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Petroleum-based plastics are useful but they pose a great threat to the environment and human health. It is highly desirable yet challenging to develop sustainable structural materials with excellent mechanical and thermal properties for plastic replacement. Here, inspired by nacre’s multiscale architecture, we report a simple and efficient so called “directional deforming assembly” method to manufacture high-performance structural materials with a unique combination of high strength (281 MPa), high toughness (11.5 MPa m 1/2 ), high stiffness (20 GPa), low coefficient of thermal expansion (7 × 10 −6  K −1 ) and good thermal stability. Based on all-natural raw materials (cellulose nanofiber and mica microplatelet), the bioinspired structural material possesses better mechanical and thermal properties than petroleum-based plastics, making it a high-performance and eco-friendly alternative structural material to substitute plastics. It is desirable yet challenging to develop sustainable structural materials to replace petroleum-based plastics. Here, the authors report a facile assembly method for manufacturing high-performance structural materials with a unique combination of high strength, toughness and stiffness.

Biological control is considered as a promising alternative to pesticide and plant resistance to manage plant diseases, but a better understanding of the interaction of its natural and societal functions is necessary for its endorsement. The introduction of biological control agents (BCAs) alters the interaction among plants, pathogens, and environments, leading to biological and physical cascades that influence pathogen fitness, plant health, and ecological function. These interrelationships generate a landscape of tradeoffs among natural and social functions of biological control, and a comprehensive evaluation of its benefits and costs across social and farmer perspectives is required to ensure the sustainable development and deployment of the approach. Consequently, there should be a shift of disease control philosophy from a single concept that only concerns crop productivity to a multifaceted concept concerning crop productivity, ecological function, social acceptability, and economical accessibility. To achieve these goals, attempts should make to develop “green” BCAs used dynamically and synthetically with other disease control approaches in an integrated disease management scheme, and evolutionary biologists should play an increasing role in formulating the strategies. Governments and the public should also play a role in the development and implementation of biological control strategies supporting positive externality.

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug‐loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG‐E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG‐E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti‐inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage‐focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF. AC73 and siUSP1 dual drug‐loaded lipid nanoparticle carrying milk fat globule epidermal growth factor 8 (MFG‐E8) (named MUA/Y) can significantly induce the macrophages phenotype transformation and effectively inhibit the source of inflammatory cytokines. Meanwhile, MUA/Y inhibits the HSCs proliferation and activation and ablates the deposited ECM to treat advanced liver fibrosis.

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers. Drug efflux through ABC transporters is a common mechanism leading to chemoresistance in cancer. Here, the authors show that mitochondrial respiration provides ATP to allow ABC transporters activity so mitochondrial respiration inhibition overcomes chemoresistance in preclinical cancer models.

As the greatest defense organ of the body, the skin is exposed to endogenous and external stressors that produce reactive oxygen species (ROS). When the antioxidant system of the body fails to eliminate ROS, oxidative stress is initiated, which results in skin cellular senescence, inflammation, and cancer. Two main possible mechanisms underlie oxidative stress-induced skin cellular senescence, inflammation, and cancer. One mechanism is that ROS directly degrade biological macromolecules, including proteins, DNA, and lipids, that are essential for cell metabolism, survival, and genetics. Another one is that ROS mediate signaling pathways, such as MAPK, JAK/STAT, PI3K/AKT/mTOR, NF-κB, Nrf2, and SIRT1/FOXO, affecting cytokine release and enzyme expression. As natural antioxidants, plant polyphenols are safe and exhibit a therapeutic potential. We here discuss in detail the therapeutic potential of selected polyphenolic compounds and outline relevant molecular targets. Polyphenols selected here for study according to their structural classification include curcumin, catechins, resveratrol, quercetin, ellagic acid, and procyanidins. Finally, the latest delivery of plant polyphenols to the skin (taking curcumin as an example) and the current status of clinical research are summarized, providing a theoretical foundation for future clinical research and the generation of new pharmaceuticals and cosmetics.

With the rapid development of the Internet of Things (IoT) and the emergence of 5G, traditional silicon-based electronics no longer fully meet market demands such as nonplanar application scenarios due to mechanical mismatch. This provides unprecedented opportunities for flexible electronics that bypass the physical rigidity through the introduction of flexible materials. In recent decades, biological materials with outstanding biocompatibility and biodegradability, which are considered some of the most promising candidates for next-generation flexible electronics, have received increasing attention, e.g., silk fibroin, cellulose, pectin, chitosan, and melanin. Among them, silk fibroin presents greater superiorities in biocompatibility and biodegradability, and moreover, it also possesses a variety of attractive properties, such as adjustable water solubility, remarkable optical transmittance, high mechanical robustness, light weight, and ease of processing, which are partially or even completely lacking in other biological materials. Therefore, silk fibroin has been widely used as fundamental components for the construction of biocompatible flexible electronics, particularly for wearable and implantable devices. Furthermore, in recent years, more attention has been paid to the investigation of the functional characteristics of silk fibroin, such as the dielectric properties, piezoelectric properties, strong ability to lose electrons, and sensitivity to environmental variables. Here, this paper not only reviews the preparation technologies for various forms of silk fibroin and the recent progress in the use of silk fibroin as a fundamental material but also focuses on the recent advanced works in which silk fibroin serves as functional components. Additionally, the challenges and future development of silk fibroin-based flexible electronics are summarized. (1) This review focuses on silk fibroin serving as active functional components to construct flexible electronics. (2) Recent representative reports on flexible electronic devices that applied silk fibroin as fundamental supporting components are summarized. (3) This review summarizes the current typical silk fibroin-based materials and the corresponding advanced preparation technologies. (4) The current challenges and future development of silk fibroin-based flexible electronic devices are analyzed.

Quantum comparators and modular arithmetic are fundamental in many quantum algorithms. Current research mainly focuses on operations between two quantum states. However, various applications, such as integer factorization, optimization, and financial risk analysis, commonly require one of the inputs to be classical. It requires many ancillary qubits, especially when subsequent computations are involved. In this paper, we propose a quantum–classical comparator based on the quantum Fourier transform. Then we extend it to compare two quantum integers and modular arithmetic. Proposed operators only require up to one ancilla qubit, which is optimal for qubit resources. We analyze limitations in the current modular addition circuit and develop it to process arbitrary quantum states in the entire n -qubit space. The proposed algorithms reduce computing resources and make them valuable for noisy intermediate-scale quantum computers.

When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male’s future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish ( Gambusia holbrooki ). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male’s future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male’s future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance.

Background Cross-resistance, a phenomenon that a pathogen resists to one antimicrobial compound also resists to one or several other compounds, is one of major threats to human health and sustainable food production. It usually occurs among antimicrobial compounds sharing the mode of action. In this study, we determined the sensitivity profiles of Alternaria alternata , a fungal pathogen which can cause diseases in many crops to two fungicides (mancozeb and difenoconazole) with different mode of action using a large number of isolates (234) collected from seven potato fields across China. Results We found that pathogens could also develop cross resistance to fungicides with different modes of action as indicated by a strong positive correlation between mancozeb and difenoconazole tolerances to A. alternata . We also found a positive association between mancozeb tolerance and aggressiveness of A. alternata , suggesting no fitness penalty of developing mancozeb resistance in the pathogen and hypothesize that mechanisms such as antimicrobial compound efflux and detoxification that limit intercellular accumulation of natural/synthetic chemicals in pathogens might account for the cross-resistance and the positive association between pathogen aggressiveness and mancozeb tolerance. Conclusions The detection of cross-resistance among different classes of fungicides suggests that the mode of action alone may not be an adequate sole criterion to determine what components to use in the mixture and/or rotation of fungicides in agricultural and medical sects. Similarly, the observation of a positive association between the pathogen’s aggressiveness and tolerance to mancozeb suggests that intensive application of site non-specific fungicides might simultaneously lead to reduced fungicide resistance and enhanced ability to cause diseases in pathogen populations, thereby posing a greater threat to agricultural production and human health. In this case, the use of evolutionary principles in closely monitoring populations and the use of appropriate fungicide applications are important for effective use of the fungicides and durable infectious disease management.

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1 H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other ( P  < 0.01). Highly sensitized asthma associated metabolites were mainly enriched in pyruvate and acetyl-CoA metabolisms. Metabolites associated with highly sensitized atopic asthma were mostly correlated with microbiota in the airways. Acetic acid, a short-chain fatty acid (SCFA), was negatively correlated with the genus Atopobium ( P  < 0.01), but positively correlated with the genus Fusobacterium ( P  < 0.05). In conclusion, metabolomics reveals microbes-related metabolic pathways associated with IgE responses to house dust mite allergens in childhood asthma. A strong correlation of metabolites related to highly sensitized atopic asthma with airway microbiota provides linkages between the host–microbial interactions and asthma endotypes.