FASEB BioAdvances

Seismic shifts within academia over the last several decades have seen the growth of biomedical PhD recipients alongside the relative stagnation of tenure-track research-intensive faculty careers (RIFCs). This hypercompetitive academic job market has prompted interest in the paths of those who attain RIFCs. Understanding what drives recent biomedical PhDs to make their career decisions and persist toward them requires a clear picture of how career perceptions, motivations, and intentions develop and crystallize over time. Using annual in-depth interviews across nearly two decades, this report explores the evolution of career thinking and differentiation among 40 who attained a RIFC from diverse starting points to their attainment of a RIFC. Participants strategies for navigating early scientific experiences were patterned by their varied educational and socioeconomic backgrounds. Nearly half of participants did not start with or maintain stable interest in RIFCs, exhibiting changes in both PhD and postdoctoral phases. Participants highlighted six drivers toward RIFCs including desire for independence/autonomy and contributing to knowledge/health. Our results are instructive for trainees and mentors guiding career exploration and differentiation.

Understanding what is requisite for attaining a biomedical faculty career is crucial for guiding trainees preparing for these roles. For nearly two decades, we have collected accounts of biomedical training and career transitions from a large cohort through annual in-depth interviews and tracking of competencies and achievements. This paper elucidates the common and varied credentials of 40 who entered research-intensive faculty careers (RIFCs). Participants completed PhDs and postdocs in a range of research-intensive institutional settings. Developing research independence and a niche were essential to RIFC attainment, and mentors played a crucial role in this development. Counter to common assumptions, high-prestige publications and grants were not in and of themselves necessary for RIFC attainment. Our findings can aid RIFC aspirants and mentors who guide them.

Graduate-level genomics courses require students to integrate dense material across subfields, concepts and methods. In modular, multi-instructor courses, students may struggle because the coherence between lectures can be difficult to navigate, while the course structure may be visible to instructors. We evaluated a 2025 navigation redesign of BIO322, a graduate genomics course at the Norwegian University of Life Sciences, while preserving course content, multi-instructor teaching, modular organization and assessment framework. The redesign includes introducing a standardized self-learning guide, expanded syllabus, enriched online quiz feedback, and added support for a final group research proposal. Using anonymized course evaluation scores from 2021-2025 and aggregated learning management system access data from 2023-2025, we examined student experience and resource use. In 2025, five of six course evaluation items reached their highest observed BIO322 scores, while one, lecture-specific score remained within the previous range. The consolidated self-learning guide was accessed by nearly all students, whereas access to optional readings declined across the course sequence, despite comparatively stable page views per accessing student. These course-level findings are consistent with improved perceived navigability following the introduction of standardized learning support. However, some students continued to report difficulty identifying priorities and connections among course components, indicating that challenges in perceived course coherence remained for part of the cohort despite the redesign. Practitioner PointsO_LIMaking course structure explicit may improve students perceived navigability in multi-instructor graduate genomics courses. C_LIO_LIA centralized self-learning guide can broaden access to preparatory guidance without changing core course content or assessment. C_LIO_LIOptional learning supports may be used unevenly, so resource availability should not be assumed to translate into uniform resource access. C_LI

Research using model organisms to tackle questions in life sciences and biomedical sciences has been in the spotlight of scientific literature for the better part of the twentieth century. This attention has perceptibly faded over the last twenty years, at least. We set to document this process by examining the publication trends of 48 journals encompassing a broad range of topics and impact factors for eight classic model organisms. We found that the representation of model-organism research has been in continuous decline in the last three decades, with a significant acceleration since 2010. We investigated the origin of the change, from the size of research communities to the shifts in topics and in use of model organisms. While model organism communities appear stable, model organism papers are outpaced by the rest of scientific literature. Also, among papers using model organisms, we note a progressive shift toward applied research, with differences between different model organism species. The mouse, in particular, logically remains the preferred system to study diseases, while non-mouse model organisms continue to be used predominantly to dissect mechanisms of life. We reflect on the consequences of the fading representation that we measured for the future of life sciences. Fundamentally, model organisms afford a direct access to causality in life sciences and their fading from the picture may impact life sciences as a whole. More pragmatically, it will also affect funding, and thereby jeopardizes the maintenance of model organism resources such as repositories built over decades.

Course-based undergraduate research experiences (CUREs) can expand undergraduates access to research and motivate students to stay in science. Yet, little research has examined how CURE instruction shapes student motivation. We leveraged a motivation-related characterization of non-content talk of 48 CURE and non-CURE instructors to predict the motivation-related outcomes of 462 students. We fit a series of multi-level models (MLM) in which we regressed students post-course scientific self-efficacy, task values, scientific identity, and science-related intentions onto instructors self-efficacy and task values-related talk, controlling for students pre-course levels. We also fit an MLM to explore whether instructors relationship-building talk (immediacy talk) was associated with students rapport with their instructor. Instructors self-efficacy talk did not affect students self-efficacy, and instructors immediacy talk had a marginally positive but non-significant association with students rapport ratings. Instructors task values talk positively influenced students scientific identity and some but not all of their task values. Instructors task values talk also positively influenced students intentions to pursue a science career, but not graduate education or research careers. Collectively, these results suggest that instructors task values talk may underpin some of the motivational effects of CURE instruction, but that task values talk need not be limited to CUREs. HIGHLIGHTWe examine whether instructor talk predicts students motivational outcomes in CURE and non-CURE lab courses. Self-efficacy talk had no effect on student self-efficacy. Task values talk positively affected students science identity and career intentions, and some value beliefs. Immediacy talk was marginally related to student-instructor rapport.

Scientific supervision is central to the experience of early-career researchers (ECRs), yet its role in shaping wellbeing and retention remains underexamined from the ECR perspective. We analyzed 2,604 anonymous survey responses from predoctoral, postdoctoral and former researchers across 65 countries. Overall, 76% of respondents reported that their supervisors attitude had a moderate or severe impact on mental health. Although most entered academia for vocational reasons, negative experiences with supervisors were among the most frequently reported reasons for leaving among former researchers (48%), comparable to job insecurity and financial instability. Harm was most often associated with poor communication, disregard for wellbeing, micromanagement and competitiveness. In contrast, ECRs valued supportive rather than boss-like supervision, regular communication, realistic expectations and respect for personal time. These findings identify supervisory behavior as a major and modifiable determinant or ECRs wellbeing and retention, and highlight the need for stronger institutional accountability, mentor training and funding incentives that recognize mentorship as a core component of research culture.

PurposeTo determine whether circadian timing defines critical molecular windows in myopia development and to assess the transferability of circadian gene programs across ocular tissues, disease stages, and species. MethodsPublicly available retinal and choroidal RNA-seq datasets from chick models of form-deprivation myopia were analyzed using unsupervised transcriptomic profiling and multistage machine-learning classification. Circadian windows were defined based on Zeitgeber time, and samples were grouped accordingly for downstream analyses. Classification model robustness was evaluated through cross-tissue and cross-stage validation and further assessed using external validation in an independent dataset. Functional translation to humans was examined using ortholog-based Gene Ontology enrichment analysis to identify conserved biological processes and higher-order regulatory pathways. ResultsA circadian critical window at ZT8-ZT12 exhibited the strongest transcriptional divergence during both myopia onset and progression. Gene signatures derived from this window generalized across retina and choroid and remained predictive across disease stages, supporting coordinated molecular regulation between ocular tissues. External validation confirmed the reproducibility of these signatures despite differences in experimental design and gene coverage. Functional mapping revealed that conserved molecular components in chicks are reorganized into more complex neuroendocrine and regulatory networks in humans, indicating cross-species conservation with increased functional complexity. ConclusionsCircadian timing strongly shapes myopia-related gene expression and underlies coordinated retina-choroid signaling. These findings highlight circadian biology as a key factor of refractive development and suggest that time-dependent mechanisms may influence myopia susceptibility, progression, and response to treatment.

PurposeThis study examined the association between traditional physical practice participation and vision-related quality of life among junior secondary school students and tested the mediating roles of exercise self-efficacy and visual function anomalies within a serial mediation framework. MethodsA four-wave time-lagged survey was conducted among 1,579 students in Grades 7-9 from schools implementing traditional physical practice activities. Variables were assessed at two-week intervals. Mediation effects were tested using the bias-corrected percentile bootstrap method with 5,000 resamples. ResultsThe total effect of traditional physical practice participation on vision-related quality of life was significant ({beta} = 0.591, p < .001). After including the mediators, the direct effect remained significant ({beta} = 0.404, 95% CI [0.348, 0.457]), accounting for 68.36% of the total effect. The total indirect effect was significant ({beta} = 0.187, 95% CI [0.160, 0.218]), representing 31.64% of the total effect. The indirect effect via exercise self-efficacy was significant ({beta} = 0.088, 95% CI [0.068, 0.112], 14.89%), as was the indirect effect via visual function anomalies ({beta} = 0.065, 95% CI [0.048, 0.086], 11.00%). The serial mediation pathway through exercise self-efficacy and visual function anomalies was also significant ({beta} = 0.034, 95% CI [0.025, 0.045], 5.75%). All confidence intervals excluded zero, supporting partial mediation. ConclusionTraditional physical practice participation was associated with vision-related quality of life both directly and indirectly through exercise self-efficacy and visual function anomalies, including a significant serial mediation pathway. The findings highlight the combined psychological and functional mechanisms underlying adolescents vision-related quality of life.

The experimental use of antibodies that have not been validated for context-specific use frequently misdirects biomedical research. Experimental results that derive from the use of inadequately validated antibodies are estimated to waste over $1 billion annually in the United States alone and to consume millions of animal and human biological samples in experiments whose conclusions may be unreliable. Community validation frameworks, reporting standards, and independent characterisation initiatives have made important progress, and multi-stakeholder coordination efforts are emerging. However, the research community lacks a formally developed, consensus-based action plan that specifies what each stakeholder group should do, by when, and with what priority. We conducted a modified Delphi study with international experts representing academic researchers, scientific publishers, research funders, antibody manufacturers, and institutional research leaders to develop actionable recommendations for improving antibody validation, selection, and reporting practices. Thirty-two participants rated 33 proposed actions on effectiveness and feasibility using 9-point scales, with consensus assessed using the RAND/UCLA Appropriateness Method. Over two rounds, the panel achieved consensus on 15 items as both effective and feasible for implementation by 2030. These spanned institutional actions (training in antibody validation, integration into research integrity frameworks, support for local expertise networks), funder actions (dedicated validation budgets, grant application requirements, endorsement of community reporting standards), publisher actions (complete antibody reporting packages, clear validation standards), manufacturer actions (assignment of unique identifiers at source), and cross-stakeholder coordination (a shared roadmap for improvement). An additional 15 items were rated as effective but with uncertain feasibility, reflecting a consistent pattern in which the panel agreed on the value of proposed interventions but expressed reservations about realistic implementation timelines. One item was rejected by the panel with concerns around effectiveness and feasibility. Participants described four interconnected barriers to progress: diffuse ownership of the problem across stakeholders; market dynamics that inadequately reward antibody quality; difficulty justifying investment when returns are distributed across the research system; and coordination challenges among actors with different incentive structures. These barriers are addressable through coordinated action, and the findings complement existing technical and data-sharing initiatives by providing the structured, stakeholder-endorsed policy framework needed to translate awareness of the problem into concrete practice and policy changes.

In the United States, STEM graduate programs and workforce do not represent the demographics of the population. Obstacles, including a lack of transparency, community, and accessible information in navigating academia, disproportionately affect students from underserved backgrounds. Peer mentoring networks can address these disparities. Here, we describe Cientifico Latino, Inc.s Graduate Student Engagement and Community (CL-GSEC) program, a nationwide, group-based peer mentorship program that has served first-year graduate students across the U.S., especially those from underserved backgrounds. Surveys indicate CL-GSEC positively impacts the first-year graduate experience. We highlight key program features, challenges, and insights, such as financial strains faced by first-year graduate students. We offer suggestions for how faculty and departments can better support students during this critical early stage of graduate training. We hope that reporting on CL-GSECs program structure, evaluations, and findings will guide educational leaders in expanding programming for junior graduate students.

PurposeAlanine transaminases (ALT), encoded by the GPT gene, catalyzes the reversible conversion of pyruvate and glutamate to alanine and alpha-ketoglutarate, thereby correlating carbohydrate and amino acid metabolism. However, its role in the human neural retina remains unclear. This study aimed to explore the expression, localization, and metabolic function of ALT in the human neural retina and its potential involvement in retinal diseases. MethodsALT1 and ALT2 expression and localization were examined in the retinas of healthy and diabetic retinopathy (DR) donors via immunoblotting and immunofluorescence. ALT function was assessed in ex vivo human retinal explants using pharmacological inhibition with beta-chloro-L-alanine (BCLA), followed by the analyses of enzyme activity, tissue injury, and transcriptomic responses. Stable-isotope tracing with 13C-and 15N-labelled substrates combined with GC-MS was used to define ALT-dependent carbon and nitrogen fluxes in macular and peripheral retinas. Redox level (NADPH/NADP+) was also evaluated under tert-butyl hydroperoxide-induced oxidative stress. ResultsALT1 and ALT2 were both expressed in the human neural retina, with prominent localization in Muller glia and photoreceptor inner segments. ALT1 displayed a diffuse cytoplasmic distribution, whereas ALT2 demonstrated a punctate pattern consistent with mitochondrial localization. In DR retinas, ALT1 expression was spatially disorganized and heterogeneous, while ALT2 remained comparatively preserved. Inhibition of ALT with BCLA markedly reduced ALT activity without causing overt cytotoxicity or major transcriptional changes. Isotope tracing demonstrated that retinal ALT predominantly channels pyruvate-derived carbon into alanine, whereas alanine was minimally contributed to pyruvate production under basal conditions. ALT inhibition suppressed alanine synthesis and release, redirected nitrogen flux towards glutamate, glutamine, and aspartate, and uncovered distinct metabolic adaptations in macular but not peripheral retinas. Under oxidative stress, ALT inhibition induced the decrease of NADP+/NADPH ratio and LDH release, indicating improved redox balance and reduced tissue injury. ConclusionsALT is previously unrecognized as a regulator of carbon and nitrogen partitioner in the human neural retina, contributing to redox homeostasis under stress. The altered distribution of ALT1 in DR retina and the protective metabolic effects of ALT inhibition suggest ALT as a potential contributor to retinal metabolic vulnerability and a candidate therapeutic target in retinal diseases.

Chronic exposure to ultraviolet (UV) radiation, known as photoaging, accelerates skin aging by inducing molecular, histological, and functional changes. This study established a mouse model using SKH-1 hairless mice to investigate chronic UV-induced photoaging over eight weeks. SKH-1 hairless mice were exposed to a combination of UVA and UVB, and the progression of skin damage was monitored through physical, histological, and molecular parameters, with a focus on erythema, transepidermal water loss, and collagen and hyaluronan (HA) metabolism. Significant reductions in HA content and alterations in DNA repair markers, such as {gamma}H2AX, were observed, highlighting the impact of chronic UV exposure on skin structure and function. Reactive adipogenesis and increased epidermal thickness were noted, reflecting adaptive responses to UV-induced damage. By investigating these parameters over the evaluation period, we provide a comprehensive time-course analysis of the progressive impact of UV-induced photoaging, offering insights into the underlying mechanisms and potential therapeutic targets to prevent or delay photoaging.

Age-related macular degeneration (AMD) is a progressive complex eye disease and one of the leading causes of blindness. AMD progression is marked by molecular changes in the retinal pigmented epithelium (RPE) which include increased reactive oxygen species (ROS) accumulation, mitochondrial dysfunction - eventually leading to dysfunctional RPE. Mitophagy regulator, Pink1, is reduced in the RPE of AMD patients and Pink1 loss leads to a shift from mitochondrial respiration to glycolysis. Serine is a non-essential amino acid which is de novo synthesized from glycolytic intermediate 3-PG via the rate limiting enzyme PHGDH. Serine is tightly integrated into anabolic processes like glutathione (GSH) cycling, maintaining NADH/NADPH pools leading to changes in AMPK signaling. Here, we show that Pink1 loss leads to a reduction in PHGDH and serine levels in the RPE leading to impaired mitochondrial structure and function, increased ROS mediated damage, increased inflammation, and hampered retinal function. Serine supplementation rescued ROS accumulation, balanced GSH abundance, and increased retinal function. Overall, our study highlights the potential of dietary serine in ROS management in AMD.

BackgroundThyroid Eye Disease (TED) is an autoimmune orbital disorder driven by pathogenic T-cell subsets, including T-helper 1 (Th1) and follicular helper T (Tfh) cells, which sustain orbital inflammation and thyroid-stimulating immunoglobulin (TSI) production. Selenium supplementation has demonstrated clinical benefit in mild TED, yet its immunological mechanisms remain poorly defined. MethodsA murine TED model was established in female BALB/c mice via TSHR plasmid immunisation. Animals maintained on a low-selenium diet (0.07 ppm) received sodium selenite supplementation at 0.2 mg/kg/day. Orbital pathology was assessed by immunohistochemistry, H&E and Massons Trichrome staining. T-cell subset abundance was quantified by flow cytometry, and serum T4, TRAb, and IL-21 levels were measured by ELISA. In vitro dose-response experiments examined the effects of selenium on Tfh cell viability, IL-21 production, apoptosis, and ferroptosis. ResultsSelenium supplementation reduced CD3 T-cell orbital infiltration, collagen fibrosis, and serum T4 and TRAb levels in TSHR-immunised mice. Flow cytometry revealed significant reductions in Tfh and Th1 cell abundance, with Th17 cells unaffected. Serum IL-21 and B-cell abundance were also markedly reduced in vivo. In vitro, selenium exhibited a biphasic, dose-dependent effect on Tfh cells: low concentrations maintained viability and IL-21 production, while higher concentrations induced ferroptosis and apoptosis. ConclusionsSelenium modulates pathogenic T-cell responses in TED, most prominently suppressing the Tfh compartment and attenuating the Tfh-B cell-autoantibody axis via ferroptosis and apoptosis. These findings suggest a mechanistic framework for the clinical benefit of selenium in mild TED and highlight the importance of dose selection within its narrow therapeutic window.

Despite questionable accuracy, subjective methods to categorize skin color are heavily relied upon in research and medicine. Objective skin color determination is expensive requiring specialized instrumentation and interpretation. We compare three subjective approaches, i) Fitzpatrick Skin Type Scale (FST), ii) Pantone SkinTone Guide (PST) and, iii) Monk Skin Tone Scale (MST), with objectively measured skin color from a spectrophotometer in 87 volunteers to understand the limitations of each method. In agreement with others, we show that the popular FST questionnaire correlates poorly with the objective approach. However, PST color swatches provide good correlation with spectrophotometer measurements. PST consists of 110+ swatches that are inexpensive and easy to use, however, similar to other reports, the volunteers found the number of swatches overwhelming and/or excessive. We found that the recently introduced MST is not representative of reality with only 3 of the 10 color groups representing our volunteers and published populations of volunteers. In future, we propose using 9 color swatches to split the spectrum of human skin color into 10 groupings (Nottingham Skin Categories - NSC) that are representative of the global population. This new approach would be easy to implement and inexpensive in research, healthcare and cosmetics settings, and maps directly to objective, quantitative, measures taken with a spectrophotometer. For the testing and development of new optical devices, NSC would provide increased comparability between studies and ensure studies are representative of local/global populations. In the clinic NSC would be useful for dermatology, photodynamic therapy and dosage assessment for topical medicine, for example.

Peer reviewers provide a critical service to NIH by evaluating the scientific and technical merit of grant applications. While the tangible rewards for this service are limited, many reviewers feel review service makes them better applicants, improving their grant competitiveness. However, empirical evidence for this claim is limited. This study evaluates relationships between early career peer review service and subsequent application behavior and funding outcomes. Using NIH administrative data, applicants who served as Early Career Reviewers (ECRs) during the 2020 - 2021 council years were compared to a matched group of ECR-eligible applicants who had not served as reviewers (n=1,120 per group). To address non-random selection of ECRs, propensity score matching was used to balance groups on research field, demographics, productivity, career stage, and institutional resources. Outcomes, assessed over a three-year follow-up period, included submission volume, peer review scores, and funding outcomes for R01 and R01-equivalent applications. ECRs submitted more applications, were more likely to have their applications discussed, and were more likely to receive a high review score than matched controls. They were also more likely to receive R01 funding. While peer review scores do not solely determine award outcomes, these findings indicate that peer review service among ECRs is associated with improved grant application outcomes.

Generative artificial intelligence (genAI) tools are increasingly used by prospective higher education (HE) applicants seeking guidance on university and programme selection. Despite rapidly expanding use, little is known about how genAI systems may introduce or amplify bias in undergraduate admissions decision-making. Here, we systematically examined patterns of bias across three widely used genAI chatbots (ChatGPT, Copilot, Gemini) using neuroscience as a representative UK undergraduate programme. We constructed 216 prompts that varied by applicant characteristics (e.g. gender, study type, academic attainment). Each prompt was submitted to all three chatbots, generating 648 responses and 3240 individual programme recommendations. Output responses underwent text analysis (e.g. n-grams, gender-coded language), and national HE markers of esteem (REF21, TEF23, NSS24) were analysed. Applicant grades and priorities produced the strongest effects on genAI outputs. Higher-grade applicants and those prioritising research received significantly more masculine-coded language, independent of applicant gender. N-gram patterns also diverged: high-grade prompts more frequently elicited terms relating to excellence and research intensity, whereas lower-grade prompts produced greater emphasis on widening access. Recommendations were systematically skewed, with higher grades, private schooling, and research-focused priorities increasing the likelihood of recommending elite institutions and programmes with higher entry requirements. Critically, the gender-coded language of outputs predicted institutional characteristics: masculine-coded responses were associated with recommendations featuring higher entry thresholds and stronger research performance, while feminine-coded responses favoured institutions with higher student satisfaction. These findings reveal clear, systematic biases in how genAI guides prospective HE applicants. Such biases risk reinforcing existing educational and socioeconomic inequalities, underscoring the need for transparency, regulation, and oversight in the use of genAI within HE decision-making. HighlightsO_LIGenAI is widely used by HE applicants despite little study of its biases. C_LIO_LI216 prompts across 3 chatbots generated 3240 programme suggestions. C_LIO_LIGrades and priorities drove major shifts in language and recommendations. C_LIO_LIGender-coded wording mapped onto research strength and entry standards. C_LIO_LIGenAI biases may reinforce inequalities in HE admissions decision-making. C_LI

Lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+) students continue to face violence, exclusion, and barriers at school, including in STEM education. A key underexamined factor in diversity, equity, and inclusion (DEI) efforts is the content of the life science curriculum, which is uniquely positioned to reinforce or refute bioessentialist, binary, and heteronormative biases. Outdated science curricula not only conflict with current scientific evidence but can also perpetuate beliefs that contribute to sexism and LGBTQIA+ marginalization. To address this, we designed four gender and sexual diversity (GSD)-inclusive biology activities, aligned with NGSS standards, and informed by inclusive curriculum frameworks. Using a mixed-methods approach, we studied 127 high school students who participated in two or more inclusive biology activities. Surveys conducted before and after implementation showed significant reductions in essential, binary beliefs about sex and gender, and increases in affirming attitudes toward sex and gender diversity. Interviews conducted after implementation further revealed differences between LGBTQIA+ and straight students conceptualizations of biological sex. Our findings demonstrate that even brief curriculum interventions can shift student attitudes, although we hope future studies will explore the impact of sustained interventions. Updating life science instruction is essential for educational equity and scientific accuracy.

This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression profiles after intraperitoneal injections to Royal College of Surgeons (RCS) rats with Retinal Pigment Epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21 (p21), RCS rats received twice a week intraperitoneal injections of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with full field scotopic & photopic electroretinography (ERG) and optokinetic testing (OKT) 1 and 4 weeks after first injection (WAFI). The rats were euthanized after the ERG and OKT (1 or 4 WAFI) and the dissected retinas and RPE were collected for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results of our study showed that high dose (4mg/kg) HNG at 4 WAFI was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. Analysis of a and b waves from scotopic and photopic ERG showed no difference between either low or high dose of HNG and sham injection at 4 WAFI. However, at 4 WAFI, the visual acuity in rats treated with high dose HNG showed significant improvement as compared to the rats treated with low dose of HNG or saline. Most significantly, our findings support that HNG administered IP can modulate RPE/neuroretina cells and improve vision, thus may be a potential treatment for retinal degeneration diseases.

We investigated effects of three aerobic exercise interventions, varying in amount and intensity with durations of 8-9-months on small RNA (smRNA) expression and regulatory pathways in skeletal muscle and plasma from 120 participants. Using untargeted smRNA sequencing focused on miRNAs and piRNAs, adjusting for demographics and bodyweight, we identified 124 muscle smRNAs altered by exercise amount and 15 by intensity, and 47 plasma smRNAs altered by intensity and one by amount. These smRNAs were enriched in metabolic, transcriptional, translational, and cell cycle pathways. Exercise-induced changes in several smRNAs-six from muscle and five from plasma-and exercise-induced reduction in body weight, aligned with improvement in insulin sensitivity (p<0.05). These findings demonstrate tissue-specific regulation of smRNAs by exercise and identify potential candidates for exercise mimetics to modulate muscle insulin sensitivity.