Punicalagin relieves lipotoxic injuries on pancreatic ß-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis.

Cellular toxicity of hyperlipidemia has been long considered a major cause of various intractable disease such as diabetes. Discovering lipotoxicity antagonist with high efficiency and low side effects is of importance to develop therapeutics for relevant diseases. In the current study, we evaluate the anti-lipotoxic potential of punicalagin (PU) on pancreatic cells and investigate its underpinning mechanism involved. The administration of PU effectively improved cell viability, quenched intracellular reactive oxygen species, alleviated lipid peroxidation, and enhanced cellular antioxidative capacity in RINm5F cells stimulated by sodium palmitate. Besides that, PU treatment significantly inhibited the overload of mitochondrial calcium ions; alleviated the activation of endoplasmic reticulum (ER) stress mediators including glucose-regulated protein 78, protein kinase RNA-like ER kinase, eukaryotic initiation factor 2α, activating transcription factor 6, caspase 12, and C/EBP homologous protein (CHOP); and attenuated the expression of cleaved caspase 3 and poly ADP-ribose polymerase in test cells. Further RNA interference experiment results and miR211-5p expression analysis revealed that PU may directly mitigate CHOP expression and upregulate the expression of miR211-5p to reduce ER stress-induced pancreatic cell death. The efficacy of PU in maintaining redox equilibrium and diminishing ER stress on pancreatic cells stressed by hyperlipidemia suggests that PU can be used as a promising dietary natural product to safeguard the pancreatic health against lipotoxicity.

Systematical assessment of digit ratio in a female masculinization disease: polycystic ovary syndrome.

Background: In recent years, the right ratio of 2nd and 4th digit length (2D:4D) is regarded as an anatomical marker of prenatal testosterone exposure. Polycystic ovary syndrome (PCOS) is a female masculinized disease and is determined by prenatal testosterone exposure. Whether the ratio in the right hand of PCOS women is reduced or not compared with non-PCOS women is under debate. To further investigate the relationship between PCOS and digit ratio, we systematically measured all the digit ratios. Methods: We recruited 34 non-PCOS women, 116 PCOS women, and 40 men and systematically measured all the ratios of digit length (2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, and 4D:5D) of right hands and left hands. Results: Left 2D:3D, 2D:4D, and 2D:5D in men were significantly lower than those in non-PCOS women. Significantly lower digit ratios of left 2D:3D and 2D:4D were observed in PCOS compared with non-PCOS women. In the subgroup analysis, the left ratio of digit length in 2D:3D and 2D:5D of the hyperandrogenism subgroup was lower than that of the non-hyperandrogenism subgroup without statistical significance. The logistic regression model of PCOS revealed that 2D:3D, 2D:4D, 2D:5D, and 3D:4D of left hands were statistically related to the diagnosis of PCOS among all the digit ratios. Conclusion: Not only 2D:4D but also other digit ratios, such as 2D:3D and 2D:5D, are a marker of prenatal testosterone exposure and may be an anatomical marker of PCOS. The majority of these significant differences included left 2D, with the following order: non-PCOS women > PCOS women > men.

Epidemiological and Clinical Characteristics of Respiratory Syncytial Virus Infections in Children Aged <5 Years in China, from 2014−2018

Respiratory syncytial virus (RSV) is an important pathogen that causes acute respiratory tract infections in children. To understand the epidemiological and clinical characteristics of RSV in children, we analyzed the RSV diagnostic testing results from the 2014−2018 surveillance of acute respiratory infections in China. Among children aged <5 years, RSV incidence during 2014−2018 was 17.3% (3449/19,898), and 89.1% of RSV-positive individuals were inpatients. Children aged < 6 months had a high proportion in RSV infected individual (n = 1234; 35.8%). The highest RSV detection rate was in winter, RSV-A and RSV-B co-circulated year-round and jointly prevailed in 2015−2016. Cough was the common symptom of RSV infection 93.2% (3216/3449). Compared with older children, those aged <6 months were more likely to show breathing difficulty or lung rale that further developed into bronchopneumonia (p < 0.001). The symptoms such as cough, running nose, and diarrhea had significant differences between the RSV-A and RSV-B groups. The rate of RSV co-detection with other viruses or bacteria was 35.4%. Those coinfected with other viruses had a significantly higher incidence of fever, whereas those coinfected with bacteria had higher incidences of breathing difficulty and severe pneumonia. Our findings highlight the need for accumulating epidemiological information for the prevention and control of RSV.

The Impact and Vaccination Coverage of Seasonal Influenza among Children Aged 6-59 Months in China in 2017-2018: An Internet Panel Survey.

Seasonal influenza vaccination is highly recommended for 6-59-month-old children. To determine the impact of seasonal influenza and the factors affecting influenza vaccine uptake among children, we conducted an opt-in Internet panel survey of parents from 21 March 2018 to 1 April 2018. Overall, 40.5% (1913/4719) of children experienced influenza-like illness (ILI), 92.4% of parents sought medical care for children with ILI (outpatients: 61.2%, inpatients: 12.8%), 39.6% of parents preferred to take their sick child to a tertiary hospital, and 57.3% of family members requested leave to care for children with ILI. There was a median of three days of absenteeism (2, 5) per sick child, and 39.4% of children received the influenza vaccine during the 2017-2018 influenza season. Vaccine coverage among children aged 6-11 months and 48-59 months was lower than that among 12-47-month-old children. The top three reasons for not vaccinating were: the influenza vaccine was not recommended by healthcare workers (21.1%), no knowledge about the influenza vaccine (19.2%), and lack of confidence in the vaccine's effectiveness (14.3%). Our findings highlight the need for awareness about the severity of influenza, hygiene behavior, and effectiveness of the influenza vaccine among children and their family members in China.

Protective role of crocin against sepsis-induced injury in the liver, kidney and lungs via inhibition of p38 MAPK/NF-κB and Bax/Bcl-2 signalling pathways.

CONTEXT: Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown. OBJECTIVE: We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action. MATERIALS AND METHODS: Five experimental groups (n = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated. RESULTS: Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1ß, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation. DISCUSSION AND CONCLUSIONS: Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.

Approximation capabilities of measure-preserving neural networks.

Measure-preserving neural networks are well-developed invertible models, however, their approximation capabilities remain unexplored. This paper rigorously analyzes the approximation capabilities of existing measure-preserving neural networks including NICE and RevNets. It is shown that for compact U⊂RD with D≥2, the measure-preserving neural networks are able to approximate arbitrary measure-preserving map ψ:U→RD which is bounded and injective in the Lp-norm. In particular, any continuously differentiable injective map with ±1 determinant of Jacobian is measure-preserving, thus can be approximated.

SympNets: Intrinsic structure-preserving symplectic networks for identifying Hamiltonian systems.

We propose new symplectic networks (SympNets) for identifying Hamiltonian systems from data based on a composition of linear, activation and gradient modules. In particular, we define two classes of SympNets: the LA-SympNets composed of linear and activation modules, and the G-SympNets composed of gradient modules. Correspondingly, we prove two new universal approximation theorems that demonstrate that SympNets can approximate arbitrary symplectic maps based on appropriate activation functions. We then perform several experiments including the pendulum, double pendulum and three-body problems to investigate the expressivity and the generalization ability of SympNets. The simulation results show that even very small size SympNets can generalize well, and are able to handle both separable and non-separable Hamiltonian systems with data points resulting from short or long time steps. In all the test cases, SympNets outperform the baseline models, and are much faster in training and prediction. We also develop an extended version of SympNets to learn the dynamics from irregularly sampled data. This extended version of SympNets can be thought of as a universal model representing the solution to an arbitrary Hamiltonian system.