Search Results (90,932)

This study aims to quantitatively evaluate bone mineral density (BMD) in women with functional hypothalamic amenorrhea (FHA), determine differences across skeletal sites, and summarise current evidence on the diagnosis and management of impaired bone health in this population. Methods: A systematic search of comparative studies evaluating BMD by dual-energy X-ray absorptiometry (DXA) in women with FHA or anorexia nervosa (AN) and healthy eumenorrhoeic controls was performed. Eleven studies met the eligibility criteria, five of which were included in the meta-analysis. The quantitative synthesis comprised 14 group comparisons, with lumbar spine and hip BMD analysed separately. Effect sizes were pooled using Hedges’ g with 95% confidence intervals (CI) under a random-effects model. Sensitivity analyses using REML estimation with Hartung–Knapp adjustment and leave-one-out analyses were performed to assess the robustness of the pooled estimates. Results: The narrative synthesis of 11 studies generally showed lower BMD in women with FHA or AN compared with healthy controls. In the meta-analysis, among women with FHA, hip BMD was significantly lower than in healthy controls (Hedges’ g = −0.60; 95% CI −1.13 to −0.06; p = 0.030; I² = 63%), while a moderate reduction was observed at the lumbar spine (Hedges’ g = −0.68; 95% CI −1.48 to 0.13; p = 0.101; I² = 83%). In women with AN, substantial reductions were observed at both the lumbar spine (Hedges’ g = −1.66; 95% CI −2.28 to −1.04; p < 0.001; I² = 71%) and the hip (Hedges’ g = −1.37; 95% CI −2.33 to −0.42; p = 0.005; I² = 89%). The lumbar spine reduction in AN remained statistically significant across sensitivity and leave-one-out analyses and was the most robust finding, whereas the statistical significance of hip BMD estimates in both FHA and AN and of lumbar spine BMD in FHA was sensitive to the analytical approach or exclusion of individual studies. The systematic review demonstrated that DXA with interpretation based on Z-scores remains the preferred method for skeletal assessment in premenopausal women with FHA. Bone health assessment is recommended after ≥6 months of amenorrhea or earlier in women with severe energy deficiency or a history of fractures. Restoration of energy availability, weight gain, and recovery of menstrual function remain the cornerstone of treatment. When amenorrhea persists and low BMD is confirmed, physiological transdermal 17β-estradiol combined with cyclic progesterone is the preferred hormonal therapy, whereas combined oral contraceptives, bisphosphonates, and denosumab are not recommended for routine management. Conclusions: Functional hypothalamic amenorrhea is associated with reduced BMD, with substantially greater skeletal deficits observed in the AN subgroup. These findings support early assessment of bone health and timely correction of low energy availability in women with FHA. The considerable between-study heterogeneity and sensitivity of some pooled estimates highlight the need for larger prospective studies using standardized diagnostic criteria and uniform skeletal outcome measures. Full article

The narrow edible window period of kiwifruit poses significant challenges for the high-value fresh fruit industry. This study comparatively evaluated the effects of 1-methylcyclopropene (1-MCP), melatonin (MT), and acetylsalicylic acid (ASA) on “Guichang” kiwifruit by analyzing their physiology, energy metabolism, and transcriptomic profiles. The results indicated that 0.5 μL/L 1-MCP, 1.0 mmol/L MT, and 2.0 mmol/L ASA were the optimal concentrations, all of which significantly inhibited ethylene production and respiration intensity. These treatments effectively maintained fruit firmness, vitamin C content, and high energy status by preserving ATP levels and the activities of H⁺-ATPase and Ca²⁺-ATPase while suppressing the activities of CCO, SDH, 6-PGDH, and G-6-PDH. Transcriptomic analysis and RT-qPCR verification revealed that these preservatives re-programmed key respiratory pathways, including glycolysis, the TCA cycle, the pentose phosphate pathway, and oxidative phosphorylation. MT exhibited transcriptomic responses highly similar to 1-MCP (sharing 13 KEGG pathways) and resulted in the lowest decay rate among treatments, whereas 1-MCP showed the strongest maintenance of core firmness. Our findings suggested that MT exhibited promising performance across multiple quality- and energy-related parameters and may serve as a potential alternative treatment for maintaining kiwifruit quality during the edible window period. Future studies should functionally validate the identified candidate genes and evaluate the effects of MT on sensory and flavor attributes under commercial storage and distribution conditions. Full article

Objective. This meta-analysis aimed to assess the effectiveness of stem cell–seeded conduits compared with autografts and empty conduits in preclinical models of peripheral nerve repair. Methods. A systematic review and meta-analysis was conducted of in vivo preclinical studies published between 2013 and 2024. Endpoints included muscle mass ratio, sciatic function index (SFI), nerve conduction velocity (NCV), compound muscle action potential (CMAP) amplitude, and nerve conduction latency. Studies were further classified by stem cell type, graft material, species, and defect length. Results. Across 30 studies, both stem cell–seeded conduits and autografts outperformed controls across functional and electrophysiological measures. Early improvements (0–3 months) in muscle mass ratio were observed with both stem cell grafts (p = 0.014) and autografts (p = 0.027). SFI improved significantly in both groups at early time points, with stem cell grafts maintaining significance beyond 3 months (p = 0.04). CMAP amplitude showed early gains for both stem cell grafts (p < 0.001) and autografts (p < 0.001), with autografts performing slightly better initially (p = 0.033). NCV improved in both groups early, with stem cell grafts maintaining significance beyond 3 months (p = 0.007). Autografts showed early improvements in latency (p = 0.048), whereas stem cell grafts trended toward benefit without reaching significance. Conclusions. These findings suggest that stem cell–seeded grafts may provide functional benefits similar to autografts in peripheral nerve repair compared with empty conduits. Clinically, this method could be valuable when autografts are unavailable or when harvesting is contraindicated. Full article

This paper addresses the set stabilization problem of probabilistic Boolean control networks (PBCNs) via a self-triggered control strategy. Firstly, the algebraic representation of the considered PBCNs is established by employing the semi-tensor product (STP) of matrices. Secondly, Lyapunov functions (LFs) are introduced for the set stabilization analysis, and a constructive algorithm for deriving such LFs is provided. On this basis, a necessary and sufficient condition in terms of the LF is obtained to determine whether a PBCN can achieve stabilization to a prescribed target set with probability one. Furthermore, a design method for self-triggered controls (STCs) is developed. Finally, the Escherichia coli lactose operon is presented as an example to validate the theoretical results of this paper. Full article

Background: Anti-Müllerian hormone (AMH) is a key biomarker of ovarian reserve, reflecting the quantity of the remaining follicular pool. While chronological age is the primary determinant of AMH concentrations, emerging evidence suggests that vitamin D, vitamin B12, folate, and iron metabolism parameters may also influence ovarian function through mechanisms involving steroidogenesis, DNA synthesis, and oxidative stress regulation. However, clinical findings regarding these associations remain inconsistent. Objective: The aim of this study was to evaluate the relationships between serum AMH concentrations and biomarkers of vitamin D status, vitamin B12, folate, ferritin, and lipid profile in women of reproductive age, and to compare the strength of these associations with that of chronological age. Methods: This retrospective, observational, cross-sectional study included 264 women who underwent AMH testing at Atlas University Hospital. Demographic and laboratory data including AMH, age, vitamin D, vitamin B12, folic acid, ferritin, and lipid parameters were extracted from electronic medical records. Bivariate correlations were assessed using Pearson’s and Spearman’s coefficients on both untransformed and Box–Cox power-transformed data, and were repeated as first-order partial correlations conditioning on chronological age. Statistical significance was set at p < 0.05. Results: The mean age was 34.61 ± 5.75 years, and median AMH was 0.96 ng/mL (Q1–Q3: 0.34–2.34). Age showed a moderate-to-strong, significant inverse correlation with AMH (Pearson’s r = −0.508, Spearman’s rho = −0.547; p < 0.001), and the linear component of this association strengthened after Box–Cox transformation (Pearson’s r = −0.553; p < 0.001). In contrast, vitamin D, vitamin B12, folic acid, ferritin, and lipid parameters (triglycerides, HDL, LDL, total cholesterol) showed no statistically significant and no clinically meaningful correlation with AMH, with all coefficients remaining below 0.20 regardless of transformation (all p > 0.05). After adjustment for age, every coefficient attenuated further towards the null (all |r_partial| < 0.10; all p ≥ 0.127), the largest being that of 25-hydroxyvitamin D (r_partial = 0.094, 95% CI −0.027 to 0.213). A sensitivity power analysis confirmed 80% power to detect an age-adjusted partial correlation of |r| = 0.172 and 91% power at |r| = 0.200. Conclusions: Age remains the principal determinant of ovarian reserve, while vitamin D, vitamin B12, folic acid, ferritin, and lipid parameters show no statistically significant or clinically meaningful association with AMH. These findings suggest that any biological influence of these micronutrients on ovarian reserve, if present, is markedly overshadowed by age-dependent follicular decline. Prospective studies incorporating longitudinal AMH measurements and standardized nutritional assessment are needed to further clarify these relationships. Full article

Chronic low back pain (cLBP) compromises daily function, but associated balance deficits remain difficult to quantify using traditional scales. We recruited 50 participants with CLBP (age: 65.68 ± 11.84) and 50 age-matched controls (age: 65.26 ± 10.73) wearing multiple inertial measurement units (IMUs) to evaluate kinematics: average absolute angular velocity ($J\omega$) and linear acceleration ($J\alpha$) across static (single-leg stance), perturbed (balance board), locomotor (walking, tandem gait), and transitional (five times sit-to-stand) tasks. Group differences were assessed using multivariate analysis of variance and Bonferroni-adjusted univariate tests. During the balance board test, $J\omega$ was significantly higher at the chest ($p$ = 0.027) and hip ($p$ = 0.003) in the CLBP group. Conversely, during the sit-to-stand tests, the CLBP group showed significantly lower $J\alpha$ and $J\omega$ (p < 0.0001) at the hip. The CLBP group exhibited globally lower $J\omega$ ($p$ < 0.01) during normal walking, while the ${Amp}_{PR}$ ($p$ = 0.001) was exclusively reduced during tandem gait. These results suggest that multi-sensor IMU-based assessments provide a sensitive tool for detecting subtle, task-specific balance deficits in CLBP, indicating that rehabilitation should target rotational mobility and reactive control rather than core stiffening alone. Larger-scale and longitudinal research is still required to determine their clinical utility. Full article

This study examines knowledge, broad reported use, and the perceived effects of artificial intelligence (AI) and related digital systems through an exploratory secondary analysis of 323 company-survey responses. The numerical source is a previously unused company-side aggregate results report from the research programme associated with an earlier published tourist study, with waves labelled 2024 (n = 162) and 2026 (n = 161). Biosphere Portugal’s practice-informed project documentation provides complementary sustainability context. The contribution is an analysis and interpretation of existing aggregate evidence, not a new primary survey or longitudinal panel. Company-level microdata were not available for this analysis. Acceptance and organisational-readiness perspectives guide four research questions. The broad survey indicator records 190 affirmative responses (58.8%) but does not establish verified AI adoption. Conflicting pooled and wave-specific technology counts are preserved as unresolved source discrepancies rather than treated as corrected ground truth. Descriptive group contrasts are reported without inferential significance claims because item-specific valid-case denominators, missing-response coding and cross-wave independence cannot be verified from the archived aggregate materials. The analysis is therefore confined to broad reported-use status and function labels, not AI-specific user effects. Published tourist findings are compared thematically rather than pooled. The implications concern the measurement discipline, context-dependent capability, governance, and sustainability assessment; perceived efficiency benefits are not treated as measured net sustainability gains. Full article

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, including Indonesia, with most patients presenting at advanced clinical stages. Reliable, minimally invasive circulating biomarkers for monitoring treatment response are lacking. This study aimed to identify candidate blood-based transcriptomic biomarkers for advanced-stage NPC through integrative bioinformatic analysis and to evaluate the expression dynamics of a prioritised candidate gene, TSPAN32, in peripheral blood of patients undergoing chemoradiation. Differentially expressed genes (DEGs) were identified from the GEO microarray dataset GSE53819 (18 advanced-stage NPC tissues vs. 18 non-cancerous nasopharyngeal tissues) using GEO2R. Candidate DEGs were prioritised through protein–protein interaction (PPI) network analysis (STRING confidence ≥ 0.9), functional enrichment analysis (GO via Enrichr; KEGG pathway via ShinyGO v0.82), and survival analysis (Kaplan–Meier). Overlapping DEGs were identified against a previously published blood-based NPC transcriptomic dataset with 11 early-stage NPC patients, 11 advanced-stage NPC patients, and 11 healthy donors. Analysis of GSE53819 identified 943 upregulated and 1503 downregulated DEGs (|log₂FC| ≥ 1; Padj < 0.05). Functional enrichment of upregulated DEGs was dominated by inflammatory response and cytokine activity pathways, while downregulated DEGs were enriched in B-cell activation and immunoglobulin receptor binding. Protein–protein interaction network construction (STRING confidence ≥ 0.9) and hub gene identification using the MCC algorithm identified six candidate genes among the downregulated DEGs: ADRA2A, SELP, TSPAN32, PEAR1, P2RX1, and DGKG. Kaplan-Meier survival analysis demonstrated that lower expression of SELP (HR = 0.57; p = 0.00053), TSPAN32 (HR = 0.56; p = 0.00025), and P2RX1 (HR = 0.48; p = 1.2 × 10⁻⁵) was significantly associated with shorter overall survival in head and neck carcinoma, supporting TSPAN32 as the primary candidate for clinical validation. RT-qPCR examination demonstrated that TSPAN32 transcript abundance in peripheral blood was significantly upregulated following chemoradiation in nine of ten patients (mean Log₂FC = 2.08 ± SD 1.09, 95% CI 1.29–2.86; one-sample t-test t(9) = 6.01, p = 0.0002; Wilcoxon signed-rank test p = 0.002). Primer specificity for TSPAN32 and ACTB was confirmed by melt-curve analysis and in silico validation (Primer-BLAST, OligoAnalyzer, UCSC In-Silico PCR). RBC transfusion status did not significantly modulate the magnitude of TSPAN32 expression change (independent-samples t-test, t = 1.86, p = 0.101). This integrative study identifies TSPAN32 as a candidate circulating biomarker responsive to chemoradiation in advanced-stage NPC. These exploratory findings require confirmation in larger, prospective, longitudinal cohorts before clinical translation. Full article

Exclusive breastfeeding (EBF) for the first six months of life is recommended by the World Health Organization, but its association with executive function (EF) in early childhood remains uncertain. This study examined whether EBF during the first six months of life and breastfeeding duration were associated with EF in early childhood and explored relevant child and family characteristics. We conducted an analytical cross-sectional study among 316 children aged 24–35 months attending the Well-Child Clinic, Health Promotion Hospital, Regional Health Promotion Center 7 Khon Kaen, Thailand. EF was assessed using the Minnesota Executive Function Scale (MEFS). The continuous MEFS Standard Score was used as the primary outcome and analyzed using multivariable linear regression. Post hoc exploratory analysis using the 55th percentile threshold and sensitivity analysis using the normative 50th percentile were also conducted. In the primary analysis, EBF was not statistically significantly associated with the MEFS Standard Score (adjusted β = −0.96, 95% CI: −2.13 to 0.21; p = 0.108). Child age was inversely associated with the MEFS Standard Score (adjusted β per 1-month increase = −0.29, 95% CI: −0.46 to −0.11; p = 0.002), whereas maternal education at the bachelor’s degree level or above was positively associated with EF (adjusted β = 2.44, 95% CI: 1.18 to 3.71; p < 0.001). Family functioning was not statistically significantly associated with EF in the primary continuous-score analysis (overall p = 0.319). The absence of a statistically significant association between EBF and EF was consistent across the alternative categorical outcome definitions. In contrast, the association with family functioning was only observed in the post hoc 55th percentile analysis and was not robust across outcome definitions. Breastfeeding duration as a continuous measure was not statistically significantly correlated with the MEFS Standard Score. In the post hoc exploratory analysis using the 55th percentile threshold, breastfeeding for >0 to 6 months was associated with higher odds of higher EF performance compared with no breastfeeding, whereas breastfeeding for >6 months was not. This pattern did not indicate a consistent dose–response association. These findings provide no statistically significant evidence of an association between EBF and EF in this sample, while maternal education was associated with EF performance. The findings regarding family functioning should be regarded as exploratory and hypothesis-generating. Full article

The semi-dwarfing gene Rht-D1b (formerly known as Rht2) was introduced into modern wheat breeding during the Green Revolution to reduce plant height, improve lodging resistance, and increase harvest index. In this study, two wheat (Triticum aestivum L.) lines carrying Rht-D1b (dwarf) and Rht-D1a (tall), respectively, were used to assess the role of Rht-D1b in salt tolerance through physiological and transcriptomic analyses under salt stress. Compared with Rht-D1a, Rht-D1b showed less growth inhibition, with smaller decreases in plant height, root length, and shoot biomass, as well as higher SPAD values. Rht-D1b also accumulated less Na⁺, had lower ROS and MDA levels, and maintained stronger POD and CAT antioxidant enzyme activities. Transcriptome analysis showed that 20 POD genes were consistently upregulated in Rht-D1b to Rht-D1a at 0, 6, and 24 h, while ion-transport- and ROS-related genes showed time-specific activation patterns linked to Na⁺ homeostasis, calcium signaling, and antioxidant defense. Together, these findings suggest that Rht-D1b may contribute to wheat seedling salt tolerance by improving ion homeostasis and redox balance. The salt-responsive genes identified in this study may also serve as candidates for future functional studies and wheat breeding. Full article

Background: Peripheral nerve injury causes substantial functional impairment and represents a major health concern worldwide. Peripheral nerve injuries are sequelae of iatrogenic injuries, occupational trauma, and motor vehicle crashes. The available therapeutic approaches, including pharmacological treatment, surgical repair, and rehabilitation, are mostly management therapies rather than curative treatments. Consequently, functional recovery is never achieved. There is a dire need for new therapeutic approaches to facilitate functional restoration. Kaempferol-3-O-rutinoside (K3R) is a plant-derived flavonoid glycoside known for its potent anti-inflammatory and antioxidant properties. Flavonoids may promote tissue recovery following injury by modulating inflammatory responses and reducing oxidative stress. However, the effect of K3R on functional recovery following peripheral nerve injury has not yet been investigated. Therefore, this study aimed to evaluate the effects of K3R on early functional recovery following sciatic nerve crush injury in mice. Methods: Twenty-four BALB/c mice were equally allocated to three groups (n = 8): (1) Sham, (2) Ctrl (Control), and (3) K3R treatment group. K3R (2.5 mg/kg) was dissolved in DMSO and administered intraperitoneally once a day from the time of sciatic nerve injury until the conclusion of the experiment. The Ctrl and sham groups received an equal volume of DMSO according to the same dosing schedule. Sensorimotor function recovery was assessed using behavioral tests, including grip strength, pinprick, sciatic functional index (SFI), and hot plate tests. Hematological and biochemical assays were performed to assess total blood count and oxidative stress markers. Muscle fiber morphology was evaluated by morphometric analysis. Proinflammatory cytokines (TNF-α and IL-6) were measured as indicators of the systemic inflammatory response, whereas S100β protein levels were measured as a marker associated with neural injury and glial responses following sciatic nerve injury. Results: K3R treatment significantly enhanced early sensorimotor function recovery compared with the Ctrl group (p < 0.001). Significant differences in oxidative stress markers TAC (p < 0.001), TOS (p < 0.001), MDA (p = 0.003), and CAT (p = 0.007) were observed among the experimental groups. When comparing the K3R-treated group to the Ctrl group, morphometric analysis revealed an increase in the diameter of muscle fibers (p = 0.011). The levels of IL-6 (p = 0.042) and TNF-α (p = 0.005) indicated attenuation of the systemic inflammatory response, while reduced S100β levels (p = 0.002) were observed in the K3R-treated group, consistent with reduced injury-associated changes. Conclusions: Our findings suggest that K3R may facilitate early functional recovery following sciatic nerve injury, potentially by attenuating oxidative stress and systemic inflammatory responses. However, the precise mechanisms underlying this remain to be elucidated. Future studies should therefore focus on identifying the molecular pathways involved in K3R-mediated recovery, as well as axonal regeneration, Schwann cell activity, and remyelination. Long-term investigations incorporating structural, morphometric, and molecular assessments will be essential to understand its regenerative efficacy and translational potential. Full article

Based on the correlation function of partially coherent perfect vortex beams (PCPVBs) in biological tissue turbulence, a transmission model was established to systematically study how biological tissue and source parameters affect the received probability. Results indicate that the self-focusing property improves the received probability of PCPVBs during propagation, yielding a performance superior to that at the initial state. However, this enhancement effect gradually diminishes with decreasing turbulence strength. Owing to the perfect property, a similar received probability can be maintained at low-order orbital angular momentum (OAM), yet an inevitable degradation occurs as the OAM order further increases. The analysis also demonstrates that a beam configuration with a longer wavelength and a smaller ring radius can achieve superior transmission performance in biological tissue turbulence characterized by a shorter cut-off correlation length, smaller outer scale, and smaller fractal dimension. Furthermore, enlarging the receiving aperture reduces received probability; however, the declining trend levels off when the aperture is sufficiently large to collect the entire intensity information. This study unveils the propagation dynamics of PCPVBs in complex biological media, providing a crucial theoretical foundation and guidance for their applications in biological tissue optical communication, optical detection, and optical imaging. Full article

Background/Objectives: Dry eye disease (DED) affects daily visual functioning and vision-related quality of life in addition to tear film stability and ocular surface integrity. In a previously published prospective cohort, lyophilized amniotic membrane (AM) eye drops were associated with significant improvements in objective ocular surface parameters. This secondary analysis evaluated whether treatment with lyophilized AM eye drops was accompanied by changes in patient-reported outcomes, specifically vision-related quality of life and dry eye symptoms. Methods: This secondary analysis included 40 consecutive patients with DED treated with lyophilized AM eye drops in repeated 14-day cycles over six study visits, while continuing their pre-existing standard DED therapy. Patient-reported outcomes were assessed at baseline and at the final visit using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and the Ocular Surface Disease Index-6 (OSDI-6). Item-level response distributions were compared between baseline and the final visit using non-parametric tests for paired ordinal data. A two-sided p value < 0.05 was considered statistically significant. Results: Global NEI VFQ-25 items, including general health, self-rated vision, and worry about eyesight, did not change significantly. In contrast, significant improvements were observed in ocular pain/discomfort (p = 0.002); near-vision activities, including reading ordinary print (p = 0.003), work or hobbies requiring near vision (p = 0.014); and finding objects on a crowded shelf or in a drawer (p = 0.008), as well as distance-related and spatial tasks, including reading street signs (p < 0.001) and noticing objects off to the side while walking (p = 0.037). Improvements were also observed in vision-related social functioning and dependence-related items. Five of six OSDI-6 items improved significantly: light sensitivity (p < 0.001), blurred vision (p = 0.008), difficulty with driving or night driving (p = 0.002), difficulty watching television (p = 0.008), and discomfort in windy conditions (p = 0.046). Discomfort in low-humidity environments showed a trend toward improvement but did not reach statistical significance (p = 0.059). Conclusions: In this secondary analysis of a prospective cohort, lyophilized AM eye drops were associated with significant improvements in several patient-reported domains of vision-related quality of life and dry eye symptoms. These findings complement previously reported objective improvements in tear film stability, ocular surface staining, meibomian gland function, and corneal sensitivity, suggesting that treatment with lyophilized AM eye drops was associated with improvements extending beyond ocular surface signs to patient-reported daily visual function and symptom burden in patients with DED. Full article

Three-dimensional (3D) and four-dimensional (4D) printing expand the design space for nano-enabled soft robots intended for cancer diagnosis and therapy. This structured narrative review separates three evidence classes: core systems satisfying all scope criteria, adjacent technologies satisfying only part of the definition, and enabling technologies not yet integrated as oncology soft robots. The revised evidence set contains 12 core reports, 7 adjacent comparators and 68 enabling methods, standards or background reports. Study-level analysis using independent manufacturing, biological, workflow and safety (M/B/W/S) axes shows that the core literature is dominated by single-platform, in vitro therapeutic demonstrations with absent or short-term safety evidence (S0-S1). No core study established cancer-specific diagnostic sensitivity or specificity, no human validation was identified, and only two systems were classified as genuine or candidate 4D platforms under a strict programmed-transformation definition. Hydrogel, magnetic, photothermal, conductive, imaging-active and melanin-based materials are evaluated together with printability, dose, localization, sterilization, retrieval, degradation and nanoparticle fate. Translation requires reproducible manufacture, quantitative application endpoints, exposure-matched safety testing and comparison with established oncology workflows. The principal gap is not the availability of additional functions, but the lack of integrated evidence connecting controlled manufacture to clinically meaningful diagnosis or therapy. These findings apply only to the studies identified within the predefined search and eligibility framework and do not establish the absence of relevant evidence elsewhere. Full article

Background/Objective: Co-exposure to heavy metals from environment and a high-fat diet (HFD) represents a growing health concern, contributing to various diseases, but their combined effects on brain health remain less explored. This study aimed to evaluate the neuroprotective potential of Shogaol-enriched ginger extract (SEGE) against heavy metals- and HFD-induced neuropathology. Plant-derived isolated pure compounds can be costly and less accessible; SEGE may offer a translatable, multi-target dietary intervention. Methods: Male Balb/c mice (8–11 weeks old) were exposed to a metal mixture of arsenic (As), lead (Pb), and aluminum (Al; 25 mg/kg/day each) in drinking water and 40% HFD in feed for 60 days. SEGE was administered via feed at two different doses (2 mg/kg/day and 12 mg/kg/day). Assessments including gene expression analyses (using Quantitative Reverse Transcription Real Time Polymerase Chain Reaction (qRT-PCR)) of synaptic and cholinergic markers, spectrophotometric measurement of acetylcholine (ACh) levels, neuronal counting in the cortex and hippocampus via histology, and Gas chromatography mass spectrometric (GC/MS) analysis for brain metabolic quantification were performed. Results: The combined toxic exposure significantly downregulated the expression of synaptic plasticity markers (Synaptophysin, Polysynaptic Density Protein 95 (PSD95), and Calcium/Calmodulin-Dependent Protein Kinase-IV (CAMK-4)) and α and β Nicotinic Acetylcholine Receptors (α7nAChR, α4nAChR, and β2nAChR) in the hippocampus and cortex. ACh levels were also reduced along with significant neuronal loss in the cortical layers and the hippocampal regions. Met + HFD disrupted the brain’s metabolic profile. SEGE treatment significantly restored these markers and attenuated the cholinergic deficits. SEGE treatment, specifically at a higher dose, demonstrated a rescuing effect on the brain’s metabolic profile when compared to the metals and HFD. SEGE further preserved the neuronal count at a higher dose (12 mg/kg/day), exhibiting superior protective effects. Conclusions: These findings suggest that SEGE mitigates neurotoxicity induced by the interaction of toxic metals and dietary factors, likely by preserving synaptic plasticity, metabolic profile, and cholinergic functions, particularly at a higher dose. Full article