Effects of different nitrogen applications and straw return depth on straw microbial and carbon and nitrogen cycles in paddy fields in the cool zone.

Straw is an important source of organic fertilizer for soil enrichment, however, the effects of different nitrogen(N) application rates and depths on straw decomposition microorganisms and carbon and nitrogen cycling under full straw return conditions in cool regions of Northeast China are not clear at this stage. In this paper, we applied macro-genome sequencing technology to investigate the effects of different N application rates (110 kg hm-2, 120 kg hm-2, 130 kg hm-2, 140 kg hm-2, 150 kg hm-2) and depths (0-15 cm, 15-30 cm) on straw decomposing microorganisms and N cycling in paddy fields in the cool zone of Northeast China. The results showed that (1) about 150 functional genes are involved in the carbon cycle process of degradation during the degradation of returned straw, of which the largest number of functional genes are involved in the methane production pathway, about 42, the highest abundance of functional genes involved in the citric acid cycle pathway. There are 22 kinds of functional genes involved in the nitrogen cycle degradation process, among which there are more kinds involved in nitrogen fixation, with 4 kinds. (2) High nitrogen application (150 kg hm-2) inhibited the carbon and nitrogen conversion processes, and the abundance of straw-degrading microorganisms and nitrogen-cycling functional genes was relatively high at a nitrogen application rate of 130 kg hm-2. (3) Depth-dependent heterogeneity of the microbial community was reduced throughout the vertical space. At 71 days of straw return, the nitrogen cycling function decreased and some carbon functional genes showed an increasing trend with the increase of straw return depth. The nitrogen cycle function decreased with the increase of straw returning depth. The microbial community structure was best and the abundance of functional genes involved in the nitrogen cycling process was higher under the conditions of 0-15 cm of returning depth and 130 kg hm-2 of nitrogen application.

TMEM64 aggravates the malignant phenotype of glioma by activating the Wnt/ß-catenin signaling pathway.

Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of ß-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/ß-catenin signaling pathway. Stimulation with the Wnt/ß-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/ß-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.

m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis.

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.

Evolutionary analysis of major histocompatibility complex variants in chytrid-resistant and susceptible amphibians.

An amphibian emerging infectious disease (EID), chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), originated in Asia but primarily led to declines and extinctions in amphibian populations outside of Asia. Host major histocompatibility complex (MHC) molecules exhibit high polymorphism, and the evolution of MHC can be influenced by recombination and pathogens. Previous studies have indicated that host MHC class II is associated with Bd resistance. In this study, I conducted recombination and selection tests on functional MHC IIß1 alleles from an Asian Bd-resistant anuran species (Bufo gargarizans) and an Australasian Bd-susceptible species (Litoria caerulea). Recombination at the same site was identified in both species, supporting the hypothesis that recombination contributes to MHC IIß1 diversity in amphibians. Positive selection was observed in MHC IIß1 alleles in both species. In L. caerulea, at least four amino acid sites were identified under significant positive selection in the MHC IIß1, whereas these sites were either negatively selected or conserved in B. gargarizans. This suggests these sites might be selected for Bd resistance. Hydrophobicity was detected in certain amino acid sites relating to Bd resistance, suggesting this physicochemical property may be a factor selected to counteract Bd infection. These findings of this study provide an evolutionary basis for understanding how amphibian MHC IIß1 may undergo selection in response to chytrid infection.

Effects of continuous glucose monitoring on glycaemic control in type 2 diabetes: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: The aim of this study was to assess the efficacy of continuous glucose monitoring (CGM) versus self-monitoring of blood glucose (SMBG) in maintaining glycaemic control among people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The protocol was registered in PROSPERO (CRD42023387583). PubMed, Web of Science, EMBASE and OVID databases were searched from 1 January 2000 until 31 December 2022 for randomized controlled trials comparing CGM with SMBG in glycaemic control among the outpatients with T2DM. The primary endpoint was glycated haemoglobin, while the secondary endpoints included time in range, time below range and time above range. Both traditional and network meta-analyses were conducted to explore the efficacy of CGM on glycaemic control in T2DM. RESULTS: Eleven high-quality studies, involving 1425 individuals with T2DM, were identified. Traditional meta-analysis revealed that CGM exhibited a significantly decreased [mean difference (MD): -0.31, 95% confidence interval (CI) (-0.45, -0.18)], time above range [MD: -9.06%, 95% CI (-16.00, -2.11)], time below range [MD: -0.30%, 95% CI (-0.49, -0.12)] and a significantly increased time in range [MD: 8.49%, 95% CI (3.96, 13.02)] compared with SMBG. The network meta-analysis showed that real-time CGM can improve the glycaemic control of patients with T2DM to the most extent. CONCLUSIONS: CGM could provide T2DM with greater benefits in glycaemic management compared with SMBG, particularly in patients using real-time CGM. These findings provide an updated perspective on previous research and offer guidance for CGM use in T2DM.

Neurosurgical application of pineal region tumor resection with 3D 4K exoscopy via infratentorial approach: a retrospective cohort study.

BACKGROUND: The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus. MATERIALS AND METHODS: In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center. RESULTS: The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome. CONCLUSIONS: The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.

Regulation of straw decomposition and its effect on soil function by the amount of returned straw in a cool zone rice crop system.

The degradation process of returned straw in rice fields can improve soil organic matter and promote sustainable agriculture. The degradation process of returned straw is a humification process as well as a mineralization process involving microorganisms and enzymes. However, the degradation process of returned straw, the effect on straw decomposing microorganisms and the regulatory mechanism on potential functionality under cool climate flooding conditions are currently unknown.For this purpose, we investigated the biodegradation of straw from a biodegradation point of view at 20, 40, 71, 104, and 137 d after return under conventional (130 kg hm-2), 1/3 straw return (2933 kg hm-2), 2/3 straw return (5866 kg hm-2), and full straw return (8800 kg hm-2) applications in cool climate rice fields.. The test found Paludibacteraceae and Archaeaceae were the dominant bacteria for straw degradation, and their relative abundance was highest when 2/3 of straw was returned to the field. The straw degradation extracellular enzyme activity was higher in the late return period (104 d). At this time, the potential functionality of the soil differed significantly among the different return amounts, with the best extracellular enzyme activity and potential functionality at the 2/3 straw return amount. Therefore, the optimal amount of rice straw returned to the field is 5866 kg hm-2 at the current conventional N application rate (130 kg hm-2) in the cold zone.

Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map.

BACKGROUND: Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). METHODS: PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). RESULTS: Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. CONCLUSIONS: Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.

Identification of major histocompatibility complex genotypes associated with resistance to an amphibian emerging infectious disease.

Amphibian chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), emerged from Asia and spread globally. By comparing functional MHC IIß1 alleles from an Asian Bd-resistant anuran species (Bufo gargarizans) with those of an Australasian Bd-susceptible species (Litoria caerulea), we identified MHC genotypes associated with Bd resistance. These alleles encode a glycine deletion (G90ß1) and adjacent motifs in the deepest pathogen-derived peptide-binding groove. Every Bd-resistant individual, but no susceptible individuals, possessed at least one allele encoding the variant. We detected trans-species polymorphism at the end of the MHC IIß1 sequences. The G90ß1 deletion was encoded by different alleles in the two species, suggesting it may have evolved independently in each species rather than having been derived from a common ancestor. These results are consistent with a scenario by which MHC adaptations that confer resistance to the pathogen have evolved by convergent evolution. Immunogenetic studies such as this are critical to ongoing conservation efforts.

The effects of adding exogenous lignocellulose degrading bacteria during straw incorporation in cold regions on degradation characteristics and soil indigenous bacteria communities.

Low temperature is one of the bottleneck factors that limits the degradation of straw during rice straw incorporation. Determining strategies to promote the efficient degradation of straw in cold regions has become a highly active research area. This study was to investigate the effect of rice straw incorporation by adding exogenous lignocellulose decomposition microbial consortiums at different soil depths in cold regions. The results showed that the lignocellulose was degraded the most efficiently during straw incorporation, which was in deep soil with the full addition of a high-temperature bacterial system. The composite bacterial systems changed the indigenous soil microbial community structure and diminished the effect of straw incorporation on soil pH, it also significantly increased rice yield and effectively enhanced the functional abundance of soil microorganisms. The predominant bacteria SJA-15, Gemmatimonadaceae, and Bradyrhizobium promoted straw degradation. The concentration of bacterial system and the depth of soil had significantly positive correlations on lignocellulose degradation. These results provide new insights and a theoretical basis for the changes in the soil microbial community and the application of lignocellulose-degrading composite microbial systems with straw incorporation in cold regions.

Cell Cycle-Related FAM64A Could be Activated by TGF-ß Signaling to Promote Glioma Progression.

Gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. FAM64A, a cell cycle-related gene, has been found to promote cell proliferation in various tumors, including gliomas. However, the regulatory mechanism and clinical significance of FAM64A in gliomas remain unclear. In this study, we investigated FAM64A expression in gliomas with different grades and constructed FAM64A silenced cell lines to study its functions. Our results demonstrated that FAM64A was highly expressed in glioblastoma (P < 0.001) and associated with a poor prognosis (P < 0.001). Expression profiles at the single-cell resolution indicated FAM64A could play a role in a cell-cycle-dependent way to promote glioma cell proliferation. We further observed that FAM64A silencing in glioma cells resulted in disrupted proliferation and migration ability, and increased cell accumulation in the G2/M phase (P = 0.034). Additionally, TGF-ß signaling upregulates FAM64A expression, and SMAD4 and FAM64A co-localize in high-grade glioma tissues. We found FAM64A knockdown inhibited TGF-ß-induced epithelial-mesenchymal transition in glioma. Our findings suggest that FAM64A could serve as a diagnostic and therapeutic target in gliomas.

Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression in macrophages by activating NF-κB pathway, and ITA produced by ACOD1 inhibits TET DNA dioxygenases to dampen the expression of inflammatory genes and the infiltration of CD8+ T cells into tumor sites. Deletion of Irg1 in mice suppresses the growth of multiple tumor types and enhances the efficacy of anti-PD-(L)1 immunotherapy. Our study provides a proof of concept that ACOD1 is a potential target for immune-oncology drugs and IRG1-deficient macrophages represent a potent cell therapy strategy for cancer treatment even in pancreatic tumors that are resistant to T cell-based immunotherapy.

Divergent allele advantage in the MHC and amphibian emerging infectious disease.

Genetic variation in the major histocompatibility complex (MHC) may be associated with resistance to the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). The pathogen originated in Asia, then spread worldwide, causing amphibian population declines and species extinctions. We compared the expressed MHC IIß1 alleles of a Bd-resistant species, Bufo gargarizans, from South Korea with those of a Bd-susceptible Australasian species, Litoria caerulea. We found at least six expressed MHC IIß1 loci in each of the two species. Amino acid diversity encoded by these MHC alleles was similar between species, but the genetic distance of those alleles known for potential broader pathogen-derived peptide binding was greater in the Bd-resistant species. In addition, we found a potentially rare allele in one resistant individual from the Bd-susceptible species. Deep next-generation sequencing recovered approximately triple the genetic resolution accessible from traditional cloning-based genotyping. Targeting the full MHC IIß1 enables us to better understand how host MHC may adapt to emerging infectious diseases.

The Anti-Glioma Effect of Juglone Derivatives through ROS Generation.

Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 µM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 µM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.

Novel chytrid pathogen variants and the global amphibian pet trade.

Global wildlife trade spreads emerging infectious diseases that threaten biodiversity. The amphibian chytrid pathogen Batrachochytrium dendrobatidis (Bd) has caused population declines and species extinctions worldwide except in Asia. Fire-bellied toads (Bombina orientalis), exported in large numbers from Asia, are tolerant of Bd and carry hypervirulent ancestral chytrid BdAsia-1 variants. We assayed the virulence of a new isolate of BdAsia-1 on the model Australasian frog host Litoria caerulea. Infected individuals (n = 15) all showed rapid disease progression culminating in death, whereas sham-inoculated individuals (n = 10) presented no clinical signs of disease and all survived (log rank test, χ2 = 15.6, df = 1, p < 0.0001). The virulence of the new isolate of BdAsia-1 is comparable to the one we assayed previously (χ2 = 0.0, df = 1, p = 0.91). Internationally traded wildlife, even when they appear healthy, can carry hypervirulent variants of pathogens. Once new pathogen variants escape into the environment, native species that have had no opportunity to evolve resistance to them may perish. Our study suggests that hypervirulent pathogens are being spread by the international pet trade. Notifiable wildlife diseases attributable to locally endemic pathogens often fail to generate conservation concern so are rarely subject to border surveillance or import controls. Because of the danger novel variants pose, national border control agencies need to implement disease screening and quarantine protocols to ensure the safety of their endemic fauna.

Variantes Patógenas Nuevas de Quitridios y el Mercado Mundial de Anfibios Mascota Resumen El mercado mundial de fauna dispersa enfermedades infecciosas emergentes que amenazan a la biodiversidad. El quitridio patógeno de anfibios Batrachochytrium dendrobatidis (Bd) ha causado declinaciones poblacionales y la extinción de especies en todo el mundo excepto Asia. El sapo Bombina orientalis, exportado en grandes cantidades desde Asia, es tolerante al Bd y carga genéticamente las variantes ancestrales hipervirulentas de quitridio BdAsia-1. Analizamos la virulencia de una nueva cepa de BdAsia-1 con el modelo de la rana australo-asiática hospedera Litoria caerulea. Todos los individuos infectados (n = 15) mostraron una progresión acelerada de la enfermedad que culminaba con la muerte, mientras que los individuos con inoculación simulada (n = 10) no presentaron señales clínicas de la enfermedad y todos sobrevivieron (prueba log de rango, χ2 = 15.6, df = 1, p < 0.0001). La virulencia de la nueva cepa de BdAsia-1 es comparable a la que analizamos previamente (χ2 = 0.0, df = 1, p = 0.91). La fauna comercializada internacionalmente, incluso cuando parece estar saludable, puede portar variantes hipervirulentas de los patógenos. Una vez que un patógeno nuevo se introduce al ambiente, pueden perecer las especies nativas que no han tenido la oportunidad de evolucionar la resistencia a estos patógenos. Nuestro estudio sugiere que los patógenos hipervirulentos se están dispersando mediante el mercado internacional de mascotas. Con frecuencia las enfermedades silvestres notificables que pueden atribuirse a los patógenos endémicos no generan interés para la conservación, así que rara vez están sujetas a la vigilancia fronteriza o el control de importación. Debido al riesgo que representan las variantes nuevas, las agencias nacionales de control fronterizo necesitan implementar evaluaciones patológicas y protocolos de cuarentena para asegurar la seguridad de su fauna endémica.

Early-diverging fungal phyla: taxonomy, species concept, ecology, distribution, anthropogenic impact, and novel phylogenetic proposals.

The increasing number of new fungal species described from all over the world along with the use of genetics to define taxa, has dramatically changed the classification system of early-diverging fungi over the past several decades. The number of phyla established for non-Dikarya fungi has increased from 2 to 17. However, to date, both the classification and phylogeny of the basal fungi are still unresolved. In this article, we review the recent taxonomy of the basal fungi and re-evaluate the relationships among early-diverging lineages of fungal phyla. We also provide information on the ecology and distribution in Mucoromycota and highlight the impact of chytrids on amphibian populations. Species concepts in Chytridiomycota, Aphelidiomycota, Rozellomycota, Neocallimastigomycota are discussed in this paper. To preserve the current application of the genus Nephridiophaga (Chytridiomycota: Nephridiophagales), a new type species, Nephridiophaga blattellae, is proposed.

Gene clusters based on OLIG2 and CD276 could distinguish molecular profiling in glioblastoma.

BACKGROUND: The molecular profiling of glioblastoma (GBM) based on transcriptomic analysis could provide precise treatment and prognosis. However, current subtyping (classic, mesenchymal, neural, proneural) is time-consuming and cost-intensive hindering its clinical application. A simple and efficient method for classification was imperative. METHODS: In this study, to simplify GBM subtyping more efficiently, we applied a random forest algorithm to conduct 26 genes as a cluster featured with hub genes, OLIG2 and CD276. Functional enrichment analysis and Protein-protein interaction were performed using the genes in this gene cluster. The classification efficiency of the gene cluster was validated by WGCNA and LASSO algorithms, and tested in GSE84010 and Gravandeel's GBM datasets. RESULTS: The gene cluster (n = 26) could distinguish mesenchymal and proneural excellently (AUC = 0.92), which could be validated by multiple algorithms (WGCNA, LASSO) and datasets (GSE84010 and Gravandeel's GBM dataset). The gene cluster could be functionally enriched in DNA elements and T cell associated pathways. Additionally, five genes in the signature could predict the prognosis well (p = 0.0051 for training cohort, p = 0.065 for test cohort). CONCLUSIONS: Our study proved the accuracy and efficiency of random forest classifier for GBM subtyping, which could provide a convenient and efficient method for subtyping Proneural and Mesenchymal GBM.

DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker.

DDX60, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of DDX60 in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, P < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of DDX60 in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. DDX60 expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = -0.24). Furthermore, DDX60 expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like CTLA-4, PD-L1, EGF, CD96, and CD226, were all positively related with DDX60 (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, P < 0.0001) and GBM cells. These results indicated that DDX60 might have important clinical significance in glioma and could serve as a potential immune therapeutic target.

The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas.

B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs "F-V-S/N-I/V" in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that B7H3 is positively correlated with VEGFA and MMP2 by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HGhigh gliomas compared to 2-HGlow glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.

A retrospective analysis of GSE84010: Cell adhesion molecules might contribute to bevacizumab resistance in glioblastoma.

Bevacizumab (BEV) is an anti-angiogenesis antibody which has shown favorable therapeutic effects on some solid tumors. However, many clinical trials showed that BEV could only improve PFS instead of OS in glioblastoma (GBM) patients. However, some studies indicate that specific molecular subtypes of GBM could still benefit from combination treatment of BEV and Stupp protocol. Through the subgroup analysis of GSE84010 dataset, we found the neural and proneural subgroup can benefit from the administration of BEV in terms of OS, which is statistically significant. The further KEGG pathway enrichment analysis showed cell adhesion molecules (CAMs) pathway was enriched, and the expression of ITGAM has a predictive value for prognosis. These findings can provide some hints for future administration of BEV in newly diagnosed GBM patients.