Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.

OBJECTIVES: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS AND METHODS: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays. RESULTS: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. CONCLUSIONS: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.

Salivary gland papillary adenocarcinoma with intestinal-like features: Clinicopathologic, immunohistochemical, and genetic study of six cases.

BACKGROUND: Salivary gland tumors with papillary architecture and intestinal-like mucinous cytologic features are rare. Their clinicopathologic and genetic features are not fully understood, and whether they represent one separate entity remains unclear. METHODS: Six salivary adenocarcinomas with papillary architecture and intestinal-like mucinous cytologic features were reported. Immunostaining was done for CK7, CK20, CDX2, SOX10, S100, MUC1, MUC2, and MUC5AC. Tumor DNA samples were extracted for Sanger sequencing. Previously reported morphology-analogous cases were reviewed. RESULTS: Six cases involved the palate (2), retromolar region (1), submandibular region (1), tongue (1), and mandible (1). Five cases were followed up, with one case of recurrence 1 year after surgery, one death from cerebral infarction 7 days after surgery, and three cases without signs of recurrence or metastasis over 5 years. All cases had abundant mucinous production and presented a typical immunophenotype common to salivary primaries, CK7 & MUC1 positive, CK20 & CDX2 negative. Sanger sequencing demonstrated recurrent AKT1 E17K mutations in four cases (4/6, 66.7%). A review of reported salivary intestinal-like tumors revealed 3 out of 13 cases presented with papillary morphology and CDX2 negative. Some salivary papillary neoplasms with mucinous cytologic features termed as intraductal papillary neoplasms or mucinous adenocarcinomas were also reported with AKT1 E17K mutations. CONCLUSION: We describe 6 cases of salivary gland papillary adenocarcinoma with intestinal-like mucinous cytologic features, which are different from conventional intestinal-type adenocarcinoma, presenting a consistent immunophenotype of CK7 & MUC1 positive, CK20 & CDX2 negative and exhibiting recurrent AKT1 E17K mutations.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. METHOD: The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. RESULTS: OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. CONCLUSION: The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.

Notch activation leads to loss of myoepithelial differentiation and poor outcome in solid adenoid cystic carcinoma.

OBJECTIVE: We aimed to investigate Notch pathway dysregulation in solid adenoid cystic carcinoma (AdCC) and to define the association of Notch activation with cell differentiation and prognosis in AdCCs. MATERIALS AND METHODS: Notch1 mutations were detected from 125 AdCCs (62 cribriform-tubular; 63 solid). RNA-seq was performed in 16 AdCCs (6 Notch-mutant; 10 wild type). Notch activation indicator NICD and myoepithelial marker p63 were detected using immunohistochemistry and double-labelling immunofluorescence. The effect of exogenous NICD overexpression on p63 expression and cell proliferation was investigated using Western blotting and live-cell imaging. RESULTS: We identified 33 Notch1 activating mutations in 27 AdCCs including 26 solid and 1 cribriform-tubular subtypes. Six tumours harboured more than one Notch1 mutation, and 18 Notch1 mutations were novel. Most (47/63, 74.6%) solid AdCCs showed NICD overexpression, whereas 61 of 62 (98.4%) cribriform-tubular tumours were negative. NICD and p63 exhibited mutually exclusive expression, and exogenous NICD overexpression promoted cell proliferation and decreased p63 expression. NICD overexpression and Notch mutations were poor indicators for overall survival and metastasis, especially bone metastasis. CONCLUSIONS: Dysregulated Notch signalling plays a critical role in AdCC severity. Notch activation may contribute to loss of myoepithelial differentiation as well as high proliferation and metastasis rates in solid AdCC.

Chemistry and Selective Tumor Cell Growth Inhibitory Activity of Polyketides from the South China Sea Sponge Plakortis sp.

Simplextone E (1), a new metabolite of polyketide origin, was isolated with eight known analogues (2-9) from the South China Sea sponge Plakortis sp. The relative configuration of the new compound was elucidated by a detailed analysis of the spectroscopic data and quantum mechanical calculation of NMR chemical shifts, aided by the newly reported DP4+ approach. Its absolute configuration was determined by the TDDFT/ECD calculation. Simplextone E (1) is proven to be one of the isomers of simplextone D. The absolute configuration at C-8 in alkyl chain of plakortone Q (2) was also assigned based on the NMR calculation. In the preliminary in vitro bioassay, compounds 6 and 7 showed a selective growth inhibitory activity against HCT-116 human colon cancer cells with IC50 values of 8.3 ± 2.4 and 8.4 ± 2.3 µM, corresponding to that of the positive control, adriamycin (IC50 4.1 µM). The two compounds also showed selective activities towards MCF-7 human breast cancer and K562 human erythroleukemia cells while compound 3 only displayed weak activity against K562 cells.

Bissubvilides A and B, Cembrane-Capnosane Heterodimers from the Soft Coral Sarcophyton subviride.

Two new biscembranoid-like compounds, bissubvilides A (1) and B (2), were isolated together with sarsolilide B (3), the proposed biogenetic precursor to 1, from the soft coral Sarcophyton subviride. The structures and absolute configurations were solved by spectroscopic analysis and TDDFT/ECD and DFT/NMR calculations. The bissubvilides represent a novel biscembranoid-like skeleton presumed to derive from a cembrane-type diene and a capnosane-type dienophile via a Diels-Alder reaction. These two molecules exerted no cytotoxicity against MG-63 or A549 tumor cells or HuH7 tumor stem cells.

[Emodin ameliorates the peritoneal dialysis-related peritoneal fibrosis via inhibiting the activation of Notch pathway].

Long term peritoneal dialysis (PD) is often associated with peritoneal fibrosis. The aim of this study was to explore the effect of emodin on PD-related peritoneal fibrosis and its related cellular and molecular mechanism. PD-related peritoneal fibrosis rats and cultured rat peritoneal mesothelial cells were recruited in the experiment. PD-related peritoneal fibrosis was induced by intraperitoneal injection of lactate-buffered solution containing 4.25% glucose. The peritoneal equilibrium test (PET) was performed at the end of 2 weeks, 4 weeks, and 6 weeks, respectively. HE staining and Masson staining were used for histopathological evaluation. Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma N-terminal procollagen III propeptide (PIIINP) level. Real-time PCR technique was used to detect the mRNA levels of Notch1, Jagged-1, and Hes-1 in peritoneal tissue. Western blot was applied to identify the protein levels of Notch1, Jagged-1, Hes-1, and Notch intracellular domain (NICD). In vitro, Notch1 overexpressing or knockdown rat peritoneal mesothelial cells were established and Western blot was used to examine the effect of emodin on the expressions of Hes-1 and Hey. Compared with the control group, HE staining revealed that PD rats suffered from decreasing in mesothelial cells, or detaching from surface of parietal peritoneum, accompanied by infiltration of inflammatory cells; Masson staining result showed thickened peritonea (P < 0.01), and the collagen deposition in the parietal peritoneum was increased; also, PIIINP level in plasma was elevated (P < 0.01). Treatment of the PD rats with emodin increased mesothelial cells in peritoneal tissue, and decreased the peritoneal thickness (P < 0.01), collagen depositions, as well as the plasma PIIINP level (P < 0.05). The expressions of Notch1, Jagged-1, Hes-1 and NICD in peritoneal tissue were also attenuated (P < 0.05 or P < 0.01). In cultured rat peritoneal mesothelial cells, compared with emodin group, emodin further inhibited the expressions of Hes-1 and Hey induced by Notch1-overexpression (P < 0.05), but not the expressions of Hes-1 and Hey induced by Notch1-knockdown (P > 0.05). Therefore, the activation of Notch pathway may be involved in the pathological process of PD-induced peritoneal fibrosis. Emodin may ameliorate the PD-related peritoneal fibrosis through inhibiting the activation of Notch pathway.

Luteolin from Flos Chrysanthemi and its derivatives: New small molecule Bcl-2 protein inhibitors.

Over-expression of the Bcl-2 anti-apoptotic proteins is closely related to tumorigenesis and associated with drug resistance. Here we report that luteolin, a main substance found in Flos Chrysanthemi, directly binds to and shows inhibitory activity against the Bcl-2 protein. We studied the binding mode of luteolin and its derivatives with target proteins, their structure-activity relationship, and their effect on the human leukemia cell line HL-60. The results suggest that luteolin and its derivatives with a benzyl group introduced to the B ring, are new small molecule Bcl-2 protein inhibitors, and their anti-tumor activity is likely related to their effect on the Bcl-2 protein.

Briarane diterpenoids from the gorgonian Dichotella gemmacea.

Seven new briarane diterpenoids, gemmacolides AS-AY (1-7), were isolated together with ten known analogues (8-17) from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data and comparison with reported data. The absolute configuration of compounds was determined based on electronic circular dichroism (ECD) experiments and genetic correlations as well. Compounds 15 and 16 were reported for the first time for the gorgonian. In the preliminary in vitro bioassays, compound 5 showed potential growth inhibitory activity against MG63 cells.

Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations.

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.

High-Performance Tin Oxide Thin-Film Transistors Realized by Codoping and Their Application in Logic Circuits.

Tin oxide is a promising channel material, offering the advantages of being low-cost and environmentally friendly and having a wide band gap. However, despite the high electron mobility of SnO2 in bulk, the corresponding thin-film transistors (TFTs) generally exhibit moderate performance, hindering their widespread application. Herein, we proposed a codoping strategy to improve both the electrical property and the stability of SnO2 TFTs. A comparative analysis between doped and undoped SnO2 was conducted. It is observed that taking advantage of the difference in ionic radii between two dopants (indium and gallium) and the tin ions in the host lattice can effectively reduce impurity-induced strain. Additionally, we investigated the effect of codoping content on SnO2 TFTs. The optimal codoped SnO2 (TIGO) TFTs demonstrate high performance, featuring a field-effect mobility of 15.9 cm2/V·s, a threshold voltage of 0.2 V, a subthreshold swing of 0.5 V/decade, and an on-to-off current ratio of 2.2 × 107. Furthermore, the devices show high stability under both positive and negative bias stress conditions with a small threshold voltage shift of 1.8 and -1.2 V, respectively. Utilizing the TIGO TFTs, we successfully constructed a resistor-loaded unipolar inverter with a high gain of 10.76. This study highlights the potential of codoped SnO2 TFTs for advanced applications in electronic devices.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

Mast cell infiltration and subtype promote malignant transformation of oral precancer and progression of oral cancer.

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear and the aim of this study was to investigate MC infiltration in oral precancer and oral cancer. Evaluation of immune cell infiltration and association with prognosis in OSCC using RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, while activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared to oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells that was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC through developing targeted therapies against MC.

The prevalence, diagnostic accuracy and genotype-phenotype correlation of GNAS mutations in fibrous dysplasia: a meta-analysis.

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.

GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw.

Differential diagnosis of fibrous dysplasia and ossifying fibroma may often pose problems for pathologists. The purpose of this study was to evaluate the value of mutational analysis of the GNAS gene in differentiating these two conditions. DNA samples from patients with fibrous dysplasia (n=30) and ossifying fibroma (n=21) were collected to analyze the presence of GNAS mutations at exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. In all, 90% (27/30) of cases with fibrous dysplasia showed missense mutations of codon 201 at exon 8, with a predilection of arginine-to-histidine substitution (p.R201H, 70%) as opposed to arginine-to-cysteine substitution (p.R201C, 30%), whereas no mutation was detected at exon 9. No mutation was found in all 21 cases with ossifying fibroma. In addition, a meta-analysis of previously published reports on GNAS mutations in fibrous dysplasia and ossifying fibroma was performed to substantiate our findings. A total of 24 reports including 307 cases of fibrous dysplasia and 23 cases of ossifying fibroma were reviewed. The overall incidence of GNAS mutations in fibrous dysplasia was 86% (264/307), and the major types of mutations were also R201H (53%) and R201C (45%). No GNAS mutation was detected in all patients with ossifying fibroma. We also reported one case with uncertain diagnosis due to overlapping clinicopathological features of fibrous dysplasia and ossifying fibroma. An R201H mutation was detected in this case, thus confirming a diagnosis of fibrous dysplasia. Taken together, our findings indicate that mutational analysis of GNAS gene is a reliable adjunct to differentiate ossifying fibroma and fibrous dysplasia of the jaws.

Structure, absolute configuration, and conformational study of 12-membered macrolides from the fungus Dendrodochium sp. associated with the sea cucumber Holothuria nobilis Selenka.

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collected from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium . The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of ß-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

Steroids glycosylated with both D- and L-arabinoses from the South China Sea gorgonian Dichotella gemmacea.

Three new 19-hydroxy steroidal glycosides, namely, junceellosides E-G (2-4), were isolated together with the known analogue junceelloside C (1) from the South China Sea gorgonian Dichotella gemmacea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. These glycosides are found to have sugar moieties of both ß-l- and ß-d-arabinopyranoses by HPLC analysis of their thiocarbamoyl-thiazolidine derivatives and those of authentic d- and l-arabinoses, leading to the structure revision of junceelloside C (1). This is the first report of steroidal glycosides from the gorgonian D. gemmacea and the first report of glycosides with ß-l-arabinopyranose from marine sources.