📋 Browse Articles

Procedural learning has been mainly tested through motor sequence learning tasks in children with neurodevelopmental disorders, especially with isolated Developmental Coordination Disorder (DCD) and Reading Disorder (RD). Studies on motor adaptation are scarcer and more controversial. This study aimed to compare the performance of children with isolated and associated DCD and RD in a graphomotor adaptation task. In total, 23 children with RD, 16 children with DCD, 19 children with DCD-RD, and 21 typically developing (TD) children wrote trigrams both in the conventional (from left to right) and opposite (from right to left) writing directions. The results show that movement speed and accuracy were more impacted by the adaptation condition (opposite writing direction) in children with neurodevelopmental disorders than TD children. Our results also reveal that children with RD have less difficulty adapting their movement than children with DCD. Children with DCD-RD had the most difficulty, and analysis of their performance suggests a cumulative effect of the two neurodevelopmental disorders in motor adaptation. Show less

Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens. Show less

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic-related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/β-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/β-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders. Show less

This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into dough system to explore their intervention effects on structural and technological properties of dough as well as physical and digestion properties of biscuits. Results showed that HPL (pullulan with molecule weight of 100- 300 kDa) could increase the intermolecular collisions, prompt the protein aggregation and limit the water migration in dough system, resulting in an integrate, continuous and dense network structure of the gel with strengthened elasticity and weakened extensibility, which caused an increase in biscuit thickness, hardness and crispness. On the contrary, LPL (pullulan with molecule weight of 3- 100 kDa) could go against the formation of stable and elastic dough through breaking down cross-linkage between protein and starch so as to provide biscuits with decreased hardness and crispness during baking. Both HPL and LPL delayed starch pasting and retrogradation process while HPL had the stronger retarding effect on starch digestibility of biscuits than LPL. These findings dedicated to a better understanding of pullulan function in dough system and provide suggestions for fractionation applications of pullulan in food field. Show less

Although polarized light can assist many animals in performing special visual tasks, current polarized light pollution (PLP) caused by urban construction has been shown to induce maladaptive behaviors of PL-sensitive animals and change ecological interactions. However, the underlying mechanisms remain unclear. Our previous work hypothesized that linearly polarized light (LPL) is an ecological trap for Oratosquilla oratoria, a common Stomatopoda species in the China Sea. Here we explored the underlying negative effects of artificially LPL on O. oratoria based on comparative transcriptomics. We identified 3616 differentially expressed genes (DEGs) in O. oratoria compound eyes continuous exposed to natural light (NL) and LPL scenarios. In comparison with the NL scenario, a total of 1972 up- and 1644 down- regulated genes were obtained from the O. oratoria compound eyes under LPL scenario, respectively. Furthermore, we performed functional annotation of those DEGs described above and identified 65 DEGs related to phototransduction, reproduction, immunity, and synapse. Based on the functional information, we suspected that continuous LPL exposure could block the light transmission, disrupt the reproductive process, and lead to the progressive failure of the immune response of O. oratoria. In conclusion, this study is the first to systematically describe the negative effects of artificial LPL exposure on O. oratoria at the genetic level, and it can improve the biological conservation theory behind PLP. Show less

MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated. Show less

On-chip polarization-sensitive photodetectors are highly desired for ultra-compact optoelectronic systems. It has been demonstrated that polarization-sensitive photodetection can be realized using intrinsic chiral and anisotropy materials. However, these photodetectors can only realize the detection of either circularly polarized light (CPL) or linear polarized light (LPL) and are not applicable to multiple-polarization-sensitive photodetection. Herein, we experimentally demonstrate a metasurface-integrated semiconductor to realize multiple-polarization-sensitive photodetection at visible wavelengths. This device is composed of a MoSe Show less

Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D). We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases). Proteomic-based risk models were developed with discrimination, calibration, reclassification assessed using area under the curve (AUC), calibration plots, and net reclassification index (NRI), respectively. Two-sample Mendelian randomization (MR) analyses using cis-protein quantitative trait loci identified in a genome-wide association study of CKB and UK Biobank for specific proteins were conducted to assess their causal relevance for T2D, along with colocalization analyses to examine shared causal variants between proteins and T2D. Overall, 33 proteins were significantly associated (false discovery rate <0.05) with risk of incident T2D, including IGFBP1, GHR, and amylase. The addition of these 33 proteins to a conventional risk prediction model improved AUC from 0.77 (0.73-0.82) to 0.88 (0.85-0.91) and NRI by 38%, with predicted risks well calibrated with observed risks. MR analyses provided support for the causal relevance for T2D of ENTR1, LPL, and PON3, with replication of ENTR1 and LPL in Europeans using different genetic instruments. Moreover, colocalization analyses showed strong evidence (pH4 > 0.6) of shared genetic variants of LPL and PON3 with T2D. Proteomic analyses in Chinese adults identified novel associations of multiple proteins with T2D with strong genetic evidence supporting their causal relevance and potential as novel drug targets for prevention and treatment of T2D. Show less

Angiopoietin-like 3 (ANGPTL3) acts as an inhibitor of lipoprotein lipase (LPL), impeding the breakdown of triglyceride-rich lipoproteins (TGRLs) in circulation. Targeting ANGPTL3 is considered a novel strategy for improving dyslipidemia and atherosclerotic cardiovascular diseases (ASCVD). Hops (Humulus lupulus L.) contain several bioactive prenylflavonoids, including xanthohumol (Xan), isoxanthohumol (Isoxan), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN), with the potential to manage lipid metabolism. The aim of this study was to investigate the lipid-lowering effects of Xan, the effective prenylated chalcone in attenuating ANGPTL3 transcriptional activity, both in vitro using hepatic cells and in vivo using zebrafish models, along with exploring the underlying mechanisms. Xan (10 and 20 μM) significantly reduced ANGPTL3 mRNA and protein expression in HepG2 and Huh7 cells, leading to a marked decrease in secreted ANGPTL3 proteins via hepatic cells. In animal studies, orally administered Xan significantly alleviated plasma triglyceride (TG) and cholesterol levels in zebrafish fed a high-fat diet. Furthermore, it reduced hepatic ANGPTL3 protein levels and increased LPL activity in zebrafish models, indicating its potential to modulate lipid profiles in circulation. Furthermore, molecular docking results predicted that Xan exhibits a higher binding affinity to interact with liver X receptor α (LXRα) and retinoic acid X receptor (RXR) than their respective agonists, T0901317 and 9-Cis-retinoic acid (9-Cis-RA). We observed that Xan suppressed hepatic ANGPTL3 expression by antagonizing the LXRα/RXR-mediated transcription. These findings suggest that Xan ameliorates dyslipidemia by modulating the LXRα/RXR-ANGPTL3-LPL axis. Xan represents a novel potential inhibitor of ANGPTL3 for the prevention or treatment of ASCVD. Show less

Although stem cells are a promising avenue for harnessing the potential of adipose tissue, conventional two-dimensional (2D) culture methods have limitations. This study explored the use of three-dimensional (3D) cultures to preserve the regenerative potential of adipose-derived stem cells (ADSCs) and investigated their cellular properties. Flow cytometric analysis revealed significant variations in surface marker expressions between the two culture conditions. While 2D cultures showed robust surface marker expressions, 3D cultures exhibited reduced levels of CD44, CD90.2, and CD105. Adipogenic differentiation in 3D organotypic ADSCs faced challenges, with decreased organoid size and limited activation of adipogenesis-related genes. Key adipocyte markers, such as lipoprotein lipase (LPL) and adipoQ, were undetectable in 3D-cultured ADSCs, unlike positive controls in 2D-cultured mesenchymal stem cells (MSCs). Surprisingly, 3D-cultured ADSCs underwent mesenchymal-epithelial transition (MET), evidenced by increased E-cadherin and EpCAM expression and decreased mesenchymal markers. This study highlights successful ADSC organoid formation, notable MSC phenotype changes in 3D culture, adipogenic differentiation challenges, and a distinctive shift toward an epithelial-like state. These findings offer insights into the potential applications of 3D-cultured ADSCs in regenerative medicine, emphasizing the need for further exploration of underlying molecular mechanisms. Show less

To investigate the modification of muscle quality of farmed tilapia through dietary fatty acid strategies, two diets were formulated. Diet SO, using soybean oil as the lipid source, and diet BO, using blended soybean and linseed oils, each including 0.58% and 1.35% α-linolenic acid (ALA), respectively, were formulated to feed juvenile tilapia for 10 weeks. The muscular nutrition composition, positional distribution of fatty acid in triglycerides (TAGs) and phospholipids (PLs), volatile flavor, lipid mobilization and oxidation were then analyzed. The results showed that there was no distinct difference between the SO and BO groups in terms of the nutrition composition, including crude protein, crude lipid, TAGs, PLs, and amino acid. Although the fatty acid distribution characteristics in ATGs and PLs showed a similar trend in the two groups, a higher level of n-3 PUFA (polyunsaturated fatty acid) and n-3 LC-PUFA (long-chain polyunsaturated fatty acid) bound to the glycerol backbone of TAGs and PLs was detected in the BO group than the SO group, whereas the opposite was true for n-6 PUFA. Additionally, the muscular volatile aldehyde and alcohol levels were higher in the BO group. Moreover, the expression of enzymatic genes and protein activities related to lipid mobilization (LPL, LPCAT, DGAT) and oxidation (LOX and GPX) was higher in the BO group. The results demonstrate that high-ALA diets may improve the fatty acid bioavailability and volatile flavor of tilapia by improving the lipid mobilization and oxidation, which provides new ideas for the improvement of muscle quality in farmed fish. Show less

To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1 Show less

In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17β-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Show less

The plant cell wall is a dynamic structure that plays an essential role in development, but the mechanism regulating cell wall formation remains poorly understood. We demonstrate that two transcription factors, SlERF.H5 and SlERF.H7, control cell wall formation and tomato fruit firmness in an additive manner. Knockout of SlERF.H5, SlERF.H7, or both genes decreased cell wall thickness, firmness, and cellulose contents in fruits during early development, especially in double-knockout lines. Overexpressing either gene resulted in thicker cell walls and greater fruit firmness with elevated cellulose levels in fruits but severely dwarf plants with lower gibberellin contents. We further identified that SlERF.H5 and SlERF.H7 activate the cellulose biosynthesis gene SlCESA3 but repress the gibberellin biosynthesis gene GA20ox1. Moreover, we identified a conserved LPL motif in these ERFs responsible for their activities as transcriptional activators and repressors, providing insight into how bifunctional transcription factors modulate distinct developmental processes. Show less

To establish typical clinical and radiological profiles of primary low-grade parotid cancers in order to tailor therapeutic strategy. Retrospective study of 57 patients operated on for primary parotid cancer between 2010 and 2021, with review of preoperative MRI and histopathology according to a standardized scoring grid. To study prognostic factors and determine the preoperative clinical and radiological profile of low-grade cancers. Good prognostic factors for specific survival were: staging ≤ cT3 (p = 0.014), absence of adenopathy on cN0 MRI (p < 0.001), superficial lobe location (p = 0.033), pN0 (p < 0.001), absence of capsular rupture (p = 0.004), as well as the absence of peri-tumoral nodules (p = 0.033), intra-parotid adenopathies (p < 0.001), vascular emboli (p < 0.001), peri-neural sheathing (p = 0.016), nuclear atypia (p = 0.031), and necrosis (p = 0.002). It was not possible to define a reliable clinical and radiological profile for low-grade cancers (sensitivity 38%, specificity 79%). Our study demonstrated multiple factors of good prognosis, but it was not possible to define a clinical and radiological profile of patients likely to benefit from more limited surgery, nor to diagnose, a priori, low-grade cancers. Show less

This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition. Show less

Why and how organismal lineages radiate is commonly studied through either assessing abiotic factors (biogeography, geomorphological processes, and climate) or biotic factors (traits and interactions). Despite increasing awareness that both abiotic and biotic processes may have important joint effects on diversification dynamics, few attempts have been made to quantify the relative importance and timing of these factors, and their potentially interlinked direct and indirect effects, on lineage diversification. We here combine assessments of historical biogeography, geomorphology, climatic niche, vegetative, and floral trait evolution to test whether these factors jointly, or in isolation, explain diversification dynamics of a Neotropical plant clade (Merianieae, Melastomataceae). After estimating ancestral areas and the changes in niche and trait disparity over time, we employ Phylogenetic Path Analyses as a synthesis tool to test eleven hypotheses on the individual direct and indirect effects of these factors on diversification rates. We find strongest support for interlinked effects of colonization of the uplifting Andes during the mid-Miocene and rapid abiotic climatic niche evolution in explaining a burst in diversification rate in Merianieae. Within Andean habitats, later increases in floral disparity allowed for the exploitation of wider pollination niches (i.e., shifts from bee to vertebrate pollinators), but did not affect diversification rates. Our approach of including both vegetative and floral trait evolution, rare in assessments of plant diversification in general, highlights that the evolution of woody habit and larger flowers preceded the colonization of the Andes, but was likely critical in enabling the rapid radiation in montane environments. Overall, and in concert with the idea that ecological opportunity is a key element of evolutionary radiations, our results suggest that a combination of rapid niche evolution and trait shifts was critical for the exploitation of newly available niche space in the Andes in the mid-Miocene. Further, our results emphasize the importance of incorporating both abiotic and biotic factors into the same analytical framework if we aim to quantify the relative and interlinked effects of these processes on diversification. Show less

Long persistent luminescence (LPL) materials open up a new avenue for information security, anticounterfeiting technology, and bioimaging thanks to their unique luminescence characteristics like ultralong exciton migration distances and multiple-colored light emission. As materials that have value for commercial applications, they attract much attention. In this paper, inexpensive, accessible, and eco-friendly niacin is used as a ligand to combine with the universally used metal ion Zn(II) to form a crystallized metal-organic complex dubbed Zn-NA. The named material possesses an ultralong room-temperature phosphorescence (RTP) with a lifetime of up to 265 ms under the atmosphere and up to 446 ms at 77 K. Notably, it exhibits a bright and multimode (excitation- and temperature-dependent) color-tunable LPL that changes from blue to cyan and then to yellow-green upon removal of the irradiation sources. Depending on its photoluminescence and theoretical calculations, the observed long-lived RTP of Zn-NA can be attributed to the coexistence of a single-molecule state induced by the heavy atom effect and an aggregated state within a dense crystalline structure. Show less

We present a rare case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM) diagnosed in a 65-year-old female initially presenting with recurrent bilateral epistaxis. Despite multiple cauterizations and a history of ineffective conventional treatments, comprehensive evaluations led to the diagnosis, underscoring the critical need for thorough investigation in persistent epistaxis cases, particularly when standard approaches fail. This case emphasizes the importance of considering indolent lymphomas in the differential diagnosis of recurrent epistaxis and showcases the diagnostic pathway leading to successful identification and treatment of a rare etiology. Laryngoscope, 134:3974-3976, 2024. Show less

Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 μm, and a maximum distance between the high peaks and the low valleys of more than 300 μm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 μm, which was reduced to 0.94 μm and 0.84 μm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 μm, was produced on the Ti Show less

Angiopoietin-like protein 3 (ANGPTL3) is a plasmatic protein that plays a crucial role in lipoprotein metabolism by inhibiting the lipoprotein lipase (LPL) and the endothelial lipase (EL) responsible for the hydrolysis of phospholipids on high-density lipoprotein (HDL). Interest in developing new pharmacological therapies aimed at inhibiting ANGPTL3 has been growing due to the hypolipidemic and antiatherogenic profile observed in its absence. The goal of this study was the in silico characterization of the interaction between ANGPTL3 and EL. Because of the lack of any structural information on both the trimeric coiled-coil N-terminal domain of ANGPTL3 and the EL homodimer as well as data regarding their interactions, the first step was to obtain the three-dimensional model of these two proteins. The models were then refined via molecular dynamics (MD) simulations and used to investigate the interaction mechanism. The analysis of interactions in different docking poses and their refinement via MD allowed the identification of three specific glutamates of ANGPTL3 that recognize a positively charged patch on the surface of EL. These ANGPTL3 key residues, i.e., Glu154, Glu157, and Glu160, could form a putative molecular recognition site for EL. This study paves the way for future investigations aimed at confirming the recognition site and at designing novel inhibitors of ANGPTL3. Show less

The aim of this study was to describe the diagnosis and treatment of grade IV lateral patellar luxation (LPL) in two adult large breed dogs with complex femoral deformities using patient-specific three-dimensionally (3D) printed osteotomy guides and implants. Computed tomography (CT) scans were obtained for virtual surgical planning (VSP) using computer-aided design (CAD) software, which allowed for 3D reconstruction and manipulation of the femoral deformities, providing a preoperative view of the correction. Of the two patients, one was affected bilaterally and the other unilaterally, but both dogs were from the same litter. Therefore, the healthy femur of the unilaterally affected patient was used as the physiological reference for the virtual surgical correction. Three distal femoral trapezoid osteotomies (DF-TO) followed by reduction and internal fixation with plates were performed using patient-specific 3D-printed osteotomy guides and implants. This type of osteotomy permitted correction of procurvatum in all the femurs to increase knee extension, raise the dog's lumbar spine and correct the kyphosis. Preoperative, expected and postoperative femoral angles were compared to evaluate the efficacy of virtual surgical planning and the outcome of surgical correction. Radiographic follow-up, passive range of motion and functional recovery were recorded. There were no major complications requiring revision surgery. Significant clinical improvement was observed in both patients. This study suggests that the treatment used represents a viable surgical alternative to restore limb alignment in patients with complex femoral deformities. Show less

The study aims to explore the relationship between lipoprotein lipase In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the The rate of rare Detecting rare variants in Show less

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α. In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats. Show less

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1 Show less

We present an analytical framework aimed at predicting the local brain activity in uncontrolled experimental conditions based on multimodal recordings of participants' behavior, and its application to a corpus of participants having conversations with another human or a conversational humanoid robot. The framework consists in extracting high-level features from the raw behavioral recordings and applying a dynamic prediction of binarized fMRI-recorded local brain activity using these behavioral features. The objective is to identify behavioral features required for this prediction, and their relative weights, depending on the brain area under investigation and the experimental condition. In order to validate our framework, we use a corpus of uncontrolled conversations of participants with a human or a robotic agent, focusing on brain regions involved in speech processing, and more generally in social interactions. The framework not only predicts local brain activity significantly better than random, it also quantifies the weights of behavioral features required for this prediction, depending on the brain area under investigation and on the nature of the conversational partner. In the left Superior Temporal Sulcus, perceived speech is the most important behavioral feature for predicting brain activity, regardless of the agent, while several features, which differ between the human and robot interlocutors, contribute to the prediction in regions involved in social cognition, such as the TemporoParietal Junction. This framework therefore allows us to study how multiple behavioral signals from different modalities are integrated in individual brain regions during complex social interactions. Show less

Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes. We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls. The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence). Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings. Show less

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement. Show less

Obesity is a threat to public health and effective new medications are required. Platycodonis Radix (PR) is a traditional medicinal/dietary plant with activities against obesity. Using mice given a diet rich in fat, the antiobesity components of PR were identified and their molecular mechanisms were clarified further in this investigation. Initially, the impacts of PR fractions on liver histology and biochemical markers were assessed. Subsequently, the degrees of lipogenic and lipolytic gene and protein expressions were determined. Oral administration of PR polysaccharides (PG) (0.80 g/kg body weight) improved liver function (alanine aminotransferase and aspartate aminotransferase) and its antioxidant activities (total superoxide dismutase, glutathione peroxidase, and malondialdehyde), as well as alleviated blood lipid (total cholesterol, total triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) values, inflammatory systemic (TNF- Show less

Linearly polarised luminescence (LPL) has a wide range of potential applications giving optical and geometric parameters for oriented lumiphores. In this work we present the first wavelength scanned LPL spectra. Analytes are either oriented on stretched polyethylene films or in flow. Applications of the wavelength-dependence of Show less