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.

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.

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.

s2MRI-ADNet: an interpretable deep learning framework integrating Euclidean-graph representations of Alzheimer's disease solely from structural MRI.

OBJECTIVE: To establish a multi-dimensional representation solely on structural MRI (sMRI) for early diagnosis of AD. METHODS: A total of 3377 participants' sMRI from four independent databases were retrospectively identified to construct an interpretable deep learning model that integrated multi-dimensional representations of AD solely on sMRI (called s2MRI-ADNet) by a dual-channel learning strategy of gray matter volume (GMV) from Euclidean space and the regional radiomics similarity network (R2SN) from graph space. Specifically, the GMV feature map learning channel (called GMV-Channel) was to take into consideration spatial information of both long-range spatial relations and detailed localization information, while the node feature and connectivity strength learning channel (called NFCS-Channel) was to characterize the graph-structured R2SN network by a separable learning strategy. RESULTS: The s2MRI-ADNet achieved a superior classification accuracy of 92.1% and 91.4% under intra-database and inter-database cross-validation. The GMV-Channel and NFCS-Channel captured complementary group-discriminative brain regions, revealing a complementary interpretation of the multi-dimensional representation of brain structure in Euclidean and graph spaces respectively. Besides, the generalizable and reproducible interpretation of the multi-dimensional representation in capturing complementary group-discriminative brain regions revealed a significant correlation between the four independent databases (p < 0.05). Significant associations (p < 0.05) between attention scores and brain abnormality, between classification scores and clinical measure of cognitive ability, CSF biomarker, metabolism, and genetic risk score also provided solid neurobiological interpretation. CONCLUSION: The s2MRI-ADNet solely on sMRI could leverage the complementary multi-dimensional representations of AD in Euclidean and graph spaces, and achieved superior performance in the early diagnosis of AD, facilitating its potential in both clinical translation and popularization.

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.

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.

RACK1 may participate in placental development at mid-gestation via regulating trophoblast cell proliferation and migration in pigs.

Intrauterine growth restriction (IUGR) is a severe complication in swine production. Placental insufficiency is responsible for inadequate fetal growth, but the specific etiology of placental dysfunction-induced IUGR in pigs remains poorly understood. In this work, placenta samples supplying the lightest weight (LW) and mean weight (MW) pig fetuses in the litter at Day 65 (D65) of gestation were collected, and the relationship between fetal growth and placental morphologies and functions was investigated using histomorphological analysis, RNA sequencing, quantitative polymerase chain reaction, and in vitro experiment in LW and MW placentas. Results showed that the folded structure of the epithelial bilayer of LW placentas followed a poor and incomplete development compared with that of MW placentas. A total of 654 differentially expressed genes (DEGs) were screened out between the LW and MW placentas, and the gene encodes receptor for activated C kinase 1 (RACK1) was found to be downregulated in LW placentas. The DEGs were mainly enriched in translation, ribosome, protein synthesis, and mammalian target of rapamycin (mTOR) signaling pathway according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In vitro experiments indicated that the decreased RACK1 in LW placentas may be involved in abnormal development of placental folds (PFs) by inhibiting the proliferation and migration of porcine trophoblast cells. Taken together, these results revealed that RACK1 may be a vital regulator in the development of PFs via regulating trophoblast cell proliferation and migration in 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.

A comprehensive characterization of hippocampal feature ensemble serves as individualized brain signature for Alzheimer's disease: deep learning analysis in 3238 participants worldwide.

OBJECTIVES: Hippocampal characterization is one of the most significant hallmarks of Alzheimer's disease (AD); rather, the single-level feature is insufficient. A comprehensive hippocampal characterization is pivotal for developing a well-performing biomarker for AD. To verify whether a comprehensive characterization of hippocampal features of gray matter volume, segmentation probability, and radiomics features could better distinguish AD from normal control (NC), and to investigate whether the classification decision score could serve as a robust and individualized brain signature. METHODS: A total of 3238 participants' structural MRI from four independent databases were employed to conduct a 3D residual attention network (3DRA-Net) to classify NC, mild cognitive impairment (MCI), and AD. The generalization was validated under inter-database cross-validation. The neurobiological basis of the classification decision score as a neuroimaging biomarker was systematically investigated by association with clinical profiles, as well as longitudinal trajectory analysis to reveal AD progression. All image analyses were performed only upon the single modality of T1-weighted MRI. RESULTS: Our study exhibited an outstanding performance (ACC = 91.6%, AUC = 0.95) of the comprehensive characterization of hippocampal features in distinguishing AD (n = 282) from NC (n = 603) in Alzheimer's Disease Neuroimaging Initiative cohort, and ACC = 89.2% and AUC = 0.93 under external validation. More importantly, the constructed score was significantly correlated with clinical profiles (p < 0.05), and dynamically altered over the AD longitudinal progression, provided compelling evidence of a solid neurobiological basis. CONCLUSIONS: This systemic study highlights the potential of the comprehensive characterization of hippocampal features to provide an individualized, generalizable, and biologically plausible neuroimaging biomarker for early detection of AD. KEY POINTS: • The comprehensive characterization of hippocampal features exhibited ACC = 91.6% (AUC = 0.95) in classifying AD from NC under intra-database cross-validation, and ACC = 89.2% (AUC = 0.93) in external validation. • The constructed classification score was significantly associated with clinical profiles, and dynamically altered over the AD longitudinal progression, which highlighted its potential of being an individualized, generalizable, and biologically plausible neuroimaging biomarker for early detection of AD.

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.

Engineered Amber-Emitting Nano Luciferase and Its Use for Immunobioluminescence Imaging In Vivo.

The NanoLuc luciferase (NLuc) and its furimazine (FRZ) substrate have revolutionized bioluminescence (BL) assays and imaging. However, the use of the NLuc-FRZ luciferase-luciferin pair for mammalian tissue imaging is hindered by the low tissue penetration of the emitting blue photons. Here, we present the development of an NLuc mutant, QLuc, which catalyzes the oxidation of a synthetic QTZ luciferin for bright and red-shifted emission peaking at ∼585 nm. Compared to other small single-domain NLuc mutants, this amber-light-emitting luciferase exhibited improved performance for imaging deep-tissue targets in live mice. Leveraging this novel bioluminescent reporter, we further pursued in vivo immunobioluminescence imaging (immunoBLI), which used a fusion protein of a single-chain variable antibody fragment (scFv) and QLuc for molecular imaging of tumor-associated antigens in a xenograft mouse model. As one of the most red-shifted NLuc variants, we expect QLuc to find broad applications in noninvasive mammalian imaging. Moreover, the immunoBLI method complements immunofluorescence imaging and immuno-positron emission tomography (immunoPET), serving as a convenient and nonradioactive molecular imaging tool for animal models in basic and preclinical research.

How segmentation methods affect hippocampal radiomic feature accuracy in Alzheimer's disease analysis?

OBJECTIVES: Hippocampal radiomic features (HRFs) can serve as biomarkers in Alzheimer's disease (AD). However, how different hippocampal segmentation methods affect HRFs in AD is still unknown. The aim of the study was to investigate how different segmentation methods affect HRF accuracy in AD analysis. METHODS: A total of 1650 subjects were identified from the Alzheimer's Disease Neuroimaging Initiative database (ADNI). The mini-mental state examination (MMSE) and Alzheimer's disease assessment scale (ADAS-cog13) were also adopted. After calculating the HRFs of intensity, shape, and textural features from each side of the hippocampus in structural magnetic resonance imaging (sMRI), the consistency of HRFs calculated from 7 different hippocampal segmentation methods was validated, and the performance of machine learning-based classification of AD vs. normal control (NC) adopting the different HRFs was also examined. Additional 571 subjects from the European DTI Study on Dementia database (EDSD) were to validate the consistency of results. RESULTS: Between different segmentations, HRFs showed a high measurement consistency (R > 0.7), a high significant consistency between NC, mild cognitive impairment (MCI), and AD (T-value plot, R > 0.8), and consistent significant correlations between HRFs and MMSE/ADAS-cog13 (p < 0.05). The best NC vs. AD classification was obtained when the hippocampus was sufficiently segmented by primitive majority voting (threshold = 0.2). High consistent results were reproduced from independent EDSD cohort. CONCLUSIONS: HRFs exhibited high consistency across different hippocampal segmentation methods, and the best performance in AD classification was obtained when HRFs were extracted by the naïve majority voting method with a more sufficient segmentation and relatively low hippocampus segmentation accuracy. KEY POINTS: • The hippocampal radiomic features exhibited high measurement/statistical/clinical consistency across different hippocampal segmentation methods. • The best performance in AD classification was obtained when hippocampal radiomics were extracted by the naïve majority voting method with a more sufficient segmentation and relatively low hippocampus segmentation accuracy.

Profiling and Bioinformatics Analysis Revealing Differential Circular RNA Expression about Storage Lesion Regulatory in Stored Red Blood Cells.

Introduction: Circular RNA (circRNA) plays an important role in regulating metabolism of red blood cells (RBCs) and their storage lesions, but the study of how circRNA expression changes in stored RBCs has rarely been conducted. Methods: The expression change of circRNA was systemically evaluated via high-throughput sequencing on healthy RBCs on day 0, 20, and 40. And then we confirmed the reliability of the high-throughput sequencing analysis by RT-qPCR characterization on selected circRNAs. A higher parental gene enrichment was used to explore circRNA function in pathways. In addition, we deciphered a dysregulated circRNA-related ceRNAs network, and identified three circRNA-miRNA-mRNA regulatory axes related to storage lesion. Results: We identified 2,586 known and 6,216 putative novel circRNAs, more than 100 circRNAs expression levels were shifted, and the number of downregulated circRNAs was greater with longer storage time. Furthermore, a higher parental gene enrichment related to circRNA was found in pathways, including cAMP signaling pathway, ubiquitin-mediated proteolysis, apoptosis, adhesion, MAPK signaling pathway, cystine methionine metabolism, RNA degradation, RNA transport, TGF-ß, and actin regulatory pathway. hsa_circ_0007127-miR-513a-5p-SMAD4, hsa_circ_0000033-miR-19a-3p-VAMP3, and hsa_circ_0005546-miR-4720-CCND3 regulatory axes related to storage lesion was found. Conclusions: Through investigation in circRNAs profile and circRNA-miRNA-mRNA interactions, this study provides insights on stored RBC circRNA expression changes, which closely relate to the storage lesion of RBCs and their physiological functions.

Genetic variants in SCNN1B and AHCYL1 are associated with eggshell quality in Chinese domestic laying ducks (Anas platyrhynchos).

1. The objective of this study was to investigate the evolution of SCNN1B and AHCYL1 proteins among 10 domestic avian and mammalian animal species, to uncover the expression patterns of SCNN1B and AHCYL1 genes in ducks, identify the genetic variants of the SCNN1B and AHCYL1 genes and analyse their effects on eggshell quality.2. Expression profiles of the SCNN1B and AHCYL1 genes in Sansui female ducks were determined using real-time fluorescence quantitative PCR to identify SNPs. The duck SCNN1B and AHCYL1 genes were amplified to identify SNPs. A total of 502 Sansui female ducks were genotyped by sequencing, and the associations between the mRNA expression/SNP genotypes and 6 eggshell quality indices were analysed using PASW Statistics 18.0.3. The results showed that the SCNN1B and AHCYL1 proteins are highly conserved in different mammalian or domestic animals, especially the AHCYL1 protein. The SCNN1B and AHCYL1 genes were widely expressed in different tissues of male and female ducks, and expression level in the uterus was greater than in other tissues. The expression of SCNN1B and AHCYL1 during the oviposition cycle indicated that expression levels were related to the eggshell mineralisation stage.4. The mRNA expression levels of the uterine SCNN1B and AHCYL1 genes were positively correlated with eggshell strength (ESS), percentage (ESP) and weight (ESW) (P < 0.05), respectively. Ten novel SNPs in SCNN1B and AHCYL1 genes from Chinese domestic laying ducks were identified through PCR amplicon sequencing.5. Genetic association analysis indicated g.797509 C > T, g.797573 C > T and g.797834 C > T in SCNN1B gene and g.169244 T > A, g.169265 T > C and g.175311 T > C in AHCYL1 gene had a significant effect on eggshell quality. Correlation analysis between the SNP genotype and SCNN1B and AHCYL1 genes expression in the uterus showed that the genotypes of g.797509 C > T, g.797573 C > T, g.797834 C > T, g.169244 T > A and g.175311 T > C sites affected the expression of SCNN1B and AHCYL1 genes in utero (P < 0.05).6. The study indicated SCNN1B and AHCYL1 as candidate genes to improve eggshell traits in ducks.

Association of three SNPs in adiponectin gene with lipid traits of Tianzhu Black Muscovy (Cairina moschata).

Adiponectin plays a critically biological role in atherosclerosis, glucose utilization, lipid and carbohydrate metabolism, and triglyceride synthesis in animals and humans. However, little is known about the effect of adiponectin on lipid metabolism of the avian species. The aim of the preset study was to investigate the potential associations between adiponectin gene single nucleotide polymorphisms (SNPs) and the lipid traits in 348 females of Tianzhu Black Muscovy. Three novel SNPs (167G>A, 290T>C and 711G>A) were detected in adiponectin gene. 167G>A and 290T>C has linked very closely, and then 711G>A with 167G>A and 290T>C has no strong linkage disequilibrium, respectively. The Chi square test showed that allelic frequency and genotype frequency of two SNPs (167G>A and 711G>A) didn't agree with the Hardy-Weinberg equilibrium (P>0.05). Four haplotypes and nine diplotypes were formed on the three SNPs of adiponectin gene. Association analysis indicated that the 167G>A genotypes were strongly associated with intramuscular fat (IMF) of chest muscle and serum total cholesterol (TC) (P < 0.01); the 290T>C genotypes were strongly associated with IMF, TC, and serum triglyceride (TG) (P < 0.01); furthermore, the 711G>A genotypes were significantly associated with TG and TC (P < 0.05); the diplotypes were strongly associated with IMF, TC, and TG (P < 0.01). Therefore, three SNPs in adiponectin were potential markers for improving IMF in Muscovy ducks.

Factors Influencing Patients' Intentions to Use Diabetes Management Apps Based on an Extended Unified Theory of Acceptance and Use of Technology Model: Web-Based Survey.

BACKGROUND: Diabetes poses heavy social and economic burdens worldwide. Diabetes management apps show great potential for diabetes self-management. However, the adoption of diabetes management apps by diabetes patients is poor. The factors influencing patients' intention to use these apps are unclear. Understanding the patients' behavioral intention is necessary to support the development and promotion of diabetes app use. OBJECTIVE: This study aimed to identify the determinants of patients' intention to use diabetes management apps based on an integrated theoretical model. METHODS: The hypotheses of our research model were developed based on an extended Unified Theory of Acceptance and Use of Technology (UTAUT). From April 20 to May 20, 2019, adult patients with diabetes across China, who were familiar with diabetes management apps, were surveyed using the Web-based survey tool Sojump. Structural equation modeling was used to analyze the data. RESULTS: A total of 746 participants who met the inclusion criteria completed the survey. The fitness indices suggested that the collected data fit well with the research model. The model explained 62.6% of the variance in performance expectancy and 57.1% of the variance in behavioral intention. Performance expectancy and social influence had the strongest total effects on behavioral intention (ß=0.482; P=.001). Performance expectancy (ß=0.482; P=.001), social influence (ß=0.223; P=.003), facilitating conditions (ß=0.17; P=.006), perceived disease threat (ß=0.073; P=.005), and perceived privacy risk (ß=-0.073; P=.012) had direct effects on behavioral intention. Additionally, social influence, effort expectancy, and facilitating conditions had indirect effects on behavioral intention that were mediated by performance expectancy. Social influence had the highest indirect effects among the three constructs (ß=0.259; P=.001). CONCLUSIONS: Performance expectancy and social influence are the most important determinants of the intention to use diabetes management apps. Health care technology companies should improve the usefulness of apps and carry out research to provide clinical evidence for the apps' effectiveness, which will benefit the promotion of these apps. Facilitating conditions and perceived privacy risk also have an impact on behavioral intention. Therefore, it is necessary to improve facilitating conditions and provide solid privacy protection. Our study supports the use of UTAUT in explaining patients' intention to use diabetes management apps. Context-related determinants should also be taken into consideration.

Activation of peroxisome proliferator activator receptor delta in mouse impacts lipid composition and placental development at early stage of gestation.

Peroxisome proliferator-activated receptor delta (Ppard) activation has been implicated in regulating a multitude of biological processes in placental development. In this study, we employed the UPLC-ESI-TOFMS approach to investigate the metabolic traits in placenta from GW501516-treated mice at Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most significant differences between control and GW501516-treated groups were identified. Among these metabolites, the fatty acids, phospholipids, and sterol lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that phosphatidylethanolamine biosynthesis and glycolysis were the top two altered metabolic pathways involved in carbohydrate metabolism, energy production, and lipid metabolism. Subsequent immunoblotting experiments provided evidence for positive correlation of PPARD level and AKT and ERK signaling pathways upon GW501516 treatment. Furthermore, the stimulation of GW501516 increased trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb), expression, suggesting a potential role of Ppard activation in promoting cytotrophoblast differentiation. Our results reveal that Ppard activation elicits dramatic changes of the metabolic activities in placenta, which is correlated to AKT and ERK signaling.

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.

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.

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.