Novel patient-derived xenograft and cell line models for therapeutic screening in NF2-associated schwannoma.

Treatment of schwannomas in patients with neurofibromatosis type 2 (NF2) is extremely unsatisfactory, and innovative therapeutic approaches are urgently needed. However, the lack of clinically relevant NF2-associated schwannoma models has severely hampered drug discovery in this rare disease. Here we report the first establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which recapitulates the morphological and histopathological features of patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannomas. Using gene expression profiling, we identified elevated PI3K/AKT/mTOR networks in human NF2-associated vestibular schwannomas. Using high-throughput screening of 157 inhibitors targeting the PI3K/AKT/mTOR pathways in vitro, we identified a dozen inhibitors (such as BEZ235, LY2090314, and AZD8055) with significant growth-suppressive effects. Interestingly, we observed that three cell lines displayed differential therapeutic responses to PI3K/AKT/mTOR inhibitors. Furthermore, we demonstrated that two orally bioavailable inhibitors, AZD8055 and PQR309, suppressed NF2-associated schwannoma growth both in vitro and in vivo. In conclusion, our novel patient-derived models of NF2-associated schwannoma closely mimic the phenotypes and genotypes of patient tumors, making them reliable preclinical tools for testing novel personalized therapies. © 2022 The Pathological Society of Great Britain and Ireland.

MYB-QKI rearrangement in angiocentric glioma.

AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. CONCLUSION: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.

An adult case of diffuse midline glioma with H3 K27M mutation.

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.

Glioneuronal tumours with features of rosette-forming glioneuronal tumours of the fourth ventricle and dysembryoplastic neuroepithelial tumours: a report of three cases.

AIMS: To study three atypical glioneuronal tumours (GNTs), in order to shed light on the clinical and pathological features of this diverse tumour group. METHODS AND RESULTS: Clinical and neuropathological data for each case were retrospectively reviewed. Case 1 involved a 17-year-old boy with left leg movement difficulty. A mass lesion in the basal ganglia was detected radiologically; histopathological features included neurocytic/perivascular rosettes and a pilocytic astrocytoma component. Case 2 involved a 33-year-old man with intractable epilepsy. His left parietal lobe contained a cyst-like mass, resembling dysembryoplastic neuroepithelial tumour and rosette-forming glioneuronal tumour of the fourth ventricle microscopically. Case 3 involved a 21-year-old woman with a mass lesion in the mesencephalic tegmentum extending to the third and fourth ventricles and the suprasellar region. The lesion contained perivascular/neurocytic rosettes and an oligodendroglioma-like component. None of the tumours expressed an isocitrate dehydrogenase I mutation of the R132H type or contained a 1p/19q deletion, a BRAF(V600E) mutation, or KIAA1549-BRAF fusion. CONCLUSIONS: We describe three GNTs with atypical histopathology and locations. Additional cases and molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system.

[Mutation of isocitrate dehydrogenase gene in Chinese patients with glioma].

OBJECTIVE: To investigate mutation status of isocitrate dehydrogenase (IDH) 1 and IDH2 genes in Chinese patients with gliomas in correlation with clinicopathological characteristics. METHODS: Formalin-fixed and paraffin-embedded (FFPE) tissue samples of 234 gliomas were collected including the matched blood samples in 30 patients. DNA was extracted, followed by PCR-Sanger sequencing to detect IDH1 and IDH2 gene mutations. Immunohistochemistry was performed using mutation-specific antibody recognizing IDH1R132H mutation. Immunostains for p53 and epidermal growth factor receptor (EGFR) were also performed. Oligodendroglial tumors with IDH mutation were double stained with IDH1R132H and GFAP by immunofluorescence to investigate the location of IDH1R132H expression. RESULTS: (1) By IDH1 heterozygous somatic mutation analysis, Arg132His (c: G395A) was found in 31.6% (74 of 234) of the cases. IDH mutations were more frequent in oligoastrocytomas (9/13), anaplastic oligoastrocytomas (7/11), oligodendrogliomas(18/26, 69.2%), anaplastic oligodendrogliomas (8/10), and less frequent in diffuse astrocytomas (17/47, 36.2%), anaplastic astrocytomas (5/18), and glioblastomas (10/69, 14.5%). The mutation rate inversely correlated with the tumor grade in a linear fashion in astrocytic tumors (P = 0.007). Primary glioblastomas were characterized by a lower frequency of mutations than secondary glioblastomas (5/55 vs. 5/14, P = 0.036); IDH mutation was not detected in pilocytic astrocytoma and ependymoma. No IDH2 mutation was identified in this study cohort. (2) Immunohistochemistry of IDH1R132H demonstrated a strong cytoplasmic staining in 80 cases, which was highly correlated with IDH mutation status (P = 0.001). IDH1R132H was highly specific to tumor cells. (3) p53 immunostain was significantly correlated the IDH mutation in diffuse astrocytoma, anaplastic astrocytoma and secondary glioblastomas (P = 0.007, 0.026, 0.038 respectively). (4) No correlation between EGFR and IDH mutation was found. CONCLUSIONS: High prevalence of IDH heterozygous somatic mutation occurs in the earlier stage of gliomas, which can be detected by mutation-specific antibody IDH1R132H. Furthermore, evaluation of p53 and EGFR expression combined with IDH mutation analysis may significantly aid in the diagnosis and differential diagnoses of gliomas in Chinese patients.

Unraveling the mechanisms of O2 activation by size-selected gold clusters: transition from superoxo to peroxo chemisorption.

The activation of dioxygen is a key step in CO oxidation catalyzed by gold nanoparticles. It is known that small gold cluster anions with even-numbered atoms can molecularly chemisorb O(2) via one-electron transfer from Au(n)(-) to O(2), whereas clusters with odd-numbered atoms are inert toward O(2). Here we report spectroscopic evidence of two modes of O(2) activation by the small even-sized Au(n)(-) clusters: superoxo and peroxo chemisorption. Photoelectron spectroscopy of O(2)Au(8)(-) revealed two distinct isomers, which can be converted from one to the other depending on the reaction time. Ab initio calculations show that there are two close-lying molecular O(2)-chemisorbed isomers for O(2)Au(8)(-): the lower energy isomer involves a peroxo-type binding of O(2) onto Au(8)(-), while the superoxo chemisorption is a slightly higher energy isomer. The computed detachment transitions of the superoxo and peroxo species are in good agreement with the experimental observation. The current work shows that there is a superoxo to peroxo chemisorption transition of O(2) on gold clusters at Au(8)(-): O(2)Au(n)(-) (n = 2, 4, 6) involves superoxo binding and n = 10, 12, 14, 18 involves peroxo binding, whereas the superoxo binding re-emerges at n = 20 due to the high symmetry tetrahedral structure of Au(20), which has a very low electron affinity. Hence, the two-dimensional (2D) Au(8)(-) is the smallest anionic gold nanoparticle that prefers peroxo binding with O(2). At Au(12)(-), although both 2D and 3D isomers coexist in the cluster beam, the 3D isomer prefers the peroxo binding with O(2).

Two-photon photoemission study of the coverage-dependent electronic structure of chemisorbed alkali atoms on a Ag(111) surface.

We report a systematic investigation of the electronic structure of chemisorbed alkali atoms (Li-Cs) on a Ag(111) surface by two-photon photoemission spectroscopy. Angle-resolved two-photon photoemission spectra are obtained for 0-0.1 monolayer coverage of alkali atoms. The interfacial electronic structure as a function of periodic properties and the coverage of alkali atoms is observed and interpreted assuming ionic adsorbate/substrate interaction. The energy of the alkali atom σ-resonance at the limit of zero coverage is primarily determined by the image charge interaction, whereas at finite alkali atom coverages, it follows the formation of a dipolar surface field. The coverage- and angle-dependent two-photon photoemission spectra provide information on the photoinduced charge-transfer excitation of adsorbates on metal surfaces. This work complements the previous work on alkali/Cu(111) chemisorption [Phys. Rev. B 2008, 78, 085419].

Structure evolution of gold cluster anions between the planar and cage structures by isoelectronic substitution: Au(n)- (n = 13-15) and MAu(n)- (n = 12-14; M = Ag, Cu).

The structural and electronic effects of isoelectronic substitution by Ag and Cu atoms on gold cluster anions in the size range between 13 and 15 atoms are studied using a combination of photoelectron spectroscopy and first-principles density functional calculations. The most stable structures of the doped clusters are compared with those of the undoped Au clusters in the same size range. The joint experimental and theoretical study reveals a new C(3v) symmetric isomer for Au(13)(-), which is present in the experiment, but has hitherto not been recognized. The global minima of Au(14)(-) and Au(15)(-) are resolved on the basis of comparison between experiment and newly computed photoelectron spectra that include spin-orbit effects. The coexistence of two isomers for Au(15)(-) is firmly established with convincing experimental evidence and theoretical calculations. The overall effect of the isoelectronic substitution is minor on the structures relative to those of the undoped clusters, except that the dopant atoms tend to lower the symmetries of the doped clusters.

Partial response to Chinese patent medicine Kangliu pill for adult glioblastoma: A case report and review of the literature.

BACKGROUND: Glioblastoma is the most common type of brain tumor and is invariably fatal, with a mean survival time of 8-15 mo for recently diagnosed tumors, and a 5-year survival rate of only 7.2%. The standard treatment for newly diagnosed glioblastoma includes surgery followed by concurrent chemoradiotherapy and further adjuvant temozolomide. However, the prognosis remains poor and long-term survival is rare. This report aimed to demonstrate a new therapeutic strategy for the treatment of glioblastoma. CASE SUMMARY: A patient was referred to the Department of Neurosurgery with an intracranial space-occupying lesion with a maximum diameter of approximately 5 cm. The tumor was compressing functional areas, and the patient accordingly underwent partial resection and concurrent chemoradiotherapy. The imaging and pathological findings were consistent with a diagnosis of glioblastoma with oligodendroglioma differentiation (World Health Organization IV). The patient was finally diagnosed with glioblastoma. However, the patient discontinued treatment due to intolerable side effects, and was prescribed Kangliu pill (KLP) 7.5 g three times/d, which he has continued to date. Significant shrinkage of the tumor (maximum diameter reduced from about 3.5 to about 2 cm) was found after 3 mo of KLP therapy, and the tumor was further reduced to about 1 cm after 3 years. The patient's symptoms of headache, limb weakness, and left hemiplegia were relieved, with no side effects. CONCLUSION: KLP has been a successful intervention for glioblastoma, and the current case indicates that traditional Chinese medicine may offer effective alternative therapies for glioblastoma.

Survival and Prognostic Factors of Adult Intracranial Ependymoma: A Single-institutional Analysis of 236 Patients.

Adult intracranial ependymomas (EPNs) are extremely rare brain tumors. Currently, clinical and molecular factors that could inform individualized treatment strategies are still lacking for EPNs in this age group. The aim of this study was to investigate potential prognostic indicators and rational therapeutic management in a large cohort of adult intracranial EPNs. Adult patients who underwent resection of World Health Organization (WHO) grade II or III intracranial EPNs were included. The demographic features, clinicopathologic manifestations, molecular subgroups, and outcomes were retrospectively analyzed. Overall survival and progression-free survival were calculated using the Kaplan-Meier analysis. Potential prognostic indicators were identified using multivariable Cox proportional hazards model. This cohort included 236 adult patients with a mean age of 36.2 years (range: 18 to 72 y) at diagnosis. The tumor location was supratentorial (ST) in 102 (43.2%) and infratentorial in 134 (56.8%). Pathologic analysis revealed 43.1% of ST-EPNs with RELA fusion and 88.1% of posterior fossa ependymomas (PF-EPNs) with positive H3K27me3 staining. Gross total removal was achieved in 169 cases (71.6%). During follow-up, 97 (41.1%) patients had disease progression and 39 (16.5%) died. Kaplan-Meier analysis showed that patients with H3K27me3-positive PF-EPN had excellent survival, whereas patients with RELA fusion-positive ST-EPN or H3K27me3-negative PF-EPN had poor prognosis (progression-free survival: P=1.3E-16, overall survival: P=2.5E-12). Multivariate analysis showed that molecular subgroup, extent of resection, and Ki-67 index were strong independent prognostic indicators. In conclusion, our study provides essential information on the prognostic prediction of adult intracranial EPNs that will assist in establishing appropriate risk stratification and individualized treatment strategies in future clinical trials.

Planar to linear structural transition in small boron-carbon mixed clusters: C(x)B(5-x)- (x = 1-5).

Bulk carbon and boron form very different materials, which are also reflected in their clusters. Small carbon clusters form linear structures, whereas boron clusters are planar. For example, it is known that the B(5)(-) cluster possesses a C(2v) planar structure and C(5)(-) is a linear chain. Here we study B/C mixed clusters containing five atoms, C(x)B(5-x)(-) (x = 1-5), which are expected to exhibit a planar to linear structural transition as a function of the C content. The C(x)B(5-x)(-) (x = 1-5) clusters were produced and studied by photoelectron spectroscopy; their geometric and electronic structures were investigated using a variety of theoretical methods. We found that the planar-to-linear transition occurs between x = 2 and 3: the global minimum structures of the B-rich clusters, CB(4)(-) and C(2)B(3)(-), are planar, similar to B(5)(-), and those of the C-rich clusters, C(3)B(2)(-) and C(4)B(-), are linear, similar to C(5)(-).

Probing the structural evolution of medium-sized gold clusters: Au(n)(-) (n = 27-35).

The structural evolution of negatively charged gold clusters (Au(n)(-)) in the medium size range for n = 27-35 has been investigated using photoelectron spectroscopy (PES) and theoretical calculations. New PES data are obtained using Ar-seeded He supersonic beams to achieve better cluster cooling, resulting in well-resolved spectra and revealing the presence of low-lying isomers in a number of systems. Density-functional theory calculations are used for global minimum searches. For each cluster anion, more than 200 low-lying isomers are generated using the basin-hopping global minimum search algorithm. The most viable structures and low-lying isomers are obtained using both the relative energies and comparisons between the simulated spectra and experimental PES data. The global minimum structures of Au(n)(-) (n = 27, 28, 30, and 32-35) are found to exhibit low-symmetry core-shell structures with the number of core atoms increasing with cluster size: Au(27)(-), Au(28)(-), and Au(30)(-) possess a one-atom core; Au(32)(-) features a three-atom triangular core; and Au(33)(-) to Au(35)(-) all contain a four-atom tetrahedral core. The global searches reveal that the tetrahedral core is a popular motif for low-lying structures of Au(33)(-) to Au(35)(-). The structural information forms the basis for future chemisorption studies to unravel the catalytic effects of gold nanoparticles.

Isomer identification and resolution in small gold clusters.

A variety of experimental techniques are used to resolve energetically close isomers of Au(7)(-) and Au(8)(-) by combining photoelectron spectroscopy and ab initio calculations. Two structurally distinct isomers are confirmed to exist in the cluster beam for both clusters. Populations of the different isomers in the cluster beam are tuned using Ar-tagging, O(2)-titration, and isoelectronic atom substitution by Cu and Ag. A new isomer structure is found for Au(7)(-), which consists of a triangular Au(6) unit with a dangling Au atom. Isomer-specific photoelectron spectra of Au(8)(-) are obtained from O(2)-titration experiment. The global minimum and low-lying structures of Au(7)(-), Au(8)(-), and MAu(n)(-) (n=6,7; M=Ag,Cu) are obtained through basin-hopping global minimum searches. The results demonstrate that the combination of well-designed photoelectron spectroscopy experiments (including Ar-tagging, O(2)-titration, and isoelectronic substitution) and ab initio calculation is not only powerful for obtaining the electronic and atomic structures of size-selected clusters, but also valuable in resolving structurally and energetically close isomers of nanoclusters.

Observation of earlier two-to-three dimensional structural transition in gold cluster anions by isoelectronic substitution: MAu(n)(-) (n=8-11; M=Ag,Cu).

The effects of isoelectronic substitution on the electronic and structural properties of gold clusters are investigated in the critical size range of the two-dimensional (2D)-three-dimensional (3D) structural transition (MAu(n)(-), n=8-11; M=Ag,Cu) using photoelectron spectroscopy and density functional calculations. Photoelectron spectra of MAu(n)(-) are found to be similar to those of the bare gold clusters Au(n+1)(-), indicating that substitution of a Au atom by a Ag or Cu atom does not significantly alter the geometric and electronic structures of the clusters. The only exception occurs at n=10, where very different spectra are observed for MAu(10)(-) from Au(11)(-), suggesting a major structural change in the doped clusters. Our calculations confirm that MAu(8)(-) possesses the same structure as Au(9)(-) with Ag or Cu simply replacing one Au atom in its C(2v) planar global minimum structure. Two close-lying substitution isomers are observed, one involves the replacement of a center Au atom and another one involves an edge site. For Au(10)(-) we identify three coexisting low-lying planar isomers along with the D(3h) global minimum. The coexistence of so many low-lying isomers for the small-sized gold cluster Au(10)(-) is quite unprecedented. Similar planar structures and isomeric forms are observed for the doped MAu(9)(-) clusters. Although the global minimum of Au(11)(-) is planar, our calculations suggest that only simulated spectra of 3D structures agree with the observed spectra for MAu(10)(-). For MAu(11)(-), only a 3D isomer is observed, in contrast to Au(12)(-) which is the critical size for the 2D-3D structural transition with both the 2D and 3D isomers coexisting. The current work shows that structural perturbations due to even isoelectronic substitution of a single Au atom shift the 2D to 3D structural transition of gold clusters to a smaller size.

Structural evolution of doped gold clusters: MAu(x)(-) (M = Si, Ge, Sn; x = 5-8).

We report a joint experimental and theoretical study on the structures of a series of gold clusters doped with a group-14 atom: MAu(x)(-) (M = Si, Ge, Sn; x = 5-8). Well-resolved photoelectron spectra were obtained and compared to calculations at several levels of theory to identify the low-lying structures of MAu(5-8)(-). We found that the structure of SiAu(5)(-) is dominated by the tetrahedrally coordinated Si motif, which can be viewed as built from the tetrahedral SiAu(4)(-) by an extra Au atom bonded to a terminal gold atom. However, SiAu(6)(-) and SiAu(7)(-) have quasi-planar structures, similar to those of GeAu(6)(-)/SnAu(6)(-) and GeAu(7)(-)/SnAu(7)(-), respectively. SiAu(8)(-) again has a tetrahedrally coordinated Si structure, which displays a structural motif of a dangling Au-Si unit sitting on a gold cluster surface, resembling that of the larger Si-doped gold cluster SiAu(16)(-). For M = Ge, Sn, our results show that the major isomers of GeAu(5-8)(-) have structures similar to those of the corresponding SnAu(5-8)(-) clusters, and they can be viewed as grown from the previously suggested square-pyramidal GeAu(4)(-) and SnAu(4)(-), respectively. Population of minor isomers was observed for SnAu(5)(-), GeAu(6)(-), SnAu(6)(-), and GeAu(8)(-). The 3D to quasi-2D to 3D structural evolution for SiAu(5)(-) to SiAu(8)(-) and the structural convergence for MAu(x)(-) (M = Si, Ge, Sn) at x = 6, 7 manifest competitions between the tendency of forming molecule-like structures around the group-14 dopant (optimizing M-Au interactions) and the strong tendency of forming planar structures for small gold anion clusters (optimizing Au-Au interactions).

Experimental and theoretical investigations of CB8-: towards rational design of hypercoordinated planar chemical species.

We demonstrated in our joint photoelectron spectroscopic and ab initio study that wheel-type structures with a boron ring are not appropriate for designing planar molecules with a hypercoordinate central carbon based on the example of CB(8), and CB(8)(-) clusters. We presented a chemical bonding model, derived from the adaptive natural density partitioning analysis, capable of rationalizing and predicting planar structures either with a boron ring or with a carbon atom occupying the central hypercoordinate position. According to our chemical bonding model, in the wheel-type structures the central atom is involved in delocalized bonding, while peripheral atoms are involved in both delocalized bonding and two-center two-electron (2c-2e) sigma-bonding. Since carbon is more electronegative than boron it favors peripheral positions where it can participate in 2c-2e sigma-bonding. To design a chemical species with a central hypercoordinate carbon atom, one should consider electropositive ligands, which would have lone pairs instead of 2c-2e peripheral bonds. Using our extensive chemical bonding model that considers both sigma- and pi-bonding we also discuss why the AlB(9) and FeB(9)(-) species with octacoordinate Al and Fe are the global minima or low-lying isomers, as well as why carbon atom fits well into the central cavity of CAl(4)(2-) and CAl(5)(+). This represents the first step toward rational design of nano- and subnano-structures with tailored properties.

Tuning the electronic properties of the golden buckyball by endohedral doping: M@Au16(-) (M = Ag,Zn,In).

The golden Au(16)(-) cage is doped systematically with an external atom of different valence electrons: Ag, Zn, and In. The electronic and structural properties of the doped clusters, MAu(16)(-) (M = Ag,Zn,In), are investigated by photoelectron spectroscopy and theoretical calculations. It is observed that the characteristic spectral features of Au(16)(-), reflecting its near tetrahedral (T(d)) symmetry, are retained in the photoelectron spectra of MAu(16)(-), suggesting endohedral structures with little distortion from the parent Au(16)(-) cage for the doped clusters. Density functional calculations show that the endohedral structures of M@Au(16)(-) with T(d) symmetry are low-lying structures, which give simulated photoelectron spectra in good agreement with the experiment. It is found that the dopant atom does not significantly perturb the electronic and atomic structures of Au(16)(-), but simply donate its valence electrons to the parent Au(16)(-) cage, resulting in a closed-shell 18-electron system for Ag@Au(16)(-), a 19-electron system for Zn@Au(16)(-) with a large energy gap, and a 20-electron system for In@Au(16)(-). The current work shows that the electronic properties of the golden buckyball can be systematically tuned through doping.

Experimental and theoretical investigation of three-dimensional nitrogen-doped aluminum clusters Al8N- and Al8N.

The structure and electronic properties of the Al(8)N(-) and Al(8)N clusters were investigated by combined photoelectron spectroscopy and ab initio studies. Congested photoelectron spectra were observed and experimental evidence was obtained for the presence of multiple isomers for Al(8)N(-). Global minimum searches revealed several structures for Al(8)N(-) with close energies. The calculated vertical detachment energies of the two lowest-lying isomers, which are of C(2v) and C(s) symmetry, respectively, were shown to agree well with the experimental data. Unlike the three-dimensional structures of Al(6)N(-) and Al(7)N(-), in which the dopant N atom has a high coordination number of 6, the dopant N atom in the two low-lying isomers of Al(8)N(-) has a lower coordination number of 4 and 5, respectively. The competition between the Al-Al and Al-N interactions are shown to determine the global minimum structures of the doped aluminum clusters and results in the structural diversity for both Al(8)N(-) and Al(8)N.

Clinico-neuropathological features of isocitrate dehydrogenase 2 gene mutations in lower-grade gliomas.

BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations. METHODS: Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test. RESULTS: Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively). CONCLUSIONS: IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.

Carbon avoids hypercoordination in CB6(-), CB6(2-), and C2B5(-) planar carbon-boron clusters.

The structures and bonding of CB6-, C2B5-, and CB62- are investigated by photoelectron spectroscopy and ab initio calculations. It is shown that the global minimum structures for these systems are distorted heptacyclic structures. The previously reported hexacyclic structures with a hypercoordinate central carbon atom are found to be significantly higher in energy and were not populated under current experimental conditions. The reasons why carbon avoids hypercoordination in these planar carbon-boron clusters are explained through detailed chemical-bonding analyses.