Se Pu. 2025 Mar;43(3):289-294. doi: 10.3724/SP.J.1123.2024.04025.

ABSTRACT

"Admiring the lofty mountains, one realizes their own lack of talent." To further promote the implementation of new curriculum standards, a comprehensive instrumental analysis experiment was designed. Metabolomics, an emerging technology developed after genomics and proteomics, is an important part of systems biology. This study aims to explore the applications of metabolomics in the fields of environment and health. Sample pretreatment technology and detection methods for separating and enriching gallium were chosen through a literature review and group discussion. Students then experimentally analyzed the changes in metabolite content in cells cultured with metal-anticancer gallium drugs, which helped them understand the widespread application of metabolomics in the fields of environment and health. Additionally, material characterization was conducted using X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TG), and the gallium metal in metabolites was qualitatively and quantitatively analyzed using inductively coupled plasma mass spectrometry (ICP-MS). During discussions of this experiment, the teacher guided students in using large-scale instruments to solve problems comprehensively, fostering a research-based teaching approach to build a solid foundation for conducting efficient instrument analysis and comprehensive experiments within the classroom in future.

PMID:40045652 | DOI:10.3724/SP.J.1123.2024.04025

The first step to NIH funding is closely reading your funding opportunity, which contains important information about eligibility, application submission, and review. Let’s take a guided video tour of the structure of a typical NIH Notice of Funding Opportunity, or NOFO. 

Here are the highlights:  

• Structure of a Funding Opportunity
• Instruction Hierarchy
• Eligibility Information
• Submission Reminders
• Application Review Information
• Key Takeaways

Clin Pharmacol Ther. 2025 Apr;117(4):895-909. doi: 10.1002/cpt.3598. Epub 2025 Mar 5.

ABSTRACT

Non-randomized studies will remain the mainstay for evidence on medications' effects in pregnancy since the number of pregnant participants in randomized clinical trials is insufficient to evaluate uncommon but serious pregnancy outcomes. There has been a growing interest in conceptualizing causal inference based on observational data as an attempt to emulate a hypothetical randomized trial: the target trial. This approach can help identify design flaws and ensuing biases and can point toward potential solutions. Adoption of the target trial emulation framework in perinatal studies raises unique challenges due to the distinct role of gestational time. Challenges include, among others, identifying the timing of conception, pregnancy losses as competing events for later outcomes, different etiologically relevant time windows depending on the outcome, and time-varying outcome risks. We discuss various considerations in developing a protocol for a target trial evaluating drug effects in pregnancy and its observational emulation in databases and registries. While not a panacea, the framework offers a valuable tool to guide us through the specification of the causal questions, the study population and the treatment strategies to be compared and helps to identify avoidable biases as well as unavoidable deviations from the optimal protocol. Making these deviations explicit elucidates the assumptions we make when drawing causal conclusions, and the types of analyses that can be undertaken to quantify the potential magnitude of such biases. Such discipline in the design, conduct, and reporting of pregnancy studies will ultimately lead to the best information possible to inform treatment decisions during pregnancy.

PMID:40045450 | DOI:10.1002/cpt.3598

Arch Toxicol. 2025 Mar 5. doi: 10.1007/s00204-025-03982-9. Online ahead of print.

ABSTRACT

A large number of drugs and compounds produced by the chemical and agrochemical industry, often referred to as 'non-genotoxic carcinogens' (NGC), score as tumour promotors in rodent models. It is unclear whether these compounds act similarly in humans. The most extensively investigated compounds have been the anti-convulsive drugs, phenobarbital (PB), and phenytoin. Liver tumours induced by PB are dependent upon the activation of the constitutive androstane receptor (CAR). However, marked species differences in CAR activation by exogenous chemicals exist with some being much more potent activators of human CAR, e.g., 6-(4-chlorophenyl)imidazo[2,1-β][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO). We have compared CITCO-induced tumour formation in the livers of mice in which murine CAR has been replaced with its human counterpart. Our findings reveal that CITCO-dependent liver tumours are only formed in mice-expressing human CAR and not in wild-type animals. In addition, contrary to one of the proposed mechanisms of NGC carcinogenicity, we show that CITCO did not induce a hyperplastic response in the liver of the humanised mice. These data raise some key questions about the mechanism of action of NGCs and identify the limitations of current rodent carcinogenicity test systems in relation to risk assessment.

PMID:40044833 | DOI:10.1007/s00204-025-03982-9

Pharmacogenomics J. 2025 Mar 5;25(1-2):5. doi: 10.1038/s41397-025-00364-3.

ABSTRACT

Reliable estimates for the number of cancer patients with a specific mutation can help quantify the size of the population that could potentially benefit from a targeted therapy. We adapt our previously developed approach for estimating gene-level mutation abundances to estimate mutation-specific (e.g., KRAS G12C) abundances by combining United States cancer epidemiology and genomic data. We demonstrate the approach by obtaining population-level estimates for all acquired somatic missense mutations that create a de novo cysteine residue. We find that approximately 14% of non-epidemiological informed estimates are more than twice the epidemiological informed estimate. Non-epidemiologically informed pan-cancer estimation of mutation rates may not be representative of the number of cancer patients with a specific mutation. Our study suggests that epidemiological and genomic information should be combined when estimating the population level abundance of specific pathogenic mutations.

PMID:40044654 | DOI:10.1038/s41397-025-00364-3

Nat Commun. 2025 Mar 6;16(1):2237. doi: 10.1038/s41467-025-57136-7.

ABSTRACT

Virtual library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking agonists for the cannabinoid-1 receptor (CB1R), we dock 74 million tangible molecules and prioritize 46 high ranking ones for de novo synthesis and testing. Nine are active by radioligand competition, a 20% hit-rate. Structure-based optimization of one of the most potent of these (Ki = 0.7 µM) leads to '1350, a 0.95 nM ligand and a full CB1R agonist of Gi/o signaling. A cryo-EM structure of '1350 in complex with CB1R-Gi1 confirms its predicted docked pose. The lead agonist is strongly analgesic in male mice, with a 2-20-fold therapeutic window over hypolocomotion, sedation, and catalepsy and no observable conditioned place preference. These findings suggest that unique cannabinoid chemotypes may disentangle characteristic cannabinoid side-effects from analgesia, supporting the further development of cannabinoids as pain therapeutics.

PMID:40044644 | DOI:10.1038/s41467-025-57136-7

Nat Commun. 2025 Mar 5;16(1):2214. doi: 10.1038/s41467-025-57520-3.

ABSTRACT

Putting pancreatic adenocarcinoma (PAAD) screening into perspective for high-risk individuals could significantly reduce cancer morbidity and mortality. Previous studies have profiled somatic mutations in PAAD. In contrast, the prevalence of mutations in PAAD predisposition genes has not been defined, especially in the Asian population. Using a multi-tier cohort design and whole genome/exome sequencing, we create a comprehensive germline mutation map of PAAD in 1,123 Chinese cancer patients in comparison with 11 pan-ethnic studies. For well-known pathogenic/likely pathogenic germline variants, Chinese patients exhibit overlapping but distinct germline mutation patterns comparing with Western cohorts, highlighted by lower mutation rates in known PAAD genes including BRCA1, BRCA2, ATM, CDKN2A, and CHEK2, and distinct mutations in CFTR, RAD51D, FANCA, ERCC2, and GNAS exclusive to Chinese patients. CFTR emerges as a top candidate gene following loss of heterozygosity analysis. Using an integrative multi-omics and functional validation paradigm, we discover that deleterious variants of uncertain significance may compromise CFTR's tumor suppressor function, and demonstrate the clinical relevance by using patient derived organoids for drug screen. Our multifaceted approach not only deepens the knowledge of population differences in PAAD germline mutations but also unveils potential avenues for targeted therapeutic interventions.

PMID:40044664 | DOI:10.1038/s41467-025-57520-3

Int J Pharm. 2025 Mar 3:125424. doi: 10.1016/j.ijpharm.2025.125424. Online ahead of print.

ABSTRACT

Lipoplexes are non-viral lipid vectors that effectively form complexes with genetic material, positioning them as promising alternatives to viral vectors in gene therapy. Their advantages include lower toxicity, reduced immunogenicity, improved targetability, and ease of large-scale production. A typical lipoplex is composed of cationic lipids, neutral lipids, and anionic nucleic acids (e.g., DNA, mRNA, miRNA, siRNA, shRNA). Neutral lipids play an auxiliary role and are often used as transfection enhancers. Enhancing lipoplex efficiency often involves modifying the cationic lipid structure through functional groups like PEG polymers and targeting ligands. The assembly of lipoplexes occurs spontaneously. This process involves the binding of the positively charged polar head group of the cationic lipid to the negatively charged DNA spontaneously as a result of electrostatic interaction, then irreversible rearrangement and condensation of the lipoplex occurs to form either lamellar or hexagonal structures. The transfection process encompasses several steps: cellular entry, endosomal escape and cargo release, cytoplasmic trafficking, and nuclear entry. The physicochemical and biological properties of lipoplexes are influenced by factors such as lipid structure, charge ratio, and environmental conditions. Despite certain limitations like low gene transfer efficiency and rapid clearance by serum proteins, lipoplexes show promise for clinical applications. They can be administered through various routes, offering potential treatments for diseases such as cancer, bone damage, infection, and cystic fibrosis. The study aims to examine the potential of lipoplexes as a promising vehicle for delivering therapeutic agents and their progression from theoretical concepts to practical clinical applications.

PMID:40043964 | DOI:10.1016/j.ijpharm.2025.125424

Eur Respir Rev. 2025 Mar 5;34(175):240201. doi: 10.1183/16000617.0201-2024. Print 2025 Jan.

ABSTRACT

INTRODUCTION: Social determinants of health (SDH), including age, sex, ethnicity, socioeconomic status and rurality, influence health outcomes. Clinical trials investigating antifibrotic agents for people with idiopathic pulmonary fibrosis (IPF) have been conducted in predominantly White and male populations; it is unclear whether other SDH have been considered. This study aimed to investigate active consideration and reporting of SDH in clinical trials of antifibrotic agents for people with IPF.

METHODS: Three registries (ClinicalTrials.gov, ANZCTR and International Standard Randomised Controlled Trial Number (ISRCTN)) plus CENTRAL (Cochrane Central Register of Controlled Trials) were searched for clinical trials investigating antifibrotic agents for people with IPF or various progressive fibrotic ILD variants registered from 1 January 2000 until 3 September 2023. Data were extracted regarding trial phase/status, recruitment strategies and eligibility criteria. If trial results were available, SDH data from demographics and subgroup analyses were extracted.

RESULTS: Of 313 records identified, 70 trials were included. The majority of trials were phase II or III (77%), 56% were completed and 61% had reported results that included eight terminated trials. All 70 trials specified age and sex, but not other SDH, within their eligibility criteria. Of 43 trials reporting results, all reported age and sex and 40 (95%) reported ethnicity. 10 387 participants were described (74% male, 77% White, 16% Asian and <1% Black). Descriptors for ethnicity varied considerably. Five trials (12%) included only White participants and three (7%) included only Asian participants. No other SDH were reported.

CONCLUSIONS: SDH beyond age, sex and ethnicity were neither considered nor reported in antifibrotic IPF trials. Trial populations were predominantly male and White. There is a need to actively consider SDH to ensure diverse and representative clinical trial populations.

PMID:40044188 | DOI:10.1183/16000617.0201-2024

Eur Respir Rev. 2025 Mar 5;34(175):230212. doi: 10.1183/16000617.0212-2023. Print 2025 Jan.

ABSTRACT

BACKGROUND: The role of objective cough monitoring systems for assessments in adults with chronic respiratory diseases (CRDs) is unclear. This systematic review aimed to synthesise current literature on frequency of use and characteristics of these systems.

METHODS: MEDLINE, Embase and CENTRAL were systematically searched to identify relevant literature evaluating cough in adults with CRDs using objective cough monitoring systems. The primary outcomes were utility and characteristics of the systems, with the secondary outcome being usability.

RESULTS: We identified 54 primary studies (4909 patients, with 3364 having idiopathic chronic cough). Included studies were generally of low risk of bias. Objective monitoring systems identified were VitaloJAK (n=19 studies), Leicester Cough Monitor (LCM, n=18), LEOSound (n=2), PulmoTrack (n=2), Hull Automated Cough Counter (HACC, n=1), LifeShirt (n=1), and unnamed devices (n=11). There was limited assessment against manual counting, with low-to-moderate correlation to patient-reported outcome measures for VitaloJAK (p<0.05), LCM (r=0.43-0.78) and unnamed devices (r=0.38-0.40). Test-retest consistency was evaluated in two studies, showing favourable results. There was at least moderate effect size of longitudinal measurement changes to various treatments for VitaloJAK (nine out of 16), LCM (two out of eight), HACC (n=1), LCM and HACC (n=1), PulmoTrack (n=1) and unnamed devices (n=3).

CONCLUSIONS: Few studies evaluated the agreement of objective cough monitoring systems against manual counting. Most studies were conducted in patients with idiopathic chronic cough, with the VitaloJAK and LCM being were the most evaluated objective cough monitoring systems. Further evaluation of objective cough monitoring systems is needed for research and clinic application.

PMID:40044185 | DOI:10.1183/16000617.0212-2023

Tissue Cell. 2025 Mar 1;94:102817. doi: 10.1016/j.tice.2025.102817. Online ahead of print.

ABSTRACT

Growth factors and cytokines in the vitreous are critical drivers of proliferative diabetic retinopathy (PDR), a condition in which many patients exhibit resistance to current therapies. PDR is characterized by the formation of fibrovascular membranes on the vitreous side of the retina, which, if untreated, can lead to retinal detachment. Nintedanib, a clinically approved drug for idiopathic pulmonary fibrosis, targets multiple tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and fibroblast growth factor receptors (FGFRs). In this study, we demonstrate that nintedanib effectively inhibits PDR vitreous-induced signaling molecules-namely, phosphorylation of VEGFR2, Akt, and Erk1/2-as well as cellular responses, including proliferation, migration, and tube formation in primary human retinal microvascular endothelial cells, at a non-toxic concentration of 1 μM. These findings suggest that nintedanib holds potential as a novel therapeutic option for the treatment of PDR.

PMID:40043340 | DOI:10.1016/j.tice.2025.102817

Nat Rev Chem. 2025 Mar 5. doi: 10.1038/s41570-025-00694-7. Online ahead of print.

ABSTRACT

Powerful single-molecule approaches have been developed for the accurate measurement of protein oligomers, but they are often low throughput and limited to the measurement of specific systems. To overcome this problem, nanopore-based detection holds the promise of providing the high throughput, broad applicability, and accuracy necessary to characterize protein oligomers in a variety of contexts. Nanopores provide accuracy comparable with that of state-of-the-art single-molecule detection methods, but with the added potential for fast and accurate measurements that may be amenable to industrial-scale manufacture. Key to enabling this expansion is combination with other emerging technologies such as DNA nanostructure tagging, machine learning-enabled signal analysis, and innovative detection device manufacture. Together, these technologies could enable widespread adoption of nanopore-based sensing in oligomer detection, revolutionizing diagnostics and biomarker detection in protein misfolding diseases.

PMID:40045069 | DOI:10.1038/s41570-025-00694-7

Nature. 2025 Mar 5. doi: 10.1038/s41586-025-08663-2. Online ahead of print.

ABSTRACT

Tropical forest canopies are the biosphere's most concentrated atmospheric interface for carbon, water and energy1,2. However, in most Earth System Models, the diverse and heterogeneous tropical forest biome is represented as a largely uniform ecosystem with either a singular or a small number of fixed canopy ecophysiological properties3. This situation arises, in part, from a lack of understanding about how and why the functional properties of tropical forest canopies vary geographically4. Here, by combining field-collected data from more than 1,800 vegetation plots and tree traits with satellite remote-sensing, terrain, climate and soil data, we predict variation across 13 morphological, structural and chemical functional traits of trees, and use this to compute and map the functional diversity of tropical forests. Our findings reveal that the tropical Americas, Africa and Asia tend to occupy different portions of the total functional trait space available across tropical forests. Tropical American forests are predicted to have 40% greater functional richness than tropical African and Asian forests. Meanwhile, African forests have the highest functional divergence-32% and 7% higher than that of tropical American and Asian forests, respectively. An uncertainty analysis highlights priority regions for further data collection, which would refine and improve these maps. Our predictions represent a ground-based and remotely enabled global analysis of how and why the functional traits of tropical forest canopies vary across space.

PMID:40044867 | DOI:10.1038/s41586-025-08663-2

Nat Commun. 2025 Mar 5;16(1):2211. doi: 10.1038/s41467-025-57313-8.

NO ABSTRACT

PMID:40044688 | DOI:10.1038/s41467-025-57313-8

Biochim Biophys Acta Mol Cell Res. 2025 Mar 3:119928. doi: 10.1016/j.bbamcr.2025.119928. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with a poor prognosis and decreased patient survival. It is intimately linked to AXL overexpression and AXL hyperactivation. Here, we explored the therapeutic potential of AX-0085, a small molecule AXL inhibitor. While AX-0085 was previously characterized in the context of lung adenocarcinoma, this study demonstrates its application in triple-negative breast cancer (TNBC) models. AX-0085 exhibited high binding affinity to the ATP binding site located beneath the conserved glycine-rich loop (P-loop) that links the β1 and β2 strands of the AXL kinase domain. Furthermore, it was demonstrated that the benzamide group of AX-0085 and LyS567's Nζ atom could generate a hydrogen bond. AX-0085 efficiently suppressed the AXL/GAS6 signaling pathway activation in TNBC cells in vitro, which in turn prevented AXL/GAS6 signaling-dependent pro-cancerous behavior like cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT). In TNBC, an AX-0085-induced cell cycle arrest that took place during the G1 phase reduced the expression of CYCLIN E and CDK2. Additionally, AX-0085 facilitated apoptotic cell death in TNBC. Treatment of AX-0085 on in vivo mouse xenografts transplanted with 4 T1 cells showed a significant tumor reduction. Thus, our findings demonstrate that AX-0085 has an effective therapeutic role in TNBC by inhibiting AXL activation.

PMID:40044045 | DOI:10.1016/j.bbamcr.2025.119928

Mol Cell Proteomics. 2025 Mar 3:100937. doi: 10.1016/j.mcpro.2025.100937. Online ahead of print.

ABSTRACT

Here, we develop PEPSeek, a web-server based software to allow higher performance in the identification of pathogen-derived epitope candidates detected via mass spectrometry in MHC class I immunopeptidomes. We apply it to human and mouse cell lines infected with either SARS-CoV-2, Listeria monocytogenes or Chlamydia trachomatis, thereby identifying a large number of novel antigens and epitopes that we prove to be recognized by CD8+ T cells. In infected cells, we identified antigenic peptide features that suggested how processing and presentation of pathogenic antigens differ between pathogens. The quantitative tools of PEPSeek also helped to define how C. trachomatis infection cycle could impact on the antigenic landscape of the host human cell system, likely reflecting metabolic changes occurred in the infected cells.

PMID:40044041 | DOI:10.1016/j.mcpro.2025.100937

Food Chem. 2025 Feb 25;477:143549. doi: 10.1016/j.foodchem.2025.143549. Online ahead of print.

ABSTRACT

Succinate is a key component of the characteristic umami-like taste of shellfish, which is similar to the umami taste elicited by glutamate, but is slightly more persistent and astringent. The taste receptors involved in the perception of succinate currently remain unknown. Therefore, we herein attempted to identify the taste receptors for succinate. We investigated whether cells heterologously expressing receptors associated with umami taste or succinate were activated by succinate and selected GPR91 as a candidate receptor. To verify the contribution of GPR91 to taste perception, the relationship between GPR91 activation and sensory activity was assessed using receptor assays and sensory evaluations. Our results suggest that the taste of succinate depends on the activation of GPR91. We propose that GPR91 functions as a gustatory receptor involved in the perception of the umami-like shellfish taste of succinate.

PMID:40043606 | DOI:10.1016/j.foodchem.2025.143549

Tuberculosis (Edinb). 2025 Mar 1;152:102626. doi: 10.1016/j.tube.2025.102626. Online ahead of print.

ABSTRACT

Mycobacterium abscessus (M. abscessus) is an emerging pathogenic mycobacterium that mainly causes pulmonary infections, especially in immunocompromised patients. This bacterium shows exhibits intrinsic resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and clinicians, thereby raising the need for innovative drug discovery. In this study, we selected phenylalanine-tRNA ligase beta unit (PheT) as a model target and used CRISPR interference to evaluate its essentiality as a therapeutic target against M. abscessus. The results show that genetically disruption of PheT leads to clear growth inhibitory phenotypes both in vitro and in vivo. Further transcriptome analysis revealed differential expression of host genes in response to PheT gene silencing, including genes involved in the cell cycle, apoptotic signaling, and inflammatory responses. Overall, PheT gene plays a crucial role in M. abscessus infection, and its silencing may represent a druggable therapeutic strategy for treating this infection.

PMID:40043507 | DOI:10.1016/j.tube.2025.102626

Arch Gerontol Geriatr. 2025 Feb 26;133:105803. doi: 10.1016/j.archger.2025.105803. Online ahead of print.

ABSTRACT

Frailty syndrome often coexists with multimorbidity, sharing several risk factors and outcomes. Therefore, considering multimorbidity when exploring frailty biomarkers may deepen our understanding of these conditions' pathophysiology. In this regard, most studies focused on inflammation, but markers of mitochondrial dysfunction, such as mitochondrial DNA damage, cell respiratory impairment, and oxidative stress, are less explored. The FRAMITO project aims to evaluate mitochondrial dysfunction in frailty, with and without multimorbidity. This cross-sectional study will enroll 75 individuals aged ≥65 years from inpatient and outpatient clinics at the Geriatrics Units of the University Hospital of Ferrara (Ferrara, Italy) and Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy). Participants will be categorized into three groups: 25 without frailty and multimorbidity, 25 with frailty but not multimorbidity, and 25 with frailty and multimorbidity. Blood samples will be collected to isolate Peripheral Blood Mononuclear Cells. Frailty biomarkers will be identified using untargeted metabolomics and functional studies on mitochondrial dysfunctions in PBMCs and their subpopulations, evaluating mitochondrial DNA damage, mitochondrial and glycolytic cellular bioenergetics, and intracellular reactive oxygen species. This project will advance our understanding of mitochondrial dysfunctions in frailty, particularly when combined with multimorbidity, revealing potential synergistic effects. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT06433427.

PMID:40043348 | DOI:10.1016/j.archger.2025.105803

Sci Rep. 2025 Mar 5;15(1):7770. doi: 10.1038/s41598-025-91476-0.

ABSTRACT

This study aims to investigate the adverse effects of immune checkpoint inhibitors (ICIs) on the female and male reproductive systems. In the FDA Adverse Event Reporting System (FAERS) database, adverse reactions under the "Reproductive system and breast disorders" category in the System Organ Classes were included, covering a period from January 1, 2015, to June 30, 2023. We identified 133,512 patients treated with ICIs. Immune checkpoint inhibitor-related reproductive adverse effects (irRAEs) were reported in 568 (0.43%) patients. Spermatogenesis abnormality (ROR025 = 7.91) had the highest signal strength associated with ICI use in males. Genital tract fistula was the only significant irRAE (ROR025 = 2.72) in females. PD-1 inhibitors pose greater risk than CTLA-4 inhibitors (OR = 1.65 [1.05-2.79], p = 0.045). Gynecologic cancers in females (OR = 3.77 [2.82-4.99], p < 0.0001) and urogenital cancers in males (OR = 1.56 [1.17-2.06], p = 0.0018) carried the highest risk compared to other cancers. Additional targeted drugs (OR = 2.32 [1.76-3.02], p < 0.0001), particularly lenvatinib (OR = 3.50 [2.48-4.94], p < 0.0001) and cabozantinib (OR = 3.71 [1.96-7.03], p < 0.0001) significantly increased the risk for females. Additional use of chemotherapy drugs was associated with a significant reduction in the risk for males (OR = 0.65 [0.42-0.96], p = 0.042) except for doxorubicin (OR = 2.58 [1.22-5.47], p = 0.013) and cyclophosphamide (OR = 2.36 [1.05-5.29], p = 0.038). This study demonstrates that ICIs could potentially lead to a wide range of adverse effects in the reproductive system in both males and females.

PMID:40044844 | DOI:10.1038/s41598-025-91476-0