Interface-induced dual-pinning mechanism enhances low-frequency electromagnetic wave loss.

Improving the absorption of electromagnetic waves at low-frequency bands (2-8 GHz) is crucial for the increasing electromagnetic (EM) pollution brought about by the innovation of the fifth generation (5G) communication technology. However, the poor impedance matching and intrinsic attenuation of material in low-frequency bands hinders the development of low-frequency electromagnetic wave absorbing (EMWA) materials. Here we propose an interface-induced dual-pinning mechanism and establish a magnetoelectric bias interface by constructing bilayer core-shell structures of NiFe2O4 (NFO)@BiFeO3 (BFO)@polypyrrole (PPy). Such heterogeneous interface could induce distinct magnetic pinning of the magnetic moment in the ferromagnetic NFO and dielectric pinning of the dipole rotation in PPy. The establishment of the dual-pinning effect resulted in optimized impedance and enhanced attenuation at low-frequency bands, leading to better EMWA performance. The minimum reflection loss (RLmin) at thickness of 4.43 mm reaches -65.30 dB (the optimal absorption efficiency of 99.99997%), and the effective absorption bandwidth (EAB) can almost cover C-band (4.72 ~ 7.04 GHz) with low filling of 15.0 wt.%. This work proposes a mechanism to optimize low-frequency impedance matching with electromagnetic wave (EMW) loss and pave an avenue for the research of high-performance low-frequency absorbers.

LRP1 in GABAergic neurons is a key link between obesity and memory function.

OBJECTIVE: Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood-brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. METHODS: Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age. RESULTS: Deletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition. CONCLUSIONS: Our findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity.

Plasmonic nanosensor and pressure-induced transparency based on coupled resonator in a nanoscale system.

Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800 nm/RIU and 7.4 nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.

[Progress on treatment of acetabular quadrilateral plate injury].

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years. Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles. A perfect classification needs to describe the displacement of bone mass in three-dimensional space to better guide reduction and fixation. The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus. Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect volume and revision techniques are still a hot topic. In this paper,the viewpoints of three-dimensional network structure of acetabular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.

Pleiotropic Role of Rainbow Trout CXCRs in Response to Disease and Environment: Insights from Transcriptional Signatures and Structure Analysis.

Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4, kidney cxcr3 and cxcr4, and spleen cxcr3, cxcr4, and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1, kidney cxcr1 and cxcr7, and liver cxcr2, cxcr3, and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.

Whole genome identification, molecular docking and expression analysis of enzymes involved in the selenomethionine cycle in Cardamine hupingshanensis.

BACKGROUND: The selenomethionine cycle (SeMTC) is a crucial pathway for the metabolism of selenium. The basic bioinformatics and functions of four enzymes involved in the cycle including S-adenosyl-methionine synthase (MAT), SAM-dependent methyltransferase (MTase), S-adenosyl-homocysteine hydrolase (SAHH) and methionine synthase (MTR), have been extensively reported in many eukaryotes. The identification and functional analyses of SeMTC genes/proteins in Cardamine hupingshanensis and their response to selenium stress have not yet been reported. RESULTS: In this study, 45 genes involved in SeMTC were identified in the C. hupingshanensis genome. Phylogenetic analysis showed that seven genes from ChMAT were clustered into four branches, twenty-seven genes from ChCOMT were clustered into two branches, four genes from ChSAHH were clustered into two branches, and seven genes from ChMTR were clustered into three branches. These genes were resided on 16 chromosomes. Gene structure and homologous protein modeling analysis illustrated that proteins in the same family are relatively conserved and have similar functions. Molecular docking showed that the affinity of SeMTC enzymes for selenium metabolites was higher than that for sulfur metabolites. The key active site residues identified for ChMAT were Ala269 and Lys273, while Leu221/231 and Gly207/249 were determined as the crucial residues for ChCOMT. For ChSAHH, the essential active site residues were found to be Asn87, Asp139 and Thr206/207/208/325. Ile204, Ser111/329/377, Asp70/206/254, and His329/332/380 were identified as the critical active site residues for ChMTR. In addition, the results of the expression levels of four enzymes under selenium stress revealed that ChMAT3-1 genes were upregulated approximately 18-fold, ChCOMT9-1 was upregulated approximately 38.7-fold, ChSAHH1-2 was upregulated approximately 11.6-fold, and ChMTR3-2 genes were upregulated approximately 28-fold. These verified that SeMTC enzymes were involved in response to selenium stress to varying degrees. CONCLUSIONS: The results of this research are instrumental for further functional investigation of SeMTC in C. hupingshanensis. This also lays a solid foundation for deeper investigations into the physiological and biochemical mechanisms underlying selenium metabolism in plants.

Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in zebrafish.

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 µM), medium (5 µM), and high (10 µM), while for PRA, the corresponding concentrations were set at low (18 µM), medium (180 µM), and high (270 µM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.

Characterization of the MIKCC-type MADS-box gene family in blueberry and its possible mechanism for regulating flowering in response to the chilling requirement.

MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.

Potential Role of Bmal1 in Lipopolysaccharide-Induced Depression-Like Behavior and its Associated "Inflammatory Storm".

Inflammation plays an important role in the pathogenesis of depression; however, the underlying mechanisms remain unclear. Apart from the disordered circadian rhythm in animal models and patients with depression, dysfunction of clock genes has been reported to be involved with the progress of inflammation. This study aimed to investigate the role of circadian clock genes, especially brain and muscle ARNT-like 1 (Bmal1), in the linkage between inflammation and depression. Lipopolysaccharide (LPS)-challenged rats and BV2 cells were used in the present study. Four intraperitoneal LPS injections of 0.5 mg/kg were administered once every other day to the rats, and BV2 cells were challenged with LPS for 24 h at the working concentration of 1 mg/L, with or without the suppression of Bmal1 via small interfering RNA. The results showed that LPS could successfully induce depression-like behaviors and an "inflammatory storm" in rats, as indicated by the increased immobility time in the forced swimming test and the decreased saccharin preference index in the saccharin preference test, together with hyperactivity of the hypothalamic-pituitary-adrenal axis, hyperactivation of astrocyte and microglia, and increased peripheral and central abundance of tumor necrosis factor-α, interleukin 6, and C-reactive protein. Moreover, the protein expression levels of brain-derived neurotrophic factor, triggering receptor expressed on myeloid cells 1, Copine6, and Synaptotagmin1 (Syt-1) decreased in the hippocampus and hypothalamus, whereas the expression of triggering receptor expressed on myeloid cells 2 increased. Interestingly, the fluctuation of temperature and serum concentration of melatonin and corticosterone was significantly different between the groups. Furthermore, protein expression levels of the circadian locomotor output cycles kaput, cryptochrome 2, and period 2 was significantly reduced in the hippocampus of LPS-challenged rats, whereas Bmal1 expression was significantly increased in the hippocampus but decreased in the hypothalamus, where it was co-located with neurons, microglia, and astrocytes. Consistently, apart from the reduced cell viability and increased phagocytic ability, LPS-challenged BV2 cells presented a similar trend with the changed protein expression in the hippocampus of the LPS model rats. However, the pathological changes in BV2 cells induced by LPS were reversed after the suppression of Bmal1. These results indicated that LPS could induce depression-like pathological changes, and the underlying mechanism might be partly associated with the imbalanced expression of Bmal1 and its regulated dysfunction of the circadian rhythm.

Deficiency of Acetyltransferase nat10 in Zebrafish Causes Developmental Defects in the Visual Function.

Purpose: N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification catalyzed by N-acetyltransferase 10 (NAT10), a critical factor known to influence mRNA stability. However, the role of ac4C in visual development remains unexplored. Methods: Analysis of public datasets and immunohistochemical staining were conducted to assess the expression pattern of nat10 in zebrafish. We used CRISPR/Cas9 and RNAi technologies to knockout (KO) and knockdown (KD) nat10, the zebrafish ortholog of human NAT10, and evaluated its effects on early development. To assess the impact of nat10 knockdown on visual function, we performed comprehensive histological evaluations and behavioral analyses. Transcriptome profiling and real-time (RT)-PCR were utilized to detect alterations in gene expression resulting from the nat10 knockdown. Dot-blot and RNA immunoprecipitation (RIP)-PCR analyses were conducted to verify changes in ac4C levels in both total RNA and opsin mRNA specifically. Additionally, we used the actinomycin D assay to examine the stability of opsin mRNA following the nat10 KD. Results: Our study found that the zebrafish NAT10 protein shares similar structural properties with its human counterpart. We observed that the nat10 gene was prominently expressed in the visual system during early zebrafish development. A deficiency of nat10 in zebrafish embryos resulted in increased mortality and developmental abnormalities. Behavioral and histological assessments indicated significant vision impairment in nat10 KD zebrafish. Transcriptomic analysis and RT-PCR identified substantial downregulation of retinal transcripts related to phototransduction, light response, photoreceptors, and visual perception in the nat10 KD group. Dot-blot and RIP-PCR analyses confirmed a pronounced reduction in ac4C levels in both total RNA and specifically in opsin messenger RNA (mRNA). Additionally, by evaluating mRNA decay in zebrafish treated with actinomycin D, we observed a significant decrease in the stability of opsin mRNA in the nat10 KD group. Conclusions: The ac4C-mediated mRNA modification plays an essential role in maintaining visual development and retinal function. The loss of NAT10-mediated ac4C modification results in significant disruptions to these processes, underlining the importance of this RNA modification in ocular development.

PI3Kγ maintains the self-renewal of acute myeloid leukemia stem cells by regulating the pentose phosphate pathway.

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML.

[Feasibility of a novel type of complex anterior cervical fixation by using Mimics software].

OBJECTIVE: To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation -- anterior transpedicular screw fixation+zero notch internal fixation. METHODS: From January 2021 to September 2022, 50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning, including 27 males and 23 females, aged from 25 to 65 years old with an average of (46.0 ± 9.0) years old. The dicom format is exported and engraved into the CD, and use the mimics software to perform 3D reconstruction of each segment. A simulated screw is placed on the image according to the critical value of zero notch screw (head and tail angle 44°, internal angle 29°). The position of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation. RESULTS: For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position, with no instances of intersection with ATPS. For the lower zero notch screw, in C3-C4 and C4-C5, 4 out of 50 subjects are in the safe position in the three-dimensional images of cervical vertebrae, and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9) ° and (36.1±2.2) °, respectively. In C5-C6 and C6-C7 segments, no lower zero notch screws intersected with ATPS, and all screws are in safe positions. CONCLUSION: Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.

Measurement of anatomical parameters of anterior transpedicular root screw intervertebral fusion system of cervical spine.

OBJECTIVE: This study aims to investigate the feasibility of the anterior transpedicular root screw (ATPRS) intervertebral fusion system for the cervical spine and provide a basis for the design of the ATPRS intervertebral fusion system. METHODS: A total of 60 healthy adult cervical spine CT images examined from our hospital were selected, including 30 males and 30 females, with an average age of 39.6 ± 4.8 years. The image data was imported into Mimics 21.0 software in DICOM format for 3D model reconstruction. Simulated screw insertion was performed on both sides of the midline of the intervertebral space. The entry point (P1) was determined when the upper and lower screw paths did not overlap. When the screw was tangent to the medial edge of the Luschka joint, the insertion point was determined as the entry point (P2). Measurements were taken and recorded for the following parameters: distance from the screw entry point to the midline of the intervertebral space (DPM), the simulated screw length, inclination angle, cranial/caudal tilted angle, the anterior-posterior (AP) and mediolateral (ML) diameters of the cervical intervertebral space, the heights of the anterior, middle, and posterior edges of the cervical intervertebral space, and the curvature diameter of the lower end plate of the cervical vertebral body. Statistical analysis was performed on the measurement results. RESULTS: The screw entry area (P1P2) showed an increasing trend from C3-C7 in both male (2.92-6.08 mm) and female (2.32-5.12 mm) groups. There were statistical differences between men and women at the same level (P < 0.05). The average screw length of men and women was greater than 20 mm, and the upper and lower screw lengths showed an increasing trend from C3 to C7. In the area where screws could be inserted, the range of screw inclination was as follows: male group upper screw (47.73-66.76°), lower screw (48.05-65.35°); female group upper screw (49.15-65.66°) and lower screw (49.42-63.29°); The range of cranial/caudal tilted angle of the screw was as follows: male group upper screw (32.06-39.56°), lower screw (29.12-36.95°); female group upper screw (30.97-38.92°) and lower screw (27.29-37.20°). The anterior-posterior diameter and mediolateral diameter of the cervical intervertebral space showed an increasing trend from C3 to C7 in both male and female groups. The middle height (MH) of the cervical intervertebral space was greater than the anterior edge height (AH) and posterior edge height (PD), with statistical differences (P < 0.05). CONCLUSIONS: Through the study of CT images of the cervical spine, it was determined that the ATPRS intervertebral fusion system has a feasible area for screw insertion in the cervical intervertebral space.

Comparison of clinical characteristics between adult-onset and juvenile-onset non-radiographic axial spondyloarthritis in Chinese patients: results from the COCAS cohort.

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. We aimed to describe the clinical characteristics of patients with non-radiographic axSpA (nr-axSpA) in China and compare the differences between adult- and juvenile-onset cases. METHODS: A cross-sectional study was conducted using data from 776 patients with nr-axSpA in the Clinical Characteristic and Outcome in Chinese Axial Spondyloarthritis (COCAS) study cohort. Patients were divided into two groups including the adult-onset group (n = 662) and the juvenile-onset group (n = 114) according to age at disease onset. Baseline demographics and clinical characteristics were compared between patients with adult-onset and juvenile-onset nr-axSpA. RESULTS: Overall, the male-to-female ratio was 1.26:1, the prevalence of HLA-B27 positivity was 72.2%, and the median age at disease onset of nr-axSpA was 22 years. Nearly 75% of nr-axSpA patients had peripheral arthritis in the disease course, and the prevalence of extra-articular manifestations was 10.4%. The juvenile-onset group contained a higher proportion of men (66.7% vs. 53.9%, P = 0.011) and a longer baseline disease duration (4.0 [4.0] vs. 1.6 [3.5], P < 0.001) than the adult-onset group. A family history of spondyloarthritis was more frequent in the juvenile-onset group than in the adult-onset group (23.7% vs. 15.4%, P = 0.028), but no significant difference in the prevalence of HLA-B27 positivity was observed between the two groups (P = 0.537). Regarding initial symptoms, peripheral arthritis occurred more often in patients with juvenile-onset nr-axSpA, whereas patients with adult-onset nr-axSpA presented more frequently with axial involvement. The prevalence of inflammatory back pain (IBP) was higher in the adult-onset group than in the juvenile-onset group (85.0% vs. 75.4%, P = 0.010), whereas the juvenile-onset group showed a higher prevalence of peripheral arthritis and enthesitis than the adult-onset group (67.5% vs. 48.5%, P < 0.001; 35.1% vs. 23.3%, P = 0.007, respectively). CONCLUSIONS: Compared with adult-onset nr-axSpA, juvenile-onset nr-axSpA was more common in men and those with a family history of spondyloarthritis. Juvenile-onset nr-axSpA presents with a "peripheral predominant" mode at disease onset and a higher frequency of peripheral arthritis and enthesitis during the disease course.

[Effect of High-Concentration Uric Acid on Nitric Oxide].

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.

Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis.

BACKGROUND: Studies investigating the association between single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and the efficacy of adalimumab (ADA) in ankylosing spondylitis (AS) therapy have reported conflicting results. We aimed to investigate the value of SNP typing of TNFα in predicting the efficacy of ADA in AS. MATERIALS AND METHODS: Eighty patients with active AS who received ADA treatment were followed up for 24 weeks. Six known SNPs of TNFα (+489G/A, -238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were subjected to the SNaPshot SNP typing method, which has been proven to be a reliable, efficient, and cost-effective method for detecting SNPs. The relationship between each SNP genotype and the therapeutic efficacy of ADA was analyzed. RESULTS: At the end of the 24-week follow-up, 58.8% of the patients with AS achieved Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), 67.5% of the patients achieved the criteria of an ASAS40 response (40% improvement on indices), and 53.8% of the patients achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement (MI). The univariate analysis showed that patients with AS carrying the TNFα +489 A allele were more likely to achieve ASAS-PR, ASAS40 response criteria, and ASDAS-MI after ADA treatment. In the multivariate regression analysis, the TNFα +489 A allele was an independent factor influencing the efficacy of ADA in treating AS (ASAS-PR odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.01-7.01; ASAS40 OR = 4.56, 95% CI = 1.39-15.00; ASDAS-MI OR = 3.31, 95% CI = 1.02-10.69). CONCLUSIONS: The patients carrying the TNFα +489 A allele may be more likely to experience better therapeutic efficacy and achieve the treatment target (ASAS-PR, ASAS40 response, or ASDAS-MI) after receiving ADA treatment. Detection of TNFα +489 G/A may predict the therapeutic efficacy of ADA, which can be used in clinical practice to tailor treatment for individual patients with AS. Further studies with larger sample sizes and longer follow-up periods with imaging evaluation are needed to verify our findings.

Divergent Pharmacology and Biased Signaling of the Four Melanocortin-4 Receptor Isoforms in Rainbow Trout (Oncorhynchus mykiss).

The melanocortin-4 receptor (MC4R) is essential for the modulation of energy balance and reproduction in both fish and mammals. Rainbow trout (Oncorhynchus mykiss) has been extensively studied in various fields and provides a unique opportunity to investigate divergent physiological roles of paralogues. Herein we identified four trout mc4r (mc4ra1, mc4ra2, mc4rb1, and mc4rb2) genes. Four trout Mc4rs (omMc4rs) were homologous to those of teleost and mammalian MC4Rs. Multiple sequence alignments, a phylogenetic tree, chromosomal synteny analyses, and pharmacological studies showed that trout mc4r genes may have undergone different evolutionary processes. All four trout Mc4rs bound to two peptide agonists and elevated intracellular cAMP levels dose-dependently. High basal cAMP levels were observed at two omMc4rs, which were decreased by Agouti-related peptide. Only omMc4rb2 was constitutively active in the ERK1/2 signaling pathway. Ipsen 5i, ML00253764, and MCL0020 were biased allosteric modulators of omMc4rb1 with selective activation upon ERK1/2 signaling. ML00253764 behaved as an allosteric agonist in Gs-cAMP signaling of omMc4rb2. This study will lay the foundation for future physiological studies of various mc4r paralogs and reveal the evolution of MC4R in vertebrates.

Cuproptosis-related genes signature and validation of differential expression and the potential targeting drugs in temporal lobe epilepsy.

Introduction: Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear. Methods: We first investigated the copper ion concentration in the hippocampus tissue. Then, using the Sample dataset and E-MTAB-3123 dataset, we analyzed the features of 12 cuproptosis-related genes in TLEs and controls using the bioinformatics tools. Then, the expression of the key cuproptosis genes were confirmed using real-time PCR and immunohistochemical staining (IHC). Finally, the Enrichr database was used to screen the small molecules and drugs targeting key cuproptosis genes in TLE. Results: The Sample dataset displayed four differentially expressed cuproptosis-related genes (DECRGs; LIPT1, GLS, PDHA1, and CDKN2A) while the E-MTAB-3123 dataset revealed seven DECRGs (LIPT1, DLD, FDX1, GLS, PDHB, PDHA1, and DLAT). Remarkably, only LIPT1 was uniformly upregulated in both datasets. Additionally, these DECRGs are implicated in the TCA cycle and pyruvate metabolism-both crucial for cell cuproptosis-as well as various immune cell infiltrations, especially macrophages and T cells, in the TLE hippocampus. Interestingly, DECRGs were linked to most infiltrating immune cells during TLE's acute phase, but this association considerably weakened in the latent phase. In the chronic phase, DECRGs were connected with several T-cell subclasses. Moreover, LIPT1, FDX1, DLD, and PDHB were related to TLE identification. PCR and IHC further confirmed LIPT1 and FDX1's upregulation in TLE compared to controls. Finally, using the Enrichr database, we found that chlorzoxazone and piperlongumine inhibited cell cuproptosis by targeting LIPT1, FDX1, DLD, and PDHB. Conclusion: Our findings suggest that cuproptosis is directly related to TLE. The signature of cuproptosis-related genes presents new clues for exploring the roles of neuronal death in TLE. Furthermore, LIPT1 and FDX1 appear as potential targets of neuronal cuproptosis for controlling TLE's seizures and progression.

A Novel Strategy for Detecting Permittivity and Loss Tangent of Low-Loss Materials Based on Cylindrical Resonant Cavity.

Accurate measurement of the permittivity and loss tangent of low-loss materials is essential due to their special applications in the field of ultra large scale integrated circuits and microwave devices. In this study, we developed a novel strategy that can accurately detect the permittivity and loss tangent of low-loss materials based on a cylindrical resonant cavity supporting the TE111 mode in X band (8-12 GHz). Based on an electromagnetic field simulation calculation of the cylindrical resonator, permittivity is precisely retrieved by exploring and analyzing the perturbation of the coupling hole and sample size on the cutoff wavenumber. A more precise approach to measuring the loss tangent of samples with various thicknesses has been proposed. The test results of the standard samples verify that this method can accurately measure the dielectric properties of samples that have smaller sizes than the high Q cylindrical cavity method.

Identification, characterization, and transcription of serotonin receptors in rainbow trout (Oncorhynchus mykiss) in response to bacterial infection and salinity changes.

Serotonergic system is involved in the regulation of physiological functions and behavioral traits including cognition, memory, aggression, stress coping, appetite and immunomodulation. Serotonin exerts its functions via binding distinct serotonin receptors which are classified into 7 groups. Salmonid exhibits expanded functional gene copies due to salmonid-specific whole genome duplication. However, serotonin receptor (htr) repertoire is not fully identified in rainbow trout (Oncorhynchus mykiss). In this study, we identified 39 htr genes, including 14 htr1, 4 htr2, 4 htr2 like, 3 htr3, 4 htr4, 2 htr5, 2 htr6, and 6 htr7 subtypes. We investigated physiological functions of serotonin receptors in response to bacterial pathogens exposure and salinity changes. We showed htr1, htr2, htr4 and htr7 subtypes were associated with immunomodulation in response to Vibrio anguillarum or Aeromonas salmonicida infection. Saltwater (salinity of 15) transfer significantly altered htr1, htr2, htr4, and htr7 subtypes, suggesting trout Htr was associated with osmoregulation. We further showed residues interacted with inverse agonist (methiothepin) and serotonin analogue (5-Carboxamidotryptamine) were conserved between trout and human, suggesting exogenous ligands targeting human HTRs might have a role in aquaculture. This study showed duplicated trout Htrs might be physiologically neofunctionalized and potentially exhibit pleiotropic effects in regulating immunomodulation and osmoregulation.