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Learning structures that effectively abstract decision policies is key to the flexibility of human intelligence. Previous work has shown that humans use hierarchically structured policies to efficiently navigate complex and dynamic environments. However, the computational processes that support the learning and construction of such policies remain insufficiently understood. To address this question, we tested 1026 human participants, who made over 1 million choices combined, in a decision-making task where they could learn, transfer, and recompose multiple sets of hierarchical policies. We propose a novel algorithmic account for the learning processes underlying observed human behavior. We show that humans rely on compressed policies over states in early learning, which gradually unfold into hierarchical representations via meta-learning and Bayesian inference. Our modeling evidence suggests that these hierarchical policies are structured in a temporally backward, rather than forward, fashion. Taken together, these algorithmic architectures characterize how the interplay between reinforcement learning, policy compression, meta-learning, and working memory supports structured decision-making and compositionality in a resource-rational way.

Spinal cord injury results in the loss of sensory, motor, and autonomic functions, which almost always produces permanent physical disability. Thus, in the search for more effective treatments than those already applied for years, which are not entirely efficient, researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach, seeking to promote neuronal recovery after spinal cord injury. Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and, consequently, boosting functional recovery. Although the majority of experimental research has been conducted in rodents, there is increasing recognition of the importance, and need, of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans. This article is a literature review from databases (PubMed, Science Direct, Elsevier, Scielo, Redalyc, Cochrane, and NCBI) from 10 years ago to date, using keywords (spinal cord injury, cell therapy, non-human primates, humans, and bioengineering in spinal cord injury). From 110 retrieved articles, after two selection rounds based on inclusion and exclusion criteria, 21 articles were analyzed. Thus, this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans, aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Abstract Breathing exercises are used to address a multitude of issues ranging from mental health to physical well-being. While they are recommended for various health conditions, access to professional support is often limited due to time and cost constraints. Virtual Reality technology offers a promising solution for enhancing mindfulness and relaxation practices, including breathing exercises. In our study, we explored the effectiveness of a computer-generated “virtual breathing coach”. Our virtual coach has a human appearance, speaks in a human voice, and displays breathing physiology while guiding the participants through a set of breathing exercises of different cycle lengths. The agent exhibits breathing behaviour with the aim of augmenting the influence the agent exerts through the mechanisms of physiological entrainment known from human-to-human interaction. Our empirical, exploratory study with 20 participants, was conducted using non-immersive VR where the system ran on a web browser. On the one hand, we investigated the perception of the virtual human coach, and on the other hand, we evaluated the usability, acceptability, and adherence of the system. We also evaluated the role of realism in acceptance of and adherence to the virtual coach. Participants’ responses were recorded using questionnaires. Participants were influenced by the virtual coach and adhered to it if they perceived the virtual coach as more realistic. The participants reported that the system ran well, and they would be willing to continue using the system in the future. Although the virtual human-to-human interaction experience provided by our system is not on par with the naturalistic human-to-human interaction, the results indicate that people are willing to replace a real human coach with a virtual coach. Systems like this are a step towards improving the affordability and on-demand access to another human, such as a coach in our system, especially where access and affordability are limited such as in healthcare. The qualities such as trust and likeability in an embodied interaction can make this interaction more efficient and effective.

Exercise-induced muscle damage (EIMD) is characterized by a severe and prolonged decline in force-generating capacity. However, the precise cellular mechanisms underlying the observed long-lasting decline in force-generating capacity associated with EIMD are still unclear. We investigated in vivo force generation and ex vivo Ca 2+ -activated force generation, Ca 2+ sensitivity, and myofiber Ca 2+ handling systems (SR and t-tubules) in human biceps brachii before and 2, 48, and 96 h after eccentrically muscle-damaging contractions and in non-exercised control arm. The force-generating capacity declined by 50 ± 13% 3 h after exercise and was still not recovered after 96 h. The force-Ca relationship of skinned myofibers revealed an impaired maximal Ca 2+ -activated force in MHC I-fibers, but not MHC II-fibers 48 h after exercise. Further, Ca 2+ sensitivity was increased in MHC II-fibers, which was reversed after incubation with a strong reductant. There was a biphasic increase in SERCA sulfonylation, and a parallel reduction in the SR Ca 2+ uptake rate, with no effects on SR vesicle leak or SR vesicle Ca 2+ release rate. T-tubules showed a progressive increase in the density of longitudinal tubules by 96 h after exercise. In conclusion, MHC II-fiber Ca 2+ sensitivity was increased 48 h after exercise, attributed to changes in the REDOX status. 96 h after exercise SR vesicle Ca 2+ uptake was impaired, and an increased number of longitudinal tubules were observed. These alterations may contribute to the impaired force generation evident at the late stage of recovery., (© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Aims: To develop a semimechanistic model that describes the kinetic profile and variability of antibody (Ab) concentrations following vaccination with Ad26.COV2.S at different doses and dosing intervals., Methods: Data were collected from participants randomized into 5 clinical trials receiving the Ad26.COV2.S vaccine. The model considered key elements of humoral immune response, dose proportionality and the evolutionary processes of the immune response. Interindividual variability and covariates were explored., Results: Fast and slow kinetic phases of Ab and their evolution over time were differentiated. After first and second administrations, Ab concentrations of both phases increased less than dose proportionally, indicating a saturation of B-cell production processes. Ab concentrations produced during the fast kinetic phase increased significantly after the second administration, indicating an underlying evolutive process after antigen exposures. For the slow kinetic phase, a less pronounced increase occurred after the second and third administrations but was relatively higher in subjects who had low concentrations after the first administration. Ab concentrations of the slow phase were higher in females and decreased with age. After multiple administrations, the fast phase had Ab maximum concentrations about 5 times higher than the slow phase. The limiting kinetic factors in the fast and slow phases were the elimination rates of Ab itself and Ab producing cells, respectively., Conclusion: The model appears suitable to quantitatively describe the inter- and intraindividual kinetics of the immune response and the impact of covariates after multiple administrations of a vaccine., (© 2024 British Pharmacological Society.)

Background: Ticks are the primary vectors of numerous zoonotic pathogens, transmitting more pathogens than any other blood-feeding arthropod. In the northern hemisphere, tick-borne disease cases in humans, such as Lyme borreliosis and tick-borne encephalitis, have risen in recent years, and are a significant burden on public healthcare systems. The spread of these diseases is further reinforced by climate change, which leads to expanding tick habitats. Switzerland is among the countries in which tick-borne diseases are a major public health concern, with increasing incidence rates reported in recent years., Methods: In response to these challenges, the "Tick Prevention" app was developed by the Zurich University of Applied Sciences and operated by A&K Strategy Ltd. in Switzerland. The app allows for the collection of large amounts of data on tick attachment to humans through a citizen science approach. In this study, citizen science data were utilized to map tick attachment to humans in Switzerland at a 100 m spatial resolution, on a monthly basis, for the years 2015 to 2021. The maps were created using a state-of-the-art modeling approach with the software extension spatialMaxent, which accounts for spatial autocorrelation when creating Maxent models., Results: Our results consist of 84 maps displaying the risk of tick attachments to humans in Switzerland, with the model showing good overall performance, with median AUC ROC values ranging from 0.82 in 2018 to 0.92 in 2017 and 2021 and convincing spatial distribution, verified by tick experts for Switzerland. Our study reveals that tick attachment to humans is particularly high at the edges of settlement areas, especially in sparsely built-up suburban regions with green spaces, while it is lower in densely urbanized areas. Additionally, forested areas near cities also show increased risk levels., Conclusions: This mapping aims to guide public health interventions to reduce human exposure to ticks and to inform the resource planning of healthcare facilities. Our findings suggest that citizen science data can be valuable for modeling and mapping tick attachment risk, indicating the potential of citizen science data for use in epidemiological surveillance and public healthcare planning., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Despite immense interest in biomarker applications of extracellular vesicles (EVs) from blood, our understanding of circulating EVs under physiological conditions in healthy humans remains limited. Using imaging and multiplex bead-based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterize their biological variation and explored demographic, clinical, and lifestyle factors contributing to observed variation. Cell-specific circulating EV subsets show a wide range of concentrations that do not correlate with cell-of-origin concentrations in blood, suggesting steady-state EV subset concentrations are regulated by complex mechanisms, which differ even for EV subsets from the same cell type. Interestingly, tetraspanin+ circulating EVs largely originate from platelets and to a lesser extent from lymphocytes. Principal component analysis (PCA) and association analyses demonstrate high biological inter-individual variation in circulating EVs across healthy humans, which are only partly explained by the influence of sex, menopausal status, age and smoking on specific circulating EV and/or tetraspanin+ circulating EV subsets. No global influence of the explored subject's factors on circulating EVs was detected. Our findings provide the first comprehensive, quantitative data towards the cell-origin atlas of plasma EVs, with important implications in the clinical use of EVs as biomarkers., (© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Conjunctival goblet cells (CGCs) are specialized epithelial cells playing key roles for ocular surface homeostasis, and their examination is important for diagnosing ocular surface diseases. Despite recent advancements in high-contrast CGC imaging for non-invasive examination, significant challenges remain for human applications. High-speed large-area imaging over the curved ocular surface is needed to assess statistically meaningful CGCs in the extensive human conjunctiva. To address this challenge, we developed a novel surface detection method and an integrated microscopy system for human use. With both a long detection range of 2 mm and a high update rate of 50 Hz, the surface detection method enabled real-time surface tracking during large-area imaging. The integrated microscopy could complete 5 × 2 patch imaging in approximately 10 s. CGC density analysis showed significantly reduced uncertainties with large-area imaging. This is the first demonstration of non-contact large-area cellular examination in humans, and this new development holds promise for non-invasive CGC examination and accurate diagnosis of ocular surface diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Abstract: Patients with cytotoxic T-lymphocyte-associated protein 4 (CTLA4) deficiency exhibit profound humoral immune dysfunction, yet the basis for the B-cell defect is not known. We observed a marked reduction in transitional-to-follicular (FO) B-cell development in patients with CTLA4 deficiency, correlating with decreased CTLA4 function in regulatory T cells, increased CD40L levels in effector CD4+ T cells, and increased mammalian target of rapamycin complex 1 (mTORC1) signaling in transitional B cells (TrBs). Treatment of TrBs with CD40L was sufficient to induce mTORC1 signaling and inhibit FO B-cell maturation in vitro. Frequent cell-to-cell contacts between CD40L+ T cells and immunoglobulin D-positive CD27- B cells were observed in patient lymph nodes. FO B-cell maturation in patients with CTLA4 deficiency was partially rescued after CTLA4 replacement therapy in vivo. We conclude that functional regulatory T cells and the containment of excessive T-cell activation may be required for human TrBs to mature and attain metabolic quiescence at the FO B-cell stage., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end-stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species-specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation-anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ-source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

As anatomically modern humans dispersed out of Africa, they encountered and mated with now extinct hominins, including Neanderthals and Denisovans. It is now well established that all non-African individuals derive approximately 2% of their genome from Neanderthal ancestors and individuals of Melanesian and Australian aboriginal ancestry inherited an additional 2%-5% of their genomes from Denisovan ancestors. Attention has started to shift from documenting amounts of archaic admixture and identifying introgressed segments to understanding their molecular, phenotypic, and evolutionary consequences and refining models of human history. Here, we review recent insights into admixture between modern and archaic humans, emphasizing methodological innovations and the functional and phenotypic effects Neanderthal and Denisovan sequences have in contemporary individuals., Competing Interests: Declaration of Competing Interest Joshua Akey reports financial support was provided by National Institute of General Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

PTPRQ plays an important role in the development of inner ear hair cell stereocilia. While many autosomal recessive variants in PTPRQ have been identified as the pathogenic cause for nonsyndromic hearing loss (DFNB84A), so far only one autosomal dominant PTPRQ variant, c.6881G>A (p.Trp2294*), has been reported for late-onset, mild-to-severe hearing loss (DFNA73). By using targeted next-generation sequencing, this study identified a novel PTPRQ truncating pathogenic variant, c.3697del (p.Leu1233Phefs*11), from a Chinese Han family that co-segregated with autosomal dominant, postlingual, progressive hearing loss. A Ptprq-3700del knock-in mouse model was generated by CRISPR-Cas9 and characterized for its hearing function and inner ear morphology. While the homozygous knock-in mice exhibit profound hearing loss at all frequencies at the age of 3 weeks, the heterozygous mutant mice resemble the human patients in mild, progressive hearing loss from age 3 to 12 weeks, primarily affecting high frequencies. At this stage, the homozygous knock-in mice have a normal hair cell count but disorganized stereocilia. Cochlear proteosome analysis of the homozygous mutant mice revealed differentially expressed genes and pathways involved in oxidative phosphorylation, regulation of angiogenesis and synaptic vesicle cycling. Our study provides a valuable animal model for further functional studies of the pathogenic mechanisms underlying DFNA73., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Men, despite having a lower likelihood of longevity compared to women, generally exhibit better health status when they achieve longevity. The role of DNA methylation in this paradox remains unclear. We performed whole-genome bisulfite sequencing on long-lived men (LLMs), long-lived women (LLWs), younger men (YMs) and younger women (YWs) to explore specific methylation characteristics in LLMs. Despite an accelerated methylation aging rate in LLMs compared to LLWs, we identify thousands of differentially methylated genomic units (DMUs) in LLMs independent of age and sex. These DMUs, validated by an elastic net classifier, can serve as methylation markers for discriminating longevity potential in men. Many are located near health-related genes. Genes like PIWIL1 and EXT1, with promoters featuring DMUs, exemplify the potential role of LLM-specific methylation patterns in suppressing age-related diseases by regulating gene transcription. Our findings provide evidence of a distinct methylation feature contributing to healthy aging and longevity of LLMs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Oncolytic viruses (OVs) are promising immunotherapeutics to treat immunologically cold tumors. However, research on the mechanism of action of OVs in humans and clinically relevant biomarkers is still sparse. To induce strong T-cell responses against solid tumors, TILT-123 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, igrelimogene litadenorepvec) was developed. TILT-123 encodes two transgenes: tumor necrosis alpha (TNFa) and interleukin-2 (IL-2). TUNIMO (NCT04695327) was a phase I clinical trial using TILT-123 in patients with advanced solid tumors aiming to assess the safety, efficacy, and immunological effects of TILT-123. Research presented in this study evaluated the immunological effects of TILT-123 in the TUNIMO trial by using biological samples collected from the patients during the study, with an objective to leverage the findings to develop possible biomarkers of response and gain insights into possible synergistic combination treatments., Methods: 20 patients with advanced solid tumors were treated with TILT-123. Response to therapy was assessed with contrast-enhanced CT and fluorodeoxyglucose positron emission tomography, along with overall survival (OS) calculation. Biological samples from patients were collected in the form of blood and tumor biopsies. Collected samples were analyzed with immunohistochemistry, transcriptomics, proteomics, and flow cytometry., Results: TILT-123 induced cyclical decreases in blood lymphocyte count, and more substantial blood lymphocyte count correlated with better radiographical response and longer OS. Lymphocyte count findings were confirmed with external control dataset of 96 patients. More substantial lymphocyte count change was linked to stronger immune activation in plasma proteome after intravenous TILT-123 and the presence of TILT-123 mRNA in tumors. Regarding other assays. tumor biopsies profiled showed increased amounts of CD8+ T cells, CD4+ T cells and NK cells after intravenous TILT-123, but not after intratumoral TILT-123. Transcriptional differences were seen in tumors after intravenous therapy and intratumoral therapy, with patients benefitting therapy showing stronger downregulation of immune activation at all time points., Conclusions: TILT-123 therapy induced accumulation of effector lymphocytes in tumors. Peripheral lymphocyte count decrease is a promising biomarker for assessing oncolytic adenovirus therapy response., Competing Interests: Competing interests: JHAC, JMS, CK and VC-C are employees and shareholders of TILT Biotherapeutics. LH, DCAQ, SS and RH are employees of TILT Biotherapeutics. KP has held advisory roles (Bayer AG, Bristol-Myers Squibb, MSD, Roche, Ipsen) and is shareholder of Faron Pharmaceuticals. AH is an employee and shareholder in TILT Biotherapeutics and shareholder in Circio Holdings ASA. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Escherichia coli is one of the critical One Health pathogens due to its vast array of virulence and antimicrobial resistance genes. This study used multiplex PCR to determine the occurrence of virulence genes bfp, ompA, traT, eaeA, and stx1 among 50 multidrug-resistant (MDR) E. coli isolates from humans (n = 15), animals (n = 29), and the environment (n = 6) in Dar es Salaam, Tanzania. Their association with antimicrobial-resistant genes (ARGs) was determined using Principal Component Analysis (PCA). All 50/50 (100%) MDR E. coli isolates carried at least one virulence gene, with 19/50 (38%) carrying four genes, bfp + traT + eaeA + ompA. The findings showed a high occurrence of virulence genes bfp (82%), traT (82%), eaeA (78%), and ompA (72%); the study detected no stx1 in any of the isolates. In humans, the most detected virulence genes were bfp and traT 14/15 (93.3%); for poultry, it was eaeA 13/14 (92.9%); for pigs, was bfp and traT 13/15 (86.7%); while for river water, it was eaeA 6/6 (100%). The study observed no significant association between virulence genes and ARGs. PCA results show the genes ompA, traT, eaeA, and bfp contributed to the virulence of the isolates, and blaTEM, blaCTX-M, and qnrs contributed to ARGs. The PCA ellipses show that isolates from pigs had more virulence genes than those isolated from poultry, river water, and humans. The high frequency of numerous virulence genes in MDR E. coli isolates from humans, animals, and the environment indicates that these isolates have a very high potential to cause diseases that are difficult to treat because they are MDR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 James et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intermediate phenotypes, such as characteristic neuroimaging patterns, offer unique insights into the genetic and stress-related underpinnings of neuropsychiatric disorders like depression. This study aimed to identify neuroimaging intermediate phenotypes associated with depression, bridging etiological factors to behavioral manifestations and connecting insights from animal models to diverse clinical populations., Methods: We analyzed datasets from both rodents and humans. The rodent studies included a genetic model (P11 knockout) and an environmental stress model (chronic unpredictable mild stress), while the human data comprised 748 participants from three cohorts. Using the amplitude of low-frequency fluctuations, we identified neuroimaging patterns in rodent models. We then applied a machine-learning approach to cluster neuroimaging subtypes of depression. To assess the genetic predispositions and stress-related changes associated with these subtypes, we analyzed genotype and metabolite data. Linear regression was employed to determine which neuroimaging features predicted core depression symptoms across species., Results: The genetic and environmental stress models exhibited distinct neuroimaging patterns in subcortical and sensorimotor regions. Consistent patterns emerged in two neuroimaging subtypes identified across three independent depressed cohorts. The subtype resembling P11 knockout demonstrated higher genetic susceptibility, with enriched expression of risk genes in brain tissues and abnormal metabolites linked to tryptophan metabolism. In contrast, the stress animal-like subtype did not show changes in genetic risk scores but exhibited enriched risk gene expression in somatic and endocrine tissues, along with mitochondrial dysfunction in the antioxidant stress system. Notably, these distinct subcortical-sensorimotor neuroimaging patterns predicted anhedonia, a core symptom of depression, in both rodent models and depressed subtypes., Conclusions: This cross-species validation suggests that these neuroimaging patterns may serve as robust intermediate phenotypes, linking etiology to anhedonia and facilitating the translation of findings from animal models to humans with depression and other psychiatric disorders., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures in these animal experiments were conducted in accordance with the guidelines of the Animal Care and Use Committee at the Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (APM23010A). The human study was approved by the Ethics Committees of Renmin Hospital of Wuhan University (WDRY2020-K191), Peking University Sixth Hospital (2016–6), and the First Affiliated Hospital of China Medical University (2015–27-2). All human participants provided written informed consent after receiving a detailed description of the study. Consent for publication: Written informed consent was obtained from all participants included in the study for the use of their clinical, demographic, and neuroimaging data in this publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Asthenozoospermia (ASZ) accounts for about 20-40% of male infertility, and genetic factors, contributing to 30-40% of the causes of ASZ, still need further exploration. Radial spokes (RSs), a T-shaped macromolecular complex, connect the peripheral doublet microtubules (DMTs) to a central pair (CP), forming a CP-RS-DMT structure to regulate the beat frequency and amplitude of sperm flagella. To date, many components of RSs and their functions in human sperm flagella remain unclear., Methods: We recruited a cohort of 323 infertile males with ASZ between August 2019 and June 2024. Genetic mutations were identified by whole-exome sequencing. Computer-aided sperm analysis, Papanicolaou staining, and electron microscopy were applied to evaluate the motility, morphology, and ultrastructure of spermatozoa, respectively. Protein mass spectrometry, western blotting, and bioinformatic analyses were performed to identify critical components of mammalian RS1 to model its structure and explore the pathological mechanism of IQUB deficiency. Intracytoplasmic sperm injection (ICSI) was applied for the patient and Iqub -/- mice., Results: We identified a novel homozygous IQUB mutation [c.842del (p.L281Pfs*28)] in an ASZ male with normal sperm morphology (ANM), which resulted in the complete loss of IQUB in sperm flagella. Deficiency of RS1, but not RS2 or RS3, was observed in both IQUB 842del patient and Iqub -/- mice, and resulted in the reduction of sperm kinetic parameters, indicating the critical role of IQUB in regulating mammalian RS1 assembly and sperm flagellar beat. More importantly, we identified twelve critical components of RS1 in humans and mice, among which RSPH3, RSPH6A, RSPH9 and DYDC1 constituting the head, DYDC1, NME5, DNAJB13 and PPIL6 assembling into the head-neck complex, AK8, ROPN1L, RSPH14, DYNLL1, and IQUB forming the stalk of RS1. Along with the RS1 defect, the IQUB deficiency caused significant down-regulation of the inner dynein arms of DNAH7 and DNAH12, highlighting their nearby location with RS1. Finally, ICSI can effectively resolve the male infertility caused by IQUB genetic defects., Conclusions: We demonstrate that IQUB may serve as an adapter for sperm flagellar RS1 in both humans and mice and consolidated the causal relationship between IQUB genetic mutations and ANM, further enriching the genetic spectrum of male infertility., Competing Interests: Declarations. Ethics approval and consent to participate: The ethical approval (No.: (2023) Ethics Review (Research) 030) was obtained from the Ethics Committee of Chongqing Health Center for Women and Children. An informed consent form was signed before the collection of peripheral blood and semen. The animal experiments were approved by the Experimental Animal Management and Ethics Committee of Chongqing Health Center for Women and Children (No.: 2023028). Consent for publication: All authors have read and agreed with the submission of the manuscript. This manuscript has not been published or presented elsewhere in part or in entirety. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Lectins are produced in almost all life forms, can interact with targets (glycans) in a cross-kingdom manner and have served as valuable tools for studying glycobiology. Previously, a bacterial lectin, named Streptomyces hemagglutinin (SHA), was found to agglutinate human type B erythrocytes. However, the binding of SHA to mammalian cell types other than human erythrocytes has not been explored. To address this, we produced a recombinant fusion protein, with the mCherry reporter protein proceeding the SHA protein (referred to as mCherry-SHA), and performed co-immunofluorescence staining analysis. We focused on the normal pancreas in this study because glycans on pancreatic cells have been associated with initiation and progression of pancreatic cancer, a deadly disease. We found that only acinar, but not ductal or endocrine cells were stained positively with mCherry-SHA from embryonic day (E) 18.5 to 35 weeks old mice; in contrast, E12.5 and E15.5 pancreas display minimal mCherry-SHA binding. In adult humans, mCherry-SHA also targeted acinar cells specifically; however, only tissue from blood type B donors, but not type A or O donors, showed positivity. Together, these results demonstrate that SHA can bind to normal murine and human pancreatic acinar cells and that SHA-binding glycans are developmentally regulated., Competing Interests: Declarations. Competing interests: M.K., Y.F-Y, and K.B. declare holder for United States Patent No. US11,767,351 B2. Date of Patent: Sept. 26, 2023. Other authors declare no conflicts of interest with the contents of this article., (© 2025. The Author(s).)

Dogs can discriminate between people infected with SARS-CoV-2 from those uninfected, although their results vary depending on the settings in which they are exposed to infected individuals or samples of urine, sweat or saliva. This variability likely depends on the viral load of infected people, which may be closely associated with physiological changes in infected patients. Determining this viral load is challenging, and a practical approach is to use the cycle threshold (Ct) value of a RT-qPCR test. The hypothesis was that dogs should have a specific Ct range at which they could detect people infected with SARS-CoV-2. Therefore, the objective was to determine this Ct range. Sweat samples and epidemiological data were collected from 89 infected and 289 non-infected individuals at real life settings (e.g. health centers, offices, football fields). To determine each person's infection status, the Norgen Biotek kit for RT-qPCR was used; targeting the N1 and N2 regions of the SARS-CoV-2 nucleocapsid N gene. The performance of 11 trained dogs was evaluated on sweat samples of 379 individuals to determine their sensitivity and specificity (± 95% Confidence Intervals; CI) in detecting SARS-CoV-2 infections. Additionally, the SARS-CoV-2 viral load was calculated from Ct values using a reference curve, and the Ct range at which dogs showed optimal performance was determined. Six dogs exhibited a marginal performance, as their sensitivity 95% CI overlapped with the region of randomness (50%). The remaining five dogs demonstrated sensitivity values between 67% and 87%, with none of their 95% CIs overlapping the randomness region. Regarding specificity, three dogs showed values between 87% and 92%, while all other dogs exhibited values of ≥ 90%. Dogs demonstrated higher detection accuracy in a range of Ct values between 18.49 and 29.17 for the N1 region and between 24.07 and 26.69 for the N2 region of the SARS-CoV-2 nucleocapsid gene. Detection significantly decreases for Ct values greater than 30 or less than 16, indicating an optimal range in which dogs are most effective. These performance values concur well with those reported for commercial rapid antigen tests for detecting SARS-CoV-2. Consequently, it is considered that using properly trained animals could offer a viable option to supplement existing diagnostic methods, allowing for rapid diagnosis while optimizing time and economic resources. Moreover, this approach is ecologically sustainable, as it generates less waste compared to the use of rapid tests, while continuing to confirm positive cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Vidal-Martínez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Franchthi Cave, in the Greek Peloponnese, is a well-known Paleolithic, Mesolithic and Neolithic site, with several human burials. In many parts of Europe there is clear evidence from archaeological and isotopic studies for a diet change between the Mesolithic and Neolithic periods. This is especially the case in coastal contexts where there is often a shift from predominantly marine food diets in the Mesolithic to terrestrial (presumably domesticated) foods in the Neolithic. However, at Franchthi Cave previous isotope research did not show changes in diets between these two periods, and also showed relatively little input from marine foods in diets in either time period, despite the coastal location of the site and the presence of marine shellfish and fish, including tuna. High-resolution compound specific amino acid isotope analysis reported here from humans from the Lower Mesolithic and Middle Neolithic periods confirms the previous bulk isotope results in showing little or no consumption of marine foods in either time period. However, it is important to note that our isotopic sample does not come from episodes when tuna is abundant and therefore do not cover the whole range of known diets from the site. Conversely, in our sample there is some evidence of marine food consumption (likely seaweed) by sheep in the Neolithic period. We also report here five direct AMS radiocarbon dates for the five analyzed humans from the site., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Martinoia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)