查看更多>>摘要：Marine organisms perform a sea of diel rhythmicity.Planktonic diel dynamics have been shown to be driven by light,energy resources,circadian rhythms,and the coordinated coupling of photoautotrophs and heterotrophic bacterioplankton.Here,we explore the diel fluctuation of viral production and decay and their impact on the total and active bacterial community in the coastal and open seawaters of the South China Sea.The results showed that the night-production diel pattern of lytic viral production was concurrent with the lower viral decay at night,contributing to the accumulation of the viral population size during the night for surface waters.The diel variations in bacterial activity,community composition,and diversity were found highly affected by viral dynamics.This was revealed by the finding that bacterial community diversity was positively correlated to lytic viral production in the euphotic zone of the open ocean but was negatively related to lysogenic viral production in the coastal ocean.Such distinct but contrasting correlations suggest that viral life strategies can not only contribute to diversifying bacterial community but also potentially piggyback their host to dominate bacterial community,suggesting the tightly synchronized depth-dependent and habitat-specific diel patterns of virus-host interactions.It further implies that viruses serve as an ecologically important driver of bacterial diel dynamics across the ocean,highlighting the viral roles in bacterial ecological and biogeochemical processes in the ocean.
查看更多>>摘要：Solid tumor cells live in a highly dynamic mechanical microenvironment.How the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an enigma.Here,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like cells.Mechanistically,integrin β8 was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and NESTIN.Inactivation also restored β8 expression,thereby forming a closed mechanical loop.Importantly,MAFG expression is correlated with worse prognosis.Our findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.
查看更多>>摘要：Comprehensive and quantitative assessment of human physical activity in daily life is valuable for healthcare,especially for those who suffer from obesity and neurological disorders or are at high risk of dementia.Common wearable devices,e.g.,smartwatches,are insufficient and inaccurate for monitoring highly dynamic limb movements and assessing human motion.Here,we report a new wearable leg movement monitoring system incorporating a custom-made motion sensor with machine learning algorithm to perceive human motion accurately and comprehensively during diverse walking and running actions.The system enables real-time multimodal perceptions of personal identity,motion state,locomotion speed,and energy expenditure for wearers.A general law of extracting real-time metabolic energy from leg movements is verified although individual gaits show differences.In addition,we propose a novel sensing configuration combining unilateral lower leg movement velocity with its angular rate to achieve high accuracy and good generalizability while simplifying the wearable system.Advanced performances in personal identification(accuracy of 98.7％)and motion-state recognition(accuracy of 93.7％)are demonstrated.The wearable system also exhibites high-precision real-time estimations of locomotion speed(error of 3.04％to 9.68％)and metabolic energy(error of 4.18％to 14.71％)for new subjects across various time-varying conditions.The wearable system allows reliable leg movement monitoring and quantitative assessment of bodily kinematic and kinetic behaviors during daily activities,as well as safe identity authentication by gait parameters,which would greatly facilitate smart life,personal healthcare,and rehabilitation training.
查看更多>>摘要：Genetic engineering technology can achieve specific gene therapy for a variety of diseases,but the current strategy still has some flaws,such as a complex system,single treatment,and large implantation trauma.Herein,the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered insitu cross-linking and cell gene transfection,and finally complete insitu gene therapy to promote bone reconstruction.First,ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen.Simultaneously,liposome loaded with Zinc-finger E-box-binding homeobox1(ZEB1)gene plasmid(Lip-ZEB1)was combined to construct an ultrasound-triggered insitu cross-linked hydrogels that can deliver Lip-ZEB1.Second,ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release,and then acted on the ZEB1/Notch signal pathway of cells,promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering.Overall,this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.
查看更多>>摘要：Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells(CSCs).However,the innate drawbacks,including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors,have become bottlenecks for clinical applications of photodynamic therapy.Here,we develop a mitochondria-targeting hemicyanine-oleic acid conjugate(CyOA),which can self-assemble into supramolecular nanoparticles(NPs)without any exogenous excipients.CyOA is also shown for targeting the mitochondrial complex Ⅱ protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia,resulting in 50.4-fold higher phototoxicity against breast cancer stem cells(BCSCs)compared to SO3-CyOA NPs that cannot target to mitochondria.In 4T1 and BCSC tumor models,CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin.This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.
查看更多>>摘要：Nonoxidative coupling of methane exhibits promising prospect in that it affords value-added hydrocarbons and hydrogen with high atom economy.However,challenge remains in direct,selective conversion of methane to more valuable hydrocarbons like olefins.The current work presents a catalyst with well-dispersed Ta atoms anchored by graphitic C3N4-supported phthalocyanine.Such a catalyst is able to convert methane selectively to ethylene and propylene at a relatively low temperature(350 ℃).The conception of the active center and construction of the catalyst have been described,and the origins of the catalytic performance are discussed.
查看更多>>摘要：Identifying pathogenetic variants and inferring their impact on protein-protein interactions sheds light on their functional consequences on diseases.Limited by the availability of experimental data on the consequences of protein interaction,most existing methods focus on building models to predict changes in protein binding affinity.Here,we introduced MIPPI,an end-to-end,interpretable transformer-based deep learning model that learns features directly from sequences by leveraging the interaction data from IMEx.MIPPI was specifically trained to determine the types of variant impact(increasing,decreasing,disrupting,and no effect)on protein-protein interactions.We demonstrate the accuracy of MIPPI and provide interpretation through the analysis of learned attention weights,which exhibit correlations with the amino acids interacting with the variant.Moreover,we showed the practicality of MIPPI in prioritizing de novo mutations associated with complex neurodevelopmental disorders and the potential to determine the pathogenic and driving mutations.Finally,we experimentally validated the functional impact of several variants identified in patients with such disorders.Overall,MIPPI emerges as a versatile,robust,and interpretable model,capable of effectively predicting mutation impacts on protein-protein interactions and facilitating the discovery of clinically actionable variants.
查看更多>>摘要：Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments.However,great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors.The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues.The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency,excellent biocompatibility,and diversiform immunomodulatory activity,thereby providing a powerful weapon for cancer immunotherapy.In past decades,supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner.In this review,we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy,including antigen delivery and presentation,T lymphocyte activation,tumor-associated macrophage elimination and repolarization,and myeloid-derived suppressor cell depletion.Based on extensive research,we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.
查看更多>>摘要：Classical-wave topological materials lacking intrinsic half-integer spins are less robust while more tunable.Here,we explore a single 3-dimensional phononic topological crystalline insulator that simultaneously exhibits a whole family of first-order quadratic surface,second-order hinge,and third-order corner states within the same bandgap.Such a topological crystalline insulator hosting all-order phases originates from the different topological nature when hierarchically projected onto different facets and lower dimensions,thus free from trivial cladding crystals.Our work offers an ideal platform for either robust wave propagation or localization in on-demand dimensions and may facilitate dimension division multiplexing technology.
查看更多>>摘要：Topological data analysis can extract effective information from higher-dimensional data.Its mathematical basis is persistent homology.The persistent homology can calculate topological features at different spatiotemporal scales of the dataset,that is,establishing the integrated taxonomic relation among points,lines,and simplices.Here,the simplicial network composed of all-order simplices in a simplicial complex is essential.Because the sequence of nested simplicial subnetworks can be regarded as a discrete Morse function from the simplicial network to real values,a method based on the concept of critical simplices can be developed by searching all-order spanning trees.Employing this new method,not only the Morse function values with the theoretical minimum number of critical simplices can be obtained,but also the Betti numbers and composition of all-order cavities in the simplicial network can be calculated quickly.Finally,this method is used to analyze some examples and compared with other methods,showing its effectiveness and feasibility.
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