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This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs and PLA-MPs were prepared, with PLA-MPs having a rougher surface and broader size distribution. In vitro, PLA-MPs showed higher cytotoxicity to granulosa cells compared to PS-MPs. In vivo, MPs exposure disrupted the estrous cycle, and damaged ovarian reserve. Granulosa cell apoptosis and cytokine activation led to transzonal projection retraction, oocyte oxidative stress, meiotic abnormalities, and reduced oocyte retrieval and polar body extrusion rate, thus reducing litter size. PS-MPs induced more severe intestinal and ovarian impairment. Analysis of feces 16S rRNA, serum metabolomics, and ovarian RNA sequencing revealed that lipoprotein lipase (LPL) was suppressed by both MPs, linking gut microbiota, lipid metabolism, and ovarian injury. Fecal microbiota transplantation as a rescue strategy in MPs exposed mice upregulated LPL, alleviating ovarian reserve decline. In PLA-MPs exposed mice, ovarian reserve related indicators partially recovered after a two-week exposure cessation. These results clarify the similarities and differences in how PS-MPs and PLA-MPs impair ovarian function via gut-ovary axis and lipid metabolism dysregulation. Show less

Metal-organic frameworks (MOFs) have been considered as ideal platforms to achieve long persistent luminescence (LPL), to utilize as optical recording devices, security systems and sensors. Despite the rapid emergence, it is still a challenge to develop single-component red LPL MOFs. In this work, two hetero-ligand MOFs are synthesized using a D-π-A-type ligand (source of red phosphorescence) and a monocyclic carboxylic ligand (appropriate void constructer), which show efficient red LPL after removal of wide excitations at ambient conditions. Experiment and calculation suggest that the effective red LPL originates from the D-π-A-type ligand, while the auxiliary carboxylic ligand mediates the orientation/arrangement of the D-π-A linker in MOFs affecting phosphorescence. The MOFs are further used in the field of multiple message encryption, initiating a new perspective for designing new red LPL MOFs. Show less

Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG's preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG's action against KYD. Show less

Fatty acids serve as a crucial energy source for tumor cells during the progression of chronic lymphocytic leukemia (CLL). The present study aims to elucidate the characteristics of fatty acid metabolism (FAM) in CLL, construct a related prognostic score, and investigate the regulatory role and mechanisms of FAM in CLL development. Bulk RNA sequencing data from CLL patients and healthy controls were analyzed to identify differentially expressed fatty acid metabolic genes. FAM-score was constructed using Cox-LASSO regression and validated. Single-cell RNA sequencing was used to analyze the expression of key FAM genes in CLL immune cell subsets and investigate cellular communication. Functional assays, including cell viability, drug sensitivity, and oxygen consumption assays, were performed to assess the impact of fatty acid oxidation (FAO) inhibition on CLL cells. Three FAM-related genes (LPL, SOCS3, CNR1) were identified with independent prognostic significance to construct the risk score. The FAM-score demonstrated superior prognostic performance compared to the Binet stage and was associated with established clinical prognostic markers. Single-cell analysis revealed distinct expression patterns of LPL, SOCS3, and CNR1 across CLL immune cell subsets. Cellular communication analysis highlighted the regulatory role of distinct B cell and Treg subsets in the CLL microenvironment. CLL patients with high FAM-score displayed distinct immune infiltration patterns, with increased FAO pathway activity. Inhibition of FAO reduced CLL cell viability, synergistically enhanced the efficacy of the PI3K inhibitor idelalisib. The present study constructed a prognostic risk score based on FAM gene expression, revealing related immune phenotypic differences and exploring the regulatory role of FAO in CLL development. Targeting fatty acid metabolism potentially modulates the CLL immune microenvironment and synergistically enhances the efficacy of PI3K inhibitors. Show less

Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker. Show less

Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in this process. Through the automatization of the mapping ability, this area progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the VWFA and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions, suggesting that populations of neurons within the VWFA distinctively encode written and spoken language. This functional organization of neural populations enables the area to respond to both written and spoken inputs. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Show less

The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role in CsA nephrotoxicity is not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza Bunge) (HD) play roles in ameliorating the nephrotoxicity of CsA, but their mechanisms still need to be fully clarified. This study innovatively aimed to analyse the coexpression of renal proteins and serum metabolites for the identification of key pathways and targets. This study provides novel insight into the mechanism by which HD ameliorates CsA-induced nephrotoxicity. We utilized HD to intervene in both in vivo and in vitro nephrotoxicity models induced by CsA. For the in vivo experiments, we constructed a coexpression network of renal proteins and serum metabolites, which was used to screen for key pathways. To validate these findings, we knocked down key proteins in vivo. For the in vitro studies, we employed MTT, Transwell, flow cytometry, and immunofluorescence assays to monitor the epithelial-mesenchymal transition (EMT) of HK-2 cells. Additionally, we used electron microscopy and Seahorse assays to examine the effects of HD on mitochondrial structure and function. Furthermore, we overexpressed Ppara to further confirm the mechanism by which HD improves renal function. HD can improve renal pathological damage and function; regulate blood lipids, inflammation and oxidative stress indicators; and reduce apoptosis in renal tissues. Joint protein and metabolomics analyses revealed that two lipid metabolism-related pathways (the PPAR signalling pathway and linoleic acid metabolism pathway) were coenriched, involving six differential proteins (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, and Pck1) and two differentially abundant metabolites (alpha-Dimorphecolic acid and 12,13-EpOME). Western blot was used to verify differentially expressed proteins. HD improved mitochondrial damage and lipid accumulation, as demonstrated by transmission electron microscopy (TEM) analysis and Oil Red O staining. Knockdown of the key protein Ppara affected the expression of ACOX1 and exacerbated RF. In vitro verification demonstrated that HD significantly inhibited CsA-induced EMT in HK-2 cells and improved mitochondrial structure and function. Ppara overexpression promoted HD-mediated regulation of mitochondrial function, reduced apoptosis, and improved HK-2 RF. HD can ameliorate CsA nephrotoxicity through renal protein-serum metabolism coexpression, the PPAR signalling pathway, and linoleic acid metabolism. HD-induced upregulation of Ppara to regulate lipid metabolism, improve mitochondrial function and reduce apoptosis are important mechanisms. The Ppara/ACOX1/TGF-β1 axis may play an important role in this process. These findings offer potential targets for the future development of therapeutic strategies and novel drugs. Show less

Quinolinic acid (QA) is a metabolite of tryptophan catabolism involved in the biosynthesis of nicotinamide adenine dinucleotide (NAD). It has been extensively studied in the context of neuropsychiatric disorders in the past decades. Recent studies have also linked high plasma QA levels to obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes. In the present study, we have explored the impact of long-term oral QA administration on glucose and lipid metabolism in mice. We observed a protective role for QA in preventing hepatic lipid accumulation in high-fat-diet fed mice, whereas oral administration of NAD showed opposite effects. We further demonstrated that QA reduces hepatic lipid uptake by inhibiting the expression of lipoprotein lipase (LPL) and fatty acid translocase (CD36) in liver, thereby mitigating liver lipid accumulation in the context of a high-fat diet. Our data suggest that QA is an important regulator of lipid homeostasis and has potential as a therapeutic target for MASLD. Show less

<b>Introduction:</b> Colonic diverticular disease (diverticulosis) is a currently worldwide increasing gastrointestinal disorder with a particularly high prevalence in Western countries. The operative treatment of acute diverticulitis could be executed through open or laparoscopic techniques. A non-resectional procedure, namely laparoscopic peritoneal lavage (LPL) and drainage, has also been adopted as a less invasive treatment strategy to treat patients with diverticular perforation and purulent peritonitis.<b>Aim:</b> The present work was conducted to pool the currently available evidence regarding the safety and efficacy of LPL for the treatment of complicated perforated diverticulitis.<b>Methods:</b> The analysis included studies that compared patients who underwent LPL to those who underwent surgical resection. Fifteen articles were eligible for this review after searching the Scopus, PubMed Central, Cochrane Library, and Google Scholar databases.<b>Results:</b> The meta-analysis demonstrated that operative time and blood loss were significantly lower in the LPL group (p<0.001). The rates of overall morbidity and reoperation were comparable in the two groups (p = 0.57 and 0.74, respectively). There were significantly lower rates of cardiovascular (p < 0.001) and respiratory complications (p = 0.01), incisional/parastomal hernia formation (p = 0.02), ICU admission (p < 0.001), length of hospital stay (p < 0.001), permanent stoma formation (p < 0.001), and mortality (p < 0.001), and higher rates of sepsis (p = 0.03), intra-abdominal abscess formation (p < 0.001), and postoperative recurrence (p < 0.001) in the LPL group.<b>Conclusions:</b> Compared to the colon resection procedures for the treatment of complicated diverticulitis, laparoscopic peritoneal lavage had comparable overall morbidity and reoperation rates and lower rates of permanent stoma formation and mortality. Still, there is concern regarding the recurrence and intra-abdominal abscess formation. Show less

The effects of starvation and re-feeding on Jian carp (Cyprinus carpio var. Jian) remain incompletely understood. This study investigated changes in growth performance, liver antioxidant capacity, intestinal morphology, fatty acid profile, and expression of genes related to lipid metabolism. Juvenile C. carpio var. Jian, with initial body weight of 29.50 ± 2.00 g, were reared in 15 cylindrical culture barrels (200L) at a stocking density of 10 fish per barrel. These fish were subjected to five feeding regimes: a continuous feeding group (control group, treatment A), complete fasting (treatment B), 1, 2, and 3 days starvation within one week, followed by re-feeding 6 days (treatment C), 5 days (treatment D), and 4 days (treatment E). The results indicated significantly lower growth performance in C. carpio var. Jian in treatments B and E compared to the control and treatment C (P < 0.05). Intestinal length (only 627 ± 13.14 μm in treatment B) was significantly reduced, and an increase in vacuoles was observed in C. carpio var. Jian with the prolonged starvation. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly (P < 0.05) improved in treatment C when compared with treatments B, D and E.. In contrast, malondialdehyde (MDA) value was lowest (12.62 ± 0.60 nmol/mL) in treatment B. Furthermore, continuous starvation significantly decreased the total lipid and fatty acids contents in the muscle (P < 0.05). Compared with the control group, the reduction of total lipid and fatty acids contents was 31.53 % and 4.57 %, respectively, particularly affecting n3PUFA and n6PUFA. However, after one-day re-feeding, these contents resumed. Lipid metabolism is closely related to fish health, while in the current study, the genes related to lipid metabolism including lipoprotein lipase (LPL), 6-phosphogluconate dehydrogenase (G6PD), and peroxisome proliferator-activated receptor alpha (PPARα) did not differ significantly in treatment C compared to the control group (P > 0.05). In contrast, expressions in treatments B, D, and E were significantly reduced (P < 0.05). Taken together, prolonged starvation (>one day per week) not only affected the growth, which may further disrupt the intestinal structure, weaken antioxidant capacity, but also attenuate lipid deposition. Show less

The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epithelial cells are the precursors of milk fat globules (MFG). However, it is unclear what happens to proteins during the transformation process from LD to MFG, and little is known about the regulation of LD diameter in vivo. In this study, 12 mid-lactation Saanen dairy goats were randomly divided into 2 groups: a control group fed a basal diet and an experimental group fed a basal diet supplemented with CLA at 90 g/d. Goat milk was collected for analysis of composition and MFG size. Mammary gland tissue was collected for analysis of LD diameter and proteins. The size of MFG was found to depend on LD diameter in the mammary glands of dairy goats. The regression equations for MFG size (Y) and LD diameter (x) were Y Show less

The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation. Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain-containing protein (ZBTB20)-Lipoprotein lipase (LPL) (ZBTB20-LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host. Show less

Hepatic steatosis, commonly referred to as fatty liver disease, is defined by the abnormal buildup of fat within liver cells. Currently, primary treatments mainly focus on lifestyle changes, underscoring a lack of direct pharmacological options. Passion fruit seed extract (PFSE) has been reported to decrease hepatosteatosis; however, the mechanism underlying this effect has not been clarified. Therefore, the objective of this research was to investigate the effects and mechanisms of action of PFSE against oleic acid (OA)-induced hepatosteatosis in HepG2 cells. OA-induced HepG2 cells were analyzed by using various cell-based experiments, including assessments of cytotoxicity, reactive oxygen species (ROS) production, apoptosis, and protein and gene expression. LC-MS-MS analysis showed that PFSE contains a variety of phytochemical compounds such as alkaloids, flavonoids, stilbenoids, coumarins, terpenoids, lipids, and fatty acid derivatives, which have the potential to exhibit various pharmacological activities. In this study, PFSE demonstrated antioxidant, anti-inflammatory, and lipid metabolism-regulating activities. It also influenced key genes related to lipid metabolism, including SREBP-1c, ACC, FASN, PPARα, CPT-1A, LPL, SCD1, and LDLR. The positive effects of PFSE on OA-induced hepatic steatosis in HepG2 cells were modulated through the Akt and ERK signaling pathways, suggesting that PFSE may offer a comprehensive approach to managing hepatic steatosis. Show less

Taurine is an amino acid widely present in animal tissues. Recent research has highlighted the importance of including taurine in the diet of various commercially relevant species. This study evaluated the impact of taurine supplementation in the diet of Seriola rivoliana on the activity of antioxidant enzymes, lysozyme, and the expression of metabolic-related genes in different tissues. Three experimental diets were designed with 0% (Control), 1%, and 2% of taurine concentrations, administered over 60 days. The results indicated that taurine supplementation significantly improved the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) in the liver and plasma. Additionally, an increase in lysozyme (LZM) activity was observed in mucus and plasma of the fish. Regarding gene expression, the 2% taurine supplementation significantly increased the expression of critical genes involved in carbohydrates and lipid metabolism, such as glucokinase (gck), hexokinase (hk1), and acetyl-CoA carboxylase (acoa1) in the liver, as well as lipase (lpl), cholecystokinin (cck), and trypsin (try1) in the intestine. These results suggest that taurine not only enhances the antioxidant and immune capacity of the fish but also optimizes their energy metabolism and digestion, which could contribute to improved aquaculture diets, promoting more excellent resistance to oxidative stress and better overall health of fish raised under intensive conditions. Show less

This study aimed to evaluate the effects of butyrate, butyric glycerides (BG) and their combination with sodium selenite (SeNa) or hydroxy-selenomethionine (OH-SeMet) on the performance and egg quality of the laying hens in post-peak period as well as the potential mechanism. A total of 900 45-week-old Hy-Line brown laying hens were randomly allocated to 5 treatment groups (n = 10 replicates/diet, 18 hens/replicate). The hens were fed the basal diet supplemented with 0.3 mg/kg selenium from SeNa (Control), Control plus 240 mg/kg butyric acid from coated butyrate (CB), Control plus 240 mg/kg butyric acid from butyric glycerides, basal diet supplemented with 0.3 mg/kg selenium from OH-SeMet plus coated butyrate (CB+OH-SeMet) or butyric glycerides (BG+OH-SeMet), respectively, for 20 weeks. Serum, liver, isthmus, uterus, and jejunum were collected at the end of the trial for biochemistry, histology, redox status, and gene expression analysis. Compared with Control, diets supplemented with BG, CB+OH-SeMet and BG+OH-SeMet increased (p < 0.05) the average egg weight (0.6-2.2 %), while only BG+OH-SeMet increased (p < 0.05) the total egg weight (7.1 %) and egg-laying rate (4.6 %) and decreased (p < 0.05) the feed/egg ratio (5.0 %) throughout the whole experiment. Furthermore, BG+OH-SeMet reduced (p < 0.05) the content of IL-6 and alanine aminotransferase (15.4-32.5 %), while elevated (p < 0.05) the content of IgA, IgY, IgM and total protein (18.7-26.8 %) in the serum in comparison to the Control. Notably, dietary supplementation of BG+OH-SeMet performed more effective antioxidant capacity in decreasing (p < 0.05) malondialdehyde (16.4-27.9 %) content and increasing (p < 0.05) the activity of total antioxidant capacity and glutathione peroxidase (17.6-36.3 %) in various tissues. Further experiment revealed that dietary BG+OH-SeMet regulated the lipid metabolism by increasing (p < 0.05) the expression of Carnitine palmitoyltransferase 1A (CPT1A) and Lipoprotein lipase (LPL) in liver. In conclusion, diets supplemented with BG and OH-SeMet could improve the laying performance via the enhancement of antioxidant capacity and regulation of lipid metabolism. Show less

Given that lipoprotein lipase (LPL) activity assays are not standardized for clinical use, we aimed to define reference values applicable to our clinical setting and identify a cut-off point to help distinguish Familial Chylomicronemia Syndrome from Multifactorial Chylomicronemia Syndrome, particularly in patients with inconclusive genetic findings. We evaluated 28 patients with a history of TG levels above 880 mg/dL (10 mmol/L), and assessed their likelihood of FCS using the Moulin score. LPL activity was measured in post-heparin plasma using a radiometric assay. Thirty normotriglyceridemic controls were used to define reference values. Genetic testing for FCS canonical genes and lipid profile was performed in all sHTG patients. The reference value for LPL activity was 33.3 (18.7-70.3) mIU, with a cut-off of 8.42 mIU (25 % of the median of NTG) to distinguish FCS from MCS. Eighteen patients without genetic variants in canonical genes, a Moulin score <9 and LPL activity >25 % of NTG, were classified as MCS. Five genetic diagnosed FCS patients, with a Moulin score>10 presented LPL activity <25 % of NTG. Four patients with inconclusive genetic results and a Moulin score>10 were classified as FCS according to LPL activity. LPL activity in patients with sHTG could be useful for differentiating FCS and MCS, particularly in patients with ambiguous or negative genetic findings, highlighting the need for specialized laboratory support in diagnostics. Show less

To investigate the effects and underlying mechanism of ionizing radiation on the adipogenic of mesenchymal stem cells (MSCs). Mouse MSCs were cultured in vitro and treated with 2 Gy and 6 Gy radiation with Bulk RNA-seq suggested that ionizing radiation promotes adipogenic differentiation of MSCs and up-regulation of oxidative stress-related genes and pathways. The results of Oil Red O staining and qPCR showed that ionizing radiation promoted the adipogenesis of MSCs, with high expression of Ionizing radiation promotes adipogenesis of MSCs in mice, and oxidative stress pathway participates in this effect, blocking Show less

This study used whole-genome sequence data on 406 beef cattle (203 Hanwoo and 203 Angus) to detect signatures of selection using four different methods; integrated haplotype score (iHS), Rsb, XP-EHH, and runs of homozygosity (ROH). Based on Rsb and XP-EHH analysis, 36 and 21 genomic regions differed significantly between Angus and Hanwoo breeds. Within breeds, we identified 108 regions (76 in Hanwoo and 32 in Angus) with the ROH analysis and 331 regions with the iHS method (298 in Hanwoo and 33 in Angus). The candidate genes related to meat quality, such as HSPA9 and LPL, were found within Hanwoo, while genes associated with growth and meat quantity traits, including ACTC1 and TMEM68, were identified within Angus. This study can assist in understanding the selection history of these breeds and identifying the genomic regions associated with the traits selected for in the breeding programs for these cattle breeds. Show less

The objective of this study was to evaluate the effects of the dietary lysine (Lys)/ methionine (Met) ratio in a low-protein diet on short-chain fatty acid (SCFA) profiles, villus morphology, antioxidant capacity, and immune status of the jejunum in Tibetan sheep. A total of 90 weaned Tibetan sheep, each 2 months old with an initial weight of 15.37 ± 0.92 kg, were randomly divided into three treatment groups. These groups were supplemented with different Lys/Met ratios of 3 [low protein-high methionine (LP-H)], 2 [low protein-medium methionine (LP-M)], and 1 [low protein-low methionine (LP-L)] in the basal diet (10% crude protein). The feeding trial lasted 100 days, including a 10-day acclimation period and a 90-day experimental period. The hematoxylin-eosin (H&E) sections showed that the LP-L group had a significantly increased villus height compared to the LP-M and LP-H groups ( Collectively, our results suggest that the dietary Met/ Lys ratio could affect the jejunal SCFA concentration by modulating the microbial community and regulating metabolism, thereby contributing to jejunal barrier function. Our findings provide a theoretical basis for the application of Lys/Met diet supplementation in the nutritional management of Tibetan sheep, particularly when reducing the dietary crude protein (CP) level. Show less

This study integrated the the effects of dietary Lys/Met ratio in a low protein diet on the meat quality in Tibetan sheep. A total of 90 weaned Tibetan sheep, 2 months old with initial weight of 15.37 ± 0.92 kg were randomly divided into 3 treatments, which were supplemented with Lys/Met ratio at 3 (LP-H), 2 (LP-M), and 1 (LP-L) in the basal diet (10 % crude protein), respectively. After slaughter (150 days of age), the growth performances and meat quality of longissimus dorsi muscle were evaluated. The LP-L group showed significantly higher final body weight compared to the LP-M group (P < 0.05). Serum albumin and total protein levels were significantly higher in the LP-L group than in the LP-H group (P < 0.05). Furthermore, meat from the LP-L group had significantly higher protein, calcium, and vitamin E content compared to the LP-M group (P < 0.05). Transcriptomic analysis revealed 3,479 differentially expressed genes enriched in pathways related to muscle growth, energy metabolism, and signaling transduction. Metabolomic analysis identified 771 differential metabolites, significantly enriched in ABC transporters, beta-alanine metabolism, and taste transduction pathways. Integrated analysis highlighted the upregulation of the ABCD4 gene and L-valine metabolite in the LP-L group, contributing to improved phenotypic traits. These findings provide molecular insights into the regulatory mechanisms underlying the effects of dietary Lys/Met ratios on Tibetan sheep meat quality and offer a basis for developing nutritional strategies to enhance premium meat production. Show less

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm Show less

Although the incidence of fatty liver disease (FLD) is increasing worldwide, the genetic basis of this disease is not fully understood. This study uses the fatty liver index (FLI) to identify and compare genetic variants associated with FLD in Taiwanese and European populations. In this study, a total of 145,356 Taiwan Biobank participants were included in the discovery analysis. Subjects with elevated FLI were found to have a significantly greater risk of developing FLD, as confirmed by imaging data (OR: 4.43; 95% CI: 3.88-5.06). Through genome-wide association studies (GWAS), we identified 6 variants previously associated with nonalcoholic fatty liver disease (NAFLD) and validated 50 shared risk variants located in ZPR1 and FTO between the Taiwanese and European populations. Conditional analysis of 423 significant variants from FLI-defined FLD further revealed 16 independent variants within 14 genes. Pathway analysis of GWAS significant genes revealed that lipid metabolism and the peroxisome proliferator-activated receptor (PPAR) signaling pathway are causes of hepatic fat accumulation. This study identified six independent NAFLD-associated variants in GCKR, LPL, TRIB1AL, and FTO and emphasized ZPR1 and FTO as shared risk genes for FLI-defined FLD in both Taiwanese and European populations. These findings support the utility of the FLI for FLD prediction, provide new genetic insights, and reveal the common genetic pathways of FLD across two ethnic groups. This research offers a valuable framework for advancing personalized medicine and therapeutic strategies for FLD. Show less

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies in patients with thromboembolic/thromboinflammatory events and/or obstetric complications. The aim of this study was to examine whether there are alterations in the platelet lipidome of APS patients in comparison with patients affected by thromboembolism without APS (control) and healthy volunteers. We applied quantitative mass spectrometry-based lipidomics to investigate the platelet lipidome of isolated resting and thrombin-stimulated platelets as well as platelet release in patients with APS, controls, and healthy volunteers. Lipidomic data revealed an increase in lysophospholipids (LPLs) in platelets from APS patients, specifically in lysophosphatidylcholine and lysophosphatidylethanolamine species. As LPLs are cleavage products generated by phospholipase A (PLA) from the corresponding phospholipid precursor, LPL/phospholipid ratios may be employed as surrogates for PLA1 and PLA2 activities. The surrogate ratios for PLA2, which participates in the release of arachidonic acid during platelet activation, were significantly increased in APS in both resting platelets and upon thrombin-induced activation for phosphatidylcholine and phosphatidylethanolamine. The phosphatidylcholine-PLA2 surrogate ratio was found to correlate with serum levels of anti-β2-glycoprotein I and anticardiolipin immunoglobulin G. Finally, receiver operator characteristic analysis demonstrated excellent discrimination of patients with APS from controls and healthy volunteers. These findings provide substantial evidence that platelet activation is enhanced in APS in vivo, involving the activation of PLA2. Show less

The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms. Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium. Summary data for 10 cardiometabolic diseases were compiled from both discovery and replication data sets. Expression quantitative trait loci data from relevant tissues were employed to evaluate significant lipid-modifying drug targets. Comprehensive analyses including colocalization, mediation, and bioinformatics were conducted to validate the results and investigate potential mediators and mechanisms. Significant causal associations were identified between lipids, lipid-modifying drug targets, and various cardiometabolic diseases. Notably, genetic enhancement of LPL (lipoprotein lipase) was linked to reduced risks of myocardial infarction (odds ratio [OR] The study substantiates the causal role of lipids in specific cardiometabolic diseases, highlighting LPL as a potent drug target. The effects of LPL are suggested to be influenced by changes in glucose and blood pressure, providing insights into its mechanism of action. Show less

A study of the lipidome and proteome was performed on milk fat globule membranes (MFGM) originating from milk samples from high (HL) and low (LL) lipolysis groups of cows. Combined univariate and multivariate statistical analyses proposed a set of variables highly associated to contrasted samples with regard to milk lipolysis. Milk from HL group were related to 4 phosphatidylinositols, 8 phosphatidylcholines, 1 sphingomyelin and 27 proteins, among them the phosphatidylcholine/phosphatidylethanolamine ratio and ORM1 may contribute to the membrane remodeling of the MFGM. The abundance of CP, CHI3L1, NECTIN2, A2M were strongly positively correlated with HL. Conversely, 3 phosphatidylinositols, 1 phosphatidylcholine and 2 phosphatidylethanolamines were assigned to the LL group. The HL group in cows is associated with a specific MFGM phospholipids and proteins profile, suggesting an impact on membrane fluidity and lipid rafts composition intervening in LPL anchoring and activation, as well as on pro-inflammatory lipids and proteins. Show less