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Antimicrobial resistance and molecular detection of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli in municipal wastewater in Marrakech

PLoS ONE Oumaima El garraoui, Amal Loqman, Fatima-Ezahra Amouat et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0325816

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) poses a major threat to public health. However, its environmental dissemination, especially through wastewater, remains insufficiently addressed. This paper examines the presence of ESBL-EC in composite influent and effluent samples from Marrakech’s wastewater treatment plant. Samples were screened on selective agar and isolated strains were identified by MALDI Biotyper® Sirius System. The sensitivity of bacteria to antibiotics was determined by disk diffusion method and phenotypic tests were conducted to detect ESBL production. Molecular identification was characterized by PCR and DNA sequencing. From a total of 72 wastewater samples, 364 resistant Enterobacteriaceae isolates were recovered, of which 134 were confirmed as ESBL-EC, with 78.35% exhibiting multidrug resistance (MDR) phenotypes. The blaCTX-M gene was the most prevalent among isolates obtained from influent samples, followed by blaTEM at 81.25% and blaSHV at 16.67%. Although biological treatment reduced the number of ESBL-EC isolates harboring resistance genes, a significant proportion remained detectable in the final effluent, even after UV disinfection, highlighting the limited efficacy of standard treatment processes in eliminating them. These findings underscore the urgent need to enhance wastewater treatment strategies. Implementing advanced technologies, such as membrane filtration or ozonation, combined with routine monitoring, is critical to reduce the environmental release of resistant bacteria and mitigate their public health risks.

Retraction: Ribosome-Dependent ATPase Interacts with Conserved Membrane Protein in Escherichia coli to Modulate Protein Synthesis and Oxidative Phosphorylation

PLoS ONE Jun 16, 2025 DOI: 10.1371/journal.pone.0326327

A machine learning based authentication and intrusion detection scheme for IoT users anonymity preservation in fog environment

PLoS ONE Khondokar Oliullah, Md Whaiduzzaman, Md. Julkar Nayeen Mahi et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0323954

Authentication is a critical challenge in fog computing security, especially as fog servers provide services to many IoT users. The conventional authentication process often requires disclosing sensitive personal information, such as usernames, emails, mobile numbers, and passwords that end users are reluctant to share with intermediary services (i.e., Fog servers). With the rapid growth of IoT networks, existing authentication methods often fail to balance low computational overhead with strong security, leaving systems vulnerable to various attacks, including unauthorized access and data interception. Additionally, traditional intrusion detection methods are not well-suited for the distinct characteristics of IoT devices, resulting in a low accuracy in applying existing anomaly detection methods. In this paper, we incorporate a two-step authentication process, starting with anonymous authentication using a secret ID with Elliptic Curve Cryptography (ECC), followed by an intrusion detection algorithm for users flagged as suspicious activity. The scheme allows users to register with a Cloud Service Provider (CSP) using encrypted credentials. The CSP responds with a secret number reserved in the Fog node for the IoT user. To access the services provided by the Fog Service Provider (FSP), IoT users must submit a secret ID. Furthermore, we introduce a staked ensemble learning approach for intrusion detection that achieves 99.86% accuracy, 99.89% precision, 99.96% recall, and a 99.91% F1-score in detecting anomalous instances, with a support count of 50,376. This approach is applied when users fail to provide a correct secret ID. Our proposed scheme utilizes several hash functions through symmetric encryption and decryption techniques to ensure secure end-to-end communication.

Interventions supporting the translation of gerontological evidence into practice to optimize functional outcomes for hospitalized older adults: A scoping review

PLoS ONE Kathleen F. Hunter, Jeffrey I. Butler, Shovana Shrestha et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0324953

Background and objectives Hospitalized older adults are at risk for both physical and cognitive functional decline. To support the implementation of interventions optimizing their function, both healthcare professional knowledge and other factors that may impact practice change should be addressed. The objective of this study was to examine the characteristics and type of interventions supporting the translation of gerontological evidence into practice to optimize functional outcomes for hospitalized older adults. Materials and methods This scoping review used the guidelines recommended by Peters et al. Six electronic databases were searched from database inception to 2024. Included studies were primary research studies that 1) described an educational intervention for healthcare professionals as part of an initiative to promote practice change and 2) assessed functional outcomes (physical and/or cognitive), Results Thirty-eight studies were deemed eligible. Numerous interventions to support implementation of knowledge to improve functional outcomes were identified. In addition to educational strategies, other interventions addressed care processes, changes to the built environment, administration/management support, leadership support/facilitation, and discharge/transition planning. Studies employed a range of measures to assess functional outcomes among hospitalized older adults. Discussion Older studies tended to focus on nurse-driven interventions, and newer ones on interprofessional interventions. Knowledge gaps were highlighted in terms of theory, research designs, intervention descriptions, country representation, policy, environmental changes, and leadership roles. Future evaluations of interventions to enhance older adults’ functioning should examine effectiveness and compare single- and multi-intervention programs. Strategies based on implementation science theory are needed to ensure successful uptake of effective interventions, while also addressing real-world issues in hospital units, such as short staffing, resource constraints, and overcrowding.

Rapid determination of sodium pentachlorophenate in bamboo and wooden cutting boards via ultrasonic-assisted liquid-liquid extraction coupled with ultra-performance liquid chromatography-high resolution mass spectrometry

PLoS ONE Ye Wang, Mingyou Hu, Fang Wang et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326129

Sodium pentachlorophenate (PCP-Na) is a toxic preservative used in wood products, posing potential health risks through food contact materials. A rapid analytical method combining ultrasonic-assisted liquid-liquid extraction with ultra-performance liquid chromatography-high resolution mass spectrometry (UA-LLE-UPLC-HRMS) was developed for the determination of PCP-Na residues in bamboo and wooden cutting boards. Sample pretreatment involved ultrasonic extraction using methanol/water (50:50 v/v, 2.0% ammonia), followed by liquid-liquid purification with n-hexane/ethyl acetate (60:40 v/v). After solvent evaporation under nitrogen, the residue was reconstituted in the initial mobile phase. Chromatographic separation was achieved on an Acquity UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 µm) using a gradient elution of methanol and 0.01% ammoniated aqueous solution. Detection was performed in negative electrospray ionization (ESI-) mode with targeted single ion monitoring (Targeted-SIM) scanning, utilizing pentachlorophenol-13C6 (PCP-13C6) as an isotopically labeled internal standard. The method exhibited excellent linearity across a concentration range of 1.0–500.0 μg/L (R2 ≥ 0.999), with a limit of detection (LOD) of 0.5 μg/kg and a limit of quantification (LOQ) of 1.5 μg/kg. Validation studies at three spiking levels (20.0, 200.0, and 400.0 μg/kg) demonstrated satisfactory recoveries of 97.2%–99.7% and precision with relative standard deviations (RSDs) of 0.8%–1.7% (n = 6). The total chromatographic runtime was optimized to 6 minutes. Application of this method to Seventy-five commercial cutting boards revealed PCP-Na residues in five samples, with concentrations ranging from 1.3 to 416 mg/kg. This approach features streamlined sample preparation, high sensitivity, robust accuracy, and rapid analysis, making it particularly suitable for routine monitoring of PCP-Na residues in bamboo and wooden food contact materials.

Correction: The Bothriolepis (Placodermi, Antiarcha) material from the Valentia Slate Formation of the Iveragh Peninsula (middle Givetian, Ireland): Morphology, evolutionary and systematic considerations, phylogenetic and palaeogeographic implications

PLoS ONE Vincent Dupret, Hannah M. Byrne, Nélia Castro et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0320508

Prehospital delay and associated factors among stroke patients in Africa: A systematic review and meta-analysis

PLoS ONE Duguma Debela Ganeti, Amanuel Oljira Dulo, Birhanu Wogane Ilala et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326323

Introduction Stroke is one of the leading causes of death and disability, predominantly affecting low- and middle-income countries. Timely intervention following stroke onset is critical for reducing stroke-related outcomes. However, delayed hospital arrival frequently compromises the effectiveness of treatment. Previous African studies on delayed hospital arrival among stroke patients have reported inconsistent prevalence rates and determinants. Therefore, this systematic review and meta-analysis aimed to assess the overall prevalence of prehospital delay and identify its contributing factors among stroke patients in African countries. Methodology This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO under record number CRD42024545741. Relevant studies were retrieved by searching databases such as PubMed, Google Scholar, the Cochrane Library, AJOL, and Hinari. Additional studies were identified through manual searches and the review of article references. The identified studies were critically evaluated for quality. Data were extracted and exported to R (version 4.2.3) and STATA (version 15.0) for analysis. The pooled prevalence of prehospital delay and the pooled odds ratios for associated factors were subsequently estimated. The risk of bias was assessed using a funnel plot and Egger’s test. The results were presented using tables, figures, and statements. Results This systematic review and meta-analysis included 16 studies. The pooled prevalence of prehospital delay among stroke patients was 80% (95% CI: 74–86%). Lack of stroke symptom awareness (AOR = 4.43, 95% CI: 1.04–7.83) and increased distance from a health facility (AOR = 1.28, 95% CI: 1.22–1.34) were significantly associated with prehospital delay. Conclusion and recommendation The prevalence of prehospital delay among stroke patients in Africa is alarmingly high, with contributing factors including a lack of stroke symptom awareness and increased distance from health facilities. Accordingly, stakeholders should implement targeted interventions that enhance community education on stroke warning signs and alleviate geographic barriers to timely care.

Correction: Expression of genes with biomarker potential identified in skin from DSLD-affected horses increases with age

PLoS ONE Jennifer Hope Roberts, Jian Zhang, Florent David et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326448

The effects of integrating the Manchester Pain Management Model and empowerment education on postoperative rehabilitation after cesarean section: A comprehensive intervention study

PLoS ONE Hailing Jiang, Ronghua Xu, Lingfang Li et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0324292

Purpose To evaluate the effect of combining the Manchester Pain Management Model (MPMM) with the enabling education model as a comprehensive intervention in maternal rehabilitation after cesarean section. Methods A total of 120 women who underwent cesarean section in our hospital from June 2021 to June 2023 were randomly divided into observation group and control group, with 60 cases in each group. The control group received standard nursing measures, while the observation group received comprehensive nursing measures combined with Manchester pain management and enabling education model. A rigorous randomized controlled trial design was employed. Data were analyzed using independent t-tests for continuous variables and chi-square tests for categorical variables, with a significance level set at P < 0.05. Postoperative pain degree (VAS score), postoperative recovery indicators, and nursing satisfaction scores were compared between the two groups. Results The pain scores at 4 hours, 12 hours and 24 hours after surgery, the first independent time out of bed activity, the first time to exhaust gas and the length of hospital stay in the observation group were significantly lower than those in the control group (P < 0.05), and the success rate of the first breastfeeding and nursing satisfaction were significantly higher than those in the control group (P < 0.01). Conclusion The combined intervention of the Manchester pain management model and empowerment education significantly improved postoperative pain control, accelerated physiological recovery, and increased overall satisfaction with nursing care. This model may provide an effective new method for rehabilitation management after clinical cesarean section.

Design, synthesis, in-vivo, and in-silico studies of 1,2,3-triazole tethered derivatives of morphine as novel anti-nociceptive agents

PLoS ONE Faeze Nourmandipour, Reihane Emadi, Peyman Salehi et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0323189

Due to the use of morphine as a well-known analgesic, a semi-synthesis of its newer triazole derivatives was performed in this project. Several derivatives were analyzed via molecular docking and a set of target molecules with acceptable docking scores were selected for the synthesis. The project focused on targeting one of the pharmacophores of morphine. The phenolic hydroxy group of morphine was reacted with propargyl bromide to furnish the terminal alkyne. This compound, as starting material for the click reaction underwent 1,3-dipolar cycloaddition reaction with different azides to produce the target 1,2,3-triazole tethered derivatives of morphine. The anti-nociceptive properties of the products were evaluated by tail flick test. It was observed that compounds 3b, 3d, and 3k with (ED50 = 0.23 mg/kg) showed superior pain relief activities in comparison with morphine (ED50 = 0.69 mg/kg). Finally, computational ADME/T studies were performed via SwissADME web server to gain a better understanding of the pharmacokinetics of the synthesized compounds in humans.

Brain microdialysis to assess trace elements dynamics in traumatic brain injury: An exploratory study

PLoS ONE Adriano Bernini, Sébastien Lenglet, Mette M. Berger et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326023

Background Trace elements (TEs) status alterations in the brain have been linked to neurodegenerative diseases. However, data on TEs in living humans and in the post-traumatic conditions are scarce. Some TEs (copper – Cu, selenium – Se, zinc – Zn) are involved in essential antioxidant defence. This study aims to measure the evolution of TEs concentrations in the brain and serum of severe traumatic brain injury (TBI) patients over time. Methods Twenty adult patients with severe TBI were monitored using cerebral microdialysis (CMD) and blood sampling within three days of intensive care unit admission. TEs levels were measured using inductively coupled plasma system coupled to mass spectrometry. Results TEs concentrations of chromium – Cr, Cu, cobalt – Co, manganese – Mn, molybdenum – Mo, Se, and Zn were quantified in brain interstitial fluid and serum. While serum and CMD levels did not differ significantly for Co, Mo and Mn, and modest differences was observed for Cr and Zn, significant differences were observed for Cu and Se with higher serum levels (8–10-fold higher) compared to CMD. No correlation was found between serum and brain TEs levels, except for Mo. Conclusion This study provides novel TEs concentration data in living TBI patients, the largest differences between brain and serum being observed for Cu and Se, serving as a basis for further research on TEs dynamics in acute brain injury.

Determinants of hypertensive crisis among hypertensive patients at adult emergency departments of public hospitals in eastern Ethiopia, 2023: A case-control study

PLoS ONE Fenta Wondimneh, Melaku Getachew, Tilahun Teshager et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326055

Background Hypertensive crisis is a life-threatening condition requiring urgent medical intervention. Identifying key determinants is essential for effective prevention and management. This study aimed to assess factors associated with hypertensive crisis among patients attending selected public hospitals in eastern Ethiopia. Methods A hospital-based unmatched case-control study was conducted among 357 participants (119 cases and 238 controls). Cases were hypertensive crisis patients, while controls were hypertensive patients without crisis in adult emergency departments of public hospitals in eastern Ethiopia from April 10th to September 10th, 2023. Data were collected using structured questionnaires and medical record reviews. Multivariable logistic regression was used to identify independent determinants of hypertensive crisis, with results presented as Adjusted Odds Ratios (AORs) and 95% Confidence Intervals (CIs). Results The mean age of participants was 54.7 ± 14.4 years for cases and 48.14 ± 15.51 years for controls. More than half of the cases (54.8%) and one-third of the controls (32.6%) were female. Multivariable analysis identified female sex (AOR = 2.91, 95% CI: 1.67–5.07), unemployment (AOR = 2.28, 95% CI: 1.20–4.33), diabetes mellitus (AOR = 3.33, 95% CI: 1.59–7.01), previous history of hypertension (AOR = 2.25, 95% CI: 1.21–4.19), drinking alcohol (AOR = 3.01, 95% CI: 1.45–6.24), and poor knowledge of hypertension (AOR = 1.86, 95% CI: 1.07–3.22) as significant determinants of hypertensive crisis (p < 0.05). Conclusion Female sex, unemployment, diabetes mellitus, history of hypertension, drinking alcohol, and poor hypertension knowledge were independent predictors of hypertensive crisis. However, the case-control design’s intrinsic limitations make it difficult to establish a temporal relationship between risk factors and outcomes. Strengthening hypertension education, promoting lifestyle modifications, and enhancing healthcare access may help mitigate the risk of hypertensive crisis.

Can anthropomorphic design in beverage packaging enhance impulse buying intention? Amazing visual and verbal cues!

PLoS ONE Yuyang Tian, Siti Farhana Zakaria, Yinghui Du et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326186

The anthropomorphic design of beverage packaging has gained significant attention as an innovative marketing strategy. This study systematically examines how anthropomorphic visual and verbal cues in beverage packaging influence consumers’ impulse buying intentions. Grounded in the Stimulus-Organism-Response model, Social Presence Theory, and Empathy Theory, the research employs a consumer survey to validate the mediating roles of positive emotions, social presence, and empathy in the relationship between anthropomorphic design and impulse buying intentions. A comprehensive causal model was developed to explore these relationships. While modern packaging techniques and visual elements enhance the appearance of beverage packaging, they did not significantly trigger empathetic responses. This suggests that emotional language and personalized expressions are more effective in fostering emotional resonance. The study also highlights the significant mediating roles of positive emotions and social presence in the relationship between anthropomorphic design and impulse buying intentions, emphasizing the importance of emotional and social factors in consumer decision-making.This research validates the theoretical model and offers practical insights for companies. It suggests that businesses should focus on consumers’ emotional needs and psychological states in packaging design and marketing strategies. By enhancing emotional language, optimizing visual anthropomorphic elements, and incorporating multi-sensory designs, companies can effectively improve consumers’ positive emotions and social presence, thereby increasing impulse buying intentions. For consumers with high levels of loneliness, strengthening anthropomorphic design elements can meet their social and emotional needs, enhancing brand loyalty and market competitiveness.

RRFNet: A free-anchor brain tumor detection and classification network based on reparameterization technology

PLoS ONE Wei Liu, Xingxin Guo Jun 16, 2025 DOI: 10.1371/journal.pone.0325483

Advancements in medical imaging technology have facilitated the acquisition of high-quality brain images through computed tomography (CT) or magnetic resonance imaging (MRI), enabling professional brain specialists to diagnose brain tumors more effectively. However, manual diagnosis is time-consuming, which has led to the growing importance of automatic detection and classification through brain imaging. Conventional object detection models for brain tumor detection face limitations in brain tumor detection owing to the significant differences between medical images and natural scene images, as well as challenges such as complex backgrounds, noise interference, and blurred boundaries between cancerous and normal tissues. This study investigates the application of deep learning to brain tumor detection, analyzing the effect of three factors, the number of model parameters, input data batch size, and the use of anchor boxes, on detection performance. Experimental results reveal that an excessive number of model parameters or the use of anchor boxes may reduce detection accuracy. However, increasing the number of brain tumor samples improves detection performance. This study, introduces a backbone network built using RepConv and RepC3, along with FGConcat feature map splicing module to optimize the brain tumor detection model. The experimental results show that the proposed RepConv-RepC3-FGConcat Network (RRFNet) can learn underlying semantic information about brain tumors during training stage, while maintaining a low number of parameters during inference, which improves the speed of brain tumor detection. Compared with YOLOv8, RRFNet achieved a higher accuracy in brain tumor detection, with a mAP value of 79.2%. This optimized approach enhances both accuracy and efficiency, which is essential in clinical settings where time and precision are critical.

Drug repositioning for pan-cancers of the digestive system: Identification of amonafide and BX795 as potential therapeutics via integrative Omics analysis

PLoS ONE Weidong Liu, Jiaying Gao, Shuqiang Ren et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0325700

Background Digestive system cancers, including esophageal, gastric, colorectal, pancreatic, hepatocellular, and biliary tract cancers, constitute a major global health challenge. Despite therapeutic advancements, prognosis remains poor, highlighting the urgent need for novel treatment strategies. We hypothesized that drug repositioning, facilitated by pan-cancer analyses, could lead to the identification of effective treatment strategies for these cancers. Results We performed a comprehensive gene expression profiling of six major digestive system cancer types using The Cancer Genome Atlas data. Through integrative omics analysis, we identified 9,978 shared differentially expressed genes (DEGs) between colorectal cancer (CRC) and liver hepatocellular carcinoma (LIHC). Functional enrichment analysis revealed nine common Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, with Cell Cycle being a significant shared pathway. Protein-protein interaction (PPI) network analysis identified core genes within these pathways, including CCNE1, CHEK1, NXF1, NCBP2, and RPS27A. A Connectivity Map (CMap) analysis matched 1,147 small molecules, leading to the identification of Amonafide and BX795 as top candidates. These two drugs were validated and shown to inhibit the proliferation and migration of CRC (HT-29) and LIHC (HepG2) cells and induce cell cycle arrest and apoptosis. Conclusion Our study demonstrates the utility of drug repositioning for identifying potential therapeutics for digestive system cancers. Amonafide and BX795 emerged as promising candidates in targeting both CRC and LIHC. Further in vivo studies and clinical trials are warranted to validate these findings.

Understanding the combined symptom medication score in the light of contexts and mechanisms

PLoS ONE Anne Møller Lohmann, Anne Poder Petersen, Johannes Martin Schmid et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326143

Background In a clinical trial of allergen‐specific immunotherapy for allergic rhinoconjunctivitis, the Combined Symptom Medication Score (CSMS) was utilized as the primary endpoint. This was aligned with the European Academy of Allergy and Clinical Immunology recommendation. However, participants wanted to elaborate on how their behaviour affected their score, so voluntary free text boxes were added to the CSMS questionnaire. This study aimed to evaluate the patient-reported outcomes registered in the free text boxes to identify and understand contexts and mechanisms that may affect the CSMS. Methods The realist evaluation methodology was followed in four iterative steps: 1) development of the initial programme theory and context-mechanism-outcome (CMO) configurations, 2) collection of evidence, 3) data analysis, and 4) interpretation and assessment of results. Results Seven CMO configurations were identified, highlighting contexts and mechanisms that may affect the CSMS. These included CMO1 – decision on preventive relief medication dosage, CMO2 – exhibiting symptom-relieving behaviour, CMO3 – being exposed to different levels of grass pollen, CMO4 – mistaking other symptoms for grass pollen-induced symptoms, CMO5 – different exposure to grass pollen when travelling abroad, CMO6 – reporting of relief medication for other allergies in CSMS, and CMO7 – failure to report symptoms not included in CSMS. Conclusion This realist evaluation contributes verified CMO configurations based on patient perspectives to understand how context and mechanisms may affect the CSMS. We recommend further investigation in quantitative studies, as awareness of these CMOs may increase the internal validity of future allergy trials using CSMS as an endpoint. Trial registration ILIT.NU: EudraCT 2020-001060-28.

Graph attention networks based multi-agent path finding via temporal-spatial information aggregation

PLoS ONE Qingling Zhang, Peng Wang, Cui Ni et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0318981

An effective Multi-Agent Path Finding (MAPF) algorithm must efficiently plan paths for multiple agents while adhering to constraints, ensuring safe navigation from start to goal. However, due to partial observability, agents often struggle to determine optimal strategies. Thus, developing a robust information fusion method is crucial for addressing these challenges. Information fusion expands the observation range of each agent, thereby enhancing the overall performance of the MAPF system. This paper explores a fusion approach in both temporal and spatial dimensions based on Graph Attention Networks (GAT). Since MAPF is a long-horizon, continuous task, leveraging historical observation dependencies is key for predicting future actions. Initially, historical observations are fused by incorporating a Gated Recurrent Unit (GRU) with a Convolutional Neural Network (CNN), extracting local observations to form an encoder. Next, GAT is used to enable inter-agent communication, utilizing the stability of the scaled dot-product aggregation to merge agents’ information. Finally, the aggregated data is decoded into the agent’s final action strategy, effectively solving the partial observability problem. Experimental results show that the proposed method improves accuracy and time efficiency by 24.5%, 47%, and 37.5%, 73% over GNN and GAT, respectively, under varying map sizes and agent densities. Notably, the performance enhancement is more pronounced in larger maps, highlighting the algorithm’s scalability.

Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated worms

PLoS ONE Jerald Tan, Chutipong Chiamkunakorn, Kanpapat Boonchuay et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326100

Metformin has been demonstrated to extend lifespan in various model organisms, and its molecular effects are observed in the cytoplasm and multiple organelles, including mitochondria. However, its association with the unfolded protein response (UPR) and its impact on stress resistance and locomotion remain uncertain. In this study, metformin was found to exert differential influences on both UPRmt and UPRer. The correlation between metformin’s lifespan-mediating effect and its interaction with UPRs was also inconsistent. We identified a metformin-mediated lifespan extension in wild-type C. elegans and in UPRmt-activated tomm-22 and cco-1 RNAi worms. Metformin suppressed the UPRmt without compromising the lifespan extension observed in tomm-22 worms. Conversely, metformin did not affect the UPRmt but extended the lifespan of long-lived cco-1 RNAi worms. Furthermore, we investigated the effects of metformin on UPRer-activated nematodes. We observed that metformin exhibited a slight increase in the UPRer in mdt-15 RNAi worms and failed to induce lifespan extension. Surprisingly, metformin appeared to mediate lifespan extension in tmem-131 RNAi worms while suppressing the UPRer. Notably, the correlation between thermotolerance, oxidative stress resistance, and the lifespan effects of metformin in UPR-activated worms was inconsistent. Activation of UPRs, but not metformin treatment, enhanced the locomotor phenotype of these worms.

High prevalence of Duck Hepatitis B virus-associated coinfection in Southwest China

PLoS ONE Xiaoming Lin, Lizhen Gong, Yajia Gou et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0324682

Currently, five types of duck hepatitis viruses have been documented, and they are all associated with liver disorders. However, the prevalence of their coinfections involving these viruses remains largely uncertain. Herein, we screened the prevalence of the five types of hepatitis viruses from A to E in 143 samples of diseased duck livers during 2019–2021 in Southwest China. We found the highest infection ratio (86.01%, 123/143) of duck hepatitis B virus (DHBV) among all five types of hepatitis viruses. Importantly, a large portion of DHBV-associated coinfections were identified, with 52.85% (65/123) co-infected with Duck Hepatitis A virus (DHAV), 39.84% (49/123) with tentative Duck Hepatitis D virus (DHDV), and 34.96% (43/123) with Duck Hepatitis E virus (DHEV), respectively. Interestingly, a positive correlation between the DHBV-positive rate and the infection rates of the other co-infected hepatitis viruses was revealed, suggesting the importance of DHBV in duck hepatitis virus co-infection events. To understand the situation of bacterial secondary infection, the prevalence of bacterial infection was simultaneously screened using standard 16S rRNA PCR, and hepatitis virus-associated bacterial infections were observed. Collectively, these findings revealed a high prevalence of DHBV-related coinfections and its association with the coinfection of the other duck hepatitis viruses and bacteria. In the future, it is important to study the impact of DHBV co-infection events on disease severity, thereby evaluating the necessity of vaccine development for DHBV.

Real-world safety profile of live attenuated Japanese encephalitis vaccine before and after the vaccine administration law

PLoS ONE Chao Zhang, Yan Liu, Xiaofu Luo et al. Jun 16, 2025 DOI: 10.1371/journal.pone.0326257

Purpose Live attenuated Japanese encephalitis vaccine (JEV-L) was included in the Expanded program on immunization on Immunization (EPI) in 2008 and has had a satisfactory effectiveness and safety profile in protecting children from JE virus infection. This study was designed to evaluate the surveillance sensitivity and changes over time of adverse event following immunization (AEFI) reports related to JEV-L based on the national AEFI surveillance system(NAEFISS) data before and after the introduction of vaccine administration law (LAW) from 2014 to2023 in Huzhou City. Methods AEFI data were collected from NAEFISS from 2014 to 2023 and included age, AEFI and diagnostic categories. AEFI incidence rates are calculated/10,000 vaccine doses and a reporting odds ratio −1.96 standard error (ROR-1.96SE) >1 defined a positive signal between AEFI and vaccine. We categorized the time interval into the pre-LAW period (2014–2019) and post-LAW period (2020–2023) to demonstrate the impact of LAW on the surveillance of AEFI. Results The NAEFISS collected 225 AEFI reports after administering 599,223 doses of JEV-L, with a AEFI reported rate of 3.75/10,000 doses. Overall AEFI reported rates increased over time with a drop in 2020 (P < 0.001, χ2 for trend). The reported rate of AEFI in post-LAW period was higher than that in the pre-LAW period (P < 0.001), accounted for increases in fever, local redness and local induration. However, the reported rate of urticaria decreased significantly in post-LAW period(P = 0.043). This study found a positive signal association between JEV-L immunization and fever in the pre- (1.394) and post-LAW period(2.833) and a signal for urticaria in the pre-LAW period (2.098). There were only 2 severe reactions reported: thrombocytopenia and epilepsy. Conclusions The implementation of the LAW significantly enhanced the surveillance capacity and sensitivity for AEFIs associated with JEV-L. This study did not find any new/unexpected safety concern in the post-LAW period. Severe reactions remain rare despite the greatly improved sensitivity of surveillance, indicating that the vaccine was comparatively safe. However, continuous epidemiological investigation are needed to systematically assessment the data provided by NAEFISS.