📋 Browse Articles

Subsurface dams have been recognized as one of the most effective measures for preventing saltwater intrusion. However, it may result in large amounts of residual saltwater being trapped upstream of the dam and take years to decades to remove, which may limit the utilization of fresh groundwater in coastal areas. In this study, field-scale numerical simulations were used to investigate the mechanisms of residual saltwater removal from a typical stratified aquifer, where an intermediate low-permeability layer (LPL) exists between two high-permeability layers, under the effect of seasonal sea level fluctuations. The study quantifies and compares the time of residual saltwater removal (Tre) for constant sea level (CSL) and seasonally varying sea level (FSL) scenarios. The modelling results indicate that, in most cases, seasonal fluctuations in sea level facilitate the dilution of residual saltwater and thus accelerate residual saltwater removal compared to a static sea level scenario. However, accounting for seasonal sea level variations may increase the required critical dam height (the minimum dam height required to achieve complete residual saltwater removal). Sensitivity analyses show that Tre decreases with increasing height of subsurface dam (Hd) under CSL or weaker sea level fluctuation scenarios; however, when the magnitude of sea level fluctuation is large, Tre changes non-monotonically with Hd. Tre decreases with increasing distance between subsurface dam and ocean for both CSL and FSL scenarios. We also found that stratification model had a significant effect on Tre. The increase in LPL thickness for both CSL and FSL scenarios leads to a decrease in Tre and critical dam height. Tre generally shows a non-monotonically decreasing trend as LPL elevation increases. These quantitative analyses provide valuable insights into the design of subsurface dams in complex situations. Show less

Lipoprotein lipase (LPL) is a critical enzyme in humans that provides fuel to peripheral tissues. LPL hydrolyzes triglycerides from the cores of lipoproteins that are circulating in plasma and interacts with receptors to mediate lipoprotein uptake, thus directing lipid distribution via catalytic and non-catalytic functions. Functional losses in LPL or any of its myriad of regulators alter lipid homeostasis and potentially affect the risk of developing cardiovascular disease-either increasing or decreasing the risk depending on the mutated protein. The extensive LPL regulatory network tunes LPL activity to allocate fatty acids according to the energetic needs of the organism and thus is nutritionally responsive and tissue dependent. Multiple pharmaceuticals in development manipulate or mimic these regulators, demonstrating their translational importance. Another facet of LPL biology is that the oligomeric state of the enzyme is also central to its regulation. Recent structural studies have solidified the idea that LPL is regulated not only by interactions with other binding partners but also by self-associations. Here, we review the complexities of the protein-protein and protein-lipid interactions that govern LPL structure and function. Show less

Neuromorphic computation draws inspiration from the remarkable features of the human brain including low energy consumption, parallelism, adaptivity, cognitive functions, and learning ability. These qualities hold the promise of unlocking groundbreaking computational techniques that surpass the limitations of traditional computing systems. This paper reports a remarkable photo-synaptic behavior in the field of rare earth ion-doped luminescent oxides by using long-persistent luminescence (LPL). This system utilizes electron trap states to regulate the synaptic behavior, operating through a fundamentally different mechanism from that of electronic-based synaptic devices. To realize this strategy, Tb Show less

The milk's nutritional value is determined by its constituents, including fat, protein, carbohydrates, and minerals. The mammary gland's ability to produce milk is controlled by a complex network of genes. Thereby, the fat, protein, and lactose synthesis must be boost in milk to increase milk production efficiency. This can be accomplished by fusing genetic advancements with proper management practices. Therefore, this study aimed to investigate the association between the Lipoprotein lipase (LPL), kappa casein CSN3, and Glucose transporter 1 (GLUT1) genes expression levels and such milk components as fat, protein, and lactose in different dairy breeds during different stages of lactation. To achieve such a purpose, 94 milk samples were collected (72 samples from 36 multiparous black-white and red-white Holstein-Friesian (HF) cows and 22 milk samples from 11 Egyptian buffaloes) during the early and peak lactation stages. The milk samples were utilized for milk analysis and genes expressions analyses using non- invasive approach in obtaining milk fat globules (MFGs) as a source of Ribonucleic acid (RNA). LPL and CSN3 genes expressions levels were found to be significantly higher in Egyptian buffalo than Holstein-Friesian (HF) cows as well as fat and protein percentages. On the other hand, GLUT1 gene expression level was shown to be significantly higher during peak lactation than early lactation. Moreover, lactose % showed a significant difference in peak lactation phase compared to early lactation phase. Also, fat and protein percentages were significantly higher in early lactation period than peak lactation period but lactose% showed the opposite pattern of Egyptian buffalo. Total RNA can be successfully obtained from MFGs. The results suggest that these genes play a role in glucose absorption and lactose synthesis in bovine mammary epithelial cells during lactation. Also, these results provide light on the differential expression of these genes among distinct Holstein-Friesian cow breeds and Egyptian buffalo subspecies throughout various lactation phases. Show less

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H Show less

This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism. Show less

Triglyceride (TG) /High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is associated with premature aging processes, risk of diabetes and increased mortality. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among subjects of European ancestry who had complete data from two exams collected about seven years apart from the Long Life Family Study (LLFS, n=1384), a study with familial clustering of exceptional longevity in the US and Denmark. Subjects with diabetes or using medications for dyslipidemia were excluded from this analysis. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS was conducted using a linear mixed model accounted for familial relatedness. Our linkage scan was built on haplotype-based IBD estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the our linkage-guided sequence analysis approach permitted our discovery of two novel gene variants Show less

Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL. An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein. Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion. Show less

Cardiovascular diseases are the leading causes of global mortality and morbidity. Hyperlipidemia is a significant risk factor for atherosclerosis and subsequent cardiovascular diseases. Hyperlipidemia is characterized by imbalances in blood cholesterol levels, particularly elevated low-density lipoprotein cholesterol and triglycerides, and is influenced by genetic and environmental factors. Current management consists of lifestyle modifications and pharmacological interventions most commonly consisting of statins. This review paper explores pathophysiology, management strategies, and pharmacotherapies including commonly used well-established medications including statins, fibrates, and ezetimibe, exciting novel therapies including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and RNA interference therapies (inclisiran), lomitapide, and bempedoic acid, highlighting their mechanisms of action, clinical efficacy, and safety profiles. Additionally, emerging therapies under clinical trials including ApoC-III inhibitors, DGAT2 inhibitors, ACAT2 Inhibitors, and LPL gene therapies are examined for their potential to improve lipid homeostasis and cardiovascular outcomes. The evolving landscape of hyperlipidemia management underscores the importance of continued research into both established therapies and promising new candidates, offering hope for more effective treatment strategies in the future. Show less

The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through multi-omics analysis and found functional components that are more similar to human milk. This study employed untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D label-free proteomics analysis techniques. The findings revealed substantial disparities in metabolites, lipids, and proteins among the five types of milk. Notably, pig milk exhibited a remarkable abundance of N-acetylneuraminic acid (Neu5Ac) and specific polar lipids. Yak milk stood out with significantly elevated levels of creatine and lipoprotein lipase (LPL) compared to other species. Buffalo milk boasted the highest concentrations of L-isoleucine, echinocystic acid, and alkaline phosphatase, tissue-nonspecific isozyme (ALPL). The concentrations of iminostilbene and osteopontin (OPN) were higher in cow milk. Show less

We investigated how naturalistic actions in a highly immersive, multimodal, interactive 3D virtual reality (VR) environment may enhance word encoding by recording EEG in a pre/post-test learning paradigm. While behavior data have shown that coupling word encoding with gestures congruent with word meaning enhances learning, the neural underpinnings of this effect have yet to be elucidated. We coupled EEG recording with VR to examine whether embodied learning improves learning and creates linguistic representations that produce greater motor resonance. Participants learned action verbs in an L2 in two different conditions: specific action (observing and performing congruent actions on virtual objects) and pointing (observing actions and pointing to virtual objects). Pre- and post-training participants performed a match-mismatch task as we measured EEG (variation in the N400 response as a function of match between observed actions and auditory verbs) and a passive listening task while we measured motor activation (mu [8-13 Hz] and beta band [13-30 Hz] desynchronization during auditory verb processing) during verb processing. Contrary to our expectations, post-training results revealed neither semantic nor motor effects in either group when considered independently of learning success. Behavioral results showed a great deal of variability in learning success. When considering performance, low performance learners showed no semantic effect and high performance learners exhibited an N400 effect for mismatch versus match trials post-training, independent of the type of learning. Taken as a whole, our results suggest that embodied processes can play an important role in L2 learning. Show less

Hypertriglyceridemia (HTG) is a complex disorder caused by genetic and environmental factors that frequently results from loss-of-function variants in the gene encoding lipoprotein lipase (LPL). Heterozygous patients have a range of symptoms, while homozygous LPL deficiency presents with severe symptoms including acute pancreatitis, xanthomas, and lipemia retinalis. We described the clinical characteristics of three Slovenian patients (an 8-year-old female, an 18-year-old man, and a 57-year-old female) and one Pakistani patient (a 59-year-old male) with LPL deficiency. We performed next-generation sequencing (NGS) targeting all coding exons and intron-exon boundaries of the Two Slovenian patients with a heterozygous pathogenic variant NM₀₀₀₂₃₇.3:c.984G>T (p.Met328Ile) were diagnosed within the first three years of life and had triglyceride (TG) values of 16 and 20 mmol/L. An asymptomatic Pakistani patient with TG values of 36.8 mmol/L until the age of 44 years, was identified as heterozygous for a pathogenic variant NM₀₀₀₂₃₇.3:c.724G>A (p.Asp242Asn). His TG levels dropped to 12.7 mmol/L on dietary modifications and by using fibrates. A Slovenian patient who first suffered from pancreatitis at the age of 18 years with a TG value of 34 mmol/L was found to be homozygous for NM₀₀₀₂₃₇.3:c.337T>C (p.Trp113Arg). Patients with LPL deficiency had high TG levels at diagnosis. Homozygous patients had worse outcomes. Good diet and medication compliance can reduce severity. Show less

In this study, we conducted an 8-week feeding trial to investigate the effects of replacing fish oil (FO) with coconut oil (CO) on the growth performance, blood components, tissue fatty acid (FA) profile, and mRNA levels of genes related to lipid metabolism in the liver of the orange-spotted grouper ( Show less

Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis. The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis. The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129-2.812, The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris. Show less

We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China. This is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention. 2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals. The LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period. ClinicalTrials.gov, identifier NCT05745545. Show less

Long persistent luminescence (LPL) has gained considerable attention for the applications in decoration, emergency signage, information encryption and biomedicine. However, recently developed LPL materials - encompassing inorganics, organics and inorganic-organic hybrids - often display monochromatic afterglow with limited functionality. Furthermore, triplet exciton-based phosphors are prone to thermal quenching, significantly restricting their high emission efficiency. Here, we show a straightforward wet-chemistry approach for fabricating multimode LPL materials by introducing both anion (Br Show less

Pathogenic variants in We performed an in vivo lipoprotein kinetic study in 6 affected patients compared with 13 healthy controls and 8 patients with type 2 diabetes. Glucose and lipid parameters, including plasma LPL (lipoprotein lipase) mass, were measured. Patients with We show that hypertriglyceridemia associated with Show less

We used a novel nonword detection task to examine the lexical competition principle postulated in most models of spoken word recognition. To do so, in Experiment 1 we presented sequences of spoken words with half of the sequences containing a nonword, and the target nonword (i.e., press a response key whenever you detect a nonword in the sequence) could either be phonologically related (a phonological neighbor) or unrelated to the immediately preceding word. We reasoned that the reactivation of a phonological neighbor during target nonword processing should delay the moment at which a nonword decision can be made. Contrary to our hypothesis, participants were faster at detecting nonwords when they were preceded by a phonological neighbor compared with an unrelated word. In Experiment 2, an inhibitory effect of phonological relatedness on nonword decisions was observed in a classic priming situation using the same set of related and unrelated word-nonword pairs. We discuss the implications of these findings in regard to the main models of spoken word recognition, and conclude that our specific experimental set-up with phonological neighbors embedded in spoken sentences is more sensitive to cooperative interactions between co-activated sublexical representations than lexical competition between co-activated lexical representations, with the latter being modulated by whether or not the words compete for the same slot in time. Show less

In ruminants, supplementing appropriate amounts of amino acids improves growth, feed utilization efficiency, and productivity. This study aimed to assess the effects of different Lys/Met ratios on the ruminal microbial community and the metabolic profiling in Tibetan sheep using 16S rDNA sequencing and non-target metabolomics. Ninety-two-month-old Tibetan rams (initial weight = 15.37 ± 0.92 kg) were divided into three groups and fed lysine/methionine (Lys/Met) of 1:1 (LP-L), 2:1 (LP-M), and 3:1 (LP-H) in low-protein diet, respectively. Results: The T-AOC, GSH-Px, and SOD were significantly higher in the LP-L group than in LP-H and LP-M groups ( Show less

Pluchea dioscoridis (L.) DC. is a flowering wild plant used traditionally in the treatment of rhematic disorders. This study investigated the phytochemical and in vitro radical scavenging activity (RSA), and in vivo anti-hyperlipidemic, antioxidant and anti-inflammatory properties of P. dioscoridis. The antihyperlipidemic efficacy was determined in a rat model of dyslipidemia. The extract and fractions of P. dioscoridis showed RSA with the ethyl acetate (EA) fraction exhibiting the most potent activity. The phytochemical analysis of P. dioscoridis EA fraction (PDEAF) led to the isolation of five compounds (lupeol, quercetin, lupeol acetate, stigmasterol, and syringic acid). To evaluate its anti-hyperlipidemic effect, three doses of PDEAF were supplemented to rats for 14 days and poloxamer-407 was administered on day 15 to induce dyslipidemia. All doses of PDEAF decreased plasma triglycerides, cholesterol, low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (vLDL-C), and increased plasma lipoprotein lipase (LPL). PDEAF upregulated hepatic LDL receptor and suppressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, decreased lipid peroxidation and tumor necrosis factor (TNF)-α and enhanced reduced glutathione (GSH) and enzymatic antioxidants in dyslipidmeic rats. In silico findings revealed the binding affinity of the isolated compounds towards LPL, HMG-CoA reductase, and LDL receptor. In conclusion, P. dioscoridis is rich in phytoconstituents, exhibited RSA and its EA fraction effectively prevented acute dyslipidemia and its associated oxidative stress and inflammatory response. Show less

Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of multi-color, -temporal, and -modal luminescence performance remains a compelling and imperative pursuit. In our work, a temperature/photon-responded dynamic self-activated luminescence originating from nonstoichiometric Zn Show less

The Butuo Black Sheep (BBS) is well-known for its ability to thrive at high altitudes, resist diseases, and produce premium-quality meat. Nonetheless, there is insufficient data regarding its genetic diversity and population-specific Single nucleotide polymorphisms (SNPs). This paper centers on the genetic diversity of (BBS). The investigation conducted a whole-genome resequencing of 33 BBS individuals to recognize distinct SNPs exclusive to BBS. The inquiry utilized bioinformatic analysis to identify and explain SNPs and pinpoint crucial mutation sites. The findings reveal that reproductive-related genes (GHR, FSHR, PGR, BMPR1B, FST, ESR1), lipid-related genes (PPARGC1A, STAT6, DGAT1, ACACA, LPL), and protein-related genes (CSN2, LALBA, CSN1S1, CSN1S2) were identified as hub genes. Functional enrichment analysis showed that genes associated with reproduction, immunity, inflammation, hypoxia, PI3K-Akt, and AMPK signaling pathways were present. This research suggests that the unique ability of BBS to adapt to low oxygen levels in the plateau environment may be owing to mutations in a variety of genes. This study provides valuable insights into the genetic makeup of BBS and its potential implications for breeding and conservation efforts. The genes and SPNs identified in this study could serve as molecular markers for BBS. Show less

Lymphoplasmacytic lymphoma (LPL) is a malignant proliferation of small lymphocytes, lymphoplasmocytoid cells and plasmocytes affecting the bone marrow, lymph nodes and spleen. Its incidence is 1/100,000 and represents 8% of all lymphomas. A total of ~5% of patients with LPL may secrete non-IgM of IgG, IgA, kappa or lambda type or be non-secretory. In the present study, a case of a 62-year-old female patient who was diagnosed with non-IgM LPL with kappa light chain monoclonal paraprotein production and normal serum immunoglobulin levels was reported. The Show less

Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens. Show less

Homozygous familial hypercholesterolemia (HoFH) is a rare and serious genetic condition characterized by premature cardiovascular disease due to severely elevated low-density lipoprotein cholesterol (LDL-C). HoFH primarily results from loss-of-function (LOF) mutations in the LDL receptor (LDLR), reducing LDL-C clearance such that patients experience severe hypercholesterolemia, exacerbating the risk of developing cardiovascular events. Treatment options such as statins, lomitapide, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and apheresis help lower LDL-C; however, many patients with HoFH still fail to reach their target LDL-C levels and many of these lipid-lowering therapies are not indicated for pediatric use. Angiopoietin-like protein 3 (ANGPTL3) has been identified as a target to treat elevated LDL-C by acting as a natural inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes involved in the hydrolysis of the triglyceride and phospholipid content of very low-density lipoproteins. Persons heterozygous for LOF mutations in ANGPTL3 were reported to have lower LDL-C than non-carriers and lower risk of coronary artery disease. Evinacumab is a first-in-class human monoclonal antibody that specifically binds to ANGPTL3 to prevent its inhibition of LPL and EL. In clinical trials, a 15 mg/kg intravenous dose every 4 weeks has shown a mean percent change from baseline in LDL-C of ~50% in adult, adolescent, and pediatric patients with HoFH. This mini review article describes the mechanism of action of evinacumab, evinacumab population PK and PD modeling, and clinical development history of evinacumab for the treatment of HoFH. Show less

Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Lys/Met ratio in a low protein diet (10%, dry matter basis) on the growth performance and hepatic function (antioxidant capacity, immune status, and glycolytic activity) in Tibetan lambs. Ninety two-month-old rams with an average weight of 15.37 ± 0.92 kg were randomly assigned to LP-L (dietary Lys/Met = 1:1), LP-M (dietary Lys/Met = 2:1) and LP-H (dietary Lys/Met = 3:1) treatments. The trial was conducted over 100 d, including 10 d of adaption to the diets. Hepatic phenotypes, antioxidant capacity, immune status, glycolytic activity and gene expression profiling was detected after the conclusion of the feeding trials. The results showed that the body weight was higher in the LP-L group when compared to those on the LP-M group (P < 0.05). In addition, the activities of the catalase (CAT) and glutathione peroxidase (GSH-Px) in the LP-L group were significantly increased compared with the LP-M group (P < 0.05), while the malondialdehyde (MDA) levels in LP-H group were significantly decreased (P < 0.05). Compared with LP-H group, both hepatic glycogen (P < 0.01) and lactate dehydrogenase (LDH) (P < 0.05) were significantly elevated in LP-L group. For the LP-L group, the hepatocytes were arranged radially with the central vein in the center, and hepatic plates exhibited tight arrangement. Transcriptome analysis identified 29, 179, and 129 differentially expressed genes (DEGs) between the LP-M vs. LP-L, LP-H vs. LP-M, and LP-H vs. LP-L groups, respectively (Q-values < 0.05 and |log2Fold Change| > 1). Gene Ontology (GO) and correlation analyses showed that in the LP-L group, core genes (C1QA and JUNB) enriched in oxidoreductase activity were positively correlated with antioxidant indicators, while the MYO9A core gene enriched in the immune response was positively associated with immune indicators, and core genes enriched in molecular function (PDK3 and PDP2) were positively correlated with glycolysis indicators. In summary, low-protein diet with a low Lys/Met ratio (1:1) could reduce the hepatic oxidative stress and improve the glycolytic activity by regulating the expression of related genes of Tibetan sheep. Show less

The intake of high-fat diets (HFD) has been shown to diminish the muscle quality of aquatic animals. Sanguinarine, as an excellent additive, exhibits the capability to reduce fat deposition and alleviate inflammation. However, its role in the muscle quality reduction caused by HFD remains unclear. An eight-week trial was conducted to investigate the impacts of dietary supplementation of sanguinarine at 1200 μg/kg (HFDS; crude fat = 10%) on the muscle quality of grass carp ( Show less