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There is a healthy research community focused on individual differences to tailor serious games for maximum effect for each person. But there is a comparative lack of research on the scalability of serious games for maximising knowledge saturation in a population. Scalability is critical in many real applications. The authors detail this neglected set of priorities as a research paradigm: Massively Scalable Learning (MSL), and delineate what kinds of domains would benefit most from MSL, summarise its specific cognitive, motivational, and practical components, and detail the factors and mechanisms that determine if MSL is relevant and effective. Existing research is examined, evaluating common educational tools and game features such as virtual tutors for their applicability to MSL, to extract some initial guidelines and principles for MSL for practitioners of serious game design, and identify the key knowledge gaps where future research needs to focus in this neglected but important area.

Vulnerability detectors based on deep learning (DL) models have proven their effectiveness in recent years. However, the shroud of opacity surrounding the decision-making process of these detectors makes it difficult for security analysts to comprehend. To address this, various explanation approaches have been proposed to explain the predictions by highlighting important features, which have been demonstrated effective in domains such as computer vision and natural language processing. Unfortunately, there is still a lack of in-depth evaluation of vulnerability-critical features, such as fine-grained vulnerability-related code lines, learned and understood by these explanation approaches. In this study, we first evaluate the performance of ten explanation approaches for vulnerability detectors based on graph and sequence representations, measured by two quantitative metrics including fidelity and vulnerability line coverage rate. Our results show that fidelity alone is insufficent for evaluating these approaches, as fidelity incurs significant fluctuations across different datasets and detectors. We subsequently check the precision of the vulnerability-related code lines reported by the explanation approaches, and find poor accuracy in this task among all of them. This can be attributed to the inefficiency of explainers in selecting important features and the presence of irrelevant artifacts learned by DL-based detectors. [ABSTRACT FROM AUTHOR]

Mammals that live in cold climates endure months of exposure to low temperature in the winter. The incidence of respiratory diseases has increased. The goal of this study was to investigate the effects of chronic cold stress on lung inflammatory networks, apoptosis, and mitochondrial function via Yorkshire pig models, as well as the ameliorative effect of glucose as energy supplements. Here, two trials were conducted (chronic cold stress and glucose supplementation). The results showed that chronic cold stress induced obvious inflammatory cell infiltration in the lungs and damaged the lung tissue structure. Compared with the Y-Con group, the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), high mobility group box 1 (HMGB1), nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3), IL-1β, IL-2, IL-6, and IFN-γ in the lungs of the Y-CS group was enhanced by chronic cold stress (p < 0.05). Moreover, chronic cold stress promoted the expression of the Bax and Mfn2 in lungs of Y-CS group (p < 0.05). Interestingly, dietary glucose supplementation significantly reduced inflammatory cell infiltration in the lungs. Moreover, glucose supplementation inhibited the expression of TLR4, MyD88, HMGB1, NLRP3, IL-1β, IL-2, IL-6, IFN-γ, and Bax during chronic cold stress. In conclusion, chronic cold stress promoted inflammatory networks, apoptosis, and mitochondrial fusion in the lungs. Dietary glucose supplementation inhibited the inflammatory network during chronic cold stress. [ABSTRACT FROM AUTHOR]

Glyphosate‐based herbicides (GBHs) are the most widely used pesticide in the world, and its extensive use has increased pressures on environmental safety and potential human and livestock health risks. This study investigated the effects of GBHs on antioxidant capacity, inflammatory cytokines, and autophagy of porcine intestinal epithelial cells (IPEC‐J2) and its molecular mechanism. Also, the protective effects of N‐acetylcysteine (NAC) against the toxicity of GBHs were evaluated. Our results showed that the activities of antioxidant enzymes (SOD, GSH‐Px) were decreased by GBHs. GBHs increased inflammatory factors (IL‐1β, IL‐6, TNF‐α) and the mRNA expression of iNOS and COX‐2. GBHs induced the up‐regulation of Nrf2/HO‐1 pathway and the phosphorylation of IκB‐α and NFκB p65, up‐regulation of LC3‐II/LC3‐I, and down‐regulation of P62, and NFκB inhibitor decreased the mRNA expression of inflammatory cytokines (IL‐1β, IL‐6, IL‐8). Moreover, NAC reduced the cytotoxicity by suppressing ROS levels, and changed the autophagy‐related proteins such as the suppression of LC3‐II conversion and up‐regulation of P62. Our findings unveil a novel mechanism of GBHs effects on IPEC‐J2 cells and NAC can reverse cytotoxicity to some extent. [ABSTRACT FROM AUTHOR]

Coupling learning is designed to estimate, discover, and extract the interactions and relationships among learning components. It provides insights into complex interactive data, and has been extensively incorporated into recommender systems to enhance the interpretability of sophisticated relationships between users and items. Coupling learning can be further fostered once the trending collaborative learning can be engaged to take advantage of the cross-platform data. To facilitate this, privacy-preserving solutions are in high demand—it is desired that the collaboration should not expose either the private data of each individual owner or the model parameters trained on their datasets. In this article, we develop a distributed collaborative coupling learning system, which enables differential privacy. The proposed system defends against the adversary who has gained full knowledge of the training mechanism and the access to the model trained collaboratively. It also addresses the privacy-utility tradeoff by a provable tight sensitivity bound. Our experiments demonstrate that the proposed system guarantees favorable privacy gains at a modest cost in recommendation quality, even in scenarios with a large number of training epochs. [ABSTRACT FROM AUTHOR]

Blockchain technology has rapidly emerged as a decentralized trusted network to replace the traditional centralized intermediator. Especially, the smart contracts that are based on blockchain allow users to define the agreed behaviour among them, the execution of which will be enforced by the smart contracts. Based on this, we propose a decentralized booking system that uses the blockchain as the intermediator between hoteliers and travellers. The system enjoys the trustworthiness of blockchain, improves efficiency and reduces the cost of the traditional booking agencies. The design of the system has been formally modelled using the CSP# language and verified using the model checker Process Analysis Toolkit. We have implemented a prototype decentralized booking system based on the Ethereum ecosystem. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets. [ABSTRACT FROM AUTHOR]

[Display omitted] • Angiogenesis impairment caused by GBHs is related to mitochondrial dysfunction. • GBHs have negative impact on placental function. • Maternal GBHs exposure during pregnancy impairs postnatal progeny health. • Betaine protects placenta and postnatal progeny against GBHs-induced damage. • The limit level of glyphosate residue by governments needs to be reappraised. Glyphosate-based herbicides (GBHs) are the most widely used pesticide worldwide and can provoke placental injury. However, whether and how GBHs damage angiogenesis in the placenta is not yet known. This work evaluated the safety of glyphosate on pregnant sows based on the limit level by governments and investigated the effects and mechanism of Low-GBHs (20 mg/kg) and High-GBHs (100 mg/kg) exposure on placental angiogenesis. Results showed that gestational exposure to GBHs decreased placental vessel density and cell multiplication by interfering with the expression of VEGFA, PLGF, VEGFr2 and Hand2 (indicators of angiogenesis), which may be in relation to oxidative stress-induced disorders of mitochondrial fission and fusion as well as the impaired function of the mitochondrial respiratory chain. Additionally, GBHs destroyed barrier function and nutrient transport in the placenta, and was accompanied by jejunum oxidative stress in newborn piglets. However, GBHs exposure had no significant differences on sow reproductive performance. As a natural antioxidant, betaine treatment protected placenta and newborn piglets against GBHs-induced damage. In conclusion, GBHs impaired placental angiogenesis and function and further damaged the health of postnatal progeny, these effects may be linked to mitochondrial dysfunction. Betaine treatment following glyphosate exposure provided modest relief. [ABSTRACT FROM AUTHOR]

ABSTRACT The Web of Things (WoT), inherited from the Internet of Things (IoT), encapsulates functionalities into publishable services on the Web to enable the IoT a seamless integration with the Web. The openness of the Web, in turn, directly exposes WoT to existing attacks from the Web. In addition, WoT possesses characteristics of high security and privacy concerns, mobility, and limited capabilities, which require specific and additional security and privacy protection beyond existing mechanisms. More importantly, WoT is inherently connected to its context, so context information must be taken into account in its security and privacy measures. To address these challenges, we propose a context-aware usage control model (ConUCON), which leverages the context information to enhance data, resource, and service protection for WoT. On the basis of ConUCON, we also design and implement a context-aware usage control framework on the middleware layer in our ongoing SmartHome project, to provide security and privacy protection. ConUCON is designed specifically to express the context-aware usage policy specification, such that security and privacy requirements can be easily specified and enforced with the proposed model and framework. Finally, we apply ConUCON to a remote appliance management prototype, as a case study, to demonstrates its feasibility in a real environment. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

At present, the public is paying more attention to the adverse effects of pesticides on human and animal health and the environment. Glyphosate is a broad-spectrum pesticide that is widely used in agricultural production. In this manuscript, the effects of diets containing glyphosate on intestinal morphology, intestinal immune factors, intestinal antioxidant capacity and the mRNA expression associated with the Nrf2 signaling pathway were investigated in weaned piglets. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) were randomly selected with an average weight of 12.24 ± 0.61 kg. Weaned piglets were randomly assigned into 4 treatment groups and fed a basal diet supplemented with 0, 10, 20, and 40 mg/kg glyphosate for a 35-day feeding trial. We found that glyphosate had no effect on intestinal morphology. In the duodenum, glyphosate increased the activities of CAT and SOD (linear, P < 0.05) and increased the levels of MDA (linear and quadratic, P < 0.05). In the duodenum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and NQO1 (linear and quadratic, P < 0.05) and reduced the relative mRNA expression levels of GPx1, HO-1 and GCLM (linear and quadratic, P < 0.05). In the jejunum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and decreased the relative mRNA expression levels of GCLM (linear and quadratic, P < 0.05). Glyphosate increased the mRNA expression levels of IL-6 in the duodenum (linear and quadratic, P < 0.05) and the mRNA expression levels of IL-6 in the jejunum (linear, P < 0.05). Glyphosate increased the mRNA expression of NF-κB in the jejunum (linear, P = 0.05). Additionally, the results demonstrated that glyphosate linearly decreased the ZO-1 mRNA expression levels in the jejunum and the mRNA expression of claudin-1 in the duodenum (P < 0.05). In the duodenum, glyphosate increased the protein expression levels of Nrf2 (linear, P = 0.025). Overall, glyphosate exposure may result in oxidative stress in the intestines of piglets, which can be alleviated by enhancing the activities of antioxidant enzymes and self-detoxification. • Glyphosate induced partial intestinal oxidative stress by altering the activity of antioxidant enzymes. • Glyphosate reduced the mRNA expression of the tight junction proteins in the duodenum and jejunum. • It is speculated that glyphosate can induce intestinal totoxicity by activating Nrf2-mediated defense response.. [ABSTRACT FROM AUTHOR]

• Protein restriction in nursery induced compensatory growth in finisher. • Protein restriction benefited the subsequent small intestine and liver development. • Compensatory growth also evident in the organ system. • Alanine and aspartate aminotransferase could be indicators of compensatory growth. • Early protein restriction may reduce the protein need of pigs in the future. Compensatory growth that can enhance the growth rate of animals and has been used commonly in production. However, the underlying mechanism is largely unknown, and the long-term effects of early protein restriction (PR) on pigs mostly remain unclear. This study aimed to investigate the long-term effects of early dietary protein restriction maintaining levels of lysine, methionine, threonine, and tryptophan on protein absorption and metabolism in pigs during the grower phase. Sixty-four weaning piglets (10.0 ± 0.73 kg) were divided into two groups: a control (NP, 200 g/kg crude protein, CP) and a protein-restricted group (RP, 140 g/kg CP). After a 30-day PR, both groups were offered the same diets ad libitum for another 74 days. PR to day 30 inhibited the growth of pigs but tended to enhance growth rate (P = 0.076) and significantly improved feed: gain in the period 70−104 days. PR significantly decreased (P < 0.01) the diarrhea rate and index. The RP group showed lower nitrogen (N) retention (P < 0.05) and higher N retention rate (P < 0.10) when the dietary protein was restricted, whereas the N digestibility and N retention rate were higher (P < 0.05) in the RP group compared with the NP group at day 104. PR reduced (P < 0.05) the liver and kidney protein content and the villus height in the jejunum during the restricted period but elevated (P < 0.05) the liver protein content and the villus height in jejunum in the compensatory period. Early PR reduced the albumin and serum urea nitrogen (SUN) in the serum, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and liver (P < 0.05) during the restricted period. However, the differences in the AST and SUN in serum and the ALT in the serum and liver were reversed at day 104. Before day 30, the mRNA expression levels of the 4F2 heavy chain (4F2hc) and cationic amino acid transporter 1(CAT-1) was downregulated (P < 0.05), peptide transporter family 1 was upregulated (PepT1) (P < 0.05). In the compensatory period, the level of 4F2hc in the RP group was enhanced, and the levels of CAT-1 and PepT1 were lower compared with the NP group (P < 0.05). The results suggest that early PR improved the development of the liver and small intestine, protein absorption and metabolism subsequent to day 30 and thus enhanced growth performance. There were no treatment effects on overall growth performance. [ABSTRACT FROM AUTHOR]

Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2 × 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal diet + 1.0 × 108 CFU/mL Cp), (3) Ni group (Ni, basal diet + 100 mg/kg Ni), and (4) Ni + Cp group (Ni + Cp, basal diet + 100 mg/kg Ni + 1.0 × 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (P < 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05

Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons. The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models (cold adaptation) and Yorkshire pig models (non-cold adaptation). Furthermore, this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs. Min pigs (Exp. 1) and Yorkshire pigs (Exp. 2) were divided into a control group (17 °C, n  = 6) and chronic cold exposure group (7 °C, n  = 6), respectively. Twelve Yorkshire pigs (Exp. 3) were divided into a cold control group and cold glucose supplementation group (8 °C). The results showed that chronic cold exposure inhibited peptide transporter protein 1 (PepT1) and excitatory amino acid transporter 3 (EAAT3) expression in ileal mucosa and cationic amino acid transporter-1 (CAT-1) in the jejunal mucosa of Yorkshire pigs ( P  < 0.05). In contrast, CAT-1, PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs ( P  < 0.05). Branched amino acids (BCAA) in the muscle of Yorkshire pigs were consumed by chronic cold exposure, accompanied by increased muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (atrogin-1) expression ( P  < 0.05). More importantly, reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs ( P  < 0.05). However, glycine concentration in the muscle of Min pigs was raised ( P  < 0.05). In the absence of interaction between chronic cold exposure and glucose supplementation, glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs ( P  < 0.05). It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle ( P  < 0.05). Moreover, dystrophin concentration was improved by glucose supplementation ( P  < 0.05). In summary, chronic cold exposure inhibits amino acid absorption in the small intestine, depletes BCAA and promotes protein degradation in muscle. Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle., Competing Interests: No conflict of interest exits in the submission of this manuscript. I (Baoming Shi) would like to declare on behalf of my co-authors (Teng Teng, Guodong Sun, Hongwei Ding, Xin Song, Haoyang Sun and Guangdong Bai) that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

The goal of this study was to investigate the effects of early fecal microbial transfer (FMT) on the microflora of recipient piglets, where Yorkshire newborn piglets and Min sows (an indigenous pig breed in China) were used as the fecal recipients and donors, respectively, to reveal the changes in immunity and development-related functions of the intestinal mucosa driven by FMT. The recipient group was inoculated with fecal microbial fluids from days 1 to 10. On day 21, the relative abundance of the Proteobacteria was reduced; the concentrations of immunoglobulin M (IgM) and immunoglobulin G (IgG) in the jejunal mucosa, and that of IgG in the ileal mucosa of the recipient group, were increased ( P < 0.05). On day 40, the relative abundance of the Firmicute s in the recipient group was increased, while that of Bacteroides was decreased. The concentrations of IgG and IgM in the ileal mucosa of the recipient group were increased. FMT protected the intestine by modulating the antimicrobial peptides of the intestinal mucosa ( P < 0.05). The results of this study revealed that early FMT can improve the gut microbiota, intestinal mucosal immunity, and intestinal development-related functions of Yorkshire piglets.