Genomic characterization reveals distinct mutational landscapes and therapeutic implications between different molecular subtypes of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has high heterogeneity, poor prognosis, and limited treatment success. Recently, an immunohistochemistry-based surrogate classification for the "Fudan University Shanghai Cancer Center (FUSCC) subtyping" has been developed and is considered more suitable for clinical application. Seventy-one paraffin-embedded sections of surgically resected TNBC were classified into four molecular subtypes using the IHC-based surrogate classification. Genomic analysis was performed by targeted next-generation sequencing and the specificity of the subtypes was explored by bioinformatics, including survival analysis, multivariate Cox regression, pathway enrichment, Pyclone analysis, mutational signature analysis and PHIAL analysis. AKT1 and BRCA1 mutations were identified as independent prognostic factors in TNBC. TNBC molecular subtypes encompass distinct genomic landscapes that show specific heterogeneities. The luminal androgen receptor (LAR) subtype was associated with mutations in PIK3CA and PI3K pathways, which are potentially sensitive to PI3K pathway inhibitors. The basal-like immune-suppressed (BLIS) subtype was characterized by high genomic instability and the specific possession of signature 19 while patients in the immunomodulatory (IM) subtype belonged to the PD-L1 ≥ 1% subgroup with enrichment in Notch signaling, suggesting a possible benefit of immune checkpoint inhibitors and Notch inhibitors. Moreover, mesenchymal-like (MES) tumors displayed enrichment in the receptor tyrosine kinase (RTK)-RAS pathway and potential sensitivity to RTK pathway inhibitors. The findings suggest potential treatment targets and prognostic factors, indicating the possibility of TNBC stratified therapy in the future.

Taxonomic and phylogenetic contributions to Diatrypaceae from southeastern Tibet in China.

In this study, we investigated the diversity of diatrypaceous fungi from southeastern Tibet in China. The phylogenetic analyses were carried out based on ITS and ß-tubulin sequences of 75 taxa of Diatrypaceae from around the world. Based on a combination of morphological features and molecular evidence, a new genus-Alloeutypa, with three new species-A. milinensis, Diatrype linzhiensis, and Eutypella motuoensis, and a new combination-A. flavovirens, were revealed by the materials in China. Alloeutypa is characterized by stromatal interior olivaceous buff, stromata producing well-developed discrete, and ascospores allantoid, subhyaline. These characteristics separate the new genus from the similar genus Eutypa. Comprehensive morphological descriptions, illustrations, and a phylogenetic tree to show the placement of new taxa are provided. All novelties described herein are morphologically illustrated and phylogeny investigated to better integrate taxa into the higher taxonomic framework and infer their phylogenetic relationships as well as establish new genera and species. Our results indicate that the diatrypaceous fungi harbor higher species diversity in China.

Multi-Locus Phylogeny and Morphology Reveal Two New Species of Hypoxylon (Hypoxylaceae, Xylariales) from Motuo, China.

Hypoxylaceous fungi are abundant in China, but their discovery and report are uneven in various provinces, with more fungi in Yunnan and Hainan and fewer fungi in Tibet. During the investigation of macro-fungi in Motuo county, Tibet Autonomous Region, we collected a number of xylarialean specimens. Six hypoxylaceous specimens growing on dead angiosperm were collected from the forests of Motuo county, and they were described and illustrated as two new species in Hypoxylon based on a combination of morphological characters and molecular evidence. Hypoxylon diperithecium was characterized by its bistratal perithecia, purple-brown stromatal granules, citrine to rust KOH-extractable pigments, and light brown to brown ascospores ellipsoid-inequilateral with conspicuous coil-like ornamentation. Hypoxylon tibeticum was distinct from other species by having pulvinate and applanate stromata, surface vinaceous, with orange granules, orange KOH-extractable pigments, and brown ascospores with inconspicuous ornamentation. The multi-gene phylogenetic analyses (ITS-LSU-RPB2-TUB) supported the two new taxa as separate lineages in the genus Hypoxylon. A key to all known Hypoxylon taxa from China is provided.

Global Taxonomy and Phylogeny of Irpicaceae (Polyporales, Basidiomycota) With Descriptions of Seven New Species and Proposals of Two New Combinations.

The phylogenetic analyses of the family Irpicaceae were carried out based on a complete global sampling. The dataset that included concatenated ITS1-5.8S-ITS2 and nrLSU sequences of 67 taxa of Irpicaceae from around the world was subjected to the maximum likelihood analyses and Bayesian inference. In the phylogenetic tree, species from 14 genera were distributed in nine clades, among which five genera-Irpex, Phanerochaetella, Byssomerulius, Cytidiella, and Meruliopsis, received high support values. The genus Efibula was shown to be paraphyletic and four subclades could be recognized, while Phanerochaete allantospora, Leptoporus mollis, and several species from Ceriporia and Candelabrochaete formed a large clade with relatively strong support. Based on the molecular and morphological evidence, seven new corticioid species- Candelabrochaete guangdongensis, Efibula grandinosa, E. hainanensis, E. shenghuae, E. taiwanensis, Irpex alboflavescens, and Phanerochaetella sinensis, were revealed from the materials mostly from East Asia. The monotypic genus Flavodontia, newly described from southwestern China, is regarded as a later synonym of Irpex, and the new combination I. rosea is proposed. In addition, Phanerochaetella queletii is proposed for a taxon first described from Italy and newly recorded from China; Phanerochaete jose-ferreirae from Portugal is determined to be a later synonym. Descriptions and illustrations of the new species and the newly combined taxa are presented, and morphological comparisons for the known species of Efibula and Phanerochaetella are provided.

Antidiabetic lanostane triterpenoids from the fruiting bodies of Ganoderma weberianum.

Eight previously undescribed lanostane triterpenoids, ganodeweberiols A âˆ¼ H (1-8), together with eighteen known compounds (9-26), were isolated from the fruiting bodies of Ganoderma weberianum. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic analysis, as well as NMR chemical shifts and electronic circular dichroism (ECD) calculations. Compounds 2, 7, 12, and 14 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 35.3 µM âˆ¼ 223.4 µM compared to the positive control acarbose (IC50, 304.6 µM). Kinetic study indicated that the most potent compound 12 was a mixed type inhibitor for α-glucosidase. Molecular docking simulation revealed the interactions of 12 with α-glucosidase. Additionally, Compounds 3 and 6 inhibited glucagon-induced hepatic glucose production in HepG2 cells with EC50 values of 42.0 and 85.9 µM, respectively. Further study revealed that compounds 3 and 6 inhibited hepatic glucose production by suppression glucagon-induced cAMP accumulation. Moreover, compounds 3 and 26 were active against HeLa cell line with IC50 values of 17.0 and 6.8 µM, respectively.

Three New Species of Hypoxylon (Xylariales, Ascomycota) on a Multigene Phylogeny from Medog in Southwest China.

During a survey of hypoxylaceous fungi in Medog county (Tibet Autonomous Region, China), three new species, including Hypoxylon damuense, Hypoxylon medogense, and Hypoxylon zangii, were described and illustrated based on morphological and multi-gene phylogenetic analyses. Hypoxylon damuense is characterized by its yellow-brown stromatal granules, light-brown to brown ascospores, and frequently indehiscent perispore. Hypoxylon medogense is morphologically and phylogenetically related to H. erythrostroma but differs in having larger ascospores with straight spore-length germ slit and conspicuously coil-like perispore ornamentation. Hypoxylon zangii shows morphological similarities to H. texense but differs in having Amber (47), Fulvous (43) and Sienna (8) KOH-extractable pigments and larger ascospores with straight spore-length germ slit. The multi-gene phylogenetic analyses inferred from the datasets of ITS-RPB2-LSU-TUB2 supported the three new taxa as separate lineages within Hypoxylon. A key to all known Hypoxylon species from China and related species worldwide is provided.

Subclassifying triple-negative breast cancers and its potential clinical utility.

The molecular subtyping of triple-negative breast cancer (TNBC) is critical to guiding individualized patient treatment. In this study, we sought to characterize the clinicopathologic features of TNBC subtypes and to identify correlates of patient survival in an effort to provide a robust foundation for treatment planning. We additionally assessed PD-L1 expression in Chinese TNBC patients and evaluated the relationship between such expression and immunotherapeutic treatment outcomes. Based on analyses of histologic characteristics including apocrine differentiation, tumor-infiltrating lymphocytes, and metaplastic features, we selected immunohistochemical (IHC) markers including CD8, FOXC1, and AR for use in classifying TNBC cases. Associations between these subtypes and a range of clinicopathologic characteristics were evaluated. We classified a cohort of 93 TNBC patients into individuals with luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune-suppressed (BLIS), and mesenchymal (MES) tumor subtypes (23, 24, 39, and 7 cases, respectively). PD-L1 positivity was observed in 49.6% of cases and was more common in individuals with IM subtype disease. Mismatch repair deficiency (dMMR) was observed in just one patient. Significant differences in histologic grade, pT stage, lymphocyte distribution patterns, large scarring areas without cells in tumor of central (central scar), and PD-L1, P53, and Rb status were observed among these TNBC subtypes, whereas no such differences were observed with respect to age, invasion pattern, or pN stage. Rates of disease progression were higher at the 40-50 month follow-up time point, but there were no significant differences in recurrence-free survival or breast cancer-specific survival among these subtypes. IHC markers associated with clinicopathologic characteristics represent a powerful approach to TNBC molecular typing, providing a foundation for precision patient treatment. PD-L1 expression may represent a relevant factor in TNBC patient immunotherapeutic treatment planning, whereas dMMR is not likely to be of substantial value when evaluating immunotherapeutic efficacy in these patients.

Three new Xylaria species (Xylariaceae, Xylariales) on fallen leaves from Hainan Tropical Rainforest National Park.

Three new species of Xylaria on fallen leaves in Hainan Province of China are described and illustrated, based on morphological and molecular evidence. Xylariahedyosmicola is found on fallen leaves of Hedyosmumorientale and featured by thread-like stromata with a long sterile filiform apex. Phylogenetically, X.hedyosmicola is closely related to an undescribed Xylaria sp. from Hawaii Island, USA and morphologically similar to X.vagans. Xylarialindericola is found on fallen leaves of Linderarobusta and characterised by its subglobose stromata and a long filiform stipe. It is phylogenetically closely related to X.siculaf.major. Xylariapolysporicola is found on fallen leaves of Polysporahainanensis, it is distinguished by upright or prostrate stromata and ascospores sometimes with a slimy sheath or non-cellular appendages. Xylariapolysporicola is phylogenetically closely related to X.amphithele and X.ficicola. An identification key to the ten species on fallen leaves in China is given.

Global Phylogeny and Taxonomy of the Wood-Decaying Fungal Genus Phlebiopsis (Polyporales, Basidiomycota).

An in-depth study of the phylogeny and taxonomy of the corticioid genus Phlebiopsis (Phanerochaetaceae) was conducted. Phylogenetic analyses of the ITS1-5.8S-ITS2 and nrLSU sequences demonstrated that Phlebiopsis is a strongly supported clade which is distinct from its sister clades of Phaeophlebiopsis, Hapalopilus, and Rhizochaete. Two genera, Australohydnum and Hjortstamia, are reduced to synonyms under Phlebiopsis as generic type species A. griseofuscescens and H. friesii, respectively, are embedded in the Phlebiopsis clade. Twenty-four lineages are resolved in the ITS phylogenetic tree of Phlebiopsis, including six new taxa, viz. P. albescens, P. brunnea, P. cylindrospora, P. magnicystidiata, P. membranacea and P. sinensis, from Sri Lanka and China. Five new combinations, viz. Phaeophlebiopsis mussooriensis, Phlebiopsis bambusicola, P. dregeana, P. griseofuscescens and P. novae-granatae, are proposed. Phlebiopsis crassa is a morphological species complex with three distinct lineages. Phlebiopsis lamprocystidiata is determined to be a later synonym of P. darjeelingensis. The new taxa are described, illustrated, and compared and contrasted to morphologically similar species. An emended description of Phlebiopsis is provided along with an identification key to 27 accepted species.

In vitro antifungal activities, molecular docking, and DFT studies of 4-amine-3-hydrazino-5-mercapto-1,2,4-triazole derivatives.

Six disubstituted Schiff base compounds were synthesized (A1-A6) and characterized using infrared spectroscopy (IR), elemental analyses (EA), 1H NMR, 13C NMR and HRMS spectroscopic techniques. Crystal structure of A1 has been determined by single crystal X-ray diffraction. The antifungal activities against three fungi were assessed, and the results showed that compounds of A1 and A2 have good activity for Wheat gibberellic with EC50 value of 15.89 and 16.99 mg/L, respectively. Compounds of A3, A4 and A6 have good bioactivity against Maize rough bacteria (the value of EC50 is 8.23, 7.56 and 7.92 mg/L, respectively). According to the result of molecular docking, compounds of A1 and A2 have the smallest docking energy (-8.33, -9.00 kcal/mol). Besides, for A1 and A2, the analysis of highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) analysis and molecular electrostatic potential map were to further elaborate the reason for the good activity with density functional theory (DFT)-B3LYP/6-31G.

Four new corticioid species in Trechisporales (Basidiomycota) from East Asia and notes on phylogeny of the order.

Four new species in Trechisporales from East Asia, Dextrinocystiscalamicola, Subulicystidiumacerosum, S.tropicum and Tubuliciumbambusicola, are described and illustrated, based on morphological and molecular evidence. The phylogeny of Trechisporales was inferred from a combined dataset of ITS-nrLSU sequences. In the phylogenetic tree, Sistotremastrum formed a family-level clade of its own, sister to the Hydnodontaceae clade formed by all other genera. Dextrinocystis, is for the first time, confirmed as a member of Hydnodontaceae. A key to all the accepted genera in Trechisporales is given.

Activities of Endogenous Lipase and Lipolysis Oxidation of Low-Salt Lactic Acid-Fermented Fish (Decapterus maruadsi).

There is increasing demand for low-salt meat products that retain traditional flavors. In this study, dry-salted fish (Decapterus maruadsi) were processed by 2 methods to obtain traditional salted fish (HS) and low-salt lactic acid-fermented fish (LAF). The relationship between lipolysis and lipid oxidation was investigated by evaluating changes in endogenous lipase (lipolytic enzymes; lipoxygenase, LOX), free fatty acid composition, thiobarbituric acid reactive substances (TBARS), and peroxide value (POV) during processing. Lipolytic enzyme activity showed a decreasing trend, in general. LOX activity initially increased and eventually decreased. Phospholipase, acid lipase, and neutral lipase activity was 0.33, 0.17, 0.57 (in HS) and 0.39, 0.25, 0.67 (in LAF) times in the final product than the activity levels observed in fresh fish. A principal component analysis indicated that phospholipase and neutral lipase play major roles in promoting lipid hydrolysis (in HS and LAF), the correlation between lipolytic activity and lipid oxidation in HS is greater than the correlation in LAF, and the contribution of LOX to lipid oxidation was minor in salted fish.

Prevalence and Treatment of Children's Asthma in Rural Areas Compared with Urban Areas in Beijing.

BACKGROUND: The prevalence of childhood asthma has been increasing in China. This study aimed to compare the prevalence, diagnosis, and treatment of asthmatic children from urban and rural areas in Beijing, China. METHODS: Schools, communities, and kindergartens were randomly selected by cluster random sampling from urban and rural areas in Beijing. Parents were surveyed by the same screening questionnaires. On-the-spot inquiries, physical examinations, medical records, and previous test results were used to diagnose asthmatic children. Information on previous diagnoses, treatments, and control of symptoms was obtained. RESULTS: From 7209 children in rural areas and 13,513 children in urban areas who completed screening questionnaires, 587 children were diagnosed as asthma. The prevalence of asthma in rural areas was lower than in urban areas (1.25% vs. 3.68%, χ2 = 100.80, P < 0.001). The diagnosis of asthma in rural areas was lower than in urban areas (48.9% vs. 73.9%, χ2 = 34.6, P < 0.001). Compared with urban asthmatic children (56.5%), only 35.6% of rural asthmatic children received inhaled corticosteroids (P < 0.05). The use of bronchodilators was also lower in rural areas than in urban areas (56.5% vs. 66.4%, χ2 = 14.2, P < 0.01). CONCLUSION: The prevalence of asthma in children was lower in rural areas compared with children in the urban area of Beijing. A considerable number of children were not diagnosed and inadequately treated in rural areas.

1-[6-(3,5-Di-methyl-pyrazol-1-yl)-1,2,4,5-tetra-zin-3-yl]guanidin-2-ium perchlorate methanol monosolvate.

In the title solvated salt, C8H12N9 (+)·ClO4 (-)·CH3OH, the dihedral angle between the tetra-zine and pyrazole rings is 26.05 (7)°. The two N atoms bonded to the 1,2,4,5-tetra-zine ring deviate from the plane defined by its four N atoms by 0.234 (2) and 0.186 (2) Å. There is an intra-molecular N-H⋯N hydrogen bond between the protonated guanidine fragment and one of the tetra-zine N atoms. In the crystal, two cations and two perchlorate anions are connected via N-H⋯O hydrogen bonds into centrosymmetric assemblies. These assemblies are further linked into a two-dimensional network parallel to (100) via bifurcated O-H⋯(N,N) hydrogen bonds formed with the bridging methanol mol-ecules.

Three new lanostanoid triterpenes from the fruiting bodies of Ganoderma tropicum.

Three new lanostanoid triterpenes, 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (1), 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (2), and 3ß,15ß-dihydroxy-7,11,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester (3) were isolated from the EtOAc extract of the fruiting bodies of Ganoderma tropicum. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as MS. The bioassay of inhibitory activity against acetylcholinesterase (AChE) of these isolates was evaluated and compound 2 exhibited definite inhibitory activity against AChE.

3,3-Dinitro-azetidinium chloride.

In the title gem-dinitro-azetidinium chloride salt, C3H6N3O4(+)·Cl(-), the cations and anions lie on a mirror plane. The azetidine ring is virtually planar, with a mean deviation from the plane of 0.0569 Å. The dihedral angle between the two nitro groups is 90.00 (5)°. In the crystal, the ions are linked by N-H⋯Cl interactions, forming a chain along the c-axis direction, and C-H⋯O inter-actions, forming a layer parallel to (010).

1-(2,4-Dinitro-phen-yl)-3,3-dinitro-azetidine.

In the title compound, C(9)H(7)N(5)O(8), the dihedral angle between the mean plane of the azetidine ring and that of the benzene ring is 26.1 (1)°; the planes of the two nitro groups of the azetidine ring are aligned at 88.7 (1)°.

1-Benzoyl-3,3-dinitro-azetidine.

In the title gem-dinitro-azetidine derivative, C(10)H(9)N(3)O(5), the azetidine ring is almost planar, the maximum value of the endocyclic torsion angle being 0.92 (14)°. The gem-dinitro groups are mutually perpendicular and the dihedral angle between the azetidine and benzene rings is 46.70 (10)°

Nonisothermal decomposition kinetics and computational studies on the properties of 2,4,6,8-tetranitro-2,4,6,8-tetraazabicyclo[3,3,1]onan-3,7-dione (TNPDU).

The thermal decomposition and the nonisothermal kinetics of the thermal decomposition reaction of 2,4,6,8-tetranitro-2,4,6,8-tetraazabicyclo[3,3,1]onan-3,7-dione (TNPDU) were studied under the nonisothermal condition by differential scanning calorimetry (DSC) and thermogravimetry-derivative thermogravimetry (TG-DTG) methods. The kinetic model function in differential form and the value of Ea and A of the decomposition reaction of TNPDU are f(alpha) = 3(1 - alpha)[-ln(1 - alpha)](2/3), 141.72 kJ mol(-1), and 10(11.99) s(-1), respectively. The critical temperature of thermal explosion of the title compound is 232.58 degrees C. The values of DeltaS(++), DeltaH(++), and DeltaG(++) of this reaction are -15.50 J mol(-1) K(-1), 147.65 kJ mol(-1), and 155.26 kJ mol(-1), respectively. The theoretical investigation on the title compound as a structure unit was carried out by the DFT-B3LYP/6-311++G** method. The IR frequencies and NMR chemical shift were performed and compared with the experimental results. The heat of formation (HOF) for TNPDU was evaluated by designing isodesmic reactions. The detonation velocity (D) and detonation pressure (P) were estimated by using the well-known Kamlet-Jacobs equation, based on the theoretical densities and HOF. The calculation on bond dissociation energy suggests that the N-N bond should be the trigger bond during the pyrolysis initiation process.