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Towards site-specific information on PET degrading enzymes using NMR near operational temperature

Scientific Reports Valeria Gabrielli, Jelena Grga, Sabine Gavalda et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22351-1

Uncovering economic impacts and dynamics of European energy policy: Evidence from DEMATEL, panel data, and cluster analysis

PLoS ONE Aldona Kluczek, Agnieszka Woźniak, Patrycja Żegleń Nov 04, 2025 DOI: 10.1371/journal.pone.0322525

This study analyzes the relationship of national diversity in energy policies between economic outcomes amid changing energy prices, climate regulations, and technological innovations across European countries. Using DEMATEL, panel data econometric models, and cluster analysis, the research three interrelated questions: whether environmental regulations can simultaneously support economic performance and innovation; how energy prices and climate policies affect inflation, economic growth, and unemployment; and whether a hybrid causal framework can reveal deeper feedback dynamics across policy, innovation, and macroeconomic variables, The results identify significant relationships between technological innovations, energy prices, climate regulations, and inflation. The analysis reveals that energy prices influence R&D expenditure, with both positive and negative effects depending on timing. Climate regulations and inflation also significantly impact technological innovations. The findings emphasize the need for strategic planning and investment in technology to manage energy prices and climate policies effectively. The study suggests that stable, innovation-oriented regulatory frameworks are more effective than short-term interventions such as subsidies or price caps in promoting green technologies, reducing economic volatility, and supporting the transition to sustainable energy systems. Limitations include the exclusion of variables such as institutional quality, consumer behavior, and readiness for energy storage infrastructure. Further research with extended time series and localized data is recommended to deepen understanding and support resilient energy policy development.

Dibromocarbene addition to bicyclo[1.1.0]butanes: A facile route to substituted bicyclo[1.1.1]pentanes

Proceedings of the National Academy of Sciences Flynn C. Attard, Andrii Slobodianyk, Roman Bychek et al. Nov 04, 2025 DOI: 10.1073/pnas.2524130122

Strained, multicyclic hydrocarbons are increasingly important structural motifs for drug discovery. In particular, substituted bicyclo[1.1.1]pentanes (BCPs) have risen to prominence as bioisosteres for the ubiquitous benzene ring. Despite their favorable pharmacokinetic properties, synthetic strategies toward BCPs suffer from significant drawbacks—namely an overreliance on [1.1.1]propellane, an operationally challenging to utilize starting material which complicates scale-up and hampers widespread adoption of these motifs. In this work, the synthesis of 2,2-dibromo BCPs is described, presenting a class of versatile substituted BCPs and circumventing the need for [1.1.1]propellane-based precursors. Scalable access to these compounds is demonstrated in a simple and inexpensive process, and their applicability for medicinal chemistry campaigns is highlighted through the synthesis of a diverse range of valuable building blocks—including highly sought-after bridge heteroarylated BCP derivatives which are prepared via an electrocatalytic cross-coupling procedure.

Enhancing grasping ability with vibrational guidance for individuals who are blind or partially sighted

Scientific Reports Katharina C. Trant, Zeynep Bolluk, Rowan A. Mohamed et al. Nov 04, 2025 DOI: 10.1038/s41598-025-21720-0

Abstract This study investigates the effectiveness of a vibrotactile bracelet in supporting goal-directed hand movements and grasping tasks for visually conditioned individuals. The research addresses the challenge of object manipulation without visual feedback, comparing tactile to auditory cues. The primary research question explores whether vibrotactile signals delivered via a wrist-worn device can accurately guide hand movements and improve grasping precision. Forty-one participants with varying degrees of limited vision completed a localization task and a grasping task under tactile and auditory guidance conditions and filled out a questionnaire featuring Likert scale items and open-ended questions. The results revealed a mean localization accuracy of 90.6% for vibrotactile signals, with some confusion between neighboring directions. In the grasping task, auditory feedback elicited quicker response times, yet 15 participants exhibited superior performance with tactile feedback. Factor analysis of participant feedback uncovered three key dimensions: confidence, comfort, and learning. Qualitative analysis underscored the need for customizable vibration intensity, enhanced precision, and ergonomic design. Findings suggest that vibrotactile feedback, while slightly slower than auditory cues, is a promising, alternative for supporting grasping without interfering with auditory awareness. Improvements in device design and personalized calibration could enhance its practical application, contributing to greater independence for visually conditioned individuals.

Telehealth Exercise Training in Peripheral Arterial Disease (TEXTPAD) study: A pilot randomised controlled trial in socioeconomically disadvantaged populations

PLoS ONE James Prentis, Arathi Radhakrishnan, Eileen Kaner et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0327633

Background Peripheral arterial disease (PAD) is a common condition among older adults, particularly those in socioeconomically disadvantaged populations. Supervised exercise is a key treatment for PAD-related claudication, but access to such programs is limited, especially following the COVID-19 pandemic. Telehealth interventions offer a promising alternative, but their feasibility and effectiveness in these populations remain unclear. Objective This study aimed to assess the feasibility of a home-based telehealth intervention combining exercise and behaviour change counselling for patients with PAD from socioeconomically deprived areas of the UK. Methods A pilot randomised controlled trial (RCT) was conducted with PAD patients (n = 36) recruited from the Vascular Unit of Freeman Hospital, Newcastle upon Tyne, UK. Participants were randomly assigned to either a telehealth intervention group (n = 19) or a control group (n = 17). The intervention consisted of weekly phone-based behaviour change counselling and twice-weekly virtual supervised exercise sessions for 12 weeks. Primary feasibility outcomes included recruitment, retention, and adherence. Secondary outcomes assessed functional capacity, quality of life, smoking and alcohol use, and dietary habits. Results Of the 102 eligible patients, 36 were recruited, falling short of the target recruitment goal of 60 participants. The intervention group attended a median of 20 supervised exercise sessions (max 24) and 11 sessions with the health improvement practitioner (max 12). Exploratory analyses suggested improvements in subjective functional capacity, as measured by walking speed and stair-climbing ability (P < 0.01), and quality of life (P < 0.01) in the intervention group compared to the control group. A 50% smoking cessation rate was observed among baseline smokers in the intervention group, while no changes were observed in the control group. No significant differences were observed between groups in objective functional capacity (as measured by the 6-minute walk test), alcohol intake, or dietary quality. Conclusion This digitally delivered, home-based telehealth intervention was feasible for PAD patients in socioeconomically disadvantaged areas. Exploratory findings suggest potential benefits in subjective function capacity and health behaviours; however, the study was not powered to evaluate effectiveness, and findings should be interpreted with caution. These data support the suitability of outcome measures and provide essential insights for designing a fully powered definitive trial to evaluate long-term clinical outcomes.

Dynamical constraints on the vertical structure of Jupiter’s polar cyclones

Proceedings of the National Academy of Sciences Nimrod Gavriel, Yohai Kaspi Nov 04, 2025 DOI: 10.1073/pnas.2503737122

Jupiter’s poles feature striking polygons of cyclones that drift westward over time, a motion governed by β -drift (vortex motion caused by the latitudinal variation of the Coriolis force). This study investigates how β -drift and the resulting westward motion depend on the depth of these cyclones. Counterintuitively, shallower cyclones drift more slowly, a consequence of stronger vortex stretching. By employing a 2D quasi-geostrophic model of Jupiter’s polar regions, we constrain the cyclones’ deformation radius, a key parameter that serves as a proxy for their vertical extent, required to replicate the observed westward drift. We then explore possible vertical structures and the static stability of the poles by solving the eigenvalue problem that links the 2D model to a 3D framework, matching the constrained deformation radius. These findings provide a foundation for interpreting upcoming Juno microwave measurements of Jupiter’s north pole, offering insights into the static stability and vertical structure of the polar cyclones. Thus, by leveraging long-term motion as a constraint on vertical dynamics, this work sets the stage for advancing our understanding of the formation and evolution of Jupiter’s enigmatic polar cyclones.

Reconstructing hourly coastal total sea levels and assessing current and future extreme sea levels threats to the Coast of China

Scientific Reports Pengzhen Liu, Ami Hassan Md Din, Mohammad Hanif Hamden Nov 04, 2025 DOI: 10.1038/s41598-025-22493-2

Application of the protection motivation theory in predicting wild mushroom consumption among university students in China

PLoS ONE Si Chen, Yu Chen, ZhenYi Li Nov 04, 2025 DOI: 10.1371/journal.pone.0335719

Background Wild mushroom poisoning represents a significant public health challenge in China, with the highest mortality rate globally. Despite extensive prevention campaigns, consumption behaviors persist, particularly among university students who may be influenced by social media and peer pressure. Objective This study applied Protection Motivation Theory (PMT) to investigate psychological factors influencing wild mushroom consumption intentions among Chinese university students and identify key predictors for targeted intervention development. Methods A cross-sectional survey was conducted among 216 Chinese university students. The PMT model included threat appraisal (perceived severity, susceptibility, benefits, costs) and coping appraisal (response efficacy, self-efficacy, response costs). Behavioral intention was assessed through scenario-based consumption likelihood measures. Structural equation modeling was used to test the theoretical model. Results The PMT model demonstrated good fit (χ²/df = 2.14, CFI = 0.94, TLI = 0.92, RMSEA = 0.073, SRMR = 0.065) and explained 42.3% of the variance in wild mushroom consumption intentions (R² = 0.423, 95% CI [0.35, 0.49]). Perceived benefits emerged as the strongest positive predictor (β = 0.385, 95% CI [0.27, 0.50], p < 0.001), while self-efficacy was the strongest negative predictor (β = −0.298, 95% CI [−0.42, −0.18], p < 0.001). Traditional threat appraisal components (severity and susceptibility) showed minimal predictive effects. Response costs also significantly predicted consumption intentions (β = 0.156, 95% CI [0.04, 0.27], p < 0.01). Conclusions PMT provides a valuable framework for understanding wild mushroom consumption behavior among Chinese university students. The dominance of perceived benefits and self-efficacy as predictors suggests that effective interventions should address positive outcome expectations while building confidence in avoidance behaviors. These findings indicate that effective interventions must move beyond traditional risk communication to address the complex interplay of perceived benefits, self-efficacy, and social factors driving consumption decisions, with implications for developing culturally-tailored, multi-component prevention strategies.

Shifting power asymmetries in scientific teams reveal China’s rising leadership in global science

Proceedings of the National Academy of Sciences Renli Wu, Christopher Esposito, James Evans Nov 04, 2025 DOI: 10.1073/pnas.2414893122

China’s emergence as one of the world’s top producers of high-quality science raises critical questions about its trajectory toward achieving scientific leadership. Traditional methods for evaluating the power of national scientific ecosystems, however, often overlook the nuances of a country’s global influence. In this perspective, we introduce a framework that highlights shifting power dynamics in international scientific collaborations, focusing on whether leadership positions in international scientific teams are moving from one country to another. Using rich sociological data from nearly 6 million scientific publications, we document a marked shift in team leadership from Western countries to China. In particular, the share of team leaders involved in U.S-China scientific collaborations that were affiliated with Chinese institutions grew from 30% of the total in 2010 to 45% in 2023. We further explore the implications of China’s rise by forecasting when Chinese scientists are projected to achieve parity in leadership vis-à-vis the United States, including in 11 critical technology areas that are focal points of technological development, and by analyzing how a potential decoupling of U.S.-Chinese science might affect Chinese scientific leadership. We conclude by considering the impacts of China’s growing investments in the training of young scientists in countries participating in the Belt and Road Initiative.

A cross-sectional study of posttraumatic stress disorder, career resilience and perceived organizational support in emergency department nurses

Scientific Reports Shouzhi Zhou, Hongqing Yin Nov 04, 2025 DOI: 10.1038/s41598-025-22378-4

Factors contributing to differences in physical activity levels in (pre)frail older adults living in rural areas of China

PLoS ONE Xin Zhang, Xiaoping Zheng, Hans Hobbelen et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335607

Introduction Physical Activity (PA) is essential for enhancing the physical function of pre-frail and frail older adults. However, among this group, PA-levels vary significantly. Identifying the factors contributing to these differences could support tailored PA interventions. This study aims to examine factors associated with physical activity levels among pre-frail and frail older adults in rural China. Methods This is a cross-sectional study. A total of 284 (pre)frail older adults (aged ≥60 years) were included from ten rural healthcare centers in Northeast China. Participants were categorized into low-moderate and high physical activity groups assessed using the Short Form International Physical Activity Questionnaire. Four-dimensional data were collected, including demographics, health behaviors, objective physical performance measures, and self-reported perceived health profiles. Extreme Gradient Boosting (XGBoost), a machine learning algorithm, was employed for binary classification (low-moderate vs. high physical activity). Model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and F1-score. To enhance interpretability, SHapley Additive exPlanations (SHAP) were utilized to identify key predictive variables. Results Mean age of participants was 70 years (59% female, 86% farmers). The low-moderate group averaged 1,187 MET/week, while the high physical activity group reached 8,162 MET/week. Physical performance tests showed significantly better scores in the high PA group. The XGBoost model achieved 82.4% accuracy (AUC: 0.769, specificity: 90%, sensitivity: 63%). SHAP analysis revealed that self-reported social support, general health, ambulation, and physical performance measures were the most important factors. Conclusion The high physical activity group demonstrated better physical function than the low-moderate physical activity group; though, both groups showed poorer physical function compared to the general older population. Self-reported health perceptions and social support significantly correlated with physical activity levels. Addressing these factors through targeted interventions—including community-based social support programs and structured mobility-enhancing exercises—may contribute to improved health outcomes and enhanced quality of life in this population.

Chemical propulsion of hemozoin crystal motion in malaria parasites

Proceedings of the National Academy of Sciences Erica M. Hastings, Tomasz Skóra, Keith R. Carney et al. Nov 04, 2025 DOI: 10.1073/pnas.2513845122

Malaria parasites infect red blood cells where they digest host hemoglobin and release free heme inside a lysosome-like organelle called the food vacuole. To detoxify excess heme, parasites form hemozoin crystals that rapidly tumble inside this compartment. Hemozoin formation is critical for parasite survival and central to antimalarial drug activity. Although the static structural properties of hemozoin have been extensively investigated, crystal motion and its underlying mechanism have remained puzzling. We used quantitative image analysis to determine the timescale of motion, which requires the intact vacuole but does not require the parasite itself. Using single particle tracking and Brownian dynamics simulations with experimentally derived interaction potentials, we found that hemozoin motion exhibits unexpectedly tight confinement but is much faster than thermal diffusion. Hydrogen peroxide, which is generated at high levels in the food vacuole, has been shown to stimulate the motion of synthetic metallic nanoparticles via surface-catalyzed peroxide decomposition that generates propulsive kinetic energy. We observed that peroxide stimulated the motion of isolated crystals in solution and that conditions that suppress peroxide formation slowed hemozoin motion inside parasites. These data suggest that surface-exposed metals on hemozoin catalyze peroxide decomposition to drive crystal motion. This work reveals hemozoin motion in malaria parasites as a biological example of an endogenous self-propelled nanoparticle. This mechanism of propulsion likely serves a physiological role to reduce oxidative stress to parasites from hydrogen peroxide produced by large-scale hemoglobin digestion during blood-stage infection.

Utilizing FUCOM and AHP methods to identify the optimal beekeeping lands: A case study from Mardin, Türkiye

PLoS ONE Çağrı Mercan, Veysi Acıbuca Nov 04, 2025 DOI: 10.1371/journal.pone.0335784

Beekeeping plays a vital role in agricultural sustainability and biodiversity conservation, yet identifying ecologically suitable areas for apiculture remains challenging. The objective of this study is to evaluate and compare two Multi-Criteria Decision-Making (MCDM) methods—the Analytical Hierarchy Process (AHP) and the Full Consistency Method (FUCOM)—within a Geographic Information Systems (GIS) framework to identify optimal beekeeping areas in Mardin Province, Türkiye. Nine environmental, climatic, topographical, logistic, and socio-economic factors were selected through literature review, legal regulations, expert consultation, and field observations. Suitability maps were generated and validated using field-verified hive locations and Receiver Operating Characteristic–Area Under the Curve (ROC–AUC) analysis. The results show that land use/cover, proximity to water sources, and precipitation were the most influential factors. Overall, 83% of hive locations coincided with areas classified as moderately suitable or higher. AHP achieved slightly higher predictive accuracy (AUC = 0.774) than FUCOM (AUC = 0.754), while FUCOM required substantially fewer pairwise comparisons, underscoring its efficiency. These findings confirm the robustness of the framework and provide a practical tool for sustainable apicultural land-use planning, offering transferable insights for policymakers, decision-makers, and beekeepers in Türkiye and other regions with similar ecological conditions.

Symbiotic solutions for colony nutrition: Conserved nitrogen recycling within the bacterial pouch of <i>Tetraponera</i> ants

Proceedings of the National Academy of Sciences Mingjie Ma, Qiang Li, Fan Wu et al. Nov 04, 2025 DOI: 10.1073/pnas.2514882122

While microbial symbioses are fundamental to the nutrition of many animal groups, current paradigms focus on symbiont functions at the host individual level. It remains unclear whether microbial symbioses can sustain colony-level fitness in social insects, whose ecological success depends on nutrient coordination across castes. Here, we investigate the specialized bacterial pouch, a symbiont-containing organ present exclusively in adult workers of Tetraponera nigra -group ants, revealing its crucial role in colony-wide nutrient provisioning. Using a combination of microscopy, amplicon and metagenomic sequencing, and 15 N-urea feeding experiments on four species in the group, we show that its adult-specific pouch-associated microbiota, primarily Tokpelaia , recycle nitrogen from urea and convert it into amino acids which are provisioned to adult workers and developing larvae. Disruption of this nitrogen-recycling symbiosis severely impairs larval growth and overall colony fitness. Our results show how caste-restricted microbial organs can centralize metabolic functions at the colony level, challenging individual-centric paradigms of host–microbe mutualism and providing insights into the pivotal role of microbial symbionts in superorganismal adaptation to nutritional constraints.

Challenges encountered by midwives performing basic neonatal resuscitation in health facilities in Kinshasa, Democratic Republic of the Congo

PLoS ONE Eric M. Mafuta, Daniel K. Ishoso, Carl L. Bose et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0334847

Worldwide, an estimated five million children under the age of five die each year; 47% of these deaths occur during the neonatal period, and the vast majority in low- and middle-income countries. Events during labor are the cause of one quarter of neonatal deaths globally. Basic resuscitation with positive pressure ventilation reduces these deaths but is challenging to execute. To characterize barriers to implementation of basic neonatal resuscitation, we conducted a qualitative study using focus group discussions with midwives at three health facilities in Kinshasa, Democratic Republic of the Congo. We analyzed qualitative data using an inductive content approach in order to identify emergent themes and trends. Twenty-four midwives participated with a median age of 49 and over 80% with more than 10 years of clinical experience. We categorized challenges to implementing basic neonatal resuscitation into three themes with subthemes: 1) limited resources (subthemes: human resource limitations, inadequate and unprepared equipment, insufficient monitoring during labor); 2) inadequate simulated and clinical experience (subthemes: poor systems to support maintenance of skills, infrequent opportunity to resuscitate); 3) emotional burden of resuscitation (subthemes: decision-making under time pressure, tendency to stick to the routine, acute stress during resuscitation, moral distress after unsuccessful outcome). Our findings suggest that while simulation training is key, learning from clinical events may be a critical companion to address these barriers. We call for a new focus on developing and evaluating strategies that support providers in learning from every newborn resuscitation.

Accessing robust vaccine coformulation stability by single adjuvant detection on a microelectrode

Proceedings of the National Academy of Sciences Azaria A. Wagner, David Perez Herrera, Avery L. Rudder et al. Nov 04, 2025 DOI: 10.1073/pnas.2522044122

A significant question in next generation vaccine development is: How long are coformulated products stable on the shelf? The recent review by the US Food and Drug Administration of a single, prefilled syringe of the SHINGRIX™ vaccine has highlighted the importance of this question. While dynamic light scattering is well suited for measuring average particle sizes across populations, fundamental principles behind scattering limit the resolution to distinguish subtle differences at the tens of nanometer scale between similar samples. To address this, we introduce an alternative approach: stochastic electrochemistry, which allows for the investigation of specific properties of individual particles, one at a time. By introducing an electrochemically active species, hexacyanoferrate(II/III) into the vaccine solution, we observe discrete current drops when particles irreversibly collide with a microelectrode. Such events can be correlated directly with particle size. As a proof of concept, we use this technique to analyze the interactions of streptavidin-functionalized poly(lactic-co-glycolic acid) beads with biotinylated bovine serum albumin at vaccine-level concentrations and apply what we learned to the components of the SHINGRIX™ vaccine. We then present a time-trial comparison of data from current commercial SHINGRIX™ vaccines using dynamic light scattering and stochastic electrochemistry, analyzing the AS01 B adjuvant alone and the AS01 B adjuvant combined with the glycoprotein E (gE protein). While our method elucidates important properties at the single adjuvant level, our results paint a quantitative kinetic picture of coformulation stability that is currently not achievable by dynamic light scattering.

Road pedestrian detection and tracking algorithm based on improved YOLOv5s and DeepSORT

PLoS ONE Guofeng Qin, Rongting Pan, Yi Deng et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0334786

To address the challenges of low accuracy, high miss detection rate, and poor tracking stability in pedestrian detection and tracking under dense occlusion and small object scenarios on traffic roads, this paper proposes a pedestrian detection and tracking algorithm based on improved YOLOv5s and DeepSORT. For the improvements in the YOLOv5s detection network, first, the Focal-EIoU loss function is used to replace the CIoU loss function. Second, a 160 × 160-pixel Small Object (SO) detection layer is added to the Neck structure. Finally, the Multi-Head Self-Attention (MHSA) mechanism is introduced into the Backbone network to enhance the model’s detection performance. Regarding the improvements in the DeepSORT tracking framework, a lightweight ShuffleNetV2 network is integrated into the appearance feature extraction network, reducing the number of model parameters while maintaining accuracy. Experimental results show that the improved YOLOv5s achieves an mAP0.5 of 80.8% and an mAP0.5:0.95 of 49.7%, representing increases of 4.4% and 3.9%, respectively, compared to the original YOLOv5s. The enhanced YOLOv5s-DeepSORT achieves an MOTA of 50.7% and an MOTP of 77.3%, improving by 3.3% and 0.5%, respectively, over the original YOLOv5s-DeepSORT. Additionally, the number of identity switches (IDs) is reduced by 11.3%, and the model size is reduced to 20% of the original algorithm, enhancing its portability. The proposed method demonstrates strong robustness and can effectively track targets of different sizes.

ZDHHC11-mediated AXL palmitoylation promotes osimertinib resistance in non-small-cell lung cancer

Proceedings of the National Academy of Sciences He Cui, Xueting Cai, Qiang Qian et al. Nov 04, 2025 DOI: 10.1073/pnas.2502778122

Receptor tyrosine kinase pathway rewiring represents a fundamental mechanism underlying acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC). While posttranslational modifications facilitate aberrant activation of bypass signaling networks, the specific contribution of ZDHHC palmitoyl acyltransferase-mediated palmitoylation remains poorly characterized. Here, ZDHHC11-mediated palmitoylation contributes to osimertinib resistance in EGFR-mutant NSCLC. Patient samples, along with in vitro and in vivo functional studies, indicated that ZDHHC11 upregulation reduces the sensitivity of tumor cells to osimertinib by promoting malignant phenotype. Mechanistically, we establish AXL receptor tyrosine kinase as the critical substrate. ZDHHC11 catalyzes AXL palmitoylation at Cys869, inducing plasma membrane retention and constitutive activation. This triggers downstream PI3K–AKT signaling, with AXL knockout alleviating the effect of ZDHHC11-driven resistance. Crucially, pharmacological inhibition ZDHHC11-mediated palmitoylation with the broad-spectrum palmitoylation inhibitor 2-bromopalmitate effectively augmented the antitumor effects of osimertinib. Collectively, ZDHHC11 regulates osimertinib resistance in a palmitoylation-dependent manner. Targeting the ZDHHC11–AXL axis may provide a promising therapeutic strategy for the treatment of osimertinib-resistant EGFR-mutant NSCLC patients with high ZDHHC11 expression.

Correction: Socio-demographic influence of food additives acceptance and avoidance among the Lebanese population: A cross-sectional study

PLoS ONE Reham E. Kotb, Souheil Hallit, Farah Asmar et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0336265

Modulating the microbiome as an approach to anticancer drug development

Proceedings of the National Academy of Sciences Jemma Arakelyan, Ho-Jung Choe, Chengnan Wu et al. Nov 04, 2025 DOI: 10.1073/pnas.2417269122

Recent studies have suggested that the commensal microbiome positively affects cancer prognosis and treatment outcomes. However, only a few strategies for regulating the microbiome composition have been reported. In this study, we identified gold(I) complexes that selectively inhibited nonbeneficial bacterial strains in vitro without affecting commensal Lactobacillus strains. In contrast, clinically used drugs demonstrated comparable effects on both commensal and noncommensal strains. Consistent with the in vitro results, the selected gold(I) complex induced favorable changes in the intratumoral and gastrointestinal microbiomes in vivo. Furthermore, its anticancer efficacy was found to be dependent on the composition of microbiome and correlated with the production of short-chain fatty acid bacterial metabolites. Structure–activity relationship studies have dissected the contribution of each structural component in both the in vivo efficacy and microbiome-modulating properties. Transcriptomic analysis of tumors revealed microbiome-associated gene signaling pathways. These findings provide valuable insights for future research on microbiome-modulating anticancer drugs, presenting potential avenues to optimize cancer treatment outcomes and mitigate side effects such as gastrointestinal dysbiosis. Furthermore, our study provides insights into the involvement of microbiome in the mechanism of action of metal-based chemotherapeutics.