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Hypermutation and malignant transformation are potential complications arising from temozolomide treatment of IDH-mutant gliomas. However, the natural history of IDH-mutant low-grade gliomas without temozolomide treatment is actually under-studied. We retrieved retrospectively from our hospitals paired tumors from 19 patients with IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas where no interim adjuvant treatment with either temozolomide or radiotherapy was given between primary resections and first recurrences. Tissues from multiple recurrences were available from two patients and radiotherapy but not temozolomide was given before the last specimens were resected. We studied the natural molecular history of these low-grade IDH-mutant astrocytomas without pressure of temozolomide with DNA methylation profiling and copy number variation (CNV) analyses, targeted DNA sequencing, TERTp sequencing, FISH for ALT and selected biomarkers. Recurrences were mostly higher grades (15/19 patients) and characterized by new CNVs not present in the primary tumors (17/19 cases). Few novel mutations were identified in recurrences. Tumors from 17/19 (89.5%) patients showed either CDKN2A homozygous deletion, MYC or PDGFRA focal and non-focal gains at recurrences. There was no case of hypermutation. Phylogenetic trees constructed for tumors for the two patients with multiple recurrences suggested a lack of subclone development in their evolution when under no pressure from temozolomide. In summary, our studies demonstrated, in contrast to the phenomenon of temozolomide-induced hypermutation, IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas which had not been treated by temozolomide, acquired new CNVs at tumor recurrences. These findings improve our understanding of the molecular life history of IDH-mutant astrocytomas., (© 2024 The Author(s). Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

To explore the characteristics of pediatric primary retroperitoneal teratoma and the influencing factors of perioperative complications. The clinical data, imaging data, pathology results, perioperative complications, etc of patients with primary retroperitoneal teratoma admitted and treated at Shanxi Children ' s Hospital from March 2013 to September 2023 were retrospectively analyzed. The patients were divided into no complication group and complication group according to whether there were perioperative complications. The differences between the two groups were compared, and the influencing factors of complications were analyzed by multivariate logistic regression model. A total of 33 patients were included in this study, including 7 males and 26 females, with an age of [ M ( Q 1 , Q 3 ), 9.0 (4.0, 24.0)] months. Nineteen cases had tumors located in the left upper abdomen and 14 cases in the right upper abdomen, among which 17 cases grew across the midline, with the maximum tumor diameter of (12.9±4.5) cm. All patients had anatomical displacement of retroperitoneal vessels and organs: the number of anatomical displaced arteries was 3 (3, 4), the number of anatomical displaced veins was 4 (3, 5), the number of anatomical displaced organs was 5 (4, 6). Pathologic examination revealed 28 mature teratomas (Grade 0 and Grade 1) and 5 immature teratomas (Grade 2 and Grade 3). There were 18 cases in no complication group and 15 cases in the complication group. The incidence of perioperative complications was 45.5% (15/33). The number of tumors crossing the midline (6/18 vs 11/15, P =0.037), the number of tumors adhering closely to the surrounding tissues (7/18 vs 12/15, P =0.033), the number of anatomical displaced veins [4 (3, 4) vs 5 (4, 5), P =0.001], and the number of anatomical displaced organs [4 (3, 5) vs 6 (5, 6), P =0.001] were significantly different between the two groups. Multivariate logistic regression model analysis showed that the number of anatomical displaced organs ( OR =8.781, 95% CI : 2.155-35.784, P =0.002) was the influencing factor for perioperative complications of pediatric primary retroperitoneal teratoma.

Background: Patients with breast cancer brain metastases (BCBM) experience a rapid decline in their quality of life. Recently, tertiary lymphoid structures (TLSs), analogs of secondary lymphoid organs, have attracted extensive attention. However, the potential clinical implications of TLSs in BCBMs are poorly understood. In this study, we evaluated the density and composition of TLSs in BCBMs and described their prognostic value., Methods: Clinicopathological data were collected from 98 patients (2015-2021). TLSs were evaluated, and a TLS scoring system was constructed. Differences in progression-free survival (PFS) and overall survival (OS) between groups were calculated using the Kaplan-Meier method. Immunohistochemistry and multiplex immunofluorescence (mIF) were used to assess TLSs heterogeneity., Results: TLSs were identified in 47 patients with BCBM. High TLSs density indicated favorable survival (OS, p=0.003; PFS, p<0.001). TLS was positively associated with OS (p=0.0172) and PFS (p=0.0161) in the human epidermal growth factor receptor type 2-positive subtype, and with prolonged OS (p=0.0482) in the triple-negative breast cancer subtype. The mIF results showed significant differences in the percentages of T follicular helper (Tfh) cells, M2 macrophages, cytotoxic T lymphocytes, and CD8 + TIM-3 + T lymphocytes between the groups of TLS scores 0-3 (cytotoxic T lymphocytes, p=0.044; Tfh, p=0.021; M2 macrophages, p=0.033; CD8 + TIM-3 + T lymphocytes, p=0.018). Furthermore, novel nomograms incorporating the TLS scores and other clinicopathological predictors demonstrated prominent predictability of the 1-year, 3-year, and 5-year outcomes of BCBMs (area under the curve >0.800)., Conclusion: Our results highlight the impact of TLSs abundance on the OS and PFS of patients with BCBM. Additionally, we described the immune composition of TLSs and proposed novel nomograms to predict the prognosis of patients with BCBM., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older ( p = 0.029). CDKN2A HD was associated with a shorter OS ( p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf) 2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730 T , was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 ℃), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730 T showed the highest similarity to Solibacillus isronensis JCM 13838 T (96.2 %), followed by Solibacillus silvestris DSM 12223 T (96.0 %) and Solibacillus kalamii ISSFR-015 T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730 T was menaquinone 7 (MK-7). The major fatty acids were iso-C 15:0 and C 16:1 ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730 T and the reference strain S. isronensis JCM 13838 T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730 T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730 T (= NBRC 116268 T  = CGMCC 1.60169 T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The hitherto unknown hexakis(halomethyl)-functionalized tribenzotriquinacenes (TBTQs) 9 and 10 were synthesized from the key 4b,8b,12b-tribromo-TBTQ derivative 6 by an improved route in 67% overall yield. Extension of the bowl-shaped framework of 9 or 10 by threefold condensation with propargylamine or 2-azidoethylamine afforded the corresponding TBTQ-trialkyne 11 and TBTQ-triazide 12 , respectively. While attempts to construct bis-TBTQ cages, including homodimerization of 11 and heterocoupling of 11 with 12 , were unsuccessful, triazide 12 was found to undergo threefold [3 + 2]-cycloaddition with 3-ethynylaniline and phloroglucinol tripropargyl ether under click chemistry conditions. The latter reaction enabled facile capping of the TBTQ bowl to give the novel cage compound 5 in 22% yield.

Competing Interests: The authors declare that they have no conflict of interest.

Pediatric high-grade gliomas (HGG) of the cerebellum are rare, and only a few cases have been documented in detail in the literature. A major differential diagnosis for poorly differentiated tumors in the cerebellum in children is medulloblastoma. In this study, we described the histological and molecular features of a series of five pediatric high-grade gliomas of the cerebellum. They actually showed histological and immunohistochemical features that overlapped with those of medulloblastomas and achieved high scores in NanoString-based medulloblastoma diagnostic assay. Methylation profiling demonstrated these tumors were heterogeneous epigenetically, clustering to GBM&#95;MID, DMG&#95;K27, and GBM&#95;RTKIII methylation classes. MYCN amplification was present in one case, and PDGFRA amplification in another two cases. Interestingly, target sequencing showed that all tumors carried TP53 mutations. Our results highlight that pediatric high-grade gliomas of the cerebellum can mimic medulloblastomas at histological and transcriptomic levels. Our report adds to the rare number of cases in the literature of cerebellar HGGs in children. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum.

Background: The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments., Methods: To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide., Results: By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model., Conclusions: Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites., Competing Interests: K.J.Z., X.L.F., J.F.G., and X.Y.L. hold ownership interests and own patents of YSCH-01 in Yuansong Biotechnology Co., Ltd. No potential conflicts of interest were disclosed by the other authors., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

A new Gram-negative, rod-shaped, flagellated bacterium was isolated from soil in the Guishan, Xinping County, Yuxi City, Yunnan Province, China, and named YIM B01952 T . Growth occurred at 10-40 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.5) and with up to ≤ 5.0% (w/v) NaCl on Tryptic Soy Broth Agar (TSA) plates. Phylogenetic analysis based on the 16S rRNA gene and draft-genome sequence showed that strain YIM B01952 T belonged to the genus Pseudomonas, and was closely related to the type strain of Pseudomonas alcaligenes (sequence similarity was 98.8%). The digital DNA-DNA hybridization (dDDH) value between strain YIM B01952 T and the parallel strain P. alcaligenes ATCC 14909 T was 49.0% based on the draft genome sequence. The predominant menaquinone was Q-9. The major fatty acids were summed feature 8 (C 18:1 ω6c and/or C 18:1 ω7c), summed feature 3 (C 16:1 ω6c and/or C 16:1 ω7c) and C 16:0 . The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, and phosphatidylglycerol. The genome size of strain YIM B01952 T was 4.341 Mb, comprising 4156 predicted genes with a DNA G + C content of 66.4 mol%. In addition, we detected that strain YIM B01952 T had some traditional functional genes (plant growth promotion and multidrug resistance), unique genes through genome comparison and analysis with similar strains. Based on genetic analyses and biochemical characterization, the strain YIM B01952 T was identified as a novel species in the genus Pseudomonas, for which the name Pseudomonas subflava sp. nov. is proposed. The type strain is YIM B01952 T (=CCTCC AB 2021498 T  = KCTC 92073 T )., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this study, a novel aerobic mesophilic bacterial strain with capable of degrading chitin, designated YIM B06366 T , was isolated and classified. The rod-shaped, Gram-stain-negative, on-spore-forming bacterium originated from rhizosphere soil sample collected in Kunming City, Yunnan Province, southwest PR China. Strain YIM B06366 T exhibited growth at temperatures between 20 and 35 °C (optimum, 30 °C) and at pH 6.0-8.0 (optimum, pH 6.0). The analysis of 16S rRNA gene sequence similarity revealed that strain YIM B06366 T was most closely related to type strain Chitinolyticbacter meiyuanensis SYBC-H1 T (98.9%). Phylogenetic analysis based on genome data indicated that strain YIM B06366 T should be assigned to the genus Chitinolyticbacter. The Average Nucleotide Identity (ANI) and digital DNA-DNA Hybridization (dDDH) values between strain YIM B06366 T and the reference strain Chitinolyticbacter meiyuanensis SYBC-H1 T were 84.4% and 27.7%, respectively. The major fatty acids included Summed Feature 3 (C 16:1 ω6c/C 16:1 ω7c), Summed Feature 8 (C 18:1 ω6c/C 18:1 ω7c), and C 16:0 . The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipids, and two unidentified phospholipids. The predominant menaquinone was Q-8, and the genomic DNA G + C content was 64.1%. Considering the polyphasic taxonomic evidence, strain YIM B06366 T is proposed as a novel species within the genus Chitinolyticbacter, named Chitinolyticbacter albus sp. nov. (type strain YIM B06366 T  = KCTC 92434 T  = CCTCC AB 2022163 T )., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re-arrangement, targeted sequencing and TERTp sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2/22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2/22q. No other molecular changes were totally unique to NF2/22q or non-NF2/22q tumors. For molecular evolution, NF2/22q meningiomas had higher cytogenetic abnormalities than non-NF2/22q meningiomas (p = 0.003). Most of the cytogenetic changes in NF2/22q meningiomas were present from the outset whereas for non-NF2/22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non-NF2/22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2/22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non-NF2/22q meningiomas showed CDKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort (p = 0.002)., (© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors., (© 2023. The Author(s).)

(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous study found that GBM patients with EGFRvIII (+) have low sensitivity to TMZ. However, the reasons and possible mechanisms of the chemoradiotherapy resistance in GBM patients with EGFRvIII (+) are not clear. (2) Methods: In this study, tissue samples of patients with GBM, GBM cell lines, glioma stem cell lines, and NSG mice were used to explore the causes and possible mechanisms of low sensitivity to TMZ in patients with EGFRvIII (+)-GBM. (3) Results: The study found that EGFRvIII promoted the proneural-mesenchymal transition of GBM and reduced its sensitivity to TMZ, and EGFRvIII regulated of the expression of ALDH1A3. (4) Conclusions: EGFRvIII activated the NF-κB pathway and further regulated the expression of ALDH1A3 to promote the proneural-mesenchymal transition of GBM and reduce its sensitivity to TMZ, which will provide an experimental basis for the selection of clinical drugs for GBM patients with EGFRvIII (+).

Background: To explore the value of human data from the Zhuang population via predicting the diameter of the hamstring tendon autograft in anterior cruciate ligament (ACL) reconstruction and determining the feasibility of preoperative ultrasound for prediction., Methods: In total, 24 Zhuang patients who underwent ACL reconstruction with a 4-strand semitendinosus and gracilis tendon autograft (4 S-STG) were enrolled in this study. Before the operation, the affected semitendinosus tendon (ST) was examined by ultrasonography, and its length, diameter, cross-sectional area, and circumference were measured. The patients' basic information and body data, ie, height, weight, body mass index, lower limb length injured, and thigh circumference injured, were recorded. Their ST and gracilis tendon lengths and diameters and 4 S-STG diameter were measured during the operation. A correlation analysis was conducted between the ultrasound measurement results and human data and intraoperative tendon measurements., Results: The ST diameter measured by ultrasound was correlated with the ST length and ST diameter measured during operation, and the ST circumference measured by ultrasound was correlated with the ST diameter measured during operation. The patients' body weight can be used to distinguish a 4 S-STG diameter of ≥8 mm (P < .01, mean difference = 11.59). The area under the receiver operating characteristic curve of body weight was 0.829. The final graft diameter ≥8 mm could be predicted with a body weight of 61.5 kg as the cutoff point; the sensitivity and specificity were 72.2% and 83.3%, respectively., Conclusion: In Zhuang patients undergoing ACL reconstruction with 4 S-STG, body weight more accurately predicted graft diameter than preoperative semitendinosus diameter., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that begins in early infancy and childhood and is characterized by impaired social communication and repetitive stereotyped behaviors., Objective: The purpose of this study was to examine the development of the corpus callosum and its relationship to neurobehavior in young children with high-risk (HR) ASD using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)., Methods: Twenty-one children with HR-ASD who visited Anhui Children's Hospital between January 2020 and December 2021 were selected as the study group, while 19 matched children with normal development during the same time were adopted as the control group. Cranial MRI+DTI were performed for all of the enrolled children and fractional anisotropy (FA) measurements were taken in each region of the corpus callosum., Results: The FA values in all regions of the corpus callosum were higher in the study group than in the control group (0.417 ± 0.016 vs. 0.412 ± 0.02 in the corpus callosum knee, 0.439 ± 0.018 vs. 0.431 ± 0.023 in the corpus callosum body, and 0.446 ± 0.017 vs. 0.434 ± 0.019 in the splenium of corpus callosum [SCC]), where the difference in the FA in the SCC was statistically significant between the two groups (P< 0.05). There was a positive correlation between the FA in the corpus callosum knee and speech scores in the neuropsychological development of the study group (P< 0.05)., Conclusion: There was a premature development tendency for corpus callosum myelination in young children with HR-ASD, and the developmental tendency was visible in the SCC. There was also a positive relationship between corpus callosum knee development and language function.

A new aerobic bacterial strain, designated strain YIM B02290 T , was isolated from the soil of Machangqing, Dali city, Yunnan Province, China. Cells were Gram-stain-positive, sporogenous, rod-shaped, and motile with peritrichous flagella. Strain YIM B02290 T showed the highest 16S rRNA gene sequence similarity with Brevibacillus laterosporus (97.6%) and Brevibacillus halotolerans (97.6%). The ANI and dDDH values between strain YIM B02290 T and the two reference strains Brevibacillus laterosporus LAM00312 T and Brevibacillus halotolerans DSM 25 T are 72.6% and 72.2%, 20.2% and 19.5% based on the draft genome sequence, respectively. The major cellular fatty acids contain anteiso-C 15: 0 and iso-C 15: 0 . The diagnostic diamino acid of the cell-wall peptidoglycan was meso-diaminopimelic acid. The predominant menaquinone was identified as menaquinone-7. The main polar lipids of strain YIM B02290 T were diphosphatidylglycerol, phosphatidylglycerol, phospholipid, phosphatidyl monomethylethanolamine. The genomic DNA G + C content was 40.6 mol%. All results showed that strain YIM B02290 T represents a novel species of the genus Brevibacillus, for which the name Brevibacillus daliensis sp. nov. is proposed. The type strain is YIM B02290 T (= CCTCC AB 2021094 T  = CGMCC 1.18802 T  = KCTC 43376 T )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, a couple of tetradentate Pt(II) enantiomers ((-)- 1 and (+)- 1 ) and a couple of tetradentate Pt(IV) enantiomers ((-)- 2 and (+)- 2 ) containing fused 5/6/6 metallocycles have been synthesized by controlling reaction conditions. Two valence forms could transform into each other through mild chemical oxidants and reductants. Single-crystal X-ray diffraction confirms the structures of (-)-1 and (-)-2. The coordination sphere of the Pt(II) cation in (-)- 1 displays a distorted square-planar geometry and a platinum centroid helix chirality. In contrast, the structure of (-)- 2 reveals a distorted octahedral geometry. The solution and the solid of (-)- 1 are highly luminescent. Complex (-)- 1 shows a prominent aggregation-induced emission enhancement (AIEE) behavior in DMSO/water solution with emission quantum yield ( Φ em ) up to 73.2%. Furthermore, highly phosphorescent Pt(II) enantiomers exhibit significant circularly polarized luminescence (CPL) with a dissymmetry factor ( g lum ) of order 10 -3 in CH 2 Cl 2 solutions at room temperature. Symmetrically appreciable CPL signals are observed for the enantiomers (-)- 1 and (+)- 1 ., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Telomerase reverse transcriptase (TERT) promoter (pTERT) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase (IDH) wild type (wt) (IDHwt), pTERTwt glioblastomas are not well known. We recruited 72 adult IDHwt, pTERTwt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDHwt, pTERT mutant (mut) glioblastomas, suggesting that pTERT mutation on its own is not a prognostic factor among IDHwt glioblastomas. Epigenetically, the tumors clustered into classic-like (11%), mesenchymal-like (32%), and LGm6-glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDHwt, pTERTmut glioblastomas. LGm6-GBM-clustered tumors were enriched for platelet derived growth factor receptor alpha (PDGFRA) amplification or mutation (p = 0.008), and contained far fewer epidermal growth factor receptor (EGFR) amplification (p < 0.01), 10p loss (p = 0.001) and 10q loss (p < 0.001) compared with cases not clustered to this group. LGm6-GBM cases predominantly showed ALT (p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/-10. Since the cases were already pTERTwt, so the three molecular properties of EGFR amplification, +7/-10, and pTERT mutation may not cover all IDHwt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A)/B was associated with a worse OS (p = 0.031) and was an independent prognosticator in multivariate analysis (p = 0.032). In conclusion, adult IDHwt, pTERTwt glioblastomas show epigenetic clustering different from IDHwt, pTERTmut glioblastomas, and IDHwt glioblastomas which are pTERTwt may however not show EGFR amplification or +7/-10 in a significant proportion of cases. CDKN2A/B deletion is a poor prognostic biomarker in this group., (© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Purpose: To evaluate the feasibility of using ultrasonography to preoperatively predict the autologous hamstring graft diameter for anterior cruciate ligament (ACL) reconstruction in the Zhuang population and determine a reliable measurement level using ultrasound. Methods: Twenty-four Zhuang patients who were scheduled for ACL reconstruction using four-strand semitendinosus tendon (ST) and gracilis tendon (G) (4S-STG) autografts were included in this study. Ultrasonographic examinations of the ST and the G on the damaged side were conducted before the operation. We recorded the transverse diameter (TD), anterior-posterior diameter (APD), cross-sectional area (CSA), and perimeter (P) of the tendons. The measurements were obtained from two levels of the tendons: the widest point of the medial femoral epicondyle (level 1) and the myotendinous junction of the sartorius (level 2). We also calculated the combined (ST + G) TD, APD, CSA, and p values. Then, we obtained the intraoperative measurements. The correlation between the ultrasonic and intraoperative measurements was analyzed, and the advantages of the ultrasonic measurements at the two different levels were compared. Results: When we measured at level 1, we found that part of the ultrasonic measurements were correlated with intraoperative measurements. The preoperative CSA of the G (P-GCSA) can be used to distinguish a 4S-STG autograft diameter of ≥8 mm ( p < 0.01, mean difference = 3.7). The area under the P-GCSA curve was 0.801 ( p < 0.05). A P-GCSA of 8.5 mm 2 could be used to predict a 4S-STG autograft diameter of ≥8 mm with a sensitivity of 61.1% and specificity of 83.3%. However, there was no correlation between the ultrasonic and intraoperative measurements at level 2. Conclusion: Preoperative ultrasound can be used to predict the sufficient diameter of 4S-STG autografts when considering patients from Zhuang who are undergoing ACL reconstruction. The ultrasonic measurement should be obtained at the widest point of the medial femoral epicondyle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Zheng, Shi, Yang, Zhang, Yang, Wang and Tan.)

A Gram-stain-negative, aerobic, rod-shaped bacteria strain, named YIM B01951 T , was isolated from a forest soil sample collected from Mopan Mountain National Forest Park, Xinping City, Yunnan Province, southwest PR China (101°58'06" N, 23°03'02" E). Growth occurred at 15-40 °C (optimum, 30 °C), pH 5.0-8.0 (optimum, pH 6.5) and with up to ≤ 3.0% (w/v) NaCl on Nutrient Agar plates. The results of 16S rRNA gene sequence similarity analysis showed that strain YIM B01951 T was closely related to the type strain of Cohnella arctica M9-62 T (96.5%) and Cohnella lupini RLAHU4B T (96.3%). YIM B01951 T contains anteiso-C 15:0 and iso-C 16:0 as the major cellular fatty acids; the main polar lipids are diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), lysylphosphatidylglycerol (PGL) and five aminophospholipids (APL). The MK-7 is the major respiratory quinone and the DNA G + C content is 49.2 mol%. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B01951 T is considered to be a novel species of the genus Cohnella, and named Cohnella mopanensis sp. nov. The type strain is YIM B01951 T (= NBRC 115331 T  = KCTC 43370 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic administration of methamphetamine (METH) leads to physical and psychological dependence. It is generally accepted that METH exerts rewarding effects via competitive inhibition of the dopamine transporter (DAT), but the molecular mechanism of METH addiction remains largely unknown. Accumulating evidence shows that mitochondrial function is important in regulation of drug addiction. In this study,  we investigated the role of Clk1, an essential mitochondrial hydroxylase for ubiquinone (UQ), in METH reward effects. We showed that Clk1 +/- mutation significantly suppressed METH-induced conditioned place preference (CPP), accompanied by increased expression of DAT in plasma membrane of striatum and hippocampus due to Clk1 deficiency-induced inhibition of DAT degradation without influencing de novo synthesis of DAT. Notably, significantly decreased iron content in striatum and hippocampus was evident in both Clk1 +/- mutant mice and PC12 cells with Clk1 knockdown. The decreased iron content was attributed to increased expression of iron exporter ferroportin 1 (FPN1) that was associated with elevated expression of hypoxia-inducible factor-1α (HIF-1α) in response to Clk1 deficiency both in vivo and in vitro. Furthermore, we showed that iron played a critical role in mediating Clk1 deficiency-induced alteration in DAT expression, presumably via upstream HIF-1α. Taken together, these data demonstrated that HIF-1α-mediated changes in iron homostasis are involved in the Clk1 deficiency-altered METH reward behaviors., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

The WHO (2021) Classification classified a group of pediatric-type high-grade gliomas as IDH wildtype, H3 wildtype but as of currently, they are characterized only by negative molecular features of IDH and H3. We recruited 35 cases of pediatric IDH wildtype and H3 wildtype hemispheric glioblastomas. We evaluated them with genome-wide methylation profiling, targeted sequencing, RNAseq, TERT promoter sequencing, and FISH. The median survival of the cohort was 27.6 months. With Capper et al.'s 36 methylation groups as a map, the cases were found to be epigenetically heterogeneous and were clustered in proximity or overlay of methylation groups PXA-like (n = 8), LGG-like (n = 10), GBM&#95;MYCN (n = 9), GBM&#95;midline (n = 5), and GBM&#95;RTKIII (n = 3). Histology of the tumors in these groups was not different from regular glioblastomas. Methylation groups were not associated with OS. We were unable to identify groups specifically characterized by EGFR or PDGFRA amplification as proposed by other authors. EGFR, PDGFRA, and MYCN amplifications were not correlated with OS. 4/9 cases of the GBM&#95;MYCN cluster did not show MYCN amplification; the group was also enriched for EGFR amplification (4/9 cases) and the two biomarkers overlapped in two cases. Overall, PDGFRA amplification was found in only four cases and they were not restricted to any groups. Cases in proximity to GBM&#95;midline were all hemispheric and showed loss of H3K27me3 staining. Fusion genes ALK/NTRK/ROS1/MET characteristic of infantile glioblastomas were not identified in 17 cases successfully sequenced. BRAF V600E was only found in the PXA group but CDKN2A deletion could be found in other methylation groups. PXA-like cases did not show PXA histological features similar to findings by other authors. No case showed TERT promoter mutation. Mutations of mismatch repair (MMR) genes were poor prognosticators in single (p ≤ 0.001) but not in multivariate analyses (p = 0.229). MGMT had no survival significance in this cohort. Of the other common biomarkers, only TP53 and ATRX mutations were significant poor prognosticators and only TP53 mutation was significant after multivariate analyses (p = 0.024). We conclude that IDH wildtype, H3 wildtype pediatric hemispheric glioblastomas are molecularly heterogeneous and in routine practice, TP53, ATRX, and MMR status could profitably be screened for risk stratification in laboratories without ready access to methylation profiling., (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Objective: We aimed to characterise glioblastomas of adolescents and young adults (AYAs) that were isocitrate dehydrogenase (IDH) wild type (wt) and H3wt., Materials and Methods: Fifty such patients (aged 16-32) were studied by methylation profiling, targeted sequencing and targeted RNA-seq., Results: Tumours predominantly clustered into three methylation classes according to the terminology of Capper et al. (2018): (anaplastic) pleomorphic xanthoastrocytoma (PXA) (21 cases), GBM&#95;midline (15 cases) and glioblastoma RTK/mesenchymal (seven cases). Two cases clustered with ANA&#95;PA, four cases with LGG classes and one with GBM&#95;MYCN. Only fifteen cases reached a calibrated score >0.84 when the cases were uploaded to DKFZ Classifier. GBM&#95;midline-clustered tumours had a poorer overall survival (OS) compared with the PXA-clustered tumours (p = 0.030). LGG-clustered cases had a significantly better survival than GBM&#95;midline-clustered tumours and glioblastoma RTK/mesenchymal-clustered tumours. Only 13/21 (62%) of PXA-clustered cases were BRAF V600E mutated. Most GBM&#95;midline-clustered cases were not located in the midline. GBM&#95;midline-clustered cases were characterised by PDGFRA amplification/mutation (73.3%), mutations of mismatch repair genes (40.0%), and all showed H3K27me3 and EZH1P loss, and an unmethylated MGMT promoter. Across the whole cohort, MGMT promoter methylation and wt TERT promoter were favourable prognosticators. Mismatch repair gene mutations were poor prognosticators and together with methylation class and MGMT methylation, maintained their significance in multivariate analyses. BRAF mutation was a good prognosticator in the PXA-clustered tumours., Conclusion: Methylation profiling is a useful tool in the diagnosis and prognostication of AYA glioblastomas, and the methylation classes have distinct molecular characteristics. The usual molecular diagnostic criteria for adult IDHwt glioblastoma should be applied with caution within the AYA age group., (© 2022 British Neuropathological Society.)

Advanced genomic techniques have now been incorporated into diagnostic practice in neuro-oncology in the literature. However, these assays are expensive and time-consuming and demand bioinformatics expertise for data interpretation. In contrast, single-gene tests can be run much more cheaply, with a short turnaround time, and are available in general pathology laboratories. The objective of this study was to establish a molecular grading scheme for adult gliomas using combinations of commonly available single-gene tests. We retrospectively evaluated molecular diagnostic data of 1,275 cases of adult diffuse gliomas from three institutions where we were testing for IDH1/2 mutation, TERTp mutation, 1p19q codeletion, EGFR amplification, 10q deletion, BRAF V600E, and H3 mutations liberally in our regular diagnostic workup. We found that a molecular grading scheme of Group 1 (1p19q codeleted, IDH mutant), Group 2 (IDH mutant, 1p19q non-deleted, TERT mutant), Group 3 (IDH mutant, 1p19q non-deleted, TERT wild type), Group 4 (IDH wild type, BRAF mutant), Group 5 (IDH wild type, BRAF wild type and not possessing the criteria of Group 6), and Group 6 (IDH wild type, and any one of TERT mutant, EGFR amplification, 10q deletion, or H3 mutant) could significantly stratify this large cohort of gliomas for risk. A total of 1,028 (80.6%) cases were thus classifiable with sufficient molecular data. There were 270 cases of molecular Group 1, 59 cases of molecular Group 2, 248 cases of molecular Group 3, 27 cases of molecular Group 4, 117 cases of molecular Group 5, and 307 cases of molecular Group 6. The molecular groups were independent prognosticators by multivariate analyses and in specific instances, superseded conventional histological grades. We were also able to validate the usefulness of the Groups with a cohort retrieved from The Cancer Genome Atlas (TCGA) where similar molecular tests were liberally available. We conclude that a single-gene molecular stratification system, useful for fine prognostication, is feasible and can be adopted by a general pathology laboratory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Shi, Li, Wang, Chen, Chung, Chan, Poon, Loong, Liu, Zhang, Mao and Ng.)

The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better prognosis. Our previous study provided an evident that IDH-mutant lower grade astrocytomas is not a homogeneous group and could be further stratified by PDGFRA amplification, CDK4 amplification and CDKN2A deletion. In this study, we detected the expressions of DNA mismatch repair (MMR) proteins (PMS2, MLH1, MSH2, MSH6) and PD-L1 by immunohistochemistry in 147 IDH-mutant lower grade astrocytomas and explored their clinical relevance. The loss of was identified in 28.6%, 1.4%, 8.8% and 13.6%, respectively. PD-L1 expression was detected in 1.4% of this cohort. Survival analysis revealed that loss of PMS2 was correlated with shorter OS (p < 0.001) and PFS (p = 0.005). Loss of PMS2 or MLH1 was associated with shorter OS (p < 0.001) and PFS (p = 0.008). In IDH-mutant lower grade astrocytomas without CDKN2A deletion, loss of PMS2 was associated with poorer OS (p < 0.001) and PFS (p = 0.001). Furthermore, among IDH-mutant lower grade astrocytomas lacking the three biomarkers (PDGFRA, CDK4 and CDKN2A), loss of PMS2 was also associated with a poorer OS (p < 0.001) and PFS (p = 0.003). Our data illustrated the potential application of MMR genes in stratification of IDH-mutant lower grade astrocytomas without PDGFRA, CDK4 and CDKN2A copy number alterations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.

The structure-mechanochromism relationship is explored with respect to packing patterns and corresponding intermolecular interactions that are affected by the number and location of -F. The distinct and reversible mechanochormic luminescence (Δλem up to ca. 90 nm) of yellow solids (-)-1-Yg, (-)-2-Yg, and (-)-3-Yg was displayed with a simultaneous crystal-to-amorphous transformation. The change of multiple triplet excited states accounted for the mechanochormic luminescence, and a switch from the 3π,π* monomer to the excimer/3MMLCT occurred in the grinding process. The mechanical force led to perturbation in the molecular packing, and aggregates with effective PtPt and π-π interactions were formed in the amorphous phase, leading to the variation of excited states. The mechanochromic luminescence could be reverted by dropping in CH2Cl2 and could be cycled multiple times without perceivable performance degradation. This work gives a reference for designing mechanochromic luminescent materials toward multicolor and multicomponent responses.

Brain edema is a common and serious complication of ischemic stroke with limited effective treatment. We previously reported that methylene blue (MB) attenuated ischemic brain edema in rats, but the underlying mechanisms remained unknown. Aquaporin 4 (AQP4) in astrocytes plays a key role in brain edema. We also found that extracellular signal-regulated kinase 1/2 (ERK1/2) activation was involved in the regulation of AQP4 expression in astrocytes. In the present study, we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), MB (3 mg/kg, for 30 min) was infused intravenously through the tail vein started immediately after reperfusion and again at 3 h after ischemia (1.5 mg/kg, for 15 min). Brain edema was determined by MRI at 0.5, 2.5, and 48 h after tMCAO. The decreases of apparent diffusion coefficient (ADC) values on diffusion-weighted MRI indicated cytotoxic brain edema, whereas the increase of T2 MRI values reflected vasogenic brain edema. We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO. In addition, MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO. In a cell swelling model established in cultured rat astrocyte exposed to glutamate (1 mM), we consistently found that MB (10 μM) attenuated cell swelling, AQP4 increases and ERK1/2 activation. Moreover, the ERK1/2 inhibitor U0126 (10 μM) had the similar effects as MB. These results demonstrate that MB improves brain edema and astrocyte swelling, which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway, suggesting that MB may be a potential choice for the treatment of brain edema.

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.

The synthesis of the enantiomerically pure, D 3 -symmetric covalent hydrocarbon cages (+)-( M , M )- 4 and (-)-( P , P )- 4 bearing two C 3 -symmetrically functionalized tribenzobenzotriquinacene (TBTQ) vertices is reported. The enantiomerically pure TBTQ building blocks (+)-( M )- 5 and (-)-( P )- 5 were prepared via the diastereomeric TBTQ triamides obtained by use of both Boc-d- and Boc-l-phenylglycine as chiral auxiliaries.

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.

Recently, the newly emerging lead-halide perovskites have received tremendous attention in the photodetection field because of their intrinsic large light absorption and high well-balanced carrier transport characteristics. Unfortunately, the issue of instability and the existence of toxic lead cations have greatly restricted their practical applications and future commercialization. Furthermore, the previous studies on perovskite photodetectors mainly operate in visible and near-infrared light region, and there are practically no relevant reports aimed at the deep-ultraviolet (DUV) region. In this study, an air-stable and DUV-sensitive photoconductive detector was demonstrated with a solution-processed ternary copper halides Cs 3 Cu 2 I 5 thin films as the light absorber. The proposed photodetector is very sensitive to wavelengths of light below 320 nm and unresponsive to the visible light. Because of the high material integrity and large surface coverage of the Cs 3 Cu 2 I 5 thin films, the detector presents an outstanding photodetection performance with a photoresponsivity of ∼17.8 A W -1 , specific detectivity of 1.12 × 10 12 Jones, and fast response speed of 465/897 μs, superior to previously reported DUV photodetectors based on other material systems. Unlike traditional lead-halide perovskites, the lead-free Cs 3 Cu 2 I 5 shows remarkable stability against heat, UV light, and environmental oxygen/moisture. Thus, the unsealed photodetector demonstrates good operation stability for 11 h of continuous running in open air. Even after 80-day storage in ambient air, its photodetection capability can nearly be maintained. The results suggest that non-toxic Cs 3 Cu 2 I 5 could be a potential candidate for stable and environment friendly DUV detectors, enabling an assembly of optoelectronic systems in the future.

A pair of homologues, [Zn(Hssa)(1,4-bib)·H2O]n (1) and [Zn3(ssa)2(1,4-bib)3·4H2O]n (2), were successfully assembled using the same metals and ligands [H3ssa = 5-sulfosalicylic acid; 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene] under solvothermal conditions. Polymer 1 is a two-dimensional (2D) sql network and polymer 2 is a three-dimensional (3D) framework. Polymer 2 can be simplified into two topology types: bct and tfc. The two polymers show significant differences in the fluorescence sensing of metal ions and proton conductivity. Their applications in detecting metal ions and proton conductivity were explored. Polymer 1 shows high sensitivity and selectivity for Fe3+, while polymer 2 can detect Hg2+ ions. The limit of detection was 1.66 μM with Fe3+ for 1 and 0.23 μM with Hg2+ for 2 in water. In addition, both 1 and 2 exhibit high water stability and proton conductivity. At 60 °C and 95% relative humidity, their conductivities were 3.45 × 10-5 and 6.26 × 10-6 S cm-1, respectively. A detailed analysis of the Hirshfeld surface and fingerprints was carried out for 1 and 2 to compare the interactions between the molecules, which is essential for analysing the relationship between their structures and material properties.

Three new compounds, namely massonside C ( 1 ), massonianoside F ( 2) , and 3, 8-dimethyl- herbacetin-7-O-β-D-glucopyranoside ( 3 ), together with five known compounds ( 4 - 8 ), were isolated from the fresh needles of Pinus massoniana . Their structures were established by 1D, 2D NMR, HRMS and comparison with the literature data. The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis. All isolated compounds were evaluated for the protective effect of human umbilical vein endothelial cells against oxidative damage.

In this study, dendritic polyamine chitosan beads with and without 2-aminomethyl pyridine were facilely prepared and characterized. Compared to CN (without the pyridine function), more adsorption active sites, larger pores, higher nitrogen content, higher specific surface area, and higher strength could be obtained for CNP (with the pyridine function). CNP microspheres afforded a larger adsorption capacity than those obtained by CN for different pH values; further, the uptake amounts of Cu(ii) were 0.84 and 1.12 mmol g -1 for CN and CNP beads, respectively, at pH 5. The CNP microspheres could scavenge Cu(ii) from highly acidic and salty solutions: the maximum simulated uptake amount of 1.93 mmol g -1 at pH 5 could be achieved. Due to the strong bonding ability and weakly basic property of pyridine groups, the adsorption capacity of Cu(ii) at pH 1 was 0.75 mmol g -1 in highly salty solutions, which was comparative to those obtained from the commercial pyridine chelating resin M4195 ( Q Cu(II) = 0.78 mmol g -1 at pH 1). In addition, a distinct salt-promotion effect could be observed for CNP beads at both pH 5 and 1. Therefore, the prepared adsorbent CNP beads can have promising potential applications in the selective capturing of heavy metals in complex solutions with higher concentrations of H + and inorganic salts, such as wastewaters from electroplating liquid and battery industries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH-mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (P = 0.036) and low-risk (P < 0.0001) groups. One limitation of this study is the relatively short follow-up period, a common confounding factor for studies on low-grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk., (© 2019 International Society of Neuropathology.)

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

Distinct circularly polarized luminescence (CPL) activity was observed in chiral (C ∧ N ∧ N)Pt(II) [(C ∧ N ∧ N) = 4,5-pinene-6'-phenyl-2,2'-bipyridine] complexes with bis- or triphenylphosphine ligands. Compared to the pseudo-square-planar geometry of chiral (C ∧ N ∧ N)Pt(II) complexes with chloride, phenylacetylene (PPV) and 2,6-dimethylphenyl isocyanide (Dmpi) ligands, the coordination configuration around the Pt(II) nucleus of chiral (C ∧ N ∧ N)Pt(II) complexes with bulk phosphine ligands is far more distorted. The geometry is straightforwardly confirmed by X-ray crystallography. The phosphines' participation enhanced the CPL signal of Pt(II) complexes profoundly, with the dissymmetry factor ( g lum ) up to 10 -3 . The distorted structures and enhanced chiroptical signals were further confirmed by time-dependent density functional theory (TD-DFT) calculations., (Copyright © 2020 Yang, Zhang, Han, Weng, Chen, Wu, Han, Zhang and Shi.)

Recently, the discovery and development of lead-free perovskite quantum dots (QDs) that are eco-friendly and stable has become an active research area in low-cost lighting and display fields. However, the low photoluminescence quantum yield (PLQY) caused by the residual surface states of such QDs severely hinders their practical applications and commercialization. In this work, a strategy of employing water-induced nanocomposites was proposed to improve the PLQY of cesium bismuth halide (Cs 3 Bi 2 X 9 ) QDs, and a substantial enhancement by ∼130% (from 20.2% to 46.4%) was achieved by an optimized water treatment of Cs 3 Bi 2 Br 9 QDs. A detailed analysis indicated that Cs 3 Bi 2 Br 9 /BiOBr nanocomposites, in which the Cs 3 Bi 2 Br 9 QD core was encapsulated into a BiOBr matrix, can effectively suppress the surface defects of QDs, resulting in a longer PL lifetime and a larger exciton binding energy compared with the pristine sample. Finally, the Cs 3 Bi 2 Br 9 /BiOBr nanocomposites were used as the color-converting phosphors for down-conversion white light-emitting devices, which show a good operation stability in ambient air, significantly better than the reference device constructed with conventional lead-halide perovskites. We believe that the method used here provides an effective strategy to improve the fluorescence efficiency of lead-free perovskite QDs, which will create opportunities for their applications in lighting and displays.

Giant cell glioblastoma (gcGBM) is a rare histological variant of GBM, accounting for about 1% of all GBM. The prognosis is poor generally though gcGBM does slightly better than the other IDH-wild-type GBM. Because of the rarity of the cases, there has been no comprehensive molecular analysis of gcGBM. Previously, single-gene study identified genetic changes in TP53, PTEN and TERT promoter mutation in gcGBM. In this report, we performed whole-exome sequencing (WES) to identify somatically acquired mutations and copy number variations (CNVs) in 10 gcGBM genomes. We also examined TERT promoter mutation and MGMT methylation in our cohort. On top of the reported mutations, WES revealed ATRX, PIK3R1, RB1 and SETD2 as the recurrent mutations in gcGBM. Notably, one tumor harbored a mutation in MutS homolog 6 (MSH6) that is a key mismatch repair (MMR) gene. This tumor demonstrated hypermutation phenotype and showed an increased number of somatic mutations. TERT promoter mutation and MGMT methylation were observed in 20% and 40% of our samples, respectively. In conclusion, we described relevant mutation profiling for developing future targeted therapies in gcGBM., (© 2019 International Society of Neuropathology.)

Objectives: To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine., Design: An overview of systematic reviews and meta-analyses (SR/MAs) for randomized controlled trials., Material and Methods: We searched PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, VIP Chinese Journal Full Text Database, WANFANG Data, and China Biology Medicine disc from their establishment to May 27, 2018. SR/MAs of randomized controlled trials comparing the effect of the acupuncture intervention with another treatment control in migraine patients were included., Results: 428 SRs were identified, and 15 of them were included. Only 4 SR/MAs were assessed by GRADE, which showed certainty of most evidence being low or very low. Assessed by AMSTAR-2, fourteen was critically low rating overall confidence in the results, and 1 was low rating overall confidence in the results. Evidence suggested that acupuncture has a significant advantage of pain improvement, efficacy, and safety relative to blank control, sham acupuncture, or drug treatment, but some of these results are contradictory., Conclusions: We found that acupuncture on treating migraine has the advantage for pain improvement and safety, but the quality of SR/MAs of acupuncture for migraine remains to be improved., Competing Interests: None of the authors has any financial conflicts of interest to disclose., (Copyright © 2019 Xia-tian Zhang et al.)

Starting from the commercially available 4-bromoindole, a concise and efficient enantioselective formal synthesis of (+)-cycloclavine ( 1 ) in 13 steps with 2.0% overall yield and a total synthesis of (+)-5- epi -cycloclavine ( 2 ) in 14 steps with 3.3% overall yield were achieved. Key features of the syntheses include the addition of a Grignard reagent to the C═N/Heck reaction sequence to construct the fused 6-5-6 ring systems, cyclopropanation, an ester aminolysis reaction, and the first example of the construction of a 3-azabicyclo[3,1,0]hexane through an intramolecular [3 + 2] cycloaddition/nitrogen extrusion.

Background: IDH -mutant glioblastoma is classified by the 2016 CNS WHO as a group with good prognosis. However, the actual number of cases examined in the literature is relatively small. We hypothesize that IDH -mutant glioblastoma is not a uniform group and should be further stratified., Methods: We conducted methylation profiles and estimated copy number variations of 57 IDH- mutant glioblastomas., Results: Our results showed that 59.6% and 40.4% of tumors belonged to glioma-CpG island methylator phenotype (G-CIMP)-high and G-CIMP-low methylation subgroups, respectively. G-CIMP-low subgroup was associated with significantly worse overall survival (OS) as compared to G-CIMP-high ( P = .005). CDKN2A deletion (42.1%) was the most common gene copy number variation, and was significantly associated with G-CIMP-low subgroup ( P = .004). Other frequent copy number changes included mesenchymal-epithelial transition ( MET ) (5.3%), CCND2 (19.3%), PDGFRA (14.0%), CDK4 (12.3%), and EGFR (12.3%) amplification. Both CDKN2A deletion ( P = .036) and MET amplification ( P < .001) were associated with poor OS in IDH -mutant glioblastomas. Combined epigenetic signature and gene copy number variations separated IDH -mutant glioblastomas into Group 1 (G-CIMP-high), Group 2 (G-CIMP-low without CDKN2A nor MET alteration), and Group 3 (G-CIMP-low with CDKN2A and/or MET alteration). Survival analysis revealed Groups 1 and 2 exhibited a favorable OS (median survival: 619 d [20.6 mo] and 655 d [21.8 mo], respectively). Group 3 exhibited a significant shorter OS (median survival: 252 d [8.4 mo]). Multivariable analysis confirmed the independent prognostic significance of our Groups., Conclusions: IDH -mutant glioblastomas should be stratified for risk with combined epigenetic signature and CDKN2A/MET status and some cases have poor outcome., (© The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)‑induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end‑diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK‑muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription‑quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO‑treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK‑8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase‑3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO‑induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO‑induced rats with HF and in ISO‑treated H9C2 cells, and that rGDF11 treatment increased ISO‑induced oxidative stress injury by upregulating Nox4 in H9C2 cells.