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The aim of the present study was to establish a simple and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method and apply it for the determination of pharmacokinetics of moxidectin-loaded microspheres (MOX-MS) in rats. Plasma samples were processed using a simplified liquid–liquid extraction method and were separated using an Agilent Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of a 10 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.4 mL/min for 5 min. Avermectin B1a was used as an internal standard (IS). The sample was injected at a volume of 10 μL with a column temperature of 35 °C and detected in a positive ion mode. A good linear response across the concentration range of 1.00–200 ng/mL (r2 > 0.99) and a lower limit of quantification (LLOQ) of 1.00 ng/mL were achieved. The extraction recovery of moxidectin exceeded 94.1%, the matrix effect was between 91.2% and 96.2%, the accuracy ranged from 100.1 to 103.6%, and the relative standard deviation (RSD) did not exceed 15% for the intra- and inter-day accuracy and precision. The pharmacokinetic results showed that MOX-MS significantly decreased Cmax, prolonged T1/2, and improved bioavailability. The developed method significantly reduced the assay volume, shortened detection time, simplified sample processing methods and saved assay costs, which may contribute to the development of the new antiparasitic drug.

Despite mounting evidence for dietary protease benefits, the mechanisms beyond enhanced protein degradation are poorly understood. This study aims to thoroughly investigate the impact of protease addition on the growth performance, intestinal function, and microbial composition of weaned piglets. Ninety 28-day-old weaned pigs were randomly assigned to the following three experimental diets based on their initial body weight for a 28-day experiment: (1) control (CC), a basic diet with composite enzymes without protease; (2) negative control (NC), a diet with no enzymes; and (3) dietary protease (PR), a control diet with protease. The results show that dietary proteases significantly enhanced growth performance and boosted antioxidant capacity, increasing the total antioxidant capacity (T-AOC) levels (p < 0.05) while reducing malonaldehyde levels (p < 0.05). Additionally, protease addition reduced serum levels of inflammatory markers TNF-α, IL-1β, and IL-6 (p < 0.05), suppressed mRNA expression of pro-inflammatory factors in the jejunum (p < 0.01), and inhibited MAPK and NF-κB signaling pathways. Moreover, protease-supplemented diets improved intestinal morphology and barrier integrity, including zonula occludens protein 1(ZO-1), Occludin, and Claudin-1 (p < 0.05). Microbiota compositions were also significantly altered by protease addition with increased abundance of beneficial bacteria (Lachnospiraceae_AC2044_group and Prevotellaceae_UCG-001) (p < 0.05) and reduced harmful Terrisporobacter (p < 0.05). Further correlation analysis revealed a positive link between beneficial bacteria and growth performance and a negative association with inflammatory factors and intestinal permeability. In summary, dietary protease addition enhanced growth performance in weaned piglets, beneficial effects which were associated with improved intestinal barrier integrity, immunological response, and microbiota composition.

The proton exchange membrane electrolysis cell (PEMEC) has attracted considerable attention for large-scale and efficient hydrogen production because of its high current density, high hydrogen purity and fast dynamic response. Flow field distributions and water and thermal management characteristics of a PEMEC are vital for electrolytic cell structure and the determination of operating condition. A three-dimensional, non-isothermal, electrochemical model of a PEMEC was established in this manuscript. The flow field distribution and water and thermal management of the PEMEC are discussed. The corresponding results showed that the pressure of the flow channel decreased diagonally from the inlet to the outlet, and the pressure and velocity distribution exhibited a downward opening shape of a parabola. At the same inlet flow rate, when the voltage was 1.6 V, the oxygen generation rate was 15.74 mol/(cm2·s), and when the voltage was 2.2 V, the oxygen generation rate was 332.05 mol/(cm2·s); due to the change in the oxygen production rate, the pressure difference at 2.2 V was 2.5 times than that at 1.6 V. When the stoichiometric number was less than two, the average temperature of the catalyst layer (CL) decreased rapidly with the increase in the water flow rate. When the voltage decreased to 2.1 V, the current density came to the highest value when the stoichiometric number was 0.7, then the current density decreased with an increase in the stoichiometric number. When stoichiometric numbers were higher than five, the surface temperature and current density remained basically stable with the increase in the water flow rate, and the water and thermal management and electrolysis characteristics performed better. The research results could optimize the water supply of electrolysis cells. According to the velocity distribution law of the flow field, the water and thermal management performance of the PEMEC could be estimated, further promoting safety and reliability.

As the thickness of an ultra-thin flattened heat pipe (UTHP) decreases, the fabrication difficulty increases exponentially, and the thermal performance deteriorates rapidly. In this study, three types of composite wicks were developed for UTHPs with a 0.6 mm thickness: copper foam and mesh wick (CFMW), two layers of different mesh wick (TDMW), and three layers of the same mesh wick (TSMW). The startup and steady-state performances of the UTHPs with liquid filling ratios of 60% to 120% were investigated. The findings indicated that the CFMW UTHP with a filling ratio of 100% exhibited the best startup performance, with the highest equilibrium temperature of 58.37 °C. The maximum heat transport capacities of the CFMW, TDMW, and TSMW UTHP samples were 9, 8, and 8.5 W, respectively, at their corresponding optimum filling ratios of 110%, 90%, and 100%. The CFMW UTHP exhibited the lowest evaporation and condensation thermal resistances of 0.151 and 0.189 K/W, respectively, which were 24.67% and 41.85% lower than those of the TSMW UTHP. CFMW can be used to improve the thermal performance of UTHPs. This study provides important guidelines for the structural design, fabrication technology, and performance improvement of high-performance UTHPs used in portable electronic devices.

Electric vehicles (EVs) are experiencing explosive developments due to their advantages in energy conservation and environmental protection. As a pivotal component of EVs, the safety performance of lithium-ion batteries directly affects driving miles and even safety; hence, a battery thermal management system (BTMS) is especially important. To improve the thermal safety performance of power battery modules, first, a new leak-proof phase change material (PCM)-coupled liquid-cooled composite BTMS for large-scale battery modules is proposed in this research. Second, the numerical simulation analysis method was utilized to analyze the influences of the fluid flow channel shape, working fluid inlet temperature, inlet velocity, and reverse flow conditions on the BTMS. Eventually, the abovementioned performances were compared with the traditional PCM-coupled liquid-cooling strategy. The relative data indicated that the Tmax was reduced by 17.5% and the ΔTmax was decreased by 19.5% compared to the liquid-cooling approach. Further, compared with conventionally designed PCM composite liquid cooling, the ΔTmax was reduced by 34.9%. The corresponding data showed that, when using the e-type flow channel, reverse flow II, the inlet flow velocity was 0.001–0.005 m/s, and the inlet temperature was the ambient temperature of the working condition. The thermal performance of the anti-leakage system with a thermal conduction slot PCM-coupled liquid-cooling composite BTMS reached optimal thermal performance. The outcome proved the superiority of the proposed BTMS regarding temperature control and temperature equalization capabilities. It also further reduced the demand for liquid-cooling components, avoided the problem of the easy leakage of the PCM, and decreased energy consumption.

Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product Limonium aureum (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.

This paper analyzed the factors that influence the seismic resilience of urban building groups and studied the laws that influence internal factors and external factors. Based on the data from the first national comprehensive risk survey of natural disasters, a refined classification study of urban building groups was carried out. Based on the existing evaluation methods of seismic resilience of individual buildings, the recovery time was selected as the resilience evaluation index to calculate the effect of internal factors on the seismic resilience of urban building groups. Then, we studied the quantitative relationship between external factors (i.e., disaster relief capacity, population density, and economic level) and the evaluation indicators of seismic resilience of urban building groups, and we proposed the kilometer grid coefficient. Based on that, we proposed a calculation method of the effect of external factors on the seismic resilience of urban building groups. Considering the influence of internal and external factors, the evaluation model for the seismic resilience of urban building groups was established. And the model was applied in a typical city. This paper proposes a method to evaluate the seismic resilience of urban building groups, which can master the functional recovery time of urban building groups after an earthquake. Based on the proposed model, we can optimize the functional recovery path and emergency rescue path of the disaster area, as well as improve the resilience of urban building systems and the construction of resilient cities.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a substrate protein of a Cullin 4B E3 ligase complex responsible for diverse cellular processes. In the lung, this receptor is responsible for the bioactivation of benzo[a]pyrene during tumorigenesis. Realizing that the AHR function is affected by its expression level, we are interested in the degradation mechanism of AHR in the lung. Here, we have investigated the mechanism responsible for AHR degradation using human lung epithelial A549 cells. We have observed that the AHR protein levels increase in the presence of chloroquine (CQ), an autophagy inhibitor, in a dose-dependent manner. Treatment with 6-aminonicotinamide (6-AN), a chaperone-mediated autophagy (CMA) activator, decreases AHR protein levels in a concentration-dependent and time-dependent manner. This decrease suppresses the ligand-dependent activation of the AHR target gene transcription, and can be reversed by CQ but not MG132. Knockdown of lysosome-associated membrane protein 2 (LAMP2), but not autophagy-related 5 (ATG5), suppresses the chloroquine-mediated increase in the AHR protein. AHR is resistant to CMA when its CMA motif is mutated. Suppression of the epithelial-to-mesenchymal transition in A549 cells is observed when the AHR gene is knocked out or the AHR protein level is reduced by 6-AN. Collectively, we have provided evidence supporting that AHR is continuously undergoing CMA and activation of CMA suppresses the AHR function in A549 cells.

Udder traits, influencing udder health and function, are positively correlated with lactation performance. Among them, breast texture influences heritability and impacts on the milk yield of cattle; however, there is a lack of systematic research on its underlying mechanism in dairy goats in particular. Here, we showed the structure of firm udders with developed connective tissue and smaller acini per lobule during lactation and confirmed that there were lower serum levels of estradiol (E2) and progesterone (PROG), and higher mammary expression of estrogen nuclear receptor (ER) α and progesterone receptor (PR), in dairy goats with firm udders. The results of transcriptome sequencing of the mammary gland revealed that the downstream pathway of PR, the receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) signal, participated in the formation of firm mammary glands. During the culture of goat mammary epithelial cells (GMECs), high RANKL level additions promote the Inhibitor kappaB (IκB)/p65/Cyclin D1 expression related to cell proliferation and decrease the phosphorylated signal transduction and transcription activator 5 (Stat5) expression related to milk-protein synthesis of GMECs, which is consistent with electron microscope results showing that there are fewer lactoprotein particles in the acinar cavity of a firm mammary. Furthermore, co-culturing with adipocyte-like cells for 7 d is beneficial for the acinar structure formation of GMECs, while there is a slightly negative effect of high RANKL level on it. In conclusion, the results of this study revealed the structure of firm udders structure and confirmed the serum hormone levels and their receptor expression in the mammary glands of dairy goats with firm udders. The underlying mechanism leading to firm udders and a decrease in milk yield were explored preliminarily, which provided an important foundation for the prevention and amelioration of firm udders and improving udder health and milk yield.

Cerebrospinal fluid (CSF) proteins are very important because they can serve as biomarkers for central nervous system diseases. Although many CSF proteins have been identified with wet experiments, the identification of CSF proteins is still a challenge. In this paper, we propose a novel method to predict proteins in CSF based on protein features. A two-stage feature-selection method is employed to remove irrelevant features and redundant features. The deep neural network and bagging method are used to construct the model for the prediction of CSF proteins. The experiment results on the independent testing dataset demonstrate that our method performs better than other methods in the prediction of CSF proteins. Furthermore, our method is also applied to the identification of glioma biomarkers. A differentially expressed gene analysis is performed on the glioma data. After combining the analysis results with the prediction results of our model, the biomarkers of glioma are identified successfully.

Oxidative stress in high-yielding dairy goats adversely affects lactation length, milk quality, and the economics of dairy products. During the lactation period, goat mammary epithelial cells (GMECs) are often in a state of disordered metabolic homeostasis primarily caused by the overproduction of reactive oxygen species (ROS). Sulforaphane (SFN), an electrophilic compound that is enriched in broccoli, is a promising antioxidant agent for future potential clinical applications. The objective of the present study was to investigate the function of SFN on hydrogen peroxide (H2O2)-induced oxidative damage in primary GMECs and the underlying molecular mechanisms. Isolated GMECs in triplicate were pretreated with SFN (1.25, 2.5, and 5 μM) for 24 h in the absence or presence of H2O2 (400 μM) for 24 h. The results showed that SFN effectively enhanced superoxide dismutase (SOD) activity, elevated the ratio of glutathione (GSH)/glutathione oxidized (GSSG), and reduced H2O2-induced ROS and malondialdehyde (MDA) production and cell apoptosis. Mechanically, SFN-induced nuclear factor erythroid 2-related factor 2 (NRF2/NFE2L2) translocation to the nucleus through the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway coupled with inhibition of the caspase apoptotic pathway. In addition, GMECs were transfected with NFE2L2 small interfering RNA (NFE2L2 siRNA) for 48 h and/or treated with SFN (5 μM) for 24 h before being exposed to H2O2 (400 μM) for 24 h. We found that knockdown of NFE2L2 by siRNA abrogated the preventive effect of SFN on H2O2-induced ROS overproduction and apoptosis. Taken together, sulforaphane suppressed H2O2-induced oxidative stress and apoptosis via the activation of the AMPK/NFE2L2 signaling pathway in primary GMECs.

Magnetic activated carbon particles (Fe3O4/active carbon composites) as auxiliary electrodes (AEs) were fixed on the surface of Ti/Sb-SnO2 foil by a NdFeB magnet to form a new magnetically assembled electrode (MAE). Characterizations including cyclic voltammetry, Tafel analysis, and electrochemical impedance spectroscopy were carried out. The electrochemical oxidation performances of the new MAE towards different simulated wastewaters (azo dye acid red G, phenol, and lignosulfonate) were also studied. Series of the electrochemical properties of MAE were found to be varied with the loading amounts of AEs. The electrochemical area as well as the number of active sites increased significantly with the AEs loading, and the charge transfer was also facilitated by these AEs. Target pollutants’ removal of all simulated wastewaters were found to be enhanced when loading appropriate amounts of AEs. The accumulation of intermediate products was also determined by the AEs loading amount. This new MAE may provide a landscape of a more cost-effective and flexible electrochemical oxidation wastewater treatment (EOWT).

Neutrophils are involved in the development of endometritis, but it remains unknown how neutrophils induce inflammation and tissue damage. Neutrophil extracellular traps (NETs) clear invading pathogens during infection but induce pyroptosis, leading to inflammation and tissue damage. Thus, our objective was to investigate whether NETs participate in bovine endometrial epithelial cell (BEEC) pyroptosis during endometritis. To confirm this, NETs and caspase-1/4; apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC); nod-like receptor protein-3 (NLRP3); and gasdermin D N-terminal (GSDMD-N), TNF-a, IL-1β, IL-6, and IL-18 in endometrial tissue were detected. Pathological section and vaginal discharge smears were performed to visually determine endometritis in the uterus. BEECs were stimulated with NETs to induce pyroptosis, which was treated with DNase I against pyroptosis. Caspase-1/4, ASC, NLRP3, GSDMD-N, TNF-a, IL-1β, IL-6, and IL-18 in BEECs were analyzed in endometrial tissue. The results showed that NET formation, as well as pyroptosis-related proteins and proinflammatory, cytokines were elevated in the endometrial tissue of cows with endometritis. Pathological sections and vaginal discharge smears showed increased neutrophils and plasma cells in the uterus, as well as tissue congestion. In BEECs, NETs increased the level of pyroptosis-related proteins and proinflammatory cytokines and were diminished by DNase I. In summary NETs participate BEEC pyroptosis during endometritis in dairy cows.

The cell membrane, as the protecting frontier of cells, is closely related to crucial biological behaviors including cell growth, death, and division. Lots of fluorescent probes have been fabricated to monitor cell membranes due to their simplicity and intuitiveness. However, the efficiency of those traditional probes has been limited by their susceptibility to photobleaching and poor water solubility. In this study, we have reported Ru(II)-coumarin complexes consisting of ruthenium, 1,10-phenanthroline, and coumarin 6 to further form self-assembled nanoprobes, for cell membrane targeting and imaging. The fluorescent property could be switchable from red to green through the dynamic disassembly of nanoprobes. Compared with commercial Dil, biocompatible nanoprobes exhibited superior stability for long-term cell imaging, along with remarkedly reduced background interference. Therefore, our self-assembled nanoprobe provides a powerful solution for investigating lipid trafficking with optical imaging.

Cerebrospinal fluid (CSF) exists in the surrounding spaces of mammalian central nervous systems (CNS); therefore, there are numerous potential protein biomarkers associated with CNS disease in CSF. Currently, approximately 4300 proteins have been identified in CSF by protein profiling. However, due to the diverse modifications, as well as the existing technical limits, large-scale protein identification in CSF is still considered a challenge. Inspired by computational methods, this paper proposes a deep learning framework, named DenSec, for secreted protein prediction in CSF. In the first phase of DenSec, all input proteins are encoded as a matrix with a fixed size of 1000 × 20 by calculating a position-specific score matrix (PSSM) of protein sequences. In the second phase, a dense convolutional network (DenseNet) is adopted to extract the feature from these PSSMs automatically. After that, Transformer with a fully connected dense layer acts as classifier to perform a binary classification in terms of secretion into CSF or not. According to the experiment results, DenSec achieves a mean accuracy of 86.00% in the test dataset and outperforms the state-of-the-art methods.

Prediction of secreted proteins in human body fluids is essential since secreted proteins hold promise as disease biomarkers. Various approaches have been proposed to predict whether a protein is secreted into a specific fluid by its sequence. However, there may be relationships between different human body fluids when proteins are secreted into these fluids. Current approaches ignore these relationships directly, and therefore their performances are limited. Here, we present MultiSec, an improved approach for secreted protein discovery to exploit relationships between fluids via multi-task learning. Specifically, a sampling-based balance strategy is proposed to solve imbalance problems in all fluids, an effective network is presented to extract features for all fluids, and multi-objective gradient descent is employed to prevent fluids from hurting each other. MultiSec was trained and tested in 17 human body fluids. The comparison benchmarks on the independent testing datasets demonstrate that our approach outperforms other available approaches in all compared fluids.

Large cations such as potassium ion (K+) and sodium ion (Na+) could be introduced into the lithium-ion (Li-ion) battery system during material synthesis or battery assembly. However, the effect of these cations on charge storage or electrochemical performance has not been fully understood. In this study, sodium ion was taken as an example and introduced into the lithium titanium oxide (LTO) anode through the carboxymethyl cellulose (CMC) binder. After the charge/discharge cycles, these ions doped into the LTO lattice and improved both the lithium-ion diffusivity and the electronic conductivity of the anode. The sodium ion’s high concentration (>12.9%), however, resulted in internal doping of Na+ into the LTO lattice, which retarded the transfer of lithium ions due to repulsion and physical blocking. The systematic study presented here shows that large cations with an appropriate concentration in the electrode would be beneficial to the electrochemical performance of the Li-ion battery.

Pulmonary fibrosis therapy is limited by the unclear mechanism of its pathogenesis. C57BL/6 mice were used to construct the pulmonary fibrosis model in this study. The results showed that Men1, which encodes menin protein, was significantly downregulated in bleomycin (BLM)—induced pulmonary fibrosis. Mice were made to overexpress or had Men1 knockdown with adeno-associated virus (AAV) infection and then induced with pulmonary fibrosis. BLM—induced pulmonary fibrosis was attenuated by Men1 overexpression and exacerbated by Men1 knockdown. Further analysis revealed the distinct roles of Men1 in fibroblasts and macrophages. Men1 inhibited fibroblast activation and extracellular matrix (ECM) protein expression while promoting macrophages to be profibrotic (M2) phenotype and enhancing their migration. Accordingly, pyroptosis was potentiated by Men1 in mouse peritoneal macrophages (PMCs) and lung tissues upon BLM stimulation. Furthermore, the expression of profibrotic factor OPN was positively regulated by menin in Raw264.7 cells and lung tissues by binding to the OPN promoter region. Taken together, although Men1 showed antifibrotic properties in BLM—induced pulmonary fibrosis mice, conflictive roles of Men1 were displayed in fibroblasts and macrophages. The profibrotic role of Men1 in macrophages may occur via the regulation of macrophage pyroptosis and OPN expression. This study extends the current pathogenic understanding of pulmonary fibrosis.

Long non-coding RNA (LncRNA) and microRNA (miRNA) are both non-coding RNAs that play significant regulatory roles in many life processes. There is cumulating evidence showing that the interaction patterns between lncRNAs and miRNAs are highly related to cancer development, gene regulation, cellular metabolic process, etc. Contemporaneously, with the rapid development of RNA sequence technology, numerous novel lncRNAs and miRNAs have been found, which might help to explore novel regulated patterns. However, the increasing unknown interactions between lncRNAs and miRNAs may hinder finding the novel regulated pattern, and wet experiments to identify the potential interaction are costly and time-consuming. Furthermore, few computational tools are available for predicting lncRNA–miRNA interaction based on a sequential level. In this paper, we propose a hybrid sequence feature-based model, LncMirNet (lncRNA–miRNA interactions network), to predict lncRNA–miRNA interactions via deep convolutional neural networks (CNN). First, four categories of sequence-based features are introduced to encode lncRNA/miRNA sequences including k-mer (k = 1, 2, 3, 4), composition transition distribution (CTD), doc2vec, and graph embedding features. Then, to fit the CNN learning pattern, a histogram-dd method is incorporated to fuse multiple types of features into a matrix. Finally, LncMirNet attained excellent performance in comparison with six other state-of-the-art methods on a real dataset collected from lncRNASNP2 via five-fold cross validation. LncMirNet increased accuracy and area under curve (AUC) by more than 3%, respectively, over that of the other tools, and improved the Matthews correlation coefficient (MCC) by more than 6%. These results show that LncMirNet can obtain high confidence in predicting potential interactions between lncRNAs and miRNAs.