Physical immune escape: Weakened mechanical communication leads to escape of metastatic colorectal carcinoma cells from macrophages.

The significance of biochemical cues in the tumor immune microenvironment in affecting cancer metastasis is well established, but the role of physical factors in the microenvironment remains largely unexplored. In this article, we investigated how the mechanical interaction between cancer cells and immune cells, mediated by extracellular matrix (ECM), influences immune escape of cancer cells. We focus on the mechanical regulation of macrophages' targeting ability on two distinct types of colorectal carcinoma (CRC) cells with different metastatic potentials. Our results show that macrophages can effectively target CRC cells with low metastatic potential, due to the strong contraction exhibited by the cancer cells on the ECM, and that cancer cells with high metastatic potential demonstrated weakened contractions on the ECM and can thus evade macrophage attack to achieve immune escape. Our findings regarding the intricate mechanical interactions between immune cells and cancer cells can serve as a crucial reference for further exploration of cancer immunotherapy strategies.

ATP-Independent Water-Soluble Luciferins Enable Non-Invasive High-Speed Video-Rate Bioluminescence Imaging of Mice.

NanoLuc luciferase and its derivatives are attractive bioluminescent reporters recognized for their efficient photon production and ATP independence. However, utilizing them for in vivo imaging poses notable challenges. Low substrate solubility has been a prominent problem, limiting in vivo brightness, while substrate instability hampers consistent results and handling. To address these issues, we developed a range of caged PEGylated luciferins with improved stability and water solubility of up to 25 mM, resulting in substantial bioluminescence increases in mouse models. This advancement has created the brightest and most sensitive luciferase-luciferin combination, enabling high-speed video-rate imaging of freely moving mice with brain-expressed luciferase. Furthermore, we developed a bioluminescent Ca 2+ indicator with exceptional sensitivity to physiological Ca 2+ changes and paired it with a new substrate to showcase non-invasive, video-rate imaging of Ca 2+ activity in a defined brain region in awake mice. These innovative substrates and the Ca 2+ indicator are poised to become invaluable resources for biological and biomedical fields.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

The Alleviating Effect of Taxifolin on Deoxynivalenol-Induced Damage in Porcine Intestinal Epithelial Cells.

Deoxynivalenol (DON) contamination in feed is a global concern that severely threatens the health of animals and humans. Taxifolin (TA) is a natural flavonoid, a member of the polyphenols, that possesses robust antioxidant properties. This study aimed to investigate the effect of TA on DON-induced damage in porcine intestinal epithelial cells (IPEC-J2). The cells were pre-incubated with a series of concentrations of TA for 24 h and exposed to DON (0.5 µg/mL) for another 24 h. The results showed that pretreatment with TA (150 µM) significantly inhibited the DON-induced decline in cell viability (p < 0.05) and cell proliferation (p < 0.01). Additionally, 150 µM TA also alleviated DON-induced apoptosis (p < 0.01). Moreover, TA decreased the production of reactive oxygen species (ROS) induced by DON (p < 0.01). In addition, TA attenuated DON-induced cell junction damage (p < 0.05). Further experiments showed that TA reversed the DON-induced reduction in antioxidant capacity in the IPEC-J2 cells, probably via activating the Nrf2 signaling pathway (p < 0.05). Collectively, these findings suggest that 150 µM TA can protect against 0.5 µg/mL DON-induced damage to IPEC-J2 cells, potentially via the activation of the Nrf2 signaling pathway. This study provides insight into TA's potential to act as a green feed additive in the pig farming industry and its efficacy in counteracting DON-induced intestinal damage.

Energy Absorption Characteristics of Composite Material with Fiber-Foam Metal Sandwich Structure Subjected to Gas Explosion.

Based on the previous research on the energy absorption of foam metal materials with different structures, a composite blast-resistant energy-absorbing material with a flexible core layer was designed. The material is composed of three different fiber materials (carbon fiber, aramid fiber, and glass fiber) as the core layer and foamed iron-nickel metal as the front and rear panels. The energy absorption characteristics were tested using a self-built gas explosion tube network experimental platform, and the energy absorption effects of different combinations of blast-resistant materials were analyzed. The purpose of this paper is to evaluate the performance of blast-resistant materials designed with flexible fiber core layers. The experimental results show that the composite structure blast-resistant material with a flexible core layer has higher energy absorption performance. The work performed in this paper shows that the use of flexible core layer materials has great research potential and engineering research value for improving energy absorption performance, reducing the mass of blast-resistant materials, and reducing production costs. It also provides thoughts for the research of biomimetic energy-absorbing materials.

Unveiling the Genetic Secrets of Chinese Indigenous Pigs from Guizhou Province: Diversity, Evolution and Candidate Genes Affecting Pig Coat Color.

The local pig breeds in Guizhou possess exceptional meat quality, robust adaptability, and resilience to harsh feeding conditions, making them ideal for producing high-quality pork. With over 10 local pig breeds in the region, we focused on 7 specific breeds: Baixi pigs (BX), Congjiang Xiang pigs (CJX), Guanling pigs (GL), Jianhe White Xiang pigs (JHBX), Jiangkou Luobo pigs (JKLB), Kele pigs (KL), and Qiandong Hua pigs (QDH). Unfortunately, these breeds face threats such as introduced species and inbreeding, resulting in a decline in population size and numbers. To better protect and utilize these breeds, we employed genome-wide single-nucleotide polymorphism (SNP) markers to investigate the population structure, genetic diversity, and selection characteristics of 283 pigs across these seven breeds. Our findings revealed distinct ancestral sources between Chinese and Western pig breeds, as demonstrated by principal component analysis, adjacent tree analysis, and ADMIXTURE analysis. Notably, JHBX exhibited a distant genetic relationship from the other six local pig breeds in Guizhou province, showcasing unique genetic characteristics. While the genetic diversity of the six Chinese native pig populations, excluding JHBX, was generally moderate in Guizhou province, the JHBX population displayed low genetic diversity. Therefore, it is imperative to intensify selection efforts to prevent inbreeding decline in JHBX while further enhancing the protection measures for the other six pig populations. Additionally, we identified candidate genes influencing the size disparity among pigs in Guizhou province through signal selection. Our study outcomes serve as a reference for developing effective conservation and utilization plans for pig breeds in Guizhou province and deepen our understanding of the genetic mechanisms underlying pig body size.

Phospholipase D Mediates Glutamine-Induced mTORC1 Activation to Promote Porcine Intestinal Epithelial Cell Proliferation.

BACKGROUND: The intestinal epithelium is one of the fastest self-renewal tissues in the body, and glutamine plays a crucial role in providing carbon and nitrogen for biosynthesis. In intestinal homeostasis, phosphorylation-mediated signaling networks that cause altered cell proliferation, differentiation, and metabolic regulation have been observed. However, our understanding of how glutamine affects protein phosphorylation in the intestinal epithelium is limited, and identifying the essential signaling pathways involved in regulating intestinal epithelial cell growth is particularly challenging. OBJECTIVES: This study aimed to identify the essential proteins and signaling pathways involved in glutamine's promotion of porcine intestinal epithelial cell proliferation. METHODS: Phosphoproteomics was applied to describe the protein phosphorylation landscape under glutamine treatment. Kinase-substrate enrichment analysis was subjected to predict kinase activity and validated by qRT-PCR and Western blotting. Cell Counting Kit-8, glutamine rescue experiment, chloroquine treatment, and 5-fluoro-2-indolyl deschlorohalopemide inhibition assay revealed the possible underlying mechanism of glutamine promoting porcine intestinal epithelial cell proliferation. RESULTS: In this study, glutamine starvation was found to significantly suppress the proliferation of intestinal epithelial cells and change phosphoproteomic profiles with 575 downregulated sites and 321 upregulated sites. Interestingly, phosphorylation of eukaryotic initiation factor 4E-binding protein 1 at position Threonine70 was decreased, which is a crucial downstream of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Further studies showed that glutamine supplementation rescued cell proliferation and mTORC1 activity, dependent on lysosomal function and phospholipase D activation. CONCLUSION: In conclusion, glutamine activates mTORC1 signaling dependent on phospholipase D and a functional lysosome to promote intestinal epithelial cell proliferation. This discovery provides new insight into regulating the homeostasis of the intestinal epithelium, particularly in pig production.

Piceatannol Alleviates Deoxynivalenol-Induced Damage in Intestinal Epithelial Cells via Inhibition of the NF-κB Pathway.

Deoxynivalenol (DON) is a common mycotoxin that is widely found in various foods and feeds, posing a potential threat to human and animal health. This study aimed to investigate the protective effect of the natural polyphenol piceatannol (PIC) against DON-induced damage in porcine intestinal epithelial cells (IPEC-J2 cells) and the underlying mechanism. The results showed that PIC promotes IPEC-J2 cell proliferation in a dose-dependent manner. Moreover, it not only significantly relieved DON-induced decreases in cell viability and proliferation but also reduced intracellular reactive oxygen species (ROS) production. Further studies demonstrated that PIC alleviated DON-induced oxidative stress damage by increasing the protein expression levels of the antioxidant factors NAD(P)H quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM), and the mRNA expression of catalase (CAT), Superoxide Dismutase 1 (SOD1), peroxiredoxin 3 (PRX3), and glutathione S-transferase alpha 4 (GSTα4). In addition, PIC inhibited the activation of the nuclear factor-B (NF-κB) pathway, downregulated the mRNA expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) to attenuate DON-induced inflammatory responses, and further mitigated DON-induced cellular intestinal barrier injury by regulating the protein expression of Occludin. These findings indicated that PIC had a significant protective effect against DON-induced damage. This study provides more understanding to support PIC as a feed additive for pig production.

Implications for miR-339-5p regulation of trophoblast proliferation and migration in placentas associated with porcine intrauterine growth retardation using integrated transcriptome sequencing analysis.

Placental dysfunction is considered as one of the main etiologies of fetal intrauterine growth retardation (IUGR). MicroRNAs (miRNAs) have been demonstrated to be a vital epigenetic modification involved in regulating the placental function and pregnancy outcomes in mammals. However, the mechanisms underlying placenta-specific miRNAs involved in the occurrence and development of pig IUGR remain unclear. In this work, we compared the placental morphologies of piglets with IUGR and normal birth weight (NBW) by using histomorphological analysis and performed a miRNA-mRNA integrative analysis of the gene expression profiles of IUGR and NBW placentas through RNA sequencing. We also investigated the role of differentially expressed ssc-miR-339-5p/GRIK3 through an in vitro experiment on porcine trophoblast cells (PTr2). IUGR piglets had significantly lower birth weight, placental weight, placental efficiency, and placental villus and capillary densities compared with the NBW piglets (P < 0.05). A total of 81 differentially expressed miRNAs and 726 differentially expressed genes in the placentas were screened out between the IUGR and NBW groups. The miRNA-mRNA interaction networks revealed the key core miRNA (ssc-miR-339-5p) and its corresponding target genes. Subsequently, we found that upregulation of ssc-miR-339-5p significantly inhibited the migration and proliferation of PTr2 cells (P < 0.05). The dual-luciferase reporter system showed that GRIK3 was the target gene of ssc-miR-339-5p, and the transcription level of GRIK3 may be negatively regulated by ssc-miR-339-5p. Additionally, overexpression of ssc-miR-339-5p significantly increased (P < 0.05) the mRNA expression levels of genes involved in the cytokine-cytokine receptor interaction pathway. These results indicate that ssc-miR-339-5p may affect the migration and proliferation of trophoblast cells by regulating the expression of GRIK3 and altering the placental inflammatory response, resulting in a suboptimal morphology and function of the placenta and the development of pig IUGR.

Expression of the umami taste receptor T1R1/T1R3 in porcine testis of: Function in regulating testosterone synthesis and autophagy in Leydig cells.

Testosterone is a vital male hormone responsible for male sexual characteristics. The taste receptor family 1 subunit 3 (T1R3) regulates testosterone synthesis and autophagy in non-taste cells, and the links with the taste receptor family 1 subunit 1 (T1R1) for umami perception. However, little is known about these mechanisms. Thus, we aimed to determine the relationship between the umami taste receptor (T1R1/T1R3) and testosterone synthesis or autophagy in testicular Leydig cells of the Xiang pig. There was a certain proportion of spermatogenic tubular dysplasia in the Xiang pig at puberty, in which autophagy was enhanced, and the testosterone level was increased with a weak expression of T1R3. Silenced T1R3 decreased testosterone level and intracellular cyclic adenosine monophosphate (cAMP) content and inhibited the messenger RNA (mRNA) expression levels of testosterone synthesis enzyme genes [steroidogenic acute regulatory protein (StAR), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (3ß-HSD1), cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and hydroxysteroid 17-beta dehydrogenase 3 (17ß-HSD3)]. In addition, T1R3 increased the number of acidic autophagy bubbles and upregulated the expression levels of autophagy markers [Microtubule-associated protein 1 A/1B-light chain 3 (LC3) and Beclin-1] in testicular Leydig cells of the Xiang pig. Using an umami tasting agonist (10 mM L-glutamate for 6 h), the activation of T1R1/T1R3 enhanced the testosterone synthesis ability by increasing the intracellular cAMP level and upregulated the expression levels of StAR, 3ß-HSD1, CYP17A1 and 17ß-HSD3 in Leydig cells. Furthermore, the number of acidic autophagy bubbles decreased in the T1R1/T1R3-activated group with the downregulation of the expression levels of the autophagy markers, including LC3 and Beclin-1. These data suggest that the function of T1R1/T1R3 expressed in testicular Leydig cells of the Xiang pig is related to testosterone synthesis and autophagy.

Factors Influencing the Behavioral Intentions and Use Behaviors of Telemedicine in Patients With Diabetes: Web-Based Survey Study.

BACKGROUND: Telemedicine has great potential for diabetes management. The COVID-19 pandemic has boosted the development of telemedicine. However, the factors influencing the behavioral intentions to use and use behaviors of telemedicine in patients with diabetes in China are not clear. OBJECTIVE: We aimed to understand the determinants of behavioral intention to use telemedicine based on an extended Unified Theory of Acceptance and Use of Technology model and to identify demographic factors associated with telemedicine use in patients with diabetes in China. METHODS: Patients with diabetes who are aged ≥18 years were surveyed from February 1 to February 7, 2023. We distributed the survey link in 3 WeChat groups including a total of 988 patients with diabetes from the outpatient department or patients discharged from Changsha Central Hospital. Structural equation modeling was used to understand the determinants of behavioral intention. A multivariate logistic regression analysis was used to identify the demographic factors associated with telemedicine use. RESULTS: In total, 514 questionnaires were collected. Of the respondents, 186 (36.2%) were diagnosed with COVID-19. The measurement model showed acceptable reliability, convergent validity, discriminant validity, and data fit indices. The model explained 63.8% of the variance in behavioral intention. Social influence, performance expectancy, and facilitating conditions positively influenced behavioral intention (ß=.463, P<.001; ß=.153, P=.02; and ß=.257, P=.004, respectively). Perceived susceptibility, perceived severity, and effort expectancy had no significant impact on behavioral intention (all P>.05). The overall use of telemedicine was 20.6% (104/514). After adjusting for the behavioral intention score, the multivariate regression analysis showed that age, education, and family income were associated with telemedicine use. Telemedicine use was higher in the 40 to 59 years and 18 to 39 years age groups than in the ≥60 years age group (odds ratio [OR] 4.35, 95% CI 1.84-10.29, P=.001; OR 9.20, 95% CI 3.40-24.88, P<.001, respectively). Telemedicine use was higher in the senior high school and the university and more groups than in junior high school education and less group (OR 2.45, 95% CI 1.05-5.73, P=.04; OR 2.63, 95% CI 1.11-6.23, P=.03, respectively). Patients with a higher family income used telemedicine more often than the patients who had an annual family income ≤¥10,000 (CNY ¥1=US $0.1398; ¥10,000-¥50,000 group: OR 3.90, 95% CI 1.21-12.51, P=.02; ¥50,000-¥100,000 group: OR 3.91, 95% CI 1.19-12.79, P=.02; >¥100,000 group: OR 4.63, 95% CI 1.41-15.27, P=.01). CONCLUSIONS: Social influence, performance expectancy, and facilitating conditions positively affected the behavioral intention of patients with diabetes to use telemedicine. Young patients, highly educated patients, and patients with high family income use telemedicine more often. Promoting behavioral intention and paying special attention to the needs of older adult patients, patients with low income, and patients with low levels of education are needed to encourage telemedicine use.

Glutamine Regulates Gene Expression Profiles to Increase the Proliferation of Porcine Intestinal Epithelial Cells and the Expansion of Intestinal Stem Cells.

The intestinal epithelium is known for its rapid self-renewal, and glutamine is crucial in providing carbon and nitrogen for biosynthesis. However, understanding how glutamine affects gene expression in the intestinal epithelium is limited, and identifying the essential genes and signals involved in regulating intestinal epithelial cell growth is particularly challenging. In this study, glutamine supplementation exhibited a robust acceleration of intestinal epithelial cell proliferation and stem cell expansion. RNA sequencing indicated diverse transcriptome changes between the control and glutamine supplementation groups, identifying 925 up-regulated and 1152 down-regulated genes. The up-regulated DEGs were enriched in the KEGG pathway of cell cycle and GO terms of DNA replication initiation, regulation of phosphatidylinositol 3-kinase activity, DNA replication, minichromosome maintenance protein (MCM) complex, and ATP binding, whereas the down-regulated DEGs were enriched in the KEGG pathway of p53 signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway and GO terms of inflammatory response and intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Furthermore, GSEA analysis revealed a significant up-regulation of the cell cycle, DNA replication initiation, ATP-dependent RNA helicase activity, and down-regulation of the TNF signaling pathway. The protein-protein association network of the intersecting genes highlighted the significance of DNA replication licensing factors (MCM3, MCM6, and MCM10) in promoting intestinal epithelial growth in response to glutamine. Based on these findings, we propose that glutamine may upregulate DNA replication licensing factors, leading to increased PI3K/Akt signaling and the suppression of TNF, JAK-STAT, and p53 pathways. Consequently, this mechanism results in the proliferation of porcine intestinal epithelial cells and the expansion of intestinal stem cells.

Extracellular Glutamine Promotes Intestinal Porcine Epithelial Cell Proliferation via Arf1-mTORC1 Pathway Independently of Rag GTPases.

Glutamine (Gln) is the major energy source of intestinal porcine epithelial cells (IPEC-J2 cells) and plays a critical role in the nutritional physiological function of the intestine. However, the underlying mechanism requires further investigation. Here, the Gln-sensing pathway in IPEC-J2 cells was investigated. The results showed that Gln increased the cell proliferation. Subsequently, an analysis of the phosphorylated proteome revealed that Gln markedly upregulated ribosomal protein S6 (RPS6) phosphorylation at serine 235/236, suggesting that Gln activated the mTORC1 pathway. mTOR inhibition revealed that Gln promotes cell proliferation through the mTORC1 pathway. Similarly, blocking ADP-ribosylation factor 1 (Arf1) activity indicated that Gln-induced mTORC1 activation promoted cell proliferation in an Arf1-dependent manner. Additionally, the RagA/B pathway did not participate in Gln-induced mTORC1 activation. Collectively, these findings suggest that Gln-induced mTORC1 activation promotes IPEC-J2 cell proliferation via Arf1, not Rag GTPases. These results broaden our understanding of functional-cell-sensing amino acids, particularly Gln, that are regulated by mTORC1.

Exploring characteristics of placental transcriptome and cord serum metabolome associated with low birth weight in Kele pigs.

The neonate with low birth weight (LBW) resulted from intrauterine growth retardation (IUGR) exists a substantial risk of postpartum death. Placental insufficiency is responsible for inadequate fetal growth; however, the pathological mechanisms of placental dysfunction-induced IUGR in pigs remain unclear. In this study, the characteristics of placental morphology, placental transcriptome, and cord serum metabolome were explored between the Kele piglets with LBW and the ones with normal birth weight (NBW). Results showed that LBW was a common occurrence in Kele piglets. The LBW placentas showed inferior villus development and lower villi density compared to NBW placentas. There were 1024 differentially expressed genes (DEGs) identified by transcriptome analysis between the LBW and NBW placentas, of which 218 and 806 genes were up- and down-regulated in the LBW placentas, respectively. PPI network analysis showed that ITGB2, CD4, IL6, ITGB3, LCK, RAC2, CD8A, JAK3, TYROBP, and CXCR4 were hub genes in all DEGs. From GO and KEGG enrichment analysis, DEGs were primarily enriched in immunological response, cell adhesion, immune response, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway. By using metabolomic analysis, a total of 115 differential metabolites in the cord serum of LBW and NBW piglets were found, mostly linked to amino acid metabolism and sphingolipid metabolism. In comparison to NBW piglets, LBW piglets had lower levels of arginine, isoleucine, and aspartic acid in the cord. Taken together, these data revealed dysplasia of the placental villus, insufficient supply of nutrients, and abnormal immune function of the placenta may be associated with the occurrence and development of LBW in Kele pigs.

Role of Polysaccharides from Marine Seaweed as Feed Additives for Methane Mitigation in Ruminants: A Critical Review.

Given the increasing concerns regarding greenhouse gas emissions associated with livestock production, the need to discover effective strategies to mitigate methane production in ruminants is clear. Marine algal polysaccharides have emerged as a promising research avenue because of their abundance and sustainability. Polysaccharides, such as alginate, laminaran, and fucoidan, which are extracted from marine seaweeds, have demonstrated the potential to reduce methane emissions by influencing the microbial populations in the rumen. This comprehensive review extensively examines the available literature and considers the effectiveness, challenges, and prospects of using marine seaweed polysaccharides as feed additives. The findings emphasise that marine algal polysaccharides can modulate rumen fermentation, promote the growth of beneficial microorganisms, and inhibit methanogenic archaea, ultimately leading to decreases in methane emissions. However, we must understand the long-term effects and address the obstacles to practical implementation. Further research is warranted to optimise dosage levels, evaluate potential effects on animal health, and assess economic feasibility. This critical review provides insights for researchers, policymakers, and industry stakeholders dedicated to advancing sustainable livestock production and methane mitigation.

Ssc-mir-221-3p regulates melanin production in Xiang pigs melanocytes by targeting the TYRP1 gene.

BACKGROUND: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate gene expression by down-regulating it. Several studies have suggested that miRNAs plays a crucial role in mammalian skin color production. The TYRP1 gene, a member of the tyrosine family, is an important candidate gene that affects melanogenesis. This study aimed to identify genes and miRNAs that affect melanin production in Xiang pigs by transcriptome sequencing, and to validate their targeted regulatory relationships. RESULTS: 17 miRNAs and 1,230 genes were significantly differentially expressed (P < 0.05) in the black and white skin tissues of Jianbai Xiang pigs. miRNA-221-3p was identified as a candidate miRNA for melanin formation and its target gene, TYRP1, was selected. The TYRP1 gene is a member of the TYR gene family, which evolved from the TYR gene through chromosome segmental duplication. The function of the gene was highly conserved throughout the evolutionary process. overexpression of TYRP1 gene significantly increased the expression of TYR, TYRP1, and DCT genes P < 0.01, which led to an increase in the relative content of melanin. Silencing of TYRP1 through the use of TYRP1-siRNA significantly reduced the expression of TYR, TYRP1, and DCT genes in Jianbai Xiang pig melanocytes P < 0.01, which in turn decreased the relative melanin content. The targeted binding relationship between ssc-miR-221-3p and TYRP1 gene was validated. After transfection of porcine melanocytes with ssc-miR-221-3p mimic, the expression of ssc-miR-221-3p was significantly up-regulated (P < 0.01). Furthermore, the mRNA and protein levels of TYR, TYRP1, and DCT genes were significantly down-regulated (P < 0.01), and melanin content in cells was significantly reduced (P < 0.01). CONCLUSION: The TYRP1 gene affects melanogenesis in melanocytes of Jianbai Xiang pigs, and ssc-miR-221-3p targets the TYRP1 gene to regulate melanogenesis in melanocytes of Jianbai Xiang pigs.

Polymer-Stabilized Liquid Crystal Films Containing Dithienyldicyanoethene-Based Chiral Photoswitch: Multi-Modulation for Environment-Adaptative Smart Windows.

A polymer-stabilized liquid crystal (PSLC)-based environment-adaptative smart window with multi-modulations is demonstrated. This PSLC system contains a right-handed dithienyldicyanoethene-based chiral photoswitch and a chiral dopant, S811, with opposite handedness, of which the reversible cis-trans photoisomerization of the switch can drive self-shading of the smart window under UV light stimulus because of the transition from nematic phase to cholesteric one. With the assistance of solar heat, the opacity of the smart window can be deepened because the heat promotes the isomerization conversion rate of the switch. This switch has no thermal relaxation at room temperature, therefore, the smart window exhibits dual stabilization: transparent state (cis-isomer) and opaque state (trans-isomer). Moreover, the incident intensity of sunlight can be regulated by an electric field, which allows the smart window to adapt to some specific situations. Such an energy-saving device can be used in buildings and vehicles to control indoor temperature and adapt to the required ambiance.

Dielectrics for Two-Dimensional Transition-Metal Dichalcogenide Applications.

Despite over a decade of intense research efforts, the full potential of two-dimensional transition-metal dichalcogenides continues to be limited by major challenges. The lack of compatible and scalable dielectric materials and integration techniques restrict device performances and their commercial applications. Conventional dielectric integration techniques for bulk semiconductors are difficult to adapt for atomically thin two-dimensional materials. This review provides a brief introduction into various common and emerging dielectric synthesis and integration techniques and discusses their applicability for 2D transition metal dichalcogenides. Dielectric integration for various applications is reviewed in subsequent sections including nanoelectronics, optoelectronics, flexible electronics, valleytronics, biosensing, quantum information processing, and quantum sensing. For each application, we introduce basic device working principles, discuss the specific dielectric requirements, review current progress, present key challenges, and offer insights into future prospects and opportunities.

Liquid-Metal-Printed Ultrathin Oxides for Atomically Smooth 2D Material Heterostructures.

Two-dimensional (2D) semiconductors are promising channel materials for continued downscaling of complementary metal-oxide-semiconductor (CMOS) logic circuits. However, their full potential continues to be limited by a lack of scalable high-k dielectrics that can achieve atomically smooth interfaces, small equivalent oxide thicknesses (EOTs), excellent gate control, and low leakage currents. Here, large-area liquid-metal-printed ultrathin Ga2O3 dielectrics for 2D electronics and optoelectronics are reported. The atomically smooth Ga2O3/WS2 interfaces enabled by the conformal nature of liquid metal printing are directly visualized. Atomic layer deposition compatibility with high-k Ga2O3/HfO2 top-gate dielectric stacks on a chemical-vapor-deposition-grown monolayer WS2 is demonstrated, achieving EOTs of ∼1 nm and subthreshold swings down to 84.9 mV/dec. Gate leakage currents are well within requirements for ultrascaled low-power logic circuits. These results show that liquid-metal-printed oxides can bridge a crucial gap in dielectric integration of 2D materials for next-generation nanoelectronics.