The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis.

Previous studies have focused on the impact of individual RNA modifications on tumor development. This study comprehensively investigated the effects of multiple RNA modifications, including m6A, alternative polyadenylation, pseudouridine, adenosine-to-inosine editing, and uridylation, on gastric cancer (GC). By analyzing 1,946 GC samples from eleven independent cohorts, we identified distinct clusters of RNA modification genes with varying survival rates and immunological characteristics. We assessed the chromatin activity of these RNA modification clusters through regulon enrichment analysis. A prognostic model was developed using Stepwise Regression and Random Survival Forest algorithms and validated in ten independent datasets. Notably, the low-risk group showed a more favorable prognosis and positive response to immune checkpoint blockade therapy. Single-cell RNA sequencing confirmed the abundant expression of signature genes in B cells and plasma cells. Overall, our findings shed light on the potential significance of multiple RNA modifications in GC prognosis, stemness development, and chemotherapy resistance.

Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer.

Introduction: Autophagy can be triggered by oxidative stress and is a double-edged sword involved in the progression of multiple malignancies. However, the precise roles of autophagy on immune response in gastric cancer (GC) remain clarified. Methods: We endeavor to explore the novel autophagy-related clusters and develop a multi-gene signature for predicting the prognosis and the response to immunotherapy in GC. A total of 1505 patients from eight GC cohorts were categorized into two subtypes using consensus clustering. We compare the differences between clusters by the multi-omics approach. Cox and LASSO regression models were used to construct the prognostic signature. Results: Two distinct clusters were identified. Compared with cluster 2, the patients in cluster 1 have favorable survival outcomes and lower scores for epithelial-mesenchymal transition (EMT). The two subtypes are further characterized by high heterogeneity concerning immune cell infiltration, somatic mutation pattern, and pathway activity by gene set enrichment analysis (GSEA). We obtained 21 autophagy-related differential expression genes (DEGs), in which PTK6 amplification and BCL2/CDKN2A deletion were highly prevalent. The four-gene (PEA15, HSPB8, BNIP3, and GABARAPL1) risk signature was further constructed with good predictive performance and validated in 3 independent datasets including our local Tianjin cohort. The risk score was proved to be independent prognostic factor. A prognostic nomogram showed robust validity of GC survival. The risk score was significantly associated with immune cell infiltration status, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules. Furthermore, the model was efficient for predicting the response to tumor-targeted agent and immunotherapy and verified by the IMvigor210 cohort. This model is also capable of discriminating between low and high-risk patients receiving chemotherapy. Conclusion: Altogether, our exploratory research on the landscape of autophagy-related patterns may shed light on individualized therapies and prognosis in GC.

Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang.

A wide sex disparity has been demonstrated in cancer incidence, tumor aggressiveness, prognosis, and treatment response of different types of cancer. The sex specificity of cancer appears to be a relevant issue in managing the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Immunotherapy plays a leading role in cancer treatment, offering a new perspective on advanced malignancies. Gender has not been considered in standard cancer treatment, suggesting increasing the recognition of sex differences in cancer research and clinical management. This paper provides an overview of sex and gender disparities in cancer immunotherapy efficacy, anti-cancer immune response, predictive biomarkers, and so on. We focus on the molecular differences between male and female patients across a broad range of cancer types to arouse the attention and practice of clinicians and researchers in a sex perspective of new cancer treatment strategies.

The integrated landscape of eRNA in gastric cancer reveals distinct immune subtypes with prognostic and therapeutic relevance.

The comprehensive regulation effect of eRNA on tumor immune cell infiltration and the outcome remains obscure. We comprehensively identify the eRNA-mediated immune infiltration patterns of gastric cancer (GC) samples. We creatively proposed a random forest machine-learning (ML) algorithm to map eRNA to mRNA expression patterns. The eRNA score was constructed using principal component analysis algorithms and validated in an independent cohort. Three subtypes with distinct eRNA expression patterns were determined in GC. There were significant differences between the three subtypes in the overall survival rate, immune cell infiltration characteristics, and immunotherapy response indicators. The patients in the high eRNA score group have a higher overall survival rate and might benefit from immunotherapy. This work revealed that eRNA regulation might be a new prognostic index and might offer a potential biomarker in the response of immunotherapy. Evaluating the eRNA regulation manner of GC will contribute to guiding more effective immunotherapy strategies.

Diatom Biodiversity and Speciation Revealed by Comparative Analysis of Mitochondrial Genomes.

Diatoms (Bacillariophyta) constitute one of the most diverse and ecologically significant groups of phytoplankton, comprising 100,000-200,000 species in three classes Bacillariophyceae, Mediophyceae, and Coscinodiscophyceae. However, due to the limited resolution of common molecular markers including 18S rDNA, 28S rDNA, ITS, rbcL, and cox1, diatom biodiversity has not been adequately ascertained. Organelle genomes including mitochondrial genomes (mtDNAs) have been proposed to be "super barcodes" for distinguishing diatom species because of their rich genomic content, and the rapid progress of DNA sequencing technologies that has made it possible to construct mtDNAs with increasing throughout and decreasing cost. Here, we constructed complete mtDNAs of 15 diatom species including five Coscinodiscophyceae species (Guinardia delicatula, Guinardia striata, Stephanopyxis turris, Paralia sulcata, and Actinocyclus sp.), four Mediophyceae species (Hemiaulus sinensis, Odontella aurita var. minima, Lithodesmioides sp., and Helicotheca tamesis), and six Bacillariophyceae species (Nitzschia ovalis, Nitzschia sp., Nitzschia traheaformis, Cylindrotheca closterium, Haslea tsukamotoi, and Pleurosigma sp.) to test the practicality of using mtDNAs as super barcodes. We found that mtDNAs have much higher resolution compared to common molecular markers as expected. Comparative analysis of mtDNAs also suggested that mtDNAs are valuable in evolutionary studies by revealing extensive genome rearrangement events with gene duplications, gene losses, and gains and losses of introns. Synteny analyses of mtDNAs uncovered high conservation among species within an order, but extensive rearrangements including translocations and/or inversions between species of different orders within a class. Duplication of cox1 was discovered for the first time in diatoms in Nitzschia traheaformis and Haslea tsukamotoi. Molecular dating analysis revealed that the three diatom classes split 100 Mya and many diatom species appeared since 50 Mya. In conclusion, more diatom mtDNAs representing different orders will play great dividends to explore biodiversity and speciation of diatoms in different ecological regions.

[Economic evaluation on the health hazards of residents caused by PM_(2.5) in Beijing, Tianjin and Hebei from 2013 to 2018].

OBJECTIVE: To learn the health hazards and health economic losses caused by PM_(2.5) pollution in Beijing, Tianjin and Hebei to the resident population. METHODS: Fine particular matter concentration and the basic demographic data of Beijing, Tianjin and Hebei from 2013 to 2018 were collected. Circulatory system disease hospitalization and other indexes were chosen as the end point of health effects, appropriate exposure-response relationship were selected, and the economic loss of health effect caused by PM_(2.5) was assessed by the combination of the cost of illness approach and human capital method. RESULTS: From 2013 to 2018, the economic loss of Beijing, Tianjin and Hebei caused by fine particular matter pollution showed a decreasing trend year by year. The health economic losses of Beijing from 2013 to 2018 were 3.815, 4.177, 4.090, 3.818, 2.567 and 2.031 billion yuan; The health economic losses of Tianjin were 3.046, 2.625, 1.882, 1.914, 1.448 and 1.000 billion yuan; The health economic losses of Hebei were 13.719, 11.850, 7.423, 7.216, 6.499 and 4.124 billion yuan, Hebei Province had the highest economic loss in 2013, accounting for 13.719 billion yuan, accounting for 0.51% of GDP in that year. Tianjin had the lowest economic loss in 2018, accounting for 10.0 billion yuan, accounting for 0.05% of GDP in that year. CONCLUSION: The health loss caused by PM_(2.5) pollution in Beijing, Tianjin and Hebei region shows a decreasing trend year by year, but the number is still very considerable, and the monitoring and control of PM_(2.5) pollution need to be further strengthened.

Complete mitochondrial genome of Rhizosolenia setigera (Coscinodiscophyceae, Bacillariophyta).

Rhizosolenia is a species-rich genus with 144 described species, many of which are harmful algal species (HABs) with significant negative ecological impact. Despite their significance in primary production and their potential to induce HABs, genome data of these species remain extremely limited. In this study, the complete mitochondrial genome (mtDNA) of Rhizosolenia setigera Brightwell 1858 was determined for the first time, which also represented the first mtDNA of the order Rhizosoleniales. The circular mtDNA was 34,792 bp in length with GC content of 23.28%. It encoded 63 genes including 35 protein-coding genes (PCGs), 24 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 2 conserved open reading frames (orfs). Phylogenetic analysis using concatenated PCGs revealed that R. setigera and Melosira undulate, which also belongs to the class Coscinodiscophyceae, clustered together as expected. However, comparison of these two mtDNAs revealed extensive genome rearrangement events, suggesting large evolutionary distance. The complete mtDNA of R. setigera will facilitate research on the phylogenetic relationship among Rhizosolenia species, which will in turn facilitate exploration of the evolutionary relationships in the class of Coscinodiscophyceae.

A Dendrite-Free Tin Anode for High-Energy Aqueous Redox Flow Batteries.

Metal-based aqueous redox flow batteries (ARFBs) such as zinc-based ARFBs have attracted remarkable attention owing to their intrinsic high energy density. However, severe dendrite issues limit their efficiency and lifespan. Here an aqueous metal anode operating between Sn(OH)6 2- (stannate) and metal Sn is presented, providing a reversible four-electron transfer at -0.921 V vs standard hydrogen electrode. In strong contrast to severe Zn dendrites, the Sn(OH)6 2- /Sn electrode shows smooth and dendrite-free morphology, which can be attributed to its intrinsic low-surface-energy anisotropy which facilitates isotropic crystal growth of Sn metal. By coupling with iodide/tri-iodide (I- /I3 - ), the static Sn-I cell demonstrates a stable cycling for 500 cycles (more than 2 months). In contrast, the state-of-the-art Zn anode suffers from serious dendrites and lasts less than 45 cycles (190 h) in Zn-I cells. A stable continuous flow cycling of Sn-I cell achieves a Sn areal capacity of 73.07 mAh cm-2 at an average discharge voltage of 1.3 V for 350 h. The alkaline Sn electrode demonstrates dendrite-free morphology and superior performance in cycle life and areal capacity compared to state-of-the-art Zn metal anodes, offering a promising metal anode for high-energy ARFBs and other metal-based rechargeable aqueous batteries.

Characterization of Two Ferroptosis Subtypes With Distinct Immune Infiltration and Gender Difference in Gastric Cancer.

Background: Iron is an essential nutrient involved in the redox cycle and the formation of free radicals. The reprogramming of iron metabolism is the main link to tumor cell survival. Ferroptosis is an iron-dependent form of regulated cell death associated with cancer; the characteristics of ferroptosis in cancers are still uncertain. This study aimed to explore the application value and gender difference of ferroptosis in prognosis and immune prediction to provide clues for targeted therapy of gastric cancer. Methods: We comprehensively evaluated the ferroptosis levels of 1,404 gastric cancer samples from six independent GC cohorts based on ferroptosis-related specific genes and systematically correlated ferroptosis with immune cell infiltrating and gender characteristics. The ferroptosis score was constructed to quantify the ferroptosis levels of individual tumors using principal component analysis (PCA) algorithms. Results: We identified two distinct ferroptosis subtypes in gastric cancer, namely Subtype-A and Subtype-B. We found that male patients in Subtype-B had the worst prognosis in contrast with the other groups. Three sex hormone receptors (AR, ER, and PR) in Subtype-B tumor patients were higher than in Subtype-A tumor patients in GC, while the HER2 displayed an opposite trend. We developed a risk model termed ferroptosis score to evaluate ferroptosis levels within individual tumors. The low-ferroptosis score group was characterized by activation of immune cells and increased mutation burden, which is also linked to increased neoantigen load and enhanced response to anti-PD-1/L1 immunotherapy. The patients with a low-ferroptosis score showed a high microsatellite instability status (MSI-H) and had a higher response to immunotherapy. Furthermore, the patients with low-ferroptosis scores have a lower estimated IC50 in the several chemotherapy drugs, including paclitaxel, gemcitabine, and methotrexate. Conclusions: We revealed that sex hormone receptors and immune cell infiltration were markedly different between ferroptosis subtypes in GC patients. The results suggested that gender difference may be critical when the ferroptosis-related strategy is applied in GC treatment. Further, ferroptosis levels were identified with an extreme variety of prognosis and tumor immune characteristics, which might benefit GC individualized treatment.