Comprehensive 3-dimensional Positional and Morphological Analyses of Condyle and Glenoid Fossa in Patients with Skeletal Class II Malocclusion following Bimaxillary Orthognathic Surgery.

This study aimed to comprehensively and quantitatively characterize 3-dimensional (3D) positional and morphological changes of the condyle and glenoid fossa in patients with skeletal Class II malocclusion treated with bimaxillary orthognathic surgery. Twenty eligible patients treated at our institution from January 2016 to December 2021 with more than 12 months of postoperative follow-up were retrospectively enrolled. Radiographic data of cone-beam computed tomography (CBCT) for each patient were collected at 3 stages: 1 week preoperatively (T0), immediately after surgery (T1), and at least 12 months postoperatively (T2). Positional changes, surface and volumetric alterations of condyle, and bone remodeling in glenoid fossa were measured and compared based on voxel- and surface registrations in visual 3D methods. Most patients exhibited a tendency for condyles to shift posteriorly, laterally, superiorly, and rotated outward, downward, and forward immediately after surgery. Posterior, medial, superior movement and outward, upward, and backward rotation of condyles were observed during follow-up (T1-T2). Bone resorption frequently occurred in the posterior area of condylar surfaces, while bone remodeling was more common in the anterior region of the glenoid fossa. Reduced volume of the condyle was found in most cases, which was not associated with the amount of mandibular advancement. Overall, the condyle and its corresponding glenoid fossa remained relatively stable during the follow-up. Our results reveal positional and morphological alterations in the condyle and the glenoid fossa after bimaxillary orthognathic surgery in patients with skeletal class II malocclusion. These changes predominantly fall within the spectrum of physical adaption.

The top 100 highly cited articles on surgery-first orthognathic surgery between 2009 and 2022: a bibliometric and visualized analysis.

OBJECTIVES: To reveal research focuses on surgery-first orthognathic surgery by a bibliometric and visualized analysis of the top 100 highly cited articles. STUDY DESIGN: Published papers related to surgery-first orthognathic surgery were retrospectively retrieved from the Web of Science Core Collection from 2009 to 2022. The number of articles, journals, countries/regions, institutions, authors, and keywords were assessed and visualized using CiteSpace software. RESULTS: The top 100 cited articles included 89 research papers and 11 reviews. The average total citation was 21. The most influential article with 146 citations was published by Dr. Liou E.J.W. in 2011. The most common level of evidence was level IV (36 articles). The Journal of Oral and Maxillofacial Surgery had the largest number of papers and the highest total citation frequency. The most productive countries and institutions were Korea/China and Chang Gung Memorial Hospital, respectively. Chen Yu-ray and Choi Jong Woo published 13 and 11 articles with 434 and 299 total citations, respectively. Research interests shifted from skeletal class III malocclusion, accuracy, stability, and relapse to quality of life and virtual surgical planning. CONCLUSION: Our bibliometric analyses provide a comprehensive landscape of the influential topics and developmental trends in surgery-first orthognathic surgery and inspire future studies in this booming field.

All-Nitrogen Energetic Material Cubic Gauche Polynitrogen: Plasma Synthesis and Thermal Performance.

Numerous theoretical calculations have demonstrated that polynitrogen with an extending polymeric network is an ultrahigh-energy all-nitrogen material. Typical samples, such as cubic gauche polynitrogen (cg-N), have been synthesized, but the thermal performance of polynitrogen has not been unambiguously determined. Herein, macroscopic samples of polynitrogen were synthesized utilizing a coated substrate, and their thermal decomposition behavior was investigated. Polynitrogen with carbon nanotubes was produced using a plasma-enhanced chemical vapor deposition method and characterized using infrared, Raman, X-ray diffraction X-ray photoelectron spectroscopy and transmission electron microscope. The results showed that the structure of the deposited polynitrogen was consistent with that of cg-N and the amount of deposition product obtained with coated substrates increased significantly. Differential scanning calorimetry (DSC) at various heating rates and TG-DSC-FTIR-MS analyses were performed. The thermal decomposition temperature of cg-N was determined to be 429 °C. The apparent activation energy (Ea) of cg-N calculated by the Kissinger and Ozawa equations was 84.7 kJ/mol and 91.9 kJ/mol, respectively, with a pre-exponential constant (lnAk) of 12.8 min-1. In this study, cg-N was demonstrated to be an all-nitrogen material with good thermal stability and application potential to high-energy-density materials.

Impaired Efferocytosis Enables Apoptotic Osteoblasts to Escape Osteoimmune Surveillance During Aging.

Macrophage efferocytosis of apoptotic osteoblasts (apoOBs) is a key osteoimmune process for bone homeostasis. However, apoOBs frequently accumulate in aged bone marrow, where they may mount proinflammatory responses and progressive bone loss. The reason why apoOBs are not cleared during aging remains unclear. In this study, it is demonstrated that aged apoOBs upregulate the immune checkpoint molecule CD47, which is controlled by SIRT6-regulated transcriptional pausing, to evade clearance by macrophages. Using osteoblast- and myeloid-specific gene knockout mice, SIRT6 is further revealed to be a critical modulator for apoOBs clearance via targeting CD47-SIRPα checkpoint. Moreover, apoOBs activate SIRT6-mediated chemotaxis to recruit macrophages by releasing apoptotic vesicles. Two targeting delivery strategies are developed to enhance SIRT6 activity, resulting in rejuvenated apoOBs clearance and delayed age-related bone loss. Collectively, the findings reveal a previously unknown linkage between immune surveillance and bone homeostasis and targeting the SIRT6-regulated mechanism can be a promising therapeutic strategy for age-related bone diseases.

Analysis of Structural Parameters of Steel-NC-UHPC Composite Beams.

The cracking of the negative moment area of steel-normal concrete (NC) composite bridges is common owning to the low tensile strength of concrete. In order to solve the problem, Ultra High Performance Concrete (UHPC) is used to enhance the tensile performance of the negative moment area. This paper conducted interface experiments to study the bonding behaviour of the UHPC-NC interface. The design parametric analysis of steel-NC-UHPC composite bridges was carried out based on the interface experimental results. Firstly, slant shear tests and flexural shear tests were carried out to study the rationality of the interface handling methods. Then, the finite element model was used to analyze the state of every component in the composite beams based on experimental results, such as the stress of UHPC, concrete and steel plate. Finally, the calculation results of finite analysis were compared and summarized. It is concluded that (1) the chiseling interface can meet the utilization requirements of physical bridges. The average shear stress and flexural tensile strength of the chiseling interface are 10.29 MPa and 1.93 MPa, respectively. In the failure state, a slight interface damage occurs for specimens with a chiseling interface. (2) The influence on overall performance is different for changes in different design parameters. The thickness of concrete has a significant influence on the stress distribution of composite slabs. (3) Reliable interface simulation is conducted in the finite element models based on interface test results. The stress variation patterns are reflected in the change of design parameters.

SIRT6-regulated macrophage efferocytosis epigenetically controls inflammation resolution of diabetic periodontitis.

Rationale: Diabetes exacerbates the prevalence and severity of periodontitis, leading to severe periodontal destruction and ultimately tooth loss. Delayed resolution of inflammation is a major contributor to diabetic periodontitis (DP) pathogenesis, but the underlying mechanisms of this imbalanced immune homeostasis remain unclear. Methods: We collected periodontium from periodontitis with or without diabetes to confirm the dysfunctional neutrophils and macrophages in aggravated inflammatory damage and impaired inflammation resolution. Our in vitro experiments confirmed that SIRT6 inhibited macrophage efferocytosis by restraining miR-216a-5p-216b-5p-217 cluster maturation through ''non-canonical'' microprocessor complex (RNA pulldown, RIP, immunostaining, CHIP, Luciferase assays, and FISH). Moreover, we constructed m6SKO mice that underwent LIP-induced periodontitis to explore the in vitro and in vivo effect of SIRT6 on macrophage efferocytosis. Finally, antagomiR-217, a miRNA antagonism, was delivered into the periodontium to treat LIP-induced diabetic periodontitis. Results: We discovered that insufficient SIRT6 as a histone deacetylase in macrophages led to unresolved inflammation and aggravated periodontitis in both human and mouse DP with accumulated apoptotic neutrophil (AN) and higher generation of neutrophil extracellular traps. Mechanistically, we validated that macrophage underwent high glucose stimulation resulting in disturbance of the SIRT6-miR-216/217 axis that triggered impeded efferocytosis of AN through targeting the DEL-1/CD36 axis directly. Furthermore, we demonstrated the inhibitory role of SIRT6 for MIR217HG transcription and identified a non-canonical action of microprocessor that SIRT6 epigenetically hindered the splicing of the primary miR-216/217 via the complex of hnRNPA2B1, DGCR8, and Drosha. Notably, by constructing myeloid-specific deletion of SIRT6 mice and locally delivering antagomir-217 in DP models, we strengthened the in vivo effect of this axis in regulating macrophage efferocytosis and inflammation resolution in DP. Conclusions: Our findings delineated the emerging role of SIRT6 in mediating metabolic dysfunction-associated inflammation, and therapeutically targeting this regulatory axis might be a promising strategy for treating diabetes-associated inflammatory diseases.

Development of a novel head and neck squamous cell carcinoma prognostic signature by bulk/single-cell sequencing data integration.

BACKGROUND: Identifying cell subpopulations conferring unfavorable prognosis in cancer holds clinical significance. Here, we sought to identify prognostic cell subsets and develop a novel, prognostic signature for head neck squamous cell carcinoma (HNSCC). METHODS: Highly prognostic cell subpopulations in HNSCC were identified by integrating single-cell and bulk transcriptomic datasets. The prognostic signature and nomogram were developed by least absolute shrinkage and selection operator and multivariate Cox regression analyses based on significantly upregulated genes in this specific cell subpopulation, respectively. The qRT-PCR experiments were utilized for independent validation in our patient cohort. RESULTS: A specific cancer cell subset associated with unfavorable prognoses was identified. Functional dissections revealed that its transcriptional programs were significantly enriched in E2F, epithelial-to-mesenchymal transition, and glycolysis. A novel prognostic signature comprising six genes was developed and further validated. Risk scores based on qRT-PCR data robustly stratified patients into subgroups with distinct prognoses. A nomogram integrated from this signature and clinical stage had superior performance. CONCLUSION: Our model derived from integrative analyses of single-cell and bulk RNA-sequencing is a novel, robust prognostic biomarker for HNSCC.

The deubiquitinase USP7 promotes HNSCC progression via deubiquitinating and stabilizing TAZ.

Dysregulated abundance, location and transcriptional output of Hippo signaling effector TAZ have been increasingly linked to human cancers including head neck squamous cell carcinoma (HNSCC). TAZ is subjected to ubiquitination and degradation mediated by E3 ligase ß-TRCP. However, the deubiquitinating enzymes and mechanisms responsible for its protein stability remain underexplored. Here, we exploited customized deubiquitinases siRNA and cDNA library screen strategies and identified USP7 as a bona fide TAZ deubiquitinase in HNSCC. USP7 promoted cell proliferation, migration, invasion in vitro and tumor growth by stabilizing TAZ. Mechanistically, USP7 interacted with, deubiquitinated and stabilized TAZ by selectively removing its K48-linked ubiquitination chain independent of canonical Hippo kinase cascade. USP7 potently antagonized ß-TRCP-mediated ubiquitin-proteasomal degradation of TAZ and enhanced its nuclear retention and transcriptional output. Importantly, overexpression of USP7 correlated with TAZ upregulation, tumor aggressiveness and unfavorable prognosis in HNSCC patients. Pharmacological inhibition of USP7 significantly suppressed tumor growth in both xenograft and PDX models. Collectively, these findings identify USP7 as an essential regulator of TAZ and define USP7-TAZ signaling axis as a novel biomarker and potential therapeutic target for HNSCC.

Clinical management of primary odontogenic sarcoma in the mandible: a case report after WHO nomination.

Ameloblastic fibro-odontosarcoma (AFOS) now designated as odontogenic sarcoma is an extremely rare odontogenic tumor, which histologically presents as a biphasic neoplasm with a malignant mesenchymal component plus ameloblastic epithelium. Here we report a 27-year-old Chinese female with the complaint of a painful swelling for half a month in the right mandible. A segmental mandibulectomy, with an immediate mandibular reconstruction using a free vascularized osteocutaneous fibular flap was performed using surgical guide models. Histological analysis revealed a primary odontogenic sarcoma. The postoperative period was uneventful, and no clinical indication of recurrence or metastasis was observed during the 3-year follow-up. No adjuvant therapy was proposed. This is the first odontogenic sarcoma case reported in China after the new World Health Organization classification of odontogenic lesions.

Comprehensive characterization of pleomorphic adenoma at intraoral unusual sites.

OBJECTIVE: The present study aimed to comprehensively characterize the epidemiologic characteristics, clinicopathologic characteristics, clinical treatments, and prognoses of pleomorphic adenoma (PA) identified at unusual intraoral sites. STUDY DESIGN: Patients diagnosed with PA in oral and maxillofacial regions at our institution in the past 16 years (2005-2020) were screened from the inpatient disease registry. All data concerning patients with PA found at unusual intraoral sites (defined as intraoral locations except sublingual gland and palate) were retrieved. Previously published cases with adequate clinicopathologic data were collected from PubMed and Embase. Eligible cases were further reviewed and included for statistical analyses. RESULTS: Among 1039 cases of PA diagnosed at our institution, 52 lesions were found at unusual intraoral sites. A literature review identified another 63 eligible cases from 32 articles. The upper lip was the most common sites for these lesions (n = 57), followed by buccal mucosa (n = 34), tongue (n = 8), lower lip (n = 8), and retromolar area (n = 2). Recurrence and malignant transformation after surgical resection were extremely rare for these lesions. CONCLUSIONS: PA might rarely develop at uncommon intraoral sites with atypical presentations, thus complicating its early diagnosis. Surgical resection is the major therapeutic strategy for this rare entity and has a favorable prognosis.

Evaluation of autofluorescence visualization system in the delineation of oral squamous cell carcinoma surgical margins.

INTRODUCTION: Delineating the margins of Oral squamous cell carcinoma (OSCC) is a critical step for optimaltumor resection. The aim of this study was to evaluate the accuracy of lesion surgical margin identification using autofluorescence visualization. MATERIALS AND METHODS: Thirty patients with OSCC were included in this study. For each lesion, the fluorescence loss boundary was determined using VELscope before ablative surgical resection (with a 1.5-2cm safety margin) was performed. A total of 126 samples were obtained from 30 surgical specimens, each containing the tissue from the fluorescence loss boundary to surgical margin. The status of each sample was determined by oral pathologists and the staining intensities of Ki-67, E-cadherin, and Vimentin at the fluorescence loss boundary and surgical margin were evaluated by immunohistochemistry. RESULTS: Fluorescence loss regions were identified in all patients. Of the 126 samples collected, HE staining identified 77 normal epithelia (61.1%), 26 mild dysplasia (20.6%), 17 severe dysplasia (13.4%) and 6 carcinomas in situ (4.9%). A significant correlation was found between the differentiation grade of tumor cells and the pathological status of the surgical marginal specimens (P<0.05). Forty-two of the 126 samples were randomly selected for further immunohistochemical staining. No significant differences were seen in Ki-67, E-cadherin, or Vimentin expression at the fluorescence loss boundary or surgical margin, however, the proteins' expression level was positively correlated with the degree of dysplasia (P<0.01). CONCLUSION: Autofluorescence visualization has potential as a simple surgical margin setting device for OSCC and may help delineate the superficial area of OSCC with acceptable accuracy. However, when considering the inherent limitations of this system, we suggest that the approach should only be applied under certain conditions, such as when dealing with superficial, well-differentiated lesions.

Identification of an autophagy-related prognostic signature in head and neck squamous cell carcinoma.

BACKGROUND: Autophagy-related genes (ARGs) have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop an ARGs-based prognostic signature for Head and neck squamous cell carcinoma (HNSCC). METHODS: Prognostic ARG candidates were identified by univariate and multivariate Cox regression analysis in the training dataset (TCGA-HNSC) and incorporated into a 3-ARGs (EGFR, FADD, and PARK2) prognostic signature which was further verified in two independent validation cohorts (GSE41613 and GSE42743). Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristics curves (ROC) were employed to evaluate the prognostic prediction of 3-ARGs signature. Differential expression of these 3 ARG between cancer and normal counterparts as well as their associations with autophagy markers were assessed in 60 pairs of freshly collected HNSCC and adjacent non-tumor samples and datasets from Human Protein Atlas, respectively. RESULTS: Patients with high-risk score had significantly inferior overall survival. Multivariate regression analyses revealed that 3-ARGs signature could be an independent prognostic factor after adjusting various clinicopathological parameters. ROC analyses revealed high predictive accuracy and sensitivity of the 3-ARGs signature. Increased mRNA and protein expression of EGFR, FADD, and PARK2 were found in HNSCC samples, and their expression significantly correlated with the abundances of ATG5, Beclin1, and LC3. CONCLUSION: Our results reveal that 3-ARGs signature is a powerful prognostic biomarker for HNSCC, which could be integrated into the current prognostic regime to realize individualized outcome prediction. EGFR, FADD, and PARK2 likely contributed to autophagy during HNSCC tumorigenesis.

Blood and Salivary MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: This meta-analysis aimed to compare and evaluate the diagnostic accuracy of blood and salivary microRNAs (miRNAs) in discriminating oral squamous cell carcinoma (OSCC). METHODS: The PubMed, Embase, Web of Science, and Cochrane Library were searched (updated to February 2020) to identify all articles describing the diagnostic value of blood and salivary miRNAs for OSCC. The pooled parameters were calculated using Revman (v.5.3) and STATA (v.14.0). RESULTS: Twenty articles involving 1,106 patients and 732 controls were included in this meta-analysis. The pooled sensitivity and specificity of salivary miRNAs were 0.70 (95% CI: 0.63-0.77) and 0.82 (95% CI: 0.72-0.90). For blood miRNAs, they were 0.79 (95% CI: 0.73-0.84) and 0.82 (95% CI: 0.77-0.86). The areas under receiver operating characteristic curve in saliva, blood, and body fluid miRNAs were 0.80 (95% CI: 0.77-0.84), 0.88 (95% CI: 0.84-0.90), and 0.87 (95% CI: 0.84-0.90), respectively. CONCLUSIONS: The results of this meta-analysis indicate a moderate diagnostic accuracy of blood and salivary miRNAs presented for OSCC. These findings may provide less invasive and relatively reliable diagnostic tools for OSCC detection.

CBCT study on the positional relationship between marginal points of pterygomaxillary junction and anterior nasal spine.

PURPOSE: This study aimed to locate the inferior end (Pti) and the superior end (Pts) of pterygomaxillary junction (PMJ) relative to anterior nasal spine (ANS) so as to provide references for pterygomaxillary separation. METHODS: The study was based on CBCT images of 109 Chinese patients. We projected Pti and Pts to the frontal plane and measured the distance as well as the positional relationship between the projection points and ANS via three-dimensional reconstruction image. RESULTS: On average, the ANS was 5.18 mm above the Pti and the horizontal distance between the Pti and ANS was 21.86 mm. The horizontal and vertical distances between Pts and ANS was 20.41 mm and 10.91 mm, respectively. The vertical height of PMJ was 16.09 mm. Scatter plots diagrammatic centered on ANS showed that 73% (160/218) Pti and 64% (140/218) Pts appeared in a 45° fan shape ranged from 20 to 25 mm radius in bilateral inferior and superior quadrant, respectively. There was no significant difference in the distance between both sides (P > 0.05). CONCLUSION: During the pterygomaxillary disjunction, it exists a risk of injuring neurovascular bundle of the pterygopalatine fossa 16.09 mm above the lowest border of the pterygomaxillary junction. The region within a 45° fan shape ranged in 20-25 mm radius in inferior quadrant centered on ANS might be suitable for the osteotome position. The positional relationship especially between the ANS and Pti found in this study provides a reference for surgeons during pterygomaxillary disjunction.

Combinational therapeutic targeting of BRD4 and CDK7 synergistically induces anticancer effects in head and neck squamous cell carcinoma.

The bromodomain and extra-terminal domain protein BRD4 has been recognized as a key oncogenic driver and a druggable target against cancer. However, these BRD4 inhibitors as monotherapy were moderate in efficacy in preclinical models. Here we utilized a small-scale drug synergy screen that combined the BRD4 inhibitor (JQ1) with 8 epigenetic or transcriptional targeted chemicals and identified THZ1 (a CDK7 inhibitor) acting synergistically with JQ1 against head neck squamous cell carcinoma (HNSCC). Combinational JQ1 and THZ1 treatment impaired cell proliferation, induced apoptosis and senescence, which were largely recapitulated by dual BRD4 and CDK7 knockdown. Combinational treatment inhibited tumor growth and progression in 4NQO-induced HNSCC and xenograft animal models. RNA-sequencing analyses identified hundreds of differentially expressed genes modulated by JQ1 and THZ1, which were significantly enriched in categories including cell cycle and apoptosis. Mechanistically, combinational treatment reduced H3K27ac enrichment in the super-enhancer region of YAP1, which inactivated its transcription and in turn induced anti-proliferative and pro-apoptotic effects. Combined BRD4 and CDK7 upregulation associated with worst prognosis in HNSCC patients. Collectively, our findings reveal a novel therapeutic strategy of pharmacological inhibitions of BRD4 and CDK7 against HNSCC.

MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2.

In various kinds of carcinomas, the special AT-rich sequence-binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR-34a downstream is the intended endeavor of this study. In te OSCCs the miR-34a expression was determined by quantitative real-time polymerase chain reaction (q-PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q-PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR-34a on the initiation of OSCC were conducted. As a direct target of the miR-34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR-34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR-34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR-34a was confirmed by the cotransfection of miR-34a mimics specifically the decrease in the expression of luciferase of SATB2-3'UTR-wt reporter. As a whole, our study confirmed the inhibition of miR-34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.

Assessment of aging characteristics of female condylar trabecular structure by cone-beam computed tomography.

OBJECTIVES: This study was performed to analyze the aging-related changes of the female condylar bone mineral density (BMD) and trabecular structure by cone-beam computed tomography (CBCT), and determine whether the condylar structure shows obvious changes after menopause. METHODS: The CBCT images of 160 female patients who met the inclusion criteria for the study were collected and divided into four groups by age (20-29 years, 30-39 years, premenopausal, and postmenopausal groups). Computer processing software CT-Analyser (Version 1.15.2.2+; SkyScan, Antwerp, Belgium) was used to measure the condylar BMD and related indexes, namely the bone volume/tissue volume ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular structure model index (SMI), and bone surface area/volume ratio (BS/BV). SPSS 12.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the radiographic findings and statistical differences. RESULTS: No significant differences were found between the bilateral condyles in each group (P > 0.05). BV/TV, Tb.N, and Tb.Th of the condyle decreased with age, and the postmenopausal group showed significantly different values for each index compared with the other groups (P < 0.01). Tb.Sp, SMI, and BS/BV of the condyle increased with age, and the postmenopausal group showed significantly different values for each index compared with the other groups (P < 0.01). CONCLUSIONS: With increasing age, the female condylar bone volume decreases, the Tb.N and Tb.Th decrease, the gap between the trabecular bone increases, and plate-like trabecular bone gradually transforms into a rod-like form. These changes are much more obvious in postmenopausal women.

Chiral Guanidine/Copper Catalyzed Asymmetric Azide-Alkyne Cycloaddition/[2+2] Cascade Reaction.

We report the development of a chiral guanidine-based copper(I) catalyst for the asymmetric azide-alkyne cycloaddition/[2+2] cascade reaction. Optically active spiroazetidinimine oxindoles were constructed by trapping the ketenimine species under mild reaction conditions. High level of enantioinduction and excellent isolated yields were achieved in the three-component reaction of various isatin-derived ketimines, sulfonyl azides, and terminal alkynes. Control experiments and X-ray crystallography were used to probe into the interaction of chiral guanidinium salt with copper salt.

Enantioselective Formal [4 + 2] Annulation of ortho-Quinone Methides with ortho-Hydroxyphenyl α,ß-Unsaturated Compounds.

The highly efficient enantioselective [4 + 2] cycloaddition of o-QMs with ortho-hydroxyphenyl-substituted α,ß-unsaturated compounds was realized by using a chiral N, N'-dioxide-Sc(III) complex as catalyst. A variety of chiral chromane derivatives with three continuous stereocenters were obtained in excellent results (up to 99% yield, >19:1 dr, and 99% ee) under as low as 0.005-1 mol % catalyst loading. Besides, a catalytic cycle with a possible transition state model was proposed to elucidate the origin of the chirality.

Asymmetric Formal [3 + 2]-Cycloaddition of Azomethine Imines with Azlactones To Synthesize Bicyclic Pyrazolidinones.

An efficient enantioselective formal [3 + 2]-cycloaddition of azomethine imines with azlactones has been realized by using a chiral bifunctional bisguanidinium hemisalt as the catalyst. Optically active bicyclic pyrazolidinone compounds were generated under mild reaction conditions in high yields (up to 99%) with good dr (up to 88:12) and excellent ee values (up to 99%). This simple and efficient strategy provides a method to construct biologically important chiral tetrahydropyrazolo[1,2-a]pyrazole-1,7-dione derivatives bearing vicinal aza-quaternary and tertiary carbon centers.