Stabilizing Dye-Sensitized Upconversion Hybrids by Cyclooctatetraene.

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert low-energy near-infrared (NIR) light into high-energy visible light, making them valuable for broad applications. UCNPs often suffer from poor light-harvesting capabilities, which can be significantly improved by incorporating organic dye antennas. However, the dye-sensitized upconversion systems are prone to severe photobleaching in an ambient atmosphere. Here, we present a synergistic approach to mitigate photobleaching by introducing triplet state quencher cyclooctatetraene (COT). COT effectively suppresses the generation of singlet oxygen by quenching the triplet states of the dye and consumes the existing singlet oxygen through oxidant reactions. The inclusion of COT extends the half-life of IR806 by 4.7-times by preventing the oxidation of its poly(methylene) chains. Without significantly affecting emission intensity and dynamics, COT effectively stabilized dye-UCNPs, demonstrating a notable 3.9-fold increase in half-life under continuous laser irradiation. Our findings suggest a new strategy to enhance the photostability of near-infrared dyes and dye-sensitized upconversion nanohybrids.

RS-MAE: Region-State Masked Autoencoder for Neuropsychiatric Disorder Classifications Based on Resting-State fMRI.

Dynamic functional connectivity (DFC) extracted from resting-state functional magnetic resonance imaging (fMRI) has been widely used for neuropsychiatric disorder classifications. However, serious information redundancy within DFC matrices can significantly undermine the performance of classification models based on them. Moreover, traditional deep models cannot adapt well to connectivity-like data, and insufficient training samples further hinder their effective training. In this study, we proposed a novel region-state masked autoencoder (RS-MAE) for proficient representation learning based on DFC matrices and ultimately neuropsychiatric disorder classifications based on fMRI. Three strategies were taken to address the aforementioned limitations. First, masked autoencoder (MAE) was introduced to reduce redundancy within DFC matrices and learn effective representations of human brain function simultaneously. Second, region-state (RS) patch embedding was proposed to replace space-time patch embedding in video MAE to adapt to DFC matrices, in which only topological locality, rather than spatial locality, exists. Third, random state concatenation (RSC) was introduced as a DFC matrix augmentation approach, to alleviate the problem of training sample insufficiency. Neuropsychiatric disorder classifications were attained by fine-tuning the pretrained encoder included in RS-MAE. The performance of the proposed RS-MAE was evaluated on four publicly available datasets, achieving accuracies of 76.32%, 77.25%, 88.87%, and 76.53% for the attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), Alzheimer's disease (AD), and schizophrenia (SCZ) classification tasks, respectively. These results demonstrate the efficacy of the RS-MAE as a proficient deep learning model for neuropsychiatric disorder classifications.

Complete genome sequence of a Histophilus somni strain 91 isolated from a beef calf with pneumonia.

Histophilus somni is an important causative agent of bovine respiratory disease complex. Here, we report the complete genome sequence of a Histophilus somni strain 91, which was isolated from a pneumonic lung tissue sample collected from a beef calf.

Antiviral activity of bovine type III interferon against bovine viral diarrhea virus is greatly reduced in bovine turbinate cells due to limited expression of IFN lambda receptor 1 (IL-28Rα).

Introduction: The antiviral activity of recombinant bovine interferon lambda 3 (bovIFN-λ3) against bovine viral diarrhea virus (BVDV) has been demonstrated in vitro in Madin-Darby bovine kidney cells (MDBK) and in vivo in cattle. However, anti-BVDV activity of bovIFN-λ3 has not been studied in bovine respiratory tract epithelial cells, supposedly a primary target of BVDV infection when entering the host by the oronasal route. Methods: Here we investigated the anti-BVDV activity of bovIFN-λ3 in bovine turbinate-derived primary epithelial cells (BTu) using BVDV infection and immunoperoxidase staining, TCID50, RT-qPCR, DNA and transcriptome sequencing, and transfection with plasmids containing the two subunits, IL-28Rα and IL-10Rß that constitute the bovIFN-λ3 receptor. Results: Our immunoperoxidase staining, RT-qPCR, and TCID50 results show that while BVDV was successfully cleared in MDBK cells treated with bovIFN-λ3 and bovIFN-α, only the latter, bovIFN-α, cleared BVDV in BTu cells. Preincubation of MDBK cells with bovIFN-λ3 before BVDV infection was needed to induce optimal antiviral state. Both cell types displayed intact type I and III IFN signaling pathways and expressed similar levels of IL-10Rß subunit of the type III IFN receptor. Sequencing of PCR amplicon of the IL-28Rα subunit revealed intact transmembrane domain and lack of single nucleotide polymorphisms (SNPs) in BTu cells. However, RT-qPCR and transcriptomic analyses showed a lower expression of IL-28Rα transcripts in BTu cells as compared to MDBK cells. Interestingly, transfection of BTu cells with a plasmid encoding IL-28Rα subunit, but not IL-10Rß subunit, established the bovIFN-λ3 sensitivity showing similar anti-BVDV activity to the response in MDBK cells. Conclusion: Our results demonstrate that the sensitivity of cells to bovIFN-λ3 depends not only on the quality but also of the quantity of the IL-28Rα subunit of the heterodimeric receptor. A reduction in IL-28Rα transcript expression was detected in BTu as compared to MDBK cells, despite the absence of spliced variants or SNPs. The establishment of bovIFN-λ3 induced anti-BVDV activity in BTu cells transfected with an IL-28Rα plasmid suggests that the level of expression of this receptor subunit is crucial for the specific antiviral activity of type III IFN in these cells.

Controlling and Tuning the Dispersion Properties of Calcined Kaolinite Particles in Various Organic Solvents via the Modification Method Using Triethoxyvinylsilane and 3-Mercaptopropionic Acid.

The surface of calcined kaolinite particles underwent chemical modification using Vinyltriethoxysilane (VTMS) and 3-mercaptopropionic acid (3-MPA). The grafting ratio of VTMS on the calcined kaolinite surface was adjusted by varying its quantity. FT-IR analysis revealed the initial grafting of VTMS onto the kaolinite surface, resulting in the formation of a C=C reactive site on the surface. Subsequently, an olefin click reaction with 3-MPA occurred, leading to the effective grafting of 3-MPA onto the kaolinite surface and the formation of an efficient coating. Thermal analysis indicated that the optimal grafting level was achieved at a modifier content V:K ratio of 0.5. The estimated grafting ratio of the modifier on the kaolinite surface was approximately 40% when V:K was 0.5. Water contact angle and dispersion experiments demonstrated that the surface properties of kaolinite were effectively controlled by this modification approach. At V:K = 0.3, the modified kaolinite particles exhibited good dispersion in both polar and non-polar solvents. In polar solvents, the average particle size of modified kaolinite was below 1100 nm, while in non-polar solvents, it did not exceed 5000 nm. Considering all aspects, a V:K ratio of 0.3 is recommended. Further investigation into the impact of adding 3-MPA on the surface properties of modified kaolinite particles based on V:K = 0.3 revealed that the hydrophilicity of the modified particles could be enhanced. However, it is advised to keep the maximum M:V ratio (3-MPA to kaolinite) at 1.0.

Unveiling Electrostatic Interaction Modulated Sensitive and Selective SERS Detection for Negatively Charged Molecules.

Strengthening the interaction between the target and SERS substrate is crucial for sensitive SERS detection; we thereby explored the molecular structure-dependent SERS sensitivity for negatively charged targets on the positively charged SERS substrate. Both experimental and theoretical studies confirm that the SERS sensitivity is determined by the electrostatic interaction between the target and linker. This interaction is not only manipulated by the protonation capacity of the linker and its surface adsorption configuration and geometry but also significantly determined by the target's structure, encompassing electronegativity and the number of interaction sites. The optimized interaction leads to a marked improvement in detection sensitivity of up to 1-3 orders of magnitude. The interaction mechanism revealed in this work not only provides theoretical guidance and technical support for electrostatically driven SERS detection but also offers a conceptual framework that can be extended to various SERS detections based on diverse surface forces.

Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

Enhancing Lower Eyelid Suspension Outcomes Through Pre-surgical Facial Nerve Reanimation: A Comparative Study.

BACKGROUND: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension. METHODS: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness. RESULTS: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry. CONCLUSIONS: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Smoking timing, genetic susceptibility, and the risk of incident atrial fibrillation: a large prospective cohort study.

AIMS: Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with risk of incident AF, and test the modification effect of genetic susceptibility. METHODS AND RESULTS: A total of 305,627 participants with detailed information for time from waking to first cigarette were enrolled from UK Biobank database. Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. Weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13,410 AF cases were documented. Compared to non-smokers, time from waking to the first cigarette showed gradient inverse associations with risk of incident AF (P-trend <0.001). The adjusted hazard ratio related to smoking timing was 1.13 (95% CI: 0.96-1.34) for >120 minutes, 1.20 (95% CI: 1.01-1.42) for 61-120 minutes, 1.34 (95% CI: 1.19-1.51) for 30-60 minutes, 1.43 (95% CI: 1.26-1.63) for 5-15 minutes, and 1.49 (95% CI: 1.24-1.63) for <5 minutes, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF. CONCLUSIONS: Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF.

Our study aimed to analyze the relationship between the time from waking to the first cigarette and incidence of AF, and the modification role of genetic susceptibility.Shorter time from waking to the first cigarette was related to elevated risk of incident atrial fibrillation.Genetic susceptibility to atrial fibrillation strengthened the gradient inverse association of time from waking to the first cigarette with incidence of AF.

Noninvasive Evaluation of Acupuncture-Induced Cortical Plasticity in Advanced Rehabilitation of Facial Paralysis.

OBJECTIVE: Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients' quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms. METHODS: Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP. RESULTS: Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group. CONCLUSIONS: Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies.

Frailty Status, Sedentary Behaviors, and Risk of Incident Bone Fractures.

BACKGROUND: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors. METHODS: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures. RESULTS: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001). CONCLUSIONS: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time.

Facial Symmetry Enhancement and Brain Network Modifications in Surgical Facial Palsy Patients After BoNT-A Treatment on the Unaffected Side.

BACKGROUND: Facial palsy, often resulting from trauma or iatrogenic treatments, leads to significant esthetic and functional impairment. Surgical interventions, such as masseteric-to-facial nerve transfer combined with static suspension, are frequently recommended to restore facial nerve function and symmetry. METHODS: This study examines how Botulinum Toxin A (BoNT-A) treatment on the unaffected side affects facial symmetry and brain connectivity in patients with severe oral commissure droop from facial nerve damage. Patients were divided into two groups: one received BoNT-A injections on the unaffected side, and the other did not. RESULTS: Our findings revealed that BoNT-A treatment not only improved facial symmetry but also induced significant modifications in brain functional network connectivity. These modifications extended beyond the sensorimotor network, involving high-level cognitive processes, and exhibited a significant correlation with the degree of facial asymmetry. CONCLUSIONS: These results provide valuable insights into the mechanisms underlying the positive effects of BoNT-A intervention on motor recovery and brain plasticity in facial palsy patients. Furthermore, the study emphasizes the importance of a multidisciplinary approach to facial palsy rehabilitation. Understanding these intricate interactions between facial symmetry restoration and brain network adaptations may pave the way for more effective treatments and improved quality of life for individuals dealing with facial palsy.

Surface Modification of Calcined Kaolinite for Enhanced Solvent Dispersion and Mechanical Properties in Polybutylene Adipate/Terephthalate Composites.

In order to regulate the surface properties of calcined kaolinite for the purpose of achieving uniform distribution within various polar dispersion media, 3-aminopropyltriethoxysilane and phenyl glycidyl ether were employed to chemically modify calcined kaolinite. The grafting rate, surface properties, and dispersion properties of calcined kaolinite particles in different polar organic media were changed by varying the dosage of the modifiers. FT-IR analysis confirmed successful surface modification, while thermogravimetric analysis indicated a maximum graft coverage of 18.44 µmol/m2 for the modified particles. Contact angle measurements and particle size distribution analyses demonstrated the effective adjustment of surface characteristics by the modifiers. Specifically, at a mass ratio of 1.0 of modifier to kaolinite particles, the modified particles exhibited a contact angle of around 125°, achieving uniform dispersion in different polarity media. Particle size distribution ranged from 1600 nm to 2100 nm in cyclohexane and petroleum ether, and from 900 nm to 1200 nm in dioxane, ethyl acetate, and DMF, showcasing a significant improvement in dispersion performance compared to unmodified particles. Concurrently, to improve the mechanical properties of PBAT, modified particles were incorporated into the PBAT matrix, and the effect of modified particle addition on the tensile strength and fracture tensile rate of the composites was investigated. The optimal amount of modified particles is 6 wt.%~8 wt.%. This article aims at synthesizing modifier molecules containing different hydrophilic and hydrophobic groups to chemically graft onto the surface of calcined kaolinite. The hydrophilic and hydrophobic groups on the modified particles can adapt to dispersed systems of different polarities and achieve good distribution within them. The modified particles are added to PBAT to achieve good compatibility and enhance the mechanical properties of the composite material.

Association between timing of labor induction and neonatal and maternal outcomes: an observational study from China.

BACKGROUND: Growing evidence suggests that elective induction of labor at 39 weeks' gestation may lead to more favorable perinatal outcomes than expectant management, however, how to weigh the pros and cons of elective labor induction at 39 weeks, the expectation of spontaneous delivery at 40 or 41 weeks, or delayed labor induction at 40 or 41 weeks on neonatal and maternal outcomes remains a practical challenge in clinical decision-making. OBJECTIVE: We compared the neonatal and maternal outcomes between elective induction of labor at 39 weeks' gestation and expectant management in a real-world setting. We also divided the expectantly managed group and compared outcomes of the spontaneous delivery at 40 or 41 weeks' gestation group and the induced group at 40 or 41 weeks' gestation with those of the elective induction at 39 weeks' gestation group. STUDY DESIGN: This retrospective cohort study included 21,282 participants who delivered between January 1, 2019, and June 30, 2022. Participants were initially categorized into 3 groups at 39 weeks' gestation, namely elective induction of labor, spontaneous delivery, and expectant management, for the primary analysis in which elective induction was compared with expectant management. Subsequently, the expectant management group at 39 weeks' gestation was divided into 3 groups at 40 weeks, and participants who underwent expectant management at 40 weeks were then divided into 2 groups at 41 weeks' gestation, namely elective induction and spontaneous delivery. In total, 6 groups were compared in the secondary analysis with the elective induction at 39 weeks' gestation group serving as the reference group. RESULTS: At 39 weeks' gestational age, participants who underwent elective induction of labor had a significantly lower risk for the primary composite outcomes than participants who were managed expectantly (adjusted odds ratio, 0.72; 95% confidence interval, 0.55-0.95), and there was no significant difference in the risk for cesarean delivery between the 2 groups. After further dividing the expectantly managed group and comparing them with participants who underwent elective induction of labor at 39 weeks' gestation, those who underwent spontaneous delivery at 40 weeks' gestation had significantly lower risks for cesarean delivery (0.61; 0.52-0.71) and chorioamnionitis (0.78; 0.61-1.00) but a higher risk for fetal distress (1.39; 1.22-1.57); those with spontaneous delivery at 41 weeks' gestation had a significantly higher risk for fetal distress (1.44; 1.16-1.79), postpartum hemorrhage (1.83; 1.26-2.66), and prolonged or arrested labor (1.61; 1.02-2.54). Moreover, when compared with participants who underwent elective induction of labor at 39 weeks' gestation, participants who were induced later in gestation had significantly higher risks for adverse neonatal and maternal outcomes, especially at 40 weeks' gestation. CONCLUSION: Our findings indicate that elective induction of labor at 39 weeks' gestation was significantly associated with lower risks for adverse short-term neonatal and maternal outcomes when compared with expectant management. Moreover, our study highlights the nuanced trade-offs in risks and benefits between elective induction at 39 weeks' gestation and waiting for spontaneous labor or delayed induction at 40 or 41 weeks' gestation, thus providing valuable insights for clinical decision-making in practice.

Mitochondria-endoplasmic reticulum crosstalk in apoptosis: The interactions of cytochrome c with monooxygenase and its reductase.

The crosstalk between endoplasmic reticulum and mitochondria is of significance in apoptosis, in which cytochrome b5 (Cyt b5) is thought to be a major target for cytochrome c (Cyt c) upon its release from the mitochondria. In the absence of Cyt b5, the role of interactions of Cyt c with CYP-dependent monooxygenase system in apoptotic regulation was explored in this study. NADPH-dependent and Cyt c-induced formation of reactive oxygen species (ROS) and NADPH-independent Cyt c unfolding were revealed. With the aid of a CPR inhibitor and CYP antibodies, the interactions among Cyt c, cytochrome P450 reductase (CPR) and cytochrome P450 (CYP) are evidenced, which are found crucial for monooxygenase-derived ROS formation. The underlying structural basis of Cyt c-CYP complex was unveiled by molecular dynamics simulations. This study provides novel insights into how Cyt c regulates ROS formation through the interactions with CPR and CYP, and is implicated for a deeper understanding of the regulation mechanism in the mitochondria-endoplasmic reticulum apoptotic pathway.

Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.

AIM: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (pinteraction = 0.017, 0.033 and 0.014, respectively). CONCLUSION: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

Ellagic acid ameliorates arsenic-induced neuronal ferroptosis and cognitive impairment via Nrf2/GPX4 signaling pathway.

Arsenic, a neurotoxic metalloid, poses significant health risks. However, ellagic acid, renowned for its antioxidant properties, has shown potential in neuroprotection. This study aimed to investigate the neuroprotective effects of ellagic acid against arsenic-induced neuronal ferroptosis and cognitive impairment and elucidate the underlying mechanisms. Using an arsenic-exposed Wistar rat model and an arsenic-induced HT22 cells model, we assessed cognitive ability, measured serum and brain arsenic levels, and evaluated pathological damage through histological analysis and transmission electron microscopy. Additionally, we examined oxidative stress and iron ion levels using GSH, MDA, ROS and tissue iron biochemical kits, and analyzed the expression of ferroptosis-related markers using western blot and qRT-PCR. Our results revealed that arsenic exposure increased both serum and brain arsenic levels, resulting in hippocampal pathological damage and subsequent decline in learning and memory abilities. Arsenic-induced neuronal ferroptosis was mediated by the inhibition of the xCT/GSH/GPX4/Nrf2 signaling axis and disruption of iron metabolism. Notably, ellagic acid intervention effectively reduced serum and brain arsenic levels, ameliorated neuronal damage, and improved oxidative stress, ferroptosis, and cognitive impairment. These beneficial effects were associated with the activation of the Nrf2/Keap1 signaling pathway, upregulation of GPX4 expression, and enhanced iron ion excretion. In conclusion, ellagic acid demonstrates promising neuroprotective effects against arsenic-induced neurotoxicity by mitigating neuronal ferroptosis and cognitive impairment.