MicroRNA-93-5p regulates odontogenic differentiation and dentin formation via KDM6B.

BACKGROUND: Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation. METHODS: The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin. RESULTS: The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3' untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin. CONCLUSIONS: MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

A New Drug-Coated Balloon for the Treatment of Superficial Femoropopliteal Artery Disease: 12-Month Results from the IN-DEPT SFA Trial.

PURPOSE: To report the outcomes of the IN-DEPT trial assessing the feasibility, preliminary safety data, and 12-month outcomes of a new drug-coated balloon (DCB) product for peripheral artery disease (PAD) in Chinese patients. MATERIALS AND METHODS: This is a prospective, multicenter, single-arm clinical trial. A total of 160 patients with superficial femoral artery (SFA) and/or proximal popliteal artery lesions were treated with a new paclitaxel-coated DCB. The preliminary effectiveness end point was 12-month primary patency. The primary safety end point was freedom from device- and procedure-related mortality over 30 days and freedom from major target limb amputation and clinically driven target lesion revascularization (CD-TLR) within 12 months after the index procedure. RESULTS: In total, 160 patients presented with 162 target lesions. A total of 139 lesions (85.8%) were treated with 1 DCB, whereas the other 23 lesions (14.2%) were treated with 2 devices. The device success rate was 100%. A total of 135 subjects reached the preliminary effectiveness end point, with a 12-month primary patency rate of 84.4%. There was no 30-day device- or procedure-related death or unplanned major target limb amputation at 12 months. Five CD-TLRs (3.1%) occurred during the 12-month follow-up period. CONCLUSIONS: Results from the IN-DEPT SFA trial showed satisfactory feasibility and safety of the new DCB over 12 months in Chinese patients with PAD and femoropopliteal de novo lesions, including both stenoses and total occlusions.

Neonatal Exposure to Polystyrene Nanoplastics Impairs Microglia-Mediated Synaptic Pruning and Causes Social Behavioral Defects in Adulthood.

The increasing prevalence and persistence of nanoplastics (NPs) have become critical environmental concerns. These particles have the potential to enter the food chain and accumulate in living organisms, which exerts their adverse effects on human health. The release of nanoparticles from feeding bottles raises concerns about potential health issues, especially for newborns exposed to NPs at the neonatal stage. In this study, we examined the impacts of neonatal exposure to polystyrene nanoplastics (PS-NPs) on neurodevelopment. Our study demonstrates that exposure to PS-NPs in newborn mice impairs microglial autophagic function and energy metabolism, leading to the disruption of microglia-mediated synaptic pruning during early neurodevelopment. These mice subsequently develop social behavioral defects in adulthood, suggesting the long-lasting effects of neonatal PS-NP exposure on brain development and behavior. Together, these data provide insights into the mechanism by which PS-NPs affect early neurodevelopment, thus emphasizing the crucial need to address plastic pollution globally.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

A case report of peroneal muscle atrophy type 2A2 with central nervous system involvement as initial presentation.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a group of single-gene hereditary diseases of peripheral nerve with high clinical variability and genetic heterogeneity. The typical clinical manifestations include progressive muscle weakness and muscle atrophy in the distal extremities, accompanied by disappearance of tendon reflexes and distal sensory disturbances. CMT2A2 (OMIM: 609260) is caused by the mutation of MFN2 (OMIM: 608507), is the most common type of axonal pattern. Although a small number of patients with X-linked CMT1 (CMT1X) present with central nervous system involvement, including reversible white matter lesions, it is rarely in CMT2A2. CASE PRESENTATION: A 3-year and 5-month-old girl had experienced motor lag, muscle tension, and abnormal gait for over a year. A reexamination of cranial MRI revealed an anterior enlargement of the abnormal signal range in the lateral ventricles and bilateral frontal lobes. And the whole exon sequencing showed that this girl carried a heterozygous missense mutation c.314C > T of MNF2 gene, inherited from her mother. CONCLUSIONS: In this study, we retrospectively analyzed the clinical and molecular genetic findings of a child with Charcot-Marie-Tooth disease A2 with central nervous system involvement as the initial presentation, and explored its pathogenic mechanism.

The outcome of combined use of iRoot BP Plus and iRoot SP for root-end filling in endodontic microsurgery: a randomized controlled trial.

OBJECTIVES: Root-end filling is important for the clinical outcome of endodontic microsurgery. Our previous study showed that combined application of iRoot BP Plus Root Repair Material (BP-RRM) and iRoot SP Injectable Root Canal Sealer (SP-RCS) in root-end filling exhibited better apical sealing as compared to the application of BP-RRM alone. The aim of this randomized controlled clinical trial was to evaluate the effect of the combined use of BP-RRM and SP-RCS on the prognosis of teeth with refractory periapical diseases after endodontic microsurgery. MATERIALS AND METHODS: 240 teeth with refractory periapical diseases scheduled for endodontic microsurgery were randomly divided into BP-RRM/SP-RCS group (n = 120) and BP-RRM group (n = 120). The patients were followed up at 3 months, 6 months, and 12 months after endodontic microsurgery. Pre- and post-operative clinical and radiographic examinations were performed to evaluate the treatment outcome. The 1-year success rate of endodontic microsurgery in BP-RRM/SP-RCS and BP-RRM groups was compared by Chi-square test. Factors that might impact the prognosis were further analyzed using Chi-square test or Fisher's exact test. RESULTS: A total of 221 teeth completed the 12-month follow-up. The 1-year success rates of the BP-RRM/SP-RCS and BP-RRM groups were 94.5% (104/110) and 92.8% (103/111), respectively. The combined use of BP-RRM and SP-RCS achieved a clinical outcome comparable to BP-RRM alone (P = 0.784). Tooth type (P = 0.002), through-and-through/apico-marginal lesion (P = 0.049), periodontal status (P < 0.0001), and Kim's lesion classification (P < 0.0001) were critical factors associated with the 1-year success of endodontic microsurgery. CONCLUSIONS: The combined use of BP-RRM and SP-RCS is a practicable method for root-end filling in endodontic microsurgery with a satisfactory 1-year clinical outcome. CLINICAL RELEVANCE: The combined application of BP-RRM and SP-RCS in EMS is an effective root-end filling method with a satisfactory 1-year clinical outcome. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052174).

A finite element analysis on the indication for extracting partially impacted mandibular third molars considering mandibular trauma.

BACKGROUND: Patients presenting with partially impacted lower third molars (M3) have a higher likelihood of experiencing angle fractures while simultaneously decreasing the risk of condylar fractures. However, the specific biomechanical mechanism responsible for this occurrence remains unclear. Moreover, there is an ongoing debate regarding whether the removal of M3s might actually increase the risk of condylar fractures. This study aimed to evaluate how the presence of M3s influences mandibular fractures resulting from blows to the symphysis and lateral mandibular body, and to determine the indication for extracting M3s in such cases. METHODS: Models of the mandible with a partially M3-impacted model (M3I), M3-extracted model (M3E), and M3-absent model (M3A) were generated using a computer. A traumatic blown force of 2000 N was applied to the symphysis and the right body of the mandible. Von Mises and principal stresses were analyzed, and failure indexes were determined. Two cases of mandibular linear fractures were chosen for model verification and interpretation. RESULTS: When force was applied to the symphysis, the condylar region exhibited the highest stress levels, while stress in the mandibular angle region was much less regardless of the M3 state. On applying the force to the right mandibular body, stress in the condylar region decreased while stress in the mandibular body increased, especially in the blown regions. Impacted tooth or cavity formation post-M3 extraction led to uneven stress distribution on the blown side of the mandible, increasing the risk of mandibular angle fractures. In cases where M3 was absent or the extraction socket had healed, stress from lateral traumatic blown force was evenly distributed along both the inner and outer oblique lines of the mandible, thereby reducing the risk of mandibular fractures. CONCLUSIONS: The reduced risk of condylar fractures in patients with partially impacted lower M3s and mandibular angle fractures is mainly due to lateral blows on the mandible, which generate less stress in the condylar region than blows on the mandibular symphysis, rather than being caused by the M3 itself. Extraction of the lower M3 can decrease the risk of mandibular fractures, with a minor influence on condylar fractures.

N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer.

BACKGROUND & AIMS: N6-methyladenosine (m6A) governs the fate of RNAs through m6A readers. Colorectal cancer (CRC) exhibits aberrant m6A modifications and expression of m6A regulators. However, how m6A readers interpret oncogenic m6A methylome to promote malignant transformation remains to be illustrated. METHODS: YTH N6-methyladenosine RNA binding protein 1 (Ythdf1) knockout mouse was generated to determine the effect of Ythdf1 in CRC tumorigenesis in vivo. Multiomic analysis of RNA-sequencing, m6A methylated RNA immunoprecipitation sequencing, YTHDF1 RNA immunoprecipitation sequencing, and proteomics were performed to unravel targets of YTHDF1 in CRC. The therapeutic potential of targeting YTHDF1-m6A-Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2) was evaluated using small interfering RNA (siRNA) encapsulated by lipid nanoparticles (LNP). RESULTS: DNA copy number gain of YTHDF1 is a frequent event in CRC and contributes to its overexpression. High expression of YTHDF1 is significantly associated with metastatic gene signature in patient tumors. Ythdf1 knockout in mice dampened tumor growth in an inflammatory CRC model. YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. Integrative multiomics analysis identified RhoA activator ARHGEF2 as a key downstream target of YTHDF1. YTHDF1 binds to m6A sites of ARHGEF2 messenger RNA, resulting in enhanced translation of ARHGEF2. Ectopic expression of ARHGEF2 restored impaired RhoA signaling, cell growth, and metastatic ability both in vitro and in vivo caused by YTHDF1 loss, verifying that ARHGEF2 is a key target of YTHDF1. Finally, ARHGEF2 siRNA delivered by LNP significantly suppressed tumor growth and metastasis in vivo. CONCLUSIONS: We identify a novel oncogenic epitranscriptome axis of YTHDF1-m6A-ARHGEF2, which regulates CRC tumorigenesis and metastasis. siRNA-delivering LNP drug validated the therapeutic potential of targeting this axis in CRC.

PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3ß/ß-catenin axis.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. METHODS: To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3ß/ß-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. RESULTS: The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3ß/ß-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. CONCLUSION: PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3ß/ß-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.

Dual-targeting multifunctional hyaluronic acid ligand-capped gold nanorods with enhanced endo-lysosomal escape ability for synergetic photodynamic-photothermal therapy of cancer.

Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug-loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual-targeting nanoplatform based on hyaluronic acid-grafted-(mPEG/triethylenetetramine-conjugated-lipoic acid/tetra(4-carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) for combined photodynamic-photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen (1 O2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF-7 tumor cells in vitro. Therefore, this work presented an AuNRs-based therapeutic nanoplatform with great potential in dual-targeting and photo-induced combination therapy of cancer.

Results of Excimer Laser Ablation Combined with Drug-Coated Balloon for Atherosclerotic Obliterans of Lower Extremity and Risk Factors for Loss of Primary Patency.

BACKGROUND: The results of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) in the treatment for atherosclerotic obliterans (ASO) remains unclear. METHODS: Retrospectively enrolled patients who underwent ELA combined with DCB in 2 centers. The primary endpoint was primary patency, and secondary endpoints included technical success, procedure-related complications, major amputation, clinically driven target lesions reintervention (CD-TLR), measurements of ankle-brachial index (ABI), and quality of life (QoL). RESULTS: 102 patients were enrolled. The primary patency was 86.7% (95% confidence interval [CI]: 72.9%-89.0%) at 12 months and 82.6% (95% CI: 78.2%-92.1%) at 24 months. The freedom from reintervention was 87.8% (95% CI: 79.5%-92.9%) at 12 months and 86.6% (95% CI: 78.1%-92.0%) at 24 months. The ABI measurement and QoL were significantly improved at each follow-up point. Sixteen (15.7%) patients lost the primary patency. Patients losing the primary patency demonstrated higher Rutherford class (P = 0.004), worse runoff (P < 0.001), higher Peripheral Arterial Calcium Scoring System (PACSS) (P < 0.001), and smaller ratio of tube diameter to reference vessel diameter (TD/RVD) (P < 0.001) compared with patients without losing it. The run-off ≥7 (adjusted odds ratio [aOR]: 34.3; 95% CI: 2.9-398.3; P = 0.005) and TD/RVD <4.9 (aOR: 24.7; 95% CI: 1.7-359.5; P = 0.019) were independent risk factors for loss of primary patency. CONCLUSIONS: ELA combined with DCB seemed an effective and safe treatment for ASO of lower extremity, and it could not only reduce the implantation of stent but significantly improve QoL. The run-off ≥7 and TD/RVD <4.9 were independent risk factors for loss of primary patency.

Association between tooth loss and frailty among Chinese older adults: the mediating role of dietary diversity.

BACKGROUND: This study aimed to examine the association between tooth loss and frailty among Chinese older adults and the mediating role of dietary diversity in this association. METHODS: Data from five waves of the Chinese Longitudinal Healthy Longevity Survey conducted between 2005 and 2018 were used. Path analyses were employed to assess both concurrent and cross-lagged relationships between tooth loss and frailty index while accounting for intrapersonal correlation. Furthermore, the mediation effect of dietary diversity was also examined. RESULTS: In concurrent models, severe tooth loss was associated with frailty after adjusting for demographic characteristics (odds ratio [OR] = 1.82, p < 0.001). The OR of frailty for severe tooth loss was only slightly decreased to 1.74 (p < 0.001) when dietary diversity was added to the model and to 1.64 (p < 0.001) when socioeconomic status, family support, and healthy lifestyles were further adjusted. In the cross-lag or longitudinal models, the ORs were mildly or moderately reduced to 1.29, 1.27, and 1.23, respectively, yet remained statistically significant (p < 0.001 or p < 0.01). The mediation analyses showed that dietary diversity had some small yet significant effects on the relationship between tooth loss and frailty in both concurrent and longitudinal settings. CONCLUSIONS: This study improves current knowledge regarding the impact of tooth loss on frailty among Chinese older adults. Future intervention strategies designed to improve healthy diets may have preventive effects against the risk of frailty among Chinese older adults with severe tooth loss.

Extraction, Modification and Biomedical Application of Agarose Hydrogels: A Review.

Numerous compounds present in the ocean are contributing to the development of the biomedical field. Agarose, a polysaccharide derived from marine red algae, plays a vital role in biomedical applications because of its reversible temperature-sensitive gelling behavior, excellent mechanical properties, and high biological activity. Natural agarose hydrogel has a single structural composition that prevents it from adapting to complex biological environments. Therefore, agarose can be developed into different forms through physical, biological, and chemical modifications, enabling it to perform optimally in different environments. Agarose biomaterials are being increasingly used for isolation, purification, drug delivery, and tissue engineering, but most are still far from clinical approval. This review classifies and discusses the preparation, modification, and biomedical applications of agarose, focusing on its applications in isolation and purification, wound dressings, drug delivery, tissue engineering, and 3D printing. In addition, it attempts to address the opportunities and challenges associated with the future development of agarose-based biomaterials in the biomedical field. It should help to rationalize the selection of the most suitable functionalized agarose hydrogels for specific applications in the biomedical industry.

Effect of various Er:YAG laser conditioning energies on dentin surface: micromorphological investigation and dentin-resin shear bond strength test.

The aim of this study is to assess the influence of various Er:YAG laser energies on dentin surface micromorphology and dentine-resin shear bond strength (SBS). Eighty dentin specimens were prepared and divided randomly into ten groups: control group (CG), phosphoric acid-etched group (AG), four laser-conditioned groups treated with various pulse energies of 40, 60, 80, and 100 mJ (L40, L60, L80, L100), and four laser-conditioned acid-etched groups (LA40, LA60, LA80, LA100). Two specimens from each group underwent scanning electron microscopy examination, while the remaining six were subjected to the dentin-resin SBS test. Statistical analyses included Welch's analysis of variance (ANOVA), followed by post hoc Tamhane's T2 multiple comparisons test, Pearson's correlation, and Fisher's exact test. Pulse energies of 60, 80, and 100 mJ fully exposed the dentin tubule orifices, although 100 mJ lead to microcracks. Laser-conditioned surfaces exhibited smaller tubule diameters compared to acid-etched surfaces, and tubule diameters positively correlated with dentin-resin SBS. Laser-conditioned groups showed lower SBS values, while laser-conditioned acid-etched groups demonstrated higher SBS values. No significant relationship was observed between dentin surface roughness and SBS. The range of laser energies used for dentin conditioning had limited effects on SBS or failure modes. Laser conditioning with energies ranging from 40 to 100 mJ effectively removes the smear layer from the dentin surface. However, to enhance dentin-resin bond strength, further acid etching of the laser-conditioned surface is necessary.

Autophagic response of intestinal epithelial cells exposed to polystyrene nanoplastics.

Growing evidence demonstrates that the bioaccumulation of polystyrene nanoplastics (PS-NPs) in the gastrointestinal tract has negative effects on health. Until now, little information has been available regarding the potential hazards of PS-NPs to intestinal epithelial barriers. In this study, we employed cellular and animal models to investigate the adverse effects of PS-NPs on intestinal epithelium and the underlying mechanism. We found that PS-NPs affected the growth and survival of intestinal epithelial cells in a time- and concentration-dependent manner. PS-NPs accumulated in the cytoplasm, resulting in an impaired autophagic flux and inducing an autophagic response. This response was also confirmed in vivo. Our results provide new insights into the internalization of PS-NPs and the resultant autophagy response in intestinal epithelial cells.

In vitro evaluation of the sealing ability of combined use of iRoot BP Plus and iRoot SP for root-end filling.

OBJECTIVES: The aim of this in vitro study was to evaluate the sealing ability of combined application of iRoot BP Plus Root Repair Material (BP-RRM) and iRoot SP Injectable Root Canal Sealer (SP-RCS) for root-end filling. MATERIAL AND METHODS: A total of 120 extracted human teeth were used in this study and were randomly divided into four groups. The BP-RRM+SP-RCS group included teeth retro-filled with combined use of BP-RRM and SP-RCS (n=45), and the BP-RRM group included teeth retro-filled by BP-RRM alone (n=45). Teeth without root-end preparation and filling were equally divided into positive control (n=15) and negative control (n=15). The apical sealing ability was evaluated by micro-CT analysis, dye penetrant examination, bacterial leakage test, and glucose leakage test. RESULTS: Micro-CT analysis showed that the total void fraction of BP-RRM+SP-RCS group was significantly lower than that of BP-RRM group, particularly at the coronal 1/3 segment of the retro-filled roots. Consistently, the maximum linear depth of dye leakage in BP-RRM+SP-RCS group was less than that of BP-RRM group. Bacterial leakage test showed that the microbial leakage in BP-RRM+SP-RCS group was significantly less than that in BP-RRM group. However, no significant difference in glucose leakage between BP-RRM+SP-RCS group and BP-RRM group was observed. CONCLUSION: Combined use of BP-RRM and SP-RCS for root-end filling promotes apical sealing in vitro. CLINICAL RELEVANCE: Combined use of BP-RRM and SP-RCS for root-end filling exhibited better apical sealing as compared to BP-RRM alone in vitro, and this may help reducing technical sensitivity and promoting clinical efficiency during endodontic microsurgery.

Effects of water flossing on gingival inflammation and supragingival plaque microbiota: a 12-week randomized controlled trial.

OBJECTIVES: The effects of water flossing on dental plaque removal have been suggested, but its ecological impact on dental plaque microbiota needs further investigation. In addition, whether this plaque control measure by water flossing promotes the control of halitosis still needs clinical validation. The aim of this study was to evaluate the effects of water flossing on gingival inflammation and supragingival plaque microbiota. MATERIALS AND METHODS: Seventy participants with gingivitis were randomly assigned to control (toothbrushing) and experimental (toothbrushing + water flossing) groups (n = 35). Participants were recalled at 4, 8, and 12 weeks, and their gingival index, sulcus bleeding index, bleeding on probing, dental plaque index, and oral malodor values were measured. The microbiota of supragingival plaque was further investigated using 16S rRNA sequencing and qPCR. RESULTS: Sixty-three participants completed all revisits (control: n = 33; experimental: n = 30). The experimental and control groups exhibited similar clinical characteristics and dental plaque microbiota at baseline. Adjunctive water flossing effectively reduced the gingival index and sulcus bleeding index as compared to the toothbrushing control group. The water-flossing group showed reduced oral malodor at week 12 as compared to the baseline. Consistently, the water-flossing group exhibited altered dental plaque microbiota at week 12, characterized by a depletion of Prevotella at genus level and Prevotella intermedia at species level as compared to the toothbrushing control. In addition, the plaque microbiota of water-flossing group exhibited a more aerobic phenotype, while the control group was more anaerobic. CONCLUSIONS: Daily water flossing can effectively alleviate gingival inflammation and reduce oral malodor, possibly by depleting oral anaerobes and altering the oral microbiota to a more aerobic phenotype. CLINICAL RELEVANCE: Water flossing adjunctive to toothbrushing effectively alleviated gingival inflammation, representing a promising oral hygiene practice to promote oral health. CLINICAL TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showprojen.aspx?proj=61797 , #ChiCTR2000038508) on September 23, 2020.

Biomechanical Analysis of Different Framework Design, Framework Material and Bone Density in the Edentulous Mandible With Fixed Implant-Supported Prostheses: A Three-Dimensional Finite Element Study.

PURPOSE: The objective of this finite element study was to investigate the effect of different framework designs, framework materials, and bone densities on the stress distribution of fixed implant-supported prostheses for edentulous mandibles. MATERIALS AND METHODS: Under the condition of 2-mm cortical bone, 16 models were created in the edentulous mandible to simulate different framework designs (1-piece or 3-piece frameworks) with different framework material (pure titanium, zirconia, polyetheretherketone, or carbon fiber-reinforced polyetheretherketone) in-high or low-density trabecular bone. Then, vertical loading and oblique loading at 75° were applied to the anterior and posterior regions. The stress distribution and stress concentration region of implant and peri-implant bone with different combinations were compared by finite element analysis. RESULTS: The use of the 1-piece zirconia framework in high-density trabecular bone improved stress distribution on implants and peri-implant bone. The region of stress concentration is located in the buccal cervix of the distal implants and the distobuccal portion of the cortical bone in all models. To improve the stress distribution on fixed implant-supported dentures for edentulous mandibles, the 1-piece framework and zirconia represent the better combination. CONCLUSION: Under the condition of 2-mm cortical bone thickness, the full-arch zirconia framework had minimum von Mises stress on implants and peri-implant bone in all models, and high trabecular bone density greatly decreased the stress on cortical bone.