ABSTRACT
Necroptosis is a programmed form of necrotic cell death that serves as a host gatekeeper for defense against invasion by certain pathogens. Previous studies have uncovered the essential role of necroptosis in tumor progression and implied the potential for novel therapies targeting necroptosis. However, no comprehensive analysis of multi-omics data has been conducted to better understand the relationship between necroptosis and tumor. We developed the necroptosis index (NI) to uncover the effect of necroptosis in most cancers. NI not only correlated with clinical characteristics of multiple tumors, but also could influence drug sensitivity in glioma. Based on necroptosis-related differentially expressed genes, the consensus clustering was used to classify glioma patients into two NI subgroups. Then, we revealed NI subgroup I were more sensitive to immunotherapy, particularly anti-PD1 therapy. This new NI-based classification may have prospective predictive factors for prognosis and guide physicians in prioritizing immunotherapy for potential responders.
ABSTRACT
BACKGROUND: Pyroptosis, also known as inflammatory necrosis, is a programmed cell death that manifests itself as a continuous swelling of cells until the cell membrane breaks, leading to the liberation of cellular contents, which triggers an intense inflammatory response. Pyroptosis might be a panacea for a variety of cancers, which include immunotherapy and chemotherapy-insensitive tumors such as glioma. Several findings have observed that long non-coding RNAs (lncRNAs) modulate the bio-behavior of tumor cells by binding to RNA, DNA and protein. Nevertheless, there are few studies reporting the effect of lncRNAs in pyroptosis processes in glioma. METHODS: The principal goal of this study was to identify pyroptosis-related lncRNAs (PRLs) utilizing bioinformatic algorithm and to apply PCR techniques for validation in human glioma tissues. The second goal was to establish a prognostic model for predicting the overall survival patients with glioma. Predict algorithm was used to construct prognosis model with good diagnostic precision for potential clinical translation. RESULTS: Noticeably, molecular subtypes categorized by the PRLs were not distinct from any previously published subtypes of glioma. The immune and mutation landscapes were obviously different from previous subtypes of glioma. Analysis of the sensitivity (IC50) of patients to 30 chemotherapeutic agents identified 22 agents as potential therapeutic agents for patients with low riskscores. CONCLUSIONS: We established an exact prognostic model according to the expression profile of PRLs, which may facilitate the assessment of patient prognosis and treatment patterns and could be further applied to clinical.
Subject(s)
Glioma , RNA, Long Noncoding , Humans , Pyroptosis/genetics , RNA, Long Noncoding/genetics , Glioma/genetics , Apoptosis , Algorithms , PrognosisABSTRACT
Polyethylene mulching film plays a critical role in agricultural production. To clarify the impact of residual film and microplastics on soil microorganisms, this study examined four cotton fields with different film coverage years in typical areas of Xinjiang and analyzed the changes in soil bacterial and fungal community structure and diversity under residual film and microplastics using high-throughput sequencing technology. The results showed that the residual film in the 0-150 mm soil layers and 150-300 mm soil layers at the same sampling point had spatial distribution characteristics of 60-70% and 30-40%, respectively. The short period of the 0-10 years film mulching treatment increased the soil microbial diversity of the cotton field, whereas continuous film mulching for 25 years significantly decreased the soil microbial diversity, in which Proteobacteria was the dominant bacterial phylum and Ascomycetes was the dominant fungal phylum. The microbial diversity of the film-covered soil was lower than that of the control group. The spatial distribution of the residual film and microplastic changed the distribution of the microbial communities. The diversity of the microbial community structure of the 0-150 mm soil layers was higher than that of the 150-300 mm soil layers. The increase in residual film and microplastics had no significant effect on the diversity of the fungal community but decreased the diversity of the soil bacterial community and decreased the relative abundance of Proteobacteria and Campylobacter. In conclusion, long-term film mulching reduced the soil microbial diversity in cotton fields. This study provides a theoretical basis for understanding the impact of film residues on microorganisms and the ecological environment in typical areas.
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A series of D-A-D and D-A-A conjugated compounds composed of a benzoxadiazole core and corresponding amino moiety were synthesized. Their photoluminescent properties in different states were investigated as well. In the solution state, some compounds were observed to possess the usual anti-Kasha's emission in toluene and the solvatofluorochromic phenomenon. Meanwhile, compound 1 a could be utilized as fluorescent chemosensor for the environmental acidity, and 2 c could be developed for detecting fluoride anion. Moreover, they were emissive in powders and films, and 2 d could be applied to the emissive layer in red OLEDs.
Subject(s)
Molecular Structure , AnionsABSTRACT
Facile synthesis of 4-allyl-/4-allenyl-4-(arylthio)-1,4-dihydroisoquinolin-3-ones via the visible-light-induced Doyle-Kirmse reaction of 4-diazo-1,4-dihydroisoquinolin-3-ones with allyl-/propargyl sulfides is reported. The reaction proceeds via the generation of free carbenes from cyclic diazo compounds followed by in situ formation of sulfonium ylide intermediates, which subsequently undergo [2,3-sigmatropic rearrangement] to give highly functionalized dihydroisoquinolinones in moderate to good yields. Broad substrate scope, and catalyst-free and mild conditions are the merits of this reaction.
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A visible-light-driven photoredox reaction of tetrahydroisoquinoline with 2H-azirines is described. 4,7-Bis(4-methoxyphenyl)benzo[c][1,2,5]thiadiazole, a benzothiadiazole (BTD) derived fluorophore, is used as an organic photoredox catalyst, and the reaction offers an efficient access to 5,6-dihydroimidazo[2,1-a]isoquinolines with a broad range of functional groups. The resulting 5,6-dihydroimidazo[2,1-a]isoquinolines present strong photoluminecence in solutions and powders and could be applied in the fabrication of blue OLED devices.
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A novel method has been developed to synthesize a unique class of highly functionalized isochromeno[4,3-c]pyridazines. This reaction features an intermolecular functionalization of terminal nitrogen atom of diazo group of 4-diazoisochoman-3-imine with two dimethylsulfonium ylide components, followed by a base promoted 6-exo-trig cyclization step. Readily available starting materials, a broad substrate scope, and operationally simple, mild, and catalyst-free reaction conditions are the prominent features of this method.
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Three D-A compounds were designed and synthesized based on a benzothiadiazole acceptor. Azepane (AP), iminodubenzyl (IDB) and iminostilbene (ISB) were used, respectively, as donors and installed on the 5-position of BTD to afford 1, 2 and 3, respectively. Their photophysical properties in different states (solution, film, crystal, and powder) are systematically investigated. Among them, AIE-active compounds 2 and 3 were found to have good sensitivity toward viscosity and display quite good linear relationship with an increase in viscosity. Compound 2 displayed dual emission in solutions which largely depended on the polarity of the solvent. Meanwhile, compound 2 exhibits a mechanochromic character with disappearance and reappearance of a dual-emissive peak induced by mechanical grinding and solvent fuming. Furthermore, these three compounds can be used in the fabrication of blue OLED devices.
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A facile and efficient method for the synthesis of novel 2-substituted 4-tosyl-4,5-dihydrooxazolo[5,4-c]isoquinolines from 4-diazoisoquinolin-3-ones and nitriles is reported. The reaction proceeded through a TfOH-promoted formal [3 + 2] cycloaddition and the products could be conveniently converted to 2-aryloxazolo[5,4-c]isoquinolines and the subsequent 2-(oxazolo[5,4-c]isoquinolin-2-yl)phenol which emitted bright green light in dilute dichloromethane solution and in solid form as well. Simple operation, metal-free and mild reaction conditions, short reaction time and broad substrate scope are the prominent features of this methodology.
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The donor-acceptor design is a classic method of synthesizing new fluorescent molecules. In this study, a series of new fluorescent compounds (1-10) were synthesized based on 2-(3,5-bis(trifluoromethyl)phenyl)-quinazoline acceptor and various amino donors. The fluorescent emissions of 1-10 cover the spectrum from 414 nm to 597 nm in cyclohexane solutions with various amino donors on 4- or 7-positions of quinazoline. Ultimately, compounds 1 and 2 presented the highest photoluminescence quantum yield (QY) over 80%, while compound 10 provided the largest Stokes shift (161 nm) in cyclohexane. Most of them have strong emissions in aggregated states such as in nanoparticles, in powders, in crystals and in films. Mechanochromic properties were observed for compounds 1, 2, 4 and 7. Furthermore, blue OLEDs were fabricated by using compound 2 or 7 as the active layer.
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The Cu(II)-catalyzed electrophilic cyclization reaction between o-hydroxyarylenaminones and 3-diazoindolin-2-imines furnished 3-indolyl-4 H-chromen-4-ones in moderate to good yields with a broad substrate scope. Several pyrido[2,3- b:6,5- b']diindoles and one pyrazino[2,3- b:5,6- b']diindole were also obtained as byproducts in some cases and tested for their photophysical properties. Pyrido[2,3- b:6,5- b']diindoles exhibited solvent-dependent emission, while pyrazino[2,3- b:5,6- b']diindole emitted strong luminescence with 25.6% quantum yield in cyclohexane.
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OBJECTIVE: To assess the application of functional neuronavigation in surgeries of adult cerebral gliomas. METHODS: We performed a retrospective analysis of 375 cases of adult cerebral glioma patients who underwent microsurgical treatment between 2011 and 2017 in our department. Among them, 142 patients underwent surgery using functional neuronavigation (group A), and the other 233 patients were operated on without the help of functional neuronavigation (group B). For both groups, we categorized them into several subgroups according to the lesion locations. RESULTS: A significant difference in the gross total resection rate was observed between group A and group B (P = 0.001 for overall; P = 0.036 for EO area; and P = 0.004 for BBT area). The postoperative complication rate of group A was much lower than that of group B (P = 0.003 for overall; and P = 0.016 for BBT area). The postoperative 6-month Karnofsky Performance Scale score of all patients in group A was significantly higher than that of group B. Kaplan-Meier survival analyses showed significant increases in the median survival time of group A compared with that of group B (P < 0.001 for overall; P = 0.012 for EO area; P = 0.006 for BBT area), and the Cox proportional regression analysis estimated the hazard ratio of the functional neuronavigation to be 0.533, helping reduce the risk of death by 46.7%. CONCLUSIONS: This study confirmed that the application of neuronavigation in adult glioma surgery can improve postoperative quality of life and lengthen the survival time of patients, especially in cases involving the brainstem and the eloquent area.
Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Microsurgery/methods , Neuronavigation/methods , Adolescent , Adult , Brain Neoplasms/diagnostic imaging , Female , Glioma/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
TfOH-catalyzed reactions between 3-diazoindolin-2-imines and electron-rich arenes were disclosed. These metal-free reactions furnished 3-aryl-2-aminoindoles in moderate to excellent yields with the tolerance of a broad range of functional groups.
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A rhodium-catalyzed reaction between 3-diazoindolin-2-imines and 2H-azirines, followed by treatment with a base, furnishes 5H-pyrazino[2,3-b]indoles in excellent yields. A number of functional groups tolerate the reaction conditions, and the resulting 5H-pyrazino[2,3-b]indoles present strong photoluminecence in solutions, powders, and films.
ABSTRACT
OBJECTIVES: To compare and analyze the differences in clinical manifestations and surgical outcomes after gross total resection (GTR) for vestibular schwannoma between elderly and younger patients. METHODS: We conducted a retrospective study of 40 elderly (≥65 years) and 40 younger (<65 years) patients, and matched operation dates and tumor size in the 2 groups were matched. All 80 patients underwent microsurgical resection though the sigmoid approach, by the same surgeon (X.Y.). We then summarized clinical manifestations, image data, perioperative complications, tumor recurrence, and functional outcomes and assessed the differences between the 2 groups. RESULTS: The mean follow-up time was 52.64 months. Elderly patients had a poorer preoperative American Society of Anesthesiology physical status scores than younger patients (62.5% vs. 30%, P = 0.004) and were more likely to have balance disorders (72.5% vs. 25%, P < 0.01), without other preoperative differences. Both groups of patients achieved GTR. The incidence of infection was slightly but not significantly greater in elderly patients (P > 0.05). There were also no significant differences in perioperative complications, recurrence rate, facial nerve function, hearing level, or Karnofsky Performance Status Scale scores between younger and older patients. CONCLUSIONS: Elderly patients tended to suffer from poorer health (American Society of Anesthesiology score) and poor balance before the operation; however, they did not experience more complications, worse nerve function, or worse quality of life in the perioperative or follow-up times. We conclude that GTR of vestibular schwannomas, even large or giant ones, is a safe and effective option for elderly patients.