Integrating Single-Cell and Spatial Transcriptomics Reveals Heterogeneity of Early Pig Skin Development and a Subpopulation with Hair Placode Formation.

The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin-related diseases in humans. Here, single-cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods.

Computer-directed rational design enhanced the thermostability of carbonyl reductase LsCR for the synthesis of ticagrelor precursor.

Carbonyl reductases are useful for producing optically active alcohols from their corresponding prochiral ketones. Herein, we applied a computer-assisted strategy to increase the thermostability of a previously constructed carbonyl reductase, LsCR (N101D/A117G/F147L/E145A), which showed an outstanding activity in the synthesis of the ticagrelor precursor (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol. The stability changes introduced by mutations at the flexible sites were predicted using the computational tools FoldX, I-Mutant 3.

Structural-guided design to improve the catalytic performance of aldo-keto reductase KdAKR.

Aldo-keto reductases (AKRs) are important biocatalysts that can be used to synthesize chiral pharmaceutical alcohols. In this study, the catalytic activity and stereoselectivity of a NADPH-dependent AKR from Kluyveromyces dobzhanskii (KdAKR) toward t-butyl 6-chloro (5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) were improved by mutating its residues in the loop regions around the substrate-binding pocket. And the thermostability of KdAKR was improved by a consensus sequence method targeted on the flexible regions.

USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination.

Background: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown.

A novel Anti-ROS osteoblast-specific delivery system for ankylosing spondylitis treatment via suppression of both inflammation and pathological new bone formation.

Ankylosing spondylitis (AS) is a common rheumatic disorder distinguished by chronic inflammation and heterotopic ossification at local entheses sites. Currently available medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors, are limited by side effects, high costs and unclear inhibitory effects on heterotopic ossification. Herein, we developed manganese ferrite nanoparticles modified by the aptamer CH6 (CH6-MF NPs) that can efficiently scavenge ROS and actively deliver siRNA into hMSCs and osteoblasts in vivo for effective AS treatment.

Coevolving stability and activity of LsCR by a single point mutation and constructing neat substrate bioreaction system.

Carbonyl reductase (CR)-catalyzed bioreduction in the organic phase and the neat substrate reaction system is a lasting challenge, placing higher requirements on the performance of enzymes. Protein engineering is an effective method to enhance the properties of enzymes for industrial applications. In the present work, a single point mutation E145A on our previously constructed CR mutant LsCR , coevolved thermostability, and activity.

Competing endogenous RNA network construction based on long non-coding RNAs, microRNAs, and mRNAs related to fat deposition in Songliao black swine.

China has a long history of pig breeding and a number of local breeds. The Songliao Black pig, bred in China in 2009, shows high variation in backfat thickness and therefore is well-suited to fat deposition research. Fat deposition is a complex trait, and the underlying regulatory factors are not fully characterized.

Inhibits Intramuscular Fat Deposition through Targeting by ceRNA Regulatory Network.

Intramuscular fat (IMF) deposition is an important determinant of pork quality and a complex process facilitated by non-coding ceRNAs. In this study, 52 Berkshire × Anqing Sixwhite crossbred pigs were slaughtered to measure eight carcass and pork quality traits. Whole-transcriptome sequencing analysis was performed using longissimus dorsi samples of six low- and high-IMF samples; 34 ceRNA networks, based on 881, 394, 158 differentially expressed (DE) lncRNAs, miRNAs, and mRNAs, were constructed.

Using Machine Learning to Identify Biomarkers Affecting Fat Deposition in Pigs by Integrating Multisource Transcriptome Information.

Fat deposition in pigs is not only closely related to pig production efficiency and pork quality but also an ideal model for human obesity. Transcriptome sequencing is widely used to study fat deposition. However, due to small sample sizes, high false positive rates, and poor consistency of results from different studies, new strategies are urgently needed.

Directed evolution of a carbonyl reductase LsCR for the enantioselective synthesis of (1S)-2-chloro-1-(3,4-difluorophenyl) ethanol.

Traditional screening methods of enzyme engineering often require building large mutant libraries to screen for potentially beneficial sites, which are often time-consuming and labor-intensive with low mining efficiency. In this study, a novel enzyme engineering strategy was established to modify carbonyl reductase LsCR for the synthesis of (1S)-2-chloro-1-(3,4-difluorophenyl) ethanol ((S)-CFPL), which is a key intermediate of anticoagulant drug ticagrelor. The strategy was developed by combining HotSpot, FireProt and multiple sequence alignment, resulting in the construction of a "small and smart" mutant library including 10 mutations.

miR-29a-5p Inhibits Prenatal Hair Placode Formation Through Targeting EDAR by ceRNA Regulatory Network.

Hair placode formation is an important stage of hair follicle morphogenesis and it is a complex process facilitated by non-coding RNAs. In this study, we conducted whole transcriptome sequencing analysis of skin, heart, liver, lung, and kidney tissues of day 41 (E41) normal and hairless pig embryos, and respectively detected 15, 8, and 515 skin-specific differentially expressed (DE) lncRNAs, miRNAs, and mRNAs. Furthermore, 18 competing endogenous RNA (ceRNA) networks were constructed.

Identification of Potential Candidate Genes From Co-Expression Module Analysis During Preadipocyte Differentiation in Landrace Pig.

Preadipocyte differentiation plays an important role in lipid deposition and affects fattening efficiency in pigs. In the present study, preadipocytes isolated from the subcutaneous adipose tissue of three Landrace piglets were induced into mature adipocytes . Gene clusters associated with fat deposition were investigated using RNA sequencing data at four time points during preadipocyte differentiation.

Identification of Long Non-Coding RNAs Involved in Porcine Fat Deposition Using Two High-Throughput Sequencing Methods.

Adipose is an important body tissue in pigs, and fatty traits are critical in pig production. The function of long non-coding RNA (lncRNA) in fat deposition and metabolism has been found in previous studies. In this study, we collected the adipose tissue of six Landrace pigs with contrast backfat thickness (n = 3, n = 3), after which we performed strand-specific RNA sequencing (RNA-seq) based on pooling and biological replicate methods.

Tuning enzymatic properties by protein engineering toward catalytic tetrad of carbonyl reductase.

Enzyme engineering toward catalytic-tetrad residues usually results in activity loss. Unexpectedly, we found that a directed evolution campaign yielded a beneficial residue A100 in KmCR (a carbonyl reductase from Kluyveromyces marxianus ZJB14056), which is a residue of catalytic tetrad and conserved according to multiple sequence alignment. Inspired by this finding, we performed saturation mutagenesis on all the four residues of catalytic tetrad of KmCR.

Identification of key genes affecting porcine fat deposition based on co-expression network analysis of weighted genes.

Background: Fat deposition is an important economic consideration in pig production. The amount of fat deposition in pigs seriously affects production efficiency, quality, and reproductive performance, while also affecting consumers' choice of pork. Weighted gene co-expression network analysis (WGCNA) is effective in pig genetic studies.

A Single-Step Genome Wide Association Study on Body Size Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs.

The body shape of a pig is the most direct production index, which can fully reflect the pig's growth status and is closely related to important economic traits. In this study, a genome-wide association study on seven body size traits, the body length (BL), height (BH), chest circumference (CC), abdominal circumference (AC), cannon bone circumference (CBC), rump width (RW), and chest width (CW), were conducted in Yorkshire pigs. Illumina Porcine 80K SNP chips were used to genotype 589 of 5,572 Yorkshire pigs with body size records, and then the chip data was imputed to sequencing data.

Novel DNA methylation markers of PRRSV-specific antibodies and their intergenerational transmission from pregnant sows to piglets.

The main strategy for preventing porcine reproductive and respiratory syndrome (PRRS) is vaccination. However, current commercial porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have limited effectiveness and may even cause infections in pigs. The identification of stable molecular markers associated with immune responses to PRRSV vaccination in pigs provides a new approach for PRRS prevention.

The GPER1/SPOP axis mediates ubiquitination-dependent degradation of ERα to inhibit the growth of breast cancer induced by oestrogen.

G protein-coupled oestrogen receptor 1 (GPER1), predicted to be a novel oestrogen receptor, has been linked to the development and progression of breast cancer. However, the molecular mechanisms underlying its functions remain elusive. Here, we show that the protein levels of GPER1 are negatively associated with those of ERα and that higher expression of GPER1 correlated with a better clinical outcome in oestrogen receptor-positive (ER+) breast cancer patients.

The FTO/miR-181b-3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer.

Background: N6-methyladenosine (m A) RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors, including breast cancer. Fat mass and obesity-associated (FTO) enzyme, initially known as the obesity-related protein, is the first identified m A demethylase. However, the relationship between FTO and breast cancer remains controversial.

Synthesis of the Carbon-Coated Nanoparticle CoS and Its Electrochemical Performance as an Anode Material for Sodium-Ion Batteries.

A CoS/C nanocomposite is prepared using a solid-state reaction followed by a facile mechanical ball-milling treatment, with sucrose as the carbon source. The phases, morphologies, and detailed structures of the CoS/C nanocomposite are well-characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. When evaluated as an anode material for sodium-ion batteries, the CoS/C nanocomposite electrode displays a reversible capacity of ∼567 mA h g in the initial cycle and maintains a reversible capacity of ∼320 mA h g after 30 cycles, indicating a larger capacity and a stable cycling performance.

[Bilateral solitary fungus balls sphenoid sinus].

Diagnosis of sphenoid sinus disease is very difficult because the location of sinus is deep and hidden within the skull and the symptoms of sphenoiditis are nonspecific. However, thanks to new technologies in imaging (CT and MRI) and nasal endoscopy, the literature on sphenoid sinus fungus ball have been published more. But all of the SSFB which have been reported are isolated or unilateral.

Interpreting the process behind endemism in China by integrating the phylogeography and ecological niche models of the Stachyridopsis ruficeps.

An area of endemism (AOE) is a complex expression of the ecological and evolutionary history of a species. Here we aim to address the principal drivers of avian diversification in shaping patterns of endemism in China by integrating genetic, ecological, and distributional data on the Red-headed Tree Babbler (Stachyridopsis ruficeps), which is distributed across the eastern Himalayas and south China. We sequenced two mtDNA markers from 182 individuals representing all three of the primary AOEs in China.