Prognostic significance of a 3-gene ferroptosis-related signature in lung cancer via LASSO analysis and cellular functions of UBE2Z.

Ferroptosis is a newly identified form of non-apoptotic programmed cell death resulting from iron-dependent lipid peroxidation. It is controlled by integrated oxidation and antioxidant systems. Ferroptosis exerts a crucial effect on the carcinogenesis of several cancers, including pulmonary cancer. Herein, a ferroptosis-associated gene signature for lung cancer prognosis and diagnosis was identified using integrative bioinformatics analyses. From the FerrDB database, 256 ferroptotic regulators and markers were identified. Of these, 25 exhibited differential expression between lung cancer and non-cancerous samples, as evidenced by the GSE19804 and GSE7670 datasets from the GEO database. Utilizing LASSO Cox regression analysis on TCGA-LUAD data, a potent 3-gene risk signature comprising CAV1, RRM2, and EGFR was established. This signature adeptly differentiates various survival outcomes in lung cancer patients, including overall survival and disease-specific intervals. Based on the 3-gene risk signature, lung cancer patients were categorized into high-risk and low-risk groups. Comparative analysis revealed 69 differentially expressed genes between these groups, with UBE2Z significantly associated with overall survival in TCGA-LUAD. UBE2Z was found to be upregulated in LUAD tissues and cells compared to normal controls. Functionally, the knockdown of UBE2Z curtailed aggressive behaviors in LUAD cells, including viability, migration, and invasion. Moreover, this knockdown led to a decrease in the mesenchymal marker vimentin while elevating the epithelial marker E-cadherin within LUAD cell lines. In conclusion, the ferroptosis-associated 3-gene risk signature effectively differentiates prognosis and clinical features in patients with lung cancer. UBE2Z was identified through this model, and it is upregulated in LUAD samples. Its knockdown inhibits aggressive cellular behaviors, suggesting UBE2Z's potential as a therapeutic target for lung cancer treatment.

Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks.

Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.

Single-Cell Sequencing: High-Resolution Analysis of Cellular Heterogeneity in Autoimmune Diseases.

Autoimmune diseases (AIDs) are complex in etiology and diverse in classification but clinically show similar symptoms such as joint pain and skin problems. As a result, the diagnosis is challenging, and usually, only broad treatments can be available. Consequently, the clinical responses in patients with different types of AIDs are unsatisfactory. Therefore, it is necessary to conduct more research to figure out the pathogenesis and therapeutic targets of AIDs. This requires research technologies with strong extraction and prediction capabilities. Single-cell sequencing technology analyses the genomic, epigenomic, or transcriptomic information at the single-cell level. It can define different cell types and states in greater detail, further revealing the molecular mechanisms that drive disease progression. These advantages enable cell biology research to achieve an unprecedented resolution and scale, bringing a whole new vision to life science research. In recent years, single-cell technology especially single-cell RNA sequencing (scRNA-seq) has been widely used in various disease research. In this paper, we present the innovations and applications of single-cell sequencing in the medical field and focus on the application contributing to the differential diagnosis and precise treatment of AIDs. Despite some limitations, single-cell sequencing has a wide range of applications in AIDs. We finally present a prospect for the development of single-cell sequencing. These ideas may provide some inspiration for subsequent research.

Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. METHODS AND RESULTS: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. CONCLUSION: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.

Causal relationship and shared genes between air pollutants and amyotrophic lateral sclerosis: A large-scale genetic analysis.

OBJECTIVE: Air pollutants have been reported to have a potential relationship with amyotrophic lateral sclerosis (ALS). The causality and underlying mechanism remained unknown despite several existing observational studies. We aimed to investigate the potential causality between air pollutants (PM2.5, NOX, and NO2) and the risk of ALS and elucidate the underlying mechanisms associated with this relationship. METHODS: The data utilized in our study were obtained from publicly available genome-wide association study data sets, in which single nucleotide polymorphisms (SNPs) were employed as the instrumental variantswith three principles. Two-sample Mendelian randomization and transcriptome-wide association (TWAS) analyses were conducted to evaluate the effects of air pollutants on ALS and identify genes associated with both pollutants and ALS, followed by regulatory network prediction. RESULTS: We observed that exposure to a high level of PM2.5 (OR: 2.40 [95% CI: 1.26-4.57], p = 7.46E-3) and NOx (OR: 2.35 [95% CI: 1.32-4.17], p = 3.65E-3) genetically increased the incidence of ALS in MR analysis, while the effects of NO2 showed a similar trend but without sufficient significance. In the TWAS analysis, TMEM175 and USP35 turned out to be the genes shared between PM2.5 and ALS in the same direction. CONCLUSION: Higher exposure to PM2.5 and NOX might causally increase the risk of ALS. Avoiding exposure to air pollutants and air cleaning might be necessary for ALS prevention.

PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR.

Cancer stem cells (CSCs) are responsible for tumor chemoresistance, and the aryl hydrocarbon receptor (AHR) is indispensable for maintaining CSC characteristics. Here, we aimed to investigate how the interaction between progesterone receptor membrane component 1 (PGRMC1) and AHR contributes to the maintenance of CSC phenotypes in non-small cell lung cancer (NSCLC). Clinical data and tissue microarray analyses indicated that patients with elevated PGRMC1 expression had poorer prognoses. Moreover, PGRMC1 overexpression enhanced CSC phenotypes and chemotherapy resistance in vitro and in vivo by modulating AHR ubiquitination. We then determined the specific interaction sites between PGRMC1 and AHR. Mass spectrometry screening identified tripartite motif containing 56 (TRIM56) as the E3 ligase targeting AHR. Notably, PGRMC1 overexpression inhibited the interaction between TRIM56 and AHR. Overall, our study revealed a regulatory mechanism that involves PGRMC1, AHR, and TRIM56, providing insights for developing CSC-targeting strategies in NSCLC treatment.

Causal association and shared genetics between telomere length and COVID-19 outcomes: New evidence from the latest large-scale summary statistics.

Background: Observational studies suggested that leukocyte telomere length (LTL) is shortened in COVID-19 patients. However, the genetic association and causality remained unknown. Methods: Based on the genome-wide association of LTL (N = 472,174) and COVID-19 phenotypes (N = 1086,211-2597,856), LDSC and SUPERGNOVA were used to estimate the genetic correlation. Cross-trait GWAS meta-analysis, colocalization, fine-mapping analysis, and transcriptome-wide association study were conducted to explore the shared genetic etiology. Mendelian randomization (MR) was utilized to infer the causality. Upstream and downstream two-step MR was performed to investigate the potential mediating effects. Results: LDSC identified a significant genetic association between LTL and all COVID-19 phenotypes (rG < 0, p < 0.05). Six significant regions were observed for LTL and COVID-19 susceptibility and hospitalization, respectively. Colocalization analysis found rs144204502, rs34517439, and rs56255908 were shared causal variants between LTL and COVID-19 phenotypes. Numerous biological pathways associated with LTL and COVID-19 outcomes were identified, mainly involved in -immune-related pathways. MR showed that longer LTL was significantly associated with a lower risk of COVID-19 severity (OR [95% CI] = 0.81 [0.71-0.92], p = 1.24 ×10-3) and suggestively associated with lower risks of COVID-19 susceptibility (OR [95% CI] = 0.96 [0.92-1.00], p = 3.44 ×10-2) and COVID-19 hospitalization (OR [95% CI] = 0.89 [0.80-0.98], p = 1.89 ×10-2). LTL partially mediated the effects of BMI, smoking, and education on COVID-19 outcomes. Furthermore, six proteins partially mediated the causality of LTL on COVID-19 outcomes, including BNDF, QPCT, FAS, MPO, SFTPB, and APOF. Conclusions: Our findings suggested that shorter LTL was genetically associated with a higher risk of COVID-19 phenotypes, with shared genetic etiology and potential causality.

Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. METHODS: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. RESULTS: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81-0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. CONCLUSIONS: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

ZC3H13 promotes ITGA6 m6A modification for chronic obstructive pulmonary disease progression.

Chronic obstructive pulmonary disease (COPD) is potentially fatal, and as society ages, its effects on human health are predicted to deteriorate. The potential function of m6A modifications within COPD has become a hot topic recently. This study was conducted to clarify the function and related mechanisms of the m6A methylation transferase ZC3H13 in COPD. The expression of m6A-associated protease and ITGA6 in COPD tissues was assessed using GEO data, qRT-PCR, and western blot. COPD models in cells and mice were established through cigarette smoke extract (CSE) and smoke exposure. Inflammatory marker levels were measured by ELISA, apoptosis by flow cytometry, and mRNA stability with Actinomycin D assay. m6A modification levels were checked by MeRIP-PCR. HE and Masson staining evaluated lung pathology, and alveolar lavage fluid analysis included total cell count and Giemsa staining. ZC3H13 and METTL3 were differentially expressed m6A regulators in COPD, with ZC3H13 being more significantly upregulated. Further analysis revealed the ZC3H13 expression-related differentially expressed genes (DEGs) functions were enriched in the immunoinflammatory pathway, indicating ZC3H13's involvement in COPD pathogenesis through inflammation, and immune responses. Knockdown studies in cellular and mouse models demonstrated ZC3H13's role in exacerbating COPD symptoms, including inflammation, apoptosis, and EMT, and its suppression led to significant improvements. The identification of ITGA6 as a target gene further elucidated the mechanism, showing that ZC3H13 enhances ITGA6 expression and mRNA stability through m6A modification, influencing bronchial epithelial cell inflammation and fibrosis. In conclusion, targeting ZC3H13/ITGA6 could be an underlying therapeutic approach for treating COPD.

The causal effect of air pollution on the risk of essential hypertension: a Mendelian randomization study.

Background: Air pollution poses a major threat to human health by causing various illnesses, such as cardiovascular diseases. While plenty of research indicates a correlation between air pollution and hypertension, a definitive answer has yet to be found. Methods: Our analyses were performed using the Genome-wide association study (GWAS) of exposure to air pollutants from UKB (PM2.5, PM10, NO2, and NOX; n = 423,796 to 456,380), essential hypertension from FinnGen (42,857 cases and 162,837 controls) and from UKB (54,358 cases and 408,652 controls) as a validated cohort. Univariable and multivariable Mendelian randomization (MR) were conducted to investigate the causal relationship between air pollutants and essential hypertension. Body mass index (BMI), alcohol intake frequency, and the number of cigarettes previously smoked daily were included in multivariable MRs (MVMRs) as potential mediators/confounders. Results: Our findings suggested that higher levels of both PM2.5 (OR [95%CI] per 1 SD increase in predicted exposure = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) and PM10 (OR [95%CI] = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) were linked to an increased risk for essential hypertension. Even though we used MVMR to adjust for the impacts of smoking and drinking on the relationship between PM2.5 exposure and essential hypertension risks, our findings suggested that although there was a direct positive connection between them, it is not present after adjusting BMI (OR [95%CI] = 1.05 [0.87-1.27], p = 6.17E-01). Based on the study, higher exposure to PM2.5 and PM10 increases the chances of developing essential hypertension, and this influence could occur through mediation by BMI. Conclusion: Exposure to both PM2.5 and PM10 is thought to have a causal relationship with essential hypertension. Those impacted by substantial levels of air pollution require more significant consideration for their cardiovascular health.

The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma.

Background: Tertiary lymphoid structure (TLS) is a unique organ that carries out tumor cell elimination at tumor sites. It is continuously stimulated by inflammatory tumor signals and has been found to augment immunotherapy response. However, the detailed mechanisms behind it still need to be defined. Methods: To explore and grasp the whole picture of TLS from a pan-cancer view, we collected nine TLS-related genes from previous studies. We performed a comprehensive analysis of 9637 samples across 33 tumor types accessed from The Cancer Genome Atlas (TCGA) database. EdU, Transwell, and flow cytometry were performed on the feature gene PTGDS in U251 cells. The regulatory role of PTGDS on PD-L1 expression and macrophage polarization was verified. Results: Alteration analysis showed that mutations of TLS-related genes were widespread and relatively high. Clustering analysis based on the expression of these nine genes obtained two distinct clusters, with high EIF1AY and PTGDS in cluster 2 and better overall survival in cluster 1. To distinguish the two clusters, we utilized six machine learning algorithms and filtrated EIF1AY, PTGDS, SKAP1, and RBP5 as the characteristic genes, among which the former two genes were proved to be hazardous. PTGDS was found to regulate PD-L1 expression and also promoted the proliferation and migration of U251 cells. The knockdown of PTGDS could reduce the migration of macrophages and inhibit the polarization of macrophages into M2-phenotype. In addition, we established a TLS score to demonstrate patients' TLS activity. The low TLS-score group overlapped with cluster 1 and displayed a better prognosis. Besides, the low TLS-score group was related to better immunotherapy responses. The HE staining of histopathological sections confirmed that the low TLS-score group exhibited higher infiltration of immune cells. Conclusion: This study reveals broad molecular, tumorigenic, and immunogenic signatures for further functional and therapeutic studies of tertiary lymphoid structure. The TLS score we established effectively predicted immunotherapy response and patients' survival. Its future application and combination await more research.

Simple and Effective Squash-PCR for Rapid Genotyping of Industrial Microalgae.

Microalgae are recognized for their versatility in providing renewable energy, biopharmaceuticals, and nutraceuticals, attributed to their sustainable, renewable, and cost-effective nature. Genetic engineering has proven highly effective in enhancing microalgae production. PCR-based genotyping is the primary method for screening genetically transformed microalgae cells. Recently, we developed a novel PCR method, namely Squash-PCR, and employed it for the molecular analysis of industrially important fungi and yeasts. In this study, we successfully implemented the Squash-PCR technique in 12 industrially significant algae species. This approach offers a quick and reliable means of obtaining DNA templates directly from squashed algal cells, eliminating the need for time-consuming and labor-intensive cultivation and genomic DNA extraction steps. Our results demonstrate the effectiveness of Squash-PCR in detecting and characterizing target genes of interest in 12 different algae species. Overall, this study establishes the Squash-PCR method as a valuable tool for molecular studies in algae, enabling researchers to rapidly screen and manipulate genetic traits in diverse algal species.

Oxidative stress is involved in immunosuppression and macrophage regulation in glioblastoma.

Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.

A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors.

BACKGROUND: Central nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single-stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes. AIMS: This review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors. METHODS: We have summarized studies of circRNA in CNS tumors in Pubmed. RESULTS: This review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA-related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics. CONCLUSIONS: CircRNA are increasingly proven to participate in decveloping CNS tumors. An in-depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.

Screening of Lipid Metabolism-Related Genes as Diagnostic Indicators in Chronic Obstructive Pulmonary Disease.

Objective: It has been observed that local and systemic disorders of lipid metabolism occur during the development of chronic obstructive pulmonary disease (COPD), but no specific mechanism has yet been identified. Methods: The mRNA microarray dataset GSE76925 of COPD patients was downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from the Kyoto Encyclopedia of Genes and Genomes database and Molecular Signature Database. The DEGs were intersected with LMRGs to obtain differentially expressed lipid metabolism-related genes (DeLMRGs). GO enrichment analysis and KEGG pathway analysis were performed on DeLMRGs, and protein-protein interaction networks were constructed and screened to identify hub genes. The GSE8581 validation set and further ELISA experiments were used to validate key DeLMRG expression. Results: Differential analysis of dataset GSE76925 identified 587 DEGs, of which 62 genes were up-regulated and 525 were down-regulated. Taking the intersection of 587 DEGs with 1102 LMRGs, 20 DeLMRGs were obtained, including 1 up-regulated gene and 19 down-regulated genes. 10 hub genes were screened by cytohubba plugin, including 9 down-regulated genes PLA2G4A, HPGDS, LEP, PTGES3, LEPR, PLA2G2D, MED21, SPTLC1 and BCHE, as well as the only up-regulated gene PLA2G7. Validation of the identified 10 DeLMRGs using the validation set GSE8581 revealed that BCHE and PLA2G7 expression levels differed between the two groups. We further constructed the ceRNA network of BCHE and PLA2G7. Cell experiments also showed that PLA2G7 expression was up-regulated and BCHE expression was down-regulated in CSE-treated RAW264.7 and THP-1 cells. Conclusion: Based on a comprehensive bioinformatic analysis of lipid metabolism genes, we identified BCHE and PLA2G7 as potentially significant biomarkers of COPD. These biomarkers may represent promising targets for COPD diagnosis and treatment.

Novel genetic tools improve Penicillium expansum patulin synthase production in Aspergillus niger.

Since the first CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system was developed for creating double-stranded DNA breaks, it has been adapted and improved for different biotechnological applications. In this issue of The FEBS Journal, Arentshorst et al. developed a novel approach to enhance transgene expression of a specific protein, patulin synthase (PatE) from Penicillium expansum, in the important industrial filamentous fungus Aspergillus niger. Their technique involved the disruption of selected genes with counter-effects on targeted protein production and simultaneous integration of glucoamylase landing sites into the disrupted gene locus such as protease regulator (prtT) in an ATP-dependent DNA helicase II subunit 1 (kusA or ku70)-deletion strain. Multiple copies of the PatE transgene expression cassette were introduced by CRISPR-Cas9-mediated insertion. The purified PatE was further used for structural and functional studies, and the technique laid the foundation for elevating the overall production of various proteins or chemicals in those industrially important fungi.

PD-L1-related IncRNAs are associated with malignant characteristics and immune microenvironment in glioma.

BACKGROUND: The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs in affecting malignant characteristics and the immune microenvironment of glioma. METHODS: Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were identified through correlation analysis, Cox and LASSO regression analysis, establishing the risk score model based on them. Bioinformatics analysis and cell experiments in vitro were adopted to verify the effects of LINC01271 on glioma. RESULTS: Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can reflect malignant characteristics and immunotherapy response of glioma. Patients with high LINC01271 expression had a worse prognosis, a higher abundance of M1 subtype macrophages in the immune microenvironment, and a higher degree of tumor malignancy. Experiments in vitro confirmed its positive regulatory effect on the proliferation and migration of glioma cells. CONCLUSIONS: The risk score model based on 6 PD-L1-related lncRNAs can reflect the malignant characteristics and prognosis of glioma. LINC01271 can independently be used as a new target for prognosis evaluation and therapy.

Identification of a specific exporter that enables high production of aconitic acid in Aspergillus pseudoterreus.

Aconitic acid is an unsaturated tricarboxylic acid that is attractive for its potential use in manufacturing biodegradable and biocompatible polymers, plasticizers, and surfactants. Previously Aspergillus pseudoterreus was engineered as a platform to produce aconitic acid by deleting the cadA (cis-aconitic acid decarboxylase) gene in the itaconic acid biosynthetic pathway. In this study, the aconitic acid transporter gene (aexA) was identified using comparative global discovery proteomics analysis between the wild-type and cadA deletion strains. The protein AexA belongs to the Major Facilitator Superfamily (MFS). Deletion of aexA almost abolished aconitic acid secretion, while its overexpression led to a significant increase in aconitic acid production. Transportation of aconitic acid across the plasma membrane is a key limiting step in its production. In vitro, proteoliposome transport assay further validated AexA's function and substrate specificity. This research provides new approaches to efficiently pinpoint and characterize exporters of fungal organic acids and accelerate metabolic engineering to improve secretion capability and lower the cost of bioproduction.

Role of nutrition in patients with coexisting chronic obstructive pulmonary disease and sarcopenia.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases in the elderly population and is characterized by persistent respiratory symptoms and airflow obstruction. During COPD progression, a variety of pulmonary and extrapulmonary complications develop, with sarcopenia being one of the most common extrapulmonary complications. Factors that contribute to the pathogenesis of coexisting COPD and sarcopenia include systemic inflammation, hypoxia, hypercapnia, oxidative stress, protein metabolic imbalance, and myocyte mitochondrial dysfunction. These factors, individually or in concert, affect muscle function, resulting in decreased muscle mass and strength. The occurrence of sarcopenia severely affects the quality of life of patients with COPD, resulting in increased readmission rates, longer hospital admission, and higher mortality. In recent years, studies have found that oral supplementation with protein, micronutrients, fat, or a combination of nutritional supplements can improve the muscle strength and physical performance of these patients; some studies have also elucidated the possible underlying mechanisms. This review aimed to elucidate the role of nutrition among patients with coexisting COPD and sarcopenia.