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Obesity and malnutrition both cause dysbiosis and dampen retinoic acid (RA) signaling pathways, which play pivotal roles in biological processes. The current study evaluates a hypothesis that colitis-associated dysbiosis also has systemic negative impacts on RA signaling. Thus, we studied the effects of inflammation, under a vitamin A-sufficient condition, on RA signaling using mouse colitis models induced by dextran sulfate sodium. That data showed that intestinal inflammation resulted in reduced RA signaling in the liver, brain, gut, and adipose tissues measured by analyzing the expression of genes encoding for the synthesis, oxidation, transport, and receptor of RA. The expression of RA-regulated gut homing molecules including α4β7 integrin, and CCR9, along with MADCAM1 were all reduced in colitis mice revealing compromised immunity due to reduced RA signaling. The data also showed that the development of colitis was accompanied by dysbiosis featured with reduced Lactobacillaceae and Verrucomicrobiaceae but an expansion of Erysipelotrichaceae and others. Colitis resulted in reduced butyrate-producing bacteria and increased methane-generating bacteria. Additionally, dysbiosis was associated with induced Il-1β, Ifn-γ, and Tnf-α mRNA but reduced Il-22, Il-17f, and Rorγt transcripts in the colon. Together, intestinal inflammation inhibits RA signaling in multiple organs. RA is essential in regulating various biological processes, it is critical to detect RA signaling reduction in tissues even when vitamin A deficiency is absent. Moreover, probiotics can potentially prevent dysbiosis and reverse compromised RA signaling, having systemic health benefits.

In the era of the digital economy, live-streaming of agricultural products has become a new means of rural revitalization, which not only promotes the transformation of the rural economy but also deepens the dual promotion of villagers' rights and identities. Based on the practice of rural women's participation in the live-streaming of agricultural products, this study discussed the extent to which the live-streaming economy reconstructed rural women's identities and reproduced their production and living spaces from the perspective of feminist geography. Based on a sampling of villages representative of Qianpai Town, Guangdong Province, this study unfolded the opportunities, processes, and effects of women's empowerment in rural spatial transformation through qualitative research methods, such as participatory observation, in-depth interviews, and discourse analysis. Findings of the present study included: (1) while the live-streaming economy was found in the rural area, not only were diversified resources, such as policy, education, material, and cultural support, brought to Qianpai Town, but also rural women who either originally worked in cities or engaged in agricultural production obtained their new empowerment power. (2) The empowerment of rural women was prominently manifested in the reconstruction process of women's identity during the practice of digital entrepreneurship. Owing to the development of the digital economy, rural women self-reconstructed their identity from "migrant workers" to "returning entrepreneurs" and from "knowledge receivers" to "culture communicators", showing that they could expand their way of livelihood by mastering the right of independent employment, as well as the expansion of women's social network and the prominence of their dominant position. (3) The rural reconstruction under the live-streaming economy was a complex and dynamic process in which rural production and living spaces, private spaces, and public spaces were intertwined. The "familiarization" of live-streaming places broke the boundary between women's production and living spaces and facilitated the economic transformation of home space and the socialization of private space, thus contributing to the reconstruction of production and living spaces in rural areas. Overall, the practice of women's digital entrepreneurship contributed to the enhancement of their sense of self-value and the reshaping of their roles at home and in society to raise their voice and status in the economic activities of the family. This study argued that the coupling of rural women and the "live-streaming economy" in the digitalization process of rural areas provides a new research ground for deepening the understanding of women's empowerment mechanism through digital technology and the evolving human-place relationship of rural China. The analysis presented contributes to the exploration of the rural transformation and development processes from the perspective of the interaction between "women" and "place" and provides actionable insights into rural restructuring. The results of this study help to better understand the effects and mechanisms of the live-streaming economy on rural women as well as on their production and living spaces, thereby presenting theoretical and practical insights into rural women's empowerment through digital technology.

BackgroundChronic consumption of high sugar and high fat diet associated with liver inflammation and cognitive decline. This paper tests a hypothesis that the development and resolution of diet-induced nonalcoholic fatty liver disease (NAFLD) has an impact on neuroplasticity and cognition.MethodsC57BL/6 wild-type mice were fed with either a healthy control diet (CD) or a fructose, palmitate, and cholesterol (FPC)-enriched diet since weaning. When mice were 3-months old, FPC diet-fed mice were randomly assigned to receive either FPC-enriched diet with or without 6% inulin supplementation. At 8 months of age, all three groups of mice were euthanized followed by analysis of inflammatory signaling in the liver and brain, gut microbiota, and cecal metabolites.ResultsOur data showed that FPC diet intake induced hepatic steatosis and inflammation in the liver and brain along with elevated RORγ and IL-17A signaling. Accompanied by microglia activation and reduced hippocampal long-term potentiation, FPC diet intake also reduced postsynaptic density-95 and brain derived neurotrophic factor, whereas inulin supplementation prevented diet-reduced neuroplasticity and the development of NAFLD. In the gut, FPC diet increased Coriobacteriaceae and Erysipelotrichaceae, which are implicated in cholesterol metabolism, and the genus Allobaculum, and inulin supplementation reduced them. Furthermore, FPC diet reduced FXR and TGR5 signaling, and inulin supplementation reversed these changes. Untargeted cecal metabolomics profiling uncovered 273 metabolites, and 104 had significant changes due to FPC diet intake or inulin supplementation. Among the top 10 most affected metabolites, FPC-fed mice had marked increase of zymosterol, a cholesterol biosynthesis metabolite, and reduced 2,8-dihydroxyquinoline, which has known benefits in reducing glucose intolerance; these changes were reversible by inulin supplementation. Additionally, the abundance of Barnesiella, Coprobacter, Clostridium XIVa, and Butyrivibrio were negatively correlated with FPC diet intake and the concentration of cecal zymosterol but positively associated with inulin supplementation, suggesting their benefits.ConclusionTaken together, the presented data suggest that diet alters the gut microbiota and their metabolites, including bile acids. This will subsequently affect IL-17A signaling, resulting in systemic impacts on both hepatic metabolism and cognitive function.

BACKGROUND: Probiotic VSL#3 is used to treat ulcerative colitis. This study examines the effect of VSL#3 in non-alcoholic steatohepatitis (NASH) that has liver carcinogenic potential. METHODS: Western diet (WD)-fed wild-type (WT) mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison. Age-, sex-, and diet-matched bile acid (BA) receptor farnesoid X receptor (FXR) knockout (KO) mice, which developed severe NASH and had the potential for liver cancer development, were supplemented with and without VSL#3 for 7 months. All the mice were euthanized when they were 10 months old. RESULTS: Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration, reduced hepatic fat content, and improved insulin sensitivity in WD-fed FXR KO mice. In addition, VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway, inducing the alternative BA pathway, and activating ileal G-protein coupled BA receptor 1 (GPBAR1)-regulated signaling. Moreover, VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae, Porphyromonadaceae, and Helicobacteraceae as well as increasing Lachnospiraceae. Further, VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium, which generate butyrate, at the genus level. It also increased the copy number of the butyrate-producing genes bcoA and buk, suggesting their anti-inflammatory and metabolic effects. CONCLUSIONS: VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis, suggesting its potential in liver cancer prevention.

Wheat is one of the most important food crops globally, and understanding the regulation of grain size is crucial for wheat breeding to achieve a higher grain yield. MicroRNAs (miRNAs) play vital roles in plant growth and development. However, the miRNA-mediated mechanism underlying grain size regulation remains largely elusive in wheat. Here, we report the characterization and functional validation of a miRNA, TamiR397a, associated with grain size regulation in wheat. The function of three TaMIR397 homoeologs was determined through histochemical β-glucuronidase-dependent assay. MiRNA expression was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the function of TamiR397a was validated through its transgenic overexpression and repression in wheat. It was found that TaMIR397-6A and TaMIR397-6B encode active TamiR397a. The expression profiling indicated that TamiR397a was differentially expressed in various tissues and gradually up-regulated during grain filling. The inhibition of TamiR397a perturbed grain development, leading to a decrease in grain size and weight. Conversely, the overexpression of TamiR397a resulted in increased grain size and weight by accelerating the grain filling process. Transcriptome analysis revealed that TamiR397a regulates a set of genes involved in hormone response, desiccation tolerance, regulation of cellular senescence, seed dormancy, and seed maturation biological processes, which are important for grain development. Among the down-regulated genes in the grains of the TamiR397a-overexpressing transgenic plants, 11 putative targets of the miRNA were identified. Taken together, our results demonstrate that TamiR397a is a positive regulator of grain size and weight, offering potential targets for breeding wheat with an increased grain yield. [ABSTRACT FROM AUTHOR]

A new series of etherification chalcone derivatives were designed and synthesized through Willimison etherification and Claisen-Schmidt condensation. Among them, compound 2-c which was given chemical name of S17, has been successfully screened out as the most potent one on gastric cancer cell line(MGC803) through the investigation for their effects against the growth of five cancer cell lines (EC109, HepG2, MCF7, MGC803, SKNSH). S17 exhibited strong anti-proliferative activity on other two gastric cancer cells (HGC27 and SGC7901), but less cytotoxicity to non-malignant gastric epithelial cells GES1. S17 potently killed gastric cancer cells with causing modulation of Bcl-2 family proteins and activation of caspase 9/3 cascade. S17 also up-regulated DR5 expression and DR5 knockdown partially reversed S17-induced apoptosis, caspase activation and MMP decrease. S17 robustly induced generation of ROS with Keap/Nrf2 pathway activated and the application of ROS scavenger N-acetyl cysteine (NAC) completely blocked these effects by S17 in MGC803 cells. Intraperitoneal administration of S17 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that S17 is a leadbrominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.

A new series of 20 brominated chalcone derivatives were designed, synthesized, and investigated for their effects against the growth of four cancer cell lines (EC109, SKNSH, HepG2, MGC803). Among them, compound 19 which given chemical name of H72, was the most potent one on gastric cancer cell lines (i.e. MGC803, HGC27, SGC7901) with IC50s ranged from 3.57 to 5.61μM. H72 exhibited less cytotoxicity to non-malignant gastric epithelial cells GES-1. H72 treatment of MGC803 and HGC27 induced generation of reactive oxygen species (ROS) leading to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. H72 also up-regulated the expression of DR5, DR4 and BimEL, and down-regulated the expression of Bid, Bcl-xL, and XIAP. N-acetyl cysteine (NAC), a ROS scavenger completely blocked these effects of H72 in MGC803 cells. Intraperitoneal administration of H72 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that H72 is a lead brominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.

Although automated vehicles could release drivers from the driving task, there are still passengers sitting in the vehicle. It is required that the driving comfort of passengers should be guaranteed. Cooperative adaptive cruise control (CACC) vehicle is of the one important type of automated vehicles using vehicle-to-vehicle (V2V) communications with various communication links. Different V2V communication links might have different driving comfort. Then, this paper focuses on exploring which link type for CACC vehicles is better from the perspective of improving driving comfort. To deal with this, car-following models of manual-driven vehicles (MDV) and CACC vehicles were first described. Then, simulations were performed using these car-following models, in which various CACC feedback link types, CACC penetration rates, and flow scenarios were taken into consideration. Simulations outputted microcosmic trajectory data of vehicles, based on which the driving comfort was evaluated using the comfort index described by the International Organization for Standardization (ISO) 2631-1. From the driving comfort perspective, simulation results suggest that CACC should monitor the immediately preceding vehicle and the third vehicle ahead when CACC penetration rates are less than approximately 50%. Additionally, if CACC penetration rates exceed 50%, the better choice is that CACC receives feedback links from two immediately successive vehicles ahead., Author(s): Yongchun Li (corresponding author) [1]; Chuanping Shan [1] 1. Introduction In transportation systems, passenger comfort is arising great interest with the increase in transit time and consumer expectations [1]. [...]

This paper studies a classic maximum entropy sampling problem (MESP), which aims to select the most informative principal submatrix of a prespecified size from a covariance matrix. MESP is widely applied to many areas, including healthcare, power systems, manufacturing, and data science. By investigating its Lagrangian dual and primal characterization, we derive a novel convex integer program for MESP and show that its continuous relaxation yields a near-optimal solution. The results motivate us to study efficient approximation algorithms and develop their approximation bounds for MESP, which improves the best known one in the literature. This paper studies a classic maximum entropy sampling problem (MESP), which aims to select the most informative principal submatrix of a prespecified size from a covariance matrix. By investigating its Lagrangian dual and primal characterization, we derive a novel convex integer program for MESP and show that its continuous relaxation yields a near-optimal solution. The results motivate us to develop a sampling algorithm and derive its approximation bound for MESP, which improves the best known bound in literature. We then provide an efficient deterministic implementation of the sampling algorithm with the same approximation bound. Besides, we investigate the widely used local search algorithm and prove its first known approximation bound for MESP. The proof techniques further inspire for us an efficient implementation of the local search algorithm. Our numerical experiments demonstrate that these approximation algorithms can efficiently solve medium-size and large-scale instances to near optimality. Finally, we extend the analyses to the A-optimal MESP, for which the objective is to minimize the trace of the inverse of the selected principal submatrix. Funding: This work was supported by the National Science Foundation Division of Information and Intelligent Systems [Grant 2246417] and Division of Civil, Mechanical and Manufacturing Innovation [Grant 2246414]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/opre.2023.2488. [ABSTRACT FROM AUTHOR]

We study the D-optimal Data Fusion (DDF) problem, which aims to select new data points, given an existing Fisher information matrix, so as to maximize the logarithm of the determinant of the overall Fisher information matrix. We show that the DDF problem is NP-hard and has no constant-factor polynomial-time approximation algorithm unless P = NP. Therefore, to solve the DDF problem effectively, we propose two convex integer-programming formulations and investigate their corresponding complementary and Lagrangian-dual problems. Leveraging the concavity of the objective functions in the two proposed convex integer-programming formulations, we design an exact algorithm, aimed at solving the DDF problem to optimality. We further derive a family of submodular valid inequalities and optimality cuts, which can significantly enhance the algorithm performance. We also develop scalable randomized-sampling and local-search algorithms with provable performance guarantees. Finally, we test our algorithms using real-world data on the new phasor-measurement-units placement problem for modern power grids, considering the existing conventional sensors. Our numerical study demonstrates the efficiency of our exact algorithm and the scalability and high-quality outputs of our approximation algorithms. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms—Discrete. Funding: Y. Li and W. Xie were supported in part by Division of Civil, Mechanical and Manufacturing Innovation [Grant 2046414] and Division of Computing and Communication Foundations [Grant 2246417]. J. Lee was supported in part by Air Force Office of Scientific Research [Grants FA9550-19-1-0175 and FA9550-22-1-0172]. M. Fampa was supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico [Grants 305444/2019-0 and 434683/2018-3]. F. Qiu and R. Yao were supported in part by the U.S. Department of Energy Advanced Grid Modeling Program under [Grant DE-OE0000875]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/ijoc.2022.0235. [ABSTRACT FROM AUTHOR]