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IntroductionCoal reservoir fractures serve as critical storage spaces and migration pathways for coalbed methane (CBM), significantly influencing CBM enrichment. The characteristics of coal reservoir fracture development can be obtained using traditional simulation methods, but these still have shortcomings. This work presents an optimization approach for the traditional method.MethodsThis study introduces an optimization approach for traditional methods with two novel contributions. This study integrates the simulation of tectonic stress fields with fracture prediction, using surface sandstone fractures as constraints to reconstruct the paleostress field of the coal seam, while also accounting for the influence of coal thickness on fracture development to calculate fracture density.ResultsThe predicted fracture density results were validated against measured values from the Bailongshan mine and Xiongdong coal mine with a relative error of approximately 12%, suggesting a reasonable degree of reliability.DiscussionBased on the results of the fracture simulation predictions, it is believed that the coal seam fracture density in the study area is mostly 10–20 lines/m and that the sweet spot for CBM development is located in the Yuwang block.

Abstract Background Metabolic remodeling and changes in tumor immune microenvironment (TIME) in osteosarcoma are important factors affecting prognosis and treatment. However, the relationship between metabolism and TIME needs to be further explored. Methods RNA-Seq data and clinical information of 84 patients with osteosarcoma from the TARGET database and an independent cohort from the GEO database were included in this study. The activity of seven metabolic super-pathways and immune infiltration levels were inferred in osteosarcoma patients. Metabolism-related genes (MRGs) were identified and different metabolic clusters and MRG-related gene clusters were identified using unsupervised clustering. Then the TIME differences between the different clusters were compared. In addition, an MRGs-based risk model was constructed and the role of a key risk gene, ST3GAL4, in osteosarcoma cells was explored using molecular biological experiments. Results This study revealed four key metabolic pathways in osteosarcoma, with vitamin and cofactor metabolism being the most relevant to prognosis and to TIME. Two metabolic pathway-related clusters (C1 and C2) were identified, with some differences in immune activating cell infiltration between the two clusters, and C2 was more likely to respond to two chemotherapeutic agents than C1. Three MRG-related gene clusters (GC1-3) were also identified, with significant differences in prognosis among the three clusters. GC2 and GC3 had higher immune cell infiltration than GC1. GC3 is most likely to respond to immune checkpoint blockade and to three commonly used clinical drugs. A metabolism-related risk model was developed and validated. The risk model has strong prognostic predictive power and the low-risk group has a higher level of immune infiltration than the high-risk group. Knockdown of ST3GAL4 significantly inhibited proliferation, migration, invasion and glycolysis of osteosarcoma cells and inhibited the M2 polarization of macrophages. Conclusion The metabolism of vitamins and cofactors is an important prognostic regulator of TIME in osteosarcoma, MRG-related gene clusters can well reflect changes in osteosarcoma TIME and predict chemotherapy and immunotherapy response. The metabolism-related risk model may serve as a useful prognostic predictor. ST3GAL4 plays a critical role in the progression, glycolysis, and TIME of osteosarcoma cells.

Background: Hematopoietic cell signal transducer (HCST) and tyrosine kinase-binding protein (TYROBP) are triggering receptors expressed on myeloid cells 2 (TREM2), which are pivotal in the immune response to disease. Despite growing evidence underscoring the significance of TREM2, HCST, and TYROBP in certain forms of tumorigenesis, a comprehensive pan-cancer analysis of these proteins is lacking. Methods: Multiple databases were synthesized to investigate the relationship between TREM2, HCST, TYROBP, and various cancer types. These include prognosis, methylation, regulation by long non-coding RNAs and transcription factors, immune signatures, pathway activity, microsatellite instability (MSI), tumor mutational burden (TMB), single-cell transcriptome profiling, and drug sensitivity. Results: TREM2, HCST, and TYROBP displayed extensive somatic changes across numerous tumors, and their mRNA expression and methylation levels influenced patient outcomes across multiple cancer types. long non-coding RNA (lncRNA) -messenger RNA (mRNA) and TF-mRNA regulatory networks involving TREM2, HCST, and TYROBP were identified, with lncRNA MEG3 and the transcription factor SIP1 emerging as potential key regulators. Further immune analyses indicated that TREM2, HCST, and TYROBP play critical roles in immune-related pathways and macrophage differentiation, and may be significantly associated with TGF-β and SMAD9. Furthermore, the expression of TREM2, HCST, and TYROBP correlated with the immunotherapy markers TMB and MSI, and influenced sensitivity to immune-targeted drugs, thereby indicating their potential as predictors of immunotherapy outcomes. Conclusion: This study offers valuable insights into the roles of TREM2, HCST, and TYROBP in tumor immunotherapy, suggesting their potential as prognostic markers and therapeutic targets for various cancers.

Lower grade gliomas (LGGs) exhibit invasiveness and heterogeneity as distinguishing features. The outcome of patients with LGG differs greatly. Recently, more and more studies have suggested that infiltrating inflammation cells and inflammation-related genes (IRGs) play an essential role in tumorigenesis, prognosis, and treatment responses. Nevertheless, the role of IRGs in LGG remains unclear. In The Cancer Genome Atlas (TCGA) cohort, we conducted a thorough examination of the predictive significance of IRGs and identified 245 IRGs that correlated with the clinical prognosis of individuals diagnosed with LGG. Based on unsupervised cluster analysis, we identified two inflammation-associated molecular clusters, which presented different tumor immune microenvironments, tumorigenesis scores, and tumor stemness indices. Furthermore, a prognostic risk model including ten prognostic IRGs (ADRB2, CD274, CXCL12, IL12B, NFE2L2, PRF1, SFTPC, TBX21, TNFRSF11B, and TTR) was constructed. The survival analysis indicated that the IRGs risk model independently predicted the prognosis of patients with LGG, which was validated in an independent LGG cohort. Moreover, the risk model significantly correlated with the infiltrative level of immune cells, tumor mutation burden, expression of HLA and immune checkpoint genes, tumorigenesis scores, and tumor stemness indices in LGG. Additionally, we found that our risk model could predict the chemotherapy response of some drugs in patients with LGG. This study may enhance the advancement of personalized therapy and improve outcomes of LGG.

Abstract Background The tumor microenvironment (TME) has a central role in the oncogenesis of osteosarcomas. The composition of the TME is essential for the interaction between tumor and immune cells. The aim of this study was to establish a prognostic index (TMEindex) for osteosarcoma based on the TME, from which estimates about patient survival and individual response to immune checkpoint inhibitor (ICI) therapy can be deduced. Methods Based on osteosarcoma samples from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, the ESTIMATE algorithm was used to estimate ImmuneScore and StromalScore. Combined differentially expressed gene analysis, weighted gene co-expression network analyses, the Least Absolute Shrinkage and Selection Operator regression and stepwise regression to construct the TMEindex. The prognostic role of TMEindex was validated in three independent datasets. The molecular and immune characteristics of TMEindex and the impact on immunotherapy were then comprehensively investigated. The expression of TMEindex genes in different cell types and its effects on osteosarcoma cells were explored by scRNA-Seq analysis and molecular biology experiments. Results Fundamental is the expression of MYC, P4HA1, RAMP1 and TAC4. Patients with high TMEindex had worse overall survival, recurrence-free survival, and metastasis-free survival. TMEindex is an independent prognostic factor in osteosarcoma. TMEindex genes were mainly expressed in malignant cells. The knockdown of MYC and P4HA1 significantly inhibited the proliferation, invasion and migration of osteosarcoma cells. A high TME index is related to the MYC, mTOR, and DNA replication-related pathways. In contrast, a low TME index is related to immune-related signaling pathways such as the inflammatory response. The TMEindex was negatively correlated with ImmuneScore, StromalScore, immune cell infiltration, and various immune-related signature scores. Patients with a higher TMEindex had an immune-cold TME and higher invasiveness. Patients with a low TME index were more likely to respond to ICI therapy and achieve clinical benefit. In addition, the TME index correlated with response to 29 oncologic drugs. Conclusions The TMEindex is a promising biomarker to predict the prognosis of patients with osteosarcoma and their response to ICI therapy, and to distinguish the molecular and immune characteristics.

Abstract Background Recent studies have shown that immunotherapies, including peptide vaccines, remain promising strategies for patients with lower grade glioma (LGG); however new biomarkers need to be developed to identify patients who may benefit from therapy. We aimed to investigate the feasibility of liquid biopsy-based gene signatures in predicting the prognosis of LGG patients, as well as the benefits of immunotherapy. Methods We evaluated the association between circulating immune cells and treatment response by analyzing peripheral blood mononuclear cell (PBMC) samples from LGG patients receiving peptide vaccine immunotherapy, identified response-related genes (RRGs), and constructed RRG-related Response Score. In addition, RRG-related RiskScore was constructed in LGG tumor samples based on RRGs; association analysis for RiskScore and characteristics of TME as well as patient prognosis were performed in two LGG tumor datasets. The predictive power of RiskScore for immunotherapy benefits was analyzed in an anti-PD-1 treatment cohort. Results This study demonstrated the importance of circulating immune cells, including monocytes, in the immunotherapeutic response and prognosis of patients with LGG. Overall, 43 significant RRGs were identified, and three clusters with different characteristics were identified in PBMC samples based on RRGs. The constructed RRG-related Response Score could identify patients who produced a complete response to peptide vaccine immunotherapy and could predict prognosis. Additionally, three subtypes were identified in LGG tumors based on RRGs, with subtype 2 being an immune “hot” phenotype suitable for immune checkpoint therapy. The constructed RRG-related RiskScore was significantly positively correlated with the level of tumor immune cell infiltration. Patients with high RiskScore had a worse prognosis and were more likely to respond to immune checkpoint therapy. The therapeutic advantage and clinical benefits of patients with a high RiskScore were confirmed in an anti-PD-1 treatment cohort. Conclusion This study confirmed the potential of liquid biopsy for individualized treatment selection in LGG patients and determined the feasibility of circulating immune cells as biomarkers for LGG. Scoring systems based on RRGs can predict the benefits of immunotherapy and prognosis in patients with LGG. This work would help to increase our understanding of the clinical significance of liquid biopsy and more effectively guide individualized immunotherapy strategies.

Abstract Purpose Glioblastoma (GBM) is the most common primary brain tumor in adults and is notorious for its lethality. Given its limited therapeutic measures and high heterogeneity, the development of new individualized therapies is important. mRNA vaccines have exhibited promising performance in a variety of solid tumors, those designed for glioblastoma (GBM) need further development. The aim of this study is to explore tumor antigens for the development of mRNA vaccines against GBM and to identify potential immune subtypes of GBM to identify the patients suitable for different immunotherapies. Methods RNA-seq data and the clinical information of 143 GBM patients was extracted from the TCGA database; microarray data and the clinical information of 181 GBM patients was obtained from the REMBRANDT cohort. A GBM immunotherapy cohort of 17 patients was obtained from a previous literature. GEPIA2, cBioPortal, and TIMER2 were used to identify the potential tumor antigens. Immune subtypes and gene modules were identified using consensus clustering; immune landscape was constructed using graph-learning-based dimensionality reduction analysis. Results Nine potential tumor antigens associated with poor prognosis and infiltration of antigen-presenting cells were identified in GBM: ADAMTSL4, COL6A1, CTSL, CYTH4, EGFLAM, LILRB2, MPZL2, SAA2, and LSP1. Four robust immune subtypes and seven functional gene modules were identified and validated in an independent cohort. Immune subtypes had different cellular and molecular characteristics, with IS1, an immune cold phenotype; IS2, an immune hot and immunosuppressive phenotype; IS3, a relatively immune cold phenotype, second only to IS1; IS4, having a moderate tumor immune microenvironment. Immune landscape revealed the immune distribution of the GBM patients. Additionally, the potential value of immune subtypes for individualized immunotherapy was demonstrated in a GBM immunotherapy cohort. Conclusions ADAMTSL4, COL6A1, CTSL, CYTH4, EGFLAM, LILRB2, MPZL2, SAA2, and LSP1 are the candidate tumor antigens for mRNA vaccine development in GBM, and IS1 GBM patients are best suited for mRNA vaccination, IS2 patients are best suited for immune checkpoint inhibitor. This study provides a theoretical framework for GBM mRNA vaccine development and individualized immunotherapy strategies.

Abstract Imbalance in copper homeostasis can be lethal. A recent study found that excess copper induces cell death in a way that has never been characterized before, which is dependent on mitochondrial stress and is referred to as “cuproptosis.” The role of cuproptosis in tumors has not yet been elucidated. In this study, we revealed the complex and important roles of cuproptosis regulators and cuproptosis activity in tumors via a comprehensive analysis of multiomics data from more than 10,000 samples of 33 tumor types. We found that the cyclin‐dependent kinase inhibitor 2A is the most frequently altered cuproptosis regulator, and the cuproptosis regulator expression is dysregulated in various tumors. Additionally, we developed a cuproptosis activity score to reflect the overall cuproptosis level. On the basis of the expression levels of cuproptosis regulators, tumors can be divided into two clusters with different cuproptosis activities and survival outcomes. Importantly, cuproptosis activity was found to be associated with the prognosis of multiple tumors and multiple tumor‐related pathways, including fatty acid metabolism and remodeling of the tumor microenvironment. Furthermore, cuproptosis increased the sensitivity to multiple drugs and exhibited potential to predict the outcome of immunotherapy. We also comprehensively identified cuproptosis‐related microRNAs, long noncoding RNAs, and transcription factors. We provided the code corresponding to the results of this study in GitHub (https://github.com/Changwuuu/Cuproptosis-pancancer.git) for reference. In summary, this study reveals important molecular and clinical characteristics of cuproptosis regulators and cuproptosis activity in tumors, and suggests the use of cuproptosis as a promising tumor therapeutic approach. This study provides an important reference point for future cuproptosis‐related research.

Regulation of chromosome condensation 2 (RCC2) is associated with the cell cycle and is a crucial regulator of the chromatin condensation 1 (RCC1) family. The members of this family were normally regulators in the process of DNA replication and nucleocytoplasmic transport. RCC2 overexpression may lead to tumor formation and poor prognosis in some tumors including breast cancer and lung adenocarcinoma. However, the possible role of RCC2 in tumor formation and its prognostic function remains unclear. In this study, expression analysis from databases including The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were combined to perform the first integrative and comprehensive analysis of RCC2 in human pan-cancer. RCC2 was highly expressed in most tumors which may lead to a poor prognosis. RCC2 expression was associated with immune/stromal infiltration, immune checkpoints, tumor mutational burden, and microsatellite instability. Thus, RCC2 could be a novel biomarker for prognosis and a promising cancer therapy target.

BackgroundNervus intermedius (NI) injuries are not given enough attention by neurosurgeons during vestibular schwannoma (VS) surgery. Preservation of NI function is essential for the integrity and continuity of the facial nerve, although this can be challenging. We identified the risk factors for NI injury and proposed our experience for optimizing NI preservation based on our cases.MethodsWe retrospectively analyzed clinical data from a consecutive series of 127 patients with VS who underwent microsurgery via the retrosigmoid approach from 2017 to 2021 at our institution. The baseline characteristics of the patients were collected from the medical records, and the incidence of NI dysfunction symptoms was obtained by outpatient and online video follow-up 6 months after surgery. The surgical procedures and techniques used were described in detail. The data were analyzed in relation to sex, age, tumor location (left or right), Koos grading scale, internal acoustic canal (IAC) invasion (TFIAC Classification), brainstem adhesion, tumor characteristics (cystic or solid), tumor necrosis, and preoperative House–Brackmann (HB) grading by univariate and multivariate analyses.ResultsGross tumor removal was achieved in 126 (99.21%) patients. Subtotal removal was performed on one patient (0.79%). Twenty-three of our cases exhibited facial nerve palsy preoperatively; 21 patients had HB grade II facial palsy, and two had HB grade III. Two months after surgery, 97 (76.38%) patients had normal function of the motor portion of the facial nerve; 25 (19.69%) patients had HB Grade II facial palsy, five had Grade III (3.94%), and zero (0%) had Grade IV. Postoperatively, 15 patients experienced newly gained dry eyes (11.81%), whereas 21 cases of lacrimal disturbances (16.54%), nine of taste disturbances (7.09%), seven of xerostomia (5.51%), five of nasal hypersecretions (3.94%), and seven of hypersalivation (5.51%) were identified in our cases. Univariate and multivariate analyses revealed that the Koos grading scale and tumor characteristics (solid or cystic) were correlated with NI injury (p

Head and neck squamous cell carcinoma (HNSCC) comprise a group of malignant tumors arising from the squamous epithelium of the oral cavity, pharynx, and larynx. HNSCC is the 6th most common cancer in the world, with approximately 650,000 new cases and 400,000 deaths annually. Although survival rates have improved, HNSCC therapy may result in short – or long-term morbidity in approximately 50% of cases. Previous studies have also indicated that the overexpression of procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenases (PLOD) family proteins could lead to certain diseases or even tumors. However, there has been no dedicated evaluation of the relationship between PLOD family members and HNSCC. Here we used data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases to explore the potential role of PLOD family proteins in HNSCC. Our evaluations suggest that increased expression of PLOD family proteins may be associated with poorer prognosis and increased immune infiltration in HNSCC, making these proteins a potential biomarker for personalized treatment of HNSCC.

The role of homologous recombination deficiency (HRD) in lower grade glioma (LGG) has not been elucidated, and accurate prognostic prediction is also important for the treatment and management of LGG. The aim of this study was to construct an HRD-based risk model and to explore the immunological and molecular characteristics of this risk model. The HRD score threshold = 10 was determined from 506 LGG samples in The Cancer Genome Atlas cohort using the best cut-off value, and patients with high HRD scores had worse overall survival. A total of 251 HRD-related genes were identified by analyzing differentially expressed genes, 182 of which were associated with survival. A risk score model based on HRD-related genes was constructed using univariate Cox regression, least absolute shrinkage and selection operator regression, and stepwise regression, and patients were divided into high- and low-risk groups using the median risk score. High-risk patients had significantly worse overall survival than low-risk patients. The risk model had excellent predictive performance for overall survival in LGG and was found to be an independent risk factor. The prognostic value of the risk model was validated using an independent cohort. In addition, the risk score was associated with tumor mutation burden and immune cell infiltration in LGG. High-risk patients had higher HRD scores and “hot” tumor immune microenvironment, which could benefit from poly-ADP-ribose polymerase inhibitors and immune checkpoint inhibitors. Overall, this big data study determined the threshold of HRD score in LGG, identified HRD-related genes, developed a risk model based on HRD-related genes, and determined the molecular and immunological characteristics of the risk model. This provides potential new targets for future targeted therapies and facilitates the development of individualized immunotherapy to improve prognosis.

With many types of salt structures developed in the Lower Cretaceous Aptian Formation, the passive continental marginal basins in the middle segment of the south Atlantic are hot areas of deep-water petroleum exploration. Based on analysis of differential deformations of salt structures, the influences of the inclination of subsalt slope, subsalt topographic reliefs and basement uplifting on the formation of salt structures were analyzed by physical modeling in this work. The experimental results show that the subsalt slopes in the middle West Africa basins are steeper, so the salt rock is likely to rapidly flow towards the ocean to form larger and fewer salt diapirs. In the Santos and Campos basins, the basement uplifts outside the basins are far from the provenances, which is conducive to the intrusion and accumulation of salt rock on the top of the basement uplifts. In contrast, in the middle West Africa, the basement uplifts are close to the basin margin, the residual salt layers above them are thin, and small triangular salt structures develop on both sides of the uplifts. Moreover, the uplifting of the African plate is also conducive to the full development of salt diapirs in the middle West Africa and results in large-scale thrust faults and folds in the front compressional zone.

Lower-grade glioma (LGG) is a group of tumors arising from the cells of the central nervous system. Although various therapy interventions are used, the prognosis remains different. Novel biomarkers are needed for the prognosis of disease and novel therapeutic strategies in LGG. The procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family contains three members and is related to multiple cancers, yet it was not investigated in LGG. Data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) cohorts were used to analyze the role of PLOD in LGG. As the PLOD family is involved in processes, such as tumor formation and cancer metastasis, we focused on its relationship to the tumor microenvironment (TME) in LGG. A high expression of the PLOD family relates to poor prognosis and high infiltration of immune cells within the TME. The expression level of the PLOD family might become a novel biomarker for prognosis and is a potential target for individual treatment decisions in LGG.

Pituitary tumor-transforming gene 1 (PTTG1) encodes a multifunctional protein that is involved in many cellular processes. However, the potential role of PTTG1 in tumor formation and its prognostic function in human pan-cancer is still unknown. The analysis of gene alteration, PTTG1 expression, prognostic function, and PTTG1-related immune analysis in 33 types of tumors was performed based on various databases such as The Cancer Genome Atlas database, the Genotype-Tissue Expression database, and the Human Protein Atlas database. Additionally, PTTG1-related gene enrichment analysis was performed to investigate the potential relationship and possible molecular mechanisms between PTTG1 and tumors. Overexpression of PTTG1 may lead to tumor formation and poor prognosis in various tumors. Consequently, PTTG1 acts as a potential oncogene in most tumors. Additionally, PTTG1 is related to immune infiltration, immune checkpoints, tumor mutational burden, and microsatellite instability. Thus, PTTG1 could be potential biomarker for both prognosis and outcomes of tumor treatment and it could also be a promising target in tumor therapy.

BackgroundManagement of tentorial notch meningiomas (TNM) remains a challenge for neurosurgeons. We demonstrate the clinical characteristics and surgical experiences of TNM based on our cases according to a proposed further classification.MethodsWe retrospectively analyzed clinical and follow-up data in a consecutive series of 53 TNM patients who underwent microsurgical operation from 2011 to 2019 in our institution. The operations were performed using various approaches. Clinical history, preoperative and postoperative neurofunction, imaging results, and surgical outcomes were collected for further classification of TNM.ResultsAll TNM cases were divided into anterior (T1), middle (T2), and posterior notch (T3). According to the direction of tumor extension and correlation with the neurovascular structures, detailed subtypes of anterior TNMs were identified as the central (T1a), posterior (T1b), and medial type (T1c). The middle TNMs were divided into the infratentorial (T2a), supratentorial (T2b), and supra-infratentorial type (T2c). The posterior TNMs were divided into superior (T3a), inferior (T3b), lateral (T3c), and straight sinus type (T3d) in reference to Bassiouni’s classification. Total removal of the tumor was achieved in 46 cases, with five cases of subtotal and two cases of partial removal without any recorded deaths in our series. In total, five subtotal resected cases underwent gamma-knife treatment and achieved stable disease. Postoperative aggravation or new onset cranial nerve dysfunction occurred in some individual cases, with incidences ranging from 3.77 to 15.10% and improved preoperative neurological deficits ranging from 0 to 100%.ConclusionFurther, TNM classification based on the intracranial location, extension direction, relationship with brainstem, and neurovascular structures guides preoperative evaluation, rational surgical approach selection, and surgical strategy formulation. Taking microsurgery as the main body, a satisfactory outcome of TNM treatment can be achieved for complicated tumors by combining stereotactic radiotherapy. This study demonstrates the surgical outcomes and complications in detail. Further classification might be helpful for treatment decisions in the future.

Background: Glioblastoma (GBM) is the most malignant intracranial tumor in adults. However, the overall management of GBM in pregnancy is rarely reported. How to balance the therapeutic benefits to the mother and risks to the fetus remains hugely challenging for clinicians. The application of specific targeting therapy combined with conventional treatment sheds light on a longer lifetime for the patients suffering from GBM.Case Presentation: We present a pregnant female at 20 weeks gestation diagnosed with GBM. Surgical resection was initially performed without adjuvant therapy, and the tumor recurred de novo 2 months later. A secondary craniotomy and cesarean section were performed simultaneously at 32 weeks gestation, both the patient and infant were survived. She was subsequently treated with traditional chemo-radiotherapy. No other identified genetic alterations indicating an optimistic prognosis were detected except for BRAF V600E mutation. Thus, the BRAF inhibitor was placed on her with achieving a good clinical outcome of more than 2-year survival without recurrence.Conclusion: Personalized multidisciplinary therapy should be considered when GBMs occur in pregnancy. Response to the therapy in this presenting case suggests that BRAF V600E mutation is a favorable biomarker for GBM. The mortality of GBM might be reduced through genetic testing and targeted treatment. However, more studies must be conducted to confirm our observation.

Immune evasion in glioma strongly correlates with clinical outcomes; however, the molecular mechanisms driving the maintenance of immunosuppression remain largely unknown. Recently studies demonstrate that Klothos are aberrantly expressed in several cancers and are potential therapeutic targets in cancers. However, their roles are still unclear in glioma. Here, we show that LCTL is highly expressed in gliomas and that its expression is regulated by DNA methylation status at the promoter. LCTL expression is also found to be significantly associated with high tumor aggressiveness and poor outcomes for glioma patients. Mechanistically, results suggested that LCTL might play an important immunosuppressive role by recruiting immunosuppressive cells and regulating tumor-associated macrophages polarization, T cell exhaustion, and epithelial–mesenchymal transition through FGF signaling in glioma. Our results establish LCTL as a key biomarker for prognosis that could be considered a potential epigenetic and immunotherapeutic target for treatment.

Objective: Ventricular infection from multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is one of the most severe complications of craniotomy. However, the availability of effective therapeutic options for these infections is limited. Thus, this report aims to describe the efficacy of abscess clearance by intraventricular and intravenous tigecycline therapy in managing patients with multidrug-resistant A. baumannii ventriculitis after neurosurgery. Moreover, the current literature on the use of tigecycline therapy for these life-threatening infections is reviewed and summarized, and a treatment regimen based on the available data is proposed.Methods: A patient with multidrug-resistant A. baumannii ventriculitis was admitted in our hospital and was provided with a detailed therapeutic schedule. Tigecycline treatments for multidrug-resistant A. baumannii ventriculitis that were reported in the literature were also reviewed and summarized.Results: The patient in our hospital underwent abscess clearance on a ventriculoscope and was subsequently subjected to multi-route tigecycline therapy 14 days after the start of the continuous ventricular irrigation (CVI) tigecycline and 3 days after the intraventricular (IVT) tigecycline. The signs of ventriculitis disappeared, and the Acinetobacter cerebrospinal fluid (CSF) load steadily decreased until CSF sterilization. Literature review identified seven cases of ventricular infection from multidrug-resistant A. baumannii treated with tigecycline. In the eight cases, all patients were male adults (>18 years), with a mean age of 46.1 (range: 22–75) years. Meningitis/ventriculitis was secondary to neurosurgery procedures for the management of various central nervous system diseases in all cases. A good clinical outcome was achieved in all eight patients with multidrug-resistant A. baumannii meningitis/ventriculitis treated with CVI and/or IVT tigecycline, and any relevant complications were not observed.Conclusions: CVI and IVT tigecycline and IVT colistin could be considered as the first-line therapy in patients with ventricular infections from MDR/extreme drug-resistant A. baumannii. However, more studies should be conducted to confirm our observation.

The Wufeng and Longmaxi organic-rich shales host the largest shale gas plays in China. This study examined the petrography, rare earth element (REE) and other trace-element geochemistry, Sm-Nd geochronology, and isotope geochemistry (87Sr/86Sr, 18O, 13C) of fracture-cementing minerals within core samples of the Wufeng and Longmaxi Formations from the Jiaoshiba shale gas field in order to (1) characterize the mineral phases occurring in the veins (mineralized fractures); (2) determine the ages of the calcite by the Sm-Nd isochron dating method; (3) understand the sources of calcite-precipitating fluids; and (4) explore the possible mechanisms responsible for calcite vein formation in shale gas systems. The fractures hosted in the Longmaxi Formation are mineralized with quartz as the predominant fracture cement, and calcite as an intracementation phase postdating the earlier quartz cement. In contrast, the fractures hosted in the Wufeng Formation are dominantly mineralized by calcite, which occurs either as the only cement present or as a cement phase predating later quartz cement. Calcite veins within the Longmaxi Formation have a Sm-Nd isochron age of 160 ± 13 Ma and 13C values of -4.71% to -3.11%, 18O values of 17.1%-17.4%, and 87Sr/86Sr values of 0.72437-0.72869. Calcite veins within the Wufeng Formation yielded a Sm-Nd isochron age of 133 ± 15 Ma and are characterized by 13C values of -2.29% to -1.03%, 18O values of 17.3%-17.7%, and 87Sr/86Sr values of 0.72202-0.72648. The similarity between 87Sr/86Sr values of the calcite and those of their respective surrounding host rocks (0.72670-0.72875 of the Longmaxi shales; 0.72030-0.72648 of the Wufeng shales), combined with relatively depleted 13C and uniform fluid 18O isotopic features, indicates that the calcite-precipitating fluids within the Wufeng and Longmaxi Formations were derived largely from their respective surrounding host-rock sources. REE data equally indicate that the distinguishable Eu anomalies (6.20-19.35; 4.45-11.91), Y anomalies (1.03- 1.50; 1.44-1.70), and Y/Ho ratios (28.80- 39.16; 38.86-45.18) of calcite veins within the Longmaxi and Wufeng Formations were controlled by their respective surrounding host rocks. The Sm-Nd isochron ages and fluid inclusion data of fracture cements suggest that fracture opening and calcite precipitation in composite veins within the Wufeng and Longmaxi Formations were triggered by gas generation overpressurization. [ABSTRACT FROM AUTHOR]