Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma Show more
Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial. Here, we comprehensively investigated the effects and the underlying molecular mechanisms of ASGR1 deficiency and overexpression on atherosclerosis and liver injury in mice. We engineered After being fed a Western diet for 12 weeks, Inhibition of ASGR1 inhibits atherosclerosis in Western diet-fed Show less
In this study, Förster resonance energy transfer (FRET) is harnessed to construct a novel stimulus-responsive long-persistent luminescence (LPL) system. Two organic molecules, DPSD and DPOD, were init Show more
In this study, Förster resonance energy transfer (FRET) is harnessed to construct a novel stimulus-responsive long-persistent luminescence (LPL) system. Two organic molecules, DPSD and DPOD, were initially found to have no afterglow under ambient conditions, but exhibited prolonged afterglow upon friction with paper, showing a significantly promoted transition of triplet excited states. Substituting paper with α-cellulose (the main composition of paper) reveals a novel host-guest long afterglow system and allows for a deeper investigation of the above paper-promoted LPL phenomenon. The activation of the LPL effect was achieved by matrixing these components through a grinding process, capitalizing on the efficient FRET from the host to the guest owing to the appropriate energy level match, and the robust intersystem crossing (ISC) capability of the guest. This model presents a new matrix strategy to achieve efficient LPL by a facile, low cost and easy-to-handle process. Furthermore, we successfully implemented anti-counterfeiting, encryption and decryption, decoration, and water/heat stimulus-responsive applications of the obtained materials. These advancements bring LPL materials one step closer to practical commercialization. Show less
Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fa Show more
Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fasting and refeeding on blood biochemical indicators and transcriptional profiles in the hypothalamus and subcutaneous adipose tissue of geese. Biochemical assays reveal that fasting significantly increases levels of free fatty acids and glucagon, while reducing concentrations of triglycerides, leptin, and insulin. Transcriptomic analyses identify a complex transcriptional response in both the hypothalamus and subcutaneous adipose tissue, affecting several metabolic pathways and key genes associated with feed intake and energy metabolism. In subcutaneous adipose tissue, fasting downregulates genes involved in fatty acid synthesis ( Show less
Phenotypic associations have been reported between heart failure (HF) and blood lipids (BLs), blood pressure (BP), and blood glucose (BG). However, the shared genetic etiology underlying these associa Show more
Phenotypic associations have been reported between heart failure (HF) and blood lipids (BLs), blood pressure (BP), and blood glucose (BG). However, the shared genetic etiology underlying these associations remains incompletely understood. Conducting a large-scale multi-trait association study for HF with these traits, we discovered 143 previously unreported genomic risk loci for HF. Results showed that 46, 35, and 14 colocalized loci were shared by HF with BLs, BP, and BG, respectively. Notably, the loci shared by HF with these traits rarely overlapped, indicating distinct mechanisms. The combination of gene-mapping, gene-based, and transcriptome-wide association analyses prioritized noteworthy candidate genes (such as lipoprotein lipase [LPL], G protein-coupled receptor kinase 5 [GRK5], and troponin C1, slow skeletal and cardiac type [TNNC1]) for HF. Enrichment analysis revealed that HF exhibited comparable characteristics to cardiovascular traits and metabolic traits correlated to BLs, BP, and BG. Finally, we reported drug repurposing candidates and plasma protein targets for HF. These results provide biological insights into the pathogenesis of these comorbidities of HF. Show less
Hanqi Wang, Xiaozhi Hu, Yuting Zhang+6 more · 2024 · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · Springer · added 2026-04-24
Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary Show more
Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary to seek novel therapeutic strategies for atherosclerosis that can not only lower lipid levels but also inhibit inflammation simultaneously. The fusion protein FD03-IL-1Ra was designed by linking the Angiopoietin-like 3 (ANGPTL3) nanobody and human interleukin-1 receptor antagonist (IL-1Ra) sequences to a mutated human immunoglobulin gamma 1 (IgG1) Fc. This construct was transfected into HEK293 cells for expression. The purity and thermal stability of the fusion protein were assessed using SDS-PAGE, SEC-HPLC, and differential scanning calorimetry. Binding affinities of the fusion protein to ANGPTL3 and IL-1 receptor were measured using Biacore T200. The biological activity of the fusion protein was validated through in vitro experiments. The therapeutic efficacy of the fusion protein was evaluated in an ApoE-/- mouse model of atherosclerosis, including serum lipid level determination, histological analysis of aorta and aortic sinus sections, and detection of inflammatory and oxidative stress markers. ImageJ software was utilized for quantitative image analysis. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc test. The FD03-IL-1Ra fusion protein was successfully expressed, with no polymer formation detected, and it demonstrated good thermal and conformational stability. High affinity for both murine and human ANGPTL3 was exhibited by FD03-IL-1Ra, and it was able to antagonize hANGPTL3's inhibition of LPL activity. FD03-IL-1Ra also showed high affinity for both murine and human IL-1R, inhibiting IL-6 expression in A549 cells induced by IL-1β stimulation, as well as suppressing IL-1β-induced activity inhibition in A375.S2 cells. Our study revealed that the fusion protein effectively lowered serum lipid levels and alleviated inflammatory responses in mice. Furthermore, the fusion protein enhanced plaque stability by increasing collagen content within atherosclerotic plaques. These findings highlighted the potential of bifunctional interleukin-1 receptor antagonist and ANGPTL3 antibody fusion proteins for ameliorating the progression of atherosclerosis, presenting a promising novel therapeutic approach targeting both inflammation and lipid levels. Show less
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype corre Show more
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype correlation, and clinical differences between FCS and multifactorial chylomicronemia syndrome (MCS). The study included 154 patients (FCS, 74; MCS, 80) from the UK FCS national registry and the UK arm of the FCS International Quality Improvement and Service Evaluation Project. FCS was relatively common in non-Europeans and those with parental consanguinity ( The frequency of gene variant distribution varies based on the ethnic origin of patients with FCS. Patients with FCS are at a higher risk of pancreatic complications while the prevalence of atherosclerotic cardiovascular disease is lower in FCS compared with MCS. Carriers of heterozygous pathogenic variants have an intermediate phenotype between FCS and variant-negative MCS. Show less
Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [P Show more
Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [PFK], pyruvate kinase [PK]) and lipolysis (fatty acid synthetase [FAS], lipoprotein lipase [LPL]) enzyme activities, anti-oxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]) activities, malondialdehyde (MDA), lactate and glycogen contents, gill histological parameters (lamellar length [SLL], width [SLW], interlamellar distance [ID]), respiratory frequency (RF), the proportion of the secondary lamellae available for gas exchange (PAGE), and hifs (hif-1α, hif-2α, hif-3α) expression were determined during long-term hypoxia and reoxygenation. Results showed that long-term hypoxia (3.34 ± 0.17 mg L Show less
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent lu Show more
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent luminescent (LPL) materials and rare-earth (RE) luminescence lies in utilizing organic host materials to sensitize RE luminescence, as well as employing Förster resonance energy transfer from hydrogen-bonded organic framework (HOF) phosphorescence to RE compound luminescence. This work introduces a one-pot, in situ pyrolytic condensation method, achieved through high-temperature melting calcination, to synthesize lanthanide ion-doped HOF materials. This method circumvents the drawback of molecular triplet energy annihilation, enabling the creation of organic LPL materials with RE characteristics. The HOF material serves as the host, exhibiting blue phosphorescence and cyan LPL. By fine-tuning the doping amount, the composite material U-Tb-100 achieves green LPL with a luminescent quantum yield of 56.4 %, and an LPL duration of approximately 2-3 s, demonstrating tunable persistence. Single-crystal X-ray diffraction, spectral analysis, and theoretical calculation unveil that U-Tb-100 exhibits exceptional quantum yield and long-lived luminescence primarily due to the efficient sensitization of U monomer to RE ions and the PRET process between U and RE complexes. This ingenious strategy not only expands the repertoire of HOF materials but also facilitates the design of multifunctional LPL materials. Show less
Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for Show more
Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for the growth and development of poultry. This study aimed to investigate the effects of embryo thermal manipulation with high (TMH, 39.5 °C, 65% RH, 8 h/d) and low (TML, 20 °C, 65% RH, 1 h/d) temperatures during 8th to 15th embryonic age on hatching performance and liver lipid metabolism in layer chicks. Additionally, the duration of TM effects was evaluated through a short-term feeding trial. The results indicated that TMH accelerated the hatching process without significantly affecting hatchability and growth performance. In contrast, TML delayed hatching time and significantly reduced hatchability and chick quality. After hatching, TML also increased residual yolk weight and reduced the relative liver weight in relation to body weight and yolk-free body mass. Moreover, lipid droplets in the liver were stained with Oil Red O, and the lipid content in the liver and serum was further detected. TMH had no significant impact on triglyceride (TG) and total-cholesterol (TCHO) content in the liver and serum but upregulated the expression of lipogenesis-related genes ACC, Fas, and Fatp1 compared to the TML group. Conversely, TML significantly reduced liver TG content, enhanced lipoprotein lipase (LPL) activity, and promoted the expression of lipid oxidation-related genes CPT-1, PGC-1α, and PPARα. At 7 d of age, liver LPL activity was significantly increased in the TMH group. However, there were no significant changes in the content of TG and TCHO in the liver and the expression of lipid metabolism-related genes in the TML group. Overall, these results indicate that embryonic TM alters hatching performance and liver lipid metabolism in layer chicks. TML reduces TG content by increasing liver lipid oxidation capacity. However, this effect is not long-lasting, as the influence of TM diminishes as the chicks develop. Show less
The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to Show more
The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins. Show less
Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge Show more
Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge challenge since it is intrinsically contradictory to the triplet- and solid-state emission nature of organic afterglow. Here, narrow-band, long-lived, and full-color organic LPL is realized by isolating multi-resonant thermally activated delayed fluorescent (MR-TADF) fluorophores in a glassy steroid-type host through a facile melt-cooling treatment. Such prepared host becomes capable of exciton dissociation and recombination (EDR) upon photoirradiation for both long-lived fluorescence and phosphorescence; and, the efficient Förster resonance energy transfer (FRET) from the host to various MR-TADF emitters leads to high-performance LPL, exhibiting small FWHM of 33 nm, long persistent time over 10 s, and facile color-tuning in a wide range from deep-blue to orange (414-600 nm). Moreover, with the extraordinary narrowband LPL and easy processability of the material, centimeter-scale flexible optical waveguide fibers and integrated FWHM/color/lifetime-resolved multilevel encryption/decryption devices have been designed and fabricated. This novel EDR and singlet/triplet-to-singlet FRET strategy to achieve excellent LPL performances illustrates a promising way for constructing flexible organic afterglow with easy preparation methods, shedding valuable scientific insights into the design of narrow-band emission in organic afterglow. Show less
Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limit Show more
Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints. Show less
It has been reported that carbonic anhydrase I (CA1) is a target for the diagnosis and therapy of atherosclerosis (AS) since CA1 can promote AS aortic calcification. We also found that methazolamide ( Show more
It has been reported that carbonic anhydrase I (CA1) is a target for the diagnosis and therapy of atherosclerosis (AS) since CA1 can promote AS aortic calcification. We also found that methazolamide (MTZ), a drug for glaucoma treatment and an inhibitor of carbonic anhydrases, can treat AS by inhibiting calcification in aortic tissues. This study focused on the therapeutic mechanism of MTZ and the pathogenic mechanism of AS. In this study, a routine AS animal model was established in ApoE-/- mice, which were treated with MTZ. The aortic tissues were analyzed using single-cell sequencing. MTZ significantly increased the proportions of B-1/MZB B cells with high expressions of Nr4A1 and Ccr7, CD8+CD122+ Treg-like cells with high Nr4A1 expression, and smooth muscle cells with high Tpm2 expression. These cells or their marker genes were reported to exert immunosuppressive, anti-proinflammatory, and atheroprotective effects. MTZ also decreased the proportions of endothelial cells with high expressions of Retn, Apoc1, Lcn2, Mt1, Serpina3, Lpl, and Lgals3; nonclassical CD14+CD16++ monocytes with high expressions of Mt1, Tyrobp, Lgals3, and Cxcl2; and Spp1+ macrophages with high expressions of Mmp-12, Trem2, Mt1, Lgals3, Cxcl2, and Lpl. These cells or their marker genes have been reported to promote inflammation, calcification, tissue remodeling, and atherogenesis. A significant decrease in the proportion of CD8+CD183 (CXCR3)+ T cells, the counterpart of murine CD8+CD122+ T cells, was detected in the peripheral blood of newly diagnosed AS patients rather than in that of patients receiving anti-AS treatments. These results suggest that MTZ can treat AS by increasing immunosuppressive cells and decreasing expressions of genes related to inflammation, calcification, and tissue remodeling. Show less
As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 Show more
As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 reached the highest expression at 60 h after the differentiation of goat intramuscular preadipocytes. Overexpression of goat NR4A1 increased the number of intracellular lipid droplets and up-regulated the expression of adipocyte-differentiation-related marker genes including Show less
Poultry is a source of meat that is in great demand in the world. The quality of meat is an imperative point for shoppers. To explore the genes controlling meat quality characteristics, the growth and Show more
Poultry is a source of meat that is in great demand in the world. The quality of meat is an imperative point for shoppers. To explore the genes controlling meat quality characteristics, the growth and meat quality traits and muscle transcriptome of two indigenous Yunnan chicken breeds, Wuding chickens (WDs) and Daweishan mini chickens (MCs), were compared with Cobb broilers (CBs). The growth and meat quality characteristics of these two indigenous breeds were found to differ from CB. In particular, the crude fat (CF), inosine monophosphate content, amino acid (AA), and total fatty acid (TFA) content of WDs were significantly higher than those of CBs and MCs. In addition, it was found that MC pectoralis had 420 differentially expressed genes (DEGs) relative to CBs, and WDs had 217 DEGs relative to CBs. Among them, 105 DEGs were shared. The results of 10 selected genes were also confirmed by qPCR. The differentially expressed genes were six enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways including lysosomes, phagosomes, PPAR signaling pathways, cell adhesion molecules, cytokine-cytokine receptor interaction, and phagosome sphingolipid metabolism. Interestingly, four genes ( Show less
Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a Show more
Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation. Show less
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 t Show more
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
Lihua Wang, Siyu Wang, Jason A Anema+12 more · 2024 · medRxiv : the preprint server for health sciences · Cold Spring Harbor Laboratory · added 2026-04-24
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 pr Show more
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
Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilit Show more
Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilities. This study aimed to investigate the impact of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the adipogenic differentiation of autologous cells. Our findings indicate that the proliferation rate of hPDLSCs increased with increasing initial cell density (0.5-8 × 10 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 mul Show more
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 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 Show more
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
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) prof Show more
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
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 Show more
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 Show more
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
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 fe Show more
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
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 Show more
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 decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with Show more
The decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy. Show less