Multi-omics analysis of functional substances and expression verification in cashmere fineness.

BACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.

Association analysis for SNPs of LIPE and ITGB4 genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.

Alkyl-Substituted N,S-Embedded Heterocycloarenes with a Planar Aromatic Configuration for Hosting Fullerenes and Organic Field-Effect Transistors.

Cycloarenes and heterocycloarenes display unique physical structures and hold great potential as organic semiconductors. However, the synthesis of (hetero)cycloarenes remains a big challenge, and there are limited reports on their applications. Herein, a series of nitrogen- and sulfur-codoped cycloarenes NS-Octulene-n (n = 2, 3, 4) with branched alkyl substituents containing linear spacer groups from C2 to C4 have been conveniently synthesized. Compared with their isoelectronic analogues Octulene and S-Octulene, both having a saddle-shaped configuration, the coincorporation of two nitrogen atoms and two sulfur atoms leads to a fully coplanar aromatic backbone structure. Each of these three planar heterocycloarenes acts as a supramolecular host for encapsulation of both fullerenes C60 and C70 with a stronger donor-acceptor interaction for the complexation between the heterocycloarene and C70 due to the unique molecular geometry and defined cavity. Meanwhile, the electron-rich nitrogen atoms also slightly increase the energies of both highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in this series of planar heterocycloarenes, indicating that they can be used as p-type semiconductors. Most importantly, benefitting from the planar π-conjugated backbone structure accompanied by excellent crystallinity and ordered molecular packing, as well as upon the engineering of the alkyl chain branching position, thin-film field-effect transistors of NS-Octulene-3 with moderate alkyl branching point exhibit the maximum hole mobility of 0.86 cm2 V-1 s-1, which is the highest for (hetero)cycloarene-based organic semiconductors. This study will shed new light on designing novel high-performance macrocyclic polycyclic aromatic hydrocarbon (PAH) semiconductors.

Fluorescent probes based on multifunctional encapsulated perylene diimide dyes for imaging of lipid droplets in live cells.

Due to their strong hydrophobicity and the aggregation-caused quenching effect, the application of perylene diimide (PDI) dyes in biological and medicinal fields lags far behind that of other dyes. Based on a multifunctional encapsulation strategy, we prepared isopropylphenyl sulfone encapsulated PDI dyes (SFPDIs). The four hydrophilic sulfone groups on the bay position of the PDIs not only effectively inhibit the fluorescence quenching caused by π-aggregation but also endow the SFPDIs with good live-cell permeability. The six lipophilic isopropylphenyl groups encapsulate PDI emitters and confer SFPDIs with excellent lipid droplet-targeting ability. Furthermore, the strong electron-withdrawing sulfone groups give the PDIs excellent anti-oxidation ability.

Transition from stochastic events to deterministic ensemble average in electron transfer reactions revealed by single-molecule conductance measurement.

Electron transfer reactions can now be followed at the single-molecule level, but the connection between the microscopic and macroscopic data remains to be understood. By monitoring the conductance of a single molecule, we show that the individual electron transfer reaction events are stochastic and manifested as large conductance fluctuations. The fluctuation probability follows first-order kinetics with potential dependent rate constants described by the Butler-Volmer relation. Ensemble averaging of many individual reaction events leads to a deterministic dependence of the conductance on the external electrochemical potential that follows the Nernst equation. This study discloses a systematic transition from stochastic kinetics of individual reaction events to deterministic thermodynamics of ensemble averages and provides insights into electron transfer processes of small systems, consisting of a single molecule or a small number of molecules.

Association between the cashmere production performance, milk production performance, and body size traits and polymorphism of COL6A5 and LOC102181374 genes in Liaoning cashmere goats.

The purpose of this study was to analyze the relationship between COL6A5 (collagen type VI alpha 5 chain) and LOC102181374 (alcohol dehydrogenase 1) genes and the production performance of Liaoning cashmere goats by single nucleotide polymorphism (SNP). We have searched for SNP loci of COL6A5 and LOC102181374 genes through sequence alignment and PCR experiments, and have used SPSS and SHEsis software to analyze production data. We obtained five SNP loci in total, including three SNP loci (G50985A, G51140T, G51175A) in COL6A5 gene and two SNP loci (A10067G, T10108C) in LOC102181374 gene. The genotypes G50985A (AG), G51140T (GT), G51175A (AA), A10067G (AA), and T10108C (CC) of these loci have certain advantages in improving the production performance of Liaoning cashmere goats. The haplotype combinations that can improve production performance in COL6A5 gene were H1H5:AGGGAG, H4H4:GGGGAA, and H4H4:GGGGAA. H3H3:GGCC and H2H4:AGTT were the dominant combinations in LOC102181374 gene. At G51175A and A10067G loci, we found that H1H2:AAAG and H1H3:AGAA have dominant effects. These results may provide some support for the molecular breeding of production traits in Liaoning cashmere goats.

Crystal Engineering of Angular-Shaped Heteroarenes Based on Cyclopenta[b]thiopyran for Controlling the Charge Carrier Mobility.

Cyclopenta[b]thiopyran, isomeric to benzo[b]thiophene while isoelectronic to azulene, is involved as a building block to construct soluble organic semiconductors for field-effect transistors. Two series of angular-shaped heteroarenes based on cyclopenta[b]thiopyran, that is, Cn-SS (n = 4, 6, 8, 10) with different linear alkyl groups and C8-SS-Clm (m = 2, 3, 4) with chlorides substituted at different positions, have been straightforward synthesized. The obtained seven S-heteroarenes exhibit intriguing and similar photophysical and electrochemical properties, such as near-infrared absorption and high-energy levels of the highest occupied molecular orbitals. Nevertheless, the S-heteroarenes with identical π-conjugated skeletons demonstrate completely different molecular packing structures, which is proofed to be the key determinate factor for the charge carrier mobilities. Upon the engineering of the pendant alkyl lengths, the highest hole mobility in the Cn-SS series is achieved for C8-SS (1.1 cm2 V-1 s-1) with moderate alkyl length. The further incorporation of chlorides on C8-SS results in the shortened intermolecular H···S contacts and the interplane distances. Most interestingly, when chlorine-containing chloroform and chlorobenzene are used as crystallization solvents, single crystals of C8-SS-Clm with different packing structures are produced owing to the intermolecular interactions among the solute and solvent molecules. Upon further engineering of the chlorination position and the crystallization solvent, the maximum hole mobility in the ambient air improves to 2.7 cm2 V-1 s-1 for C8-SS-Cl2 crystallized from chlorobenzene, suggesting that the introduction of the accessible chlorides is a feasible pathway to engineering the crystal structures and controlling the charge transport characteristics.

BN-Embedded Polycyclic Aromatic Hydrocarbon Oligomers: Synthesis, Aromaticity, and Reactivity.

BN-embedded oligomers with different pairs of BN units were synthesized by electrophilic borylation. Up to four pairs of BN units were incorporated in the large polycyclic aromatic hydrocarbons (PAHs). Their geometric, photophysical, electrochemical, and Lewis acidic properties were investigated by X-ray crystallography, optical spectroscopy, and cyclic voltammetry. The B-N bonds show delocalized double-bond characteristics and the conjugation can be extended through the trans-orientated aromatic azaborine units. Calculations reveal the relatively lower aromaticity for the inner azaborine rings in the BN-embedded PAH oligomers. The frontier orbitals of the longer oligomers are delocalized over the inner aromatic rings. Consequently, the inner moieties of the BN-embedded PAH oligomers are more active than the outer parts. This is confirmed by a simple oxidation reaction, which has significant effects on the aromaticity and the intramolecular charge-transfer interactions.

B2 N2 -Embedded Polycyclic Aromatic Hydrocarbons with Furan and Thiophene Derivatives Functionalized in Crossed Directions.

A series of polycyclic aromatic hydrocarbons (PAHs), consisting of two pairs of BN units, have been designed and their synthesis has been achieved by electrophilic C-H borylation. Two conjugation extension directions can be found in these B2 N2 -embedded PAHs. The B2 N2 -containing backbone with shorter effective conjugation length is isoelectronic with diaryl-fused anthracene, whereas the second derivative, with longer effective conjugation length, is isoelectronic with bis(trans-arylvinyl)benzene. By incorporating different aryl groups, i.e., furyl, thienyl, benzo[b]furyl, and benzo[b]thienyl groups, into the two crossed directions of the B2 N2 -embedded PAHs, their electronic and optical properties have been comparatively investigated by photophysical, electrochemical, and theoretical approaches. It is found that both the substituents and their conjugation extension directions have significant effects on the aromatic and photophysical properties of the B2 N2 -embedded PAHs. The conjugation extension in the shorter backbone is more pronounced on the effective conjugation length than the longer backbone. Moreover, all the B2 N2 -embedded PAHs behave as both Lewis acids and Lewis bases, and reversible photoluminescence switching can be observed by simply neutralizing the added Lewis acid or Lewis base.

Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. METHODS: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. RESULTS: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. CONCLUSION: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.

Charge Transfer Switching in Donor-Acceptor Systems Based on BN-Fused Naphthalimides.

Six-membered azaborine rings have been straightforwardly fused on naphthalimide-based donor-acceptor systems, and a series of BN-containing heteroaromatic compounds BN1-BN3 were constructed. Electron-donating triphenylamines were functionalized in the extended direction of the 3- or/and 4-position of the naphthalimide unit. For comparison, reference BN0 without triphenylamine was also prepared. The intramolecular charge transfer (ICT) interactions in the resulting BN-fused naphthalimides (BN0-BN3) together with their precursors (N0-N3) and fluoride-coordinated analogues (FBN0-FBN3) have been systematically investigated by photophysical, electrochemical, and theoretical approaches. It is found that the fusion of the azaborine ring has a great effect on the ICT properties of the D-A systems based on BN-fused naphthalimides. For the precursors without boron, the extension of an electron donor from the 3-position of naphthalimide is superior in enhancing the D-A interactions. On the contrary, upon fusion of the azaborine ring on naphthalimide, the dominant orientation of the ICT interactions conversely converts to the extended direction of the 4-position of naphthalimide in the D-A molecules based on BN-fused naphthalimides. Most interestingly, upon coordinating the boron by a fluoride ion, the ICT interactions are dramatically enlarged and the substitution position of the triphenylamino group has a negligible effect on the ICT properties of the fluoride-coordinated analogues.

Electron donor and acceptor functionalized dithienylethenes: effects of charge density on photochromic properties.

Electron-donating triphenylamine and/or electron-withdrawing pyromellitic diimide (PMDI) are functionalized on dithienylethene (DTE) and three novel photochromic materials have been designed and successfully synthesized. All the compounds display reversible photochromism due to the molecular switching between ring-closed isomers upon UV light irradiation and ring-open isomers upon exposure to visible light. Thus they can be applied as an anti-counterfeiting ink. Moreover, the study of the photoswitching kinetics reveals that both the ring-closing and ring-opening reactions are first-order reactions. Further charge population analysis discovers that the electron densities of the substituents at the DTE core have a dramatic influence on the photochromic properties. The incorporation of electron-donating triphenylamine groups at the α-position of the thiophene rings in the DTE unit facilitates the ring-closing reaction upon UV light irradiation. In contrast, the substitution of an electron-withdrawing PMDI unit in the DTE unit is beneficial to the ring-opening reaction upon irradiation of visible light. This work may help to understand the photochromism of DTE derivatives and provide a pathway for designing DTE-based photochromes with more or less sensitivity to UV or visible light.

A Mobile Outdoor Augmented Reality Method Combining Deep Learning Object Detection and Spatial Relationships for Geovisualization.

The purpose of this study was to develop a robust, fast and markerless mobile augmented reality method for registration, geovisualization and interaction in uncontrolled outdoor environments. We propose a lightweight deep-learning-based object detection approach for mobile or embedded devices; the vision-based detection results of this approach are combined with spatial relationships by means of the host device's built-in Global Positioning System receiver, Inertial Measurement Unit and magnetometer. Virtual objects generated based on geospatial information are precisely registered in the real world, and an interaction method based on touch gestures is implemented. The entire method is independent of the network to ensure robustness to poor signal conditions. A prototype system was developed and tested on the Wuhan University campus to evaluate the method and validate its results. The findings demonstrate that our method achieves a high detection accuracy, stable geovisualization results and interaction.

Revealing Dynamics of Protein Phosphorylation: A Study on the Cashmere Fineness Disparities in Liaoning Cashmere Goats.

Exploring the landscape of protein phosphorylation, this investigation focuses on skin samples from LCG (Liaoning Cashmere Goats), characterized by different levels of cashmere fineness. Employing LC-MS/MS technology, we meticulously scrutinized FT-LCG (fine-type Liaoning Cashmere Goats) and CT-LCG (coarse-type Liaoning Cashmere Goats). Identifying 512 modified proteins, encompassing 1368 phosphorylated peptide segments and 1376 quantifiable phosphorylation sites, our exploration further revealed consistent phosphorylation sites in both groups. Analysis of phosphorylated peptides unveiled kinase substrates, prominently featuring Protein Kinase C, Protein Kinase B and MAPK3-MAPK1-MAPK7-NLK-group. Differential analysis spotlighted 28 disparate proteins, comprising six upregulated and twenty-two downregulated. Cluster analysis showcased the robust clustering efficacy of the two sample groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses underscored the significance of the purine metabolism pathway, suggesting its pivotal role in modulating cashmere fineness in LCG. Notably, through differential protein analysis, two crucial proteins were identified: HSL-X (hormone-sensitive lipase isoform X1) and KPRP (keratinocyte proline-rich protein). Further evidence supports LIPE and KPRP as key genes regulating cashmere fineness, paving the way for promising avenues in further research. These findings not only contribute to a nuanced understanding of protein-level dynamics in cashmere but also provide a theoretical foundation for the selective breeding of superior Liaoning Cashmere Goat strands.

Common proteins analysis of different mammals' mature milk by 4D-Label-Free.

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

Analysis for different flavor compounds in mature milk from human and livestock animals by GC × GC-TOFMS.

Breast milk plays a crucial role in the taste development of infants, which cannot be replicated by other mammalian milk or formulas. This study aimed to identify and characterize the flavor substances in 15 different types of milk and analyze the differences among them. The results showed that human milk contained high levels of esters, particularly fatty acid ethyl esters, which contribute to its unique flavor. The four substances that had the highest flavor contribution in all species were identified as 2,3-butanedione, trimethylamine, isophorone, and acetaldehyde. Furthermore, the analysis of differences revealed that thermal-oxidation of lipids could explain the variation between human milk and other species in terms of flavor compounds. The key differential flavor compounds identified in milk from all species were trimethylamine, propanal, 1-pentanol, pyridine 2-methyl, and 2-butanone. These findings can potentially aid in developing formulas that better meet the taste needs of infants.

From closed-shell edge-extended kekulenes to open-shell carbonylated cycloarene diradicaloid.

The precise synthesis of cycloarenes remains a challenging topic in both organic chemistry and materials science due to their unique fully fused macrocyclic π-conjugated structure. Herein, a series of alkoxyl- and aryl-cosubstituted cycloarenes (kekulene and edge-extended kekulene derivatives, K1-K3) were conveniently synthesized and an unexpected transformation of the anthryl-containing cycloarene K3 into a carbonylated cycloarene derivative K3-R was disclosed by controlling the temperature and gas atmosphere of the Bi(OTf)3-catalyzed cyclization reaction. All their molecular structures were confirmed by single-crystal X-ray analysis. The crystallographic data, NMR measurements, and theoretical calculations reveal their rigid quasi-planar skeletons, dominant local aromaticities, and decreasing intermolecular π-π stacking distance with extension of the two opposite edges. The much lower oxidation potential for K3 by cyclic voltammetry explains its unique reactivity. Moreover, carbonylated cycloarene derivative K3-R shows a remarkable stability, large diradical character, a small singlet-triplet energy gap (ΔES-T = -1.81 kcal mol-1), and weak intramolecular spin-spin coupling. Most importantly, it represents the first example of carbonylated cycloarene diradicaloids as well as the first example of radical-acceptor cycloarenes and will shed some light on synthesis of extended kekulenes and conjugated macrocyclic diradicaloids and polyradicaloids.

Analysis for lipid nutrient differences in the milk of 13 species from a quantitative non-targeted lipidomics perspective.

Lipids are essential organic components in milk and have been associated with various health benefits for newborns. However, a comprehensive analysis of lipid profiles across multiple species and levels has been lacking. In this study, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to accurately determine the absolute content of lipid molecules. It revealed that ruminants exhibit a higher concentration of short-chain fatty acids compared to non-ruminants. Additionally, we identified ALC (camel), MGH (horse), and DZD (donkey) as species that display similarities to components found in human milk fat. Remarkably, it reveals that porcine milk fat is characterized by long chain lengths, low saturation, and a high proportion of essential fatty acids. PS (22:5_18:2) could potentially serve as a biomarker in porcine milk. These unique characteristics present potential opportunities for the utilization of porcine milk. Overall, our findings provide valuable insights into the lipidomics profiles of milk from different species.

Metabonomic analysis of human and 12 kinds of livestock mature milk.

Mature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.

Constrain Effect of Charge Traps in Organic Field-Effect Transistors with Ferroelectric Polymer as a Dielectric Interfacial Layer.

Traps play crucial roles in the charge transport of disordered organic semiconductors and can significantly influence the electrical performance of organic functional devices. The constrain effect of charge traps in organic field-effect transistors with a ferroelectric polymer as a dielectric interfacial layer has been studied at temperatures ranging from 30 °C to temperature beyond the Curie point of the ferroelectric polymers by utilizing a thermally stable polymer as the semiconducting channel. It has been observed that the charge traps are constrained within a shallow energy level with the ferroelectric interfacial layer. The change in the density of traps involved in the trap-filling process at temperatures across the Curie point shows that the decrease in shallow traps is almost proportional to the increase in deep traps, indicating the transition between shallow and deep traps in the semiconducting channel. These findings suggest potential in stability increase and performance enhancement of future organic functional devices via modulation of traps by a ferroelectric interfacial layer.