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Epidemic policy-making, as a special data-mining task, is proposed to predict the proper intensities of certain epidemic prevention and control policies based on the spatial-temporal data related to regional epidemics. Previous studies are currently constrained by two issues: First, existing methods are all strongly supervised by policy effect evaluation, since only a small proportion of factors in real-world policy-making are modeled, policies made by the existing models are then easily become extreme or unreasonable. Second, the subjectivity and the cognitive limitation of humans make historical policies not always optimal for the training of decision models. To this end, we present a novel Policy Combination Synthesis (PCS) model for epidemic policy-making. In particular, to prevent extreme decisions, we introduce adversarial learning between the model-made policies and the real policies to force the output policies to be more human-like. On the other hand, to minimize the impact of sub-optimal historical policies, we employ contrastive learning to let the model draw on experience from the best historical policies under similar scenarios. Both adversarial learning and contrastive learning are adaptive to the comprehensive effects of real policies, therefore ensuring that the model always learns useful information. Extensive experiments on real-world data show that policies made by the proposed model outperform the baseline models on both the epidemic containment effect and the economic impact, thereby proving the effectiveness of our work.

Owing to the inherently gradual nature of coagulation, the body fails in covalently crosslinking to stabilize clots rapidly, even with the aid of topical hemostats, thus inducing hemostatic failure and potential rebleeding. Although recently developed adhesives confer sealing bleeding sites independently of coagulation, interfacial blood hampers their adhesion and practical applications. Here, we report a covalently reactive hemostat based on blood-imbibing and -crosslinking microparticles. Once contacting blood, the microparticles automatically mix with blood via imbibition and covalently crosslink with blood proteins and the tissue matrix before natural coagulation operates, rapidly forming a fortified clot with enhanced mechanical strength and tissue adhesion. In contrast to commercial hemostats, the microparticles achieve rapid hemostasis (within 30 seconds) and less blood loss (approximately 35 mg and 1 g in the rat and coagulopathic pig models, respectively), while effectively preventing blood-pressure-elevation-induced rebleeding in a rabbit model. This work advances the development and clinical translation of hemostats for rapid hemostasis and rebleeding prevention. Hemostatic failure and the risk of rebleeding present significant challenges. Here, Chen et al. design a covalently reactive hemostat based on blood-imbibing and -crosslinking microparticles, achieving rapid hemostasis and preventing rebleeding.

Segmental large-sized long bone defects remain a significant challenge in clinical practice. The standard treatment, involving autologous or allogeneic graft implantation, is often insufficient due to the limited availability of donor bone. As an alternative therapy for long bone defects, guided bone regeneration (GBR) presents a promising approach, effectively enhancing bone augmentation by preventing bone defects from soft tissue infiltration and facilitating osteoblast migration. This technique employs a biomaterial membrane as a protective barrier on the bone surface, promoting osteogenesis. This study proposed a GBR membrane designed specifically for long bone defects for fabrication. A photocurable hydrogel and light-processing 3D printing, based on 3D-scanned long bone models, were utilized to achieve fabrication. A mineralization-inducing compound was also incorporated into the material to enhance cell adhesion and osteogenesis. The 3D-printed GBR membranes demonstrated precise attachment to the long bone surface, confirming successful fabrication. The efficacy of the 3D-printed GBR membranes was evaluated in rabbit radius bone defect models. Graphic abstract

Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut‐brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4‐month TRF ameliorated cognitive impairments among Alzheimer's disease (AD) patients. Experiments in 5xFAD mice corroborated the gut microbiota‐dependent effect of TRF on mitigating cognitive dysfunction, amyloid‐beta deposition, and neuroinflammation. Multi‐omics integration linked Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) with key genes in AD pathogenesis. Oral supplementation of B. pseudolongum or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood‐brain barrier penetration, while knockdown of the free fatty acid receptor 3 (FFAR3) diminished TRF's cognitive benefits. Notably, we observed a positive correlation between fecal PA and improved cognitive function in an AD cohort, further indicating that TRF enhanced PA production. These findings highlight the microbiota‐metabolites‐brain axis as pivotal in TRF's cognitive benefits, proposing B. pseudolongum or PA as potential AD therapies. A 4‐month of time‐restricted feeding (TRF) intervention alleviated cognitive impairments in Alzheimer's disease (AD) patients, while a 3‐month TRF regimen improved spatial memory, reduced amyloid‐beta accumulation, and promoted microglial aggregation around plaques in AD mice. Antibiotic‐induced gut microbiota depletion partly abolished TRF's benefits. Through creatively integrating gut microbiota, metabolites, and hippocampal genes, Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) were identified as key contributors to TRF's cognitive effects, with supplementation of either mimicking TRF's protective benefits. Positron emission tomography imaging revealed that PA directly crossed the blood‐brain barrier, and PA supplementation restored disrupted metabolism in AD mice. Knockdown of its receptor free fatty acid receptor 3 (FFAR3) diminished TRF's protective effects. A case‐control study showed a negative association between PA and cognitive status, while the TRF clinical intervention linked fecal PA to cognitive status. These findings suggest PA as a potential biomarker and underscore precise TRF‐based nutritional interventions as a promising strategy for managing neurodegenerative diseases. Highlights Time‐restricted feeding (TRF) improved cognitive function in Alzheimer's disease (AD) patients, with notable enhancement in executive function. Multi‐omics integrated analysis in AD mice identified Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) as key mediators of TRF's cognitive benefits. The potential molecular mechanism by which TRF alleviates cognitive impairment induced by AD involves the B. pseudolongum–PA‐free fatty acid receptor 3 (FFAR3) pathway. Case‐control study and TRF clinical intervention demonstrated PA as a potential biomarker for AD.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. UC treatments are limited by significant adverse effects associated with non‐specific drug delivery, such as systematic inhibition of the host immune system. Endoscopic delivery of a synthetic hydrogel material with biocompatible gelation that can efficiently cover irregular tissue surfaces provides an effective approach for targeted drug delivery at the gastrointestinal (GI) tract. An ideal integration of synthetic material with intestinal epithelium entails an integrated and preferable chemically bonded interface between the hydrogel and mucosal surface. In this study, a photo‐triggered coupling reaction is leveraged as the crosslinking platform to develop a mucosal‐adhesive hydrogel, which is compatible with endoscope‐directed drug delivery for UC treatment. The results demonstrated superior spatiotemporal specificity and drug pharmacokinetics with this delivery system in vivo. Delivery of different drugs with the hydrogel leads to greatly enhanced therapeutic efficacy and significantly reduced systemic drug exposure with rat colitis models. The study presents a strategy for targeted and persistent drug delivery for UC treatment. This study introduces a novel photo‐triggered coupling reaction to develop a mucosal‐adhesive hydrogel for endoscopic delivery in ulcerative colitis (UC) treatment. The hydrogel, with its biocompatible gelation and efficient coverage of irregular tissue surfaces, offers targeted drug delivery at the gastrointestinal tract, reducing systemic drug exposure and enhancing therapeutic efficacy. This innovative approach presents significant potential for improving UC treatment outcomes by minimizing adverse effects associated with non‐specific drug delivery methods.

Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions. A biohybrid nanorobot platform combining a magnetically driven nanorobot surface modified with 2‐hydroxypropyltrimethyl ammonium chloride chitosan and glycoengineered extracellular vesicles loaded with mangiferin is developed. It alleviates oxidative stress, improves endothelial cell and fibroblast functions, and promotes wound re‐epithelialization, collagen deposition, and angiogenesis through dual‐enhanced cell and tissue penetration, thus showing great promise for diabetic wound repair.

Naturally occurring fluorescent proteins (FPs) are the most widely used tools for tracking cellular proteins and sensing cellular events. Here, we chemically evolved the self-labeling SNAP-tag into a palette of SNAP-tag mimics of fluorescent proteins (SmFPs) that possess bright, rapidly inducible fluorescence ranging from cyan to infrared. SmFPs are integral chemical-genetic entities based on the same fluorogenic principle as FPs, i.e., induction of fluorescence of non-emitting molecular rotors by conformational locking. We demonstrate the usefulness of these SmFPs in real-time tracking of protein expression, degradation, binding interactions, trafficking, and assembly, and show that these optimally designed SmFPs outperform FPs like GFP in many important ways. We further show that the fluorescence of circularly permuted SmFPs is sensitive to the conformational changes of their fusion partners, and that these fusion partners can be used for the development of single SmFP-based genetically encoded calcium sensors for live cell imaging.

Epidemic policy-making, as a special data-mining task, is proposed to predict the proper intensities of certain epidemic prevention and control policies based on the spatial-temporal data related to regional epidemics. Previous studies are currently constrained by two issues: First, existing methods are all strongly supervised by policy effect evaluation, since only a small proportion of factors in real-world policy-making are modeled, policies made by the existing models are then easily become extreme or unreasonable. Second, the subjectivity and the cognitive limitation of humans make historical policies not always optimal for the training of decision models. To this end, we present a novel P olicy C ombination S ynthesis (PCS) model for epidemic policy-making. In particular, to prevent extreme decisions, we introduce adversarial learning between the model-made policies and the real policies to force the output policies to be more human-like. On the other hand, to minimize the impact of sub-optimal historical policies, we employ contrastive learning to let the model draw on experience from the best historical policies under similar scenarios. Both adversarial learning and contrastive learning are adaptive to the comprehensive effects of real policies, therefore ensuring that the model always learns useful information. Extensive experiments on real-world data show that policies made by the proposed model outperform the baseline models on both the epidemic containment effect and the economic impact, thereby proving the effectiveness of our work.

Hydrogel materials show promise for diverse applications, particular as biocompatible materials due to their high water content. Despite advances in hydrogel technology in recent years, their application is often severely limited by inadequate mechanical properties and time-consuming fabrication processes. Here we report a rapid hydrogel preparation strategy that achieves the simultaneous photo-crosslinking and establishment of biomimetic soft–hard material interface microstructures. These biomimetic interfacial-bonding nanocomposite hydrogels are prepared within seconds and feature clearly separated phases but have a strongly bonded interface. Due to effective interphase load transfer, biomimetic interfacial-bonding nanocomposite gels achieve an ultrahigh toughness (138 MJ m−3) and exceptional tensile strength (15.31 MPa) while maintaining a structural stability that rivals or surpasses that of commonly used elastomer (non-hydrated) materials. Biomimetic interfacial-bonding nanocomposite gels can be fabricated into arbitrarily complex structures via three-dimensional printing with micrometre-level precision. Overall, this work presents a generalizable preparation strategy for hydrogel materials and acrylic elastomers that will foster potential advances in soft materials.Hydrogels are promising materials but are often limited by inadequate mechanical properties and time-consuming fabrication processes. Here the authors demonstrate a rapid biomimetic interfacial-bonding nanocomposite strategy for ultra-tough hydrogels with high tensile strength.

Fluorescent RNAs (FRs), aptamers that bind and activate fluorescent dyes, have been used to image abundant cellular RNA species. However, limitations such as low brightness and limited availability of dye/aptamer combinations with different spectral characteristics have limited use of these tools in live mammalian cells and in vivo. Here, we develop Peppers, a series of monomeric, bright and stable FRs with a broad range of emission maxima spanning from cyan to red. Peppers allow simple and robust imaging of diverse RNA species in live cells with minimal perturbation of the target RNA’s transcription, localization and translation. Quantification of the levels of proteins and their messenger RNAs in single cells suggests that translation is governed by normal enzyme kinetics but with marked heterogeneity. We further show that Peppers can be used for imaging genomic loci with CRISPR display, for real-time tracking of protein–RNA tethering, and for super-resolution imaging. We believe these FRs will be useful tools for live imaging of cellular RNAs.