Preoperative peripheral inflammatory markers are predictors of postoperative central diabetes insipidus in craniopharyngioma patients: a retrospective study.

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

A novel EGFR variant EGFRx maintains glioblastoma stem cells through STAT5.

BACKGROUND: Glioblastomas are universally lethal brain tumors containing tumor-propagating glioblastoma stem cells (GSCs). EGFR gene amplification or mutation is frequently detected in GBMs and is associated with poor prognosis. However, EGFR variants in GSCs and their role in the maintenance of GSCs and progression of GBM are unclear. METHODS: EGFR variants were detected through bioinformatic HISAT-StringTie-Ballgown pipeline and verified through 5' RACE, RT-PCR, ribonuclease protection, and northern blotting assays. EGFRx function was investigated through neurosphere, cell viability, intracranial xenograft and RNA-seq assays. EGFRx-STAT5 signaling was investigated through western blotting, coimmunoprecipitation, immunofluorescence, luciferase reporter, RT-PCR and CUT&Tag assays. RESULTS: We identified a novel EGFR variant (EGFRx), that is specifically expressed in GSCs. Unlike the EGFRvIII variant, which lacks exons 2-7, EGFRx is characterized by the absence of exons 2-14, and encodes an EGFR protein that does not possess the entire extracellular ligand-binding domain. We observed that EGFRx exhibits significant glycosylation, is required for GSC self-renewal, proliferation, and tumorigenesis, and highly active in glioblastomas compared to normal brain tissue. Mechanistically, EGFRx constitutively and specifically activates STAT5 in GSCs through spontaneous asymmetric dimerization of the kinase domain. CONCLUSIONS: EGFRx plays essential roles in the maintenance of the GSC phenotype through constitutive activation of STAT5 and promotes GBM progression, suggesting that EGFRx-STAT5 signaling represents a promising therapeutic target for GBM.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Hypoxia-induced galectin-8 maintains stemness in glioma stem cells via autophagy regulation.

BACKGROUND: Glioma stem cells (GSCs) are the root cause of relapse and treatment resistance in glioblastoma (GBM). In GSCs, hypoxia in the microenvironment is known to facilitate the maintenance of stem cells, and evolutionally conserved autophagy regulates cell homeostasis to control cell population. The precise involvement of autophagy regulation in hypoxic conditions in maintaining the stemness of GSCs remains unclear. METHODS: The association of autophagy regulation and hypoxia was first assessed by in silico analysis and validation in vitro. Glioma databases and clinical specimens were used to determine galectin-8 (Gal-8) expression in GSCs and human GBMs, and the regulation and function of Gal-8 in stemness maintenance were evaluated by genetic manipulation in vitro and in vivo. How autophagy was stimulated by Gal-8 under hypoxia was systematically investigated. RESULTS: Hypoxia enhances autophagy in GSCs to facilitate self-renewal, and Gal-8 in the galectin family is specifically involved and expressed in GSCs within the hypoxic niche. Gal-8 is highly expressed in GBM and predicts poor survival in patients. Suppression of Gal-8 prevents tumor growth and prolongs survival in mouse models of GBM. Gal-8 binds to the Ragulator-Rag complex at the lysosome membrane and inactivates mTORC1, leading to the nuclear translocation of downstream TFEB and initiation of autophagic lysosomal biogenesis. Consequently, the survival and proliferative activity of GSCs are maintained. CONCLUSIONS: Our findings reveal a novel Gal-8-mTOR-TFEB axis induced by hypoxia in the maintenance of GSC stemness via autophagy reinforcement, highlighting Gal-8 as a candidate for GSCs-targeted GBM therapy.

Development of hydroxypropyl cellulose and graphene oxide modified molecularly imprinted polymers for separation and enrichment of podophyllotoxin.

A novel hydroxylpropyl cellulose (HPC) modified graphene oxide (GO)-based molecularly imprinted polymers (HPC-GO-MIP) have been developed as a solid phase extraction (SPE) material for the selective separation and extraction of podophyllotoxin. In this strategy, the cellulose with rich hydroxyl groups was introduced to form bi-functional monomers with methacrylic acid to provide more recognition sites for the improving of extraction efficiency, then GO was added as a two-dimensional substrate for MIP to improve the material morphology and surface area. The extraction performances of obtained HPC-GO-MIP material were tested, and the results prove its high efficiency and selectivity for podophyllotoxin extraction. The saturated adsorption capacity reached 23.1 µg/mg, and high enrichment efiiciency of 463.8 folds was realized under the premise of ensuring the recovery rate. The selective imprinting factor was much higher than those of kaempferol and quercetin, which were the main compounds in podophyllum fruit. Under the optimized SPE conditions, the HPC-GO-MIP based SPE-HPLC method showed the detection limit of 14.2 ng/mL for podophyllotoxin assay. When applied to podophyllum fruit samples, the material showed excellent ability of selective separation and enrichment of podophyllotoxin, and the relative standard deviations (RSD) of intra and inter batches were less than 8.1 % and 5.7 % in real samples detection. The HPC-GO-MIP SPE method broadened the application for high multiple extraction in trace analyte samples and provided a valuable solution to improve the selective separation and detection.

Ultrasonic Vibration-Assisted Stamping of Serpentine Micro-Channel for Titanium Bipolar Plates Used in Proton-Exchange Membrane Fuel Cell.

Metallic bipolar plates (BPPs) are key components in the proton-exchange membrane fuel cell (PEMFC), which can replace traditional fossil fuels as a kind of clean energy. However, these kinds of plates, characterized by micro-channels with a high ratio between depth and width, are difficult to fabricate with an ultra-thin metallic sheet. Then, ultrasonic-vibration-assisted stamping is performed considering the acoustic softening effect. Additionally, the influence of various vibration parameters on the forming quality is analyzed. The experimental results show that ultrasonic vibration can obviously increase the channel depth. Among the vibration parameters, the vibration power has the maximum influence on the depth, the vibration interval time is the second, and the vibration duration time is the last. In addition, the rolling direction will affect the channel depth. When the micro-channels are parallel to the rolling direction, the depth of a micro-channel is the largest. This means that the developed ultrasonic-vibration-assisted stamping process is helpful for improving the forming limitation of micro-channels used for the bipolar plates in PEMFC.

Risk Factor and Replacement Therapy Analysis of Pre- and Postoperative Endocrine Deficiencies for Craniopharyngioma.

BACKGROUND: Pituitary hormone deficiency (PHD) is one of the most common symptoms and postoperative complications of craniopharyngiomas (CPs). However, the risk factors for PHD in CPs are little known. The purpose of this study was to analyze the risk factors of pre- and postoperative PHD and to investigate replacement therapy for CP patients. METHODS: A retrospective study of 126 patients diagnosed with CP was performed. Univariate analysis was performed using Pearson's chi-squared test or Fisher's exact test, and a multiple logistic binary regression model was used to identify the influencing factors of pre- and postoperative PHD in craniopharyngioma. RESULTS: Children and patients with hypothalamic involvement were more likely to have preoperative PHD. Patients with suprasellar lesions had a high risk of postoperative PHD, and preoperative PHD was a risk factor for postoperative PHD. CONCLUSION: Children have a high incidence of preoperative PHD. Preoperative PHD can serve as an independent risk factor for postoperative PHD. Preoperative panhypopituitarism can serve as an indication of pituitary stalk sacrifice during surgery. The management of replacement therapy for long-term postoperative endocrine hormone deficiency in patients with craniopharyngioma should be enhanced.

Targeting FGL2 in glioma immunosuppression and malignant progression.

Glioblastoma (GBM) is the most malignant type of glioma with the worst prognosis. Traditional therapies (surgery combined with radiotherapy and chemotherapy) have limited therapeutic effects. As a novel therapy emerging in recent years, immunotherapy is increasingly used in glioblastoma (GBM), so we expect to discover more effective immune targets. FGL2, a member of the thrombospondin family, plays an essential role in regulating the activity of immune cells and tumor cells in GBM. Elucidating the role of FGL2 in GBM can help improve immunotherapy efficacy and design treatment protocols. This review discusses the immunosuppressive role of FGL2 in the GBM tumor microenvironment and its ability to promote malignant tumor progression while considering FGL2-targeted therapeutic strategies. Also, we summarize the molecular mechanisms of FGL2 expression on various immune cell types and discuss the possibility of FGL2 and its related mechanisms as new GBM immunotherapy.

Prognostic Value and Biological Function of Galectins in Malignant Glioma.

Malignant glioma is the most common solid tumor of the adult brain, with high lethality and poor prognosis. Hence, identifying novel and reliable biomarkers can be advantageous for diagnosing and treating glioma. Several galectins encoded by LGALS genes have recently been reported to participate in the development and progression of various tumors; however, their detailed role in glioma progression remains unclear. Herein, we analyzed the expression and survival curves of all LGALS across 2,217 patients with glioma using The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Rembrandt databases. By performing multivariate Cox analysis, we built a survival model containing LGALS1, LGALS3, LGALS3BP, LGALS8, and LGALS9 using TCGA database. The prognostic power of this panel was assessed using CGGA and Rembrandt datasets. ESTIMATE and CIBERSORT algorithms confirmed that patients in high-risk groups exhibited significant stromal and immune cell infiltration, immunosuppression, mesenchymal subtype, and isocitrate dehydrogenase 1 (IDH1) wild type. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), CancerSEA, and Gene Set Enrichment Analysis (GSEA) showed that pathways related to hypoxia, epithelial-to-mesenchymal transition (EMT), stemness, and inflammation were enriched in the high-risk group. To further elucidate the function of LGALS in glioma, we performed immunohistochemical staining of tissue microarrays (TMAs), Western blotting, and cell viability, sphere formation, and limiting dilution assays following lentiviral short hairpin RNA (shRNA)-mediated LGALS knockdown. We observed that LGALS expression was upregulated in gliomas at both protein and mRNA levels. LGALS could promote the stemness maintenance of glioma stem cells (GSCs) and positively correlate with M2-tumor-associated macrophages (TAMs) infiltration. In conclusion, we established a reliable survival model for patients with glioma based on LGALS expression and revealed the essential roles of LGALS genes in tumor growth, immunosuppression, stemness maintenance, pro-neural to mesenchymal transition, and hypoxia in glioma.

Clinical Features, Diagnosis, and Treatment of Primary Intraventricular Lymphoma: Insights From a Monocentric Case Series.

Objective: Primary ventricular lymphoma (PVL) is an extremely rare and commonly misdiagnosed disease. Previous studies were predominantly case reports, and literature regarding the diagnosis and treatment of PVL is limited. Therefore, this study aimed to evaluate the characteristics of patients with PVL. Methods: The data of patients with pathologically confirmed PVL were assessed. Epidemiological data, imaging findings, surgery, pathological results, and prognosis were retrospectively analyzed. A systematic review of relevant literature was also conducted. Results: A total of eight patients with PVL were identified. The main symptom was increased intracranial pressure. Radiographically, five patients had single lesion and three had multiple lesions; typical findings on magnetic resonance imaging included hypointensity on T1- and T2-weighted imaging, adjacent brain edema, and homogeneous enhancement on contrast-enhanced T1-weighted images. Preoperatively, six cases were misdiagnosed and two cases did not get a definite diagnosis. Craniotomy was performed on all patients, and four achieved gross total resection. Hydrocephalus was relieved after surgical resection in four patients. Pathology revealed diffuse large B-cell lymphoma in all patients. Only one patient had a severe complication. A total of three patients received concomitant adjuvant treatment, whereas five patients refused any adjuvant therapy. At the time of follow-up, the median survival time of patients was 15 months. Conclusion: Primary ventricular lymphoma mainly presented with symptoms of increased intracranial pressure and had several imaging characteristics for the diagnosis, but the condition still tends to be misdiagnosed. Surgical resection is a feasible treatment for patients with isolated nodules, especially those with acute obstructive hydrocephalus.

Investigation on Microsheet Metal Deformation Behaviors in Ultrasonic-Vibration-Assisted Uniaxial Tension with Aluminum Alloy 5052.

Ultrasonic vibration (UV) is widely used in the forming, joining, machining process, etc. for the acoustic softening effect. For parts with small dimensions, UV with limited output energy is very suitable for the microforming process and has been gaininf more and more attention. In this investigation, UV-assisted uniaxial tensile experiments were carried out utilizing GB 5052 thin sheets of different thicknesses and grain sizes, respectively. The coupling effects of UV and the specimen dimension on the properties of the material were analyzed from the viewpoint of acoustic energy in activating dislocations. A reduction of flow stress was found for the existing acoustic softening effects of UV. Additionally, the residual effects of UV were demonstrated when UV was turned off. The uniform deformation ability of thin sheet could be improved by increasing the hardening exponent with UV. The experimental results indicate that UV is very helpful in improving the forming limit in microsheet forming, e.g., microbulging and deep drawing processes.

Investigation of Electrically-Assisted Rolling Process of Corrugated Surface Microstructure with T2 Copper Foil.

Electrically-assisted (EA) forming is a low-cost and high-efficiency method to enhance the formability of materials. In the study, EAF tensile tests are carried out to study the properties of T2 copper foil in an annealed state, and the effect of the electric current on the forming quality of corrugated foils is further studied in the EA rolling forming process. The result shows that the current reduces the flow stress and the fracture strain, which is different from the result of rolled samples. The joule heating effect on mechanical properties is significant in EA tension, and the softening effect of the surface layer can be observed at tensile strength, due to the grain size effect. Moreover, the current can weaken the grain size effect. In the rolling forming process, the influence of different electrical parameters on the forming height is remarkable, especially for the rolled T2 copper. The appropriate electrical parameters can improve the forming height, while keeping a small thickness thinning. Nevertheless, the high current density will lead to local rupture. This study proves that the current can improve the forming quality of the corrugated foils and is a promising surface texture forming process.

Graphene oxide based molecularly imprinted polymers modified with ß-cyclodextrin for selective extraction of di(2-ethylhexyl) phthalate in environmental waters.

Graphene oxide based molecularly imprinted polymers modified with ß-cyclodextrin were prepared as solid-phase extraction column sorbents for specific recognition and sensitive detection of di(2-ethylhexyl) phthalate in water samples. The morphology and composition of synthesized sorbents were characterized by scanning electron microscopy, thermo-gravimetric analysis, Raman spectroscopy, and Fourier-transform infrared spectroscopy. The conditions affecting the performance of extraction procedures such as desorption solvent types and volume, sample pH and volume were investigated. The loading capacity (8.2 µg/mg) of the prepared sorbents increased eight times after modification with ß-cyclodextrin. The developed extraction procedures coupled to high-performance liquid chromatography exhibited good linearity (0.2-500 µg/L), low limit of detection (0.052 µg/L), and good precision (relative standard deviation˂5.7%) under optimized conditions. The developed solid-phase extraction technique with prepared sorbents has been successfully applied in extracting trace di(2-ethylhexyl) phthalate from real natural waters with high efficiency, good selectivity, and desirable recoveries.

Dispersive solid-phase microextraction with graphene oxide based molecularly imprinted polymers for determining bis(2-ethylhexyl) phthalate in environmental water.

A novel graphene oxide-molecularly imprinted polymers (GO-MIPs) was prepared and applied for selective extraction and preconcentration of bis(2-ethylhexyl) phthalate (DEHP) in environmental water samples by using the dispersive solid-phase microextraction (DSPME) method. The GO-MIPs was synthesized via precipitation polymerization using GO, DEHP, methacrylic acid, and ethylene dimethacrylate as supporting materials, template molecules, functional monomer, and cross-linker, respectively. The prepared GO-MIPs were characterized by scanning electron microscope and Fourier transform infrared spectroscopy. The GO-MIPs-DSPME conditions including type and volume of elution solvents, adsorbents amount, initial concentration of DEHP, pH and ionic strength of water samples were investigated. Under optimized conditions, the DEHP was selectively and effectively extracted in real water samples and enrichment factors of over 100-fold were achieved. Good linearity was obtained with correlation coefficients (R2) over 0.999 and the detection limit (S/N=3) was 0.92ngmL-1. The average recoveries of the spiked samples at three concentration levels of DEHP ranged from 82% to 92% with the relative standard deviations less than 6.7%. The results indicated that the proposed GO-MIPs-DSPME extraction protocol combined with HPLC-UV determination could be applied for selective and sensitive analysis of trace DEHP phthalate in environmental water samples.

Occurrence and photodegradation of methylmercury in surface water of Wen-Rui-Tang River network, Wenzhou, China.

The spatial distribution and seasonal variations of methylmercury (MeHg) in Wen-Rui-Tang (WRT) River network were investigated by monitoring the MeHg concentrations in surface water samples collected from 30 sites across the river network over four seasons. Detection frequencies and concentrations of MeHg were generally higher in January, indicating that low sunlight irradiation, wind speed, and temperature conditions might enhance the persistence of MeHg in surface water. The MeHg levels varied with sampling locations, with the highest concentrations being observed in the industrial area especially around wastewater outfall, revealing that the mercury contamination in WRT River mainly comes from the industrial wastewater. Photodegradation of MeHg in WRT River surface water and the effects of natural constituents such as fulvic acid (FA), ferric ions (Fe3+), nitrate (NO3-), and dissolved oxygen on the MeHg photodegradation in aqueous solutions were studied under the simulated sunlight. The experimental data indicated that the indirect photodecomposition of MeHg occurred in WRT River surface water. Photodegradation of MeHg in FA solution was initiated by triplet 3FA* or MeHg-FA* via electron transfer interaction under light irradiations. The Fe3+ and NO3- can absorb light energy to produce ·OH and enhance the photochemical degradation of MeHg. The MeHg photodecompositions in FA, nitrate, and Fe3+ solutions were markedly accelerated after removing the dissolved oxygen.