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C-H bond functionalization involving C,C-palladacycle intermediates provides a unique platform for developing novel reactions. However, the vast majority of studies have been limited to the transformations of C(aryl),C-palladacycles. In sharp contrast, catalytic reactions involving C(alkyl),C(alkyl)-palladacycles have rarely been reported. Herein, we disclose an unprecedented cascade C(sp3)-H annulation involving C(alkyl),C(alkyl)-palladacycles. In this protocol, alkene-tethered cycloalkenyl bromides undergo intramolecular Heck/C(sp3)-H activation to generate C(alkyl),C(alkyl)-palladacycles, which can be captured by α-bromoacrylic acids to afford tricyclic fused pyridinediones. In addition, this strategy can also be applied to indole-tethered cycloalkenyl bromides to construct pentacyclic fused pyridinediones via suquential Heck dearomatization/C(sp3)-H activation/decarboxylative cyclization. Notably, the removal of α-bromoacrylic acids in the reaction of alkene-tethered cycloalkenyl bromides can build an interesting tricyclic skeleton containing a four-membered ring. Preliminary mechanistic experiments indicate that five-membered C(alkyl),C(alkyl)-palladacycles serve as the key intermediates. Meanwhile, density functional theory (DFT) calculations have provided insights into the reaction pathway.
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The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from â¼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.
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Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, the clinical use of TMZ is limited by its various side effects and resistance to chemotherapy. The present study revealed the synergistic inhibition of glioblastoma through the combined administration of TMZ and perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in the suppression of DNA repair mechanisms. Furthermore, the combination of TMZ and perifosine elicited caspase-dependent apoptosis, decreasing glioblastoma cell viability and proliferation. The observed synergistic effect of this combination therapy on glioblastoma was validated in vivo, as evidenced by the substantial reduction in glioblastoma xenograft growth following combined treatment with TMZ and perifosine. In recurrent glioma patients, higher BRCA1 expression is associated with worse prognosis, especially the ones that received TMZ-treated. These findings underscore the potent antitumor activity of the AKT inhibitor perifosine when combined with TMZ and suggest that this approach is a promising strategy for clinical glioblastoma treatment.
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Rice, a primary staple food, may be improved in value via fermentation. Here, ten medicinal basidiomycetous fungi were separately applied for rice fermentation. After preliminary screening, Ganoderma boninense, Phylloporia pulla, Sanghuangporus sanghuang and Sanghuangporus weigelae were selected for further LC-MS based determination of the changes in metabolic profile after their fermentation with rice, and a total of 261, 296, 312, and 355 differential compounds were identified, respectively. Most of these compounds were up-regulated and involved in the metabolic pathways of amino acid metabolism, lipid metabolism, carbohydrate metabolism and the biosynthesis of other secondary metabolites. Sanghuangporus weigelae endowed the rice with the highest nutritional and bioactive values. The metabolic network of the identified differential compounds in rice fermented by S. weigelae illustrated their close relationships. In summary, this study provides insights into the preparation and application of potential functional food via the fermentation of rice with medicinal fungi.
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Fermentação , Alimento Funcional , Metabolômica , Oryza , Oryza/metabolismo , Oryza/química , Oryza/microbiologia , Alimento Funcional/análise , Basidiomycota/metabolismo , Basidiomycota/crescimento & desenvolvimento , Basidiomycota/química , Espectrometria de Massas , Fungos/metabolismoRESUMO
Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.
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A palladium-catalyzed divergent cascade decarboxylative annulation of aryl iodides and α-oxocarboxylic acids using norbornene (NBE) derivatives as a controlled switch is reported. When NBE is used as a mediator, fluorenones are synthesized with moderate to excellent yields via a Catellani reaction that involves sequential ortho-C-H arylation and ipso-decarboxylative acylation of aryl iodides. Employing oxanorbornadiene (ONBD) instead of NBE enables the assembly of dibenzo[a,c]cycloheptenones by a retro-Diels-Alder reaction rather than the release of an ONBD. Additionally, the synthetic utility of this method is demonstrated by the diversification of the products.
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Ganoderma is a well-known medicinal macrofungal genus, of which several species have been thoroughly studied from the medicinal perspective, but most species are rarely involved in. In this study, we focus on the polysaccharides extracted from Ganoderma boninense and their antioxidant activity. Ganoderma boninense is a serious pathogen of oil palms that are cultivated commercially in Southeast Asia. Response surface methodology was conducted to optimize the liquid medium composition, and the mycelia biomass reached 7.063 g/L, that is, 1.4-fold compared with the seed medium. The crude and purified polysaccharides extracted from the fermentation broth showed well 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging abilities, and the scavenging abilities of purified polysaccharides reached 94.47 % and 99.88 %, respectively. Six fractions of polysaccharides were extracted and purified from fruiting bodies, mycelia and fermentation broth separately with the elution buffers of distilled water and 0.1 M NaCl solution. Generally, the polysaccharides from fruiting bodies showed stronger protective effect on H2O2-induced HepG2 cell oxidative damage than other fractions. A total of five to seven monosaccharides were identified in the six fractions of polysaccharides. The correlation analysis revealed that the content of fucose was significantly correlated with the antioxidant activity of polysaccharides, while xylose showed negative correlation results. In summary, the polysaccharides from G. boninense have a potential to be used as natural antioxidants.
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Antioxidantes , Ganoderma , Antioxidantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Polissacarídeos/farmacologiaRESUMO
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.
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Sequenciamento de Cromatina por Imunoprecipitação , Cromatina , Bases de Dados Genéticas , Análise de Célula Única , Cromatina/genética , Epigênese Genética , Humanos , AnimaisRESUMO
OBJECTIVE: To conduct a quantitative analysis of published studies on hematoma enlargement after intracerebral hemorrhage. METHODS: Studies on hematoma enlargement after cerebral hemorrhage were retrieved from the Web of Science database on June 30, 2023. Microsoft Excel, VOSviewer, and CiteSpace software were used for bibliometric analysis and visualization, focusing on the quantitative characteristics of the literature. RESULTS: A total of 444 articles were published in 161 journals, with 2161 authors from 41 countries and 717 institutions. The most published authors, countries, and institutions were Goldstein, the USA, and Massachusetts General Hospital. Stroke published the most studies, but the average citation number per year of Lancet Neurology far exceeded that of other journals. The research field of hematoma enlargement is mainly divided into 3 focuses, including mechanisms, identification (computed tomography signs, predictive models), and treatment (hemostasis, antihypertensive therapy). Most bursts in publication number have been since 2010, where the highest burst was from research on spot signs, and the latest burst focused on tranexamic acid. Treatment using tranexamic acid based on different computed tomography signs is a focus of current research, but the effectiveness still requires further exploration. CONCLUSIONS: This bibliometric analysis analyzed the research framework and hotspots on hematoma enlargement after cerebral hemorrhage, which can help researchers better understand this field and provide potential suggestions for collaborations and research.
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Acidente Vascular Cerebral , Ácido Tranexâmico , Humanos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Bibliometria , Hematoma/diagnóstico por imagem , HipertrofiaRESUMO
AIM: Glioblastoma (GBM) has been reported to be the most common high-grade primary malignant brain tumor in clinical practice and has a poor prognosis. O6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation has been related to prolonged overall survival (OS) in GBM patients after temozolomide treatment. METHODS: Proteomics and metabolomics were combined to explore the dysregulated metabolites and possible protein expression alterations in white matter (control group), MGMT promoter unmethylated GBM (GBM group) or MGMT promoter methylation positive GBM (MGMT group). RESULTS: In total, 2745 upregulated and 969 downregulated proteins were identified in the GBM group compared to the control group, and 131 upregulated and 299 downregulated proteins were identified in the MGMT group compared to the GBM group. Furthermore, 131 upregulated and 299 downregulated metabolites were identified in the GBM group compared to the control group, and 187 upregulated and 147 downregulated metabolites were identified in the MGMT group compared to the GBM group. The results showed that 94 upregulated and 19 downregulated proteins and 20 upregulated and 16 downregulated metabolites in the MGMT group were associated with DNA repair. KEGG pathway enrichment analysis illustrated that the dysregulated proteins and metabolites were involved in multiple metabolic pathways, including the synthesis and degradation of ketone bodies, amino sugar and nucleotide sugar metabolism. Moreover, integrated metabolomics and proteomics analysis was performed, and six key proteins were identified in the MGMT group and GBM group. Three key pathways were recognized as potential biomarkers for recognizing MGMT promoter unmethylated GBM and MGMT promoter methylation positive GBM from GBM patient samples, with areas under the curve of 0.7895, 0.7326 and 0.7026, respectively. CONCLUSION: This study provides novel mechanisms to understand methylation in GBM and identifies some biomarkers for the prognosis of two different GBM types, MGMT promoter unmethylated or methylated GBM, by using metabolomics and proteomics analyses.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Biomarcadores/metabolismo , Neoplasias Encefálicas/patologia , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Glioblastoma/patologia , Prognóstico , ProteômicaRESUMO
Wood-inhabiting fungi have important economic values as well as playing a major ecological role in forest ecosystem cycles. The Dabie Mountains, at the junction of Henan, Hubei, and Anhui Provinces, Central China, provide an ideal climate and favorable niches for the speciation and diversification of various forms of life including fungi. We studied the species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi that revealed 175 wood-inhabiting basidiomycetous species, of which 20 represented unidentified species, based on morphological and phylogenetic analyses of 575 specimens collected from ten sampling sites. These species belonged to two classes, 11 orders, 42 families, and 106 genera of Basidiomycota, and included 12 edible species, 28 medicinal species, four poisonous species, and seven forest pathogens. Four types of fungal distribution pattern at the genus level were recognized for 65 genera, while another 41 genera could not be placed in any known distribution pattern. The five sampling sites in the eastern part of the Dabie Mountains had significantly higher species diversity and phylogenetic diversity of wood-inhabiting basidiomycetous fungi than those in the western part, and thus deserve priority in terms of conservation. The community of wood-inhabiting basidiomycetous fungi in the Dabie Mountains is generally affected by a combination of habitat filtering and competitive exclusion. This study provides a basis on which to build actions for the comprehensive recognition, utilization, and conservation of wood-inhabiting basidiomycetous fungi in the region.
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Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants that pose a threat to human health. Among these PAHs, benzo[a]pyrene (BaP), a five-ring compound, exhibits high resistance to biodegradation. White-rot fungus Phlebia acerina S-LWZ20190614-6 has demonstrated higher BaP degradation capabilities compared with Phanerochaete chrysosporium and P. sordida YK-624, achieving a degradation rate of 57.7% after 32 days of incubation under a ligninolytic condition. To further enhance the biodegradation rate, three nonionic surfactants were used, and the addition of 1 or 2 g·L-1 of polyethylene glycol monododecyl ether (Brij 30) resulted in nearly complete BaP biodegradation by P. acerina S-LWZ20190614-6. Interestingly, Brij 30 did not significantly affect the activity of manganese peroxidase and lignin peroxidase, but it did decrease laccase activity. Furthermore, the impact of cytochrome P450 on BaP degradation by P. acerina S-LWZ20190614-6 was found to be relatively mild. Transcriptomic analysis provided insights into the degradation mechanism of BaP, revealing the involvement of genes related to energy production and the synthesis of active enzymes crucial for BaP degradation. The addition of Brij 30 significantly upregulated various transferase and binding protein genes in P. acerina S-LWZ20190614-6. Hence, the bioremediation potential of BaP by the white-rot fungus P. acerina S-LWZ20190614-6 holds promise and warrants further exploration.
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Interest in edible and medicinal macrofungi is millennial in terms of their uses in health and food products in Central Asia, while interest in inedible and medicinal macrofungi has grown in popularity in recent years. Edible and inedible medicinal basidiomycetes were collected during field surveys from different regions of Uzbekistan. The morphological characters and similarity assessment of rDNA-Internal Transcribed Spacer sequence data were used to measure diversity and habitat associations. A number of 17 species of medicinal macrofungi of ethnomycological and medicinal interest was found associated with 23 species of trees and shrubs belonging to 11 families and 14 genera. Polyporaceae and Hymenochaetaceae were represented by the highest number of species followed by Ganodermataceae, Fomitopsidaceae, Auriculariaceae, Cerrenaceae, Grifolaceae, Phanerochaetaceae, Laetiporaceae, Schizophyllaceae, and Stereaceae. The highest number of medicinal basidiomycete species was reported in the following host genera: Acer, Betula, Celtis, Crataegus, Juglans, Juniperus, Lonicera, Malus, Morus, Platanus, Populus, Prunus, Quercus, and Salix. An updated list of edible and inedible medicinal mushrooms identified in Uzbekistan, their morphological characteristics, and phylogenetic placement are given for the first time. Information is provided on their uses in traditional and modern medicine. Their bioactive compounds and extracts can be applied as medicines, as well as food and cosmetic ingredients.
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Background: Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors. Methods: We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR). Results: In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14, p = 1.04 × 10-5], benign (OR = 4.81, p < 0.05), benign cerebral (OR = 5.36, p < 0.05), and benign unspecified meningioma (OR = 8.26, p < 0.05). The same results were obtained for the LTL-9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR = 4.94, p < 0.05), benign (OR = 3.14, p < 0.05), and benign cerebral meningioma (OR = 3.59, p < 0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR = 1.01, p < 0.05). No heterogeneity or horizontal pleiotropy was detected. Conclusion: In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations.
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In the era of molecular phylogeny as dominant evidence in fungal taxonomy, the taxonomic framework of fungi adopted from morphological characteristics has been largely updated. Compared with other fungal groups, macrofungi underwent fewer updates at the order and higher level. In this study, the taxonomic placement of a poorly known macro-basidiomycetous genus Xenasmatella is studied. Phylogenetic and molecular clock analyses inferred from a seven-locus dataset support that the genus represents an order rank lineage. Accordingly, a monotypic order Xenasmatellales and a monotypic family Xenasmatellaceae are newly introduced for Xenasmatella within Agaricomycetes. The species diversity and relationships of Xenasmatella are further clarified with the aid of the phylogenetic analysis inferred from a four-locus dataset. In association with morphological characteristics, a new species Xenasmatella hjortstamii is described. Moreover, the distribution of Xenasmatella ailaoshanensis, X. gossypina, and X. wuliangshanensis previously known only from type localities in Yunnan Province, China are expanded. In addition, two unnamed single-specimen lineages of Xenasmatella from Victoria State, Australia and Sichuan, China are revealed, likely representing two potential new species of this genus. In summary, the current study updates the taxonomic framework of Agaricomycetes and provides a crucial supplement for comprehensively understanding the evolutionary history of this fungal class.
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[This corrects the article DOI: 10.3389/fmed.2022.939776.].
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Sanghuangporus sanghuang is a large wood-decaying mushroom highly valued in traditional Chinese medicine due to its medicinal properties, including hypoglycemic, antioxidant, antitumor, and antibacterial properties effects. Its key bioactive compounds include flavonoids and triterpenoids. Specific fungal genes can be selectively induced by fungal elicitors. To investigate the effect of fungal polysaccharides derived from Perenniporia tenuis mycelia on the metabolites of S. sanghuang, we conducted metabolic and transcriptional profiling with and without elicitor treatment (ET and WET, respectively). Correlation analysis showed significant differences in triterpenoid biosynthesis between the ET and WET groups. In addition, the structural genes associated with triterpenoids and their metabolites in both groups were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Through metabolite screening, three triterpenoids were identified: betulinol, betulinic acid, and 2-hydroxyoleanolic acid. Excitation treatment increased the level of betulinic acid by 2.62-fold and 2-hydroxyoleanolic acid by 114.67-fold compared to WET. The qRT-PCR results of the four genes expressed in secondary metabolic pathways, defense gene activation, and signal transduction showed significant variation between the ET and WET groups. Overall, our study suggests that the fungal elicitor induced the aggregation of pentacyclic triterpenoid secondary metabolites in S. sanghuang.
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The genus is a special and crucial taxonomic rank compared with others above the species level, because a species has to be placed in a certain genus instead of any other higher ranks. With more and more new species being described, the placements of their generic position are sometimes incorrect due to the simple phylogenies resulting from inappropriate sampling. Here, we focus on the taxonomy of a small wood-inhabiting fungal genus Hyphodermella. With the most comprehensive sampling to date, the phylogenetic position of Hyphodermella within Phanerochaetaceae is rearranged by employing the same ITS and nLSU regions as in previous studies and also the ITS, nLSU, rpb1, rpb2 and tef1α regions. Three species are excluded from Hyphodermella: H. poroides is placed in a newly introduced monotypic genus Pseudohyphodermella, while H. aurantiaca and H. zixishanensis are transferred to Roseograndinia. Hyphodermella suiae is described as a new species from South China and Vietnam. Keys to eight species in Hyphodermella and five in Roseograndinia are provided. Beyond solving the taxonomic issue of Hyphodermella itself, the current study also aims to suggest that all fungal taxonomists especially beginners should keep in mind to sample as many comprehensive taxa as possible in phylogenetic analyses.
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Glioblastoma (GBM) is a highly lethal neurological tumor that presents significant challenge for clinicians due to its heterogeneity and high mortality rate. Despite extensive research, there is currently no effective drug treatment available for GBM. Research evidence has consistently demonstrated that the epidermal growth factor receptor (EGFR) promotes tumor progression and is associated with poor prognosis in several types of cancer. In glioma, EGFR abnormal amplification is reported in approximately 40% of GBM patients, with overexpression observed in 60% of cases, and deletion or mutation in 24% to 67% of patients. In our study, Sitravatinib, a potential EGFR inhibitor, was identified through molecular docking screening based on protein structure. The targeting of EGFR and the tumor inhibitory effect of Sitravatinib on glioma were verified through cellular and in vivo experiments, respectively. Our study also revealed that Sitravatinib effectively inhibited GBM invasive and induced DNA damage and cellular senescence. Furthermore, we observed a novel cell death phenotype induced by Sitravatinib, which differed from previously reported programmed death patterns such as apoptosis, pyroptosis, ferroptosis, and necrosis.
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Neoplasias Encefálicas , Receptores ErbB , Glioblastoma , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Simulação de Acoplamento MolecularRESUMO
Sanghuangporus sanghuang, the generic type of Sanghuangporus belonging to Hymenochaetaceae, is a precious medicinal wood-inhabiting macrofungus with high commercial potential. To facilitate the medicinal utilization of this fungal resource, transcriptome sequences are newly generated from S. sanghuang strain MS2. In association with the previously generated genome sequences from the same strain by our lab and all available fungal homologous protein sequences in the UniProtKB/Swiss-Prot Protein Sequence Database, a new methodology was employed for genome assembly and annotation. A total of 13,531 protein-coding genes were identified from the new version of the genome of S. sanghuang strain MS2 with a complete BUSCOs of 92.8%, which indicates a remarkable improvement in the accuracy and completeness of the genome assembly. In general, more genes involved in medicinal functions were annotated compared with the original version of the genome annotation, and most of these genes were also found in the transcriptome data of the currently sampled growth period. Given the above, the current genomic and transcriptomic data provides valuable insights into the evolution and metabolites analysis of S. sanghuang.