Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla -/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla -/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla -/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla -/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla -/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

This paper examines whether changes in US presidential administration and central bank turnover during the period 1976–2016 caused regime shifts in Taylor rule deviations. Using a dynamic stochastic general equilibrium model to construct the welfare-maximizing policy rule and deviations from the optimal rule, we find evidence that politics indeed play a key role in explaining these deviations. In addition to politics, unemployment rates and the interest rate spread significantly account for regime shifts in Taylor rule deviations.

Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) are the most common sexually transmitted pathogens, which can cause cervicitis, pelvic inflammation and infertility in female. In the present study, we collected the basic information, clinical results of leucorrhoea and human papillomavirus (HPV) infection of patients, who were involved in both MG and CT RNA detection in West China Second Hospital of Sichuan University from January 2019 to April 2021, ranging from 18 to 50 years old. The results showed that the infection frequencies of MG and CT were 2.6% and 6.5%, respectively. The infection rate of CT in gynaecological patients was significantly higher than that of MG (P < 0.001). Moreover, patients with CT infection often had symptoms of gynaecological diseases, while patients with MG infection remain often asymptomatic. By exploring the connection between MG or CT infection and vaginal secretions, we found that the infection of MG or CT promoted to the increase of vaginal leukocytes, and CT infection exacerbated the decrease of the number of Lactobacillus in the vagina. Further analysis suggested that independent infection and co-infection of MG or CT resulted in abnormal vaginal secretion, affecting the stability of vaginal environment, which may induce vaginal diseases. Unexpectedly, our study found no association between MG or CT infection and high-risk HPV infection. In conclusion, our study explored the infection of MG and CT among women in Southwest China for the first time, and revealed that the infection of MG or CT would affect the homeostasis of vaginal environment, which laid a foundation for the clinical diagnosis and treatment of MG and CT infection.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were −0·65 ± 1·58 for cases and −1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (P trend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-β) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-β levels, were associated with increased preeclampsia risk.

Theoretical results of frequentist model averaging mainly focus on asymptotic optimality and asymptotic distribution of the model averaging estimator. However, even for basic least squares model averaging, many theoretical problems have not been well addressed yet. This article discusses asymptotic properties of a class of least squares model averaging methods with nested candidate models that includes the Mallows model averaging (MMA) of Hansen (2007, Econometrica 75, 1175–1189) as a special case. Two scenarios are considered: (i) all candidate models are under-fitted; and (ii) the true model is included in the candidate models. We find that in the first scenario, the least squares model averaging method asymptotically assigns weight one to the largest candidate model and the resulting model averaging estimator is asymptotically normal. In the second scenario with a slightly special weight space, if the penalty factor in the weight selection criterion is diverging with certain order, the model averaging estimator is asymptotically optimal by putting weight one to the true model. However, MMA with fixed model dimensions is not asymptotically optimal since it puts nonnegligible weights to over-fitted models. The theoretical results are clearly summarized with their restrictions, and some critical implications are discussed. Monte Carlo simulations confirm our theoretical results.

A study of small-amplitude shape oscillations of a viscous compound droplet suspended in a viscous host fluid is performed. A generalized eigenvalue problem is formulated and is solved by using the spectral method. The effects of the relevant non-dimensional parameters are examined for three cases, i.e. a liquid shell in a vacuum and a compound droplet in a vacuum or in a host fluid. The fundamental mode $l=2$ is found to be dominant. There exist two oscillatory modes: the in phase and the out of phase. In most situations, the interfaces oscillate in phase rather than out of phase. For the in-phase mode, in the absence of the host, as the viscosity of the core or the shell increases, the damping rate increases whereas the oscillation frequency decreases; when the viscosity exceeds a critical value, the mode becomes aperiodic with the damping rate bifurcating into two branches. In addition, when the tension of the inner interface becomes smaller than some value, the in-phase mode turns aperiodic. In the presence of the unbounded host fluid, there exists a continuous spectrum. The viscosity of the host may decrease or increase the damping rate of the in-phase mode. The mechanism behind it is discussed. The density contrasts between fluids affect oscillations of the droplet in a complicated way. Particularly, sufficiently large densities of the core or the host lead to the disappearance of the out-of-phase mode. The thin shell approximation predicts well the oscillation of the compound droplet when the shell is thin.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case–control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography–tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose–response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

We present an overview of the SkyMapper optical follow-up programme for gravitational-wave event triggers from the LIGO/Virgo observatories, which aims at identifying early GW170817-like kilonovae out to $\sim200\,\mathrm{Mpc}$ distance. We describe our robotic facility for rapid transient follow-up, which can target most of the sky at $\delta<+10\deg $ to a depth of $i_\mathrm{AB}\approx 20\,\mathrm{mag}$ . We have implemented a new software pipeline to receive LIGO/Virgo alerts, schedule observations and examine the incoming real-time data stream for transient candidates. We adopt a real-bogus classifier using ensemble-based machine learning techniques, attaining high completeness ( $\sim98\%$ ) and purity ( $\sim91\%$ ) over our whole magnitude range. Applying further filtering to remove common image artefacts and known sources of transients, such as asteroids and variable stars, reduces the number of candidates by a factor of more than 10. We demonstrate the system performance with data obtained for GW190425, a binary neutron star merger detected during the LIGO/Virgo O3 observing campaign. In time for the LIGO/Virgo O4 run, we will have deeper reference images allowing transient detection to $i_\mathrm{AB}\approx 21\,\mathrm{mag}$ .

A southern population (S) from Xiushui County (29°1′N, 114°4′E) and a northern population (N) from Shenyang city (41°48′N, 123°23′E) of the cabbage beetle, Colaphellus bowringi vary greatly in their life-history traits, and may serve as an excellent model with which to study the inheritance of life-history traits. In the present study, we performed intraspecific hybridization using the two populations, comparing the key life-history traits (fecundity, development time, body weight, growth rate, and sexual size dimorphism (SDD)) between the two populations (S♀ × S♂ and N♀ × N♂) and their two hybrid populations (S♀ × N♂ and N♀ × S♂ populations) at 19, 22, 25, and 28°C. Our results showed that there were significant differences in life-history traits between the two parental populations, with the S population having a significantly higher fecundity, shorter larval development time, larger body weight, higher growth rate, and greater weight loss during metamorphosis than the N population at almost all temperatures. However, these life-history traits in the two hybrid populations were intermediate between those of their parents. The life-history traits in the S × N and N × S populations more closely resembled those of the maternal S population and N population, respectively, showing maternal effects. Weight loss for both sexes was highest in the S population, followed by the S × N, N × S, and N populations at all temperatures, suggesting that larger pupae lost more weight during metamorphosis. The changes in SSD with temperature were similar between the S and the S × N populations and between the N and the N × S populations, also suggesting a maternal effect. Overall, our results showed no drastic effect of hybridization on C. bowringi, being neither negative (hybrid inferiority) nor positive (heterosis). Rather, the phenotypes of hybrids were intermediate between the phenotypes of their parents.

Bile acids (BA) have emerged as signalling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, for example, lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 d of age and allocated into control (CON, n 14) or probiotic (PRO, n 14) group fed 50 mg of Lactobacillus plantarum daily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing damage of enterocytes, IPEC-J2 cells were treated with LCA, lipopolysaccharide (LPS) and LCA + LPS and expressions of genes related to inflammation, antioxidant capacity and nutrient transport were determined. Compared with the CON group, the PRO group showed lower total LCA level in the ileum and higher relative abundance of the Lactobacillus genus in faeces. In contrast, the relative abundances of Bacteroides, Clostridium_sensu_stricto_1, Parabacteroides and Ruminococcus_1, important bacteria genera in BA biotransformation, were all lower in the PRO than in the CON group. Moreover, PRO piglets had lower postprandial glucagon-like peptide-1 level, while higher glucose level than CON piglets. Co-administration of LPS and LCA led to down-regulated expression of glucose and peptide transporter genes in IPEC-J2 cells. Altogether, oral L. plantarum altered BA profile probably by modulating relative abundances of gut microbial genera that play key roles in BA metabolism and might consequently impact glucose homoeostasis. The detrimental effect of LCA on nutrient transport in enterocytes might be aggravated under LPS challenge.

Ketosis is a metabolic disease of dairy cows often characterized by high concentrations of ketone bodies and fatty acids, but low milk protein and milk production. The Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) and the mechanistic target of rapamycin (mTOR) signaling pathways are central for the regulation of milk protein synthesis. The effect of high levels of fatty acids on these pathways and β-casein synthesis are unknown in dairy cows with clinical ketosis. Mammary gland tissue and blood samples were collected from healthy (n = 15) and clinically-ketotic (n = 15) cows. In addition, bovine mammary epithelial cells (BMEC) were treated with fatty acids, methionine (Met) or prolactin (PRL), respectively. In vivo, the serum concentration of fatty acids was greater (P > 0.05) and the percentage of milk protein (P > 0.05) was lower in cows with clinical ketosis. The JAK2-STAT5 and mTOR signaling pathways were inhibited and the abundance of β-casein was lower in mammary tissue of cows with clinical ketosis (P > 0.05). In vitro, high levels of fatty acids inhibited the JAK2-STAT5 and mTOR signaling pathways (P > 0.05) and further decreased the β-casein synthesis (P > 0.05) in BMEC. Methionine or PRL treatment, as positive regulators, activated the JAK2-STAT5 and mTOR signaling pathways to increase the β-casein synthesis. Importantly, the high concentration of fatty acids attenuated the positive effect of Met or PRL on mTOR, JAK2-STAT5 pathways and the abundance of β-casein (P > 0.05). Overall, these data indicate that the high concentrations of fatty acids that reach the mammary cells during clinical ketosis inhibit mTOR and JAK2-STAT5 signaling pathways, and further suppress β-casein synthesis.