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PubMed2026

The interplay between circadian misalignment or sleep disturbances and cognition and brain function in individuals with different degrees of insulin resistance - a systematic review.

Disruption of sleep increases the risk of type 2 diabetes and worsens cognitive outcomes, yet few studies have evaluated the interaction between insulin resistance and sleep parameters in relation to cognitive outcomes or the risk of dementia. This systematic review examines how circadian misalignment and sleep disturbances affect cognition and neuroimaging findings in individuals with varying degrees of insulin resistance. Across 27 studies, disrupted circadian rhythmicity and sleep disturbances were negatively associated with brain health, possibly through its effects on insulin sensitivity, whereas the impact of sleep duration and quality were inconclusive. Methodological heterogeneity, reliance on cross-sectional designs, and limited control for confounders restricted definitive conclusions and highlighted the need for longitudinal and interventional studies with objective measurements. Nonetheless, the findings support circadian rhythmicity as a potentially modifiable risk factor for preserving cognition in insulin-resistant populations. Future research should prioritise prospective and interventional studies and focus on biological markers rather than self-reported outcomes.

Humans↗

PubMed2026

Prevalence and cardiometabolic impact of mild autonomous cortisol secretion in primary aldosteronism: a systematic review and meta-analysis.

Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed "Connshing syndrome." The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized. To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity. PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE. Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1-28.4; I2 = 24.2%; prediction interval: 21.6-31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07-2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00-1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events. Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.

Humans↗

PubMed2026

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing↗

PubMed2026

Beyond Photometric Consistency: Addressing Loss Insensitivity to Depth Noise in Endoscopic Estimation via Error Calibration.

Self-supervised monocular depth estimation in endoscopy is fundamentally constrained by the ill-posed nature of photometric supervision. In this work, we identify a critical yet overlooked cause of this ambiguity: the inherent insensitivity of photometric loss to depth noise. To overcome this intrinsic limitation, we propose Depth Error Calibration Learning (DECL), a two-stage framework that suppresses prediction variance and mitigates residual errors in self-supervised depth estimation. In Stage I (Variance Reduction), a cyclic depth generation strategy produces multiple depth hypotheses for the input image. The per-pixel empirical variance is quantified and integrated into a dedicated variance loss term, which penalizes inconsistent predictions and encourages the network to generate more stable and reliable depth estimates. In Stage II (Bias Calibration), an image-conditioned diffusion model refines the Stage-I depth prior and mitigates structured residuals through iterative denoising, thereby improving geometric accuracy and global consistency. Extensive experiments on three public endoscopic datasets demonstrate that DECL achieves consistent improvements over representative self-supervised monocular depth estimation methods under the evaluated protocols. Moreover, ablation studies on two representative backbones indicate that DECL is not restricted to a single network implementation, while broader validation on additional backbone families remains necessary. The source code is publicly available at https://github.com/DavidLuBit/EndoDenoising.

Journal Article↗

PubMed2026

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.

The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2 years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2 years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4 years. Continued monthly ZOL beyond 2 years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (≥0.30 μg/L) and TRAcP (≥4 U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2 years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.

Humans↗

PubMed2026

Glycemic and safety outcomes of the insulin-only bionic pancreas in older adults and individuals with impaired awareness of Hypoglycemia: a post hoc analysis of a randomized pivotal trial.

AIMS: Evaluate the efficacy and safety of iLet Bionic Pancreas (BP) in older adults and individuals with impaired awareness of hypoglycemia (IAH). METHODS: This post hoc analysis used individual participant-level data from the Insulin-Only Bionic Pancreas Pivotal Trial (n = 440; NCT04200313). Eligible participants (n = 96) with type 1 diabetes, aged ≥ 60 years and/or had IAH (Clarke score ≥ 4), were randomized to BP with aspart/lispro (BP-Asp/Lis; n = 45), BP with fast-acting aspart configuration (BP-Fiasp; n = 31), or standard care (SC; n = 20) for 13 weeks. RESULTS: Compared with SC, time-in-range (70-180 mg/dL) significantly increased by 7.49 % (95 % CI: 2.61 to 12.38; ∼1.8 h/day) with BP-Asp/Lis and by 8.28 % (95 % CI: 3.15 to 13.41; ∼2.0 h/day) with BP-Fiasp, driven by reduced hyperglycemia. No significant differences were observed in hypoglycemia exposure. Severe hypoglycemia occurred in four participants (four events) on BP-Asp/Lis and one participant (two events) on SC. One diabetic ketoacidosis event occurred on BP-Fiasp due to an infusion set failure. CONCLUSIONS: In high-risk, clinically vulnerable populations, the BP system significantly improved glycemic control while maintaining safety parity with respect to hypoglycemia risk, providing a resilient therapeutic alternative for vulnerable cohorts.

Humans↗

PubMed2026

Effects of Cognitive Behavioral Couple Therapy With Integrated Mindfulness on Mindful Attention, Depressive Symptoms, and Dyadic Adjustment in Low-Income Couples: A Pilot Randomized Clinical Trial.

Psychosocial distress can exacerbate marital conflict, maladjustment, and mental health vulnerability. This pilot randomized clinical trial examined cognitive-behavioral couple therapy (CBCT) integrated with mindfulness in low-income Brazilian couples (per-capita household income up to one minimum wage). Thirty-four participants (17 heterosexual couples) were randomized (independent computer-generated sequence) to an experimental (n = 16) or waitlist control group (n = 18). We assessed dyadic adjustment, mindful attention, marital social skills, and depressive symptoms (R-DAS, MAAS, IHSC, BDI-II) at baseline, post-treatment, and 3-month follow-up. The intervention was eight 80-min conjoint sessions plus daily home exercises. Time × group effects favored the experimental group for dyadic adjustment, mindful attention, and depressive symptoms (all p < 0.001, = 0.20-0.37), but not marital social skills (p = 0.14). Because two outcomes differed at baseline, effects were confirmed with baseline- and dependence-adjusted sensitivity analyses. These findings provide preliminary evidence that CBCT with mindfulness may benefit disadvantaged couples.

Adult↗

PubMed2026

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans↗

PubMed2026

Transverse testicular ectopia with fused vas deferens: A systematic review.

BACKGROUND: Transverse testicular ectopia (TTE) with fused vas deferens is an extremely rare anomaly, often diagnosed intraoperatively. Current TTE classifications do not address internal ductal variations, limiting surgical guidance. OBJECTIVE: To systematically review cases of TTE with fused vas deferens, summarize presentation, operative strategies, outcomes and identify patterns that highlight the need for classification refinement. METHODS: A PRISMA 2020-compliant systematic review (PROSPERO; CRD420251247785) was performed across PubMed, ScienceDirect and citation of included articles through December 2025. Case reports and series confirming fused vas deferens were included. Data extracted comprised demographics, presentation, imaging, surgical approach, and outcomes. Quality assessment used JBI checklists. RESULTS: 12 studies (16 patients) were included. Most presented with unilateral inguinal hernia (62%) and contralateral undescended testis (68%); 81% were diagnosed intraoperatively. Anatomical patterns included common/proximal fused vas (87%), Y-shaped fusion (6%), and long-loop vas (6%). Trans-septal orchidopexy was the preferred approach, with preservation of vas integrity. Postoperative outcomes were favorable; long-term follow-up was limited. CONCLUSION: TTE with fused vas deferens represents a distinct variant requiring careful intraoperative recognition. We propose a Type IV TTE category for internal ductal fusion to guide surgical planning and classification refinement. Further accumulation of case-based evidence may help clarify its anatomical patterns and operative implications.

Humans↗

PubMed2026

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight‑threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up‑to‑date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans↗

PubMed2026

Parallel evolutionary trajectories rewire enteropathogenic Escherichia coli adhesion to restore host attachment.

Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.

Bacterial Adhesion↗

PubMed2026

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female↗

PubMed2026

Association between SGLT2 inhibitors and reporting of phimosis/paraphimosis: a comparative pharmacovigilance analysis of the WHO database.

PURPOSE: Recent data have discussed occurrence of phimosis with Sodium-glucose co-transporter-2 (SGLT2) inhibitors. However, the potential risk among the different SGLT2 inhibitors is unknown. METHODS: Using Individual Case Safety Reports (ICSRs) registered in the WHO pharmacovigilance database (01/01/2000-30/06/2025), comparisons between the different SGLT2 inhibitors and versus other drugs used in diabetes (DUD) were performed. Results are shown as Reporting Odds Ratios (ROR). RESULTS: Among 11 342 810 ICSRs, 227 were phimosis/paraphimosis with SGLT2 inhibitors, mainly between 45 and 64 years. The higher ROR value was found with empagliflozin followed by dapagliflozin and canagliflozin. ROR for SGLT2 inhibitors was higher that of all other DUD [34.72 (25.86-46.62)]. The reporting risk of phimosis/paraphimosis with SGLT2 inhibitors was also higher than that of each pharmacological class of DUD. CONCLUSION: The results suggest an association between SGLT2 inhibitors use and phimosis ICSRs. Empagliflozin had the higher reporting risk.

Humans↗

PubMed2026

Characterization and functional insights of histone deacetylases in bivalves: implications for temperature and immune response in Chlamys nobilis.

Histone deacetylases serve as pivotal epigenetic regulators that modulate chromatin remodeling and gene transcription, playing critical roles in immune defense and environmental stress responses in aquatic organisms. However, the evolutionary characteristics and functional roles of the HDAC family in bivalves remain poorly understood. In this study, genome-wide identification of the HDAC family across 30 bivalve species yielded 558 HDAC genes. Phylogenetic reconstruction categorized these genes into four conserved groups and revealed a unique, bivalve-specific SIRT8 clade. Using the noble scallop Chlamys nobilis as a representative model, expression profiling revealed distinct expression patterns among CnHDAC members. Class I and most Class III members were predominantly expressed in the gonads, while Class II members were enriched in immune-related tissues, implying their potential involvement in bivalve immunity. Upon temperature stress, CnHDAC1/2, CnHDAC11-1, CnHDAC11-2, CnSIRT2-1, CnSIRT4, CnSIRT6, and CnSIRT8-3 were significantly induced, highlighting their critical roles in temperature adaptation. Upon Vibrio exposure, CnHDAC1/2, CnHDAC8, CnSIRT4, and CnSIRT6 were upregulated, while CnHDAC4/5/7/9, CnHDAC6/10, CnSIRT2-2, CnSIRT5, CnSIRT7, and CnSIRT8-3 were downregulated, suggesting a coordinated epigenetic regulatory mechanism underlying host immune defense. In conclusion, this study systematically elucidates the evolutionary landscape of the HDAC family and underscores its potential involvement in environmental resilience and host immunity, providing a theoretical basis for the breeding of disease-resistant and stress-tolerant aquaculture bivalves.

Animals↗

PubMed2026

Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies.

BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.

Humans↗

PubMed2026

Effect of Motor-Control Exercises on Scapulohumeral and Scapulothoracic Muscle Activations in Athletes With Secondary Subacromial Impingement Syndrome.

CONTEXT: Unbalanced or uncoordinated activity across either the scapulohumeral or the scapulothoracic muscle may impair scapulohumeral rhythm during arm elevation. OBJECTIVE: To compare the effects of progressive resistance exercises (PREs), integrated with and without facilitatory motor-control exercises (MCEs), on scapulohumeral and scapulothoracic myoelectric activities in overhead athletes diagnosed with secondary subacromial impingement syndrome (SAIS). DESIGN: Randomized controlled clinical trial. SETTING: Neuromuscular Rehabilitation Research Center. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes diagnosed with secondary SAIS were assigned randomly to 3 parallel groups: 2 intervention groups and 1 control group. INTERVENTIONS: All groups received contemporary physical therapy modalities every other day for 8 weeks. Intervention groups I and II also completed scapulohumeral and scapulothoracic PREs, integrated, respectively, with and without facilitatory MCEs targeting infraspinatus and lower trapezius muscles. MAIN OUTCOME MEASURES: Scapulohumeral and scapulothoracic myoelectric activities were recorded during scapular arm abduction between 80° and 110° before and after the prescribed treatment protocols. RESULTS: Scapulohumeral and scapulothoracic PREs reduced the corresponding myoelectric activities during scapular arm abduction within the groups (P ≤ .02, partial η2 ≥ 0.127). Facilitatory biofeedback-guided exercises integrated into PREs preserved scapulohumeral and scapulothoracic myoelectric activities (P ≤ .03), excluding teres minor myoelectric activity (P > .99). CONCLUSIONS: Scapulohumeral and scapulothoracic PREs reduced the corresponding muscle activations during scapular arm abduction in overhead athletes with secondary SAIS. Facilitatory MCEs targeting infraspinatus and lower trapezius muscles, integrated into PREs, preserved scapulohumeral and scapulothoracic muscle activations.

Humans↗

PubMed2026

Translational reprogramming of TGF-β signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGFβR1. This amplifies downstream TGF-β/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGFβR1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male↗

PubMed2026

A combined stimulus of acute fasting and exercise modulates hippocampal mitochondrial quality control in healthy mice.

BACKGROUND AND AIMS: Exercise and fasting are recognized for their ability to improve brain health and mitigate neurodegeneration. However, little is known about how these interventions acutely impact mitochondrial quality control mechanisms including mitophagy. METHODS: We examined the effects of a single bout of fasting and exercise (FEx) on hippocampal mitochondrial function and proteomic remodeling in male and female mice. To assess in vivo autophagy dynamics, we combined proteomics with chloroquine (CQ) inhibition of autophagic flux. Mice were assigned to sedentary (Sed), fasting (F), exercise (Ex), or combined FEx groups and received unilateral intrahippocampal injections of CQ or PBS following treatments. Four hours later, hippocampi were collected for analysis. RESULTS: LC3-II levels significantly increased in the FEx group only following CQ treatment, indicating enhanced autophagic flux. Proteomic profiling showed sedentary males failed to mount a robust response to FEx however females exhibited upregulation of proteins involved in the TCA cycle, glutathione metabolism, and oxidative phosphorylation, suggesting greater mitochondrial adaptability. Functional assays supported these findings, females showed increased complex IV activity post-FEx. The mitochondrial DNA / nuclear DNA ratio increased after FEx regardless of sex, and upstream regulator analysis predicted activation of mitochondrial biogenesis. CONCLUSIONS: Together, these data reveal sex-specific mitochondrial remodeling in response to acute fasting and exercise. Defining these normative responses is critical for understanding how mitochondrial adaptability shapes resilience or vulnerability to neurological challenges.

Animals↗