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The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRAS MUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)–conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA–protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non–small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush–ASO conjugate is a promising therapeutic platform for the treatment of KRAS -driven human cancers and warrant further preclinical and clinical development.

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme–cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

Seagrass-herbivore interactions play a principal role in regulating the structure and function of coastal food webs, which were affected by nutrient enrichment. Seawater nutrient enrichment might change seagrass palatability by altering seagrass physical and chemical traits, consequently modulating herbivory patterns, but this remains elusive. In this study, the dominant tropical seagrass Thalassia hemprichii was cultured in different ammonium concentrations to examine the response of seagrass nutritional quality, deterrent secondary metabolites, and leaf toughness, as well as the subsequent effect of the changed physical (e.g., leaf toughness) and chemical traits (e.g., nitrogen content; total phenol) on the grazing activity of the herbivorous snail Cerithidea rhizophorarum. Ammonium enrichment enhanced seagrass nutritional quality and decreased physical defence. Low ammonium enrichment increased total phenol content, while high ammonium enrichment reduced it. Both low and high ammonium enrichment enhanced the grazing intensity of C. rhizophorarum on seagrass. Interestingly, nutritional quality mostly determined the herbivory preference of C. rhizophorarum on the intact seagrass having physical structure, with a chemical deterrent (total phenol) playing a secondary role. In contrast, chemical deterrent mainly determined the grazing intensity on agar seagrass food which was made artificially to exclude physical structure. This indicated that seagrass leaf physical structure might hinder phenol compounds from deterring herbivores. Overall, the results presented here demonstrate that ammonium enrichment remarkably increased seagrass palatability and subsequently induced higher susceptibility to herbivory, which might induce seagrass loss.

It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore-forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl-modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA-based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.

Three-dimensional bioprinting represents promising approach for fabricating standalone and perfusable vascular conduits using biocompatible materials. Here we describe a step-by-step method by using a multichannel coaxial extrusion system (MCCES) and a blend bioink constituting gelatin methacryloyl, sodium alginate, and eight-arm poly(ethylene glycol)-acrylate with a tripentaerythritol core for the fabrication of standalone circumferentially multilayered hollow tubes. This microfluidic bioprinting method allows the fabrication of perfusable vascular conduits with a core lumen, an inner endothelial layer resembling the tunica intima, and an outer smooth muscle cell layer resembling the tunica media of the blood vessel. Biocompatible and perfusable blood vessels with a widely tunable size range in terms of luminal diameters and wall thicknesses can be successfully fabricated using the MCCES.

Three-dimensional bioprinting represents promising approach for fabricating standalone and perfusable vascular conduits using biocompatible materials. Here we describe a step-by-step method by using a multichannel coaxial extrusion system (MCCES) and a blend bioink constituting gelatin methacryloyl, sodium alginate, and eight-arm poly(ethylene glycol)-acrylate with a tripentaerythritol core for the fabrication of standalone circumferentially multilayered hollow tubes. This microfluidic bioprinting method allows the fabrication of perfusable vascular conduits with a core lumen, an inner endothelial layer resembling the tunica intima, and an outer smooth muscle cell layer resembling the tunica media of the blood vessel. Biocompatible and perfusable blood vessels with a widely tunable size range in terms of luminal diameters and wall thicknesses can be successfully fabricated using the MCCES.

Background Sediment is crucial for the unique marine angiosperm seagrass growth and successful restoration. Sediment modification induced by eutrophication also exacerbates seagrass decline and reduces plantation and transplantation survival rates. However, we lack information regarding the influence of sediment on seagrass photosynthesis and the metabolics, especially regarding the key secondary metabolic flavone. Meanwhile, sulfation of flavonoids in seagrass may mitigate sulfide intrusion, but limited evidence is available. Results We cultured the seagrass Thalassia hemprichii under controlled laboratory conditions in three sediment types by combining different ratios of in-situ eutrophic sediment and coarse beach sand. We examined the effects of beach sand mixed with natural eutrophic sediments on seagrass using photobiology, metabolomics and isotope labelling approaches. Seagrasses grown in eutrophic sediments mixed with beach sand exhibited significantly higher photosynthetic activity, with a larger relative maximum electron transport rate and minimum saturating irradiance. Simultaneously, considerably greater belowground amino acid and flavonoid concentrations were observed to counteract anoxic stress in eutrophic sediments without mixed beach sand. This led to more positive belowground stable sulfur isotope ratios in eutrophic sediments with a lower Eh. Conclusions These results indicated that coarse beach sand indirectly enhanced photosynthesis in T. hemprichii by reducing sulfide intrusion with lower amino acid and flavonoid concentrations. This could explain why T. hemprichii often grows better on coarse sand substrates. Therefore, it is imperative to consider adding beach sand to sediments to improve the environmental conditions for seagrass and restore seagrass in eutrophic ecosystems.

Aims Sediment composition is highly crucial for seagrass growth and survival. Eutrophication has been suggested a major cause of seagrass decline globally. We investigated the effects of beach sand supplementation to natural sediments under eutrophic condition on the growth and survival of tropical dominant seagrass Thalassia hemprichii. Methods We cultured seagrass T. hemprichii under the controlled laboratory conditions in three sediment types by combining different ratio of in-situ eutrophic sediment and coarse beach sand. We examined the effect of beach sand mixing to natural eutrophic sediments on the growth of seagrass using photobiology, metabolomics and isotope labeling approaches. Results Seagrass grown in eutrophic sediments mixed with sand exhibited significantly higher photosynthetic activity with high relative maximum electron transport rate and minimum saturating irradiance. Simultaneously, considerably greater belowground amino acid and flavonoid concentrations were observed to counteract anoxic stress in eutrophic sediment without mixing sand. This led to more positive belowground stable sulfur isotope in the eutrophic sediment with lower Eh. Conclusions These results indicated coarse beach sand indirectly enhanced photosynthesis and growth for T. hemprichii by reducing sulfide intrusion with lower concentrations of amino acid and flavonoid. This could possibly explain why T. hemprichii often grow better in the coarse sand substrate. Therefore, it is imperative to consider adding sand soil in the sediments to improve the growth condition for seagrass and restoring the seagrass shoots during transplantation in eutrophicated ecosystem.

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Our study reports a unique method of resolution enhancement purely relying on post-printing treatment of hydrogel constructs. By immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge, shrinking can rapidly occur resulting in various degrees of reduced dimensions comparing to the original pattern. This phenomenon, caused by complex coacervation and water expulsion, enables us to reduce linear dimensions of printed constructs while maintaining cytocompatible conditions in a cell type-dependent manner. We anticipate our shrinking printing technology to find widespread applications in promoting the current 3D printing capacities for generating higher-resolution hydrogel-based structures without necessarily having to involve complex hardware upgrades or other printing parameter alterations., Three-dimensional (3D) hydrogel printing enables production of volumetric architectures but achieving good resolutions for miniaturized features remains challenging. Here the authors demonstrate shrinking of a printed structure by immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge.

Individual selection, as an effective mechanism, is often used in spatial evolutionary games to promote cooperation. Previous research assumes that, individual selection usually occurs with people who fail to meet a certain criterion. However, individual selection is usually inevitable, regardless of whether players in population cooperate or defect. This paper studies the effects of wealth-based rule in costly public goods games when individual selection is inevitable. Specifically, we assume that only the top V individuals with relatively high cumulative payoffs in each group can be selected for costly PGG. The results show that when V is large, the increase of participation cost has slight inhibitory effects on the evolution of cooperation, but it alleviates the polarization of individuals. However, when V is small, the increase of participation cost within a certain range promotes cooperation prosperity, but it also causes an increase in the proportion of polarized individuals and a widening of the wealth gap between rich and poor individuals.

Rapid urbanization leads to an accelerating decline of seagrass beds. The status of seagrass beds along the entire coastline of a rapidly urbanizing area, Guangdong Province, was examined to document the change in seagrass beds and to explore the determinants of seagrasses characteristics and their plasticity. Thirteen seagrass beds were newly discovered with a total area as 679.04 ha, whereas eleven known seagrass beds have decreased from 972.55 ha to 858.67 ha with seven of them having disappeared in recent decade primarily due to exacerbated construction of artificial shorelines and beach dams, increased nutrient inputs from fish caging and shrimp pond culture, oyster culture, mangrove planting and shellfish collection. The leaf nitrogen content of Halophila ovalis, which dominated the largest beds, increased from (2.09 ± 0.24)% in 2011 to (3.39 ± 0.18)% in 2017, indicating enhanced eutrophication. The optimum seawater dissolved inorganic nitrogen and dissolved inorganic phosphorus levels for Halophila beccarii were 40 μmol/L and 2.5 μmol/L, respectively. The standing stock and plant dimensions of H. beccarii were positively correlated with sediment mud content. Longer, wider leaves, and greater aboveground and belowground biomass were observed at lower salinities, indicating that H. beccarii prefers hyposaline habitats. High shoot density could induce intraspecific competition followed by self-thinning in H. beccarii, leading to reduced leaf area, aboveground and belowground biomass, and root length. Thus, long-term monitoring of seagrass beds along the rapidly urbanizing coastline of Guangdong Province is needed to unravel the mechanisms of decline and to develop effective management strategies.

Seagrass beds act as blue carbon sinks globally; however, little attention has been given to carbon dynamics in the seagrass rhizosphere. Hence, in this study, the quantity and characteristics of dissolved organic carbon (DOC) from root exudation of the three dominant tropical seagrasses (Thalassia hemprichii, Enhalus acoroides, and Cymodocea rotundata) and sediment pore water beneath them were compared, to examine their interspecific differences, and to establish a connection between seagrass root exudation and sediment carbon. The rate of root-exuded DOC from T. hemprichii (2.15 ± 1.06 mg g DW root-1 h-1) was significantly higher (p

Emotion emerges along with individuals’ interactions, and numerous experimental studies have shown that emotion plays an important role in individual decision making. However, how emotion affects the evolution of cooperation in structured population is largely unknown. Here we introduce emotion into network reciprocity, where emotion is considered quantifiable and cumulative, and then divide individuals into two types, namely non-competitive individuals whose social value orientation is mutually beneficial and competitive individuals whose social value orientation is maximizing outcomes for the self. Here, we explore the effects of the proportion of non-competitive individuals and emotional cumulative length on the evolution of cooperation. Simulation results show that the existence of non-competitive individuals promotes cooperation in the system. Furthermore, we also find that emotional cumulative length plays a key role in promoting overall cooperation, but surprisingly, the cooperation rate of competitive individuals peaks at an intermediate value of emotional cumulative length.

Affected by geographical or social factors, human communities are organized with changeless groups for teamwork. Within groups, defection dominates because the payoffs of defectors are often higher than those of cooperators; among groups, higher cooperation level makes individuals wealthier. For the previous mechanism of evolutionary dynamics leading individuals to imitate the rich in their groups, defective strategy evolves. However, individuals who belong to different groups and have no direct interaction of interests actually could influence each other. Due to the similarity of environment, the strategies among groups have the channel and necessity of dissemination. To this end, we propose an evolutionary game model with inter-group selection of strategy. By simulations, the effects of groups’ selection preference, group size, multiplier factor, imitation intensity and competition among groups on cooperative evolution in populations are studied. We find that when the group makes selection without preference, the intensity of the choice positively affects the level of cooperation; the strategy selection with preference can effectively increase the group cooperation rate.

It is known that the vaccination is essential for suppressing the periodic prevalence of an infectious disease, while the vaccination decision is influenced by external factors. Whether or not to take vaccination depends not only on the expected benefit of individual, but also on the behavior of others. Nowadays, the speed of information transmission on the social media is fast with wide range, which extremely expands the scope of imitation, but it is unknown whether it is beneficial to vaccination. Inspired by this situation, a vaccination game model on two-layer network which increases the intensity of information sharing is proposed. The vaccination game layer and the information sharing layer are established to study the interaction between individual vaccination decisions and strategic exchanges. We find that although information sharing has inhibited individual vaccination decisions to some extent, the overall scale of disease spreading in society has decreased with increasing information sharing.

Zn, Pb, Cr, Cu, Ni, Cd concentration and ecological risk were studied in three bays to evaluate the heavy metal (HM) contamination of seagrasses. Seasonal HM accumulation varied according to locations, seagrass species and tissues. Halophila beccarii had much higher HM concentrations except for Cr in Zhelin Bay, however, bioconcentration factors (BCF) of Cu, Ni, Pb, Zn were higher in Liusha than Zhelin Bay. Cr was much enriched in Thalassia hemperichii and Enhalus acoroides than Halophila beccarii and Halophila ovalis. Cr, Cu, Ni, Pb were easy to accumulate in belowground tissues in Halophila ovalis. In contrast, almost all HM were more enriched in aboveground tissues in other species. Generally, BCF exceeding 1 and high metal pollution index suggested HM had potential ecological risk on seagrasses. The results provide the reference for managing and protecting seagrass ecosystem in South China, and are significant to expand the global seagrass detection network.

Cooperation is ubiquitous, but our innate selfishness greatly challenge our motivation to cooperate since natural selection favors the fittest individuals in all the ecosystems. In addition, cooperation is costly, implementing it weighs down the individual wealth and the prosperity of human society. Therefore, how to deal with social dilemma has attracted numerous scholars’ attentions. Among previous researches, indirect reciprocity acts a crucial role in the promotion of cooperation. However, scholars focus more on the consistency and constancy of all the players’ reputation fluctuation, and ignore its potential features, the heterogeneity and dynamic of the reputation increment. In real world, such a scenario can reflect it, for example, a famous person and a notorious person have a totally distinct reputation variation even if they have coincident actions. Inspired by aforesaid particularity of reputation variation, a new mechanism, heterogeneity of reputation increment driven by individual influence is introduced, in which players who have more payoffs than the average of their neighbors’ would be more influential, and their actions would lead to a bigger scale of reputation fluctuation due to more attentions from others. Simulation results show that cooperation is facilitated effectively by our new mechanism, compared with traditional model with constant reputation variation.

On‐site, prehospital care is vital for minimizing the severity of injuries caused by acute burns, especially those of the second and third degrees. Burn wounds typically have irregular shapes and depths and cover a large total body area. Due to the severity and complexity of burn wounds, traditional sheet‐like wound dressings are not always suitable. Alternatively, sprayable wound dressings can be used for convenient, quick, and large‐scale dressing changes. They can also prevent infection and secondary trauma depending on their reagent content. Sprayable wound dressings function as a therapeutic barrier that provides moisturization and pain relief, absorbs extrudates, protects against bacterial infections, and acts as a delivery system for small molecules and drugs. This review discusses the recent developments in sprayable hydrogel‐based wound dressings for high‐degree burns. An introduction to burn wound classifications, the ideal burn dressing designs and characteristics, and the current availability of commercial spray‐on burn dressings are presented. To achieve the optimal healing capacities using sprayable wound dressings, researchers are currently focusing on modifying the solution viscosities, propellant systems, and pump nozzle designs for spray formulations. Finally, the use of hydrogel‐based dressings to replace skin graft surgeries for tissue regeneration is discussed.