title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=57 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Breaking epigenetic shackles: targeting ARID1A methylation and the PI3K/AKT/mTOR-PD-L1 axis to overcome immune escape in gastric cancer link: https://peerj.com/articles/20251 last-modified: 2025-11-06 description: ObjectiveAT-rich interaction domain 1A (ARID1A), is frequently mutated in cancer, leading to loss-of-function and posing challenges to therapeutic targeting. This study aimed to systematically explore epigenetic regulation of ARID1A, specifically promoter hypermethylation, in gastric cancer (GC) and its functional/immunological consequences.MethodsWe employed multi-omics bioinformatics analyses (UALCAN, cBioPortal, MEXPRESS and UCSC Xena) combined with in vitro functional validation in GC cell lines, including pharmacological demethylation using 5-Aza-2’-deoxycytidine (5-aza-CdR) and mechanistic interrogation via AKT agonism (SC79).ResultsPromoter hypermethylation was identified as a key mechanism silencing ARID1A transcriptional, showing a significant negative correlation between methylation β-values and mRNA expression (Spearman’s ρ =  − 0.29, p = 2.06 × 10−8). 5-aza-CdR treatment restored ARID1A expression (p  <  0.001), suppressed malignant phenotypes (proliferation, invasion, and apoptosis resistance), and revealed that ARID1A lose activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (elevated p-AKT, p-mTOR) and upregulates PD-L1. Rescue experiments with SC79 reversed 5-aza-CdR’s effects, confirming the ARID1A-PI3K/AKT/mTOR-PD-L1 axis. Integrative analysis linked ARID1A hypermethylation to elevated immune/ESTIMATE scores (p  <  0.05).ConclusionARID1A promoter hypermethylation drives an epigenetic-immune checkpoint cascade in GC. Combined with its association with immune signatures and PD-L1 upregulation, ARID1A hypermethylation emerges as a candidate biomarker for predicting immune checkpoint blockade (ICB) responsiveness and patient stratification in GC. Future studies should evaluate 5-aza-CdR-ICB-AKT inhibitor regimens in advanced models to guide clinical translation. creator: Xueqin Duan creator: Xingfa Huo creator: Yuming Zhang creator: Hongwei Lan creator: Fangfang Yang creator: Xiaochun Zhang creator: Na Zhou uri: https://doi.org/10.7717/peerj.20251 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Duan et al. title: Retrospective study on the association between paternal occupational exposure to agrochemicals and childhood leukemia in Michoacán de Ocampo, México link: https://peerj.com/articles/20219 last-modified: 2025-11-06 description: ObjectivesThe constant use of agrochemicals in avocado plantations, because of their susceptibility to pests and diseases, continuously exposes those who work or reside near these orchards to health risks. The purpose of this study was to investigate the association between childhood leukemia cases in Michoacán, paternal occupational exposure to agrochemicals, and environmental exposure due to residential proximity.MethodsA retrospective observational cohort study was performed. We analyzed 430 cases of leukemia in children under 18 years of age diagnosed between 2010-2023. Logistic regression models were used to estimate odds ratios and 95% confidence intervals, adjusted for sociodemographic factors. Survival was analyzed using Kaplan-Meier curves.ResultsA total of 46.6% of the parents of children with leukemia in this study had jobs related to the use of agrochemicals (e.g., day laborers, peasants, farmers). Additionally, 65.4% of the leukemia cases occurred in municipalities producing avocado, the most important perennial crop in the state. Regarding the residential area analysis (mapping), many cases were found in contiguous zip codes and in areas densely occupied by avocado orchards. In addition, paternal occupations related to agrochemical use were associated with the avocado-growing zone, with an OR = 1.764 (95% CI [1.034–3.009], p = 0.0379). Interestingly, survival associated with agrochemical-related occupations has a higher mean survival (139.3 months) than all other parental occupations (p = 0.0148).ConclusionsThe epidemiologic evidence found in this study supports the association between paternal occupational exposure to agrochemicals and childhood leukemia. Furthermore, children with leukemia who live in avocado-growing regions have a higher survival rate. creator: Paola Jiménez-Alcántar creator: Anel Gómez-García creator: Joel E. López-Meza creator: Alejandra Ochoa-Zarzosa creator: Luis Andrés Espino-Barajas creator: Luis Miguel Morales-Manilla creator: Eloy Pérez-Rivera creator: Luz Yadira Zúñiga-Quijano creator: Sergio Gutiérrez-Castellanos uri: https://doi.org/10.7717/peerj.20219 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2025 Jiménez-Alcántar et al. title: Auditory processing ability in Thai native speakers with the Gaps-In-Noise (GIN) test link: https://peerj.com/articles/20207 last-modified: 2025-11-06 description: IntroductionAuditory processing disorder (APD) arises from dysfunctions within the central auditory nervous system (CANS). One key tool for assessing temporal auditory processing capabilities is the Gaps-In-Noise (GIN) test. While the GIN test serves as a critical tool, its accuracy may be influenced by linguistic factors. This research aims to establish preliminary normative data for the GIN test among young adult native Thai speakers and to compare potential performance differences across ears and various linguistic backgrounds.MethodsThis study included 52 native Thai speakers aged 18 to 25, all of whom had normal hearing confirmed through pure-tone audiometry, to examine auditory processing using the GIN test. The testing was conducted in an anechoic chamber to ensure standardized conditions. The results were analyzed based on the approximate gap-detection threshold (A.th.) value and the overall percent correct (OPC) value metrics.ResultsThe study revealed that, among young adult native Thai speakers, the A.th. values were 5.12–0.81 milliseconds (ms.) in the right ear, 5.08–0.81 ms. in the left ear, and 5.04–0.68 ms. for both ears. The corresponding averages of OPC values were 69.94–7.66% for the right ear, 71.37–7.21% for the left ear, and 71.35–6.72% for both ears, respectively. While no significant differences were observed in the threshold between ears, a notable discrepancy in response accuracy was noted, with the right ear showing lower accuracy than the left ear. Significant differences were also found when compared to English, Korean, and Portuguese language users, but not when compared to Polish language users.ConclusionThe study revealed comparable temporal processing abilities among young adult native Thai speakers, as indicated by similar A.th. values across both ears. However, differences in the OPC value responses suggest potential asymmetries in auditory processing mechanisms. Additionally, linguistic factors appeared to influence the outcomes, as evidenced by variations in the A.th. values between Thai speakers and individuals from other linguistic backgrounds. These findings underscore the importance of incorporating language-specific norms when assessing the APD. creator: Supakarn Jeanbunjongkij creator: Pawichaya Suphinnapong creator: Patcharaorn Limkitisupasin creator: Yuttana Roongthumskul creator: Nattawan Utoomprurkporn uri: https://doi.org/10.7717/peerj.20207 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Jeanbunjongkij et al. title: Analysis of the chitin synthase gene family in Ganoderma lucidum: its structure, phylogeny, and expression patterns link: https://peerj.com/articles/20302 last-modified: 2025-11-05 description: BackgroundChitin synthases are essential enzymes in fungi, contributing to various biological processes such as hyphal growth, sporulation, and cell wall stability. Despite their well-documented functions in other fungal species, the specific roles of chitin synthases in Ganoderma lucidum remain unexplored. This investigation systematically characterized the complete chitin synthase gene family in Ganoderma lucidum.MethodsA comprehensive analysis was conducted using bioinformatics tools to examine genomic localization, gene structure, conserved domains, and phylogenetic evolution. By employing bioinformatic approaches, the study investigated promoter cis-elements and expression patterns to elucidate the regulatory mechanisms of these genes in G. lucidum.ResultsIn G. lucidum, eight chitin synthase (GlCS) family members were identified and phylogenetically classified into five distinct classes. Our investigation revealed stage-specific expression patterns of GlCS genes throughout the fungal development process. GlCS1, GlCS2, GlCS5, GlCS6, and GlCS8 exhibited significantly greater expression levels in the early fruiting body (EA) stage than in the other developmental phases. In the mature fruiting body (MA) stage, GlCS3 was predominantly expressed. In the primordium formation (PR) stage, GlCS7 exhibited peak expression levels. Six genes (GlCS1, GlCS3, GlCS4, GlCS6, GlCS7, and GlCS8) were markedly upregulated under 40 °C thermal stress, suggesting their potential roles in thermotolerance mechanisms. These findings demonstrate functional diversification among GlCS family members across different developmental stages and stress conditions. creator: Linling Liu creator: Yiming Yang creator: Jintao Li creator: Yanliang Gao creator: Meixia Yan uri: https://doi.org/10.7717/peerj.20302 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Liu et al. title: CD81 inhibits the proliferation of acute megakaryoblastic leukemia cells link: https://peerj.com/articles/20286 last-modified: 2025-11-05 description: CD81 is a cell surface protein that plays an important part in tumor development. Several studies have shown that CD81 plays a role in cancer cell proliferation, invasion, and metastasis, particularly in leukemia. It has been reported that CD81 is overexpressed in non-Down syndrome acute megakaryoblastic leukemia (non-DS AMKL). In this article, we hypothesize that CD81 may play a vital role in acute megakaryoblastic leukemia (AMKL). We constructed the CD81 knockdown cell line using shRNA and found that CD81 knockout can inhibit the proliferation of AMKL and increase the apoptosis of AMKL in vitro. Therefore, CD81 may be a target of AMKL. creator: Narun Su creator: Xiaohao Hu uri: https://doi.org/10.7717/peerj.20286 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Su and Hu title: Biocontrol-relevant diversity of wheat-associated Pseudomonas: prevalence of P. sivasensis and identification of the novel species P. arvensis sp. nov. link: https://peerj.com/articles/20177 last-modified: 2025-11-05 description: The role of microbial communities in plant health and productivity has become increasingly evident. In this study, we investigated the diversity and functional potential of Pseudomonas spp. associated with Belgian cereal crops, focusing on wheat and spelt. From 444 Pseudomonas isolates, we identified 11 species, with several strains exhibiting strong antagonistic activity against major wheat pathogens. Notably, we report the high prevalence and efficient colonization abilities of Pseudomonas sivasensis, including its capacity to translocate from seed to leaf and suppress Zymoseptoria tritici infection in planta. Furthermore, we describe Pseudomonas arvensis sp. nov., a newly characterized species within the wheat microbiome, with DR1PS3 designated as the type strain. Our results advance the understanding of beneficial plant-microbe interactions in cereals and highlight the promise of native Pseudomonas species as biocontrol agents for sustainable disease management. creator: Mathieu Delitte creator: Benjamin Dubois creator: Louis Morandini creator: Alain Bultreys creator: Jacques Mahillon creator: Frederic Debode creator: Claude Bragard uri: https://doi.org/10.7717/peerj.20177 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Delitte et al. title: Gardnerella species exhibit synergy in their ability to displace Lactobacillus crispatus adhered to HeLa cells link: https://peerj.com/articles/20076 last-modified: 2025-11-05 description: BackgroundBacterial vaginosis (BV) is the most common vaginal infection in reproductive-age women. It is associated with adverse pregnancy complications, such as preterm birth and low birth weight, in addition to an increased risk of acquisition of HIV and sexually transmitted infections. BV is characterized by a vaginal dysbiosis, involving loss of protective Lactobacillus species (including L. crispatus) and overgrowth of facultative and strict anaerobic bacteria, with Gardnerella species playing a predominant role. However, despite extensive research on BV pathogenesis, its etiology remains unclear, and the sequence of events leading to the displacement of lactobacilli by anaerobic bacteria in women has not yet been fully elucidated. Until 2019, all bacteria belonging to the Gardnerella genus were considered part of the species G. vaginalis. However, it is now recognized that different Gardnerella species exist, each with varying virulence potentials. Recent data have shown that multiple subgroups of Gardnerella spp. are frequently detected simultaneously in the vaginal microbiota of women with BV. With this in mind, we aimed to test the hypothesis that different combinations of known Gardnerella species, isolated from the vaginal microbiota of women with BV, have an enhanced ability to compete against Lactobacillus crispatus, pre-adhered to HeLa cells, thereby facilitating the early stages of BV development.MethodsAdhesion assays of dual combinations of Gardnerella spp. (G. vaginalis, G. leopoldii, G. swidsinskii, G. piotii) were performed on an in vitro model of HeLa cells, covered with and without L. crispatus. Quantification of the species used in our assays was subsequently performed using quantitative polymerase chain reaction (qPCR).ResultsOur results revealed synergy between different Gardnerella spp., demonstrating their ability to overcome the presumed protective effect of L. crispatus, thereby creating favorable conditions for the development of a polymicrobial biofilm characteristic of BV. The combination of G. vaginalis and G. leopoldii showed the greatest synergistic effect on initial adhesion to HeLa cells while the combination of G. leopoldii and G. swidsinskii had the greatest ability to reduce L. crispatus colonization.ConclusionsAlthough this in vitro study does not unequivocally prove that BV is initiated by the disruption of normal vaginal microbiota by Gardnerella spp., it strongly supports this possibility, contributing to a better understanding of BV etiology. creator: Ângela Lima creator: Joana Castro creator: Christina A. Muzny creator: Nuno Cerca uri: https://doi.org/10.7717/peerj.20076 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Lima et al. title: MicroRNA-597-3p targets MACC1 to suppress proliferation and invasion of human ovarian cancer cells link: https://peerj.com/articles/20316 last-modified: 2025-11-04 description: BackgroundOvarian cancer is a lethal gynecological malignancy, largely due to late-stage diagnosis and poor prognosis. MicroRNA-597-3p (miR-597-3p) has been identified as a tumor suppressor in several cancers, while metastasis-associated colon cancer 1 (MACC1) functions as an oncogene that promotes metastasis. This study investigated the role of miR-597-3p and its regulation of MACC1 in ovarian cancer progression.MethodsOvarian cancer cell lines and the normal ovarian epithelial cell line IOSE-398 were used. Quantitative real-time PCR (qRT-PCR) measured the expression of miR-597-3p and MACC1. Functional assays (MTT, colony formation, AO/EB staining, and Transwell invasion) evaluated cell proliferation, cell death, and invasion. Dual-luciferase reporter assays confirmed the interaction between miR-597-3p and MACC1, while bioinformatics analysis identified potential targets. Western blotting was used to validate MACC1 and downstream proteins, MMP-2, and MMP-9 at the protein level.ResultsMiR-597-3p was significantly downregulated (P < 0.05) in ovarian cancer cells, whereas MACC1 was upregulated. Overexpression of miR-597-3p suppressed cell viability, colony formation, and invasion, and increased cell death with a pro-apoptotic shift in Bax/Bcl-2 expression. Mechanistically, miR-597-3p directly targeted MACC1, leading to reduced expression of MMP-2 and MMP-9 at both transcript and protein levels. Notably, MACC1 overexpression reversed the tumor-suppressive effects of miR-597-3p.ConclusionsMiR-597-3p functions as a tumor suppressor in ovarian cancer by directly targeting MACC1, thereby inhibiting proliferation, invasion, and survival. These findings highlight the miR-597-3p/MACC1 axis as a potential therapeutic target and suggest miR-597-3p as a promising biomarker for ovarian cancer. creator: Ahmed Abdullah Al Awadh creator: Abdulaziz M.S. Alqahtani creator: Fahad Alshahrani creator: Mohammed Merae Alshahrani uri: https://doi.org/10.7717/peerj.20316 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2025 Al Awadh et al. title: Quantifying the scale dependence of primary productivity-species-richness relationships link: https://peerj.com/articles/20297 last-modified: 2025-11-04 description: Vegetation productivity is expected to correlate with species richness, but there is debate about whether the relationship form (non-existent, negative, positive, unimodal) of productivity-species-richness relationships (PSRR) depends on the spatial extent and productivity measure used. Previous assessments employed coarse distance categories to examine scale dependence and did not consider scale dependence for alternative productivity measures. I used spatially varying coefficient models to precisely estimate the distances over which PSRRs change and to map spatial patterns of form for breeding birds across the conterminous United States. I created separate models for three measures summarizing intra-annual estimates of gross primary productivity: sum, minimum, and seasonality (coefficient of variation). Models demonstrated that PSRRs were scale-dependent, and PSRR relationships changed at median distances ranging from 1,010 to 2,184 km depending on the productivity measure. Previously used coarse distance categories would not have resolved the modeled distance estimates. Differences in median distance estimates across productivity measures were not statistically important. Across measures, PSRR form generally alternated between non-existence and positive, but there were pockets where seasonality negatively related to species richness in the western United States. While spatial patterns of form differed across measures, species richness in a small region of the western United States displayed a positive association with all three measures. Spatial patterns were related to prevailing productivity conditions. For example, sum tended to have a positive association with bird species richness in areas characterized by low annual productivity. This study novelly applies spatially varying coefficient models to address the long-debated scale-dependence of PSRR form, and the same approach is broadly applicable across geographies and taxonomic groups. creator: Brian G. Tavernia uri: https://doi.org/10.7717/peerj.20297 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Tavernia title: Cognitive domain-specific impairments and associated risk factors in type 2 diabetes mellitus: a cross-sectional observational study based on neuropsychological assessment from Xiamen, China link: https://peerj.com/articles/20292 last-modified: 2025-11-04 description: BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment, yet limited research has been conducted in subtropical regions of China.ObjectiveTo examine the characteristics of cognitive impairment and identify the potential risk factors in patients with T2DM in Xiamen.MethodsThis cross-sectional observational study included 84 patients with T2DM from Zhongshan Hospital Xiamen University. Patients were grouped based on their Montreal Cognitive Assessment (MoCA) scores into a cognitively impaired group (T2DM-CI group, n = 52) and a cognitively normal group (T2DM-NCI group, n = 32). Multivariate logistic regression was used to identify independent risk factors.ResultsAmong the 52 patients in the T2DM-CI group, the most commonly affected cognitive domains were executive function (82.7%), language (75.0%), memory (61.5%), and attention (48.1%), with 59.6% exhibiting impairments in three or more domains. Compared with the T2DM-NCI group, the T2DM-CI group showed poorer performance in most MoCA subdomains—including visuospatial/executive function, language, delayed recall, abstraction, and orientation—as well as in individual cognitive domain tests (all P < 0.05), except for the Clock Drawing Test. Older age (OR = 1.167, 95% CI [1.045–1.303], P = 0.006) and higher lipoprotein (a) levels (OR = 1.109, 95% CI [1.020–1.205], P = 0.015) were independently associated with cognitive impairment in T2DM patients.ConclusionCognitive impairment in T2DM affects multiple domains, with executive dysfunction most prominent. Age and elevated lipoprotein(a) may increase risk. Routine cognitive screening is warranted, particularly in older patients and those with vascular risk factors. creator: Xueling Xiao creator: Luling Chen creator: Jingqi Liu creator: Jiayan Cai creator: Manxiang Deng uri: https://doi.org/10.7717/peerj.20292 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Xiao et al.