Emotional "Contagion" in Piglets after Sensory Avoidance of Rewarding and Punishing Treatment.

In the pig farming industry, it is recommended to avoid groups when treating individuals to reduce adverse reactions in the group. However, can this eliminate the adverse effects effectively? Piglets were assigned to the Rewarding Group (RG), the Punishing Group (PG), and the Paired Control Group (PCG). There were six replicates in each group, with two paired piglets per replicate. One piglet of the RG and PG was randomly selected as the Treated pig (TP), treated with food rewards or electric shock, and the other as the Naive pig (NP). The NPs in the RG and PG were unaware of the treatment process, and piglets in the PCG were not treated. The behavior and heart rate changes of all piglets were recorded. Compared to the RG, the NPs in the PG showed longer proximity but less contact behavior, and the TPs in the PG showed more freezing behavior. The percentage change in heart rate of the NPs was synchronized with the TPs. This shows that after sensory avoidance, the untreated pigs could also feel the emotions of their peers and their emotional state was affected by their peers, and the negative emotions in the pigs lasted longer than the positive emotions. The avoidance process does not prevent the transfer of negative emotions to peers via emotional contagion from the stimulated pig.

Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation.

Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Emotional Contagion and Social Support in Pigs with the Negative Stimulus.

This study expects to confirm the existence of emotional transmission in pigs from multiple perspectives and to provide theoretical references for improving animal welfare in livestock farming. A group that could directly observe (DO) and a group that could not directly observe (NO) were created based on whether or not their peers observed the treatment process, as the treated pig (TP) was treated with electrical shock and the companion pig (CP) either witnessed the treatment inflicted upon TP or not, and a third group was a control group, in which neither pig was stimulated. The behavioral responses of both the TPs and CPs were recorded to evaluate the emotional reaction. The results found that in both the DO and NO groups, the frequency of TP freezing was significantly higher than that of CP, and CP was significantly higher than that of the control group. Interestingly, although the social interaction responses of the CPs were not similar in the DO and NO groups, there were no significant differences between the behaviors of TPs in the DO and NO groups, except for nose-nose contact and a single approach to the partition, which allowed us to conclude that, whether or not the pigs directly observed the negative treatment, they were able to respond accordingly to fear and provide similar social support to their companions who were treated negatively.

Mailuoning oral liquid attenuates convalescent cerebral ischemia by inhibiting AMPK/mTOR-associated apoptosis and promoting CREB/BDNF-mediated neuroprotection.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is divided into acute, subacute and convalescent phases according to the time of onset. Clinically, Mailuoning oral liquid (MLN O) is a traditional Chinese patent medicine for treating ischemic stroke. Previous studies have shown that MLN O could prevent acute cerebral ischemia-reperfusion. However, its underlying mechanism remains unclear. AIM OF THE STUDY: To investigate the relationship between neuroprotection and apoptosis for clarifying MLN O mechanism in the recovery phase of ischemic stroke. MATERIALS AND METHODS: We imitated stroke using middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models. The infarct volume, neurological deficit scores, HE staining, Nissl staining, TUNEL staining, immunohistochemistry, and Western blot were correspondingly performed to find pathological changes and detect neuronal apoptosis in rat cerebral cortex. The contents of LDH, Cyt-c, c-AMP and BDNF in rat plasma and cerebral cortex were detected by ELISA. Cell viability was measured by CCK8 assay. Cell morphology, Hoechst 33342 staining and Annexin-V-Alexa Fluor 647/PI staining were performed to assess neuronal apoptosis. The expression levels of proteins were evaluated by western blotting. RESULTS: MLN O obviously reduced brain infarct volume and neurological deficit scores in MCAO rats. MLN O inhibited inflammatory cell infiltration and neuronal apoptosis, but promoted gliosis, neuronal survival, and neuroprotection in the cortical region of MCAO rats. Additionally, MLN O decreased the amount of LDH and cytochrome c, while increasing the expression of c-AMP in the plasma and ischemic cerebral cortex of MCAO rats, and promoting the expression of BDNF in the cortical tissue of MCAO rats. Besides, MLN O improved cell viability, restored cell morphology, while attenuating cell damage, inhibiting neuronal apoptosis following OGD/R in PC-12 cells. Moreover, MLN O inhibited apoptosis by suppressing the expression of pro-apoptotic-associated proteins, including Bax, cytochrome c, Cleaved caspase 3 and HIF-1α, whereas accelerating the expression of Bcl-2 in vivo and in vitro. Furthermore, MLN O inhibited the activity of AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR), but activated the signaling pathway of cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) in MCAO rats and OGD/R-stimulated PC-12 cells. CONCLUSIONS: These results demonstrated that MLN O inhibited AMPK/mTOR to affect apoptosis associated with mitochondria, leading to improve CREB/BDNF-mediated neuroprotection in the recovery period of ischemic stroke in vivo and in vitro.

ß-Hydroxybutyric acid upregulated by Suhuang antitussive capsule ameliorates cough variant asthma through GSK3ß/AMPK-Nrf2 signal axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown. AIM OF THE STUDY: This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress. MATERIALS AND METHODS: Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and ß-hydroxybutyric acid (ß-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then ß-HB on CVA rats, NLRP3 inflammasome and GSK3ß/AMPK/Nrf2 signalling pathway were detected by western blotting. RESULTS: The results showed that Suhuang treatment significantly enhanced the serum level of ß-HB. Interestingly, exposure to exogenous ß-HB was also protective against OVA-induced CVA. ß-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, ß-HB increased the nuclear accumulation of Nrf2 by activating the GSK3ß/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation. CONCLUSIONS: The results of this study shows that ß-HB can reduce inflammation and oxidative stress, the increased production of ß-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.

Machine Learning Based on Event-Related EEG of Sustained Attention Differentiates Adults with Chronic High-Altitude Exposure from Healthy Controls.

(1) Objective: The aim of this study was to examine the effect of high altitude on inhibitory control processes that underlie sustained attention in the neural correlates of EEG data, and explore whether the EEG data reflecting inhibitory control contain valuable information to classify high-altitude chronic hypoxia and plain controls. (2) Methods: 35 chronic high-altitude hypoxic adults and 32 matched controls were recruited. They were required to perform the go/no-go sustained attention task (GSAT) using event-related potentials. Three machine learning algorithms, namely a support vector machine (SVM), logistic regression (LR), and a decision tree (DT), were trained based on the related ERP components and neural oscillations to build a dichotomous classification model. (3) Results: Behaviorally, we found that the high altitude (HA) group had lower omission error rates during all observation periods than the low altitude (LA) group. Meanwhile, the ERP results showed that the HA participants had significantly shorter latency than the LAs for sustained potential (SP), indicating vigilance to response-related conflict. Meanwhile, event-related spectral perturbation (ERSP) analysis suggested that lowlander immigrants exposed to high altitudes may have compensatory activated prefrontal cortexes (PFC), as reflected by slow alpha, beta, and theta frequency-band neural oscillations. Finally, the machine learning results showed that the SVM achieved the optimal classification F1 score in the later stage of sustained attention, with an F1 score of 0.93, accuracy of 92.54%, sensitivity of 91.43%, specificity of 93.75%, and area under ROC curve (AUC) of 0.97. The results proved that SVM classification algorithms could be applied to identify chronic high-altitude hypoxia. (4) Conclusions: Compared with other methods, the SVM leads to a good overall performance that increases with the time spent on task, illustrating that the ERPs and neural oscillations may provide neuroelectrophysiological markers for identifying chronic plateau hypoxia.

Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol.

Although natural sesame oil has been shown to facilitate the lymphatic delivery and oral bioavailability of the highly lipophilic drug cannabidiol (CBD), considerable variability remains an unresolved challenge. Vegetable oils differ substantially in composition, which could lead to differences in promotion of intestinal lymphatic transport of lipophilic drugs. Therefore, the differences in composition of sesame, sunflower, peanut, soybean, olive and coconut oils and their corresponding role as vehicles in promoting CBD lymphatic targeting and bioavailability were investigated in this study. The comparative analysis suggests that the fatty acids profile of vegetable oils is overall similar to the fatty acids profile in the corresponding chylomicrons in rat lymph. However, arachidonic acid (C20:4), was introduced to chylomicrons from endogenous nondietary sources. Overall, fatty acid composition of natural vegetable oils vehicles affected the intestinal lymphatic transport and bioavailability of CBD following oral administration in this work. Olive oil led to the highest concentration of CBD in the lymphatic system and in the systemic circulation in comparison to the other natural vegetable oils following oral administration in rats.

Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling. AIM OF THE STUDY: This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. MATERIALS AND METHODS: To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)-NF-E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro. RESULTS: SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice. CONCLUSION: Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress.

Thyroid nodules risk stratification through deep learning based on ultrasound images.

PURPOSE: Clinically, the risk stratification of thyroid nodules is usually used to formulate the next treatment plan. The American College of Radiology (ACR) thyroid imaging reporting and data system (TI-RADS) is a type of medical standard widely used in classification diagnosis. It divides the nodule's ACR TI-RADS level into five levels by quantitative scoring, from benign to high suspicion of malignancy. However, such assessment often relies on the radiologists' experience and is time consuming. So computer-aided diagnosis is necessary. But many deep learning (DL) models are difficult for doctors to understand, limiting their applicability in clinical practice. In this work, we mainly focus on how to achieve automatic thyroid nodules risk stratification based on deep integration of deep learning and clinical experience. METHODS: An automatic hierarchical method of thyroid nodules risk based on deep learning is proposed, called risk stratification network (RS-Net). It incorporates medical experience based on ACR TI-RADS. The convolutional neural network (CNN) is used to classify the five categories in ACR TI-RADS and assign their points respectively. According to the point totals, the level of risk can be obtained. In addition, a dataset involving 13 984 thyroid ultrasound images is established to develop and evaluate the proposed method. RESULTS: We have extensively compared the results of this paper with the evaluation results of sonographers. The accuracy of the risk stratification (TR1 to TR5) of the proposed method is 65%, and the mean absolute error (MAE) is 0.54. The MAE of the point totals (0 to 13 points) is 1.67. The Pearson's correlation between our method evaluation and doctor evaluation reached 0.84. For the benign and malignant classification, the performance indices accuracy, sensitivity, specificity, PPV, and NPV were 88.0%, 98.1%, 79.1%, 80.5%, and 97.9%, respectively. Our method's level of thyroid nodules risk stratification is comparable to that of a senior doctor. CONCLUSIONS: This work provides a way to automate the risk stratification of thyroid nodules. Our method can effectively avoid missed diagnosis and misdiagnosis caused by the difference of observers so as to assist doctors to improve efficiency and diagnosis rate. Compared with the previous benign and malignant classification, the proposed method incorporates clinical experience. So it can greatly increase the clinicians' trust in the DL model, thereby improving the applicability of the model in clinical practice.

Fournier Gangrene Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Pharmacovigilance Study with Data from the U.S. FDA Adverse Event Reporting System.

BACKGROUND: The U.S. Food and Drug Administration (FDA) released a safety warning of Fournier gangrene (FG), a rare but serious adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors in August 2018. However, existing studies have focused mainly on individual FG case reports. Although several previous studies conducted reviews of cases, objective scientific analysis was not applied, and the prognosis data were inadequate. OBJECTIVE: This study is aimed at presenting data supplementary to existing studies by analysing postmarketing adverse event reports in the FDA Adverse Events Reporting System (FAERS) database. Multiple statistical analysis methods were applied to evaluate the potential association between SGLT2 inhibitors and FG, thus providing reliable and professionalized medication usage recommendations for SGLT2 inhibitors in clinical practice. METHODS: Disproportionality analysis and Bayesian analysis were applied for data mining among the suspected adverse event reports of FG associated with SGLT2 inhibitors recorded in the FAERS database during the period from January 2004 to September 2019. RESULTS: There were 542 FG cases identified in the FAERS database in patients receiving SGLT2 inhibitors. Among all SGLT2 inhibitor therapies, empagliflozin was associated with the highest number of FG reports (232 in total), while empagliflozin plus metformin had the strongest association with FG occurrence with the reporting odds ratio (ROR 54.79, 95% two-sided CI 31.56 to 95.12) and proportional reporting ratio (PRR 53.36, χ 2 666.70). There were 391 patients who underwent initial or prolonged hospitalization (72.14%), and 26 patients died (4.81%). Three new FG cases caused by ertugliflozin were found in 2019. CONCLUSION: The analysis of SGLT2 inhibitor-associated FG reports in the FAERS database identified signals between the drug and adverse events of interest. It also provides comprehensive information on the characteristics of FG onset and prognosis. Clinicians should pay more attention to this rare but severe adverse event when prescribing SGLT2 inhibitors in clinical practice.

POSS-Derived Synthesis and Full Life Structural Analysis of Si@C as Anode Material in Lithium Ion Battery.

Polyhedral oligomeric silsesquioxane (POSS)-derived Si@C anode material is prepared by the copolymerization of octavinyl-polyhedral oligomeric silsesquioxane (octavinyl-POSS) and styrene. Octavinyl-polyhedral oligomeric silsesquioxane has an inorganic core (-Si8O12) and an organic vinyl shell. Carbonization of the core-shell structured organic-inorganic hybrid precursor results in the formation of carbon protected Si-based anode material applicable for lithium ion battery. The initial discharge capacity of the battery based on the as-obtained Si@C material Si reaches 1500 mAh g-1. After 550 charge-discharge cycles, a high capacity of 1430 mAh g-1 was maintained. A combined XRD, XPS and TEM analysis was performed to investigate the variation of the discharge performance during the cycling experiments. The results show that the decrease in discharge capacity in the first few cycles is related to the formation of solid electrolyte interphase (SEI). The subsequent rise in the capacity can be ascribed to the gradual morphology evolution of the anode material and the loss of capacity after long-term cycles is due to the structural pulverization of silicon within the electrode. Our results not only show the high potential of the novel electrode material but also provide insight into the dynamic features of the material during battery cycling, which is useful for the future design of high-performance electrode material.

In-Situ Synthesized Si@C Materials for the Lithium Ion Battery: A Mini Review.

As an important component, the anode determines the property and development of lithium ion batteries. The synthetic method and the structure design of the negative electrode materials play decisive roles in improving the property of the thus-assembled batteries. Si@C compound materials have been widely used based on their excellent lithium ion intercalation capacity and cyclic stability, in which the in-situ synthetic method can make full use of the structural advantages of the monomer itself, thus improving the electrochemical performance of the anode material. In this paper, the different preparation technologies and composite structures of Si@C compound materials by in-situ synthesis are introduced. The research progress of Si@C compound materials by in-situ synthesis is reviewed, and the prospect of future development of Si@C compound materials has been tentatively commented.