title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=46 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: The safety and efficacy of phosphodiesterase type 5 inhibitors in the treatment of diabetic erectile dysfunction: a systematic review and meta-analysis link: https://peerj.com/articles/20147 last-modified: 2025-10-07 description: BackgroundPrevious studies have confirmed the efficacy of phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) in treating diabetic erectile dysfunction (DED), but they still have research value in terms of efficacy comparison and individualized safety. This study, while evaluating safety and efficacy, also focused on the sources of heterogeneity and innovatively explored the nonlinear relationship between therapeutic effect and age.AimThis study aimed to systematically evaluate the safety and efficacy of PDE-5 inhibitors for the treatment of DED and the related application effects and to provide a clinical basis for its treatment.MethodsBy searching PubMed, Embase, Web Of Science, Cochrane Library, China Knowledge Network (CNKI), Wipro (VIP), Wanfang, and China Biomedical Literature Database (CBM) before December 31, 2024, and reading the retrieved articles and references, PDE-5 inhibitors for diabetic erectile dysfunction in randomized controlled trials (RCTs). The literature of the included studies was evaluated using the Cochrane Literature Quality Assessment Tool. The meta-analysis was registered to PROSPERO (CRD42025637725).OutcomesThe International Index of Erectile Function (IIEF-5) overall and related evaluation questionnaires were used as the primary efficacy evaluation indicators, and adverse events were used as secondary indicators.ResultsMeta-analysis was performed using Rever Manager 5.3 and STATA18 software. A total of 10 studies were included, and random-effects model meta-analysis analyzed the post-treatment efficacy of the 10 articles with a combined RR = 2.91, 95% CI of [1.95–4.34], P < 0.001. Fixed-effects model meta-analysis investigated adverse effects with RR = 2.0, 95% CI of [1.53–2.61], P < 0.001. There was a non-linear relationship between age and PDE-5 inhibitors.ConclusionPDE-5 inhibitors can safely and effectively improve diabetic erectile dysfunction, but the degree of effectiveness of different types of drugs, the occurrence of related adverse effects, and the differences that exist between individuals still need to be taken into account during use. creator: Zexin Zhu creator: Jian Xu creator: Bo Dai creator: Minghao Lin creator: Huhu Yang creator: Shilin Liu creator: Pengjie Bao creator: Zheng Nan uri: https://doi.org/10.7717/peerj.20147 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zhu et al. title: Comprehensive analysis of DNA methylation patterns in recurrent miscarriage: imprinted/non-imprinted genes and their regulation across sperm and fetal-maternal tissues link: https://peerj.com/articles/20125 last-modified: 2025-10-07 description: BackgroundEpigenetic regulation, including DNA methylation, is essential for normal embryonic development and maternal-fetal interactions. Recurrent miscarriage (RM), defined as the loss of two or more consecutive pregnancies, poses significant clinical and emotional challenges. However, the role of epigenetic alterations in RM, particularly in gametes and placental tissues, remains underexplored. This study aims to investigate global DNA methylation profiles and imprinting gene expression in the context of RM, providing insights into epigenetic mechanisms that contribute to pregnancy failure.MethodsGenome-wide DNA methylation profiling was performed on sperm and chorionic villi from RM patients and control couples undergoing artificial abortion using the Illumina HumanMethylation 450 BeadChip platform. Genes related to differentially methylated probes (DMPs) in functionally critical genomic regions, including enhancers, promoters, and DNase hypersensitive sites (DHS), were identified and submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Key imprinting genes (CPA4 and PRDM16) were validated at the protein level using Western blotting.ResultsRM samples exhibited a significant increase in hypermethylated DMPs across all analyzed tissues, with villi and decidua showing the highest numbers of epigenetic changes. Enrichment analyses highlighted pathways implicated in tissue morphogenesis, immune regulation, and cell signaling, including the PI3K-Akt, TGF-beta, and Wnt signaling pathways. Among imprinting genes, CPA4 and PRDM16 showed distinct hypomethylation at enhancer regions, corresponding to elevated protein expression in RM villi tissues.ConclusionsThis study identifies profound epigenetic dysregulation in RM-associated tissues, emphasizing the contribution of imprinting gene methylation abnormalities to pregnancy loss. Future studies incorporating functional assays and animal models are essential to elucidate the causal roles of candidate genes in RM pathogenesis and maternal-fetal health. creator: Yanru Niu creator: Lanlan Yin creator: Yulan Zhou creator: Xiaoyan Pang creator: Yunqinq Li creator: Cailing Peng creator: Meihua Yao creator: Guoling Zhang creator: Kaijie Yang creator: Tianzhong Ma uri: https://doi.org/10.7717/peerj.20125 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Niu et al. title: Sucking lice in bandicoot rats with first complete description of Hoplopleura malabarica nymphs link: https://peerj.com/articles/20115 last-modified: 2025-10-07 description: BackgroundStudies of insect biodiversity and parasitism are often based on adult stages, as immature stages are poorly known and often cannot be identified to species level. However, sucking lice (Anoplura) are permanent, hematophagous parasites with single-host life cycles, making it possible to track the occurrence of all life stages. Only the complete identification of all life stages provides a full picture of parasitism, including infestation levels, parasite topography preferences on the host, and host specificity. The detection of different development stages on a host provides strong evidence that lice of a particular species are actively reproducing and completing their life cycle on that host, making full use of its resources. Conversely, the presence of adult lice alone, particularly when found sporadically, may suggest a failed or incidental attempt at host colonization rather than an established parasitic association.MethodologyThe description of the nymphal stages of Hoplopleura malabarica is based on specimens of sucking lice from the greater bandicoot rat Bandicota indica from Southeast Asia, specifically from the Vientiane area of Lao PDR. The study used morphometric analysis and scanning microscopy techniques.ResultsThis study presents the first description of the nymphal stages of Hoplopleura malabarica, an oligoxenous parasite of rodents of the genus Bandicota. In addition, a global checklist of Anoplura parasitizing rodents of the genus Bandicota was provided.ConclusionsThe detection of different life stages of lice within the host confirms that they reproduce and develop on a given host species, fully utilizing its resources. creator: Paulina Kozina creator: Joanna N. Izdebska creator: Serge Morand creator: Alexis Ribas uri: https://doi.org/10.7717/peerj.20115 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Kozina et al. title: Transcriptome reveals differential expression of flavor and color in closely related strains of tomato (Solanum lycopersicum) link: https://peerj.com/articles/20113 last-modified: 2025-10-07 description: Fruit flavor and color are critical quality characteristics of tomatoes (Solanum lycopersicum). Numerous studies have demonstrated that tomato flavor is primarily linked to the sugar-acid content and its ratio, while fruit color is predominantly determined by the composition and concentration of carotenoids and flavonoids. To elucidate the regulatory mechanisms underlying the differences in sugar-acid and color formation during fruit ripening, transcriptome analysis was conducted for the first time on the breaker stage (Br) and mature fruit stage (MF) of the closely related strains yellow-fruited tomato (No. 19) and red-fruited tomato (No. 20). This analysis aimed to identify key regulatory genes and biosynthetic pathways associated with the formation of flavor and color in tomato fruits. The transcriptome analysis revealed that 1,546 differentially expressed genes (DEGs) were identified in the Br19_vs_Br20 comparison, of which 507 were up-regulated and 1,039 were down-regulated. In the MF19_vs_MF20 comparison, 2,178 DEGs were detected, with 1,235 up-regulated and 943 down-regulated. Upon further analysis of the DEGs, we identified several key genes in the sugar-acid metabolic pathway, including sucrose synthase (SUS), phosphofructokinase (PFK), fructose-bisphosphate aldolase (FBA), citrate synthase (CS), and succinate dehydrogenase (SuDH), which may significantly influence tomato flavor. Additionally, differential genes related to carotenoid and flavonoid metabolism, such as cytochrome P450 98A (CYP98A), caffeoyl-CoA3-O-methyltransferase (CCoAMT), carotenoid isomerase (CRTISO), lycopene beta cyclase (LCYB), zeaxanthin epoxidase (ZEP), violaxanthin deepoxidase (VDE), and 9-cis-epoxycarotenoid dioxygenase (NCED), as well as genes linked to ethylene synthesis, such as 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), may play a role in the color changes observed in tomatoes. The findings of this study provide insights into the underlying mechanisms of flavor and color development in tomato fruit, offering valuable information for the genetic improvement of tomatoes. creator: Chunmei Guo creator: Xiuyuan Liu creator: Yingfeng Ding creator: Zhaoyilan He creator: Songmei Shi creator: Yumei Ding creator: Hui Shen creator: Zhengan Yang uri: https://doi.org/10.7717/peerj.20113 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Guo et al. title: Comparison of animal models for immune premature ovarian insufficiency link: https://peerj.com/articles/20091 last-modified: 2025-10-07 description: Premature ovarian insufficiency (POI) severely impacts women’s reproductive and overall health, yet effective treatments remain elusive. Research on its pathogenic mechanisms and therapeutic strategies is therefore critical. Due to the scarcity of ovarian samples from POI patients, animal models have become indispensable tools for investigation. Notably, immune-related POI accounts for an increasing proportion of cases, with over half of idiopathic POI cases hypothesized to involve immune dysregulation. Consequently, immune-mediated POI animal models are widely used to study immune-related mechanisms. This article compares the advantages, limitations, and applications of various immune-related POI animal models, aiming to guide researchers in selecting the most appropriate model for their specific research goals and experimental designs. creator: Anchun Hu creator: Yanli Mu creator: Guanyou Huang creator: Shuyun Zhao uri: https://doi.org/10.7717/peerj.20091 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Hu et al. title: Geology correlates with gut microbial community composition in the Mountainsnails (Oreohelicidae: Oreohelix) link: https://peerj.com/articles/20080 last-modified: 2025-10-07 description: BackgroundSpecies that require soil mineral macronutrients for survival may depend on specific microbiome communities to aid in nutrient processing. Land snails, which utilize environmental minerals to synthesize a shell of calcium carbonate (CaCO3), may rely on or possess distinct gut microbiome communities depending on soil mineral characteristics. Here, we investigate whether the occurrence of calcareous vs. non-calcareous soils is associated with shifts the composition of the gut microbiome of the calciphilous and highly diverse land snail genus Oreohelix from the Western United States.MethodsWe collected snail and soil samples from nine sites in central Idaho: five near, and four away from calcium-rich geology. We sequenced the V4 region of the 16S rRNA gene of these samples to assess the gut microbiome compositions of Oreohelix land snails on and off calcium-rich substrates. After data clean-up and filtering we had 68 snail and 25 soil microbiome samples.ResultsWe found that snail gut microbiomes differed significantly from the surface soil microbiome, with many amplicon sequence variants being unique and ubiquitous in the snails. We also found small, but significant, differences between snails on and off calcium-rich rocks. Our findings indicate that the gut microbial community assembly process of land snails is complex and does not reflect a simple relationship with the underlying soil microbiome. While we find a pattern of differences associated with the proximity of calcium-rich geology, the snail microbiome communities are likely forming based on a variety of other factors, including diet and host filtering. Furthermore, we found multiple microbial taxa that were ubiquitous in the snails and rare in the nearby substrate microbiomes. Future work should focus on disentangling the role of habitat and the functional importance (or lack thereof) of the microbial taxa that are common to almost every sampled snail. creator: Ian M. Oiler creator: T. Mason Linscott creator: Christine E. Parent uri: https://doi.org/10.7717/peerj.20080 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Oiler et al. title: Diagnostic accuracy of the atherogenic index of plasma in metabolic syndrome: a diagnostic meta-analysis link: https://peerj.com/articles/20074 last-modified: 2025-10-07 description: ObjectiveThis study aims to assess the diagnostic performance of the atherogenic index of plasma (AIP) in estimating the risk of metabolic syndrome (MetS) among adults across various geographic regions.MethodsA comprehensive search was conducted across EMBASE, Web of Science, PubMed, and the Cochrane Library from their inception until September 29, 2024. Eligible studies were selected and evaluated for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) framework. Statistical analyses were performed using STATA 15.1. Sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios, the summary receiver operating characteristic (SROC), curve, and 95% confidence intervals (CI) were calculated to assess the diagnostic accuracy of AIP for MetS. Statistical significance was defined as a p-value < 0.05.ResultsEleven observational studies involving 36,463 participants were included. The analysis showed that AIP is an effective biomarker for identifying the risk of MetS, with an area under the curve (AUC) of 0.84 (95% CI [0.81–0.87]). AIP demonstrated comparable diagnostic value in both males and females, with an AUC of 0.82, highlighting its potential utility in sex-specific assessments. Geographic region, diagnostic reference standards, and publication year were identified as potential sources of heterogeneity.ConclusionsThis study demonstrates that AIP is a relatively accurate tool for detecting MetS, supporting its role in prevention and in reducing the risk of associated chronic diseases. Further research with larger sample sizes and multi-center designs is needed to explore the combined use of AIP with other biomarkers to enhance diagnostic accuracy for MetS. creator: Yuge Gao creator: Chengcheng He creator: Jia Mi uri: https://doi.org/10.7717/peerj.20074 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Gao et al. title: Genetic modifiers of response to thalidomide in transfusion-dependent beta-thalassemia patients: a whole-exome sequence analysis link: https://peerj.com/articles/20038 last-modified: 2025-10-07 description: BackgroundThalidomide induces fetal hemoglobin and renders most thalassemia patients transfusion-independent. Some patients, however, do not respond. Underlying genetic variations responsible for variable responses to thalidomide are unexplored.Aims and objectivesTo discover genetic variations that influence response to thalidomide in transfusion-dependent beta-thalassemia patients.MethodsTwenty beta-thalassemia patients (14 excellent responders and six non-responders) who had received thalidomide were included in the study by a non-probability purposive sampling technique. Patients who showed a rise of >2 mg/dl in hemoglobin level and/or whose hemoglobin levels reached 9 gm/dl without blood transfusions were designated as excellent responders. Patients whose hemoglobin levels did not show an increment rise of >2 and/or whose hemoglobin levels did not rise above 5.9 gm/dl and needed blood transfusions to maintain optimal hemoglobin levels were designated as non-responders. DNA was extracted, and whole-exome sequencing was performed on an Illumina HiSeq System. Aligning and variant calling were done by the Sentieon software. Annotation was done by Annovar.ResultsThe age of study participants ranged from 1–12 years, with a mean of 5.45 ± 3.81 years. There were 17 (85%) males and three (15%) females. A total of 222,180 germline variants were identified across 20 subjects, from which 24 candidate variants across 24 genes were identified. The three most common polymorphisms in the excellent responder group were found in the exon region of CHI3L1 (rs880633), NPNT (rs35132891), and ZNF 208 (rs10425763), which were found in 92%, 85%, and 71% cases, respectively. The commonest polymorphisms in the non-responder group were found in the PM20D1 gene (rs7518979), LGR6 (rs75658797), MYH15 (rs4299484), and RESF1 (rs3207618), each of which was found in 66.6% cases.ConclusionThis study shows a significant association of single-nucleotide polymorphisms rs880633, rs35132891, and rs10425763 with excellent response status, while rs7518979, rs75658797, rs4299484, and rs3207618 are associated with non-response status. creator: Waleed Mohammed Bawazir creator: Muhammad Ihtesham Khan creator: Mohannad Saeed Hazzazi creator: Ammar Abdullah Basabrain creator: Muhammad Tariq Masood Khan creator: Sami Siraj creator: Majed Naser Almashjary creator: Osman Radhwi creator: Steve Harakeh creator: Yasar Mehmood Yousafzai uri: https://doi.org/10.7717/peerj.20038 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Bawazir et al. title: Soil storage temperature and air-drying did not significantly change bacterial taxa in the short-term link: https://peerj.com/articles/20162 last-modified: 2025-10-06 description: Analysing soil microbial communities is vital for understanding ecosystem health, but samples from remote locations often require preservation before DNA can be extracted. In this study, we used the 16S rRNA amplicon sequencing to investigate how different storage methods affect soil microbial diversity over 4 weeks. We implemented storage temperature and moisture as two experimental factors. Three topsoils (sandy, silty loam, and clay loam) were collected and stored under four conditions: frozen at −20 °C, refrigerated at 4 °C, room temperature, and air-dried. DNA extractions and sequencing were performed at 1, 3, 7, 14, and 28 days. Our results revealed that storage temperature and moisture did not substantially change bacterial diversity and composition across all three soil types. Rare taxa showed a similar pattern to abundant taxa but were more variable in beta diversity. Overall, all tested methods effectively preserved both abundant and rare taxa in the short term. However, the long-term impacts of the sample storage, particularly on rare taxa, need further exploration. creator: Mingming Du creator: Peipei Xue creator: Budiman Minasny uri: https://doi.org/10.7717/peerj.20162 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Du et al. title: Bioinformatic analysis and experimental validation of hub autophagy-related genes as novel biomarkers for type 2 diabetes mellitus and Alzheimer’s disease link: https://peerj.com/articles/20143 last-modified: 2025-10-06 description: Background & ObjectivesAlzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) share considerable similarities in their proposed patho mechanisms. Autophagy, an intrinsic cellular process involved in the degradation of dysfunctional organelles and abnormal proteins, has been implicated in the pathogenesis of both AD and T2DM. This study aims to identify potential shared biomarkers related to autophagy in AD and T2DM by analyzing hub differentially expressed autophagy-related genes (DEARGs) and examining their potential functions.MethodsGene expression profiles for AD and T2DM were acquired from the Gene Expression Omnibus (GEO) database (training sets: GSE109887 for AD and GSE104674 for T2DM; validation sets: GSE122063 for AD and GSE64998 for T2DM). Autophagy-related genes (ARGs) were extracted from multiple databases. DEARGs were identified and integrated with module genes derived from weighted gene co-expression network analysis (WGCNA) to determine key shared ARGs. Then, the STRING database was used to construct a protein-protein interaction (PPI) network, from which hub genes were identified. These hub genes were validated using independent microarray datasets through differential expression analysis, and ROC curves were generated to assess their diagnostic value. Moreover, the expression of the hub genes was validated in brain tissues of T2DM mouse models using qRT-PCR.ResultsA total of 33 shared DEARGs were identified, among which 12 were designated as hub genes (ANXA5, CCND1, MAP2K1, HSPB1, BNIP3, BAG3, YAP1, MET, FBXW7, CCL2, PFKFB3, CDKN1A) in both AD and T2DM patients. Validation using other datasets confirmed that ANXA5, BAG3, and CDKN1A remained significantly upregulated, while MET remained downregulated in both AD and T2DM patients. Additionally, PFKFB3 showed an inverse expression pattern between the two diseases. The diagnostic performance of these five hub genes was assessed using ROC curves, with all five exhibiting values of area under the curve (AUC) exceeding 0.7 for T2DM in both training and validation sets. However, only MET and PFKFB3 demonstrated good diagnostic efficacy in AD patients. In animal models, qRT-PCR analysis revealed that the expression of ANXA5, BAG3, and MET was consistent with the bioinformatics results. In contrast, the expression of PFKFB3 and CDKN1A did not differ significantly between db/db model mice and db/m control mice.ConclusionsOur integrated bioinformatics analyses, supported by preliminary experimental validations, identified several hub ARGs shared between AD and T2DM. Among these, ANXA5, BAG3, and MET exhibited consistent expression trends across datasets and experimental models, while CDKN1A and PFKFB3 showed inconsistent expression patterns. These findings underscore the complexity of autophagy-related crosstalk in AD-T2DM comorbidity and highlight the need for further research to clarify their diagnostic and therapeutic potential. creator: Rui Zhang creator: Ruowei Wang creator: Shuna Zhai creator: Chunhong Shen creator: Yu An creator: Quanri Liu uri: https://doi.org/10.7717/peerj.20143 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zhang et al.