Peroral endoscopic myotomy (POEM) is an established treatment for achalasia. Conventionally, esophageal myotomy of 6-10cm length is performed, although its necessity in type-I and type-II achalasia remains debatable. Recent studies suggest that a shorter myotomy may offer similar efficacy with potential advantages. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing short vs. standard (long) esophageal myotomy during POEM in patients with type-I and type-II achalasia. This review was conducted in accordance with PRISMA 2020 guidelines and registered with PROSPERO (CRD42024611252). A systematic search of PubMed, Embase and Scopus was performed to identify RCTs comparing short and long esophageal myotomy during POEM. The primary outcome was clinical success at ≥ 1year (Eckardt score ≤ 3). Secondary outcomes included procedure time, adverse events, post-POEM integrated relaxation pressure (IRP), barium column height and gastroesophageal reflux disease (GERD). Risk of bias was assessed using the Cochrane RoB 2.0 tool and the certainty of evidence was evaluated using the GRADE framework. Four RCTs including 419 patients (short, n = 206; long, n = 213) were analyzed. Clinical success at one year was comparable between the two groups (OR 2.17; 95% CI = 0.76-6.23; p = 0.15; I2 = 12%). Procedure time was significantly shorter with short myotomy (MD - 17.69min; p < 0.001). Rates of adverse events and physiological outcomes (IRP, barium retention) were similar. While overall GERD rates were comparable, esophageal acid exposure was significantly lower in the short myotomy group (OR 0.69; p = 0.04). Short esophageal myotomy is non-inferior to long myotomy in clinical efficacy with the added benefit of shorter procedure time and potentially reduced acid exposure. These findings support the use of short myotomy as a safe and efficient alternative in type-I and type-II achalasia.

Gene-engineered T cell therapies, particularly chimeric antigen receptor (CAR)-T cells, have demonstrated remarkable clinical success. However, concerns regarding insertional mutagenesis and other risks associated with genetic modification remain. Here, a non-genetic strategy is presented for T cell engineering using glycopolymer modification. It develops glycopolymer-modified T (G-T) cells based on antigen-specific T cells by integrating metabolic glycoengineering and click chemistry, yielding cells that retain T cell functionality while significantly enhancing tumor enrichment. The polyvalent glycopolymer-receptor interactions significantly improved the binding affinity of G-T cells to various glucose transporter 1 (GLUT1)-overexpressing tumor cells, resulting in increased cytotoxicity compared to unmodified T cells. In the tumor microenvironment, G-T cells engaged in stronger immune crosstalk with dendritic cells (DCs), upregulating interferon-gamma (IFN-γ) and interleukin-12 (IL-12) secretion and amplifying the anti-tumor immune response. Notably, despite the lower specificity of glycan-receptor interactions compared to antigen-antibody binding, the findings reveal an unexpected advantage: the "less restrictive" nature of glycan-receptor recognition enhances both tumor and immune cell interactions, triggering a potent immune cascade. This study establishes a universal, non-genetic T cell engineering strategy with broad applicability, offering a new perspective for tumor immunotherapy by merging biomedical polymer materials with immune modulation.

This split-mouth randomized controlled clinical trial aimed to assess the 12-month clinical and radiographic outcomes of four different pulpotomy materials in primary molars. The materials evaluated were Mineral Trioxide Aggregate (MTA), Biodentine, Ferric Sulfate (FS), and Sodium Hypochlorite (NaOCl) gel. Healthy children aged 4-7 with four primary molars requiring pulpotomy were included. Coronal pulpotomy was performed, followed by application of one of the four materials, and restoration with stainless steel crowns. Clinical and radiographic assessments were conducted at 6 and 12months. Success rates were compared using Fisher's Exact and Cochran's Q tests. A total of 22 children (88 teeth) completed the study. At 12months, clinical success was 100% in the MTA, Ferric sulfate and NaOCl gel groups, and 95.5% in the Biodentine group. Radiographic success was 100% for MTA and NaOCl gel, 95.5% for Biodentine, and 81.8% for FS (p < 0.05). Most failures occurred in first primary molars. MTA and Biodentine demonstrated high clinical and radiographic success, with Biodentine offering a faster procedure. NaOCl gel showed promising outcomes comparable to MTA. However, FS had lower radiographic success, indicating limitations for long-term use.Trial registration number: NCT07120321. Data: 08 August 2025. Retrospectively registered.

Abstract Purpose To describe the technique and evaluate the safety and clinical efficacy of CT-guided thermal ablation for postoperative isolated bile leakage (IBL) in patients with disconnected bile ducts. Materials and Methods This retrospective study included 14 patients with postoperative IBL following liver resection between 2016 and 2024. All patients underwent CT-guided radiofrequency ablation (RFA) as treatment for IBL. Technical success was defined as appropriate coverage of the leakage site on post-ablation CT. Clinical success was defined as cessation of IBL; time to leak cessation was recorded accordingly. Total percutaneous biloma drainage time and peri-/post-interventional complications were evaluated accordingly. Results Technical success was achieved in all ablation procedures with no major adverse events. Clinical success was observed in 93% ( n = 13) of patients. One patient experienced recurrence of IBL within 30 days. Median total drainage time was 33.5 (IQR 20–62) days. The median time to leak cessation after RFA was 4.5 (IQR 4–6) days. Conclusion CT-guided thermal ablation appears to be an effective and safe treatment option for postoperative IBL, helping to reduce the duration of drainage therapy. Graphical Abstract

The proinflammatory cytokine IL-17 is crucial for host defense but has also been linked to various inflammatory and autoimmune diseases. Antibody-based IL-17 inhibitors like secukinumab (Cosentyx) have demonstrated clinical success in psoriasis, psoriatic arthritis, and ankylosing spondylitis, sparking efforts to develop orally bioavailable small molecule alternatives. However, most small molecule IL-17 inhibitors failed in preclinical and clinical stages due to safety concerns and other challenges. This work describes the discovery of a 1,2,4-triazole scaffold that acts as an amide bioisostere. Its unique vector toward the Trp90 pocket, a key cavity for ligand binding, required the development of novel motifs. A structure-based library approach, considering the high plasticity of the Gln117 side chain, yielded structurally diverse Trp90 pocket binding motifs. The X-ray structures of the most potent hits guided subsequent optimization, resulting in triazole-based IL-17 inhibitors with low nanomolar cellular activity, which are promising leads for further development.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an emerging alternative to percutaneous transhepatic biliary drainage (PTBD) in patients with a malignant biliary obstruction, in case of technical failure of endoscopic retrograde cholangiopancreatography (ERCP). However, this procedure is technically challenging, and dedicated stents have only recently become available. This study prospectively evaluated the safety and feasibility of EUS-HGS with a dedicated stent. This prospective single-center study included patients with inoperable malignant biliary obstruction that underwent an EUS-HGS. The primary outcome was safety. Technical and clinical success were evaluated as secondary endpoints. We used a partially covered self-expandable metal stent (pcSEMS) (30% uncovered and 70% covered) with anti-migration features. EUS-HGS was attempted in 28 patients, achieving technical and clinical success rates of 89% (25/28) and 96% (22/23), respectively. Three patients (11%) experienced grade IIIA adverse events (AEs) (all cholangitis) within 30days: two with undrained right-sided bile ducts requiring percutaneous drainage, and one patient due to blockage of a side branch at the level of the covered part of the stent for which an endoscopic stent exchange was successfully performed. Five patients died < 30days due to disease progression, none of these patients experienced procedure-related AEs. Six out of the 22 patients with clinical success developed recurrent biliary obstruction after a median of 78days (IQR 45-108). Obstruction was caused by hyperplasia at the uncovered portion of the stent (n = 3) and due to sludge obstructing the stent (n = 3). Successful re-intervention was performed in all patients. This prospective study shows that EUS-HGS with a dedicated pcSEMS is feasible and safe. Tissue hyperplasia in the uncovered part of the stent and sludge obstruction may compromise long-term stent patency. Larger, comparative prospective studies are needed to assess optimal stent design and timing of EUS-HGS within the therapeutic algorithm.

Peptide therapeutics are rapidly emerging as a new drug modality, bridging the gap between small molecules and biologics to target diseases such as diabetes, cancer, and cardiovascular disorders. Despite their advantages, challenges like metabolic instability, low permeability, and rapid clearance hinder their clinical development. This perspective focuses on addressing challenges in the metabolism of peptides by exploring key strategies including structural modifications (cyclization, incorporation of noncanonical amino acids, PEGylation, and lipidation) alongside advancements in delivery technologies (nanoparticles and protein conjugation). Low permeability and bioavailability of peptides are also briefly covered. Case studies, including semaglutide, MK-0616, LUNA18, sulanemadlin, and oxytocin analogs, illustrate successful applications of these strategies, highlighting how rational design and optimization have advanced peptide candidates from discovery to clinical stage.

BackgroundImmune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have achieved major clinical success in cancer therapy. However, IgG-based checkpoint inhibitors face limitations such as large molecular size restricting tumor penetration and Fc effector–mediated depletion of PD-1–expressing T cells. While IgG antibodies can be engineered to modulate these effects, such tunability often requires complex modifications. To overcome these drawbacks, alternative protein scaffolds that retain checkpoint specificity while enabling more compact design and greater engineering flexibility are needed. Wild-type PD-L1, a native ligand of PD-1, exhibits micromolar binding affinity and limited therapeutic utility, highlighting the need for ligand-based engineering approaches that provide improved modularity and predictable receptor engagement.ResultsWe developed a compact and tunable PD-L1 variant through yeast surface display–based directed evolution. A mutagenized PD-L1 ectodomain library was screened to isolate high-affinity variants, yielding a double mutant (DM) with a 173-fold enhancement in PD-1 binding over the wild-type. In silico immunogenicity analysis predicted that the DM variant maintains low potential immunogenicity, comparable to native PD-L1, despite the engineered mutations. Structural modeling revealed that this affinity gain was driven by a de novo interfacial salt bridge and enhanced hydrophobic complementarity at the PD-1 interface. Functional assays demonstrated that the DM variant restored T cell activity, as evidenced by increased interferon-γ and interleukin-2 secretion in co-culture systems. The DM variant retained favorable biophysical properties and is compatible with modular fusion formats for therapeutic integration.ConclusionThis study demonstrates the successful application of directed evolution to generate a compact PD-L1 variant with high-affinity PD-1 binding, low immunogenicity risk, and tunable architecture. The DM variant expands the design space of ligand-based checkpoint inhibitors and offers a versatile platform for next-generation immunotherapeutics engineered through synthetic biology frameworks.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13036-025-00577-x.

ObjectiveThe aim of this study was to investigate the surface roughness, gloss and microhardness values ​​of 3D-printed permanent resins after the use of polishing systems.Materials and methodsIn this study, a total of 112 specimens were prepared from permanent resin using SLA and DLP 3D printers, with each material group comprising 56 specimens of 10 mm in diameter and 2 mm in thickness. One-step, two-step and multi-step polishing systems were applied to the prepared samples. Polishing systems were classified into two subgroups according to the use of diamond polishing paste. Surface roughness, microhardness, and gloss values were measured for all specimens following the polishing procedures. Statistical analysis was conducted using a two-way analysis of variance (ANOVA) (p < 0.05).ResultsApplication of one-step, two-step and multi-step polishing systems to 3D-printed resin specimens resulted in significantly lower surface roughness and higher gloss values (p < 0.05). The use of polishing paste following all systems further reduced surface roughness and increased gloss (p < 0.05). After two-step and multi-step polishing systems, the surface roughness of the paste-applied groups decreased below 0.2 μm and the gloss increased above 80 GU. Polishing procedures also enhanced the microhardness of the specimens (p < 0.05). However, the application of polishing paste after one-step, two-step, and multi-step systems did not result in a statistically significant difference in microhardness values (p > 0.05).ConclusionsApplication of two-step and multi-step polishing systems to 3D-printed permanent resin specimens significantly reduces surface roughness while enhancing microhardness and gloss values. While the application of polishing paste after polishing systems did not influence microhardness, it positively affected surface roughness and gloss, thereby potentially enhancing clinical success.

Achalasia is a rare esophageal motility disorder marked by impaired lower esophageal sphincter relaxation. Peroral endoscopic myotomy (POEM) has become a first-line therapy owing to its minimally invasive approach and proven efficacy. This study aimed to define the POEM learning curve for experienced endoscopists at a tertiary Chinese medical center. We retrospectively reviewed 168 POEM procedures performed between 2015 and 2021 by three endoscopists, each with experience in > 100 endoscopic submucosal dissections (ESD) cases and trainings on three animal-model. Cumulative sum (CUSUM) analysis of procedure time was the primary measure. Secondary outcomes included complications, length of hospital stay, and 3-year clinical success rate (Eckardt score ≤ 3). Learning curve inflection points occurred at 15-20 cases, after which procedure time decreased significantly (94.9 ± 27.4 vs. 55.5 ± 15.5min, p < 0.001). Complication rates were stable (competence phase: 19.6% vs. proficiency phase: 17.1%, p = 0.70), while hospital stay was shorter in the proficiency phase (7.6 ± 2.5 vs. 6.6 ± 2.0days, p = 0.009). Both phases achieved high 3-year success rates (90% vs. 95%, p = 0.563), consistent with published benchmarks. For endoscopists with prior ESD expertise, POEM proficiency can be achieved after 15-20 cases, with safety and efficacy maintained throughout training. Shorter hospital stays in the proficiency phase likely reflect improvements in perioperative management.

To evaluate the technical and clinical success, as well as the safety, of single-operator, single-session percutaneous cholangioscopy for the management of biliary stone disease. Thirty-four non-surgical patients (median age 69years; 14 female, 20 male) from two tertiary care hospitals underwent 37 percutaneous cholangioscopy-guided stone extraction procedures between March 2023 and August 2025. Patient characteristics, procedural details, technical and clinical success, and complications were retrospectively reviewed. Twenty-six patients underwent percutaneous cholecystostomy (PC) and eight underwent percutaneous transhepatic biliary drainage (PTBD) prior to cholangioscopy. Primary technical success was 91.2% (31/34; 95% CI, 76.3-98.1)-88.5% in the PC cohort (23/26) and 100% in the PTBD cohort (8/8). After three repeat procedures, secondary technical success reached 100%. Clinical success, defined as the absence of recurrent cholecystitis or biliary colic, was achieved in 91.2% of patients over a median follow-up of 413days. The median drain dwell time was 113days, with a median interval of 14days from stone extraction to drain removal. Two procedure-related complications occurred-one cystic duct injury and one pleural effusion (CIRSE classification 1a and 3b, respectively)-along with one non-procedure-related complication of prolonged delirium (CIRSE classification 3b). Single-session percutaneous cholangioscopy-guided biliary stone management demonstrates high technical and clinical success with minimal complications and appears to be a viable treatment option for high-risk patients who are not candidates for surgery or peroral endoscopic interventions.

Ceramic materials have gained outstanding popularity in restorative and prosthetic dentistry due to their combination of high biocompatibility, mechanical durability, and natural esthetics. Among the most important developments in this field are the use of zirconia- and glass-based ceramics for various applications. Zirconia ceramics, especially yttria-stabilized tetragonal zirconia polycrystals (Y-TZP), are famous for their high mechanical strength, transformation toughening, chemical stability, and great biocompatibility. Newer generations like 4Y/5Y-PSZ zirconia have addressed the demand for higher translucency, meeting esthetic requirements. Glass–ceramics, including lithium disilicate and leucite-reinforced systems, are preferred for their optical properties, etchability, and strong adhesive bonding. Their microstructure provides a balance between strength and esthetics, supporting minimally invasive restorations with long-term clinical success. Both zirconia and glass–ceramics exhibit favorable biological responses, including low plaque accumulation and soft tissue compatibility. The goal of ongoing research is to overcome limitations, such as low-temperature degradation, bonding limitations, and surface durability. Also, to improve mechanical performance and functional integration, new approaches include 3D printing, graded materials, nanostructuring, and bioactive coatings. This review aims to provide a comprehensive overview of the composition, properties, clinical applications, current limitations, and future perspectives of zirconia- and glass-based ceramics in restorative dentistry.

Despite the clinical success of tropomyosin receptor kinases (TRKs) inhibitors in NTRK fusion-positive cancers, prolonged administration has resulted in acquired resistance, particularly xDFG mutations, for which no approved therapies are available. Herein, we first presented a series of bifunctional agents as potent TRK inhibitors and degraders featuring a novel 5-amino-4-carbamoylpyrazole scaffold. The representative compounds 19 and 20 demonstrated potent antiproliferative activities against Ba/F3-LMNA-NTRK1G667C cells with IC50 values of 0.29 and 2.48 nM, respectively, and induced pronounced TRKA G667C degradation (DC50 = 5.86 and 24.69 nM; Dmax > 90%), while sparing the wild-type protein. Further in vivo assay displayed that 20 effectively inhibited tumor growth with no apparent toxicity in the Ba/F3-LMNA-NTRK1G667C xenograft model. Overall, these findings indicated that, unlike conventional inhibitors, such bifunctional agents represent the first class of monovalent small molecules capable of effectively degrading TRK xDFG mutants, providing valuable insights into overcoming TRK xDFG-mediated clinical resistance.

Statins are clinically effective drugs for treating dyslipidemia and have been proposed as promising antineoplastic and adjuvant agents in cancer therapy for years due to their impact on dysregulated cell growth processes, including cell signaling, energetics, and membrane synthesis. Despite being potent inhibitors of mevalonate synthesis and its downstream products, their limited clinical success highlights the need to further explore their mechanistic effects. Leveraging the observed sensitivity of muscle cells to atorvastatin in clinical settings and utilizing untargeted metabolomic analysis of atorvastatin-treated RD rhabdomyosarcoma cells, we identified reduced levels of aminoadipic acid, an intermediate in lysine catabolism. We investigated whether metabolic sensitization of RD cells to lysine-related metabolites (lysine, aminoadipic acid, pipecolic acid, glutamic acid, α-ketoglutarate, and lysine-p-nitroanilide) prior to atorvastatin treatment enhances its cytotoxic effects. Metabolic sensitization or reprogramming involves cellular processes wherein cells adapt their metabolism to environmental changes, reflecting alterations in enzymatic activity, transport, and stress response thresholds. These adaptations enable cells to cope with specific environmental pressures but may impair their ability to respond to other stressors or stimuli. To evaluate the impact of metabolic supplementation, we analyzed cellular stress response markers via western blot. The results revealed that lysine-p-nitroanilide increased BiP, the master regulator of the unfolded protein response, and augmented the phosphorylation at threonine 172 of AMPK, an indicator of altered cellular energetics. Further analysis demonstrated that combining lysine-p-nitroanilide with atorvastatin disrupted mitochondrial homeostasis and reduced glycolysis, both desirable outcomes in antineoplastic treatments. Lysine-p-nitroanilide acts as an in vitro inhibitor of α-aminoadipic semialdehyde synthase, enzyme essential for lysine metabolism via the saccharopine pathway. However, we demonstrated that it is catabolically cleaved to p-nitroanilide, with this molecule driving the cytotoxic activity observed in our experiments. Although lysine metabolism was not fully suppressed by lysine-p-nitroanilide, these findings provide valuable insights for developing novel therapies for rhabdomyosarcoma.

Bioelectric devices such as gastric electrical stimulation (GES) are used to treat severe upper gastrointestinal motility disorders in both younger and older patients. We compared clinical, physiologic, quality of life, and full-thickness gastric biopsy results between younger and older patients undergoing GES. We analyzed 245 patients (45 males, 200 females; median age 42 [range 2-80 years] 47.6% with delayed solid gastric emptying and 52.4% nondelayed). All patients underwent temporary GES trials, followed by full-thickness gastric biopsies and physiologic assessments during permanent GES placement. Histologic evaluation used standardized cellular markers. Validated patient-reported outcomes were assessed at baseline and 1 year, with a 1-point improvement as clinical success. Younger patients (n = 37; 9 males, 28 females; median age 17 [range 2-25 years]); reported less severe anorexia (3.0 vs. 3.5, p = 0.005) and bloating (2.0 vs. 3.5, p < 0.001) at baseline, while nausea and vomiting severity were similar to 208 older adults. Biopsy analysis showed fewer CD3+ and CD8+ cells in younger patients (p = 0.032 and p = 0.002) and fibrosis was more common in older adults (41.2% vs. 16.1%, p = 0.008). Younger patients with gastroparesis (Gp) syndromes have full-thickness gastric biopsy abnormalities and clinical measures that are similar, but not identical to older patients. These findings indicate the need for broader use of tissue analysis and other clinical measures in severely symptomatic patients with Gp symptoms undergoing the bio-electric therapy of gastric electrical stimulation to optimize perioperative counseling and postoperative symptom management.

The hydrophilic amorphous layer around bone apatite promotes osteogenesis.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have emerged as one of the most transformative classes of targeted therapeutics in modern oncology. Despite of their clinical success, especially in hormone receptor-positive breast cancer, the molecular mechanisms driving differential patient response, acquired resistance, and off-target effects remain incompletely understood. In this work, we present a comprehensive and integrative analysis that combines molecular docking, structure-activity relationships, and mechanistic biochemical insights to unravel the key factors governing CDK4/6 inhibitor performance. By evaluating ligand binding dynamics, conformational shifts within the ATP-binding pocket, and the impact of chemical substituents on drug-protein interactions, we reveal a set of structural features that strongly correlate with potency, selectivity, and resistance propensity. Our study further highlights previously overlooked allosteric regions that may serve as next-generation design targets. Together, these findings offer a deeper molecular-level understanding of CDK4/6 inhibition and provide a roadmap for engineering more effective anticancer agents with enhanced specificity and reduced toxicity. This work aims to accelerate rational drug design efforts and support the development of superior therapeutic strategies for CDK4/6-drigen malignancies. This study provides an in-depth computational analysis of three FDA-approved CDK4/6 inhibitors - Abemaciclib (ABB), Palbociclib (PAB), and Ribociclib succinate (RIB) - using DFT, docking, MD simulations, and pharmacokinetic profiling. Structural optimization and vibrational analyses were conducted alongside FMO and MEP mapping to identify reactive sites.

BackgroundThis study aimed to compare the efficacy and safety of colistimethate sodium (CMS) and polymyxin B (PMB) in treating carbapenem-resistant Gram-negative bacteria (CR-GNB)-induced bloodstream infection (BSI) based on real-world data. While international studies on CMS and PMB have yielded conflicting results, there is a lack of direct comparative data from Chinese cohorts, where the pathogen distribution may influence outcomes.MethodsA retrospective analysis was conducted on 373 Chinese patients with CR-GNB-induced BSI who received CMS-containing therapy (n=132) or PMB-containing therapy (n=241) between Dec 2021 and Dec 2023. Propensity score matching was used to balance the two groups at a ratio of 1:2. The primary outcome was clinical success. The secondary outcomes included inpatient days, in-hospital mortality, 28-day all-cause mortality, and incidence of adverse events. Statistical analysis was performed with Wilcoxon rank sum test, Student’s t-test, chi-square test, and Fisher’s exact test as appropriate.ResultsIn this cohort, Acinetobacter baumannii was the predominant pathogen (53.4%). No significant differences were observed in efficacy outcomes between the two groups (p>0.05). For safety, the difference in hyperpigmentation incidences between the two groups was statistically significant (CMS vs PMB: 0.0% vs 6.36%, p=0.04). Incidences of hypersensitivity, neurotoxicity, and nephrotoxicity were similar between groups (p>0.05). A longer treatment course (>12 days), while associated with a higher incidence of hyperpigmentation, was linked to significantly improved clinical outcomes, including higher success rate, reduced in-hospital mortality, and lower 28-day all-cause mortality (p<0.05).ConclusionThis study provides the first large, real-world comparative evidence from a Chinese cohort with CR-GNB BSIs. In this setting, CMS and PMB demonstrated comparable efficacy. The critical difference lay in the safety profile, with CMS associated with a markedly lower incidence of hyperpigmentation. This finding provides a tangible basis for antibiotic stewardship, positioning CMS as a valuable first-line polymyxin option.

Immune-checkpoint molecules have essential roles in regulating immune responses, which maintain the delicate balance between physiological immune reactions and autoimmunity. The clinical success of immune checkpoint blockade for cancer therapy, and the occurrence of immune-related adverse events during cancer immunotherapy, highlight the profound effect of modulating these receptors on both tumour-specific and 'self'-specific responses. As a result, interest in exploring how these molecules can be targeted to treat autoimmune and rheumatological diseases is expanding. Targeting of the immune-checkpoint molecules PD-1, B and T lymphocyte attenuator (BTLA) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) to induce immune tolerance has shown therapeutic promise in pre-clinical models and, in some instances, clinical trials. A comprehensive understanding of how these receptors function in various immune cell populations, particularly T cells, and across different diseases is crucial for the successful translation of these findings to clinical applications.

High-speed sintering has emerged as a promising innovation for enhancing the efficiency of dental prosthesis fabrication. However, its impact on marginal adaptation remains a critical factor in ensuring the long-term clinical success of restorations. The aim of the study to evaluate the marginal fit of high-speed and regular-speed-sintered zirconia crowns. A maxillary right second molar on a typodont was prepared for an all-ceramic crown. A PVS impression was taken and a Type V stone master cast was fabricated. This cast was scanned via a laboratory scanner to produce 20 milled zirconia crowns. The crowns were divided into two groups (n = 10). Group A was subjected to a fast-sintering program, whereas group B was sintered via a conventional-speed-sintering program. Marginal fit was assessed via a stereoscopic microscope at four well-defined points (mid-distal, mid-lingual, mid-mesial, and mid-buccal) on each crown. Three readings were taken at each point. The marginal gaps of both groups were compared via the Wilcoxon signed-rank test. Statistically significant difference between groups A and B (p < 0.001) was revealed. Although the mean marginal gap in both groups was below the clinically acceptable limit (< 90μm), the fast-sintering program produced restorations with a larger marginal gap than the restorations sintered via the conventional program. Crowns produced via both sintering programs were clinically acceptable, although the regular-speed-sintering program yielded a significantly superior marginal fit.