Point mutations in the catalytic domain disrupt cellulose synthase (CESA6) vesicle trafficking and protein dynamics.

Cellulose, the main component of the plant cell wall, is synthesized by the multimeric cellulose synthase (CESA) complex (CSC). In plant cells, CSCs are assembled in the endoplasmic reticulum or Golgi and transported through the endomembrane system to the plasma membrane (PM). However, how CESA catalytic activity or conserved motifs around the catalytic core influence vesicle trafficking or protein dynamics is not well understood. Here, we used yellow fluorescent protein (YFP)-tagged AtCESA6 and created 18 mutants in key motifs of the catalytic domain to analyze how they affected seedling growth, cellulose biosynthesis, complex formation, and CSC dynamics and trafficking in Arabidopsis thaliana. Seedling growth and cellulose content were reduced by nearly all mutations. Moreover, mutations in most conserved motifs slowed CSC movement in the PM as well as delivery of CSCs to the PM. Interestingly, mutations in the DDG and QXXRW motifs affected YFP-CESA6 abundance in the Golgi. These mutations also perturbed post-Golgi trafficking of CSCs. The 18 mutations were divided into 2 groups based on their phenotypes; we propose that Group I mutations cause CSC trafficking defects, whereas Group II mutations, especially in the QXXRW motif, affect protein folding and/or CSC rosette formation. Collectively, our results demonstrate that the CESA6 catalytic domain is essential for cellulose biosynthesis as well as CSC formation, protein folding and dynamics, and vesicle trafficking.

Clinical outcomes of endodontic microsurgery in complicated cases with large or through-and-through lesions: a retrospective longitudinal study.

OBJECTIVES: To investigate the clinical outcomes of endodontic microsurgery in complicated cases presenting with large or through-and-through lesions. MATERIALS AND METHODS: We retrospectively collected and analyzed preoperative, intraoperative, and follow-up data from 143 complicated cases that underwent endodontic microsurgery. Clinical outcomes were assessed in terms of tooth survival and surgery success. Cox regression analysis was used to evaluate the survival rate and identify associated risk factors. Additionally, the success rate was compared across different postoperative periods, and potential factors contributing to surgical failure were identified through binary logistic regression. RESULTS: The overall survival and success rates were 93.0% and 91.7%, respectively. The Cox regression model identified four risk factors affecting tooth survival, including apicoectomy of four teeth (HR = 35.488; P = 0.0002), an open apex observed on preoperative radiographs (HR = 6.300; P = 0.025), the performance of guided tissue regeneration technique (HR = 8.846; P = 0.028), and a palatal surgical approach (HR = 8.685; P = 0.030). The success rate demonstrated an initial increase in the early postoperative period (from 0.5 to 2 years; P = 5.8124e-30), followed by stabilization (from 2 to 9 years; P = 0.298). Surgery success rate significantly declined when apicoectomy involved four teeth (OR = 109.412; P = 0.002). CONCLUSIONS: Endodontic microsurgery demonstrates satisfactory outcomes in complicated cases, maintaining a stable success rate after two years. However, tooth survival and surgery success are significantly compromised when apicoectomy involves four teeth. Factors such as guided tissue regeneration, an open apex, and the palatal surgical approach are associated with an increased risk of tooth extraction. CLINICAL RELEVANCE: Despite achieving acceptable outcomes in complicated cases, endodontic microsurgery is adversely affected by the apicoectomy of four teeth.

Endosidin20 Targets the Cellulose Synthase Catalytic Domain to Inhibit Cellulose Biosynthesis.

Plant cellulose is synthesized by rosette-structured cellulose synthase (CESA) complexes (CSCs). Each CSC is composed of multiple subunits of CESAs representing three different isoforms. Individual CESA proteins contain conserved catalytic domains for catalyzing cellulose synthesis, other domains such as plant-conserved sequences, and class-specific regions that are thought to facilitate complex assembly and CSC trafficking. Because of the current lack of atomic-resolution structures for plant CSCs or CESAs, the molecular mechanism through which CESA catalyzes cellulose synthesis and whether its catalytic activity influences efficient CSC transport at the subcellular level remain unknown. Here, by performing chemical genetic analyses, biochemical assays, structural modeling, and molecular docking, we demonstrate that Endosidin20 (ES20) targets the catalytic site of CESA6 in Arabidopsis (Arabidopsis thaliana). Chemical genetic analysis revealed important amino acids that potentially participate in the catalytic activity of plant CESA6, in addition to previously identified conserved motifs across kingdoms. Using high spatiotemporal resolution live cell imaging, we found that inhibiting the catalytic activity of CESA6 by ES20 treatment reduced the efficiency of CSC transport to the plasma membrane. Our results demonstrate that ES20 is a chemical inhibitor of CESA activity and trafficking that represents a powerful tool for studying cellulose synthesis in plants.

Microplastic transport during desertification in drylands: Abundance and characterization of soil microplastics in the Amu Darya-Aral Sea basin, Central Asia.

Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.

Endosidin20-1 is more potent than endosidin20 in inhibiting plant cellulose biosynthesis and molecular docking analysis of cellulose biosynthesis inhibitors on modeled cellulose synthase structure.

Endosidin20 (ES20) is a recently identified cellulose biosynthesis inhibitor (CBI) that targets the catalytic site of plant cellulose synthase (CESA). Here, we screened over 600 ES20 analogs and identified nine active analogs named ES20-1 to ES20-9. Among these, endosidin20-1 (ES20-1) had stronger inhibitory effects on plant growth and cellulose biosynthesis than ES20. At the biochemical level, we demonstrated that ES20-1, like ES20, directly interacts with CESA6. At the cellular level, this molecule, like ES20, induced the accumulation of cellulose synthase complexes at the Golgi apparatus and inhibited their secretion to the plasma membrane. Like ES20, ES20-1 likely targets the catalytic site of CESA. However, through molecular docking analysis using a modeled structure of full-length CESA6, we found that both ES20 and ES20-1 might have another target site at the transmembrane regions of CESA6. Besides ES20, other CBIs such as isoxaben, C17, and flupoxam are widely used tools to dissect the mechanism of cellulose biosynthesis and are also valuable resources for the development of herbicides. Here, based on mutant genetic analysis and molecular docking analysis, we have identified the potential target sites of these CBIs on a modeled CESA structure. Some bacteria also produce cellulose, and both ES20 and ES20-1 inhibited bacterial cellulose biosynthesis. Therefore, we conclude that ES20-1 is a more potent analog of ES20 that inhibits intrinsic cellulose biosynthesis in plants, and both ES20 and ES20-1 show an inhibitory effect on bacterial growth and cellulose synthesis, making them excellent tools for exploring the mechanisms of cellulose biosynthesis across kingdoms.

MXene Composite Membranes with Enhanced Ion Transport and Regulated Ion Selectivity.

Two-dimensional (2D) material-based membranes are promising candidates for various separation applications. However, the further enhancement of membrane ion conductance is difficult, and the regulation of membrane ion selectivity remains a challenge. Here, we demonstrate the facile fabrication of MXene composite membranes by incorporating spacing agents that contain SO3H groups into the MXene interlayers. The synthesized membrane shows enhanced ion conductance and ion selectivity. Subsequently, the membranes are utilized for salinity gradient power (SGP) generation and lithium-ion (Li+) recovery. The membrane containing poly(sodium 4-styrenesulfonate) (PSS) as the spacing agent shows a much higher power density for SGP generation as compared to the pristine MXene membrane. Using artificial seawater and river water, the power density reaches 1.57 W/m2 with a testing area of 0.24 mm2. Also, the same membrane shows Li+/Na+ and Li+/K+ selectivities of 2.5 and 3.2, respectively. The incorporation of PSS increases both the size and charge density of the nanochannels inside the membrane, which is beneficial for ion conduction. In addition, the density functional theory (DFT) calculation shows that the binding energy between Li+ and the SO3H group is lower than other alkali ion metals, and this might be one major reason why the membrane possesses high Li+ selectivity. This study demonstrates that incorporating spacing agents into the 2D material matrix is a viable strategy to enhance the performance of the 2D material-based membranes. The results from this study can inspire new membrane designs for emerging applications including energy harvesting and monovalent ion recovery.

The Mode of Action of Endosidin20 Differs from That of Other Cellulose Biosynthesis Inhibitors.

Endosidin20 (ES20) was recently identified as a cellulose biosynthesis inhibitor (CBI) that targets the catalytic domain of CELLULOSE SYNTHASE 6 (CESA6) and thus inhibits the growth of Arabidopsis thaliana. Here, we characterized the effects of ES20 on the growth of other plant species and found that ES20 is a broad-spectrum plant growth inhibitor. We tested the inhibitory effects of previously characterized CBIs (isoxaben, indaziflam and C17) on the growth of Arabidopsis cesa6 mutants that have reduced sensitivity to ES20. We found that most of these mutants are sensitive to isoxaben, indaziflam and C17, indicating that these tested CBIs have a different mode of action than ES20. ES20 also has a synergistic inhibitory effect on plant growth when jointly applied with other CBIs, further confirming that ES20 has a different mode of action than isoxaben, indaziflam and C17. We demonstrated that plants carrying two missense mutations conferring resistance to ES20 and isoxaben can tolerate the dual inhibitory effects of these CBIs when combined. ES20 inhibits Arabidopsis growth in growth medium and in soil following direct spraying. Therefore, our results pave the way for using ES20 as a broad-spectrum herbicide, and for the use of gene-editing technologies to produce ES20-resistant crop plants.

MR/NIRF Dual-Mode Imaging of αvß3 Integrin-Overexpressing Tumors Using a Lipopeptide-Based Contrast Agent.

Early diagnosis and noninvasive detection of hepatocellular carcinoma have profound clinical implications for treatment quality and improved prognosis. To obtain high-resolution macroscopic anatomical information and high-sensitivity microscopic optical signals to detect tumors, it is highly desirable to develop dual-mode magnetic resonance imaging (MRI) and near-infrared fluorescent (NIRF) probes. An MR/NIRF dual-mode targeted contrast agent was created by encapsulating cyclic arginine-glycine-aspartate (cRGD) and Cy5.5 in liposomes and characterized by the particle size distribution, cytotoxicity, targeting, and MRI relaxivity. The MR T2 intensity and fluorescence intensity were evaluated in the tumors, livers, and muscles after the injection of cRGD-Liposome-Cy5.5 and Liposome-Cy5.5 at different time points. The average size of cRGD-Liposome-Cy5.5 was 62.33 ± 4.648 nm. The transverse relaxivity (R2) values had a negative correlation with the concentration of molecular probes. The MR signal intensity was enhanced in tumors after the cRGD-Liposome-Cy5.5 injection and not enhanced in liver parenchyma and muscles at the same time. The fluorescence intensity was enhanced in tumors after cRGD-Liposome-Cy5.5 injection in the targeted group. cRGD -Liposome-Cy5.5 as an entirely organic T2-positive dual-mode MR/NIRF targeted contrast agent is therefore able to detect early-stage hepatocellular carcinoma by targeting integrin αvß3, providing advantages for potential clinical utility and ease of clinical transformation.

All-Organic Dielectrics with High Breakdown Strength and Energy Storage Density for High-Power Capacitors.

Polymer-based film capacitors with high breakdown strength and excellent flexibility are crucial in the field of advanced electronic devices and electric power systems. Although massive works are carried to enhance the energy storage performances, it is still a great challenge to improve the energy density of polymer composites under the premise of large-scale industrial production. Herein, a general strategy is proposed to improve the intrinsic breakdown strength and energy storage performances by blending core-shell structured methyl methacrylate-butadiene-styrene (MBS) rubber particles into a polymer matrix. Good compatibility and uniform dispersion state of MBS particles are observed in the matrix. Polarizing microscopy images show that blended films exhibit clear reduction of crystalline grains with the addition of MBS particles. Accordingly, an increased breakdown strength of 515 MV m-1 and discharged energy density of 12.33 J cm-3 are observed in poly(vinylidene fluoride-co-hexafluoropropylene)-based composite films. Through comprehensive characterizations, it is believed that the superior energy storage performance of composite films is attributed to decreased crystalline grains, improved mechanical properties, and restriction on carrier motion. These results provide a novel design of dielectric polymers for high breakdown strength and discharged energy density applications.

Clinical efficacy of curcumin versus chlorhexidine as an adjunct to scaling and root planing for the treatment of periodontitis: A systematic review and meta-analysis.

This study aims to evaluate the clinical efficacy of curcumin versus chlorhexidine as adjuncts to scaling and root planing (SRP) for periodontitis treatment. We searched PubMed, EMbase, Cochrane Library, and ClinicalTrials.gov from inception to February 18, 2021 and identified studies with relevant randomized controlled trials (RCTs) using curcumin or chlorhexidine as an adjunct to SRP. Nine RCTs involving 420 patients/sites were included. A meta-analysis with a random-effects model revealed that curcumin and chlorhexidine, as an adjunct to SRP, reduced probing pocket depth (PPD) at similar levels during a 3-, 4-, 6-, and 12-week follow-up. No significant differences were observed in reducing clinical attachment loss (CAL) between curcumin and chlorhexidine as an adjunct to SRP at 4 weeks and 6 weeks. Furthermore, gingival index (GI) and plaque index (PI) were similar using curcumin versus chlorhexidine as an adjunct to SRP at the 4-week-, 6-week-, and 12-week follow-up. Based on the available evidence in RCTs, compared with chlorhexidine as an adjunct to SRP, curcumin has a similar effect on reducing PPD, CAL, GI, and PI. The quality of evidence is low, limited by the number of studies and their limitations. Further studies are needed to firmly establish the clinical efficacy of curcumin.

Study on the Transport Mechanism of a Freestanding Graphene Oxide Membrane for Forward Osmosis.

Graphene oxide membranes (GOMs) are promising separation technologies. In forward osmosis (FO), we found that the water flux from the feed solution to the draw solution can prevent ions from diffusing to the feed solution in a highly tortuous and porous GOM. In reverse osmosis (RO), we found that the salt rejection is low compared to that in commercially available RO membranes. While this prohibits the use of GOMs for RO and FO water desalination, we believe that such membranes could be used for other water treatment applications and energy production. To examine the transport mechanism, we characterized the physical and chemical properties of GOMs and derived mass transfer models to analyze water and salt transport inside freestanding GOMs. The experimental reverse salt flux was between the largest and smallest theoretical values, which corresponds to the lowest and highest tortuosity, respectively, in FO. Furthermore, the concentration profile for the reverse salt flux shortened as the NaCl draw concentration increased because the water flux increased and the electrical double layer (EDL) decreased with increasing NaCl in the draw solution. We provide insights into the transport mechanisms in GOMs and provide guidance for future exploration of GOMs in efficient water treatment and energy production processes.

Rattle-Type Gold Nanorods/Porous-SiO2 Nanocomposites as Near-Infrared Light-Activated Drug Delivery Systems for Cancer Combined Chemo-Photothermal Therapy.

Rattle-type nanostructures with movable cores, porous shells, and hollow interiors have become attractive nanoplatforms in the field of nanomedicine, especially for targeted and stimuli-responsive drug delivery. In this work, rattle-type gold nanorods@void@porous-SiO2 (GVPS) nanocomposites were fabricated facilely using the surface-protecting etching method and exhibited high photothermal conversion efficiency. Taking advantage of the porous shell and hollow interior, the nanocomposites have abundant space for drug loading and successfully improved the drug loading capacity up to ∼19.6%. To construct a multifunctional drug delivery system, GVPS was further functionalized with polyethylene glycol (PEG) and cyclic RGD peptides to improve biocompatibility as well as selectivity toward the targeted cancer cells. Besides, to achieve precise regulation and near-infrared laser activation of the drug release, a phase-changing material, 1-tetradecanol (1-TD, Tm: 39 °C), was employed as gatekeepers in this system. After incubation with an αVß3 integrin receptor-overexpressed cell line, the as-prepared GVPSPR-DOX/TD nanocomposites exhibited great performances in combined photothermal therapy and chemotherapy. It is worth noting that the combined therapy showed superior efficiency in cancer cell killing to chemotherapy or photothermal therapy alone.

Salt-Induced Regenerative Surface for Bacteria Killing and Release.

Antibacterial surfaces with both bacteria killing and release functions show great promise in biological and biomedical applications, in particular for reusable medical devices. However, these surfaces either require a sophisticated technique to create delicate structures or need rigorous stimuli to trigger the functions, greatly limiting their practical application. In this study, we made a step forward by developing a simple system based on a salt-responsive polyzwitterionic brush. Specifically, the salt-responsive brush of poly(3-(dimethyl (4-vinylbenzyl) ammonium) propyl sulfonate) (polyDVBAPS) was endowed with bactericidal function by grafting an effective bactericide, i.e., triclosan (TCS). This simple functionalization successfully integrated the bacteria attach/release function of polyDVBAPS and bactericidal function of TCS. As a result, the surface could kill more than 95% attached bacteria and, subsequently, could rapidly detach ∼97% bacteria after gently shaking in 1.0 M NaCl for 10 min. More importantly, such high killing efficiency and release rate could be well retained (unchanged effectiveness of both killing and release after four severe killing/release cycles), indicating the highly efficient regeneration and long-term reusability of this system. This study not only contributes zwitterionic polymers by conferring new functions but also provides a new, highly efficient and reliable surface for "killing-release" antibacterial strategy.

Design, synthesis, and biological evaluation of anti-EV71 agents.

Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. In this article, design, chemical synthesis, and biological evaluation of various anti-EV71 agents which incorporate Michael acceptors are described. Further SAR study demonstrated that lactone type of Michael acceptor provided a new lead of anti-EV71 drug candidates with high anti-EV71 activity in cell-based assay and enhanced mouse plasma stability. One of the most potent compounds (2K, cell-based anti-EV71 EC50=0.028µM), showed acceptable stability profile towards mouse plasma, which resulted into promising pharmacokinetics in mouse via IP administration.

Nurse-physician collaboration impacts job satisfaction and turnover among nurses: A hospital-based cross-sectional study in Beijing.

This study aims to explore the impact of physician-nurse collaboration on nurse job satisfaction and turnover in a dental hospital. Physician-nurse collaboration is important for the stability of the entire nursing team. Few studies have shown the impact on job satisfaction and turnover among nurses working in Chinese dental hospitals. This was a prospective, cross-sectional study and investigated nurses from a tertiary dental hospital in Beijing using convenience non-randomized sampling. A structured questionnaire was used to collect data, which included general information, the Index of Work Satisfaction, the Nurse-Physician Collaboration Scale and the Turnover Intention Scale. The scores of physician-nurse collaboration correlated positively with those for job satisfaction and negatively with the stated likelihood of turnover intention. Physician-nurse collaboration scores positively predicted job satisfaction and negatively predicted the likelihood of quitting the current job. In conclusion, improving the level of physician-nurse collaboration is helpful to enhance job satisfaction and reduce turnover among nurses in a dental hospital.

A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree.

Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically heterogeneous group of inherited neuropathies. Here, we report a five-generation family of eight affected individuals with CMT disease type 2, CMT2. Genome-wide linkage analysis showed that the disease phenotype is closely linked to chromosomal region 10p13-14, which spans 5.41 Mb between D10S585 and D10S1477. DNA-sequencing analysis revealed a nonsense mutation, c.1455T>G (p.Tyr485(∗)), in exon 8 of dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1) in all eight affected individuals, but not in other unaffected individuals in this family or in 250 unrelated normal persons. DHTKD1 mRNA expression levels in peripheral blood of affected persons were observed to be half of those in unaffected individuals. In vitro studies have shown that, compared to wild-type mRNA and DHTKD1, mutant mRNA and truncated DHTKD1 are significantly decreased by rapid mRNA decay in transfected cells. Inhibition of nonsense-mediated mRNA decay by UPF1 silencing effectively rescued the decreased levels of mutant mRNA and protein. More importantly, DHTKD1 silencing was found to lead to impaired energy production, evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels. In conclusion, our data demonstrate that the heterozygous nonsense mutation in DHTKD1 is one of CMT2-causative genetic alterations, implicating an important role for DHTKD1 in mitochondrial energy production and neurological development.

Engineering DNA nanoparticles as immunomodulatory reagents that activate regulatory T cells.

Nanoparticles containing DNA complexed with the cationic polymer polyethylenimine are efficient vehicles to transduce DNA into cells and organisms. DNA/polyethylenimine nanoparticles (DNPs) also elicit rapid and systemic release of proinflammatory cytokines that promote antitumor immunity. In this study, we report that DNPs possess previously unrecognized immunomodulatory attributes due to rapid upregulation of IDO enzyme activity in lymphoid tissues of mice. IDO induction in response to DNP treatment caused dendritic cells and regulatory T cells (Tregs) to acquire potent regulatory phenotypes. As expected, DNP treatment stimulated rapid increase in serum levels of IFN type I (IFN-αß) and II (IFN-γ), which are both potent IDO inducers. IDO-mediated Treg activation was dependent on IFN type I receptor signaling, whereas IFN-γ receptor signaling was not essential for this response. Moreover, systemic IFN-γ release was caused by TLR9-dependent activation of NK cells, whereas TLR9 signaling was not required for IFN-αß release. Accordingly, DNPs lacking immunostimulatory TLR9 ligands in DNA stimulated IFN-αß production, induced IDO, and promoted regulatory outcomes, but did not stimulate potentially toxic, systemic release of IFN-γ. DNP treatment to induce IDO and activate Tregs blocked Ag-specific T cell responses elicited in vivo following immunization and suppressed joint pathology in a model of immune-mediated arthritis. Thus, DNPs lacking TLR9 ligands may be safe and effective reagents to protect healthy tissues from immune-mediated destruction in clinical hyperimmune syndromes.

Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration.

Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.

Limitations and Management of Dynamic Navigation System for Locating Calcified Canals Failure.

Nonsurgical endodontic teeth treatment with severe pulp canal obliteration poses challenges, primarily locating canals. By combining 3-dimensional reconstruction and spatial location registration, the dynamic navigation technique uses an optical tracking system to guide the clinician to drill in real time according to the predesigned path until access to the canal is established. Several in vitro studies and case reports have shown that calcified canal location with dynamic navigation system (DNS) is more accurate and efficient, yet the technique has limitations. In 4 cases with 7 teeth, this work presents manipulation process and clinical outcomes of DNS helping in calcified canal location. We performed handpiece adaptation and elucidated the failure to locate the canals with DNS in 2 teeth, resulting in canal geometry alteration and canal path deviation. Subsequently, the more experienced endodontist located the canals by combining cone-beam computed tomographic imaging and dental operating microscopy. All patients were completely asymptomatic after treatment. At the 1-year follow-up visit, the bone healing of periapical lesions progressed well according to the periapical radiography or cone-beam computed tomographic imaging. These findings indicate that DNS is a promising technique for locating calcified canals; however, it needs to be refined before clinical use.

GelMA-based hydrogel biomaterial scaffold: A versatile platform for regenerative endodontics.

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.