2 have strong binding affinity to hairpin-structured pri-miRNAs and can sequester them from SE. Moreover, SAID1/2 directly inhibit pri-miRNA processing by microprocessor in vitro. Whereas SAID1/2 did not impact SE subcellular compartmentation, the proteins themselves exhibited liquid-liquid phase condensation that is nucleated on SE. Thus, we propose that SAID1/2 reduce miRNA production through hijacking pri-miRNAs to prevent microprocessor activity while promoting SE phosphorylation and its destabilization in Arabidopsis.

Impact of sex differences on the clinical presentation, pathogenesis, treatment and prognosis of Sjögren's syndrome.

Sjögren's syndrome is a common chronic autoimmune disease that manifests as dry mouth, dry eyes and systemic complications. There are sex differences in the clinical manifestations between men and women, with the average age of onset being around 55 years and the majority of female patients developing the disease during the menopausal years. Understanding the impact of sex differences on SS may help in the treatment and prognosis of patients. Studies have confirmed that a number of factors are associated with the onset of SS, but the exact mechanisms are not fully understood. Sex hormones (especially oestrogens and androgens) play a very important role, and the balance of sex hormone levels in the body is crucial for maintaining homeostasis in the acinar cells of the lacrimal and salivary glands. In addition, chromosomes play a very important role in the sex differences in SS. The gut microbiota also has some influence on sex differences in SS. In this review, we focus on oestrogens and androgens, which are important in the pathogenesis of SS, and summarize the progress of non-clinical studies. Sex differences may influence differences in individualized treatment regimens and further studies are needed.

Dynamic Stomach Model-Capillary Electrophoresis-ICPMS for Evaluation of Release and Transformation Behaviors of Arsenic Species from Microplastics during Digestion.

Microplastics (MPs) can act as carriers of environmental arsenic species into the stomach with food and release arsenic species during digestion, which threatens human health. Herein, an integrated dynamic stomach model (DSM)-capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICPMS) is developed for online monitoring of the release and transformation behaviors of arsenic species loaded on MPs (As-MPs) in the simulated human stomach. The 3D-printed DSM with a soft stomach chamber enables the behaviors of gastric peristalsis, gastric and salivary fluid addition, pH adjustment, and gastric emptying (GE) to be controlled by a self-written program after oral ingestion of food with As-MPs. The gastric extract during digestion is introduced into the spiral channel to remove the large particulate impurity and online filtered to obtain the clarified arsenic-containing solution for subsequent speciation analysis of arsenic by CE-ICPMS. The digestion conditions and pretreatment processes of DSM are tracked and validated, and the release rates of As-MPs digested by DSM are compared with those digested by the static stomach model and DSM without GE. The release rate of inorganic arsenic on MPs is higher than that of organic arsenic throughout the gastric digestion process, and 8% of As(V) is reduced to As(III). The detection limits for As(III), DMA, MMA, and As(V) are 0.5-0.9 µg L-1 using DSM-CE-ICPMS, along with precisions of ≤8%. This present method provides an integrated and convenient tool for evaluating the release and transformation of As-MPs during human gastric digestion and provides a reference for exploring the interactions between MPs and metals/metalloids in the human body.

Portable Photoacoustic Analytical System Combined with Wearable Hydrogel Patch for pH Monitoring in Chronic Wounds.

Timely diagnosis, monitoring, and management of chronic wounds play crucial roles in improving patients' quality of life, but clinical evaluation of chronic wounds is still ambiguous and relies heavily on the experience of clinician, resulting in increased social and financial burden and delay of optimal treatment. During the different stages of the healing process, specific and dynamic changes of pH values in the wound exudate can be used as biomarkers to reflect the wound status. Herein, a pH-responsive agent with well-behaved photoacoustic (PA) properties, nitrazine yellow (NY), was incorporated in poly(vinyl alcohol)/sucrose (PVA/Suc) hydrogel to construct a wearable pH-sensing patch (PVA/Suc/NY hydrogel) for monitoring of pH values during chronic wound healing. According to Rosencwaig-Gersho theory and the combination of 3D printing technology, the PA chamber volume and chopping frequency were systematically optimized to improve the sensitivity of the PA analytical system. The prepared PVA/Suc/NY hydrogel patch had excellent mechanical properties and flexibility and could maintain conformal contact with skin. Moreover, combined with the miniaturized PA analytical device, it had the potential to detect pH values (5.0-9.0) free from the color interference of blood and therapeutic drugs, which provides a valuable strategy for wound pH value monitoring by PA quantitation. This strategy of combining the wearable hydrogel patch with portable PA analysis offers broad new prospects for the treatment and management of chronic wounds due to its features of simple operation, time savings, and anti-interference.

Lanthanide Inorganic Nanoparticles Enhance Semiconducting Polymer Nanoparticles Afterglow Luminescence for In Vivo Afterglow/Magnetic Resonance Imaging.

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.

Adaptation mechanism of three Impatiens species to different habitats based on stem morphology, lignin and MYB4 gene.

BACKGROUND: Impatiens is an important genus with rich species of garden plants, and its distribution is extremely extensive, which is reflected in its diverse ecological environment. However, the specific mechanisms of Impatiens' adaptation to various environments and the mechanism related to lignin remain unclear. RESULTS: Three representative Impatiens species,Impatiens chlorosepala (wet, low degree of lignification), Impatiens uliginosa (aquatic, moderate degree of lignification) and Impatiens rubrostriata (terrestrial, high degree of lignification), were selected and analyzed for their anatomical structures, lignin content and composition, and lignin-related gene expression. There are significant differences in anatomical parameters among the stems of three Impatiens species, and the anatomical structure is consistent with the determination results of lignin content. Furthermore, the thickness of the xylem and cell walls, as well as the ratio of cell wall thickness to stem diameter have a strong correlation with lignin content. The anatomical structure and degree of lignification in Impatiens can be attributed to the plant's growth environment, morphology, and growth rate. Our analysis of lignin-related genes revealed a negative correlation between the MYB4 gene and lignin content. The MYB4 gene may control the lignin synthesis in Impatiens by controlling the structural genes involved in the lignin synthesis pathway, such as HCT, C3H, and COMT. Nonetheless, the regulation pathway differs between species of Impatiens. CONCLUSIONS: This study demonstrated consistency between the stem anatomy of Impatiens and the results obtained from lignin content and composition analyses. It is speculated that MYB4 negatively regulates the lignin synthesis in the stems of three Impatiens species by regulating the expression of structural genes, and its regulation mechanism appears to vary across different Impatiens species. This study analyses the variations among different Impatiens plants in diverse habitats, and can guide further molecular investigations of lignin biosynthesis in Impatiens.

Two {CuI[P4Mo6]2}-Based Coordination Polymers Incorporating In Situ Converted Tetrapyridyl Ligands for Trace Analysis of Nitrofuran Antibiotics.

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4″,4‴-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.

Association between masticatory function and depression in older adults: Results from NHANES 2009 to 2018.

AIM: Depression is prevalent among older adults. Although the number of missing teeth is considered to be associated with depression, the relationship between masticatory function, which is usually indicated by functional tooth units (FTUs), and depression in older adults remains unclear. MATERIALS AND METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. The number of FTUs was defined as pairs of opposing natural and artificial teeth. Depression was accessed using the Patient Health Questionnaire (PHQ-9), and participants who scored ≥10 on PHQ-9 were diagnosed with depression. Logistic regression analyses, propensity score matching (PSM) analyses and subgroup analyses were conducted to assess the association between FTU and depression. RESULTS: The analysis included 5764 individuals over 60 years. An association between FTU and the risk of depression among older adults was detected (odds ratio [OR] = 0.951, 95% confidence interval [CI] 0.915-0.989), suggesting protective roles of more FTUs. Significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was observed compared with 10 ≤ FTUs ≤ 12 (OR = 1.819, 95% CI 1.157-2.858). However, no significant increase in the risk of depression in 4 ≤ FTUs ≤ 9 was found. After PSM, significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was still detected compared with 4 ≤ FTUs ≤ 12 (OR = 1.484, 95% CI 1.030-2.136). Subgroup analyses demonstrated consistent results in all subgroups, except for individuals aged 76-80 and drinking regularly. CONCLUSIONS: The findings suggested the association between impaired masticatory function and the risk of depression among older adults. Longitudinal studies are needed to elucidate the role of masticatory function impairment in the development of depression further.

Enhanced control of periodontitis by an artificial intelligence-enabled multimodal-sensing toothbrush and targeted mHealth micromessages: A randomized trial.

AIM: Treatment of periodontitis, a chronic inflammatory disease driven by biofilm dysbiosis, remains challenging due to patients' poor performance and adherence to the necessary oral hygiene procedures. Novel, artificial intelligence-enabled multimodal-sensing toothbrushes (AI-MST) can guide patients' oral hygiene practices in real-time and transmit valuable data to clinicians, thus enabling effective remote monitoring and guidance. The aim of this trial was to assess the effect of such a system as an adjunct to clinical practice guideline-conform treatment. MATERIALS AND METHODS: This was a single-centre, double-blind, standard-of-care controlled, randomized, parallel-group, superiority trial. Male and female adults with generalized Stage II/III periodontitis were recruited at the Shanghai Ninth People's Hospital, China. Subjects received a standard-of-care oral hygiene regimen or a technology-enabled, theory-based digital intervention consisting of an AI-MST and targeted doctor's guidance by remote micromessaging. Additionally, both groups received guideline-conform periodontal treatment. The primary outcome was the resolution of inflamed periodontal pockets (≥4 mm with bleeding on probing) at 6 months. The intention-to-treat (ITT) analysis included all subjects who received the allocated treatment and at least one follow-up. RESULTS: One hundred patients were randomized and treated (50 tests/controls) between 1 February and 30 November 2022. Forty-eight tests (19 females) and 47 controls (16 females) were analysed in the ITT population. At 6 months, the proportion of inflamed periodontal pockets decreased from 80.7% (95% confidence interval [CI] 76.5-84.8) to 52.3% (47.7-57.0) in the control group, and from 81.4% (77.1-85.6) to 44.4% (39.9-48.9) in the test group. The inter-group difference was 7.9% (1.6-14.6, p < .05). Test subjects achieved better levels of oral hygiene (p < .001). No significant adverse events were observed. CONCLUSIONS: The tested digital health intervention significantly improved the outcome of periodontal therapy by enhancing the adherence and performance of self-performed oral hygiene. The model breaks the traditional model of oral health care and has the potential to improve efficiency and reduce costs (NCT05137392).

The potential causal path between periodontitis stage diagnosis and vegetable consumption is mediated by loss of posterior functional tooth units and masticatory function.

AIM: Emerging evidence points to a two-way relationship between periodontitis and dietary choices and, thus, nutrition. This study aimed to assess the potential cause-effect relationship between the periodontitis stage, loss of functional tooth units (FTUs), masticatory function, and intake of different food groups using path analysis. MATERIALS AND METHODS: A single calibrated examiner determined the periodontitis stage of a consecutive sample of 241 Chinese subjects reporting for tooth replacement. Their masticatory function was quantified by the mixing ability of a two-colour chewing gum. Validated food frequency questionnaires were used to calculate the intake of 33 food group items by an experienced calibrated rater. After verification of assumptions, visual structural equation modeling was performed with Amos 23. The consistency of results and the potential modifying effect of age were assessed in 9043 subjects from the NHANES database. RESULTS: Highly significant models were constructed using periodontitis stage and age as exogenous factors. Periodontitis stage diagnosis significantly affected the number of posterior FTUs and oral health-related quality of life (OHRQoL, path coefficient [PC] = -0.55 and -0.20, p < .05, respectively). In the model, FTUs also had an independent effect on OHRQoL (PC = 0.23, p < .05). FTUs determined the level of masticatory function (PC = -0.38, p < .05), which in turn affected vegetable intake but not fruit or meat intake (PC = -0.18, p < .0.5, PC = 0.06, NS and PC = 0.11, NS, respectively). The effect of age was significant for vegetable and meat intake and was also correlated with periodontitis stage diagnosis. Analysis of the NHANES database confirmed the negative impact of periodontitis on the number of occluding pairs and vegetable consumption for the 18-44, 45-60 and >60 age groups. CONCLUSIONS: Periodontitis showed a potential cause-effect pathway affecting vegetable intake across cultures and age groups. The size of the effect is potentially of clinical and public health significance. Additional studies, including intervention trials, are required to test this potential mechanism linking oral health to nutrition.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis.

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Minimally invasive surgical removal of bilateral impacted mandibular supernumerary teeth using 3D surgical guide template: a case report.

Impacted supernumerary teeth are defined as the presence of one or more teeth in a patient's upper and lower jaws in addition to the normal number of teeth in the dental arch. It has an incidence rate of approximately 1%-14% and more frequently occurs in males than females, may be single or multiple, unilateral or bilateral, erupted or impacted. In this article, we describe the case of a patient with two supernumerary teeth between the roots of the mandibular second premolar and the first molar, which influenced the effectiveness of the first orthodontic treatment. The special anatomical position of the complex supernumerary teeth made tooth extraction challenging. Given the higher risk status of surgery, we implemented a novel tooth extracting technique for this patient. Thus, in this study, we describe a case of minimally invasive extraction of bilateral mandibular impacted supernumerary teeth using a digital 3D positioning guide plate.

Synthesis of Bispecific Antibody Conjugates Using Functionalized Poly-ADP-ribose Polymers.

Poly-ADP-ribose (PAR) is a natural type of polymer derived from enzymatic reactions catalyzed by cellular poly(ADP-ribose) polymerases (PARPs). Given its notable solubility and biocompatibility, the PAR polymer may function as effective carriers for therapeutics in addition to modulating biomolecular interactions in cells. To explore its therapeutic potential, we herein developed a PAR polymer-based bispecific antibody targeting both human epidermal growth factor receptor 2 (HER2) and T-cell CD3 antigens. This was accomplished by conjugating anti-HER2 and anti-CD3 monoclonal antibodies to azido-functionalized PAR polymers through click chemistry. The generated PAR polymer-anti-HER2/anti-CD3 antibody conjugate could not only bind specifically to both HER2- and CD3-expressing target cells but also display potent cytotoxicity against HER2-positive breast cancer cells in the presence of non-activated human peripheral blood mononuclear cells (PBMCs). Functionalized PAR polymers provide a new strategy for synthesizing bispecific antibodies and may enable generation of PAR polymer-based conjugates with unique pharmacological activities for biomedical applications.

A Novel Azo-Linked Polymer Bearing Trifluoromethyl Groups for I2 Capture.

In this work, a novel three nitro-group-bearing monomer 3,6-dinitro-9-(2-trifluoromethyl-4-nitrophenyl)-carbazole (Car-3NO2 -CF3 ) via a CN coupling reaction between 3,6-dinitro-9H-carbazole (Car-2NO2 ) and 2-chloro-5-nitrobenzotrifluoride is synthesized, and obtained single crystal and single crystal analysis data for this compound. The crystal system of Car-3NO2 -CF3 is monoclinic and it has a P 21/c space group. This new monomer (Car-3NO2 -CF3 ) is also utilized to synthesize a novel azo-linked polymer (Azo-Car-CF3 ). The trifluoromethyl group has polar CF bonds, and thus it is an effective functional group for the capture of iodine. Azo-Car-CF3 has great thermal stability with a mass loss of only 10% at 414 °C, as well as good chemical stability as is demonstrated by its low solubility in common organic solvents such as tetrahydrofuran (THF), acetone, methanol, ethanol, and N,N-dimethylformamide (DMF). The specific surface area of Azo-Car-CF3 can reach as high as 335 m2  g-1 . Azo-Car-CF3 exhibits an excellent capacity for iodine adsorption and can reach up to 1198 mg g-1 in cyclohexane solution, and its adsorption capacity for iodine vapor can get to 2100 mg g-1 . In addition, ethanol can be used to trigger the release of the captured iodine to be easily released from Azo-Car-CF3 .

One-piece versus two-piece zirconia abutment supported single implant crown in the esthetic region: 3-Year results from a split-mouth randomized controlled clinical trial.

OBJECTIVES: To compare the clinical, radiographic, and immunological outcomes between one-piece versus two-piece zirconia abutments supported single implant crowns in the esthetic region. MATERIALS AND METHODS: The study followed a split-mouth, double-blind, and randomized controlled clinical design for a duration of 3 years. Twenty-two eligible patients with 44 implants were randomly assigned to two groups: Group 1 (one-piece zirconia abutment with zirconia base, n = 22) and Group 2 (two-piece zirconia abutment with titanium base, n = 22). The primary outcome was the technical complication rate. Additionally, survival rates, cytokines concentrations in peri-implant crevicular fluid (PICF), peri-implant conditions, marginal bone loss, and pink/white esthetics score (PES/WES) were assessed as secondary outcomes. RESULTS: Twelve of 22 patients attended the 1-year follow-up (due to the COVID pandemic), and 19 patients attended the 3-year examination. Two abutments in Group 1 were fractured after 10 and 12 months in function. Additionally, one screw loosening occurred in Group 1 at 1-year follow-up. The 3-year technical complication rate was significantly higher in Group 1 than that in Group 2 (15.79% vs. 0%, p < .001). The 3-year implant survival rate was 100% in both groups. The concentration of IFN-γ in PICF was significantly upregulated in Group 2 (p = .018). Furthermore, the IL-6 concentration was positively correlated with BOP% (p = .020). CONCLUSIONS: Two-piece zirconia abutments exhibited superior technical performance compared to one-piece designs during a 3-year follow-up in the anterior region. However, further long-term research is necessary to verify the immunological stability of two-piece zirconia abutments.

Caspase-3/GSDME-mediated pyroptosis leads to osteogenic dysfunction of osteoblast-like cells.

OBJECTIVE: Cell pyroptosis is implicated in progressive bone loss in dental inflammatory diseases. We induced caspase-3/Gasdermin E (GSDME)-mediated pyroptosis in osteoblast-like cells and evaluated the effects on osteogenesis. MATERIALS AND METHODS: Osteoblast-like cells were treated with various concentrations of sodium butyrate (NaB) to identify the most appropriate for inducing caspase-3/GSDME-mediated pyroptosis. Cells were divided into control, NaB and NaB+Ac-DEVD-CHO (specific caspase-3 inhibitor) groups. Pyroptosis level was evaluated by immunofluorescence, morphological observation, flow cytometry, lactate dehydrogenase (LDH) release assays, mRNA and protein levels of pyroptosis-related markers. Then, inflammation level, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) expression and osteogenic function were detected. RESULTS: Treatment with 10 mM NaB increased caspase-3 expression, GSDME cleavage, LDH release and the number of pyroptotic cells, with morphologic changes, indicating GSDME-mediated pyroptosis induction. The pyroptosis-related changes were abolished by caspase-3 inhibition. Caspase-3/GSDME-mediated pyroptosis triggered the expression of inflammatory cytokines and RANKL, downregulated alkaline phosphatase (ALP) activity, mineralisation level, mRNA and protein levels of multiple osteogenic markers. These effects were partly reversed by Ac-DEVD-CHO. CONCLUSION: Caspase-3/GSDME-mediated pyroptosis induced by NaB activated the inflammatory response, reduced osteogenic differentiation and disturbed OPG/RANKL axis, leading to osteogenic dysfunction in osteoblast-like cells.

Effect of different implant angulations on the biomechanical performance of prosthetic screws in two implant-supported, screw-retained prostheses: A numerical and experimental study.

STATEMENT OF PROBLEM: A mesiodistal angle frequently forms between 2 splinted implant-supported, screw-retained fixed dental prostheses (TIS-FDPs). Mechanical complications commonly occur in prosthetic screws. Studies regarding the effect of the degree of implant angulation on the biomechanical performance of prosthetic screws in TIS-FDPs are sparse. PURPOSE: The purpose of this numerical and experimental study was to investigate the effects of different implant angulations on the biomechanical performance, including stress distribution, stability of the screw joint, and surface morphology change of the prosthetic screws in TIS-FDPs. MATERIAL AND METHODS: TIS-FDPs were classified into 4 groups: 0, 10, 20, and 30 degrees based on the degree of mesiodistal angle between the long axes of the 2 implants. In the finite element analysis (FEA), 4 series of 3D models were constructed and loaded with simulated occlusal forces. The von Mises stresses and rotational angles of the prosthetic screws were then calculated. In the mechanical test, each group of 5 TIS-FDPs with 10 prosthetic screws was tested under 1 million loading cycles by using a universal testing machine. The removal torque values (RTVs) and the surface roughness of the prosthetic screws were measured after cyclic loading. The normality of the outcome variables was assessed by the Shapiro-Wilk test. Analysis of variance and the Kruskal-Wallis test were used for further analysis (α=.05). RESULTS: The FEA results showed that the von Mises stresses of the prosthetic screws were concentrated in the first screw thread crest engaged with the abutment, and the maximum values of the threads and the rotation angles of the prosthetic screws increased in the 2-implant mesiodistal angulation from 0 to 30 degrees. The mechanical tests showed that the RTVs of the prosthetic screws in each group were not significantly different after 1 million loading cycles (P=.107). The surface roughness of the crest of the first 2 threads of the prosthetic screws in the 30-degree group changed significantly compared with those in the other groups. CONCLUSIONS: When TIS-FDPs were delivered, larger angulations of the 2 splinted implants seemed to increase the stress concentrated on the crest of the first engaged thread and the rotation angles of the prosthetic screws. After 1 million loading cycles, significant surface adhesive wear was identified on the crest of the first 2 threads of the prosthetic screws in the 30-degree group compared with groups with a smaller angulation.

Construction of 131I-RGDyC-PEG-PAMAM-DTX targeted drug delivery system and study of its physicochemical properties and biological activity.

OBJECTIVE: To construct a novel targeted drug delivery nanoprobe: iodine-131-arginine-glycine-aspartate-tyrosine-cysteine peptide-polyethylene glycol-fifth generation polyamide-amine-docetaxel (131I-RGDyC-PEG-PAMAM-DTX) and to investigate its physicochemical properties and biological activity. MATERIALS AND METHODS: Docetaxel was wrapped by solvent volatilization method, and the regression curve of DTX was constructed by high-performance liquid chromatography to determine its drug loading. The particle size of RGDyC-PEG-PAMAM-DTX was detected by dynamic light scattering. The 131I labeling was performed by a chloramine-T method and purified by Sephadex-G50 column chromatography, and it is in vitro stability and lipid-water partition coefficient was investigated. The cytotoxicity of RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX on A549 cells in vitro was detected by Cell Counting Kit-8 assay. RESULTS: Arginine-glycine-aspartate-tyrosine-cysteine peptide-PEG-PAMAM-DTX was successfully prepared by solvent volatilization with a loading capacity of about 44µg/mg. The average particle size of RGDyC-PEG-PAMAM-DTX was 57.8nm; the labeling rate of 131I-RGDyC-PEG-PAMAM-DTX by the chloramine-T method was 74.09%-76.09%, and the radiochemical purity was 88.9%-92.6% after purification. The in vitro stability showed that the radiochemical purity was above 80% after 72h in fetal bovine serum and PBS buffer (25oC and 37oC).CCK-8 assay showed that RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX had more pronounced cytotoxic effects than free DTX and 131I. CONCLUSION: Iodine-131-RGDyC-PEG-PAMAM-DTX has good physicochemical properties and apparent cytotoxic effectsandis expected to be used in treating tumors.

A Photoorganizable Triple Shape Memory Polymer for Deployable Devices.

Inspired by the action and healing process from living organisms, developing deployable devices using stimuli-responsive materials, or "smart" deployable devices, is desired to realize remote-controlled programmable deformation with additional in situ repair to perform multiple tasks while extending their service life in aerospace. In this work, a photoorganizable triple shape memory polymer (POTSMP) is reported, which is composed of an azobenzene-containing thermoplastic polyurethane. Upon UV and visible illumination, this POTSMP performs arbitrary programming of two temporary shapes and precise and stepwise shape recovery, exhibiting various temporary shapes adapted to different aerospace applications. On the other hand, rapid light-reconfiguration in seconds, including light-reshaping and light-welding, is achieved in response to UV irradiation, allowing in situ localized process and repair of permanent shape. Combining these photoorganizable operations, deformable devices with complex 2D/3D structures are facilely manufactured with no need of special molds. It is envisioned that this POTSMP can expand the potential of photoresponsive TSMPs in smart deployable devices.