Serum cystatin-C and all-cause mortality in patients with hypertrophic cardiomyopathy: a retrospective cohort study
Background Numerous studies across various populations have revealed that elevated cystatin-C levels are associated with an excessive risk of mortality. However, the prognostic value of cystatin-C remains unidentified in hypertrophic cardiomyopathy (HCM) patients. The objective of this study was to investigate whether serum cystatin-C could predict all-cause mortality independently in HCM patients. Methods Data from 456 HCM patients treated at West China Hospital were collected and stratified into two groups based on the median baseline serum cystatin-C level. All-cause mortality was the primary outcome. Cox regression models were used to analyze the association between cystatin-C levels and mortality risk. Results A total of 90 deaths were recorded over a median follow-up period of 4.67 years. Patients with higher cystatin-C levels had an increased risk of all-cause mortality (adjusted hazard ratio (HR): 2.11, 95% CI [1.30–3.42], p = 0.003) compared to those with lower levels. Time-dependent area under the curves (AUC) of cystatin-C in different time points, ranging from initial measurement to follow-up, showed a relatively stable fluctuation between 0.70 and 0.80. In comparison, the commonly used renal function markers, estimated glomerular filtration rate (eGFR) and serum creatinine, yielded lower AUC values. Restricted cubic spline curves showed that with median value of cystatin-C (1.01 mg/L) as reference, there was a gradual rise in risk of all-cause mortality with cystatin-C increasing. Subgroup analyses in female, in the patients ≥ 58 years old, and in the patients with eGFR ≥ 60 mL/min/1.73 m2 consistently confirmed robustness of the main findings. Conclusion Elevated serum cystatin-C levels are associated with a higher risk of all-cause mortality in HCM patients, providing valuable prognostic information beyond traditional renal function markers such as eGFR and serum creatinine.
Liu et al. (2025) Serum cystatin-C and all-cause mortality in patients with hypertrophic cardiomyopathy: a retrospective cohort study. PeerJ 13:e19631 https://doi.org/10.7717/peerj.19631
Prognostic implications of microRNA-107 in esophageal cancer: a retrospective cohort study
Background Esophageal squamous cell carcinoma (ESCC) imposes a heavy disease burden in China, accounting for over 50% of global cases and approximately 301,000 annual deaths. Current prognostic markers inadequately predict recurrence in early-stage patients. This study investigates microRNA-107 (miR-107) as a novel prognostic biomarker for ESCC. Methods Tumor tissues (n = 66) and adjacent normal tissues (n = 28) were collected from ESCC patients undergoing radical surgery (2010–2012). miR-107 expression was quantified via reverse transcription quantitative polymerase chain reaction (RT-qPCR) (normalized to U6 snRNA). Clinicopathological correlations and survival outcomes were analyzed using χ2 tests, Kaplan–Meier/log-rank tests, and Cox regression. Comparative analysis of miR-107 levels was performed in human esophageal squamous cell carcinoma line 109 (EC109) cancer cells versus human esophageal epithelial cell (HEEC) normal epithelial cells. Results miR-107 expression was significantly lower in esophageal cancer tissues (0.801 ± 0.737) compared to adjacent non-cancerous tissues (1.390 ± 1.346), p = 0.006. Low miR-107 expression (cutoff = median) correlated with advanced tumor, node, metastasis stage (TNM stage) (I vs. V: 100% vs. 21.4%, P < 0.001), lymph node metastasis (73.1% vs. 35%, P < 0.001), and larger tumor size (70% vs. 33.3%, P < 0.001). Patients with low miR-107 had shorter median overall survival (10 vs. 59 months; Hazard Ratio (HR) = 0.475, 95% Confidence Interval (CI) [0.247–0.915]; P < 0.001). Multivariate Cox analysis confirmed miR-107 as an independent prognostic factor alongside TNM stage (HR = 3.586, 95% CI [2.253–5.708]; P < 0.001). Consistently, EC109 cells exhibited 59% lower miR-107 levels than HEEC (P = 0.029). Conclusions miR-107 downregulation is a robust predictor of aggressive ESCC phenotypes and poor survival. It holds promise as a clinical biomarker for risk stratification and personalized therapy. Future studies should validate these findings in multicenter cohorts and elucidate miR-107’s functional mechanisms.
Sun et al. (2025) Prognostic implications of microRNA-107 in esophageal cancer: a retrospective cohort study. PeerJ 13:e20327 https://doi.org/10.7717/peerj.20327
Effect of short-term exposure to air pollution on ischemic stroke incidence and mortality: a five-year time-series study in Jining, China
Background Short-term exposure to air pollutants is associated with an increased risk of ischemic stroke incidence and mortality. However, there is a lack of research based on data from disease surveillance systems. This study used disease surveillance system data to quantitatively analyze the association between air pollution and ischemic stroke incidence and mortality in Jining, China. Methods The stroke registration system of the Jining City Center for Disease Control and Prevention (CDC) includes information on confirmed stroke cases reported by all medical institutions in the jurisdiction, covering a population of 8.9 million. Generalized linear regression models combined with distributed lag nonlinear models (DLNM) were used to determine the association between air pollutants and ischemic stroke incidence and mortality. Stratified analyses by sex, age, and season were also conducted. Results During the study period (January 1, 2018, to December 31, 2022), there were 209,949 ischemic stroke incidence cases and 23,565 ischemic stroke-related deaths. There were more ischemic stroke incidence and death cases in males compared to females. The number of incidence cases was higher in the warm season (52.6%) than in the cold season (47.4%), while this pattern was reversed for the number of deaths, with a higher number of deaths in the cold season (55.9%) than in the warm season (44.1%). This study showed that exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and carbon monoxide (CO) was associated with ischemic stroke incidence, and exposure to PM2.5, PM10, sulfur dioxide (SO2), and CO was associated with ischemic stroke mortality. The relative risks (RRs, with 95% CIs) for ischemic stroke incidence at the maximum single-lag effect day for each interquartile range (IQR) increment for PM2.5, PM10, NO2, and CO were 1.007 (1.001–1.014), 1.004 (1.000–1.008); 1.031 (1.011–1.051), and 1.008 (1.001–1.015), respectively. The RRs (with 95% CIs) for mortality for PM2.5, PM10, SO2, and CO were 1.049 (1.025–1.073), 1.031 (1.014–1.048), 1.021 (1.001–1.041), and 1.044 (1.017–1.071), respectively. Furthermore, the association between air pollution and ischemic stroke incidence risk was modified by age and season. Individuals aged >75 years were more vulnerable to SO2-induced ischemic stroke incidence risk, and PM2.5 and CO were more harmful in the cold season. Conclusion These findings suggest that short-term exposure to PM2.5, PM10, SO2, NO2, and CO leads to increased ischemic stroke morbidity and mortality. The elderly population, as well as the general population, should be better protected during the cold season.
Kong et al. (2025) Effect of short-term exposure to air pollution on ischemic stroke incidence and mortality: a five-year time-series study in Jining, China. PeerJ 13:e20298 https://doi.org/10.7717/peerj.20298
Are caves enough to represent karst groundwater biodiversity? Insights from geospatial analyses applied to European obligate groundwater-dwelling copepods
Caves are recognized as biodiversity hotspots for groundwater fauna, including obligate groundwater-dwelling copepods (Crustacea: Copepoda), exhibiting high species richness, endemism, and phylogenetic rarity. However, the extent to which caves alone provide a representative estimate of copepod species richness in karst areas remains uncertain. Taking advantage of the recently published EGCop dataset, the first expert-validated, Europe-wide occurrence dataset for obligate groundwater-dwelling copepods (hereinafter, GW copepods), this study investigates the distribution of GW copepods into karst areas, comparing species richness in caves versus other karst groundwater habitats (e.g., springs, karst streams, artificial wells), within and among the European karst units. The main aims are: (i) identifying karst areas which represent hotpots of GW copepod species richness; (ii) assessing to which extent caves, as open windows to the subterranean environments, contribute to define hotspots of GW copepods’ species richness into karst areas across Europe. EGCop comprises 6,986 records from 588 copepod species/subspecies distributed among four orders: Cyclopoida (3,664 records, 184 species), Harpacticoida (3,288 records, 395 species), Calanoida (32 records, seven species), and Gelyelloida (two records, two species). To perform geospatial analyses, we filtered the dataset by: (i) selecting only the records with spatial uncertainty in the associated coordinates lower than 10 km; (ii) searching for those records falling within, or very close to, the polygons representing European karst areas. Species richness hotspots were then estimated through geospatial analyses in geographic information system (GIS) environment. Within the selected records, those specifically referring to karst habitats (2,526 records, 369 species) are primarily represented by Harpacticoida (1,199 records, 228 species) and Cyclopoida (1,293 records, 132 species). Among species collected from karst habitats, records from caves (1,867, 73.9%) belong to 318 species (Harpacticoida = 189, Cyclopoida = 122, Calanoida = 7), representing 86.1% of the total species richness of karst habitats. Geospatial analyses reveal that the European hotspots of GW copepods’ species richness recorded exclusively in caves reflect the spatial arrangement of postglacial refugia in southern karst regions, though representing a subset of the broader diversity found across all karst groundwater habitats. Our findings highlight that the contribution of cave systems in groundwater biodiversity assessments and related conservation planning may vary depending on the evolution and morphologies of the target karst regions—often pointing to a high representativeness of caves for subterranean biodiversity, sometimes revealing their lower explanatory power within the broader karst systems.
Galmarini et al. (2025) Are caves enough to represent karst groundwater biodiversity? Insights from geospatial analyses applied to European obligate groundwater-dwelling copepods. PeerJ 13:e20285 https://doi.org/10.7717/peerj.20285
Breaking epigenetic shackles: targeting ARID1A methylation and the PI3K/AKT/mTOR-PD-L1 axis to overcome immune escape in gastric cancer
Objective AT-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. Methods We 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). Results Promoter 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). Conclusion ARID1A 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.
Duan et al. (2025) Breaking epigenetic shackles: targeting ARID1A methylation and the PI3K/AKT/mTOR-PD-L1 axis to overcome immune escape in gastric cancer. PeerJ 13:e20251 https://doi.org/10.7717/peerj.20251
Retrospective study on the association between paternal occupational exposure to agrochemicals and childhood leukemia in Michoacán de Ocampo, México
Objectives The 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. Methods A 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. Results A 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). Conclusions The 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.
Jiménez-Alcántar et al. (2025) Retrospective study on the association between paternal occupational exposure to agrochemicals and childhood leukemia in Michoacán de Ocampo, México. PeerJ 13:e20219 https://doi.org/10.7717/peerj.20219
Auditory processing ability in Thai native speakers with the Gaps-In-Noise (GIN) test
Introduction Auditory 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. Methods This 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. Results The 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. Conclusion The 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.
Jeanbunjongkij et al. (2025) Auditory processing ability in Thai native speakers with the Gaps-In-Noise (GIN) test. PeerJ 13:e20207 https://doi.org/10.7717/peerj.20207
Analysis of the chitin synthase gene family in Ganoderma lucidum: its structure, phylogeny, and expression patterns
Background Chitin 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. Methods A 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. Results In 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.
Liu et al. (2025) Analysis of the chitin synthase gene family in Ganoderma lucidum: its structure, phylogeny, and expression patterns. PeerJ 13:e20302 https://doi.org/10.7717/peerj.20302
CD81 inhibits the proliferation of acute megakaryoblastic leukemia cells
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.
Su et al. (2025) CD81 inhibits the proliferation of acute megakaryoblastic leukemia cells. PeerJ 13:e20286 https://doi.org/10.7717/peerj.20286
Biocontrol-relevant diversity of wheat-associated Pseudomonas: prevalence of P. sivasensis and identification of the novel species P. arvensis sp. nov.
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.
Delitte et al. (2025) Biocontrol-relevant diversity of wheat-associated Pseudomonas: prevalence of P. sivasensis and identification of the novel species P. arvensis sp. nov.. PeerJ 13:e20177 https://doi.org/10.7717/peerj.20177