Recurrent PTPRZ1-MET fusion and a high occurrence rate of MET exon 14 skipping in brain metastases.

Identifying molecular features is an essential component of the management and targeted therapy of brain metastases (BMs). The molecular features are different between primary lung cancers and BMs of lung cancer. Here we report the DNA and RNA mutational profiles of 43 pathological samples of BMs. In addition to previously reported mutational events associated with targeted therapy, PTPRZ1-MET, which was previously exclusively identified in glioma, was present in two cases of BMs of lung cancer. Furthermore, MET exon 14 skipping may be more common (6/37 cases) in BMs of lung cancer than the frequency previously reported in lung cancer. These findings highlight the clinical significance of targeted DNA plus RNA sequencing for BMs and suggest PTPRZ1-MET and MET exon 14 skipping as critical molecular events that may serve as targets of targeted therapy in BMs.

Systematically profiling the expression of eIF3 subunits in glioma reveals the expression of eIF3i has prognostic value in IDH-mutant lower grade glioma.

BACKGROUND: Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown. METHODS: Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (n = 272) and The Cancer Genome Atlas (TCGA) (n = 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction. RESULTS: In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588)] and TCGA [eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others. CONCLUSIONS: Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.

[Study on the Interaction in Resveratrol-Hordein Nanoparticle].

In order to clarify the interaction mechanism of the formation of the resveratrol-hordein nanoparticle, the fluorescence, UV-Vis spectroscopic, FTIR and DSC were used to study the binding reaction between resveratrol and hordein. The fluorescent emission of hordein was inhibited by resveratrol in a dose dependent manner. Fluorescence spectroscopy and DSC indicated that resveratrol interacted with hordein and formed a new complex by a static process. The binding constant (K(A(298 K)) = 2.21 x 10(5) L x mol(-1), K(A(310 K)) =1.53 x 10(4) L x mol(-1)) and the number of binding sites ((n298 K) = 1.23, (n310 K) 0.94) were calculated based on the quenching effect of resveratrol on hordein. Thermodynamic parameter and FTIR indicated that the interaction force between resveratrol and hordein was mainly hydrogen binding and van der Waals force. The binding distance (r0 = 3. 25 nm) between resveratrol and hordein and the energy transfer efficiency (E = 0.227) were obtained according to non-radiative energy transfer theory. The effect of resveratrol on the conformation of hordein was further analyzed by using synchronous fluorescence spectrometry. The results indicated that resveratrol changed the hydrophobicity of tryptophan residue, which caused an obvious influence on the conformation of hordein.

Sporadic meningioangiomatosis with and without meningioma: analysis of clinical differences and risk factors for poor seizure outcomes.

BACKGROUND: Meningioangiomatosis (MA) is a rare cerebral lesion. Sporadic MA occasionally combines with meningioma (MA-M). The aim of the present study was to clarify whether MA-M and pure MA have clinical differences and to determine risk factors for unsatisfactory seizure outcomes in sporadic MA. METHODS: We reported 14 sporadic MA cases in our center and conducted a literature review. We compared the demographic, clinical, imaging, electrophysiological and pathological features and surgical outcomes. Logistic regression analysis was performed to evaluate the risk factors for poor seizure outcomes. RESULTS: MA-M cases showed a more prominent male predilection (4.2 times vs. 1.6 times, p = 0.04), a shorter duration of symptoms (2.8 ± 0.8 years vs. 5.2 ± 0.6 years, p = 0.02), and a lower seizure incidence (53.6 % vs. 89.3 %, p < 0.001) as compared to pure MA. A gyriform alteration on imaging was exclusively associated with pure MA. The Ki-67 was higher in the meningioma component than in the MA component in MA-M (1.2 ± 0.3 % vs. 6.1 ± 1.1 %, p < 0.001). Lesions located in the temporal lobe predicted poor seizure outcomes (p = 0.02, OR = 4.4, 95 % confidence interval, 1.24-15.89). CONCLUSION: Clinical differences may be caused by the different biological natures. MA-M seems to be a neoplastic lesion, while pure MA seems to be a non-neoplastic lesion. Long-term follow-up is required for MA-M. Because the coexistence of hippocampal sclerosis may explain the poor seizure outcomes of MA located in the temporal lobe, it is important to identify underlying hippocampal sclerosis and to perform complete resection.

[Clinicopathologic features of papillary tumors of the pineal region].

OBJECTIVE: To study the clinicopathologic features of papillary tumor of the pineal region (PTPR). METHOD: Three hundred and eighty six cases of pineal region and posterior third ventricle tumors, two newborn and two adult pineal glands were analyzed by HE, PAS and immunohistochemistry of 16 antibodies (EnVision method). RESULTS: Five cases of PTPR were diagnosed with mixed papillary features and densely cellular areas, and included one recurrent case. In the papillary areas, the vessels were lined by one or several layers of cuboidal/columnar cells; the vessel wall was hyalinized. In the densely cellular areas, sheets or nests of tumor cells were seen. The tumor cells of these five cases were immunoreactive to CK, CK8/18, synaptophysin, MAP2, nestin, S-100, and vimentin. Four cases were immunoreactive to NSE and CgA; and 2 cases were immunoreactive to NF. All five cases were negative for EMA, CK5/6, CEA, and NeuN. Ki-67 labeling index ranged from 1% to 6%.Three patients were alive, and the recurrent one died. CONCLUSIONS: PTPR occurs in patients with over a wide age range, from children to adults, and is more commonly found in male than female. PTPR is composed of both papillary and solid areas, characterized by epithelial cytology, and needs to be differentiated from ependymoma. PTPR may originate from the specialized ependymocytes of the subcommissural organ. The prognostic factors are early diagnosis, complete surgical resection and radiotherapy.

Update on Radiotherapy Changes of Nasopharyngeal Carcinoma Tumor Microenvironment.

The utilization of radiotherapy (RT) serves as the principal approach for managing nasopharyngeal carcinoma (NPC). Consequently, it is imperative to investigate the correlation between the radiation microenvironment and radiation resistance in NPC. PubMed and China National Knowledge Infrastructure (CNKI) databases were accessed to perform a search utilizing the English keywords "nasopharyngeal cancer", "radiotherapy", and "microenvironment". The search time spanned from the establishment of the database until January 20, 2023. A total of 82 articles were included. The post-radiation tumor microenvironment (TME), or the radiation microenvironment, includes several components, such as the radiation-immune microenvironment and the radiation-hypoxic microenvironment. The radiation-immune microenvironment includes various factors like immune cells, signaling molecules, and extracellular matrix. RT can reshape the TME, leading to immune responses with both cytotoxic effects (T cells, B cells, natural killer (NK) cells) and immune escape mechanisms (regulatory T cells (Tregs), macrophages). RT enhances immune responses through DNA release, type I interferons, and immune cell recruitment. Radiation-hypoxic microenvironment affects metabolism and molecular changes. RT-induced hypoxia causes vascular changes, fibrosis, and vessel compression, leading to tissue hypoxia. Hypoxia activates hypoxia-inducible factor (HIF)-1α/2α, promoting angiogenesis and glycolysis in tumor cells. TME changes due to hypoxia also involve immune suppressive cells like myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Tregs. The radiation microenvironment is involved in radiation resistance and holds a significant effect on the prognosis of patients with NPC. Exploring the radiation microenvironment provides new insights into RT and NPC research.

Determination of volatile flavor compounds in raw and treated duck meats of different body parts.

The compounds in volatile flavor substances in duck meats of three different body parts (breast, leg, and wing) were extracted by headspace solid-phase micro-extraction and determined by gas chromatography-mass spectrometry. A total of 16 main volatile compounds including 4 hydrocarbons, 4 alcohols, 2 acids, 3 aldehydes, and 3 others (N-containing, S-containing) were identified in raw duck meats from three different body parts. The hydrocarbon compounds account for more than 50% of all volatile substances in all three body parts. And the percentage of hydrocarbon compounds in raw duck breast meat reaches 82.76%. A total of 81 volatile compounds including 15 hydrocarbons, 10 alcohols, 7 acids, 12 aldehydes, 4 esters, 19 S-containing and N-containing compounds, and 14 others were isolated and identified in 1 hr-marinated and cooked duck meats. A total of 101 kinds of volatile flavor compounds including 13 hydrocarbons, 14 alcohol, 7 acids, 8 aldehydes, 12 esters, 23 S-containing and N-containing compounds, and 24 others were detected in 3 hr-marinated duck meats of the three body parts. It was proved in this study that under the same conditions, the volatile compounds in duck legs are more than those in duck breasts and wings, and the types of volatile flavor substances increase significantly in duck meats after cooked. PRACTICAL APPLICATIONS: Prepared and cooked duck meat, especially wings and legs are popular food in China. The results suggest that Pickling makes duck meat more flavory while proper pickling time is less than 3 hr. Duck wings are better for marinating and cooking compared with duck breasts and legs. The acceptance study of duck meat from different body parts and the analysis of volatile flavor compounds are beneficial for optimizing utilization of whole parts of duck meat.

Gene Expression Profiling Stratifies IDH-Wildtype Glioblastoma With Distinct Prognoses.

Objectives: In the present study, we aimed to determine the candidate genes that may function as biomarkers to further distinguish patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM), which are heterogeneous with respect to clinical outcomes. Materials and Methods: We selected 41 candidate genes associated with overall survival (OS) using univariate Cox regression from IDH-wildtype GBM patients based on RNA sequencing (RNAseq) expression data from the Chinese Glioma Genome Atlas (CGGA, n = 105) and The Cancer Genome Atlas (TCGA, n = 139) cohorts. Next, a seven-gene-based risk signature was formulated according to Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm in the CGGA RNAseq database as a training set, while another 525 IDH-wildtype GBM patient TCGA datasets, consisting of RNA sequencing and microarray data, were used for validation. Patient survival in the low- and high-risk groups was calculated using Kaplan-Meier survival curve analysis and the log-rank test. Uni-and multivariate Cox regression analysis was used to assess the prognosis value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were performed for the functional analysis of the seven-gene-based risk signature. Results: We developed a seven-gene-based signature, which allocated each patient to a risk group (low or high). Patients in the high-risk group had dramatically shorter overall survival than their low-risk counterparts in three independent cohorts. Univariate and multivariate analysis showed that the seven-gene signature remained an independent prognostic factor. Moreover, the seven-gene risk signature exhibited a striking prognostic validity, with AUC of 78.4 and 73.9%, which was higher than for traditional "age" (53.7%, 62.4%) and "GBM sub-type" (57.7%, 52.9%) in the CGGA- and TCGA-RNAseq databases, respectively. Subsequent bioinformatics analysis predicted that the seven-gene signature was involved in the inflammatory response, immune response, cell adhesion, and apoptotic process. Conclusions: Our findings indicate that the seven-gene signature could be a potential prognostic biomarker. This study refined the current classification system of IDH-wildtype GBM and may provide a novel perspective for the research and individual therapy of IDH-wildtype GBM.

A Novel DNA Methylation-Based Signature Can Predict the Responses of MGMT Promoter Unmethylated Glioblastomas to Temozolomide.

Glioblastoma (GBM) is the most malignant glioma, with a median overall survival (OS) of 14-16 months. Temozolomide (TMZ) is the first-line chemotherapy drug for glioma, but whether TMZ should be withheld from patients with GBMs that lack O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is still under debate. DNA methylation profiling holds great promise for further stratifying the responses of MGMT promoter unmethylated GBMs to TMZ. In this study, we studied 147 TMZ-treated MGMT promoter unmethylated GBM, whose methylation information was obtained from the HumanMethylation27 (HM-27K) BeadChips (n = 107) and the HumanMethylation450 (HM-450K) BeadChips (n = 40) for training and validation, respectively. In the training set, we performed univariate Cox regression and identified that 3,565 CpGs were significantly associated with the OS of the TMZ-treated MGMT promoter unmethylated GBMs. Functional analysis indicated that the genes corresponding to these CpGs were enriched in the biological processes or pathways of mitochondrial translation, cell cycle, and DNA repair. Based on these CpGs, we developed a 31-CpGs methylation signature utilizing the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. In both training and validation datasets, the signature identified the TMZ-sensitive GBMs in the MGMT promoter unmethylated GBMs, and only the patients in the low-risk group appear to benefit from the TMZ treatment. Furthermore, these identified TMZ-sensitive MGMT promoter unmethylated GBMs have a similar OS when compared with the MGMT promoter methylated GBMs after TMZ treatment in both two datasets. Multivariate Cox regression demonstrated the independent prognostic value of the signature in TMZ-treated MGMT promoter unmethylated GBMs. Moreover, we also noticed that the hallmark of epithelial-mesenchymal transition, ECM related biological processes and pathways were highly enriched in the MGMT unmethylated GBMs with the high-risk score, indicating that enhanced ECM activities could be involved in the TMZ-resistance of GBM. In conclusion, our findings promote our understanding of the roles of DNA methylation in MGMT umethylated GBMs and offer a very promising TMZ-sensitivity predictive signature for these GBMs that could be tested prospectively.

Effective extraction of elastase from Bacillus sp. fermentation broth using aqueous two-phase system.

This paper presents the evaluation of an aqueous two-phase system (ATPS) for extracting elastase produced by Bacillus sp. EL31410. The elastase and cell partition behavior in polyethylene glycol (PEG)/salt systems was investigated. The suitable system for elastase extraction was PEG/KH(2)PO(4)-K(2)HPO(4), in which elastase is mainly partitioned into the PEG-rich phase, while the cells remained in the other phase. The influence of defined system parameters (e.g. PEG molecular mass, pH, NaCl addition) on the partitioning behavior of elastase is described. The concentration of phase forming components, PEG and KH(2)PO(4)-K(2)HPO(4), was optimized for elastase recovery by means of response surface methodology, and it was found that they greatly influenced extraction recovery. The optimal ATPS was 23.1% (w/w) PEG 2 000 and 11.7% (w/w) KH(2)PO(4)-K(2)HPO(4). The predicted recovery was about 89.5%, so this process is suggested to be a rapid and convenient method for elastase extraction.

Effect of temperature on batch elastase production by Bacillus sp. EL31410.

The production of elastase by Bacillus sp. EL31410 at various temperatures was investigated. In order to study the effect of temperature on elastase fermentation, different cultivation temperatures, ranging from 39 degrees C to 28 degrees C, were evaluated in shake flask. The result indicated that 37 degrees C was best for cell growth at earlier stage; while maximum elastase activity was obtained when the cells were cultivated at 30 degrees C. This result was verified by batch fermentation in 5-L bioreactor under 37 degrees C and 30 degrees C temperature, respectively. The specific cell growth rate at 37 degrees C was higher than that at 30 degrees C during earlier stage of cultivation. The maximum value [5.5 U/(h x g DCW)] of elastase formation rate occurred at 24 h at 30 degrees C compared to 4.6 U/(h x g DCW) at 30 h at 37 degrees C. Based on these results, two-stage temperature shift strategy and oscillatory temperature cultivation mode were evaluated in the next study. When compared to single temperature of 37 degrees C or 30 degrees C, both two-stage temperature shift strategy and oscillatory temperature strategy improved biomass but did not yield the same result as expected for elastase production. The maximum biomass (both 8.6 g/L) was achieved at 30 h at 37 degrees C, but at 42 h using two-stage temperature cultivation strategy. The highest elastase production (652 U/ml) was observed at 30 degrees C in batch process. It was concluded that cultivation at constant temperature of 30 degrees C was appropriate for elastase production by Bacillus sp. EL31410.