Spherical Assembly of Halloysite Clay Nanotubes as a General Reservoir of Hydrophobic Pesticides for pH-Responsive Management of Pests and Weeds.

The development of smart systems for pesticidal delivery presents a significant advancement in enhancing the utilization efficiency of pesticides and mitigating environmental risks. Here an acid-responsive pesticidal delivery system using microspheres formed by the self-assembly of halloysite clay nanotubes (HNTs) is proposed. Insecticide avermectin (AVM) and herbicide prometryn (PMT) are used as two models of hydrophobic pesticide and encapsulated within the porous microspheres, followed by a coating of tannic acid/iron (TA/FeIII) complex films to generate two controlled-release pesticides, named as HCEAT and HCEPT, resulting in the loading capacity of AVM and PMT being 113.3 and 120.3 mg g-1, respectively. Both HCEAT and HCEPT exhibit responsiveness to weak acid, achieving 24 h-release ratios of 85.8% and 80.5% at a pH of 5.5. The experiment and simulation results indicate that the coordination interaction between EDTA2- and Ca2+ facilitates the spherical aggregation of HNTs. Furthermore, these novel pesticide formulations demonstrate better resistance against ultraviolet (UV) irradiation, higher foliar affinity, and less leaching effect, with negligible impact of the carrier material on plants and terrestrial organisms. This work presents a promising approach toward the development of efficient and eco-friendly pesticide formulations, greatly contributing to the sustainable advancement of agriculture.

Exploring sparsity in graph transformers.

Graph Transformers (GTs) have achieved impressive results on various graph-related tasks. However, the huge computational cost of GTs hinders their deployment and application, especially in resource-constrained environments. Therefore, in this paper, we explore the feasibility of sparsifying GTs, a significant yet under-explored topic. We first discuss the redundancy of GTs based on the characteristics of existing GT models, and then propose a comprehensive Graph Transformer SParsification (GTSP) framework that helps to reduce the computational complexity of GTs from four dimensions: the input graph data, attention heads, model layers, and model weights. Specifically, GTSP designs differentiable masks for each individual compressible component, enabling effective end-to-end pruning. We examine our GTSP through extensive experiments on prominent GTs, including GraphTrans, Graphormer, and GraphGPS. The experimental results demonstrate that GTSP effectively reduces computational costs, with only marginal decreases in accuracy or, in some instances, even improvements. For example, GTSP results in a 30% reduction in Floating Point Operations while contributing to a 1.8% increase in Area Under the Curve accuracy on the OGBG-HIV dataset. Furthermore, we provide several insights on the characteristics of attention heads and the behavior of attention mechanisms, all of which have immense potential to inspire future research endeavors in this domain. Our code is available at https://github.com/LiuChuang0059/GTSP.

Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Graph structure reforming framework enhanced by commute time distance for graph classification.

As a graph data mining task, graph classification has high academic value and wide practical application. Among them, the graph neural network-based method is one of the mainstream methods. Most graph neural networks (GNNs) follow the message passing paradigm and can be called Message Passing Neural Networks (MPNNs), achieving good results in structural data-related tasks. However, it has also been reported that these methods suffer from over-squashing and limited expressive power. In recent years, many works have proposed different solutions to these problems separately, but none has yet considered these shortcomings in a comprehensive way. After considering these several aspects comprehensively, we identify two specific defects: information loss caused by local information aggregation, and an inability to capture higher-order structures. To solve these issues, we propose a plug-and-play framework based on Commute Time Distance (CTD), in which information is propagated in commute time distance neighborhoods. By considering both local and global graph connections, the commute time distance between two nodes is evaluated with reference to the path length and the number of paths in the whole graph. Moreover, the proposed framework CTD-MPNNs (Commute Time Distance-based Message Passing Neural Networks) can capture higher-order structural information by utilizing commute paths to enhance the expressive power of GNNs. Thus, our proposed framework can propagate and aggregate messages from defined important neighbors and model more powerful GNNs. We conduct extensive experiments using various real-world graph classification benchmarks. The experimental performance demonstrates the effectiveness of our framework. Codes are released on https://github.com/Haldate-Yu/CTD-MPNNs.

Vemurafenib inhibits necroptosis in normal and pathological conditions as a RIPK1 antagonist.

Necroptosis, a programmed cell death with necrotic-like morphology, has been recognized as an important driver in various inflammatory diseases. Inhibition of necroptosis has shown potential promise in the therapy of multiple human diseases. However, very few necroptosis inhibitors are available for clinical use as yet. Here, we identified an FDA-approved anti-cancer drug, Vemurafenib, as a potent inhibitor of necroptosis. Through direct binding, Vemurafenib blocked the kinase activity of receptor-interacting protein kinases 1 (RIPK1), impeded the downstream signaling and necrosome complex assembly, and inhibited necroptosis. Compared with Necrostain-1, Vemurafenib stabilized RIPK1 in an inactive DLG-out conformation by occupying a distinct allosteric hydrophobic pocket. Furthermore, pretreatment with Vemurafenib provided strong protection against necroptosis-associated diseases in vivo. Altogether, our results demonstrate that Vemurafenib is an effective RIPK1 antagonist and provide rationale and preclinical evidence for the potential application of approved drug in necroptosis-related diseases.

Comprehensive Graph Gradual Pruning for Sparse Training in Graph Neural Networks.

Graph neural networks (GNNs) tend to suffer from high computation costs due to the exponentially increasing scale of graph data and a large number of model parameters, which restricts their utility in practical applications. To this end, some recent works focus on sparsifying GNNs (including graph structures and model parameters) with the lottery ticket hypothesis (LTH) to reduce inference costs while maintaining performance levels. However, the LTH-based methods suffer from two major drawbacks: 1) they require exhaustive and iterative training of dense models, resulting in an extremely large training computation cost, and 2) they only trim graph structures and model parameters but ignore the node feature dimension, where vast redundancy exists. To overcome the above limitations, we propose a comprehensive graph gradual pruning framework termed CGP. This is achieved by designing a during-training graph pruning paradigm to dynamically prune GNNs within one training process. Unlike LTH-based methods, the proposed CGP approach requires no retraining, which significantly reduces the computation costs. Furthermore, we design a cosparsifying strategy to comprehensively trim all the three core elements of GNNs: graph structures, node features, and model parameters. Next, to refine the pruning operation, we introduce a regrowth process into our CGP framework, to reestablish the pruned but important connections. The proposed CGP is evaluated over a node classification task across six GNN architectures, including shallow models graph convolutional network (GCN) and graph attention network (GAT), shallow-but-deep-propagation models simple graph convolution (SGC) and approximate personalized propagation of neural predictions (APPNP), and deep models GCN via initial residual and identity mapping (GCNII) and residual GCN (ResGCN), on a total of 14 real-world graph datasets, including large-scale graph datasets from the challenging Open Graph Benchmark (OGB). Experiments reveal that the proposed strategy greatly improves both training and inference efficiency while matching or even exceeding the accuracy of the existing methods.

Glutathione metabolism is conserved in response to excessive copper exposure between mice liver and Aurelia coerulea polyps.

BACKGROUND: Copper (Cu) is a trace element that is engaged in various routine physiological processes. Excessive copper exposure can cause damage to organisms; however, it is unknown if the mechanisms underlying the response to Cu2+ among different species are conserved. METHODS: Aurelia coerulea polyps and mice models were exposed to Cu2+ to assess its effects on survival status and organ damage. Transcriptomic sequencing, BLAST, structural analysis, and real-time quantitative PCR were carried out to analyze the similarities and differences in the molecular composition and response mechanisms between two species when exposed to Cu2+. RESULTS: Excessive Cu2+ exposure led to toxic effects on both A. coerulea polyps and mice. The polyps were injured at a Cu2+ concentration of 3.0 mg L-1. In the mice, increasing Cu2+ concentrations were correlated with, the degree of liver damage, which manifested as hepatocyte apoptosis. In the 300 mg L-1 Cu2+ group of mice, livers cell death was primarily triggered by the phagosome and Toll-like signaling pathways. We found the glutathione metabolism was significantly altered in response to copper stress in both A. coerulea polyps and mice. Moreover, the similarity of gene sequences enriched at the two same sites in this pathway was as high as 41.05 %-49.82 % and 43.61 %-45.99 % respectively. Among them, there was a conservative region in the structure of A. coerulea polyps GSTK1 and mice Gsta2, but the overall difference is large. CONCLUSION: Glutathione metabolism is a conserved copper response mechanism in evolutionary distant organisms such as A. coerulea polyps and mice, although mammals have a more complex regulatory network when it comes to copper-induced cell death.

Effectiveness of WeChat-group-based parental health education in preventing unintentional injuries among children aged 0-3: randomized controlled trial in Shanghai.

BACKGROUND: Unintentional injuries to children are a major public health problem. The online social media is a potential way to implement health education for caregivers in online communities. Using WeChat, a free and popular social media service in China, this study evaluated the effectiveness of social online community-based parental health education in preventing unintentional injuries in children aged 0-3. METHODS: We recruited 365 parents from two community health centers in Shanghai and allocated them into intervention and control groups randomly. Follow-up lasted for one year. The intervention group received and followed their WeChat group and a WeChat official account for dissemination of reliable medical information. The control group received only the WeChat group. RESULTS: Between the intervention and control groups, changes in unintentional injuries (OR = 1.71, 95% CI: 1.02-2.87, P = .04), preventability (ß = 0.344, 95% CI: 0.152-0.537, P < .001), daily supervision behavior (ß = 0.503, 95% CI: 0.036-0.970, P = .04), and behaviors for preventing specific injuries (ß = 2.198, 95% CI: 1.530-2.865, P < .001) were significantly different, and change in first-aid skills for treating a tracheal foreign body were nearly significant (P = .06). CONCLUSIONS: The WeChat-group-based parental health education can reduce the occurrence of unintentional child injuries by improving parents' skills, beliefs, and behaviors. Online social communities promote health education and reduce unintentional injuries among children. TRIAL REGISTRATION: ChiCTR1900020753. Registered on January 17, 2019.

Identification and investigation of a novel NADP+-dependent secoisolariciresinol dehydrogenase from Isatis indigotica.

Cofactors are crucial for the biosynthesis of natural compounds, and cofactor engineering is a useful strategy for enzyme optimization due to its potential to enhance enzyme efficiency. Secoisolariciresinol dehydrogenase (SIRD) was reported to convert secoisolariciresinol into matairesinol in an NAD+-dependent reaction. Here, a SIRD designated as IiSIRD2 identified from Isatis indigotica was found to utilize NADP+ as the cofactor. To explore the structural basis for this unique cofactor preference, model-based structural analysis was carried out, and it was postulated that a variation at the GXGGXG glycine-rich motif of IiSIRD2 alters its cofactor preference. This study paves way for future investigations on SIRD cofactor specificity and cofactor engineering to improve SIRD's catalytic efficiency.

A combined protein toxin screening based on the transcriptome and proteome of Solenopsis invicta.

BACKGROUND: Multi-omics technology provides a good tool to analyze the protein toxin composition and search for the potential pathogenic factors of Solenopsis invicta, under the great harm of the accelerated invasion in southern China. METHODS: Species collection, functional annotation, toxin screening, and 3D modeling construction of three interested toxins were performed based on the successfully constructed transcriptome and proteome of S. invicta. RESULTS: A total of 33,231 unigenes and 721 proteins were obtained from the constructed transcriptome and proteome, of which 9,842 (29.62%) and 4,844 (14.58%) unigenes, as well as 469 (65.05%) and 71 (99.45%) proteins were annotated against the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. After comparing with the uniprot toxin database, a total of 316 unigenes and 47 proteins (calglandulin, venom allergen 3, and venom prothrombin activator hopsarin-D, etc.) were successfully screened. CONCLUSIONS: The update of annotations at the transcriptome and proteome levels presents a progression in the comprehension of S. invicta in China. We also provide a protein toxin list that could be used for further exploration of toxicity as well as its antagonistic strategy by S. invicta.

The medusa of Aurelia coerulea is similar to its polyp in molecular composition and different from the medusa of Stomolophus meleagris in toxicity.

BACKGROUND: The incidents of Aurelia sp. stinging have recently increased because of a bloom in offshore area. However, their symptoms are much milder than those from another scyphozoan jellyfish, Stomolophus meleagris. METHODS: The molecular composition of the medusa and polyp of Aurelia coerulea was analyzed by sequencing the transcriptome and proteome. The toxicity of tentacle extract from A. coerulea medusa (A-TE) and S. meleagris medusa (S-TE) was measured by the survival rates of mice, their blood indexes, and integrity of red blood cells. RESULTS: The medusa and polyp of A. coerulea are similar in molecular composition, while their gene expressions are significantly different at both transcriptome and proteome levels. A-TE displayed no in vitro hemolysis and caused mild damage to the liver, heart and kidney instead of lethality. In contrast, S-TE showed strong hemolytic toxicity, and lethal effect with serious damage to the liver, heart and kidney. The toxin screening in the medusae showed that there were similar toxin categories though the number of toxin species in A. coerulea was larger than that in S. meleagris. Among them, lactotransferrin and venom prothrombin activator were the two predominant protein toxins in the medusae of A. coerulea and S. meleagris, respectively. CONCLUSIONS: A. coerulea medusa and polyp have similar molecular compositions, though there are observable morphological differences. The toxicity of A. coerulea medusa is significantly weaker than that of S. meleagris medusa of which the variation in toxin expressions is feasibly an important reason.

Cadmium accelerates bacterial oleic acid production to promote fat accumulation in Caenorhabditis elegans.

Environmental cadmium, with a high dietary intake and long biological half-life, is a severe health risk by harming physiological function directly or through gut microbiota. However, the toxicity mechanisms of environmental cadmium on microbes and host systems remain unclear. Herein, we established three C. elegans and E. coli cultivated systems to investigate the vital role of microorganisms in cadmium-induced lipid toxicity and depict the interaction between environmental cadmium, bacteria, and the host. We found that only nematodes in the system with live bacteria, rather than UV-killed bacteria or no bacteria, could be induced to fat accumulation by cadmium exposure, suggesting that bacteria mediated the effect of environmental cadmium on body fat. Cadmium caused perturbation of metabolite in bacteria, most notably oleic acid, elevated the synthesis genes expression, and enhanced the bacterial oleic acid production, which further promoted the expression of lipid metabolism-related genes and fat deposition in C. elegans regardless of the cultivated system. Finally, we showed the potential protective effect of Vitamin D3 which prevented cadmium- or oleic acid-induced fat storage significantly. In conclusion, this study illustrates the mechanism underlying cadmium-induced lipid accumulation in body through bacterial metabolites and reveals the interplay between environmental cadmium, microorganisms, and the host.

Using online social networks to provide a parental health-education intervention for preventing unintentional injuries among children aged 0-3 years: A randomized controlled trial and social network analysis in Shanghai, China.

Introduction: Unintentional injury among children represents a major public health problem. Online-social-network-based parental-health-education is a potential way to reduce child unintentional injuries. The study aimed to explore the mechanisms by which online-social-network-based health education may reduce the unintentional injuries among children aged 0-3 years. Methods: We conducted a participant-blinded, randomized controlled, online-social-network-based health-education intervention study from March 2019 to February 2020 in Shanghai. We established four WeChat groups (two intervention groups and two control groups). For the intervention groups, a doctor's assistant regularly delivered information regarding unintentional injuries among children, and community childcare doctors answered parents' questions concerning their children's health, including unintentional injuries. Meanwhile, the control groups did not receive any information from the assistant. The study selected one intervention group and one control group and compared the ego network and whole network indicators to determine the differences between the intervention and control groups. Results: In the intervention and control groups, 64.5% and 31.9% of the members, respectively, engaged in communication, and 1,736 and 273 records, respectively, were obtained. Regarding ego network, the doctor showed the largest network in the intervention group, and the size of the intervention group's network was twice that of the control group; the number of ties in the intervention group was nine times that of the control group. Fourteen and four parents in the intervention and control group played an active role, respectively. Regarding centrality, all WeChat groups were loose and multiple centers existed. Regarding subgroup cohesion, the intervention group had 28 cliques with 27 members, and the control group had 4 cliques with 4 members. For structural hole, 23.7% and 7.5% members in the intervention and control group actively participated in interactions, respectively, having strong control and influence over other parents; 69.2% and 59.1% members in the intervention and control group, respectively, had values of < 1.000, showing that they had strong ability to cross-jump structural holes. Discussion: Online-social-networks-based health education interventions could enhance communication among parents, and between parents and community childcare doctors, and also shorten the social distance between them. Thus, online-social-network-based parental-health-education-intervention can be a feasible and generalizable means of preventing unintentional injuries among children.

Parents' attitudes as mediators between knowledge and behaviours in unintentional injuries at home of children aged 0-3 in Shanghai, Eastern China: a cross-sectional study.

OBJECTIVE: Parental behaviours are important in preventing unintentional injury at home among young children. Previous research showed an inconsistent relationship between knowledge and behaviours, indicating that the mechanisms may vary for different behaviours. This study aimed to examine the mediating roles of different attitudes in the mechanism of knowledge acting on different behaviours. DESIGN: Cross-sectional study. SETTING: Eastern China. PARTICIPANTS: Participants were recruited using stratified community-based sampling. A total of 488 parents of children aged 0-3 years participated in the study and 476 (97.5%) valid questionnaires were recovered. PRIMARY OUTCOME MEASURES: Parents' knowledge, attitudes (including injury attribution, preventability and responsibility) and behaviours (including supervision behaviours, risky behaviours and providing a safe home environment). RESULTS: The results of mediation analysis showed that the mediator variables were different for different behaviours and that all associations were positive. Parents' knowledge (ß 0.19, 95% CI 0.13 to 0.24) and attitude of injury attribution (ß 0.37, 95% CI 0.21 to 0.46) were directly associated with risky behaviours. Attitude of preventability was directly associated with parents' supervision behaviour (ß 0.27, 95% CI 0.14 to 0.40). Parents' attitude of preventability mediated the positive association between knowledge, attitudes of injury attribution and responsibility, and supervision behaviours, as well as providing a safe home environment. In addition, the occurrence of child injuries at home was directly associated with home environment (ß -0.41, 95% CI -0.82 to -0.01). CONCLUSIONS: The current findings confirm that attitudes play varying mediating roles between knowledge and different behaviours. An important recommendation is that parents' attitudes, especially towards preventability and responsibility, need to be considered when health providers develop health education programmes targeted at improving parental supervision behaviours and providing a safe home environment.

Structure-based engineering of substrate specificity for pinoresinol-lariciresinol reductases.

Pinoresinol-lariciresinol reductases (PLRs) are enzymes involved in the lignan biosynthesis after the initial dimerization of two monolignols, and this represents the entry point for the synthesis of 8-8' lignans and contributes greatly to their structural diversity. Of particular interest has been the determination of how differing substrate specificities are achieved with these enzymes. Here, we present crystal structures of IiPLR1 from Isatis indigotica and pinoresinol reductases (PrRs) AtPrR1 and AtPrR2 from Arabidopsis thaliana, in the apo, substrate-bound and product-bound states. Each structure contains a head-to-tail homodimer, and the catalytic pocket comprises structural elements from both monomers. ß4 loop covers the top of the pocket, and residue 98 from the loop governs catalytic specificity. The substrate specificities of IiPLR1 and AtPrR2 can be switched via structure-guided mutagenesis. Our study provides insight into the molecular mechanism underlying the substrate specificity of PLRs/PrRs and suggests an efficient strategy for the large-scale commercial production of the pharmaceutically valuable compound lariciresinol.

Isatis indigotica: from (ethno) botany, biochemistry to synthetic biology.

Isatis indigotica Fort. (Chinese woad) is a species with an ancient and well-documented history as an indigo dye and medicinal plant. It is often confused with Isatis tinctoria L. (European woad), a medicinal plant in Europe. Here, the differences between I. indigotica and I. tinctoria are systematically described. The usage development history, clinical applications and pharmacological activities, and chemical components of I. indigotica are also summarized. Lignans, indole alkaloids, and their corresponding derivatives have been identified as the major active ingredients of I. indigotica and are associated with anti-viral, anti-inflammatory, anti-cancer, and other health-promoting activities. Notable progress has been made in understanding the biosynthetic pathway and regulation mechanism of lignans and indole alkaloids in I. indigotica, the results from which should facilitate the process of targeted metabolic engineering or synthetic biology. Moreover, multiple biotechnology methods such as polyploid breeding and genetic engineering have been used with I. indigotica to result in, for example, greater yields, higher levels of bioactive component accumulation, and enhanced stress tolerance to salt, drought, and insects. Some issues require additional analyses, and suggestions for future research on I. indigotica are also discussed.

p -Laplacian Regularization for Scene Recognition.

The explosive growth of multimedia data on the Internet makes it essential to develop innovative machine learning algorithms for practical applications especially where only a small number of labeled samples are available. Manifold regularized semi-supervised learning (MRSSL) thus received intensive attention recently because it successfully exploits the local structure of data distribution including both labeled and unlabeled samples to leverage the generalization ability of a learning model. Although there are many representative works in MRSSL, including Laplacian regularization (LapR) and Hessian regularization, how to explore and exploit the local geometry of data manifold is still a challenging problem. In this paper, we introduce a fully efficient approximation algorithm of graph p -Laplacian, which significantly saving the computing cost. And then we propose p -LapR (pLapR) to preserve the local geometry. Specifically, p -Laplacian is a natural generalization of the standard graph Laplacian and provides convincing theoretical evidence to better preserve the local structure. We apply pLapR to support vector machines and kernel least squares and conduct the implementations for scene recognition. Extensive experiments on the Scene 67 dataset, Scene 15 dataset, and UC-Merced dataset validate the effectiveness of pLapR in comparison to the conventional manifold regularization methods.

Titanium dioxide nanoparticles prime a specific activation state of macrophages.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in foods, cosmetics, and medicine. Although the inhalation toxicity of TiO2 NPs has been studied, the potential adverse effects of oral exposure of low-dose TiO2 NPs are largely unclear. Herein, with macrophage cell lines, primary cells, and mouse models, we show that TiO2 NPs prime macrophages into a specific activation state characterized by excessive inflammation and suppressed innate immune function. After a month of dietary exposure in mice or exposure in vitro to TiO2 NPs (10 and 50 nm), the expressions of pro-inflammatory genes in macrophages were increased, and the expressions of anti-inflammatory genes were decreased. In addition, for macrophages exposed to TiO2 NPs in vitro and in vivo, their chemotactic, phagocytic, and bactericidal activities were lower. This imbalance in the immune system could enhance the susceptibility to infections. In mice, after a month of dietary exposure to low doses of TiO2 NPs, an aggravated septic shock occurred in response to lipopolysaccharide challenge, leading to elevated levels of inflammatory cytokines in serum and reduced overall survival. Moreover, TLR4-deficient mice and primary macrophages, or TLR4-independent stimuli, showed less response to TiO2 NPs. These results demonstrate that TiO2 NPs induce an abnormal state of macrophages characterized by excessive inflammation and suppressed innate immune function in a TLR4-dependent manner, which may suggest a potential health risk, particularly for those with additional complications, such as bacterial infections.