Acetyl-CoA Derived from Hepatic Peroxisomal ß-Oxidation Inhibits Autophagy and Promotes Steatosis via mTORC1 Activation.

Autophagy is activated by prolonged fasting but cannot overcome the ensuing hepatic lipid overload, resulting in fatty liver. Here, we describe a peroxisome-lysosome metabolic link that restricts autophagic degradation of lipids. Acyl-CoA oxidase 1 (Acox1), the enzyme that catalyzes the first step in peroxisomal ß-oxidation, is enriched in liver and further increases with fasting or high-fat diet (HFD). Liver-specific Acox1 knockout (Acox1-LKO) protected mice against hepatic steatosis caused by starvation or HFD due to induction of autophagic degradation of lipid droplets. Hepatic Acox1 deficiency markedly lowered total cytosolic acetyl-CoA levels, which led to decreased Raptor acetylation and reduced lysosomal localization of mTOR, resulting in impaired activation of mTORC1, a central regulator of autophagy. Dichloroacetic acid treatment elevated acetyl-CoA levels, restored mTORC1 activation, inhibited autophagy, and increased hepatic triglycerides in Acox1-LKO mice. These results identify peroxisome-derived acetyl-CoA as a key metabolic regulator of autophagy that controls hepatic lipid homeostasis.

Integration of expression QTLs with fine mapping via SuSiE.

Genome-wide association studies (GWASs) have achieved remarkable success in associating thousands of genetic variants with complex traits. However, the presence of linkage disequilibrium (LD) makes it challenging to identify the causal variants. To address this critical gap from association to causation, many fine-mapping methods have been proposed to assign well-calibrated probabilities of causality to candidate variants, taking into account the underlying LD pattern. In this manuscript, we introduce a statistical framework that incorporates expression quantitative trait locus (eQTL) information to fine-mapping, built on the sum of single-effects (SuSiE) regression model. Our new method, SuSiE2, connects two SuSiE models, one for eQTL analysis and one for genetic fine-mapping. This is achieved by first computing the posterior inclusion probabilities (PIPs) from an eQTL-based SuSiE model with the expression level of the candidate gene as the phenotype. These calculated PIPs are then utilized as prior inclusion probabilities for risk variants in another SuSiE model for the trait of interest. By prioritizing functional variants within the candidate region using eQTL information, SuSiE2 improves SuSiE by increasing the detection rate of causal SNPs and reducing the average size of credible sets. We compared the performance of SuSiE2 with other multi-trait fine-mapping methods with respect to power, coverage, and precision through simulations and applications to the GWAS results of Alzheimer's disease (AD) and body mass index (BMI). Our results demonstrate the better performance of SuSiE2, both when the in-sample linkage disequilibrium (LD) matrix and an external reference panel is used in inference.

Regeneration of the human segmentation clock in somitoids in vitro.

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.

Hybrid Integration of Wearable Devices for Physiological Monitoring.

Wearable devices can provide timely, user-friendly, non- or minimally invasive, and continuous monitoring of human health. Recently, multidisciplinary scientific communities have made significant progress regarding fully integrated wearable devices such as sweat wearable sensors, saliva sensors, and wound sensors. However, the translation of these wearables into markets has been slow due to several reasons associated with the poor system-level performance of integrated wearables. The wearability consideration for wearable devices compromises many properties of the wearables. Besides, the limited power capacity of wearables hinders continuous monitoring for extended duration. Furthermore, peak-power operations for intensive computations can quickly create thermal issues in the compact form factor that interfere with wearability and sensor operations. Moreover, wearable devices are constantly subjected to environmental, mechanical, chemical, and electrical interferences and variables that can invalidate the collected data. This generates the need for sophisticated data analytics to contextually identify, include, and exclude data points per multisensor fusion to enable accurate data interpretation. This review synthesizes the challenges surrounding the wearable device integration from three aspects in terms of hardware, energy, and data, focuses on a discussion about hybrid integration of wearable devices, and seeks to provide comprehensive guidance for designing fully functional and stable wearable devices.

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease.

Despite significant advances in medical treatments and drug development, atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide. Dysregulated lipid metabolism is a well-established driver of ASCVD. Unfortunately, even with potent lipid-lowering therapies, ASCVD-related deaths have continued to increase over the past decade, highlighting an incomplete understanding of the underlying risk factors and mechanisms of ASCVD. Accumulating evidence over the past decades indicates a correlation between amino acids and disease state. This review explores the emerging role of amino acid metabolism in ASCVD, uncovering novel potential biomarkers, causative factors, and therapeutic targets. Specifically, the significance of arginine and its related metabolites, homoarginine and polyamines, branched-chain amino acids, glycine, and aromatic amino acids, in ASCVD are discussed. These amino acids and their metabolites have been implicated in various processes characteristic of ASCVD, including impaired lipid metabolism, endothelial dysfunction, increased inflammatory response, and necrotic core development. Understanding the complex interplay between dysregulated amino acid metabolism and ASCVD provides new insights that may lead to the development of novel diagnostic and therapeutic approaches. Although further research is needed to uncover the precise mechanisms involved, it is evident that amino acid metabolism plays a role in ASCVD.

Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for HCC.

BACKGROUND AND AIMS: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. APPROACH AND RESULTS: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 ( LPCAT1 ) and ceramide synthase 5 ( CERS5 ) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. CONCLUSIONS: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.

Histone deacetylase GhHDA5 negatively regulates Verticillium wilt resistance in cotton.

Verticillium wilt (VW) caused by Verticillium dahliae (V. dahliae) is one of the most destructive diseases in cotton (Gossypium spp.). Histone acetylation plays critical roles in plant development and adaptive responses to biotic and abiotic stresses. However, the relevance of histone acetylation in cotton VW resistance remains largely unclear. Here, we identified Histone Deacetylase 5 (GhHDA5) from upland cotton (Gossypium hirsutum L.), as a negative regulator of VW resistance. GhHDA5 expression was responsive to V. dahliae infection. Silencing GhHDA5 in upland cotton led to improved resistance to V. dahliae, while heterologous expression of GhHDA5 in Arabidopsis (Arabidopsis thaliana) compromised V. dahliae tolerance. GhHDA5 repressed the expression of several lignin biosynthesis-related genes, such as 4-coumarate: CoA ligase gene Gh4CL3 and ferulate 5-hydroxylase gene GhF5H, through reducing the acetylation level of Histone H3 Lysine 9 and 14 (H3K9K14ac) at their promoter regions, thereby resulting in an increased deposition of lignin, especially S monomers, in the GhHDA5-silenced cotton plants. The silencing of GhF5H impaired cotton VW tolerance. Additionally, the silencing of GhHDA5 also promoted the production of reactive oxygen species (ROS), elevated the expression of several pathogenesis-related genes (PRs), and altered the content and signaling of the phytohormones salicylic acid (SA), jasmonic acid (JA) and strigolactones (SLs) after V. dahliae infection. Taken together, our findings suggest that GhHDA5 negatively regulates cotton VW resistance through modulating disease-induced lignification and the ROS- and phytohormone-mediated defense response.

Loss of Macrophage mTORC2 Drives Atherosclerosis via FoxO1 and IL-1ß Signaling.

BACKGROUND: The mTOR (mechanistic target of rapamycin) pathway is a complex signaling cascade that regulates cellular growth, proliferation, metabolism, and survival. Although activation of mTOR signaling has been linked to atherosclerosis, its direct role in lesion progression and in plaque macrophages remains poorly understood. We previously demonstrated that mTORC1 (mTOR complex 1) activation promotes atherogenesis through inhibition of autophagy and increased apoptosis in macrophages. METHODS: Using macrophage-specific Rictor- and mTOR-deficient mice, we now dissect the distinct functions of mTORC2 pathways in atherogenesis. RESULTS: In contrast to the atheroprotective effect seen with blockade of macrophage mTORC1, macrophage-specific mTORC2-deficient mice exhibit an atherogenic phenotype, with larger, more complex lesions and increased cell death. In cultured macrophages, we show that mTORC2 signaling inhibits the FoxO1 (forkhead box protein O1) transcription factor, leading to suppression of proinflammatory pathways, especially the inflammasome/IL (interleukin)-1ß response, a key mediator of vascular inflammation and atherosclerosis. In addition, administration of FoxO1 inhibitors efficiently rescued the proinflammatory response caused by mTORC2 deficiency both in vitro and in vivo. Interestingly, collective deletion of macrophage mTOR, which ablates mTORC1- and mTORC2-dependent pathways, leads to minimal change in plaque size or complexity, reflecting the balanced yet opposing roles of these signaling arms. CONCLUSIONS: Our data provide the first mechanistic details of macrophage mTOR signaling in atherosclerosis and suggest that therapeutic measures aimed at modulating mTOR need to account for its dichotomous functions.

High-Density Dual-Structure Single-Atom Pt Electrocatalyst for Efficient Hydrogen Evolution and Multimodal Sensing.

Herein, we report a high-density dual-structure single-atom catalyst (SAC) by creating a large number of vacancies of O and Ti in two-dimensional (2D) Ti3C2 to immobilize Pt atoms (SA Pt-Ti3C2). The SA Pt-Ti3C2 showed excellent performance toward the pH-universal electrochemical hydrogen evolution reaction (HER) and multimodal sensing. For HER catalysis, compared to the commercial 20 wt % Pt/C, the Pt mass activities of SA Pt-Ti3C2 at the overpotentials of ∼30 and 110 mV in acid and alkaline media are 45 and 34 times higher, respectively. More importantly, during the alkaline HER process, an interesting synergetic effect between Pt-C and Pt-Ti sites that dominated the Volmer and Heyrovsky steps, respectively, was revealed. Moreover, the SA Pt-Ti3C2 catalyst exhibited high sensitivity (0.62-2.65 µA µM-1) and fast response properties for the multimodal identifications of ascorbic acid, dopamine, uric acid, and nitric oxide under the assistance of machine learning.

Integrated multi-omics analysis identifies features that predict human pluripotent stem cell-derived progenitor differentiation to cardiomyocytes.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are advancing cardiovascular development and disease modeling, drug testing, and regenerative therapies. However, hPSC-CM production is hindered by significant variability in the differentiation process. Establishment of early quality markers to monitor lineage progression and predict terminal differentiation outcomes would address this robustness and reproducibility roadblock in hPSC-CM production. An integrated transcriptomic and epigenomic analysis assesses how attributes of the cardiac progenitor cell (CPC) affect CM differentiation outcome. Resulting analysis identifies predictive markers of CPCs that give rise to high purity CM batches, including TTN, TRIM55, DGKI, MEF2C, MAB21L2, MYL7, LDB3, SLC7A11, and CALD1. Predictive models developed from these genes provide high accuracy in determining terminal CM purities at the CPC stage. Further, insights into mechanisms of batch failure and dominant non-CM cell types generated in failed batches are elucidated. Namely EMT, MAPK, and WNT signaling emerge as significant drivers of batch divergence, giving rise to off-target populations of fibroblasts/mural cells, skeletal myocytes, epicardial cells, and a non-CPC SLC7A11+ subpopulation. This study demonstrates how integrated multi-omic analysis of progenitor cells can identify quality attributes of that progenitor and predict differentiation outcomes, thereby improving differentiation protocols and increasing process robustness.

Mechanistic Investigation into Single-Electron Oxidative Addition of Single-Atom Cu(I)-N4 Site: Revealing the Cu(I)-Cu(II)-Cu(I) Catalytic Cycle in Photochemical Hydrophosphinylation.

Understanding the valency and structural variations of metal centers during reactions is important for mechanistic studies of single-atom catalysis, which could be beneficial for optimizing reactions and designing new protocols. Herein, we precisely developed a single-atom Cu(I)-N4 site catalyst via a photoinduced ligand exchange (PILE) strategy. The low-valent and electron-rich copper species could catalyze hydrophosphinylation via a novel single-electron oxidative addition (OA) pathway under light irradiation, which could considerably decrease the energy barrier compared with the well-known hydrogen atom transfer (HAT) and single electron transfer (SET) processes. The Cu(I)-Cu(II)-Cu(I) catalytic cycle, via single-electron oxidative addition and photoreduction, has been proven by multiple in situ or operando techniques. This catalytic system demonstrates high efficiency and requires room temperature conditions and no additives, which improves the turnover frequency (TOF) to 1507 h-1. In particular, this unique mechanism has broken through the substrate limitation and shows a broad scope for different electronic effects of alkenes and alkynes.

Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.

BACKGROUND: Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. METHODS: Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. RESULTS: We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-ß signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-ß-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. CONCLUSION: By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.

Vallesamidine and schizozygane alkaloids: rearranged monoterpene indole alkaloids and synthetic endeavours.

Covering 1963 to 2023Monoterpene indole alkaloids are the main sub-family of indole alkaloids with fascinating structures, stereochemistry, and diverse bioactivities (e.g., anticancer, anti-malarial and anti-arrhythmic etc.). Vallesamidine alkaloids and structurally more complex schizozygane alkaloids are small groups of rearranged monoterpene indole alkaloids with a unique 2,2,3-trialkylated indoline scaffold, while schizozygane alkaloids can generate a further rearranged skeleton, isoschizozygane, possessing a tetra-substituted, bridged tetrahydroquinoline core. In this review, the origin and structural features of vallesamidine and schizozygane alkaloids are introduced, and a discussion on the relationship of these alkaloids with aspidosperma alkaloids and a structural rearrangement hypothesis based on published studies is followed. Moreover, uncommon skeletons and potential bioactivities, such as anti-malarial and anti-tumour activities, make such alkaloids important synthetic targets, attracting research groups globally to accomplish total synthesis, resulting in impressive works on novel total synthesis, formal synthesis, and construction of key intermediates. These synthetic endeavours are systematically reviewed and highlighted with key strategies and efficiencies, providing different viewpoints on molecular structures and promoting the extension of chemical space and mining of new active scaffolds.

Helical Micropillar Processed by One-Step 3D Printing for Solar Thermal Conversion.

Solar thermal utilization has broad applications in a variety of fields. Currently, maximizing the photo-thermal conversion efficiency remains a research hotspot in this field. The exquisite plant structures in nature have greatly inspired human structural design across many domains. In this work, inspired by the photosynthesis of helical grass, a HM type solar absorber made in graphene-based composite sheets is used for solar thermal conversion. The unique design promoted more effective solar energy into thermal energy through multiple reflections and scattering of solar photons. Notably, the Helical Micropillar (HM) is fabricated using a one-step projection 3D printing process based on a special 3D helical beam. As a result, the solar absorber's absorbance value can reach 0.83 in the 400-2500 nm range, and the surface temperature increased by ≈128.3% relative to the original temperature. The temperature rise rate of the solar absorber reached 22.4 °C min-1, demonstrating the significant potential of the HM in practical applications of solar thermal energy collection and utilization.

Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription­quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial-mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.

TaNAC1 boosts powdery mildew resistance by phosphorylation-dependent regulation of TaSec1a and TaCAMTA4 via PP2Ac/CDPK20.

The integrity of wheat (Triticum aestivum) production is increasingly jeopardized by the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), particularly amid the vicissitudes of climate change. Here, we delineated the role of a wheat transcription factor, TaNAC1, which precipitates cellular apoptosis and fortifies resistance against Bgt. Utilizing BiFC, co-immunoprecipitation, protein quantification, luciferase report assays, we determined that cytoplasmic TaNAC1-7A undergoes phosphorylation at the S184/S258 sites by TaCDPK20, facilitating its nuclear translocation. This migration appears to prime further phosphorylation by TaMPK1, thereby enhancing transcriptional regulatory activity. Notably, the apoptotic activity of phosphorylated TaNAC1-7A is negatively modulated by the nuclear protein phosphatase PP2Ac. Furthermore, activation of TaNAC1 phosphorylation initiates transcription of downstream genes TaSec1a and TaCAMTA4, through binding to the C[T/G]T[N7]A[A/C]G nucleic acid motif. Suppression of TaNAC1, TaCDPK20, and TaMPK1 in wheat compromises its resistance to Bgt strain E09, whereas overexpression of TaNAC1 and silencing of PP2Ac markedly elevate resistance levels. Our results reveal the pivotal role of TaNAC1 in basal resistance which is mediated by its effects on homotypic fusion, vacuolar protein sorting, and the expression of defense-related genes. The findings highlight the potential through targeting TaNAC1 and its regulators as a strategy for improving wheat's resistance to fungal pathogens.

A negative feedback regulatory module comprising R3-MYB repressor MYBL2 and R2R3-MYB activator PAP1 fine-tunes high light-induced anthocyanin biosynthesis in Arabidopsis.

Anthocyanins, a group of flavonoids, play diverse roles in plant growth and environmental adaptation. The biosynthesis and accumulation of anthocyanin are regulated by environmental cues, such as high light. However, the precise mechanism underlying anthocyanin biosynthesis under high light conditions remains largely unclear. Here, we report that the R3-MYB repressor MYB-LIKE 2 (MYBL2) negatively regulates high light-induced anthocyanin biosynthesis by repressing two R2R3-MYB activators, PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) and PAP2, which are core components of the MYB-bHLH-WD40 (MBW) complex. We found that MYBL2 interacts with PAP1/2 and reduces their transcriptional activation activities, thus disrupting the expression of key genes involved in anthocyanin biosynthesis, such as DIHYDROFLAVONOL 4-REDUCTASE (DFR) and TRANSPARENT TESTA 19 (TT19). Additionally, MYBL2 attenuates the transcriptional activation of PAP1 on its own expression, but not PAP2. Conversely, PAP1 collaborates with TT8, a bHLH member of the MBW complex, to activate MYBL2 transcription when excessive anthocyanins are accumulated. Taken together, our findings reveal a negative feedback regulatory module composed of MYBL2 and PAP1 that fine-tunes high light-induced anthocyanin biosynthesis through modulating MBW complex assembly.

Chiral Amphiphilic Au23 Cluster and Its Specific Recognition to Remote Di-amines.

The atomic precision of metal nanoclusters and variability of surface ligands pave the way for its rational design and functionalization, whereas the property strengthening in multiple ways has been long challenging. Herein, improved amphiphilicity, chirality, thermostability, and strong CPL (circularly polarized luminescence) properties have been accomplished by facile ligand exchange of [Au23(CHT)16]- with HCapt (HCHT and HCapt denote cyclohexanethiol and captopril). In addition, the obtained chiral [Au23(SR)16]- (short for [Au23(CHT)16-x(Capt)x]-) clusters show specific binding affinity to remote-diamines (such as arginine and single/double strand DNA), originating from the hydrogen bonding and Van der Walls interaction among the surface Capt ligands and the di-amine groups.

Lactobacillus amylovorus Promotes Lactose Utilization in Small Intestine and Enhances Intestinal Barrier Function in Intrauterine Growth Restricted Piglets.

BACKGROUND: Intrauterine growth restriction (IUGR) resulted in high mortality and many physiological defects of piglets, causing huge economic loss in the swine industry. Lactobacillus amylovorus (L. amylovorus) was identified as one of the main differential bacteria between IUGR and normal piglets. However, the effects of L. amylovorus on the growth performance and intestinal health in IUGR piglets remained unclear. OBJECTIVES: This study aimed to investigate the promoting effects of L. amylovorus Mafic1501, a new strain isolated from normal piglets, on the growth performance and intestinal barrier functions in IUGR piglets. METHODS: Newborn mice or piglets were assigned into 3 groups: CON (normal birth weight, control), IUGR (low birth weight), and IUGR+L. amy (low birth weight), administered with sterile saline or L. amylovorus Mafic1501, respectively. Growth performance, lactose content in the digesta, intestinal lactose transporter, and barrier function parameters were profiled. IPEC-J2 cells were cultured to verify the effects of L. amylovorus Mafic1501 on lactose utilization and intestinal barrier functions. RESULTS: L. amylovorus Mafic1501 elevated body weight and average daily gain of IUGR mice and piglets (P < 0.05). The lactose content in the ileum was decreased, whereas gene expression of glucose transporter 2 (GLUT2) was increased by L. amylovorus Mafic1501 in IUGR piglets during suckling period (P < 0.05). Besides, L. amylovorus Mafic1501 promoted intestinal barrier functions by increasing the villus height and relative gene expressions of tight junctions (P < 0.05). L. amylovorus Mafic1501 and its culture supernatant decreased the lactose level in the medium and upregulated gene expressions of transporter GLUT2 and tight junction protein Claudin-1 of IPEC-J2 cells (P < 0.05). CONCLUSION: L. amylovorus Mafic1501 improved the growth performance of IUGR piglets by promoting the lactose utilization in small intestine and enhancing intestinal barrier functions. Our results provided the new evidence of L. amylovorus Mafic1501 for its application in the swine industry.