Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Exogenous Bile Acids on Antioxidant Status and Gut Microbiota in Heat-Stressed Broiler Chickens

Bile acids are critical for lipid absorption, however, their new roles in maintaining or regulating systemic metabolism are irreplaceable. The negative impacts of heat stress (HS) on growth performance, lipid metabolism, and antioxidant status have been reported, but it remains unknown whether the bile acids (BA) composition of broiler chickens can be affected by HS. Therefore, this study aimed to investigate the modulating effects of the environment (HS) and whether dietary BA supplementation can benefit heat-stressed broiler chickens. A total of 216 Arbor Acres broilers were selected with a bodyweight approach average and treated with thermal neutral (TN), HS (32°C), or HS-BA (200 mg/kg BA supplementation) from 21 to 42 days. The results showed that an increase in average daily gain (P < 0.05) while GSH-Px activities (P < 0.05) in both serum and liver were restored to the normal range were observed in the HS-BA group. HS caused a drop in the primary BA (P = 0.084, 38.46%) and Tauro-conjugated BA (33.49%) in the ileum, meanwhile, the secondary BA in the liver and cecum were lower by 36.88 and 39.45% respectively. Notably, results were consistent that SBA levels were significantly increased in the serum (3-fold, P = 0.0003) and the ileum (24.89-fold, P < 0.0001). Among them, TUDCA levels (P < 0.01) were included. Besides, BA supplementation indeed increased significantly TUDCA (P = 0.0154) and THDCA (P = 0.0003) levels in the liver, while ileal TDCA (P = 0.0307), TLCA (P = 0.0453), HDCA (P = 0.0018), and THDCA (P = 0.0002) levels were also increased. Intestinal morphology of ileum was observed by hematoxylin and eosin (H&E) staining, birds fed with BA supplementation reduced (P = 0.0431) crypt depth, and the ratio of villous height to crypt depth trended higher (P = 0.0539) under the heat exposure. Quantitative RT-PCR showed that dietary supplementation with BA resulted in upregulation of FXR (P = 0.0369), ASBT (P = 0.0154), and Keap-1 (P = 0.0104) while downregulation of iNOS (P = 0.0399) expression in ileum. Moreover, 16S rRNA gene sequencing analysis and relevance networks revealed that HS-derived changes in gut microbiota and BA metabolites of broilers may affect their resistance to HS. Thus, BA supplementation can benefit broiler chickens during high ambient temperatures, serving as a new nutritional strategy against heat stress.
Integrative Morphological, Physiological, Proteomics Analyses of Jujube Fruit Development Provide Insights Into Fruit Quality Domestication From Wild Jujube to Cultivated Jujube

Jujube (Ziziphus jujuba) was domesticated from wild jujube (Z. jujuba var. spinosa). Here, integrative physiological, metabolomic, and comparative proteomic analyses were performed to investigate the fruit expansion and fruit taste components in a jujube cultivar ‘Junzao’ and a wild jujube ‘Qingjiansuanzao’ with contrasting fruit size and taste. We revealed that the duration of cell division and expansion largely determined the final fruit size, while the intercellular space in the mesocarp dictated the ratio of mesocarp volume in mature fruits. The high levels of endogenous gibbereline3 (GA) and zeatin in the growing fruit of ‘Junzao’ were associated with their increased fruit expansion. Compared with ‘Junzao,’ wild jujube accumulated lower sugars and higher organic acids. Furthermore, several protein co-expression modules and important member proteins correlated with fruit expansion, sugar synthesis, and ascorbic acid metabolism were identified. Among them, GA20OX involved in GA biosynthesis was identified as a key protein regulating fruit expansion, whereas sucrose-6-phosphate synthase (SPS) and neutral invertase (NINV) were considered as key enzymes promoting sugar accumulation and as major factors regulating the ratio of sucrose to hexose in jujube fruits, respectively. Moreover, the increase of Nicotinamide adenine dinucleotide-Malate dehydrogenase (NAD-MDH) activity and protein abundance were associated with the malic acid accumulation, and the high accumulation of ascorbic acid in wild jujube was correlated with the elevated abundance of GalDH, ZjAPXs, and MDHAR1, which are involved in the ascorbic acid biosynthesis and recycling pathways. Overall, these results deepened the understanding of mechanisms regulating fruit expansion and sugar/acids metabolisms in jujube fruit.
Alphataxin, a Small-Molecule Drug That Elevates Tumor-Infiltrating CD4+ T Cells, in Combination With Anti-PD-1 Therapy, Suppresses Murine Renal Cancer and Metastasis

By promoting the cytotoxic function of CD8+ T cells, immune checkpoint inhibitor therapy, e.g. programmed cell death protein-1 (PD-1), effectively inhibits tumor growth in renal cell carcinoma. Yet, as many as 87% of cancer patients do not respond to immune checkpoint therapy. Importantly, cytotoxic CD8+ T cell function crucially relies on CD4+ T helper cell cytokines, in particular, tumor necrosis factor beta (TNFβ) and its CD8+ T cell receptor (TNFR2) in the opposing manner as immune checkpoints and their receptors. Remarkably, despite advances in immunotherapy, there are no pharmaceutical treatments that increase circulating CD4+ T cell counts. Nor has there been much attention given to tumor-infiltrating CD4+ T cells. Using data from a clinical trial (NCT01731691), we discovered that the protein alpha-1 proteinase inhibitor (α1PI, alpha-1 antitrypsin) regulates the number of circulating CD4+ T cells. The orally available small-molecule drug Alphataxin acts as a surrogate for α1PI in this pathway. We aimed to examine how Alphataxin affected tumor growth in a murine model of renal cell carcinoma. Alphataxin, in combination with anti-PD-1 antibody, significantly elevated the ratio of circulating and tumor-infiltrating CD4+ T cells. In one study, following orthotopic implantation of syngeneic renal adenocarcinoma cells, combination treatment resulted in 100% regression of tumor growth. Moreover, in mice implanted orthotopically with one log more tumor cells, doubling Alphataxin dose in combination treatment led to 100% regression in one-third of mice and 81% suppression of tumor growth in the remaining two-thirds of mice. Lung metastasis was present in monotherapy, but significantly reduced in combination-treated mice. Orally available Alphataxin, the first and only drug developed to increase CD4+ T cells, in combination with anti-PD-1, is a powerful therapeutic method that provides long-term remission in renal cell carcinoma and potentially other T cell-responsive cancers by increasing the number of CD4+ tumor-infiltrating T cells.
A Core Omnigenic Non-coding Trait Governing Dex-Induced Osteoporotic Effects Identified Without DEXA

Iatrogenic glucocorticoid (GC)-induced osteoporosis (GIO) is an idiosyncratic form of secondary osteoporosis. Genetic predisposition among individuals may give rise to variant degree of phenotypic changes but there has yet been a documented unified pathway to explain the idiosyncrasy. In this study, we argue that the susceptibility to epigenetic changes governing molecular cross talks along the BMP and PI3K/Akt pathway may underline how genetic background dictate GC-induced bone loss. Concordantly, osteoblasts from BALB/c or C57BL/6 neonatal mice were treated with dexamethasone for transcriptome profiling. Furthermore, we also confirmed that GC-pre-conditioned mesenchymal stem cells (MSCs) would give rise to defective osteogenesis by instigating epigenetic changes which affected the accessibility of enhancer marks. In line with these epigenetic changes, we propose that GC modulates a key regulatory network involving the scavenger receptor Cd36 in osteoblasts pre-conditioning pharmacological idiosyncrasy in GIO.
Dissolved Oxygen in Heterogeneous Environments Dictates the Metabolic Rate and Thermal Sensitivity of a Tropical Aquatic Crab

Oxygen availability, together with water temperature, greatly varies in coastal habitats, especially in those characterized by elevated primary production. In this study, we investigate the combined role of dissolved oxygen and temperature on the thermal physiological response of the mud crab Thalamita crenata living in an equatorial system of coastal habitats. We sampled temperature, oxygen and salinity in T. crenata habitats, mangrove creeks and fringes and seagrass meadows, at Gazi Bay (Kenya). We found that seagrass meadows exhibited higher temperature and oxygen saturation than the mangrove habitats during the day, creating conditions of oxygen supersaturation. By investigating the effect of different levels of oxygen saturation on the thermal response of T. crenata, we demonstrated that the respiratory physiology of this ectotherm has a pronounced resistance to heat, directly influenced by the amount of dissolved oxygen in the water. Under low oxygen saturation levels, the mud crab significantly reduced its metabolism, becoming temperature-independent. This result shows that aquatic species can modulate their thermal response in a stringent dependency with water oxygen saturation, corroborating previous findings on the thermal response of T. crenata under supersaturation. This contribution provides further support for the need to adopt an ecologically-relevant approach to forecast the effect of climate change on marine ectothermal species.
Dissecting Motor and Cognitive Component Processes of a Finger-Tapping Task With Hybrid Dopamine Positron Emission Tomography and Functional Magnetic Resonance Imaging

Striatal dopamine is involved in facilitation of motor action as well as various cognitive and emotional functions. Positron emission tomography (PET) is the primary imaging method used to investigate dopamine function in humans. Previous PET studies have shown striatal dopamine release during simple finger tapping in both the putamen and the caudate. It is likely that dopamine release in the putamen is related to motor processes while dopamine release in the caudate could signal sustained cognitive component processes of the task, but the poor temporal resolution of PET has hindered firm conclusions. In this study we simultaneously collected [11C]Raclopride PET and functional Magnetic Resonance Imaging (fMRI) data while participants performed finger tapping, with fMRI being able to isolate activations related to individual tapping events. The results revealed fMRI-PET overlap in the bilateral putamen, which is consistent with a motor component process. Selective PET responses in the caudate, ventral striatum, and right posterior putamen, were also observed but did not overlap with fMRI responses to tapping events, suggesting that these reflect non-motor component processes of finger tapping. Our findings suggest an interplay between motor and non-motor-related dopamine release during simple finger tapping and illustrate the potential of hybrid PET-fMRI in revealing distinct component processes of cognitive functions.
Controls of Wind-Driven Jet on the Distribution of Pelagic Cnidarians in the Midwestern South China Sea

The coastal water transported by the combined action of southwest wind jet and anticyclonic eddy substantially influences the biological processes in the midwestern South China Sea. However, how the wind-driven jet affects the zooplankton community remains unclear. In this study, the species number, abundance, and vertical distribution of medusae were investigated in the wind-driven jet (WJR) and non-wind-driven jet regions (NWJR). The low-salinity and nutrient-rich coastal water substantially influenced species composition, abundance, and vertical distribution of medusae in the WJR. The species number of the meroplanktonic hydromedusae in the WJR was approximately twice that in the NWJR due to the horizontal transport of wind-driven jets. The abundances of holoplanktonic hydromedusae in WJR were 38.2 ± 9.3 ind⋅m–3, which were thrice of that in the NWJR regions, caused by the abundant diet in the WJR. Additionally, only the abundance of medusae above the thermocline was affected by the coastal water in WJR, while these showed no significant difference below the thermocline between the WJR and the NWJR. Generalized additive model analyses suggested that the diet was the most important factor affecting the abundance of the holoplanktonic hydromedusae and siphonophore, whereas meroplanktonic hydromedusae were influenced by the combination of temperature, salinity, and diet.
Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development

Although long non-coding RNAs (lncRNAs) is one of the most abundant classes of RNAs encoded within the mammalian genome and are highly expressed in the adult brain, they remain poorly characterized and their roles in the brain development are not well understood. Here we identify the lncRNA Lacuna (also catalogued as NONMMUT071331.2 in NONCODE database) as a negative regulator of neuronal differentiation in the neural stem/progenitor cells (NSCs) during mouse brain development. In particular, we show that Lacuna is transcribed from a genomic locus near to the Tbr2/Eomes gene, a key player in the transition of intermediate progenitor cells towards the induction of neuronal differentiation. Lacuna RNA expression peaks at the developmental time window between E14.5 and E16.5, consistent with a role in neural differentiation. Overexpression experiments in ex vivo cultured NSCs from murine cortex suggest that Lacuna is sufficient to inhibit neuronal differentiation, induce the number of Nestin+ and Olig2+ cells, without affecting proliferation or apoptosis of NSCs. CRISPR/dCas9-KRAB mediated knockdown of Lacuna gene expression leads to the opposite phenotype by inducing neuronal differentiation and suppressing Nestin+ and Olig2+ cells, again without any effect on proliferation or apoptosis of NSCs. Interestingly, despite the negative action of Lacuna on neurogenesis, its knockdown inhibits Eomes transcription, implying a simultaneous, but opposite, role in facilitating the Eomes gene expression. Collectively, our observations indicate a critical function of Lacuna in the gene regulation networks that fine tune the neuronal differentiation in the mammalian NSCs.
Hfq Regulates Efflux Pump Expression and Purine Metabolic Pathway to Increase Trimethoprim Resistance in Aeromonas veronii

Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis, and brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qβ replication) participates in the regulations of the virulence, adhesion, and nitrogen fixation, effecting on the growth, metabolism synthesis and stress resistance in bacteria. The deletion of hfq gene in A. veronii showed more sensitivity to trimethoprim, accompanying by the upregulations of purine metabolic genes and downregulations of efflux pump genes by transcriptomic data analysis. Coherently, the complementation of efflux pump-related genes acrA and acrB recovered the trimethoprim resistance in Δhfq. Besides, the accumulations of adenosine and guanosine were increased in Δhfq in metabonomic data. The strain Δhfq conferred more sensitive to trimethoprim after appending 1 mM guanosine to M9 medium, while wild type was not altered. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.
Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.
Dissolution Study on Grape Polyphenol Hard Gelatin Capsule Dietary Supplements

Methods for a dissolution study by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC-QqQ/MS) analysis of grape polyphenol dietary supplements, namely, grape seed extract (GSE) and resveratrol (RSV) capsules, were developed following the guidance of United States Pharmacopeia (USP) <2040>. Two dissolution media, 0.1 N hydrochloric acid (pH 1.2) and 0.05 M acetate buffer (pH 4.6), were evaluated with dissolution apparatus (USP 1), 100 rpm rotation speed, and 900 ml dissolution medium volume. Dissolution profiling was performed over 120 min. Major phenolic compounds of gallic acid, catechin, epicatechin, and procyanidin B2 were quantitated to obtain the dissolution profile of GSE capsules, and trans-RSV was used for RSV capsules. Results indicated that the released trans-RSV for RSV capsules in both of the dissolution media meets the USP standards, and that for the GSE capsules, all the four marker compounds passed the dissolution test in the HCl medium but did not reach a 75% release within 60 min in the acetate buffer. These promising results suggest that the general USP dissolution protocols are adequate for the successful release of RSV capsules in HCl medium and acetate buffer and GSE capsules (in HCl medium), but may be inadequate for GSE capsules in acetate buffer. These results showed that under a low pH of 1.2 (simulated stomach environment), bioactive compounds were released on time from the GSE capsules and met the USP guidelines; however, under a higher pH of 4.6 (simulated duodenum environment), the same biomarkers failed, suggesting the need to further improve the dissolution of GSE over a wider range of pH environments to enhance bioavailability and efficacy.
Development of an Oxidative Phosphorylation-Related and Immune Microenvironment Prognostic Signature in Uterine Corpus Endometrial Carcinoma

Background: As the fourth most common malignant tumors in women, uterine corpus endometrial carcinoma (UCEC) requires novel and reliable biomarkers for prognosis prediction to improve the overall survival. Oxidative phosphorylation (OXPHOS) is found to be strongly correlated with the progression of tumor. Here, we aimed to construct an OXPHOS-related and immune microenvironment prognostic signature to stratify UCEC patients for optimization of treatment strategies. Method: Prognosis-associated OXPHOS-related differentially expressed genes were identified by multivariable Cox regression from TCGA–UCEC cohort. Based on the candidate genes, an OXPHOS-related prognostic signature was constructed by the train set data and verified by the entire set. When integrated with relevant clinical characteristics, a nomogram was also created for clinical application. Through comparison of tumor microenvironment between different risk groups, the underlying mechanism of the model and the inner correlation between immune microenvironment and energy metabolism were further investigated. Results: An OXPHOS-related signature containing ATP5IF1, COX6B1, FOXP3, and NDUFB11 was constructed and had better predictive ability compared with other recently published signatures in UCEC. Patients with lower risk score showed higher immune cell infiltration, higher ESTIMATE score (p = 2.808E−18), lower tumor purity (p = 2.808E−18), higher immunophenoscores (IPSs) (p < 0.05), lower expression of mismatch repair (MMR) proteins (p < 0.05), higher microsatellite instability (MSI), lower expression of markers of N6-methyladenosine (m6A) mRNA methylation regulators, higher tumor mutation burden (TMB) (p = 1.278E−9), and more sensitivity to immune checkpoint blockade (ICB) (p < 0.001) and chemotherapy drugs, thus, possessing improved prognosis. Conclusion: An OXPHOS-related and immune microenvironment prognostic signature classifying EC patients into different risk subsets was constructed in our study, which could be used to predict the prognosis of patients and help to select a specific subset of patients who might benefit from immunotherapy and chemotherapy, thus, improving the overall survival rate of UCEC. These findings may contribute to the discovery of novel and robust biomarkers or target therapy in UCEC and give new insights into the molecular mechanism of tumorigenesis and progression of UCEC.
A Willingness-to-Pay Associated Right Prefrontal Activation During a Single, Real Use of Lipsticks as Assessed Using Functional Near-Infrared Spectroscopy

Understanding consumer preferences and behavior is a major goal of consumer-oriented companies. The application of neuroscience to this goal is a promising avenue for companies. Previously, we observed a positive correlation during actual cosmetic use between the right dorsolateral prefrontal cortex (dlPFC) activity, measured by functional near-infrared spectroscopy (fNIRS), and the associated willingness-to-pay (WTP) values. However, we were unable to find any consistent group differences in the right dlPFC between different powdery foundations. Thus, the main objective of this study was to replicate the previous study and in addition, we aimed to refine the method of the previous study to increase the chance that a difference in valuation between different products can be detected. Twenty-five frequent lipstick using females were asked to apply six different lipsticks to their lips and to record how much they were willing to pay. To maximize the variation of the subjective experience of the products and the associated brain activity, the most preferred color lipstick and a less preferred color lipstick were chosen for each participant, and each color of lipstick had three different textures (Lo, Mid, and Hi). The time series was analyzed with the general linear model (GLM) and the correlation between the right dlPFC beta scores for the lipsticks and their respective WTP values conducted for each participant. This revealed a significant positive correlation and replicated our previous study. Surprisingly, the lipstick color and the texture manipulations did not result in any consistent differences in WTP and similarly no consistent group differences in brain activations. This study replicates our previous study extending it to a different type of cosmetic. The right dlPFC activity during the use of cosmetics may be a potential brain-based personalization or product selection process biomarker.