Overexpression of PER2 Promotes De Novo Fatty Acid Synthesis, Fatty Acid Desaturation, and Triglyceride Accumulation in Bovine Mammary Epithelial Cells.

The core clock gene is associated with mammary gland development and lipid synthesis in rodents and has recently been found to have a diurnal variation in the process of lactation, but has not yet been demonstrated in bovine mammary epithelial cells (BMECs). To explore the regulatory function of on milk fat synthesis in bovine mammary epithelial cells, we initially assessed the expression of clock genes and milk fat metabolism genes for 24 h using real-time quantitative PCR and fitted the data to a cosine function curve. Subsequently, we overexpressed the in BMECs using plasmid vector (pcDNA3.

Time-Resolved Inspection of Ionizable Lipid-Facilitated Lipid Nanoparticle Disintegration and Cargo Release at an Early Endosomal Membrane Mimic.

Advances in lipid nanoparticle (LNP) design have contributed notably to the emergence of the current clinically approved mRNA-based vaccines and are of high relevance for delivering mRNA to combat diseases where therapeutic alternatives are sparse. LNP-assisted mRNA delivery utilizes ionizable lipid-mediated cargo translocation across the endosomal membrane driven by the acidification of the endosomal environment. However, this process occurs at a low efficiency, a few percent at the best.

A metagenomics study reveals the gut microbiome as a sex-specific modulator of healthy aging in Hainan centenarians.

Background: Sex differences in health status and life expectancy are widely accepted to exist. The mechanisms underlying it are still poorly understood. In this study, we aimed to clarify the influences and contributions of sex on the gut microbiome in healthy centenarians and to explore the different roles played by the gut microbiome in healthy aging between the sexes.

Hereditary hemorrhagic telangiectasia involving portal venous system: A case report and review of the literature.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population. It is characterized by vasodilation, which affects specific organs, such as the skin, mucous membranes, brain, lungs, gastrointestinal tract, liver, and others. However, HHT rarely involves the portal venous system to cause serious clinical complications.

Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis.

We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 10 cfu), mixed probiotics (Mixed, 5 × 10 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively.

Regulation of serotonin production by specific microbes from piglet gut.

Background: Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague.

Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions.

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs).

Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion.

Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of mRNA therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed at the anionic endosomal membrane prior to mRNA release. We used surface-sensitive fluorescence microscopy with single LNP resolution to investigate the pH dependency of the binding kinetics of ionizable lipid-containing LNPs to a supported endosomal model membrane.

Amino acid utilization allows intestinal dominance of Lactobacillus amylovorus.

The mammalian intestine harbors heterogeneous distribution of microbes among which specific taxa (e.g. Lactobacillus) dominate across mammals.

Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics.

The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most microbial studies on longevity are commonly based on metagenomic sequencing which may lose information about the functional microbes with extremely low abundance. Here, we combined in-depth metagenomic sequencing and large-scale culturomics to reveal the unique gut microbial structure of a Chinese longevity population, and to explore the possible relationship between intestinal microbes and longevity.

Transcriptome profiling of mRNAs in muscle tissue of Pinan cattle and Nanyang cattle.

Mammalian muscle development is regulated by complex gene networks at the molecular level. The revelation of gene regulatory mechanisms is an important basis for the study of muscle development and molecular breeding. To analyze the excellent meat performance of Pinan cattle at the molecular level, we performed high-throughput RNA sequencing to analyze the key regulatory genes that determine the muscle quality traits in Pinan cattle (n = 3) and Nanyang cattle (n = 3).

Circadian Gene Silencing Downregulates and and Suppresses Lipid Synthesis in Bovine Mammary Epithelial Cells.

a circadian clock gene, is associated with mammary gland development and lipid synthesis in rodents, partly via regulating peroxisome proliferator-activated receptor gamma (). Whether such a type of molecular link existed in bovines was unclear. We hypothesized that was associated with lipid metabolism and regulated cell cycles and apoptosis in bovine mammary epithelial cells (BMECs).

Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein.

Metagenomics Study Reveals Changes in Gut Microbiota in Centenarians: A Cohort Study of Hainan Centenarians.

Several studies based on 16SrDNA analysis have revealed certain unique characteristics of gut microbiome in centenarians. We established a prospective cohort of fecal microbiota and conducted the first metagenomics-based study among centenarians. The objective was to explore the dynamic changes of gut microbiota in healthy centenarians and centenarians approaching end of life and to unravel the characteristics of aging-associated microbiome.

Asymmetric cationic liposomes designed for heat-activated association with cells.

Improved anticancer drugs and drug carriers are needed in combination therapies, such as hyperthermia-assisted chemotherapy. Liposomal drug carriers with advanced functions are attractive candidates for targeted accumulation and drug release in response to heat stimulus. We report on the design of liposomes with a heat-activated surface function.

Temperature and electric-field induced phase transitions, and full tensor properties of [011] -poled domain-engineered tetragonal 0.63Pb(MgNb)-0.37PbTiO single crystals.

The phase-transition sequence of 0.67Pb(MgNb)-0.37PbTiO (PMN-0.

Effects of Al(3+) on Phosphocholine and Phosphoglycerol Containing Solid Supported Lipid Bilayers.

Aluminum has attracted great attention recently as it has been suggested by several studies to be associated with increased risks for Alzheimer's and Parkinson's disease. The toxicity of the trivalent ion is assumed to derive from structural changes induced in lipid bilayers upon binding, though the mechanism of this process is still not well understood. In the present study we elucidate the effect of Al(3+) on supported lipid bilayers (SLBs) using fluorescence microscopy, the quartz crystal microbalance with dissipation (QCM-D) technique, dual-polarization interferometry (DPI), and molecular dynamics (MD) simulations.

Recent advances on the circadian gene and metabolic rhythm of lactation of mammary gland.

Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in developing the milk duct and maintaining the polarity and the morphology of the mammary epithelium; at the same time, it is also closely related with the metabolism of milk protein and milk fat. This paper summarized recent researches on gene and related researches on mammary gland development and metabolism to provide some information for the studies of the theory and technology on physiological functions of the mammary gland and milk quality control.

Heat-activated liposome targeting to streptavidin-coated surfaces.

There is a great need of improved anticancer drugs and corresponding drug carriers. In particular, liposomal drug carriers with heat-activated release and targeting functions are being developed for combined hyperthermia and chemotherapy treatments of tumors. The aim of this study is to demonstrate the heat-activation of liposome targeting to biotinylated surfaces, in model experiments where streptavidin is used as a pretargeting protein.

Formation of supported lipid bilayers on silica: relation to lipid phase transition temperature and liposome size.

DPPC liposomes ranging from 90 nm to 160 nm in diameter were prepared and used for studies of the formation of supported lipid membranes on silica (SiO2) at temperatures below and above the gel to liquid-crystalline phase transition temperature (Tm = 41 °C), and by applying temperature gradients through Tm. The main method was the quartz crystal microbalance with dissipation (QCM-D) technique. It was found that liposomes smaller than 100 nm spontaneously rupture on the silica surface when deposited at a temperature above Tm and at a critical surface coverage, following a well-established pathway.

Phase transition-controlled flip-flop in asymmetric lipid membranes.

Lipid membrane asymmetry is of fundamental importance for biological systems and also provides an attractive means for molecular control over biomaterial surface properties (including drug carriers). In particular, temperature-dependent changes of surface properties can be achieved by taking advantage of distinct phase transitions in lipid membrane coatings where lipids exchange (flip-flop) between leaflets. In this study, temperature is used to control flip-flop of lipids in asymmetric lipid membranes on planar solid supports, where the two leaflets of the lipid membrane are in different phase states.

Ultrasound-triggered smart drug release from multifunctional core-shell capsules one-step fabricated by coaxial electrospray method.

Multifunctional core-shell capsules that triggered release by ultrasound stimulus were one-step fabricated by the coaxial electrospray method. The TiO(2) shell suppressed the initial burst release of the paclitaxel. Fe(3)O(4) and graphene quantum dots inside the oil core functioned successfully for magnetic targeting and fluorescence imaging, respectively.

A novel catalyst based on electrospun silver-doped silica fibers with ribbon morphology.

Mesoporous silica nanofibers and Ag-doped composite nanoribbons were synthesized by a facile combination of an electrospinning technique and the sol-gel method. Tetraethyl orthosilicate, polyvinylpyrrolidone (PVP), triblock poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), copolymer Pluronic P123, and silver nitrate (AgNO(3)) were the components of sol for the production of Ag-doped hybrid silica ribbons. Heat removal of structure-directing agent P123 in the hybrid fibers at high temperatures resulted in a mesoporous morphology, and the degradation of PVP caused AgNO(3) to convert into silver in the form of nanoparticles.