Single-cell analysis and machine learning identify psoriasis-associated CD8+ T cells serve as biomarker for psoriasis.

Psoriasis is a chronic inflammatory skin disease, the etiology of which has not been fully elucidated, in which CD8+ T cells play an important role in the pathogenesis of psoriasis. However, there is a lack of in-depth studies on the molecular characterization of different CD8+ T cell subtypes and their role in the pathogenesis of psoriasis. This study aims to further expound the pathogenesy of psoriasis at the single-cell level and to explore new ideas for clinical diagnosis and new therapeutic targets. Our study identified a unique subpopulation of CD8+ T cells highly infiltrated in psoriasis lesions. Subsequently, we analyzed the hub genes of the psoriasis-specific CD8+ T cell subpopulation using hdWGCNA and constructed a machine-learning prediction model, which demonstrated good efficacy. The model interpretation showed the influence of each independent variable in the model decision. Finally, we deployed the machine learning model to an online website to facilitate its clinical transformation.

Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes.

Kleine-Levin syndrome (KLS) is a rare, recurring sleep disorder that easily ignored. Episodic upward-gaze palsy is an uncommon manifestation observed in patients of KLS, which further complicates this disorder. Although peripheral microbial infection have been recognized as most common triggers for KLS, the underlying pathophysiology of this disorder remains unclear. We reported an unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid (CSF) at the early stage. The CSF returned to normal over time while the attacks continued to recur frequently. Episodic upward-gaze palsy was observed during attacks and clinical symptoms were exacerbated following a subsequent COVID-19 infection. This report presents a classic KLS case with distinctive characteristics, which should facilitate more accurate and earlier diagnosis for clinicians. Furthermore, it provides a new perspective for understanding the pathogenesis of this rare disease.

Enhancing water quality and ecosystems of reclaimed water-replenished river: A case study of Dongsha River, Beijing, China.

The use of reclaimed water for urban river replenishment has raised concerns regarding its impact on water quality and aquatic ecosystems. This study aims to reveal the improvements seen in an urban river undergoing a practical water eco-remediation after being replenished with reclaimed water. A one-year monitoring of water quality, phytoplankton, and zooplankton was carried out in Dongsha River undergoing eco-remediation in Beijing, China. The results showed that compared to the unrestored river, the concentrations of COD, NH4+-N, TP, and TN decreased by 28.22 ± 7.88 %, 40.24 ± 11.77 %, 44.17 ± 17.29 %, and 28.66 ± 10.39 % in the restoration project area, respectively. The concentration of Chlorophyll-a in the restoration area was maintained below 40 µg/L. During summer, when algal growth is vigorous, the density of Cyanophyta in the unrestored river decreased from 46.84 × 104cells/L to 16.32 × 104cells/L in the restored area, while that of Chlorophyta decreased from 41.61 × 104cells/L to 11.87 × 104cells/L, a reduction of 65.16 % and 71.47 %, respectively. The dominant phytoplankton species were replaced with Bacillariophyta, such as Synedra sp. and Nitzschia sp., indicating that the restoration of aquatic plants reduces the risk of Cyanophyta blooms. Zooplankton species also changed in the restoration area, especially during summer. The density of pollution-tolerant Rotifer and Protozoa decreased by 31.06 % and 27.22 %, while the density of clean water indicating Cladocera increased by 101.19 %. We further calculated the diversity and evenness index of phytoplankton and zooplankton within and outside the restoration area. The results showed that the Shannon-Weaver index for phytoplankton and zooplankton in the restoration area was 2.1 and 1.91, which was higher than those in the river (1.84 and 1.82). This further confirmed that aquatic plant restoration has positive effects. This study can provide a practical reference and theoretical basis for the implementation of water ecological restoration projects in other reclaimed water rivers in China.

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG).

N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Predictive role of E2F6 in cancer prognosis and responses of immunotherapy.

BACKGROUND: E2F6 is a member of the E2F transcription factor family. Numerous studies have demonstrated that E2F6 is critical to cancer development and progression, but its role in cancer immunotherapy remains unclear. METHODS: Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to obtain RNA-seq data for cancer and normal tissues, and we utilized the cBioPortal to analyze E2F6 genomic alterations in pan-cancer. The protein localization of E2F6 was obtained using the Human Protein Atlas (HPA), and the upregulation of E2F6 expression in clinical glioblastoma multiforme (GBM) tissues was detected by Western blot analysis. The ComPPI website was used to analyze the protein interaction information of E2F6. To evaluate the role of E2F6 in pan-cancer prognosis, we used univariate Cox regression and Kaplan-Meier methods, and gene set enrichment analysis (GSEA) was utilized to identify markers associated with E2F6 expression in tumors. TIMER 2.0 was used to study E2F6-related immune cell infiltration in tumor tissues, and the correlation of E2F6 with immunotherapy biomarkers was investigated using Spearman correlation analysis. The role of E2F6 in the cell cycle was analyzed by flow cytometry, and the Cell Counting Kit-8 (CCK-8) and colony formation assays were utilized to determine the proliferative ability of cells. RESULTS: In most tumor types, E2F6 was highly expressed and was a good predictor of prognosis. E2F6 was significantly related to markers of immune activation, tumor immune cell infiltration, and immune regulators. Furthermore, E2F6 knockdown significantly attenuated the proliferative ability of glioma cells. Finally, E2F6 effectively predicted anti-programmed cell death 1 (PD1) treatment response. CONCLUSION: E2F6 is an effective biomarker that predicts the prognosis of cancer patients treated with anti-immune checkpoint therapy.

Melatonin attenuates chronic sleep deprivation-induced cognitive deficits and HDAC3-Bmal1/clock interruption.

BACKGROUND AND AIMS: Sleep is predicted as a key modulator of cognition, but the underlying mechanisms are poorly understood. In this study, we investigated the effects of melatonin on chronic rapid eye movement sleep deprivation (CRSD)-induced cognitive impairment and circadian dysfunction in rat models. METHODS: Thirty-six Sprague-Dawley male rats were divided into three groups: CRSD with saline treatment, CRSD with chronic melatonin injection (20 mg/kg/day), and non-sleep-deprived control. The cognitive behavioral tests as well as the expression of clocks and HDAC3 were evaluated in all groups. RESULTS: CRSD significantly reduced recognition index in novel object location, increased escape latency and distance traveling in Morris water maze while melatonin treatment attenuated CRSD-induced hippocampal-dependent spatial learning and memory deficits. Furthermore, the mRNAs of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1(Bmal1) and circadian locomotor output cycles kaput (Clock) were globally down-regulated by CRSD with constant intrinsic oscillation in both hippocampus and peripheral blood. The protein levels of hippocampal Bmal1, Clock, and HDAC3 were also remarkably down-regulated following CRSD. Melatonin treatment reversed CRSD-induced alterations of Bmal1/Clock and HDAC3 on both mRNA levels and protein levels. CONCLUSIONS: Our data indicate that melatonin treatment attenuates CRSD-induced cognitive impairment via regulating HDAC3-Bmal1/Clock interaction. These findings explore a broader understanding of the relationship between sleep and cognition and provide a potential new therapeutic target for cognitive impairment.

Characteristics of vitiligo patients with versus without associated autoimmune thyroid disease.

BACKGROUND: Clinical data are limited in patients with vitiligo with or without autoimmune thyroid disease. OBJECTIVES: The objective of the study was to investigate the clinical features and basic data of patients with vitiligo, especially those with autoimmune thyroid disease. METHODS: The study was a single-center retrospective study. A total of 1305 patients with vitiligo from June 2018 to May 2023 were included, and the clinical characteristics and basic information of the patients were recorded in detail. RESULTS: We identified an association between sex (odds ratio [OR]: 2.380; 95% confidence interval [CI]: 1.772-1.198), vitiligo duration (OR: 1.449; 95% CI: 1.076-1.952), skin involvement exceeding 5% of the body surface area (OR: 3.764; 95% CI: 2.134-6.640), negative emotions (OR: 3.076; 95% CI: 2.292-4.127), vitiligo type (OR: 1.974; 95% CI: 1.096-3.555), family history of AITD (OR: 4.979; 95% CI: 2.687-9.225), and family history of AD (OR: 2.418; 95% CI: 1.410-4.146) and patients with vitiligo. CONCLUSIONS: For patients with statistically significant associated risk factors, differential diagnosis and early intervention should be performed.

Gut dysbacteriosis induces expression differences in the adult head transcriptome of Spodoptera frugiperda in a sex-specific manner.

Mounting evidence indicates that the gut microbiota influences the neurodevelopment and behavior of insects through the gut-brain axis. However, it is currently unclear whether the gut microbiota affect the head profiles and immune pathway in pests. Here, we find that gut bacteria is essential for the immune and neural development of adult Spodoptera frugiperda, which is an extremely destructive agricultural pest worldwide. 16 S rRNA sequencing analysis showed that antibiotics exposure significantly disturbed the composition and diversity of gut bacteria. Further transcriptomic analysis revealed that the adult head transcripts were greatly affected by gut dysbacteriosis, and differently expression genes critical for brain and neural development including A4galt, Tret1, nsun4, Galt, Mitofilin, SLC2A3, snk, GABRB3, Oamb and SLC6A1 were substantially repressed. Interestingly, the dysbacteriosis caused sex-specific differences in immune response. The mRNA levels of pll (serine/threonine protein kinase Pelle), PGRP (peptidoglycan-sensing receptor), CECA (cecropin A) and CECB (cecropin B) involved in Toll and Imd signaling pathway were drastically decreased in treated male adults' heads but not in female adults; however, genes of HIVEP2, ZNF131, inducible zinc finger protein 1-like and zinc finger protein 99-like encoding zinc-finger antiviral protein (ZAP) involved in the interferon (IFNα/ß) pathway were significantly inhibited in treated female adults' heads. Collectively, these results demonstrate that gut microbiota may regulate head transcription and impact the S. frugiperda adults' heads through the immune pathway in a sex-specific manner. Our finding highlights the relationship between the gut microbiota and head immune systems of S. frugiperda adults, which is an astonishing similarity with the discoveries of other animals. Therefore, this is the basis for further research to understand the interactions between hosts and microorganisms via the gut-brain axis in S. frugiperda and other insects.

Frontal lobe epilepsy: an eye tracking study of memory and attention.

Objective: To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology. Method: We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker. Results: Memory scale scores of FLE patients including digit span (U = 747.50, p = 0.007), visual recognition (U = 766.50, p = 0.010), and logical memory (U = 544.00, p < 0.001) were significantly lower than HC. The patients with FLE took longer to complete the four levels of difficulty of the short-term memory game than healthy controls (level 1: U = 2974.50, p = 0.000; level 2: U = 3060.50, p = 0.000; level 3: U = 2465.00, p = 0.000; level 4: U = 2199.00, p = 0.000). During the memory decoding period, first fixation on the targets took significantly longer for FLE patients for all difficulty levels compared to controls (level 1: U = 3407.00, p = 0.008; level 2: U = 3618.00, p = 0.036; level 3: U = 3345.00, p = 0.006; level 4: U = 2781.00, p = 0.000). The average fixation duration per target among patients with FLE was found to be significantly longer compared to HC (level 1: U = 2994.50, p = 0.000; level 2: U = 3101.00, p = 0.000; level 3: U = 2559.50, p = 0.000; level 4: U = 2184.50, p = 0.000). The total fixation duration on AOI/total completion time of FLE patients was significantly lower than those of HC for levels 1 to 3 (level 1: U = 1557.00, p = 0.000; level 2: U = 2333.00, p = 0.000; level 3: U = 2757.00, p = 0.000). Furthermore, the eye tracking data during the memory decoding phase were correlated with neuropsychological scale scores (p < 0.05). Conclusion: Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE.

Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis. METHODS: Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis. RESULTS: The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome. CONCLUSION: Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.

Transient polymorphisms in parental care strategies drive divergence of sex roles.

The parental roles of males and females differ considerably between and within species. By means of individual-based evolutionary simulations, we strive to explain this diversity. We show that the conflict between the sexes creates a sex bias (towards maternal or paternal care), even if the two sexes are initially identical. When including sexual selection, there are two outcomes: either female mate choice and maternal care or no mate choice and paternal care. Interestingly, the care pattern drives sexual selection and not vice versa. Longer-term simulations exhibit rapid switches between alternative parental care patterns, even in constant environments. Hence, the evolutionary lability of sex roles observed in phylogenetic studies is not necessarily caused by external changes. Overall, our findings are in striking contrast to the predictions of mathematical models. We show that the discrepancies are caused by transient within-sex polymorphisms in parental strategies, a factor largely neglected in current sex-role theory.

The HNF4A-CHPF pathway promotes proliferation and invasion through interactions with MAD1L1 in glioma.

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferases that participates in the biosynthesis of chondroitin sulfate (CS). Our previous study showed that silencing CHPF expression inhibited glioma cell proliferation in vitro, but the molecular mechanisms by which CHPF contributes to development of glioma have not been characterized. In this study, we found that CHPF was up-regulated in glioma tissues and was positively correlated with malignant clinical pathological characteristics of patients with glioma. Silencing CHPF expression inhibited proliferation, colony formation, migration, and cell cycle of glioma cells. Moreover, silencing CHPF suppressed glioma malignance in vivo. Immunoprecipitation, co-immunoprecipitation, GST pulldown, and liquid chromatography-mass spectrometry (LC-MS/MS) assays were used to verify the interaction between CHPF and Mitotic arrest deficient 1-like 1 (MAD1L1). In addition, Chromatin Immunoprecipitation (ChIP)-PCR analysis showed that HNF4A bound to the CHPF promoter region, which indicated that the transcription factor hepatocyte nuclear factor 4A (HNF4A) could regulate the expression of CHPF in glioma cells.

Clinical Reasoning: A 74-Year-Old Woman Presenting With Monocular Ptosis and Binocular Diplopia.

A 74-year-old woman presented with acute-onset right ptosis and binocular diplopia. CT scan showed low-density lesions in the bilateral basal ganglia and adjacent to lateral ventricles. Intracranial aneurysm was not detected. This case highlights the importance of neurologic localization of ophthalmoplegia based on physical examination and the microanatomy of the oculomotor nerve.

Clinical diagnosis model of spinal meningiomas based on the surveillance, epidemiology, and end results database.

Most spinal meningiomas (SM) are benign lesions of the thoracic spine and are usually treated surgically. This study aimed to explore treatment strategies and construct a nomogram for SM. Data on patients with SM from 2000 to 2019 were extracted from the Surveillance, Epidemiology, and End Results database. First, the distributional properties and characteristics of the patients were descriptively evaluated, and the patients were randomly divided into training and testing groups in a 6:4 ratio. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the survival predictors. Kaplan-Meier curves explained survival probability by different variables. The nomogram was constructed based on the results of LASSO regression. The predictive power of the nomogram was identified using the concordance index, time-receiver operating characteristics, decision curve analysis, and calibration curves. We recruited 1,148 patients with SM. LASSO results for the training group showed that sex (coefficient, 0.004), age (coefficient, 0.034), surgery (coefficient, -0.474), tumor size (coefficient, 0.008), and marital status (coefficient, 0.335) were prognostic factors. The nomogram prognostic model showed good diagnostic ability in both the training and testing groups, with a C-index of 0.726, 95% (0.679, 0.773); 0.827, 95% (0.777, 0.877). The calibration and decision curves suggested that the prognostic model had better diagnostic performance and good clinical benefit. In the training and testing groups, the time-receiver operating characteristic curve showed that SM had moderate diagnostic ability at different times, and the survival rate of the high-risk group was significantly lower than that of the low-risk group (training group: p = 0.0071; testing group: p = 0.00013). Our nomogram prognostic model may have a crucial role in predicting the six-month, one-year, and two-year survival outcomes of patients with SM and may be useful for surgical clinicians to formulate treatment plans.

Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy.

INTRODUCTION: Increasing evidence has revealed the key activity of protein disulfide isomerase A4 (PDIA4) in the endoplasmic reticulum stress (ERS) response. However, the role of PDIA4 in regulating glioblastoma (GBM)-specific pro-angiogenesis is still unknown. METHODS: The expression and prognostic role of PDIA4 were analyzed using a bioinformatics approach and were validated in 32 clinical samples and follow-up data. RNA-sequencing was used to search for PDIA4-associated biological processes in GBM cells, and proteomic mass spectrum (MS) analysis was used to screen for potential PDIA4 substrates. Western blotting, real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assays (ELISA) were used to measure the levels of the involved factors. Cell migration and tube formation assays determined the pro-angiogenesis activity of PDIA4 in vitro. An intracranial U87 xenograft GBM animal model was constructed to evaluate the pro-angiogenesis role of PDIA4 in vivo. RESULTS: Aberrant overexpression of PDIA4 was associated with a poor prognosis in patients with GBM, although PDIA4 could also functionally regulate intrinsic GBM secretion of vascular endothelial growth factor-A (VEGF-A) through its active domains of Cys-X-X-Cys (CXXC) oxidoreductase. Functionally, PDIA4 exhibits pro-angiogenesis activity both in vitro and in vivo, and can be upregulated by ERS through transcriptional regulation of X-box binding protein 1 (XBP1). The XBP1/PDIA4/VEGFA axis partially supports the mechanism underlying GBM cell survival under ER stress. Further, GBM cells with higher expression of PDIA4 showed resistance to antiangiogenic therapy in vivo. CONCLUSIONS: Our findings revealed the pro-angiogenesis role of PDIA4 in GBM progression and its potential impact on GBM survival under a harsh microenvironment. Targeting PDIA4 might help to improve the efficacy of antiangiogenic therapy in patients with GBM.

Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers.

OBJECTIVE: To evaluate the safety and effectiveness of polylactic acid/gelatin nanofibre membranes (PGNMs) in treating hard-to-heal lower extremity venous ulcer wounds. METHOD: In this prospective study, patients with venous leg ulcers (VLUs) were treated with PGNMs or standard of care. Wounds were assessed once a week until the wound was fully healed. RESULTS: The treatment group was comprised of 10 patients with VLUs, aged between 47-64 years, with an average age of 56.58±6.19 years. The wounds were located in the lower leg and/or ankle. Average wound area was 8.91±13.57cm2 (range: 1.5-52.5cm2). Average wound healing time was 18.75±16.36 days. Of the patients, nine (90%) rated their pain as lighter when removing the dressing, with an average pain value of 2.0±1.0 points. There was less secondary trauma to the wound surface, and less bleeding. At six months after the wound healing, the scar evaluation (using the Vancouver Scar Scale) result was 3.75±1.96 points. CONCLUSION: In this study, the PGNMs were safe and effective in treating hard-to-heal lower extremity VLUs.

Intrinsic immune evasion patterns predict temozolomide sensitivity and immunotherapy response in lower-grade gliomas.

BACKGROUND: Although intrinsic immune-evasion is important in cancer proliferation, metastasis and response to treatment, it is unclear whether intrinsic immune-evasion patterns of gliomas can aid in predicting clinical prognosis and determining treatment. METHODS: A total of 182 immune-evasion genes intrinsic to cancer were subjected to consensus clustering to identify immune-evasion patterns in 1421 patients with lower-grade glioma (LGG). The levels of each cancer hallmark were determined by the Gene Set Variant Analysis (GSVA) method, and immune cell infiltrations were quantified using two algorithms, the single-sample Gene Set Enrichment Analysis (ssGSEA) and the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methods. IEVscore was determined by a method that combined univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA). RESULTS: Transcriptional and genomic analysis showed that most immune evasion genes (IEVGs) were upregulated in LGGs, with aberrant expression driven by alterations in copy number variants (CNV). Based on the mRNA expression profiles of cancer-intrinsic IEVGs could be divided into three LGG subgroups with distinct prognosis, clinicopathological features and immune infiltrations. A combined scoring scheme designed to assess the immune-evasion levels of LGGs divided these 1421 patients into two subgroups that differed in IEVscores. LGG patients with low-IEVscore had a better prognosis, would be more likely to benefit from immune check-point inhibitors and would be more susceptible to temozolomide (TMZ) chemotherapy. CONCLUSION: Intrinsic immune evasion in the tumor microenvironment (TME) has a crucial effect on glioma formation. Quantitatively assessing the IEV scores of individual LGG patients could enhance knowledge about the intra-glioma microenvironment and lead to the development of individualized therapeutic strategies for patients with LGG.

Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer.

BACKGROUND: The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored. METHODS: We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx). RESULTS: Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells. CONCLUSIONS: Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

Immune Characteristics and Prognosis Analysis of the Proteasome 20S Subunit Beta 9 in Lower-Grade Gliomas.

Glioma is a common intracranial malignancy in adults and has a high mortality due to its poor prognosis and high recurrence rate. Dysregulation of protein degradation is one of the main promoting factors in glioma development. As an indispensable unit of the proteasome, Proteasome 20S Subunit Beta 9 (PSMB9) is one of the major enzymes in ubiquitin-dependent protein degradation in cells. In addition, proteasomes also participate in a series of cellular processing, like immune regulation, nerve signal transduction, material transport through channels, cell adhesion, and various signaling pathways. However, the relationship between the PSMB9 expression and the occurrence of lower-grade glioma (LGG) is still unknown. First, we collected the RNA-seq and clinical information about LGG clinical samples from The Cancer Genome Atlas (TCGA) cohort, Chinese Glioma Genome Atlas (CGGA; including CGGAseq1 and CGGAseq2) cohort, and Gene Expression Omnibus (GEO; GSE16011, GSE61374, and Rembrandt) cohort. Then, these data were used for differential analysis, survival analysis, enrichment analysis, clinical model construction, etc. In addition, we combine immune-related data for immune-related analysis, including immune infiltration and immunotherapy. Through the above research, we have provided a new biomarker for LGG prognosis prediction and more comprehensively explained the role of PSMB9 in the development of LGG. This study determined that PSMB9 can be used as an immunotherapy target through the analysis of immune data, providing new ideas for the clinical treatment of LGG.