Machine learning-based identification of a cell death-related signature associated with prognosis and immune infiltration in glioma.

Accumulating evidence suggests that a wide variety of cell deaths are deeply involved in cancer immunity. However, their roles in glioma have not been explored. We employed a logistic regression model with the shrinkage regularization operator (LASSO) Cox combined with seven machine learning algorithms to analyse the patterns of cell death (including cuproptosis, ferroptosis, pyroptosis, apoptosis and necrosis) in The Cancer Genome Atlas (TCGA) cohort. The performance of the nomogram was assessed through the use of receiver operating characteristic (ROC) curves and calibration curves. Cell-type identification was estimated by using the cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and single sample gene set enrichment analysis methods. Hub genes associated with the prognostic model were screened through machine learning techniques. The expression pattern and clinical significance of MYD88 were investigated via immunohistochemistry (IHC). The cell death score represents an independent prognostic factor for poor outcomes in glioma patients and has a distinctly superior accuracy to that of 10 published signatures. The nomogram performed well in predicting outcomes according to time-dependent ROC and calibration plots. In addition, a high-risk score was significantly related to high expression of immune checkpoint molecules and dense infiltration of protumor cells, these findings were associated with a cell death-based prognostic model. Upregulated MYD88 expression was associated with malignant phenotypes and undesirable prognoses according to the IHC. Furthermore, high MYD88 expression was associated with poor clinical outcomes and was positively related to CD163, PD-L1 and vimentin expression in the in-horse cohort. The cell death score provides a precise stratification and immune status for glioma. MYD88 was found to be an outstanding representative that might play an important role in glioma.

Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma.

BACKGROUND: Gliomas account for the majority of fatal primary brain tumors, and there is much room for research in the underlying pathogenesis, the multistep progression of glioma, and how to improve survival. In our study, we aimed to identify potential biomarkers or therapeutic targets of glioma and study the mechanism underlying the tumor progression. METHODS: We downloaded the microarray datasets (GSE43378 and GSE7696) from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to screen potential biomarkers or therapeutic targets related to the tumor progression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm and TIMER (Tumor Immune Estimation Resource) database were used to analyze the correlation between the selected genes and the tumor microenvironment. Real-time reverse transcription polymerase chain reaction was used to measure the selected gene. Transwell and wound healing assays were used to measure the cell migration and invasion capacity. Western blotting was used to test the expression of epithelial-mesenchymal transition (EMT) related markers. RESULTS: We identified specific module genes that were positively correlated with the WHO grade but negatively correlated with OS of glioma. Importantly, we identified that 6 collagen genes (COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2) could regulate the immunosuppressive microenvironment of glioma. Moreover, we found that these collagen genes were significantly involved in the EMT process of glioma. Finally, taking COL3A1 as a further research object, the results showed that knockdown of COL3A1 significantly inhibited the migration, invasion, and EMT process of SHG44 and A172 cells. CONCLUSIONS: In summary, our study demonstrated that collagen genes play an important role in regulating the immunosuppressive microenvironment and EMT process of glioma and could serve as potential therapeutic targets for glioma management.

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis.

Methyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial-mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

[Application of intraoperative MRI combined with neuronavigation in microsurgical resection for insular glioma].

OBJECTIVE: To evaluate the value of intraoperative magnetic resonance imaging (iMRI) combined with neuronavigation for the resection of insular gliomas.
 Methods: From August 2014 to October 2017 in the First Hospital Affiliated to Sun Yat-sen University, clinical data of 41 patients with insular glioma, who underwent the surgery assisted with 3.0T iMRI and neuronavigation, were analyzed retrospectively, and the resection extent, complications and prognosis were evaluated.
 Results: Subtotal tumor resection was achieved in 21 patients and partial resection was done in 20 after iMRI scanning. After further resection, total tumor resection was achieved in 16 patients, subtotal resection in 18 and partial resection in 7. There was a statistical significant difference in tumor resection between pre-iMRI and post-iMRI according to the Fisher test (P<0.05). In the follow-up from 3 months to 3 years, the symptoms of the 41 patients had improved.
 Conclusion: iMRI corrected the shift of brain. Neuronavigation can accurately and timely assess the degree of resecting tumor. The combination of neuronavigation with surgery can maximally and safely resect insular glioma.

Association of TNFRSF19 with a TNF family-based prognostic model and subtypes in gliomas using machine learning.

Purpose: TNF family members (TFMs) play a crucial role in different types of cancers, with TNF Receptor Superfamily Member 19 (TNFRSF19) standing out as a particularly important member in this category. Further research is necessary to investigate the potential impact of TFMs on prognosis prediction and to elucidate the function and potential therapeutic targets linked to TNFRSF19 expression in gliomas. Methods: Three databases provided the data on gene expression and clinical information. Fourteen prognostic members were found through univariate Cox analysis and subsequently utilized to construct TFMs-based model in LASSO and multivariate Cox analyses. TFMs-based subtypes based on the expression profile were identified using an unsupervised clustering method. Machine learning algorithm identified key genes linked to prognostic model and subtype. A sequence of immune infiltrations was evaluated using the ssGSEA and ESTIMATE algorithms. Immunohistochemistry was used to examine the patterns of expression and the clinical significance of TNFRSF19. Results: Our development of a prognostic model and subtypes based on the TNF family was successful, resulting in accurate predictions of prognosis. The findings indicate that TNFRSF19 exhibited strong performance. Upregulation of TNFRSF19 was correlated with malignant phenotypes and poor prognosis, which was confirmed through immunohistochemistry. TNFRSF19 played a role in reshaping the immunosuppressive microenvironment in gliomas, and multiple drug-targeted TNFRSF19 molecules were identified. Conclusions: The TMF-based prognostic model and subtype can facilitate treatment decisions for glioma. TNFRSF19 is an outstanding representative of a predictor of prognosis and immunotherapy effect in gliomas.

LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy.

In hepatocellular carcinoma (HCC), immunotherapy is vital for advanced-stage patients. However, diverse individual responses and tumor heterogeneity have resulted in heterogenous treatment outcomes. Our mechanistic investigations identified LAPTM4B as a crucial gene regulated by ETV1 (a transcription factor), especially in liver cancer stem cells (LCSCs). The influence of LAPTM4B on LCSCs is mediated via the Wnt1/c-Myc/ß-catenin pathway. CXCL8 secretion by LAPTM4B drove myeloid-derived suppressor cell (MDSC) migration, inducing unfavorable patient prognosis. LAPTM4B affected PD-L1 receptor expression in tumor microenvironment and enhanced tumor suppression induced by PD-L1 monoclonal antibodies in HCC patients. LAPTM4B up-regulation is correlated with adverse outcomes in HCC patients, sensitizing them to PD-L1 monoclonal antibody therapy.

Analysis of differences in aroma and sensory characteristics of the mainstream smoke of six cigars.

Cigars have unique aroma and style characteristics. In order to clarify the differences of aroma components between domestic and imported cigars and the material basis of the stylistic characteristics of different cigars, gas chromatography-mass spectrometry (GC-MS) and sensory evaluation were used to compare and analyze the aroma components in the mainstream smoke of four domestic cigars and two imported cigars. The GC-MS results showed that a total of 97 aroma components were measured in the smoke of the six cigars, and the types of aroma components were similar, but there were differences in their contents. In comparison with those of domestic cigars, imported cigars had suitable nicotine content, and higher contents of phytol, neophytadiene, 3-methylpentanoic acid, and (+)-δ-cadinene. To further explore the differences in the aroma components of the six cigars, GC-MS data combined with chemometrics were used to screen out 14 key aroma components based on P-value (P) < 0.05, Variable Importance Projection (VIP) > 1, and Aroma Activity Values (OAV) > 1. The key aroma components of each cigar were obtained, Snow Dream No. 5: cedrol; Wangguan Guocui: 6-methyl-5-hepten-2-one, pyridine, 2-ethyl-6-methylpyrazine; General Achileus No. 3: p-cresol, 2-methylbutyraldehyde, methyl cyclopentenolone; Montecristo No. 4: cedrol, 2-methylbutyraldehyde, guaiacol, 4-vinylguaiacol, methyl cyclopentenolone; Romeo y Julieta Wide Churchills: cedrol, 2,6-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-heptanone, phenethyl alcohol; Great Wall No. 2: p-cresol, phenethyl alcohol, geranylacetone, methyl cyclopentenolone, dihydroactinidiolide. The odor descriptors of these compounds were consistent with the aroma profiles that were prominent in the senses of each cigar. This experiment initially explored the differences in aroma composition and style characteristics of cigars and provided data to support the quality improvement of domestic cigars.

Spinal extradural arachnoid cysts: A novel formation mechanism and dural defect location technology.

Purpose: The formation mechanism of spinal extradural arachnoid cysts (SEACs) remains unclear. There are several hypotheses for the formation of SEACs, but none of them can fully explain its pathological findings and surgical procedures. In this study, we retrospectively analyzed the cases of SEACs, aiming to clarify the formation mechanism of SEACs. In addition, we summarize a concise method for locating dural defects preoperatively and formulate a putative explanation of this method. Methods: The clinical data of 14 patients with SEACs underwent surgery in our hospital from January 2017 to December 2021 were retrospectively analyzed. Results: Fourteen patients were identified during the study period. The cysts all spanned the T12/L1 segment, and dural defects were also located at the T12/L1 level (2 cases not recorded) as well as the middle or the upper-middle level of the cysts. Nine cases were treated with total cyst excision, 2 cases were treated with dural defect closure only, and 3 cases were treated with total cyst excision and dural defect closure. Histopathological examination demonstrated that the cyst wall contained both the arachnoid epithelial and compact fibrous connective tissue. The symptoms were relieved in all patients, and no recurrence was observed. Conclusions: According to intraoperative and pathological findings, the dural outer layer cyst (DOLC) is a more reasonable hypothesis about SEACs formation. When CT myelography or cinematic MRI cannot determine the location of the dural defect preoperatively, it can be located according to the middle level of the SEACs with high accuracy.

TANK shapes an immunosuppressive microenvironment and predicts prognosis and therapeutic response in glioma.

Background: Glioma, the most prevalent malignant intracranial tumor, poses a significant threat to patients due to its high morbidity and mortality rates, but its prognostic indicators remain inaccurate. Although TRAF-associated NF-kB activator (TANK) interacts and cross-regulates with cytokines and microenvironmental immune cells, it is unclear whether TANK plays a role in the immunologically heterogeneous gliomas. Methods: TANK mRNA expression patterns in public databases were analyzed, and qPCR and IHC were performed in an in-house cohort to confirm the clinical significance of TANK. Then, we systematically evaluated the relationship between TANK expression and immune characteristics in the glioma microenvironment. Additionally, we evaluated the ability of TANK to predict treatment response in glioma. TANK-associated risk scores were developed by LASSO-Cox regression and machine learning, and their prognostic ability was tested. Results: TANK was specifically overexpressed in glioma and enriched in the malignant phenotype, and its overexpression was related to poor prognosis. The presence of a tumor microenvironment that is immunosuppressive was evident by the negative correlations between TANK expression and immunomodulators, steps in the cancer immunity cycle, and immune checkpoints. Notably, treatment for cancer may be more effective when immunotherapy is combined with anti-TANK therapy. Prognosis could be accurately predicted by the TANK-related risk score. Conclusions: High expression of TANK is associated with the malignant phenotype of glioma, as it shapes an immunosuppressive tumor microenvironment. Additionally, TANK can be used as a predictive biomarker for responses to various treatments and prognosis.

A critical assessment of the Candida strains isolated from cigar tobacco leaves.

Introduction: Candida genus plays a crucial role in cigar fermentation, and strains from different sources might have differences in metabolic characteristics. Therefore, this study conducted directional isolation of Candida strains from cigar tobacco leaves and compared their fermentabilities to screen suitable strains for cigar fermentation, thereby improving the cigar quality. Methods: First, the Candida strains from cigars tobacco leaves in different production areas were directionally isolated by pure culture. Then, the isolated strains were screened based on chemical indexes and flavor component contents. Finally, the fermentabilities of preferred strains were verified by sensory evaluation. Results: Five strains of C. parapsilosis and four strains of C. metapsilosis were obtained through directional isolation. By comparing the physicochemical indexes of nine strains of Candida, it was found that C. parapsilosis P1 and C. metapsilosis M4 not only reduced the alkaloids content (by 25.3% and 32.6%, respectively) but also increased the flavor components content (by 25.2% and 18.9%, respectively). Among them, P1 could raise the content of chlorophyll degradation products, carotenoid degradation products, and Maillard reaction products, and enhance the beany and nutty flavor of cigars. M4 could raise the content of chlorophyll degradation products, cembranoids degradation products, and Maillard reaction products, and improve the baking, nutty, cocoa, and honey flavor of the cigar. Discussion: In this study, the Candida strains were directionally isolated from cigars tobacco leaves in different production areas, and two functional strains suitable for cigar fermentation were screened based on physicochemical indexes and sensory evaluation, which would contribute to the directed regulation of cigar quality and flavor diversification.

Effects of a novel microbial fermentation medium produced by Tremella aurantialba SCT-F3 on cigar filler leaf.

Introduction: Adding a fermentation medium is an effective way to improve the quality of cigar tobacco leaves. Methods: A novel microbial fermentation medium produced by an edible medicinal fungus, Tremella aurantialba SCT-F3 (CGMCC No.23831) was used to improve the quality of cigar filler leaves (CFLs). Changes in sensory quality, chemical components, volatile flavor compounds (VFCs), and the structure and function of microbes were investigated during the fermentation process. Results: The sensory quality of CFLs supplemented with the T. aurantialba SCT-F3 fermentation medium significantly improved. Adding the fermentation medium increased the total alkaloid, reducing sugar, total sugar, and 12 VFCs significantly. A total of 31 microbial genera were significantly enriched, which increased the microbial community's richness and diversity. Microbial functions increased, including nucleotide biosynthesis, amino acid biosynthesis, fatty acid and lipid biosynthesis, nicotine degradation, and nicotinate degradation. During fermentation, the total alkaloid, reducing sugar, and total sugar content decreased. The richness and diversity of the microbial community decreased, whereas bacterial enzyme activity increased. At the end of fermentation, the sensory quality was excellent. The microbial structure gradually stabilized, and functional genes were low. The contents of the four Maillard reaction products and three nicotine degradation products increased significantly. 2-Ethyl-6-methylpyrazine, methylpyrazine, D,L-anatabine, ß-nicotyrine, nicotinic degradation products, and total nitrogen were significantly and positively correlated with sensory quality. Methylpyrazine, D,L-anatabine, and ß-nicotyrine were negatively correlated with Luteimonas, Mitochondria, Paracoccus, Stemphylium, and Stenotrophomonas. Conclusion: This research provides not only a new microbial fermentation medium that utilizes edible and medicinal fungi to improve the quality of fermented CFLs, but also new ideas for the development and application of other edible medicinal fungi to improve the quality of cigar tobacco leaves.

One-pot freezing-thawing preparation of cellulose nanofibrils reinforced polyvinyl alcohol based ionic hydrogel strain sensor for human motion monitoring.

Ionic conductive hydrogels have been widely applied in sensors, energy storage and soft electronics recently. However, most of the polyvinyl alcohol (PVA) based ionic hydrogels are mainly fabricated by soaking the hydrogels in high concentration electrolyte solution which can induce the waste of electrolyte and solvent. Herein, we have designed cellulose nanofibrils (CNF) and ZnSO4 reinforced PVA based hydrogels through a one-pot simple freezing-thawing method at low ZnSO4 concentration without any soaking process. Furthermore, the hydrogel with 0.4% CNF exhibited stress up to 0.79 MPa (242% strain) and high ionic conductivity of 0.32 S m-1 (0.07 M ZnSO4). Moreover, hydrogel sensor displayed high linear gauge factor 1.70 (0-200% strain), excellent stability, durability and reliability. The integrated hydrogel sensor also showed excellent sensor performance for human motion monitoring. This work provides a new prospect for the design of cellulose reinforced conductive hydrogels via a facile method.

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma.

Background: Diffuse glioma, the most common intracranial malignant tumor, is characterized by immunosuppression. The prognostic significance and potential therapeutic value of SYK remain obscure. Here, we explored the performance of SYK in predicting patient outcomes and as a therapeutic target. Methods: The mRNA expression and clinical data for pancancer and normal tissues and more than 2,000 glioma samples were collected from public databases. The expression level of SYK was evaluated by qPCR and IHC. The prognostic value of SYK was assessed using the Kaplan-Meier curves and univariate and multivariate Cox regression analyses. A sequence of immune and stromal infiltration analyses was calculated based on the ESTIMATE algorithm, ssGSEA algorithm, TIMER, and single-cell analysis. The SYK-related subtypes were identified via a Consensus Cluster Plus analysis. Results: SYK was significantly differentially expressed in multiple tumors and normal tissues. Importantly, high-expression SYK was enriched in malignant phenotypes of diffuse gliomas, which was further validated by qPCR and IHC. Survival analysis uncovered that SYK was an independently unfavorable prognostic marker in diffuse glioma. Functional enrichment analysis and immune and stromal infiltration analyses showed that SYK was involved in shaping the immunosuppressive microenvironment of diffuse glioma. Additionally, SYK expression was closely associated with some immune checkpoint molecules and M2 macrophage infiltration, which was validated by IHC and single-cell analysis. Diffuse glioma with Sub1 exhibited a worse prognosis, immunosuppressive microenvironment, and higher expression of immune checkpoint genes. Conclusion: SYK is involved in shaping the immunosuppressive microenvironment and served as a promising prognosis biomarker and immunotherapeutic target for diffuse glioma.

Relationship between postoperative hypothalamic injury and water and sodium disturbance in patients with craniopharyngioma: A retrospective study of 178 cases.

Objective: To investigate the relationship between postoperative hypothalamo-hypophyseal injury (HHI) and postoperative water and sodium disturbances in patients with craniopharyngioma. Methods: The medical records, radiological data, and laboratory results of 178 patients (44 children and 134 adults) who underwent microsurgery for craniopharyngioma in a single center were reviewed. Postoperative HHI was assessed using magnetic resonance imaging. Structural defects of the hypothalamo-hypophyseal system (pituitary, pituitary stalk, floor and lateral wall of the third ventricle) were assessed in four standard T1-weighted images. The defect of each structure was assigned 1 score (0.5 for the unilateral injury of the third ventricle wall), and a HHI score was calculated. Results: The number of patients with HHI scores of 0-1, 2, 2.5-3, and >3 was 35, 49, 61, and 33, respectively. Diabetes insipidus (DI) worsened in 56 (31.5%) patients with preoperative DI, while 119 (66.9%) patients were diagnosed with new-onset DI. Hypernatremia and hyponatremia developed in 127 (71.3%) and 128 (71.9%) patients after surgery, respectively. Syndrome of inappropriate antidiuresis occurred in 97(54.5%) patients. During hospitalization, hypernatremia recurred in 33 (18.5%) patients and in 54 (35.7%) during follow-up, of which 18 (11.9%) were severe. DI persisted in 140 (78.7%) patients before discharge. No relationship was found between the HHI score and incidence of early DI, hyponatremia, syndrome of inappropriate diuretic hormone, or prolonged DI. Compared with patients with a score of 0-1, those with scores =2.5-3 (OR = 5.289, 95% CI:1.098-25.477, P = 0.038) and >3 (OR = 10.815, 95% CI:2.148-54.457, P = 0.004) had higher risk of developing recurrent hypernatremia. Patients with a score >3 had higher risk of developing severe hypernatremia during hospitalization (OR = 15.487, 95% CI:1.852-129.539, P = 0.011) and at follow-up (OR = 28.637, 95% CI:3.060-267.981, P = 0.003). Conclusions: The neuroimaging scoring scale is a simple tool to semi-quantify HHI after surgery. Recurrent and severe hypernatremia should be considered in patients with a high HHI score (>2.5). An HHI score >3 is a potential predictor of adipsic DI development. Preventive efforts should be implemented in the perioperative period to reduce the incidence of potentially catastrophic complications.

FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies.

FBXW7, a member of the F-box protein family within the ubiquitin-proteasome system, performs an indispensable role in orchestrating cellular processes through ubiquitination and degradation of its substrates, such as c-MYC, mTOR, MCL-1, Notch, and cyclin E. Mainly functioning as a tumor suppressor, inactivation of FBXW7 induces the aberrations of its downstream pathway, resulting in the occurrence of diseases especially tumorigenesis. Here, we decipher the relationship between FBXW7 and the hallmarks of cancer and discuss the underlying mechanisms. Considering the interplay of cancer hallmarks, we propose several prospective strategies for circumventing the deficits of therapeutic resistance and complete cure of cancer patients.

Effects of Inoculation With Acinetobacter on Fermentation of Cigar Tobacco Leaves.

Metabolic activity of the microbial community greatly affects the quality of cigar tobacco leaves (CTLs). To improve the quality of CTLs, two extrinsic microbes (Acinetobacter sp. 1H8 and Acinetobacter indicus 3B2) were inoculated into CTLs. The quality of CTLs were significantly improved after fermentation. The content of solanone, 6-methyl-5-hepten-2-one, benzeneacetic acid, ethyl ester, cyclohexanone, octanal, acetophenone, and 3,5,5-trimethyl-2-cyclohexen-1-one were significantly increased after inoculated Acinetobacter sp. 1H8. The inoculation of Acinetobacter sp. 1H8 enhanced the normal evolutionary trend of bacterial community. The content of trimethyl-pyrazine, 2,6-dimethyl-pyrazine, and megastigmatrienone were significantly increased after inoculated Acinetobacter indicus 3B2. The inoculation of Acinetobacter indicus 3B2 completely changed the original bacterial community. Network analysis revealed that Acinetobacter was negatively correlated with Aquabacterium, positively correlated with Bacillus, and had significant correlations with many volatile flavor compounds. This work may be helpful for improving fermentation product quality by regulating microbial community, and gain insight into the microbial ecosystem.

Potential mechanisms underlying the promoting effects of 3D collagen scaffold culture on stemness and drug resistance of glioma cells.

BACKGROUND: 3D collagen scaffold culture is a good tool to study glioma metastasis and recurrence in vitro. METHODS: The effect of 3D collagen culture on the colony formation, the sphere formation, and drug sensitivity of glioma cells was observed by soft-agar colony formation assays, sphere formation assays, and CCK-8 assays, respectively. 3D-glioma-drug genes were identified by previous results and online databases. Gene enrichment and PPI analyses were performed by R software and Metacsape. Hub 3D-glioma-drug genes were screened by STRING and Cytoscape. TCGA and CGGA databases and R software were used to analyze the distribution of hub genes in glioma and their effects on the prognosis. Western Blot was used to verify the effect of 3D collagen culture on the expression of hub genes. miRNAs targeting hub genes were predicted by ENCORI. RESULTS: 3D collagen scaffold culture promoted colony formation, sphere formation, and drug resistance of glioma cells. There were 77 3D-glioma-drug genes screened, and the pathways enriched in the protein interaction network mainly included responses to stressors, DNA damage and repair, and drug metabolism. Hub 3D-glioma-drug genes were AKT1, ATM, CASP3, CCND1, EGFR, PARP1, and TP53. These genes and predicted miRNAs were expressed differentially in glioma samples and partially affected the prognosis of patients with glioma. These findings suggested these hub genes and miRNAs may play a key role in the effects generated by the 3D culture model and become new markers for glioma diagnosis and treatment.

TBL1X and Flot2 form a positive feedback loop to promote metastasis in nasopharyngeal carcinoma.

Metastasis is the main cause of death in patients with nasopharyngeal carcinoma (NPC). The molecular mechanisms underlying the metastasis of NPC remain to be elucidated. TBL1X has been shown abnormally expressed in diverse cancers. However, the role and mechanism of TBL1X in NPC remain unknown. Here, we showed TBL1X expression was significantly higher in metastatic NPC tissues compared to non-metastatic tissues and significantly correlated with TNM stage and metastasis of NPC patients. In addition, NPC patients with high TBL1X expression had a poor prognosis. TBL1X interacted with TCF4 to trans-activate Flot2 expression. TBL1X promoted NPC cell migration and invasion in vitro and in vivo through Flot2. Moreover, Flot2 increased the expression of TBL1X by upregulating c-myc, which was identified to be a positively regulatory transcription factor of TBL1X. TBL1X could restore the functional changes of NPC cells resulting from Flot2 alteration. TBL1X and Flot2 were positively correlated in NPC. Patients with high expression of both TBL1X and Flot2 possessed poorer overall survival (OS) and disease-free survival (DFS) compared to patients with high expression of any single one of the two proteins. Our findings demonstrate that TBL1X and Flot2 positively regulate each other to promote NPC metastasis, which provides novel potential molecular targets for NPC treatment.

The role of lncRNA just proximal to XIST (JPX) in human disease phenotypes and RNA methylation: The novel biomarker and therapeutic target potential.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are closely related to the initialization and development of human diseases. lncRNA just proximal to XIST (JPX), as a newly identified lncRNA, has been reported to be aberrantly expressed and associated with pathophysiological traits in numerous diseases, particularly cancers. More importantly, JPX has been proven to play important roles in various biological functions, including cell proliferation, migration, invasion, apoptosis, chemoresistance, and differentiation. In addition, we discuss the diverse molecular mechanisms and correlation with RNA methylation of JPX in several cancers. In this Review, we summarize current studies on JPX's roles in diseases and its potential application as a biomarker for both diagnoses and prognoses and a therapeutic target in human diseases.