Loss of diurnal behavioral rhythms and impaired lipid metabolism in growing pigs with mistimed feeding.

The misalignment of eating time and the endogenous circadian rhythm impairs the body's ability to maintain homeostasis. Although it is well established that children and growing animals differ from adults in their energy metabolism and behavioral patterns, little is known about how mistimed feeding disturbs the diurnal rhythms of behavior and metabolism in children and growing diurnal animals. In this study, growing pigs (diurnal animal) were randomly assigned to the daytime-restricted feeding (DRF) and nighttime-restricted feeding (NRF) groups for 5 weeks. Compared with observations in the DRF group, NRF disrupted the diurnal rhythm of behavior and clock genes and lowered the serum ghrelin, dopamine, and serotonin levels during the daytime and nighttime. Microbiome analysis results suggested that NRF altered the diurnal rhythm and composition of the gut microbiota, and increased log-ratios of Catenibacterium:Butyrivibrio and Streptococcus:Butyrivibrio. Based on the serum proteome, the results further revealed that rhythmic and upregulated proteins in NRF were mainly involved in oxidative stress, lipid metabolism, immunity, and cancer biological pathways. Serum physiological indicators further confirmed that NRF decreased the concentration of melatonin and fibroblast growth factor 21 during the daytime and nighttime, increased the diurnal amplitude and concentrations of very-low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increased the apolipoprotein B/ApoA1 ratio, which is a marker of metabolic syndrome. Taken together, this study is the first to reveal that mistimed feeding disrupts the behavioral rhythms of growing pigs, reprograms gut microbiota composition, reduces the serum levels of hormones associated with fighting depression and anxiety, and increases the risk of lipid metabolic dysregulation.

Night-restricted feeding improves locomotor activity rhythm and modulates nutrient utilization to accelerate growth in rabbits.

An unfavorable lifestyle disrupts the circadian rhythm, leading to metabolic dysfunction in adult humans and animals. Increasing evidence suggests that night-restricted feeding (NRF) can effectively prevent ectopic fat deposition caused by circadian rhythm disruption, and reduce the risk of metabolic diseases. However, previous studies have mainly focused on the prevention of obesity in adults by regulating dietary patterns, whereas limited attention has been paid to the effect of NRF on metabolism during growth and development. Here, we used weaning rabbits as models and found that NRF increased body weight gain without increasing feed intake, and promoted insulin-mediated protein synthesis through the mTOR/S6K pathway and muscle formation by upregulating MYOG. NRF improved the circadian clock, promoted PDH-regulated glycolysis and CPT1B-regulated fatty-acid ß-oxidation, and reduced fat content in the serum and muscles. In addition, NRF-induced body temperature oscillation might be partly responsible for the improvement in the circadian clock and insulin sensitivity. Time-restricted feeding could be used as a nondrug intervention to prevent obesity and accelerate growth in adolescents.

Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells.

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits.

The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

[A new form of cell death: Parthanatos].

Parthanatos is a form of cell death, which often occurs in many diseases such as stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury. In a cell, the activation of PARP-1 caused by excitotoxicity leads to Parthanatos, which is also known as PARP-1-dependent cell death. There are multiple cell signaling pathways involved in the process of Parthanatos, which have not been fully understood. The main focus of this article is underlying molecular mechanisms of Parthanatos.

Modeling the effect of temperature on dengue virus transmission with periodic delay differential equations.

Dengue fever is a re-emergent mosquito-borne disease, which prevails in tropical and subtropical regions, mainly in urban and peri-urban areas. Its incidence has increased fourfold since 1970, and dengue fever has become the most prevalent mosquito-borne disease in humans now. In order to study the effect of temperature on the dengue virus transmission, we formulate a dengue virus transmission model with maturation delay for mosquito production and seasonality. The basic reproduction number $\mathbb{R}_0$ of the model is computed, and results suggest that the dengue fever will die out if $\mathbb{R}_0$ < 1, and there exists at least one positive periodic solution and the disease will persist if $\mathbb{R}_0$ > 1. Theoretical results are applied to the outbreak of dengue fever in Guangdong province, China. Simulations reveal that the temperature change causes the periodic oscillations of dengue fever cases, which is good accordance with the reported cases of dengue fever in Guangdong province. Our study contributes to a better understanding of dengue virus transmission dynamics and proves beneficial in preventing and controlling of dengue fever.

Polyamines are essential in embryo implantation: expression and function of polyamine-related genes in mouse uterus during peri-implantation period.

Polyamines are key regulators in cell growth and differentiation. It has been shown that ornithine decarboxylase (Odc) was essential for post-implantation embryo development, and overexpression of spermidine/spermine N1-acetyltransferase will lead to ovarian hypofunction and hypoplastic uteri. However, the expression and function of polyamine-related genes in mouse uterus during early pregnancy are still unknown. In this study we investigated the expression, regulation, and function of polyamine-related genes in mouse uterus during the peri-implantation period. Odc expression was strongly detected at implantation sites and stimulated by estrogen treatment. The expression of Odc antizyme 1 and spermidine/spermine N1-acetyltransferase was also highly shown at implantation sites and regulated by Odc or polyamine level in uterine cells. Embryo implantation was significantly inhibited by alpha-difluoromethylornithine, an Odc inhibitor. Moreover, the reduction of Odc activity caused by alpha-difluoromethylornithine treatment was compensated by the up-regulation of S-adenosylmethionine decarboxylase gene expression. Collectively, our results indicated that the coordinated expression of uterine polyamine-related genes may be important for embryo implantation.

Effects of fermented Chinese herbal medicines on milk performance and immune function in late-lactation cows under heat stress conditions.

Heat stress (HS) causes significant economic losses and has become a continual challenge in the dairy industry worldwide. The objective of this study was to evaluate the effects of a dietary supplement on milk performance and immune function in late-lactation cows under HS conditions. The supplement was a fermented Chinese herbal medicines (CHMs) mixture consisting of 18 herbs. Forty lactating Holstein cows (560 ± 51.0 kg of initial BW, 230 ± 10.0 DIM, 16 ± 3.0 kg of milk per day) were randomly assigned into 4 treatment groups (10 cows per group). Each group was fed a dietary supplemented with 0, 25, 50, or 100 g CHMs per cow per day. Cows were housed at high ambient temperature-humidity index (average 74.5) for an experimental period of 42 d during the summer months. Milk yield, composition, immune responses involving blood lymphocyte apoptosis rate, serum biochemical parameters, and genes expression in lymphocytes were evaluated on days 14, 28, and 42, respectively. Results showed that milk yield, milk fat, and protein content were greater (all P < 0.05) for 50 or 100 g/d CHMs compared with the group without CHMs supplements throughout the experimental period. On the other hand, increasing CHMs dose demonstrated a greater lymphocyte or leukocyte count (P < 0.01). By flow cytometry analysis, early or late apoptosis rate of the lymphocytes was decreased (P < 0.05) by CHMs supplements. The immunity-related biochemistry and genes transcript responses involving cytokines (IL-1, IL-2, IL-6, and IL-12), apoptosis (Bak, Mcl-1, Bax, Bcl-2, Bcl-xl, and P53), and immunoglobulins (IgA, IgG, and IgM) were investigated. Compared with the unsupplemented group, the serum IL-2 and IL-6 levels, as well as IL-2 mRNA expression, increased (P < 0.05) for 100 g/d. However, the serum IL-1 level tended to decrease (P = 0.08) with increasing CHMs dose, and IL-1 mRNA expression was down-regulated (P = 0.02) by up to 24% for 100 g/d. Additionally, the serum Bax level decreased (P < 0.01) and Bcl-2 level increased (P = 0.01) for 100 g/d. Bax and Bak mRNA expressions were down-regulated (P < 0.05), and Bcl-2 and Bcl-xl expression were up-regulated (P < 0.05) for 50 or 100 g/d. The mRNA expressions of P53 and Mcl-1 were not affected by CHMs (P > 0.10). Besides, serum IgG levels were greater (P < 0.01) for 50 or 100 g/d, compared with unsupplemented group. In conclusion, CHMs supplements may improve milk performance and immune function in dairy cows under HS conditions.

Temporal and spatial expression of AIF in the mouse uterus during early pregnancy.

Apoptosis-inducing factor (AIF) is a phylogenetically old, bifunctional protein with a pro-apoptotic function and redox activity. AIF regulates apoptosis and also plays a role in the defense against stress depending on its subcellular localization. Embryo implantation is a complicated process, in which an activated blastocyst interacts with a receptive uterus. The expression and regulation of AIF were investigated in this study in the mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization and under hormonal treatment using in situ hybridization, immunohistochemistry and real-time PCR. During early pregnancy, temporally and spatially regulated patterns of AIF expression were found in the mouse uterus; AIF expression in the luminal epithelium and glandular epithelium is regulated by steroid hormones; AIF mRNA expression in the stroma is influenced by the active blastocyst; and AIF protein was found to be located in the cytoplasm rather than the nucleus through confocal microscope. Our data suggest that AIF might play an important role during mouse embryo implantation and that the role of AIF might be implemented through its physiological activity rather than through its pro-apoptotic function in the mouse uterus during this period.