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Periodontitis is a prevalent chronic infectious condition affecting the oral cavity. This research was conducted to analyze the role of GATA6 in LPS-stimulated human periodontal ligament cells (hPDLCs). Dysregulated genes associated with periodontitis were acquired from the GEO database (GSE23586). Cell viability was measured utilizing the MTT assay, while apoptosis was analyzed through flow cytometry. The expression levels of mRNA and proteins were examined using qRT-PCR and Western blot techniques, respectively. Levels of IL-1β, IL-6, and TNF-α were measured using specific ELISA kits. The mouse periodontitis model was established to evaluate the effect of GATA transcription factor 6 (GATA6) in vivo.The results demonstrated that GATA6 was downregulated in periodontitis and LPS-stimulated hPDLCs. Overexpression of GATA6 enhanced cell viability, while inhibited apoptosis in hPDLCs. It also reduced the levels of IL-1β, IL-6, and TNF-α in LPS-stimulated hPDLCs. Additionally, after transfection with a GATA6 overexpression vector, the expressions of Caspase 3 and Bax proteins were suppressed, while Bcl2 was upregulated. Furthermore, in LPS-stimulated hPDLCs, the protein levels of Notch1, Hey1, and Hey2 were enhanced after GATA6 overexpression. Silencing of Notch1 neutralized the effects of GATA6 in LPS-stimulated hPDLCs. In addition, GATA6 overexpression alleviated the progression of periodontitis in vivo. In conclusion, GATA6 alleviated the progression of periodontitis by activating the Notch signaling pathway. Show less

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Show less

Moderate-to-vigorous physical activity (MVPA) is inversely associated with risks of cancer, cardiovascular diseases (CVD), type 2 diabetes (T2D), and their co-occurrence, defined as multimorbidity; however, the underlying biological pathways remain unclear. In 33,806 UK Biobank participants with 2911 measured blood proteins, a proteomic signature of MVPA was derived with linear and LASSO regressions. Multivariable Cox models, adjusted for MVPA, estimated prospective associations with cancer, CVD, T2D, and multimorbidity. We show that after multiple testing corrections, 220 proteins are retained in the MVPA signature. Proteins related to food intake, metabolism, and cell growth (e.g., LEP, MSTN) are inversely associated, while those involved in immune cell migration and musculoskeletal integrity (e.g., integrins, COMP) are positively associated with MVPA. Several proteins positively associated with MVPA are inversely associated with disease risk (e.g., integrins, CLEC4A for cancer; LPL, LEP for T2D), while proteins negatively associated with MVPA are positively associated with disease risk (e.g., CD38, TGFA for CVD). The proteomic signature score is inversely associated with cancer risk (hazard ratio per interquartile range: 0.87; 95% confidence interval: 0.78, 0.96) and T2D (0.66; 0.60, 0.72). For multimorbidity, proteins inversely related to MVPA align with expected risk patterns (e.g., GGT1, HR: 1.32; 95% CI: 1.12, 1.57), but the proteomic signature score is not associated. This study identifies several proteins associated with MVPA that are also associated with cancer, CVD, T2D, and the multimorbidity of these conditions. Further studies investigating the causal nature of these associations are welcome. Show less

The transition period is critical for dairy cows, characterized by negative energy balance (NEB), excessive adipose mobilization, and metabolic challenges. This study investigated the effects of dietary omega-3 fatty acids (O3) and N-acetyl-tryptophan (NAT) on blood metabolites and adipose tissue gene expression in Holstein cows. Forty-eight multiparous cows were assigned to four groups (control, O3, NAT, O3+NAT) from -21 to +42 days relative to calving. Body weight (BW) and body condition score (BCS) were recorded, and plasma non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), insulin, and glucose were measured at -21, 0 (calving), +21, and +42 days. Adipose biopsies at +21 and +42 days postpartum were used to perform qPCR analysis of lipogenesis-related genes (Acetyl-CoA carboxylase alpha (ACACA), peroxisome proliferator-activated receptor gamma (PPARγ), lipoprotein lipase (LPL)), fatty acid oxidation (Acyl-CoA oxidase 1 (ACOX1)), lipolysis (hormone-sensitive lipase (LIPE), adipose triglyceride lipase (ATGL)), and adiponectin receptors (AdipoR1, AdipoR2). Statistical analysis used two-way ANOVA with repeated measures. Cows supplemented with O3+NAT maintained higher BW (p<0.05) and BCS (p<0.05), exhibited lower NEFA and BHBA (p<0.05), and had increased insulin (p<0.05) and tended to have higher glucose (p=0.08) compared with controls. PPARγ, LPL, and adiponectin receptors (AdipoR1, AdipoR2) were upregulated in all supplemented groups compared to controls (p<0.05). ACOX1 was downregulated in O3, NAT, and O3+NAT groups compared to control (p<0.05). Network analysis revealed strong positive correlations between insulin and AdipoR1/2 (r>0.7) and positive correlations between NEFA/BHBA and LIPE/β2AR (r>0.75) at d 21. These results demonstrate that O3 and NAT act via complementary mechanisms to attenuate lipolysis, promote lipid storage, and enhance metabolic homeostasis during the transition period. Show less

For the advancements of photoresponsive materials with tunable properties, the usage of multidimensional signals is desired. Using the polarization of the light in addition to the wavelength represents a further parameter to control the materials properties. Here, the first-time dynamic and reversible manipulation of the guest-host properties of a nanoporous material by linearly polarized light (LPL) is reported. The material is based on a metal-organic framework (MOF) with photoresponsive azobenzene side groups covalently connected to the MOF structure. The azobenzene moieties are reversibly reoriented by LPL, making the MOF structure and, thus, the pores anisotropic. As a result, the mobility of the guest molecules in the pores of the initially isotropic material becomes anisotropic, which can be dynamically controlled by the light polarization. The experiments by impedance spectroscopy are supported by molecular dynamics (MD) simulations. The study shows that the light polarization can be a further parameter to modify the material properties, allowing a more complex and more refined level of control for smart materials. Show less

Patients with severe hypertriglyceridemia (sHTG) have variable lipoprotein lipase (LPL) activity levels that may influence therapeutic response. This exploratory analysis investigated post-heparin triglyceride lipase and phospholipase activities in three cohorts of patients with sHTG who received evinacumab (angiopoietin-like 3 inhibitor) for 12 or 24 weeks during a phase 2 trial: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function (LOF) LPL pathway mutations; cohort 2, multifactorial chylomicronemia syndrome (MCS) with heterozygous LOF LPL pathway mutations; and cohort 3, MCS without LPL pathway mutations. Post-heparin plasma samples were obtained at baseline and at week 24 (end of the treatment period). Triglyceride lipase activities (LPL and hepatic lipase [HL]) were measured using both a colorimetric and a scintillation assays. Phospholipase activities (HL and endothelial lipase [EL]) were measured using a colorimetric assay. Baseline post-heparin LPL triglyceride lipase activity was lowest in cohort 1; treatment with evinacumab for 12 or 24 weeks did not alter activity at week 24 versus baseline across cohorts using the colorimetric assay. Non-HL triglyceride lipase activity (mostly LPL) assessed using the scintillation assay showed a significant increase in cohort 1 at 24 weeks versus baseline (P = 0.04). Neither HL nor EL phospholipase activities differed among cohorts or changed with evinacumab treatment. High intra- and inter-patient variability in lipase activity was observed with all methods. Post-heparin LPL triglyceride lipase activity was lower in patients with sHTG with bi-allelic LPL pathway mutations and increased in that group with evinacumab. The high variability in lipase activities observed via differing methods supports the need for more robust assays. Show less

A significant association between lower preheparin serum lipoprotein lipase mass (pre-LpL mass) and coronary artery disease (CAD) has been reported in several clinical studies. However, the predictor of a pre-LpL mass as a CAD event in patients with chronic kidney disease (CKD) remains unclear. This prospective study aimed to investigate the clinical significance of a pre-LpL mass as a predictor of primary CAD events in patients with CKD. A total of 480 CKD patients who did not develop CAD among outpatients who visited the clinic were enrolled. Using receiver operating characteristic curve analysis for a primary CAD event, participants were divided into two groups (low pre-LpL mass (group L, n = 211) or high pre-LpL mass (group H, n = 269)) by pre-LpL mass, and significance of a pre-LpL mass as a predictor for the primary CAD events was performed. At baseline, skin autofluorescence, an indicator of advanced glycation end products The prospective study showed that a decrease in pre-LpL mass is a useful predictor of a primary CAD event in patients with CKD. Additionally, background factors such as an increase in advanced glycation end products and inflammation are also an important factor in these patients. Show less

The transition from pre-reading to early word reading skill in early childhood is a time of profound developmental change. To understand changes in brain networks associated with reading development, this study examined individual differences in functional connectivity for reading at the start of formal literacy instruction. Sixty-six kindergarteners (ages 5-6) completed a visual word processing task during functional magnetic resonance imaging (fMRI). Based on standardized literacy assessments, participants were characterized as Pre-Readers (alphabetic knowledge but unable to read words) or Beginning Readers (some word reading ability). We compared patterns of task-based functional connectivity between children at different stages of literacy development using confirmatory subgroup Group Iterative Multilevel Model Estimation (cs-GIMME). cs-GIMME is a data-driven method that estimates individualized network connections between a priori regions of interest. Pre- and Beginning Readers did not differ in overall network complexity (number of functional connections between regions of interest). However, distinct periods of reading development corresponded to differences in network centrality, defined as the proportion of network connections involving specific regions of interest. Pre-Readers had more distributed connections and greater within-right hemisphere connectivity. In comparison, Beginning Readers demonstrated more symmetrical network organization, and greater centrality of the Visual Word Form Area and other left hemisphere language hubs. Increased reading skill was linearly associated with increased left lateralization, potentially reflecting more mature networks and greater print processing efficiency. These findings provide novel insights into child brain development during the first year of formal schooling by revealing links between emerging literacy skills and functional neural connectivity. Show less

Circularly polarized luminescence (CPL) has attracted significant attention for applications in displays, data encryption, anti-counterfeiting, and bioimaging. However, extending the emission lifetime beyond the second timescale remains a challenge. Here, we report circularly polarized long-persistent luminescence (CP-LPL) and the first evidence of circularly polarized photostimulated luminescence (CP-PSL) in purely organic systems. Using the chiral emitter R/S-OBN-Cz, we establish two complementary design strategies: (i) a three-component Förster resonance energy transfer (FRET) system, where the energy of long-lived charge-separated states between the donor and the acceptor is transferred to the chiral dopant, and (ii) a two-component upconversion system, where the locally excited state of chiral emitter is restored upon charge recombination. Both approaches result in CP-LPL with mirror-image CPL signals. Moreover, in the three-component FRET system, trapped charges in the chiral dopant can be released upon near-infrared stimulation, regenerating circularly polarized emission. This work establishes new proof of concept in chiroptical materials research, paving the way toward the practical applications in encrypted optical storage and advanced photonic devices. Show less

Previous studies have reported that IGF-1 single nucleotide polymorphism is associated with milk fat traits, but they are limited to trait association analysis. We previously identified a synonymous mutation c.258 A > G (rs322131043) in IGF-1, which influenced IGF-1 expression and caused differences in metabolism. This study aims to reveal a new regulatory function of IGF-1 c.258 A > G on milk fat metabolism. Livers transcriptomics was used to identify differentially expressed genes between wild type mice (WT) and IGF-1 c.258 A > G mice (Homozygous mutation, Ho). Subsequently, lipid phenotyping, followed by metabolomics of mammary glands was conducted to verify transcriptomic findings. Finally, the potential mechanisms underlying IGF-1 c.258 A > G-induced changes in milk fat metabolism were explored though integrated transcriptomics-metabolomics analysis and Western blot validation. IGF-1 c.258 A > G changed the expression of genes related to lipid metabolism in livers of 8-week-old mice, including a 10-fold ‌lipoprotein lipase (LPL) expression (P < 0.01) and ‌80-90 % downregulation of acyl-CoA thioesterase 3 (Acot3), enoyl-Coenzyme A delta isomerase 3 (Eci3), fatty acid synthase (FASN), and sterol regulatory element binding protein1 (SREBP1) expression (P < 0.01). The milk fat content of Ho dams on the second day of lactation (L2D) was decreased 50 % than that of WT dams (P < 0.05), although there was no significant difference in adipose tissue of 8-week-old WT/Ho mice. The levels of triglycerides, sphingolipids and their related fatty acyl chains (10:0, 26:0, 14:2, 20:4, 11:3, 19:0) in mammary glands of L2D Ho dams were reduced 10-50 % observed by lipid metabolomics. And combined with transcriptomics and Western blot, the data suggested that a ‌2.5-fold upregulation of LPL expression‌ (P < 0.05) may contribute to the milk fat metabolism changes mediated by the ‌ IGF-1 c.258 A > G. This study revealed new function of IGF-1 c.258 A > G on milk fat metabolism, thereby informing the development of targeted genetic breeding on milk fat trait. Show less

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Unfortunately, the early stages of this disease are poorly understood, which has led to limited treatment options. Investigating normal changes in tissues eventually affected by AMD can further elucidate the mechanisms of disease progression and lead to novel therapeutic targets. The primary cell layer affected in AMD is the retinal pigment epithelium (RPE), which forms the outer blood-retinal barrier (oBRB). Beneath the RPE lies Bruch's membrane, a proteinaceous layer that naturally thickens and stiffens with age. These changes to Bruch's membrane are also implicated in RPE dysfunction and AMD progression. To investigate the relationship between normal, age-related changes in Bruch's membrane and AMD development, we engineered a tunable in vitro model of Bruch's membrane to support primary porcine RPE cells. We performed transepithelial electrical resistance (TEER) measurements, viability assays, morphological analysis, immunocytochemistry, and enzyme-linked immunosorbent assays (ELISA) to evaluate monolayer integrity and angiogenic factor expression. Cells cultured on our aged model exhibited changes similar to those seen in AMD, including reduced monolayer integrity, the formation of sub-RPE deposits, and eventual cell death. Notably, apolipoprotein E (ApoE), a known drusen component and Alzheimer's disease marker, was overexpressed prior to deposit accumulation and cell death. Regions of ApoE overexpression corresponded with disrupted expression of zonula occludens-1, a junctional protein. While most angiogenic factors remained unchanged, tissue inhibitor of metalloproteinases-1 (TIMP-1) was transiently overexpressed before cell death. These findings suggest that ApoE and TIMP-1 may play key roles in early AMD pathogenesis and represent potential targets for future therapeutic intervention. Show less

Based on epidemiological and genetic studies in recent decades, lipoprotein(a) (Lp(a)) has been accepted as a causal risk factor for atherosclerotic cardiovascular disease and aortic stenosis. Although inter-ethnic differences exist, Lp(a) level ≥50 mg/dL is commonly reported to indicate elevated cardiovascular risk. Blood Lp(a) levels are largely determined based on genetic background, and the kringle IV type 2 repeat variant is a major factor. Lp(a) is structurally similar to low-density lipoprotein (LDL) but also contains apolipoprotein(a) (apo(a)), which includes kringle domains associated with diverse effects depending on particles and individuals. The LDL-like property of Lp(a) and effect of apo(a) on vascular cells can promote atherosclerosis. Apo(a) competes with plasminogen and can inhibit the role of plasmin during fibrinolysis. Furthermore, oxidized phospholipids on apo(a) may induce oxidative stress to enhance atherosclerosis and can affect valve calcification. Trials on new therapeutics targeting Lp(a) RNA, including antisense oligonucleotide (e.g., pelacarsen), siRNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and small molecules (e.g., muvalaplin), are under way. Depending on the study or dose, these agents lowered Lp(a) levels by 80-100% compared with the control; however, results of clinical outcomes have yet to be reported. Show less

Accumulating research has demonstrated a significant association between early-life inflammation and behavioral disorders later in life. However, the effects of early-life inflammation on aggressive behavior in adulthood remain poorly understood. Here, we show that early-life inflammation induced by lipopolysaccharide (LPS) upregulated neuronal dynamin-related protein 1 (DRP1) and impaired mitochondrial function in medial prefrontal cortex (mPFC) of adult mice, thereby increasing aggressive behavior in adulthood. We further identify that CCAAT/enhancer binding protein β (C/EBPβ) is the transcription factor of Dnm1l, which was activated by an increased release of lysophosphatidic acid (LPA) induced by early-life inflammation. Moreover, the overproduction of LPA was due to a specific increase in astrocyte-secreted autotaxin (ATX). Specific knockdown of astrocytic ATX reduced early-life inflammation-induced aggression in wild-type mice, but not in Thy1-C/EBPβ transgenic mice. Remarkably, coenzyme Q10 decreased early-life inflammation-induced aggressive behavior in adult mice. Altogether, these findings provide new insights into the molecular mechanisms by which early inflammation promotes aggressive behavior in adulthood. Show less

About 20-40% of prostate cancer (PCa) develop biochemical recurrence (BCR) after surgery, and propionate metabolism may contribute to tumor progression. BCR remains a major clinical challenge in PCa, as current tools based on histopathology and prostate-specific antigen (PSA) fail to capture the molecular heterogeneity driving the disease. While metabolic reprogramming is known to facilitate post-treatment adaptation, the specific role of propionate metabolism in this context remains largely unexplored. Therefore, this study aimed to systematically investigate propionate metabolism-related genes (PMRGs) to develop a novel prognostic model for the improved early prediction of recurrence. In this study, The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD), GSE70770 and 412 PMRGs were employed. Differentially expressed genes (DEGs) in PCa and control and DEGs2 in BCR and no BCR samples obtained by differential analysis were intersected with PMRGs to get candidate genes. After Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, biomarkers were identified to construct risk models. Biomarkers including In this study, PMRGs were regarded as biomarkers in PCa for risk model construction, which suggest that propionate metabolism represents a biologically relevant axis in PCa recurrence and may offer a novel framework for biomarker-driven risk assessment. Show less

The 2025 update of the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on dyslipidemia introduce important innovations based on new evidence. The risk assessment is now conducted using the systematic coronary risk evaluation 2 (SCORE2) and SCORE2-OP (older persons), which enable improved stratification, particularly in older individuals. In addition, risk modifiers, such as family history, ethnicity, comorbidities and the biomarkers elevated highly sensitive C‑reactive protein (hs-CRP) or lipoprotein(a) (Lpa), have been introduced. Risk categories have been refined while low-density lipoprotein cholesterol (LDL-C) target values and the principle of stepwise treatment remain unchanged. A major focus is on the acute coronary syndrome: the immediate initiation of high-intensity statin treatment, mostly in combination with ezetimibe is recommended. Increasingly more important are elevated Lp(a) levels and special subgroups: in people with human immunodeficiency virus (HIV), statin treatment is recommended over the age of 40 years regardless of the LDL‑C as well as in high-risk patients undergoing anthracycline treatment. The use of dietary supplements and vitamins for prevention, however, are discouraged. The update reinforces the principle of risk-adapted LDL‑C target values, expands the treatment options and emphasizes the need for early, consistent lipid-lowering with practical recommendations. Show less

High-level cognitive skill development relies on genetic and environmental factors, tied to brain structure and function. Inter-individual variability in language and music skills has been repeatedly associated with the structure of the auditory cortex: the shape, size and asymmetry of the transverse temporal gyrus (TTG) or gyri (TTGs). TTG is highly variable in shape and size, some individuals having one single gyrus (also referred to as Heschl's gyrus, HG) while others presenting duplications (with a common stem or fully separated) or higher-order multiplications of TTG. Both genetic and environmental influences on children's cognition, behavior, and brain can to some to degree be traced back to familial and parental factors. In the current study, using a unique MRI dataset of parents and children (135 individuals from 37 families), we ask whether the anatomy of the auditory cortex is related to reading skills, and whether there are intergenerational effects on TTG(s) anatomy. For this, we performed detailed, automatic segmentations of HG and of additional TTG(s), when present, extracting volume, surface area, thickness and shape of the gyri. We tested for relationships between these and reading skill, and assessed their degree of familial similarity and intergenerational transmission effects. We found that volume and area of all identified left TTG(s) combined was positively related to reading scores, both in children and adults. With respect to intergenerational similarities in the structure of the auditory cortex, we identified structural brain similarities for mother-child pairs of the 1st TTG (HG) (in terms of volume, area and thickness for the right HG, and shape for the left HG) and of the lateralization of all TTG(s) surface area for father-child pairs. Both the HG and TTG-lateralization findings were significantly more likely for parent-child dyads than for unrelated adult-child pairs. Furthermore, we established characteristics of parents' TTG that are related to better reading abilities in children: fathers' small left HG, and a small ratio of HG to planum temporale. Our results suggest intergenerational transmission of specific structural features of the auditory cortex (not directly linked to children's reading outcomes); these may arise from genetics and/or from shared environment. Show less

This article presents a case of a rare lymphoplasmacytic lymphoma (LPL) complicated by spherocytosis in a 74-year-old male. The patient reported progressive fatigue and anemia and had a medical history of type 2 diabetes, hypertension, and cerebral infarction. Laboratory tests indicated moderate anemia (hemoglobin 80 g/L) and a monoclonal increase in serum IgG. A bone marrow biopsy combined with immunohistochemistry confirmed the diagnosis of lymphoplasmacytic lymphoma (IgG-κ type, MYD88 L265P negative). A peripheral blood smear revealed an increase in spherocytes, a positive acidified glycerolysis test (AGLT50), abnormal erythrocyte osmotic fragility, and a negative direct antiglobulin test. Genetic screening for hereditary erythrocyte diseases showed no pathogenic variations. The patient's condition stabilized following targeted therapy with zanubrutinib and rituximab (ZR regimen). This case underscores the complexity of diagnosing dual hematological anomalies, highlights the importance of multidisciplinary collaboration, and seeks to explore the potential pathophysiological link between LPL and spherocytosis, offering a reference for diagnosis and treatment in similar clinical scenarios. Show less

Understanding the effects of captivity on wild animals is essential, as it helps to improve the physical health and welfare of captive wild animals. The changes in environment, diet and other factors during the captivity may reshape their internal microbiota and affect the body’s metabolism. Using 16S rRNA gene sequencing, we analyzed gut and tracheal microbiota from wild and captive chipmunks, and examined differences in serology, histopathology, fat metabolism, and muscle quality. The dominant bacterial phyla in the gut and tracheal microbiota of chipmunks are Firmicutes, Bacteroidota, and Proteobacteria, with the gut and tracheal microbiota of captive chipmunks showing an increase in the Spirochaetota and Patescibacteria at the phylum level. No major organ (the heart, lung, colon, muscle and kidney) damage was observed in captive chipmunks. Fat metabolism analysis revealed increased expression of genes related to fat processing (PPARG, ACACA, FASN, ELOVL1, LPL, and SCD). Muscle gene expression analysis showed higher levels of MYH1, MYH2, and MYH7, in captive chipmunks. These findings suggest that core bacterial types remained largely stable, but there were shifts in bacterial types that aid digestion during the laboratory captivity. Meanwhile, the fat metabolism of the captive chipmunks also changed, which supports muscle fatty acid absorption, and shifts muscle fiber types from fast to slow, promoting muscle synthesis and energy efficiency in captive chipmunks. Our study provides new insights into the influence of laboratory captivity on wild animals, establishes a foundation for facilitating the transformation of wild chipmunks into experimental animals. The online version contains supplementary material available at 10.1186/s12866-026-04857-4. Show less

Optimizing the use of dietary emulsifiers and prebiotics in relation to fat source may enhance nutrient-utilization efficiency in broiler production. This 42-d study evaluated the effects of an emulsifier (lysophospholipid; LPL) and inulin supplementation in diets with two fat sources on growth performance, nutrient digestibility, muscle fatty acid composition, digestive enzyme activity, and intestinal histomorphology. Eight hundred 1-d-old male broiler chickens were assigned to eight treatments in a 2 × 2 × 2 factorial design with two fat sources (soybean oil or beef tallow), two LPL levels (0 or 1 g/kg), and two inulin levels (0 or 1 g/kg). Interactive effects were detected for fat source × inulin on average daily gain (ADG), mortality, and the European Production Index (EPI), with inulin addition to soybean-oil-based diets yielding superior growth and survival rates (P < 0.05). The LPL × inulin interaction increased feed intake and improved gain-to-feed ratio (P < 0.05). The fat source × LPL interaction significantly influenced lipid-metabolism-related traits (P < 0.05); in tallow-based diets, LPL supplementation increased fat digestibility and AMEn, reduced breast fat deposition, and improved the fatty acid profile of thigh muscle by elevating n-3 PUFA and lowering the n-6/n-3 ratio, whereas no significant effects occurred in soybean-oil-based diets. When interaction terms were not significant, LPL increased protease and lipase activities and improved duodenal villus height and surface area, whereas inulin increased protease activity, improved protein digestibility, and enhanced jejunal villus architecture (P < 0.05). In conclusion, LPL is particularly beneficial in tallow-based diets by enhancing lipid digestibility, energy utilization, and the thigh-muscle fatty acid profile, while inulin improves growth performance, especially in soybean-oil-based diets-offering a practical strategy to optimize broiler production. Show less

Adherence to antiretroviral therapy is essential for achieving viral suppression. Plasma separation cards (HemaSep; HS-DBS) provide advantages for pharmacokinetic (PK) analysis and adherence monitoring, including simplified sample collection. This study compared the PK of dolutegravir (DTG), nucleoside reverse transcriptase inhibitors (NRTIs), and their intracellular metabolites in the dried plasma and cellular fractions of HS-DBS against the appropriate gold-standard matrices: liquid plasma for parent drugs and Whatman DBS (WM-DBS) for NRTI metabolites. The APT-POCT-01 clinical trial (NCT04302896) is an open-label study assessing drug concentrations following cessation in healthy volunteers. Participants were randomized (1:1) to receive DTG/FTC/TAF or DTG/3TC/TDF for 15 days. Paired liquid plasma (L-pL), HS-DBS, and WM-DBS samples were collected on Day 15 and following treatment cessation (0-336 hours post-final dose). 29 individuals were included in the PK analysis (15-TDF/14-TAF). Tenofovir diphosphate (TFV-DP) was quantifiable up to 14 days post-cessation in HS-DBS (TAF/TDF) and WM-DBS (TDF) (HS-DBS t½ > 17 days, WM-DBS t½ = 15 days). 3TC-TP and FTC-TP were eliminated more rapidly. Nucleoside di/triphosphate concentrations were 3-7-fold higher, with prolonged half-lives (TFV-DP, FTC-TP), compared with WM-DBS. TFV-DP levels were ~12-fold higher with TDF compared to TAF. For NRTI and DTG, HS-plasma resulted in 1.8-fold higher exposures compared to L-pL. Measurable HS-DBS concentrations were correlated with L-pL and WM-DBS, with Bland-Altman analysis indicating agreement between methods. This study provides important insights into the elimination kinetics of NRTI, their intracellular metabolites and DTG. Plasma separation cards are a promising alternative for adherence monitoring, enabling simultaneous quantification of parent and intracellular moieties from a single sample. Differences in TFV-DP levels between TDF and TAF regimens, and DBS sampling method, underscore the need for matrix and regimen-specific interpretation to validate adherence benchmarks. Show less

Adipose tissue-derived stem cells (ADSCs) possess multipotent differentiation potential and significant immunomodulatory properties, making them valuable in regenerative medicine. However, their adipogenic differentiation can lead to triglyceride accumulation, chronic inflammation, and metabolic dysfunction. This study evaluated the effects of Radio Electric Asymmetric Conveyer (REAC) technology tissue optimization regenerative adipogenesis reprogramming (TO RGN-AR) on ADSC differentiation, focusing on its ability to preserve stemness, suppress adipogenesis, and promote beneficial phenotypes. REAC TO RGN-AR treatment significantly increased the expression of stemness-related genes (Oct-4, Sox2, and Nanog) while downregulating the expression of adipogenic markers (PPAR-γ, LPL, and ACOT2). Additionally, REAC TO RGN-AR treated cells presented a phenotypic shift toward beige adipocytes, characterized by increased TMEM26 expression and reduced ASC-1 expression. These findings underscore the novelty of using REAC TO RGN-AR to modulate cellular endogenous bioelectrical activity, presenting a noninvasive and operator-independent approach to enhance ADSC-based therapies. This work highlights the potential of this treatment to address metabolic disorders and chronic inflammation while advancing regenerative medicine. Show less

Increased fasting and postprandial triglyceride levels are risk factors for cardiovascular disease (CVD). Partially metabolized triglyceride-rich lipoproteins (TRLs) termed remnants are created when intestinally-derived chylomicrons and liver secreted very low density lipoproteins (VLDLs) interact with lipoprotein lipase (LpL) situated on the luminal surface of capillary endothelial cells. Higher circulating remnant levels have been implicated as the reason for the relationship between TRL levels and CVD. We hypothesized that nascent lipoproteins not only remnants are atherogenic. To test this, we created mice with induced whole-body lipoprotein lipase (LpL) deficiency combined with LDL receptor (LDLR) deficiency. On an atherogenic Western-type diet (WD), male and female mice with induced global LpL deficiency (iLpl Show less

Children with complex congenital heart disease (CCHD) are at high risk for early neurodevelopmental delays across all domains. Neuromotor delay often emerges first and may impact broader development. Identifying early biomarkers of motor function could capture a critical window for intervention. We assessed the prognostic value of neuron-specific enolase (NSE) and S100B in predicting 4-month motor outcomes in newborns undergoing cardiac surgery with cardiopulmonary bypass (CPB). Between December 2021 and October 2024, we conducted a prospective, single-centre study including term neonates with (CCHD) who required cardiac surgery within the first two months of life. NSE and S100B levels were measured at five perioperative time points. Blinded Alberta Infant Motor Scale (AIMS) assessment at four months evaluated motor outcomes. Of 35 newborns, 27 completed follow-up. Preoperative NSE levels were significantly higher in infants with AIMS scores below the 10th percentile (32.7 vs. 20.9 ng/mL, p = 0.044) and negatively correlated with AIMS percentiles (ρ = -0.617, p = 0.006. There was no significant association between motor outcomes, MRI findings or S100B levels. Higher preoperative NSE levels predict poor early motor outcomes in CCHD and may be a marker for early risk stratification and intervention. Neuron-specific enolase (NSE) may serve as an early biomarker of neuromotor development in newborns with complex congenital heart disease (CCHD). Elevated preoperative NSE levels were associated with poorer motor outcomes at four months. NSE may serve as an additional biomarker within a multimodal risk stratification strategy, complementing clinical, imaging, and electrophysiological assessments to refine prognostic evaluation. These findings highlight the prognostic value of perioperative biomarkers for predicting early motor outcomes and support earlier identification of at-risk newborns, enabling targeted neurodevelopmental interventions. This work adds new evidence to limited literature on biological predictors of motor development after neonatal cardiac surgery. Show less

Chylomicronemia is characterized by extreme hypertriglyceridemia (triglyceride values >10 mmol/L). It may be caused by a biallelic combination of a pathogenic variant [familial chylomicronemia syndrome (FCS)] or by genetic susceptibility combined with comorbidities and environmental factors [multifactorial chylomicronemia syndrome (MCS)]. Acute pancreatitis (AP) is the most serious complication of chylomicronemia. In the general population, the prevalence of AP during pregnancy is estimated to be <0.35%. As triglyceride levels significantly increase during pregnancy, it may affect the course of pregnancy and further increase the risk of AP in women with chylomicronemia. One hundred sixteen pregnancies involving 49 European and North American women with a history of chylomicronemia (20 FCS, 29 MCS) were retrospectively reviewed. The occurrence of AP, the course of pregnancy, fetal development, and delivery were evaluated. Forty-two percent of FCS and 10% of MCS women experienced at least 1 AP episode during pregnancy (P = .01). Compared to MCS, women with FCS presented a higher percentage of pregnancies with AP (17% vs 5%, P = .02). Among all reviewed pregnancy-related AP, 56% occurred in primigravida FCS women compared to 0% in MCS. Premature deliveries were elevated in both groups, although they were more frequent in FCS (56%) vs MCS (19%) (P = .01). The percentages of miscarriages (11.8% vs 10.7%) and fetal failure to thrive (5.9% vs 9.2%) were not significantly different between the 2 cohorts. In this study, pregnant women with chylomicronemia had a 30-fold (MCS) to 120-fold (FCS) higher occurrence of AP compared to the general population. Chylomicronemia per se does not seem to influence fetal development. Show less

Suicidal ideation (SI) and behavior are complex phenotypes, with multiple contributing risk-factors. This study used longitudinal data from the Million Veteran Program Mental Health Survey to identify SI profiles among Veterans based on trajectories of ideation and depression severity and compared them to a non-suicidal (no-SI) control group. Latent profile analysis (LPA) was performed to identify SI profiles using data from Veterans (n = 34,322) endorsing SI in their electronic health record. LPA identified four highly reproducible SI profiles: mild ideators with and without depression, variable ideators, and persistent ideators. Veterans across the SI profiles were significantly more likely to have diagnoses of suicidal ideation or behavior, mental disorders, and TBI compared to Veterans with no-SI. The variable ideators showed higher rates of comorbid conditions. The mild ideators without depression and persistent ideators had a significantly higher proportion of deaths by suicide than the no-SI Veterans. European and African American GWAS and pan-ancestry meta-analyses of SI profiles compared to no-SI controls were also performed, which identified genome-wide significant loci across all SI profiles proximal to genes implicated in auditory and vestibular functioning, Alzheimer's, diabetes, and asthma. In summary, SI profiles identified were associated with novel genetic variants not identified by previous suicide GWAS studies. Additionally, Veterans within the mild SI profile that did not present with high-risk comorbidities had the highest rate of suicide deaths, indicating the need for upstream suicide risk prevention interventions across the SI risk continuum. Show less

Parkinson's disease is a neurodegenerative disorder that affects the elderly population worldwide. Rotenone (ROT) is an environmental toxin that impairs mitochondrial dynamics by inhibiting respiratory chain complex I and thus inducing oxidative stress. Farnesol (FSL) is a dietary sesquiterpene with antioxidant and anti-inflammatory properties reported in various in vivo models. To evaluate the efficacy of FSL in the management of PD, Wistar rats were injected with ROT (2.5 mg/kg, i.p) and pretreated with FSL. Immunohistochemical staining measured tyrosine hydroxylase-positive cells in the substantia nigra and striatum. Western blotting was employed to determine protein expression of inflammatory, apoptotic, and autophagic markers. Our results indicate that FSL significantly protected against ROT-induced inflammation by suppressing microglial and astrocytic activation through the downregulation of Toll-Like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inhibitor of kappa B (IkB), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), matrix metalloproteinase-9 (MMP-9) expression. FSL has also demonstrated an antioxidant effect by enhancing the activity of superoxide dismutase and catalase while reducing the level of Malondialdehyde and nitric oxide. Moreover, it restored homeostasis in ROT-induced imbalance between pro- and anti-apoptotic proteins. Impaired autophagy observed in ROT-injected rats was corrected by FSL treatment, which upregulated phosphorylated mammalian target of rapamycin (p-mTOR) expression and downregulated P62, an autophagosome marker. The protective effect of FSL was further supported by preserving the brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase in the brain. These findings demonstrate the neuroprotective ability of FSL and its potential to be developed as a pharmaceutical or nutraceutical agent for the prevention and treatment of PD by mitigating neuropathological changes observed in dopaminergic neurodegeneration. Show less