Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis.

High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM's gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease.

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials. The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca2+ influx is critical for neuronal function. An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca2+ mainly via N-methyl-D-aspartate receptors, particularly of those at the extrasynaptic site. This Ca2+-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mild but sustained Ca2+ increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic, but gradually set off deteriorating Ca2+-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways. Based on the Ca2+ hypothesis of Alzheimer's disease and recent advances, this Ca2+-activated "silent" degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis. The N-methyl-D-aspartate receptor subunit GluN3A, primarily at the extrasynaptic site, serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity. Ischemic stroke and Alzheimer's disease, therefore, share an N-methyl-D-aspartate receptor- and Ca2+-mediated mechanism, although with much different time courses. It is thus proposed that early interventions to control Ca2+ homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia. This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Lethal and sublethal effects of spinosad on dengue vector mosquito, Aedes albopictus and bancroftian filariasis vector mosquito, Culex pipiens pallens.

BACKGROUND OBJECTIVES: Aedes albopictu and Culex pipiens pallens are important vectors of many viruses and have had resistance to chemical pesticide. Spinosad is a selective biological insecticide to control urban mosquito. The aim of this study was to reveal the sublethal effects of spinosad on mosquito and provide reference basis for integrated mosquito management. METHODS: The toxicity of spinosad against Ae. albopictus and Cx. pipiens pallens were determined under laboratory conditions by exposing early third-instar larvae to different concentrations. RESULTS: The LC50 values of spinosad to Ae. albopictus and Cx. Pipiens pallens larvaes were 4.44×10-3 mg∙L-1 and 1.93×10-3 mg∙L-1 respectively after 72 h exposure. Spinosad at sublethal concentrations has many negative effects on Ae. albopictus and Cx. Pipiens pallens larval, pupae, adult and offspring eggs, including significantly reduced their larvae pupation rate by 51.37% and 58.47%, significantly prolonged pupae length by 21.43% and 16.18%, reduced female wing-spans by 20.19% and 14.89%, reduced male wing-spans by 3.84% and 7.54%, reduced female weight by 29.04% and 31.52%, reduced male weight by 7.47% and 9.07%, reduced female and male ratio by 51.98% and 45.21%, reduced individual egg-laying amount by 15.73% and 35.51%, in addition, offspring egg hatchability were dramatically decreased by 25.71% and 34.04%, egg periods were significantly prolonged by 14.42% and 62.82% respectively. No significant effect on larval period, pupae emergence rate, female bite rates were observed. INTERPRETATION CONCLUSION: These results suggest that spinosad might affect pest population dynamics significantly and is fairly expected to be a candidate biological pesticide for mosquito control.

Automated Estimation of Thoracic Rotation in Chest X-ray Radiographs: A Deep Learning Approach for Enhanced Technical Assessment.

OBJECTIVES: This study aims to develop an automated approach for estimating the vertical rotation of the thorax, which can be used to assess the technical adequacy of chest X-ray radiographs (CXRs). METHODS: Total 800 chest radiographs were used to train and establish segmentation networks for outlining the lungs and spine regions in chest X-ray images. By measuring the widths of the left and right lungs between the central line of segmented spine and the lateral sides of the segmented lungs, the quantification of thoracic vertical rotation was achieved. Additionally, a life-size, full body anthropomorphic phantom was employed to collect chest radiographic images under various specified rotation angles for assessing the accuracy of the proposed approach. RESULTS: The deep learning networks effectively segmented the anatomical structures of the lungs and spine. The proposed approach demonstrated a mean estimation error of less than 2° for thoracic rotation, surpassing existing techniques and indicating its superiority. CONCLUSIONS: The proposed approach offers a robust assessment of thoracic rotation and presents new possibilities for automated image quality control in chest X-ray examinations. ADVANCES IN KNOWLEDGE: This study presents a novel deep learning-based approach for the automated estimation of vertical thoracic rotation in chest X-ray radiographs. The proposed method enables a quantitative assessment of the technical adequacy of CXR examinations and opens up new possibilities for automated screening and quality control of radiographs.

Low handgrip strength with asymmetry is associated with elevated all-cause mortality risk in older Chinese adults with abdominal obesity.

BACKGROUND AND OBJECTIVES: Low handgrip strength (HGS) and abdominal obesity (AO) have been reported to be linked to an increased all-cause mortality risk in older adults. However, the combined impact of AO with low HGS and/or HGS asymmetry on mortality risk remains unclear. Therefore, this study aimed to investigate the synergistic effects of AO and abnormal HGS on mortality risk among Chinese older adults. METHODS: Baseline data of the China Health and Retirement Longitudinal Study in 2011, along with mortality outcomes obtained in 2018 were used for the analysis. Low HGS was identified as HGS <18 kg in women or <28 kg in men, while HGS asymmetry is defined as an HGS of either hand > 10% stronger than the other. AO was characterized by a waist circumference ≥90 cm in men and ≥85 cm in women. Logistic regression analysis was used to evaluate the relationship between AO, abnormal HGS and mortality risk. RESULTS: A total of 5186 subjects aged 60 years or older were enrolled, 50.6% of whom were male. The proportions of participants with only AO, only low HGS, only HGS asymmetry, low HGS with asymmetry, both AO and low HGS, both AO and asymmetric HGS, and AO with both low HGS and asymmetry were 20.0%, 6.1%, 16.6%, 8.3%, 3.2%, 13.4%, and 3.9%, respectively. Over the course of a 7-year follow-up interval, 970 of these individuals died, with 13.4%, 12.4%, 13.6%, 15.5%, 4.1%, 10.1% and 6.9% of deaths in the above groups, respectively. The adjusted logistic regression analysis model confirmed that only low HGS (OR = 1.897, 95%CI: 1.386-2.596, p<0.001), low HGS with asymmetry (OR = 1.680, 95%CI: 1.265-2.231, p<0.001), and AO combined with both low HGS and asymmetry (OR = 2.029, 95%CI: 1.381-2.981, p<0.001) were associated with a higher risk of mortality. CONCLUSIONS: Low HGS, with or without asymmetry, is associated with increased mortality risk in older Chinese adults without AO, and the combination of low HGS and HGS asymmetry further elevates mortality risk in those with AO.

Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.

Schlank orchestrates insect developmental transition by switching H3K27 acetylation to trimethylation in the prothoracic gland.

Insect developmental transitions are precisely coordinated by ecdysone and juvenile hormone (JH). We previously revealed that accumulated H3K27 trimethylation (H3K27me3) at the locus encoding JH signal transducer Hairy is involved in the larval-pupal transition in insects, but the underlying mechanism remains to be fully defined. Here, we show in Drosophila and Bombyx that Rpd3-mediated H3K27 deacetylation in the prothoracic gland during the last larval instar promotes ecdysone biosynthesis and the larval-pupal transition by enabling H3K27me3 accumulation at the Hairy locus to induce its transcriptional repression. Importantly, we find that the homeodomain transcription factor Schlank acts to switch active H3K27 acetylation (H3K27ac) to repressive H3K27me3 at the Hairy locus by directly binding to the Hairy promoter and then recruiting the histone deacetylase Rpd3 and the histone methyltransferase PRC2 component Su(z)12 through physical interactions. Moreover, Schlank inhibits Hairy transcription to facilitate the larval-pupal transition, and the Schlank signaling cascade is suppressed by JH but regulated in a positive feedback manner by ecdysone. Together, our data uncover that Schlank mediates epigenetic reprogramming of H3K27 modifications in hormone actions during insect developmental transition.

Influence of endovascular surgery on abdominal aortic aneurysm management strategies from a national health insurance database survey.

BACKGROUND: Abdominal aortic aneurysm (AAA) poses a considerable global health challenge; however, population-based studies on AAA are scarce. The current study determined the hospitalization rates, surgical trends, mortality, and reintervention rates for ruptured (r-AAA) and nonruptured (nr-AAA) AAA by using a national health insurance database. METHODS: We conducted a population-based retrospective cohort study by analyzing data from 2007 to 2018 from the Taiwanese National Health Insurance Research Database. Individuals over 20 years of age with a new diagnosis of AAA were included in this study. RESULTS: A total of 70 457 patients were given a diagnosis of aortic aneurysm or dissection over the study period; 22 538 (32%) adult patients (≥20 years) had AAA. The annual incidence of AAA was approximately 7.7 to 10.3 per 100 000 (r-AAA: 0.8-1.3 per 100 000 versus nr-AAA: 6.8-9.0 per 100 000). Most of the patients with AAA were older adults (85%); 15 392 (68%) patients had a documented hospitalization, and 4885 (32%) underwent surgery within 14 days of diagnosis. The percentage of patients receiving endovascular aneurysm repair (EVAR) increased from 28% to 96% over the study period. The long-term survival rates were higher among the patients who underwent open surgical repair (OSR) compared with those of the patients who received EVAR or conservative treatment, regardless of whether they had r-AAA or nr-AAA. CONCLUSION: AAA is more common among older individuals, and the annual standardized incidence indicates a downward trend. Since the introduction of EVAR, the proportion of patients undergoing EVAR has continually increased, whereas that of those undergoing OSR have decreased. Although EVAR and OSR were both associated with lower mortality rates among patients with r-AAA, OSR resulted in better long-term survival outcomes.

Systems-level reconstruction of kinase phosphosignaling networks regulating endothelial barrier integrity using temporal data.

Phosphosignaling networks control cellular processes. We built kinase-mediated regulatory networks elicited by thrombin stimulation of brain endothelial cells using two computational strategies: Temporal Pathway Synthesizer (TPS), which uses phosphoproetiomics data as input, and Temporally REsolved KInase Network Generation (TREKING), which uses kinase inhibitor screens. TPS and TREKING predicted overlapping barrier-regulatory kinases connected with unique network topology. Each strategy effectively describes regulatory signaling networks and is broadly applicable across biological systems.

Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It's recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.

Using machine learning to dissect host kinases required for Leishmania internalization and development.

The Leishmania life cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes (i.e., neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators of Leishmania promastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique yet overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several putative host kinases that regulate receptor-mediated phagocytosis and/or the uptake of L. amazonensis. Findings included kinases previously implicated in Leishmania uptake (such as Src family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)), but we also uncovered many novel kinases. Our methods also predicted host kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course of Leishmania infection, and that the kinases required for the parasite's life cycle may differ substantially depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that appear to preferentially regulate the uptake of parasites over beads, indicating that the methods required for Leishmania to be internalized by macrophages may differ significantly from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.

Self-Administered Botulinum Injection Causing Rare Masquerade of Systemic Botulism.

This report describes the case of a patient who presented to the Emergency Department (ED) with a one-week history of difficulty in breathing, generalized weakness, dysphagia, and difficulty in walking. She had self-administered 100 units of onabotulinumtoxin A (BoNT-A) by injection into her face two weeks prior for cosmetic purposes. This case study highlights the rare but potential complication of systemic botulism.

Pediatric trauma during the COVID-19 lockdown: caregiver abuse and self-harm in a vulnerable population.

PURPOSE: This retrospective cohort study explores the impact of the COVID-19 pandemic on pediatric trauma cases in Singapore's National University Hospital from January 2015 to July 2021. The pandemic prompted unprecedented measures, altering societal dynamics. The study hypothesizes a reduction in major trauma incidents during the pandemic period. METHODS: This is a single-center retrospective study including all pediatric patients presenting with trauma-related ICD-9 codes, and an Injury Severity Score (ISS) greater than 8. Patients were stratified into two time periods: pre-pandemic (January 2015 to March 2020) and pandemic (April 2020 to July 2021) periods. RESULTS: Out of 254 pediatric trauma cases, 201 occurred pre-pandemic, and 53 during the pandemic. While overall trauma incidence remained similar, the pandemic period saw a shift in injury patterns. Home-based falls increased, vehicular accidents decreased, while deliberate self-harm and caregiver abuse rose significantly. The incidence of serious trauma attributed to non-accidental injury increased during the pandemic. CONCLUSION: The study reveals changing trauma patterns, emphasizing the importance of understanding societal impacts during pandemics. Notably cases of deliberate self-harm and caregiver abuse surged, echoing global concerns highlighted in other studies during the pandemic. The study underscores the need to preempt physical and psychological stressors in vulnerable populations during future pandemics.

Emergent coronary revascularization with percutaneous coronary intervention and coronary artery bypass grafting in patients receiving extracorporeal cardiopulmonary resuscitation.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue for refractory cardiac arrest, of which acute coronary syndrome is a common cause. Data on the coronary revascularization strategy in patients receiving ECPR remain limited. METHODS: The ECPR databases from two referral hospitals were screened for patients who underwent emergent revascularization. The baseline characteristics were matched 1:1 using propensity score between patients who underwent coronary artery bypass grafting (CABG) and those who received percutaneous coronary intervention (PCI). Outcomes, including success rate of weaning from extracorporeal membrane oxygenation (ECMO), hospital survival, and midterm survival in hospital survivors, were compared between CABG and PCI. RESULTS: After matching, most of the patients (95%) had triple vessel disease. Compared with PCI (n = 40), emergent CABG (n = 40) had better early outcomes, in terms of the rates of successful ECMO weaning (71.1% vs 48.7%, P = 0.05) and hospital survival (56.4% versus 32.4%, P = 0.04). After a mean follow-up of 2 years, both revascularization strategies were associated with favourable midterm survival among hospital survivors (75.3% after CABG vs 88.9% after PCI, P = 0.49), with a trend towards fewer reinterventions in patients who underwent CABG (P = 0.07). CONCLUSIONS: In patients who received ECPR because of triple vessel disease, the hospital outcomes were better after emergent CABG than after PCI. More evidence is required to determine the optimal revascularization strategy for patients who receive ECPR.

Effectiveness of a delirium risk assessment and multidisciplinary care approach in reducing delirium incidence among surgical intensive care unit patients: A retrospective pre-post intervention study.

BACKGROUND: Delirium is a common complication in intensive care unit (ICU) patients. It can lead to various adverse events. In this study, we investigated the effectiveness of combining the use of the PREdiction of DELIRium (PRE-DELIRIC) model for delirium risk assessment and the use of a multicomponent care bundle for delirium assessment, prevention, and care in terms of reductions in the incidence of delirium among surgical ICU patients. METHODS: This retrospective study included surgical ICU patients who had received PRE-DELIRIC-guided SMART/SmART care (SMART care: SmART bundle plus multidisciplinary team; SmART care: Sleep/sweet sense of home (creating a comforting and restful environment for patients), Assessment (regular and thorough evaluation of patient needs and conditions), Release (revised endotracheal tube care/removal, restraint device care, and immobility reduction for patient comfort), and Time (reorientation of time to optimize patient care schedules) in our hospital between May 2022 and March 2023 (intervention group) and individuals who had received usual care between January 2021 and April 2022 (historical control group). The SmART intervention involves providing care in the following domains: sleep/sweet sense of home, assessment, release, and time. Patients with a PRE-DELIRIC score of >30% received SMART care, which includes multidisciplinary (physicians, pharmacists, respiratory therapists, and physiotherapists) care in addition to SmART care. For the control group, usual care was provided following the guidelines for the prevention and management of pain, agitation, delirium, immobility, and sleep disruption. The primary outcome was delirium incidence during ICU stay, which was assessed using the Intensive Care Delirium Screening Checklist. The secondary outcomes were the duration of ICU stay, rate of unplanned self-extubation, and status of ICU discharge. RESULTS: The intervention and control groups comprised 184 and 197 patients, respectively; their mean ages were 63.7 ± 18.4 years and 62.4 ± 19.5 years, respectively. The incidence of delirium was significantly lower (p = 0.001) in the intervention group (22.3%) than in the control group (47.7%). CONCLUSION: Our findings suggest that the PRE-DELIRIC-guided SMART/SmART care intervention is effective in preventing and managing delirium among surgical ICU patients.

Identification of autophagy-related signatures in nonalcoholic fatty liver disease and correlation with non-parenchymal cells of the liver.

Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease. The incidence and prevalence of NAFLD have increased greatly in recent years, and there is still a lack of effective drugs. Autophagy plays an important role in promoting liver metabolism and maintaining liver homeostasis, and defects in autophagy levels are considered to be related to the development of NAFLD. However, the molecular mechanisms of autophagy in NAFLD still remain unknown. In this study, we identified 6 autophagy-associated hub genes using gene expression profiles obtained from the GSE48452 and GSE89632 datasets. Biomarkers were screened according to gene significance (GS) and module membership (MM) using weighted gene co-expression network analysis (WGCNA), and the immune infiltration landscape of the liver in NAFLD patients was explored using the CIBERSORT algorithm. Subsequently, we analyzed the relationship between liver non-parenchymal cells and autophagy-related hub genes using scRNA-seq data (GSE129516). Finally, we separated the NAFLD patients into two groups based on 6 hub genes by consensus clustering and screened 10 potential autophagy-related small molecules based on the cMAP database.

Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.

Age and gender differences of normative values of spleen diffusion MRI parameters.

This study investigates age and gender differences of normative values of spleen diffusion MRI parameters.We recruited 124 volunteers with MRI conducted at 1.5T. Diffusion imaging had b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast, and DDVD (diffusion-derived vessel density) were computed. DDVD is the signal difference between the b=0 s/mm2 image and b=2, 4 s/mm2 image. Only images without apparent artifacts and with good curving fitting were included in the analysis. Finally, 34 females (age: 20-71 years) and 69 males (22-70 years) were measured with ADC; 20 females (20-71 years) and 48 males (22-67 years) were measured with IVIM; 32 females (20-71 years) and 65 males (22-70 years) were measured with DDVD parameter.An age-related decrease in ADC was noted for females, while such a trend was not noted for males. A very high level of heterogeneity was noted for the data for the males, with the highest ADC value being 1.710 × 10-3mm 2/s and the lowest ADC value being 0.705 × 10-3 mm2/s when b=0 and 600 s/mm 2 were used for ADC calculation. A male-female data comparison did not show a statistically significant difference between the ADC median value. However, ADCs > 1.3 × 10-3 mm2/s were only seen among males. A very high level of heterogeneity was also noted for males' Dslow, with the highest value being 1.468 × 10-3 mm2/s and the lowest value being 0.600 × 10-3 mm2/s. Both PF and Dfast demonstrated a trend of age-related increase for older subjects. PF values were higher among males than females. However, no difference was noted for Dfast between males and females. DDVD did not show an age-related trend both for females and males. No difference was noted in DDVD values between males and females.Interpreting normal spleen diffusion MRI parameters should consider age and gender factors. · An age-related decrease in spleen ADC and IVIM-Dslow was seen for healthy females.. · There is a high level of heterogeneity for spleen ADC and IVIM-Dslow data for healthy males.. · IVIM modelled perfusion fraction and Dfast demonstrate an artificial trend of age-related increase for older subjects.. · Vessel density measured on diffusion imaging does not show an age-related trend.. · Yu W, Ma FZ, Huang H et al. Age and gender differences of normative values of spleen diffusion MRI parameters. Fortschr Röntgenstr 2024; DOI 10.1055/a-2357-9741.