Different Responses of Microbiota across Intestinal Tract to Enterococcus faecium HDRsEf1 and Their Correlation with Inflammation in Weaned Piglets

Enterococcus faecium HDRsEf1 (HDRsEf1) was identified to reduce the incidence of diarrhea in weaned piglets, but the mechanism has not been elucidated yet. Based on the fact that gut microbiota plays a crucial role in regulating inflammatory responses, the effects of HDRsEf1 on microbiota across the intestinal tract in weaned piglets were investigated. Microbiota from the luminal contents and the mucosa of the ileum, cecum, and colon of HDRsEf1-treated piglets were explored by 16S rRNA sequencing and qPCR. It was demonstrated that microbiota in different gut niches responded specifically to HDRsEf1, with major alterations occurring in the ileum and cecum. The total bacterial load of microbiota in ileal luminal contents and the relative abundance of Escherichia-Shigella in the ileal mucosa was significantly down-regulated by HDRsEf1 administration, while the relative abundance of butyrate-producing bacteria (including Clostridiaceae-1, Rumencoccidae, and Erysipelotrichaceae) in cecal luminal contents was significantly up-regulated. Moreover, the utilization of HDRsEf1 improved intestinal morphological development and reduced the inflammatory response, which were negatively correlated with the relative abundance of Escherichia-Shigella in the ileal mucosa and butyrate-producing bacteria in cecal luminal contents, respectively. Collectively, this study suggests that the administration of HDRsEf1 alters gut microbiota, thereby alleviating inflammation and improving intestinal morphological development in weaned piglets

Parameter Identification of Electrochemical Model for Vehicular Lithium-Ion Battery Based on Particle Swarm Optimization

The dynamic characteristics of power batteries directly affect the performance of electric vehicles, and the mathematical model is the basis for the design of a battery management system (BMS).Based on the electrode-averaged model of a lithium-ion battery, in view of the solid phase lithium-ion diffusion equation, the electrochemical model is simplified through the finite difference method. By analyzing the characteristics of the model and the type of parameters, the solid state diffusion kinetics are separated, and then the cascade parameter identifications are implemented with Particle Swarm Optimization. Eventually, the validity of the electrochemical model and the accuracy of model parameters are verified through 0.2–2 C multi-rates battery discharge tests of cell and road simulation tests of a micro pure electric vehicle under New European Driving Cycle (NEDC) conditions. The results show that the estimated parameters can guarantee the output accuracy. In the test of cell, the voltage deviation of discharge is generally less than 0.1 V except the end; in road simulation test, the output is close to the actual value at low speed with the error around ±0.03 V, and at high speed around ±0.08 V

E3 Ubiquitin Ligase FBXO3 Drives Neuroinflammation to Aggravate Cerebral Ischemia/Reperfusion Injury

Ischemic stroke, one of the most universal causes of human mortality and morbidity, is pathologically characterized by inflammatory cascade, especially during the progression of ischemia/reperfusion (I/R) injury. F-Box Protein 3 (FBXO3), a substrate-recognition subunit of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes, has recently been proven to be severed as an underlying pro-inflammatory factor in pathological processes of diverse diseases. Given these considerations, the current study aims at investigating whether FBXO3 exerts impacts on inflammation in cerebral I/R injury. In this study, first, it was verified that FBXO3 protein expression increased after a middle cerebral artery occlusion/reperfusion (MCAO/R) model in Sprague–Dawley (SD) rats and was specifically expressed in neurons other than microglia or astrocytes. Meanwhile, in mouse hippocampal neuronal cell line HT22 cells, the elevation of FBXO3 protein was observed after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment. It was also found that interference of FBXO3 with siRNA significantly alleviated neuronal damage via inhibiting the inflammatory response in I/R injury both in vivo and in vitro. The FBXO3 inhibitor BC-1215 was used to confirm the pro-inflammatory effect of FBXO3 in the OGD/R model as well. Furthermore, by administration of FBXO3 siRNA and BC-1215, FBXO3 was verified to reduce the protein level of Homeodomain-Interacting Protein Kinase 2 (HIPK2), likely through the ubiquitin–proteasome system (UPS), to aggravate cerebral I/R injury. Collectively, our results underline the detrimental effect FBXO3 has on cerebral I/R injury by accelerating inflammatory response, possibly through ubiquitylating and degrading HIPK2. Despite the specific interaction between FBXO3 and HIPK2 requiring further study, we believe that our data suggest the therapeutic relevance of FBXO3 to ischemic stroke and provide a new perspective on the mechanism of I/R injury

Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells

Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na+,K+-ATPase, much still remains unclear about PLTX’s mechanism of action. Here, we tested different concentrations of PLTX on HaCaT cells and studied its distributions in cells, its impact on gene expression, and the associated pathways via proteomics combined with bioinformatics tools. We found that PLTX could cause ferroptosis in HaCaT cells, a new type of programmed cell death, by up-regulating the expression of VDAC3, ACSL4 and NCOA4, which lead to the occurrence of ferroptosis. PLTX also acts on the MAPK pathway, which is related to cell apoptosis, proliferation, division and differentiation. Different from its effect on ferroptosis, PLTX down-regulates the expression of ERK, and, as a result, the expressions of MAPK1, MAP2K1 and MAP2K2 are also lower, affecting cell proliferation. The genes from these two mechanisms showed interactions, but we did not find overlap genes between the two. Both ferroptosis and MAPK pathways can be used as anticancer targets, so PLTX may become an anticancer drug with appropriate modification

Expression of Pinellia pedatisecta Lectin Gene in Transgenic Wheat Enhances Resistance to Wheat Aphids

Wheat aphids are major pests during the seed filling stage of wheat. Plant lectins are toxic to sap-sucking pests such as wheat aphids. In this study, Pinellia pedatisecta agglutinin (ppa), a gene encoding mannose binding lectin, was cloned, and it shared 92.69% nucleotide similarity and 94% amino acid similarity with Pinellia ternata agglutinin (pta). The ppa gene, driven by the constitutive and phloem-specific ribulose bisphosphate carboxylase small subunit gene (rbcs) promoter in pBAC-rbcs-ppa expression vector, was transferred into the wheat cultivar Baofeng104 (BF104) by particle bombardment transformation. Fifty-four T0 transgenic plants were generated. The inheritance and expression of the ppa gene were confirmed by PCR and RT-PCR analysis respectively, and seven homozygous transgenic lines were obtained. An aphid bioassay on detached leaf segments revealed that seven ppa transgenic wheat lines had lower aphid growth rates and higher inhibition rates than BF104. Furthermore, two-year aphid bioassays in isolated fields showed that aphid numbers per tiller of transgenic lines were significantly decreased, compared with wild type BF104. Therefore, ppa could be a strong biotechnological candidate to produce aphid-resistant wheat

Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells

Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na+,K+-ATPase, much still remains unclear about PLTX’s mechanism of action. Here, we tested different concentrations of PLTX on HaCaT cells and studied its distributions in cells, its impact on gene expression, and the associated pathways via proteomics combined with bioinformatics tools. We found that PLTX could cause ferroptosis in HaCaT cells, a new type of programmed cell death, by up-regulating the expression of VDAC3, ACSL4 and NCOA4, which lead to the occurrence of ferroptosis. PLTX also acts on the MAPK pathway, which is related to cell apoptosis, proliferation, division and differentiation. Different from its effect on ferroptosis, PLTX down-regulates the expression of ERK, and, as a result, the expressions of MAPK1, MAP2K1 and MAP2K2 are also lower, affecting cell proliferation. The genes from these two mechanisms showed interactions, but we did not find overlap genes between the two. Both ferroptosis and MAPK pathways can be used as anticancer targets, so PLTX may become an anticancer drug with appropriate modification

Effects of temperature anomaly on sperm quality: A multi-center study of 33,234 men

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility