Programmed cell death disrupts inflammatory tumor microenvironment (TME) and promotes glioblastoma evolution.

Glioblastoma (GBM) is the most common malignant brain tumor and has a dismal prognosis even under the current first-line treatment, with a 5-year survival rate less than 7%. Therefore, it is important to understand the mechanism of treatment resistance and develop new anti-tumor strategies. Induction of programmed cell death (PCD) has become a promising anti-tumor strategy, but its effectiveness in treating GBM remains controversial. On the one hand, PCD triggers tumor cell death and then release mediators to draw in immune cells, creating a pro-inflammatory tumor microenvironment (TME). One the other hand, mounting evidence suggests that PCD and inflammatory TME will force tumor cells to evolve under survival stress, leading to tumor recurrence. The purpose of this review is to summarize the role of PCD and inflammatory TME in the tumor evolution of GBM and promising methods to overcome tumor evolution.

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Glioma hexokinase 3 positively correlates with malignancy and macrophage infiltration.

BACKGROUND: Glioma is the main subtype of primary central nervous system (CNS) tumor with high malignancy and poor prognosis under current therapeutic approaches. Glycolysis and suppressive tumor microenvironment (TME) are key markers of glioma with great importance for aggressive features of glioma and inferior clinical outcomes. Hexokinase 3 (HK3) is an important rate-limiting enzyme in glycolysis, but its function in glioma remains unknown. METHODS: This study comprehensively assessed the expression distribution and immunological effect of HK3 via pan-cancer analysis based on datasets from Genotype Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA). Furthermore, it explored the malignant phenotype and genomic landscape between low-HK3 and high-HK3 expression groups in gliomas from Chinese Glioma Genome Atlas (CGGA) and TCGA. Moreover, data from the TIMER website predicted the relationship between macrophage infiltration and HK3 expression. Also, single-cell sequencing data were used to validate the relationship. RESULTS: For pan-cancer patients, HK3 was expressed in various cancers. The results showed that HK3 was highly expressed in gliomas and positively correlated with tumor-infiltrating immune cells (TIICs), immune checkpoints, immunomodulators, and chemokines. Meanwhile, HK3 expression was highest in normal immune cells and tissues. In gliomas, the expression of HK3 was found to be closely correlated with the malignant clinical characteristics and the infiltration of macrophages. Also, HK3 was proven to be positively associated with macrophage through single-cell sequencing data and immunohistochemistry techniques. Finally, it is predicted that samples with high HK3 expression are often malignant entities and also significant genomic aberrations of driver oncogenes. CONCLUSIONS: This is the first comprehensive research to figure out the relationship between HK3 and TME characteristics in gliomas. HK3 is positively associated with macrophage infiltration and can induce the immunosuppressive TME and malignant phenotype of gliomas.

Influence of the Au-Ti Active Site of the Titanosilicate MWW Zeolite on the Catalytic Activity of Ethane Dehydrogenation in the Presence of O2.

The titanosilicate zeolite with a MWW topology structure was synthesized by the atom-planting method through the dehydrochlorination of the hydroxyl group in the deboronated ERB-1 zeolite (D-ERB-1) and TiCl4, and Au was further loaded with the deposition precipitation method to apply for the ethane direct dehydrogenation (DH) and dehydrogenation of ethane in the presence of O2 (O2-DH). It was found that Au nanoparticles (NPs) below 5 nm exhibited good activity for ethane direct dehydrogenation and O2-DH. The addition of titanium can not only anchor more Au but also make Au have a more dispersed homogeneous distribution. The ethane O2-DH catalytic performances of Au-loaded Ti-incorporated D-ERB-1 (Ti-D-ERB-1) were compared to those of Au-loaded ZnO-D-ERB-1 and pure silicate D-ERB-1. The results confirm that ethane O2-DH catalyzed by Au-Ti paired active sites is a tandem reaction of catalytic ethane DH and selective H2 combustion (SHC) of generated H2. According to the experimental results and calculated kinetic parameters, such as the activation energy of DH and SHC reaction heat of O2-DH, SHC catalyzed by the Au/Ti-D-ERB-1 catalyst containing the Au-Ti active site can not only break the ethane dehydrogenation thermodynamic equilibrium limitation to improve the ethylene yield but also suppress the CO2 and CO selectivity.

Constituents, Antibacterial Effect, and Cytotoxicity of Essential Oil from Aerial Parts of Notopterygium incisum.

Notopterygium incisum Ting ex H. T. Chang (N. incisum) is a precious Chinese traditional medicine distributed in high-altitude regions of southwest China. The aim of this study was to investigate the composition, antibacterial activity, and cytotoxicity of essential oil from aerial parts of N. incisum. N. incisum essential oil (NI-EO) was extracted by hydro-distillation, and gas chromatography/mass spectrometry (GC-MS) analysis showed that the major components of NI-EO were D-limonene (18.42%) and γ-terpinene (15.03%). The antibacterial activity and mechanism study showed that the diameters of inhibition zone (DIZs) of NI-EO against E. coli and S. aureus were 14.63 and 11.25 mm and the minimum inhibitory concentrations were 3.75 and 7.5 µL/mL, respectively. NI-EO not only caused intracellular biomacromolecule leakage and cell deformation by destroying bacterial cell wall integrity and cell membrane permeability, but also degraded the mature biofilm. The low toxicity of NI-EO was demonstrated in an assay on bovine mammary epithelial cells. These results implied that NI-EO was mainly composed of monoterpenes and sesquiterpenes and had excellent antibacterial activity and showed low levels of cytotoxicity. It is expected to be applied as a natural antibacterial agent in the future.

A nonsense mutation in VHL causing Von Hippel-Lindau syndrome in a large Chinese family-a genetic study of familial neoplastic disease.

Von Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in the central nervous system (CNS), retina, and visceral lesions, which are mainly caused by germline mutations in VHL. We aimed to detect novel mutations in VHL gene in families with VHL. Here, a large consanguineous four-generation family with variant phenotypes of VHL syndrome was recruited, and its molecular genetics were tested via Sanger sequencing. And various tools and databases were used to predict the variant pathogenicity, frequency, and protein function. Genetic investigation detected a c.351G > A nonsense mutation in VHL that altered the downstream reading frame and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from most public databases, and functional prediction bioinformatic tools demonstrated that this residue is conserved and that this variant is highly likely to be deleterious. The c.315G > A nonsense mutation in VHL is the causal mutation of this kindred that may lead to clear familial aggregation of VHL syndrome because of the dysfunction of the truncated pVHL.

[Clinical features and genetic analysis of a patient with type 2 neurofibromatosis manifested as oculomotor nerve palsy].

OBJECTIVE: To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis. METHODS: A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4). CONCLUSION: The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

A Co3O4 Nanoparticle-Modified Screen-Printed Electrode Sensor for the Detection of Nitrate Ions in Aquaponic Systems.

In this study, a screen-printed electrode (SPE) modified with cobalt oxide nanoparticles (Co3O4 NPs) was used to create an all-solid-state ion-selective electrode used as a potentiometric ion sensor for determining nitrate ion (NO3-) concentrations in aquaculture water. The effects of the Co3O4 NPs on the characterization parameters of the solid-contact nitrate ion-selective electrodes (SC-NO3--ISEs) were investigated. The morphology, physical properties and analytical performance of the proposed NO3--ion selective membrane (ISM)/Co3O4 NPs/SPEs were studied by X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), potentiometric measurements, and potentiometric water layer tests. Once all conditions were optimized, it was confirmed that the screen-printed electrochemical sensor had high potential stability, anti-interference performance, good reproducibility, and no water layer formation between the selective membrane and the working electrode. The developed NO3--ISM/Co3O4 NPs/SPE showed a Nernstian slope of -56.78 mV/decade for NO3- detection with a wide range of 10-7-10-2 M and a quick response time of 5.7 s. The sensors were successfully used to measure NO3- concentrations in aquaculture water. Therefore, the electrodes have potential for use in aquaponic nutrient solution applications with precise detection of NO3- in a complicated matrix and can easily be used to monitor other ions in aquaculture water.

A Composition Analysis and an Antibacterial Activity Mechanism Exploration of Essential Oil Obtained from Artemisia giraldii Pamp.

The goal of this work was to use the GC-MS technique to explore the chemical components of Artemisia giraldii Pamp essential oil (AgEo) and to uncover its antibacterial activity, specifically the antibacterial mechanism of this essential oil. There were a total of 63 chemical constituents in the AgEo, monoterpenes (10.2%) and sesquiterpenes (30.14%) were found to be the most common chemical components, with camphor (15.68%) coming in first, followed by germacrene D. (15.29%). AgEo displayed significant reducing power and good scavenging ability on hydroxyl radicals, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals, and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals, according to antioxidant data. The diameter of the inhibition zone (DIZ) of AgEo against S. aureus and E. coli was (14.00 ± 1.00) mm and (16.33 ± 1.53) mm, respectively; the minimum inhibitory concentration (MIC) of AgEo against E. coli and S. aureus was 3 µL/mL and 6 µL/mL, respectively; and the minimum bactericidal concentration (MBC) of AgEo against E. coli and S. aureus was 6 µL/mL and 12 µL/mL, respectively. The antibacterial curve revealed that 0.5MIC of AgEo may delay bacterial growth while 2MIC of AgEo could totally suppress bacterial growth. The relative conductivity, alkaline phosphatase (AKP) activity, and protein concentration of the bacterial suspension were all higher after the AgEo treatment than in the control group, and increased as the essential oil concentration was raised. In addition, the cell membrane ruptured and atrophy occurred. The study discovered that AgEo is high in active chemicals and can be used as an antibacterial agent against E. coli and S. aureus, which is critical for AgEo's future research and development.

Dietary supplementation with oregano essential oil and monensin in combination is antagonistic to growth performance of yearling Holstein bulls.

Our previous work indicated that feeding oregano essential oil (OEO) in combination with monensin (MON) may not be mutually beneficial to dairy calf growth performance. To evaluate this observation further, a 240-d long-term growth experiment was conducted using 12 young growing Holstein bulls using a 2 × 2 factorial treatment arrangement. Main factors were OEO and MON arranged in 4 individual treatments: (1) ration fed without OEO or MON (control), (2) OEO fed at 26 mg/kg of dry matter (DM), (3) MON fed at 25 mg/kg of DM, and (4) OEO and MON fed in combination (OEO+MON). Holstein bulls were 70 d of age and similar in body weight (BW; 93.3 ± 4.54 kg) and individually fed for 240 d. The targeted feeding rates of OEO and MON were blended into 200 g of concentrate and top dressed each morning to a corn stalklage-based ration. Body weights, frame measurements, and blood samples were collected monthly. Interactions of OEO by MON were detected for BW, BW gain, average daily gain, and a trend for feed conversion. Bulls fed OEO or MON demonstrated greater final BW (368, 385, 381, and 358 kg for control, OEO, MON, and OEO+MON, respectively), and BW gains (278, 292, 285, and 265 kg) and average daily gain (1.16, 1.22, 1.19, 1.11 kg/d) were greatest for bulls fed OEO or MON compared with bulls fed OEO+MON; bulls fed the control were intermediate and similar to bulls fed MON. Intake of DM was greater for bulls fed OEO (6.55, 6.99, 6.60, and 6.42 kg/d) compared with bulls fed remaining treatments. Frame growth gain measurements for heart girth, abdominal girth, withers height, body length, and cannon bone circumference were similar for bulls fed all treatments. Serum triglyceride (0.23, 0.25, 0.28, and 0.24 mmol/L) concentrations were greater for bulls fed MON compared with bulls fed the control and OEO+MON, and bulls fed OEO were intermediate and similar. Cholesterol (2.06, 2.29, 2.20, and 2.07 mmol/L) concentrations were greater for bulls fed OEO compared with bulls fed the control and OEO+MON, and bulls fed MON were intermediate and similar. Serum antioxidant measurements were similar for bulls fed all treatments. Serum IgA, IgG, and IgM concentrations were similar for bulls fed all treatments. Feeding OEO or MON separately can improve growth performance of growing Holstein bulls. We do not know why the combination of OEO and MON is antagonistic to growth performance of Holstein bulls. However, these technologies should not be fed in combination to growing dairy cattle.

Correlation of alteration of HLA-F expression and clinical characterization in 593 brain glioma samples.

BACKGROUND: Human gliomas are highly fatal tumors with a significant feature of immune suppression. The association of the immune system in gliomas is gradually revealed, and immunotherapy is expected to improve the survival of glioma patients. In-depth understanding of the immune microenvironment of gliomas and their associated immunotherapy was increased exponentially in recent years. Gliomas provide clinical targets for immunotherapy during the search of key regulators of immune response. Our study focused on the human leukocyte antigen (HLA) system that is responsible for regulating the immune system, and discovered the relationship between HLA-F expression and clinical prognosis in gliomas. METHODS: A total of 593 patients with gliomas were included in our research. Of these, 325 patients were from the Chinese Glioma Genome Atlas (CGGA) and 268 were from the GSE 16011 set. Kaplan-Meier (KM) analysis was performed to explore the prognostic value of HLA-F. t test analysis was used to find the distribution difference in various groups. R language packages are used for other statistical computations and figure drawing. RESULTS: HLA-F was negatively correlated with overall survival (OS) in all grades of glioma and glioblastoma (GBM). Moreover, HLA-F was enriched in GBM and isocitrate dehydrogenase 1 wild-type (IDH1 wt) group and considered HLA-F as a mesenchymal subtype marker. Pearson correlation test showed that HLA-F was correlated with other HLA-I molecules. CONCLUSION: HLA-F expression was positively correlated with malignant phenotype and negatively correlated with OS, indicating that HLA-F could predict the immune state of gliomas and might be a clinical target of glioma immunotherapy.

An immune-related lncRNA signature for patients with anaplastic gliomas.

We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937, AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in patients with anaplastic gliomas. Patients in the low-risk group showed longer overall survival (OS) and progression-free survival than those in the high-risk group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower Karnofsky performance score (KPS). Moreover, the signature was an independent factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR) = 1.434). These findings were further validated in two additional datasets (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune status based on principal components analysis. Our results showed that the nine immune-related lncRNAs signature has prognostic value for anaplastic gliomas.

CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression.

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan-Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan-Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma.

Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling.

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman's rank correlation test conducted between tumor grade and gene expression. We assigned a risk score based on IC47 to each glioma patient. We demonstrated that the risk score effectively predicted overall survival in glioma patients. Next, we screened IC47 in different molecular glioma subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis and gene set variation analysis (GSVA) for the functional annotation of IC47 showed that patients with high-risk scores tended to exhibit the decreased expression of proteins associated with the apoptosis and cell adhesion, and higher expression of proteins associated with the cell cycle and cell proliferation. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

Segmentation of the left atrial appendage based on fusion attention.

In clinical practice, the morphology of the left atrial appendage (LAA) plays an important role in the selection of LAA closure devices for LAA closure procedures. The morphology determination is influenced by the segmentation results. The LAA occupies only a small part of the entire 3D medical image, and the segmentation results are more likely to be biased towards the background region, making the segmentation of the LAA challenging. In this paper, we propose a lightweight attention mechanism called fusion attention, which imitates human visual behavior. We process the 3D image of the LAA using a method that involves overview observation followed by detailed observation. In the overview observation stage, the image features are pooled along the three dimensions of length, width, and height. The obtained features from the three dimensions are then separately input into the spatial attention and channel attention modules to learn the regions of interest. In the detailed observation stage, the attention results from the previous stage are fused using element-wise multiplication and combined with the original feature map to enhance feature learning. The fusion attention mechanism was evaluated on a left atrial appendage dataset provided by Liaoning Provincial People's Hospital, resulting in an average Dice coefficient of 0.8855. The results indicate that the fusion attention mechanism achieves better segmentation results on 3D images compared to existing lightweight attention mechanisms.

MOTC: Abdominal Multi-objective Segmentation Model with Parallel Fusion of Global and Local Information.

Convolutional Neural Networks have been widely applied in medical image segmentation. However, the existence of local inductive bias in convolutional operations restricts the modeling of long-term dependencies. The introduction of Transformer enables the modeling of long-term dependencies and partially eliminates the local inductive bias in convolutional operations, thereby improving the accuracy of tasks such as segmentation and classification. Researchers have proposed various hybrid structures combining Transformer and Convolutional Neural Networks. One strategy is to stack Transformer blocks and convolutional blocks to concentrate on eliminating the accumulated local bias of convolutional operations. Another strategy is to nest convolutional blocks and Transformer blocks to eliminate bias within each nested block. However, due to the granularity of bias elimination operations, these two strategies cannot fully exploit the potential of Transformer. In this paper, a parallel hybrid model is proposed for segmentation, which includes a Transformer branch and a Convolutional Neural Network branch in encoder. After parallel feature extraction, inter-layer information fusion and exchange of complementary information are performed between the two branches, simultaneously extracting local and global features while eliminating the local bias generated by convolutional operations within the current layer. A pure convolutional operation is used in decoder to obtain final segmentation results. To validate the impact of the granularity of bias elimination operations on the effectiveness of local bias elimination, the experiments in this paper were conducted on Flare21 dataset and Amos22 dataset. The average Dice coefficient reached 92.65% on Flare21 dataset, and 91.61% on Amos22 dataset, surpassing comparative methods. The experimental results demonstrate that smaller granularity of bias elimination operations leads to better performance.

Gut microbiota disorders aggravate terbuthylazine-induced mitochondrial quality control disturbance and PANoptosis in chicken hepatocyte through gut-liver axis.

Terbuthylazine (TBA) is a widely prevalent pesticide pollutant, which is a global concern due to its environmental residual. However, the toxic mechanism of TBA have not been fully solved. Here, we explored that TBA exposure disrupts the intestinal flora and aggravated disturbance of mitochondrial quality control and PANapoptosis in hepatocytes via gut-liver axis. Our findings demonstrated that TBA exposure induced significant damage to the jejunum barrier, evidenced by a marked decrease in the expression of Occludin and ZO-1. Moreover. TBA led to intestinal microflora disorder, manifested as the decreased abundance of Firmicutes, and increased abundance of the Nitrospirota, Chloroflexi, Desulfobacterota, Crenarchaeota, Myxococcota, and Planctomycetota. Meanwhile, intestinal microflora disorder affected the biological processes of lipid metabolism and cell growth and death of hepatocytes by RNA-Seq analysis. Furthermore, TBA could induced mitochondrial quality control imbalance, including mitochondrial redox disorders, lower activity of mitochondrial fusion and biogenesis decrease, and increasing level of mitophagy. Subsequently, TBA significantly increased expression levels of pyroptosis, apoptosis and necroptosis-related proteins. In general, these results demonstrated the underlying mechanisms of TBA-induced hepatotoxicity induced via the gut-liver axis, which provides a theoretical basis for further research of ecotoxicology of TBA.

Clinical characteristics and prognostic analysis of patients with HIV and glioma: A case series and literature review.

Cerebral glial tumors have become increasingly common in human immunodeficiency virus (HIV)-positive patients. The present study aimed to report a series of such cases, explore their clinical and pathological characteristics and subject all the reported cases to a survival analysis. The characteristics, management and prognosis of 10 HIV-positive patients with brain gliomas enrolled in a single hospital were investigated in detail. Immunohistochemical assessment of CD31, CD68 and CD163 was performed in the 10 HIV-positive patients with glioma and 18 HIV-negative patients with glioma. The relevant literature was also reviewed using relevant search terms. The potential predictive factors were screened by univariate and multivariate logistic regression analyses, and a nomogram was established based on the potential predictive factors. A total of 50 patients, including the 10 primary cases, were included in the survival analysis. The median survival time was 9 months. The gliomas of HIV-negative patients had a lower cell count of CD163+ cells than those of HIV-positive patients. High CD4+ T-cell count and the use of highly active antiretroviral therapy (HAART) tended to increase the median survival duration, although not significantly according to the log-rank analysis. In the univariate analysis, only surgery, radiotherapy (RT) and World Health Organization (WHO) tumor grade had significant associations with overall survival. In the multivariate analysis, only RT and WHO grade were independent predictors. In conclusion, gliomas may occur more frequently in HIV-positive populations than is currently recognized. The survival duration of most HIV-positive patients with glioma is determined by the tumor rather than HIV status. Adjuvant radiotherapy and the WHO grade of the glioma are predicted to be independent prognostic factors. Surgical resection followed by RT plus regular HAART is recommended for patients with glioma who are HIV-positive.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.