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Siphon is an effective method to transfer liquid from a higher to a lower level, which has many applications in hygienic design, clinical apparatus, and hydraulic engineering. Traditional operation requires energy to overcome gravity and establish flow in a closed system. Achieving sustainable high flux siphon drainage without energy input remains a challenge due to viscous dissipation. Here, an unexpected open siphon behavior on the South American pitcher plant Heliamphora minor consisting of trichomes covered pitcher and a wedge-shaped sheath is examined. Exploiting the concept of Digital Twin, a new biomimetic research method by transforming the biological sample to a virtual 3D model is proposed and unveiled that maintained connection of wicking on sub-millimeter long trichomes due to asymmetric pressure distribution and ascending in wedge sheath under unbalanced pressure forms continuous surface flow. Exploring this mechanism, a biomimetic siphon device achieving continuous high flux exposed to ambient air is constructed. Besides, particles floating on the meniscus in the outside wedge move under a curvature gradient as water ascends, which implies a biological nutrient capture method and new dust collection manner in the drainage system. Applying the underlying principle enhances the siphon efficiency of floor drains and has the potential for other liquid transfer device design improvements.
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Various creatures, such as spider silk and cacti, have harnessed their surface structures to collect fog for survival. These surfaces typically stay dry and have a large contact hysteresis enabling them to move a condensed water droplet, resulting in an intermittent transport state and a relatively reduced speed. In contrast to these creatures, here we demonstrate that Nepenthes alata offers a remarkably integrated system on its peristome surface to harvest water continuously in a humid environment. Multicurvature structures are equipped on the peristome to collect and transport water continuously in three steps: nucleation of droplets on the ratchet teeth, self-pumping of water collection that steadily increases by the concavity, and transport of the acquired water to overflow the whole arch channel of the peristome. The water-wetted peristome surface can further enhance the water transport speed by â¼300 times. The biomimetic design expands the application fields in water and organic fogs gathering to the evaporation tower, laboratory, kitchen, and chemical industry.
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The rapid removal of rain droplets at the leaf apex is critical for leaves to avoid damage under rainfall conditions, but the general water drainage principle remains unclear. We demonstrate that the apex structure enhances water drainage on the leaf by employing a curvature-controlled mechanism that is based on shaping a balance between reduced capillarity and enhanced gravity components. The leaf apex shape changes from round to triangle to acuminate, and the leaf surface changes from flat to bent, resulting in the increase of the water drainage rate, high-dripping frequencies, and the reduction of retention volumes. For wet tropical plants, such as Alocasia macrorrhiza, Gaussian curvature reconfiguration at the drip tip leads to the capillarity transition from resistance to actuation, further enhancing water drainage to the largest degree possible. The phenomenon is distinct from the widely researched liquid motion control mechanisms, and it offers a specific parametric approach that can be applied to achieve the desired fluidic behavior in a well-controlled way.
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Alocasia/anatomia & histologia , Alocasia/fisiologia , Drenagem , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Chuva , Água/fisiologiaRESUMO
Synthetic biology has promoted the development of microbial therapy, but the scope of applicable microbial species is limited and transgenic microorganisms also display safety risks for in vivo applications. Interestingly, symbiotic microorganisms in nature can achieve functional updates by metabolic cooperation. Here, we report on a nongenetic method for engineering microorganisms to construct a heavy metal ion reduction system, which was prepared by linking Shewanella oneidensis MR-1 (SO) and Lactobacillus rhamnosus GG (LGG). SO could reduce metal ions but is limited by finite substrates in vivo. LGG could metabolize glucose to lactate as a substrate for SO, promoting extracellular electron transfer by SO and heavy metal ion reduction. Meanwhile, SO could generate electron donor cytochrome C to promote metabolism of LGG, forming metabolic synergy and circulation between these two bacteria. The SO-LGG system shows splendid ability to remove heavy metal ions and inflammatory modulation in acute or chronic heavy metal poisoning.
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Metais Pesados , Shewanella , Transporte de Elétrons , ÍonsRESUMO
Effective, long-range, and self-propelled water elevation and transport are important in industrial, medical, and agricultural applications. Although research has grown rapidly, existing methods for water film elevation are still limited. Scaling up for practical applications in an energy-efficient way remains a challenge. Inspired by the continuous water cross-boundary transport on the peristome surface of Nepenthes alata, here we demonstrate the use of peristome-mimetic structures for controlled water elevation by bending biomimetic plates into tubes. The fabricated structures have unique advantages beyond those of natural pitcher plants: bulk water diode transport behavior is achieved with a high-speed passing state (several centimeters per second on a milliliter scale) and a gating state as a result of the synergistic effect between peristome-mimetic structures and tube curvature without external energy input. Significantly, on further bending the peristome-mimetic tube into a "candy cane"-shaped pipe, a self-siphon with liquid diode behavior is achieved. Such a transport mechanism should inspire the design of next generation water transport devices.
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Biomimética/métodos , Capilares/fisiologia , Caryophyllales/anatomia & histologia , Microfluídica/métodos , Materiais Biomiméticos/química , Caryophyllales/fisiologia , Hidrogéis/química , Álcool de Polivinil/química , Impressão TridimensionalRESUMO
We investigate the mutual interaction of two spatially-separated Airy beams in the nonlinear Schrödinger equation with the fractional Laplacian. Depending on the beam separation (d), relative phase and Lévy index (α), we observed an anomalous attraction or repulsion between the Airy beams. Anomalous attraction leads to a single breather soliton with a period that grows exponentially as α increases. In this region of the parameter space, we identify a crossover between two asymmetric regimes: as the Lévy index exceeds a critical value α c, the period of breather soliton for d>0 is orders of magnitude larger than for d<0, while the opposite occurs as α<α c. Our results reveal a novel scenario for Airy beams interaction in the framework of fractional nonlinear Schrödinger equation and provide an alternative mechanism to control breather soliton generation.
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Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H2O2 and a robust catalyst. However, it has faced severe challenges including the limited amounts of H2O2 and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied H2O2 and TA-mediated acceleration of Fe(III)/Fe(II) conversion. In the ATP-overexpressed tumor cells, the outer shell MPN of GOx@ZIF@MPN was degraded into Fe(III) and tannic acid (TA) and the internal GOx was exposed. Then, GOx reacted with the endogenous glucose to produce plenty of H2O2, and TA reduced Fe(III) to Fe(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H2O2 was catalyzed by Fe(II) to generate highly toxic hydroxyl radical (â¢OH) and Fe(III). The produced Fe(III) with low catalytic activity was quickly reduced to reactive Fe(II) mediated by TA, forming an accelerated Fe(III)/Fe(II) conversion to guarantee efficient Fenton reaction-mediated CDT. This autocatalytic Fenton nanosystem might provide a good paradigm for effective tumor treatment.
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Free radicals have emerged as new-type and promising candidates for hypoxic tumor treatment, and further study of their therapeutic mechanism by real-time imaging is of great importance to explore their biomedical applications. Herein, we present a smart free-radical generator AuNC-V057-TPP for hypoxic tumor therapy; the AuNC-V057-TPP not only exhibits good therapeutic effect under both hypoxic and normoxic conditions but also can monitor the release of free radicals in real-time both in vitro and in vivo. What is more, with the mitochondria-targeting ability, the AuNC-V057-TPP is demonstrated with improved antitumor efficacy through enhanced free radical level in mitochondria, which leads to mitochondrial membrane damage and ATP production reduction and finally induces cancer cell apoptosis.
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Sistemas de Liberação de Medicamentos/métodos , Radicais Livres/metabolismo , Ouro , Neoplasias Mamárias Animais , Nanopartículas Metálicas , Mitocôndrias , Imagem Molecular/métodos , Hipóxia Tumoral , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacologia , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologiaRESUMO
This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.
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Hipertermia Induzida , Nanofibras/química , Neoplasias/patologia , Fototerapia , Animais , Morte Celular , Cobre/química , Células Hep G2 , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/metabolismo , Luminescência , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Células RAW 264.7 , Esferoides Celulares/patologia , Esferoides Celulares/ultraestrutura , Sulfetos/química , TemperaturaRESUMO
By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation-induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity-decomposable calcium carbonate (CaCO3 ) nanoparticles concurrently tethered by hyaluronic acid. This hybrid nanotherapeutic shows a strong tendency to accumulate in tumors postinjection due to the cooperation between passive and active targeting mechanisms. The GOD-driven oxidation reaction deprives tumors of glucose for starvation therapy and concomitantly induces tumorous abnormality amplifications including elevated acidity and exacerbated hypoxia. Programmatically, the acidity amplification causes CaCO3 decomposition, offering not only spatial control over the liberation of embedded TPZ just within tumors but also the temporal control over timely chemotherapy initiation to match the occurrence of hypoxia amplification and thus benefiting perfect synergism between starvation therapy and chemotherapy.
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Antineoplásicos/química , Carbonato de Cálcio/química , Nanopartículas/química , Pró-Fármacos/química , Tirapazamina/química , Glucose Oxidase/metabolismo , Ácido Hialurônico/químicaRESUMO
Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core-shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH-sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core-shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia-inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD-L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD-1) antibody, the dual inhibition of the PD-1/PD-L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.
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Antineoplásicos/farmacologia , Antígeno B7-H1/metabolismo , Biomimética/métodos , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Hipóxia Tumoral/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/metabolismo , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Doxorrubicina/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imidazóis/química , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/imunologia , Neoplasias/patologia , Oxigênio/farmacologia , Zeolitas/químicaRESUMO
Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ability of p53 and the Fenton reaction inducing capability of metal-organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a "bystander effect" to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.
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Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Estruturas Metalorgânicas/administração & dosagem , Neoplasias/terapia , Polifenóis/química , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Morte Celular , Linhagem Celular Tumoral , Genes p53 , Terapia Genética , Humanos , Estruturas Metalorgânicas/farmacologia , Nanoestruturas , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Plasmídeos , Propriedades de SuperfícieRESUMO
A novel single-molecular fluorescent probe was developed for spatiotemporal matrix metalloproteinase-2 (MMP-2) and caspase-3 imaging with distinct fluorescence signals. Due to the multi-Förster resonance energy transfer (FRET) processes, the probe could respond to MMP-2 and caspase-3 independently with high signal-to-noise ratio. Moreover, the overexpression of MMP-2 in cancer cell lines and the cisplatin induced cell apoptosis were spatiotemporal imaged with distinct fluorescence emissions. Because of the independent process of the probe for MMP-2 and caspase-3 imaging, the probe could meet the demands for precise disease diagnosis and cancer theranostic applications, which could extensively simplify the processes for precise cancer diagnosis and imaging.
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Caspase 3/metabolismo , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Metaloproteinase 2 da Matriz/metabolismo , Animais , Células COS , Caspase 3/química , Linhagem Celular Tumoral , Chlorocebus aethiops , Citometria de Fluxo , Humanos , Metaloproteinase 2 da Matriz/química , Microscopia ConfocalRESUMO
Separation of micro-scaled water-in-oil droplets is important in environmental protection, bioassays, and saving functional inks. So far, bulk oil-water separation has been achieved by membrane separation and sponge absorption, but micro-drop separation still remains a challenge. Herein we report that instead of the "plug-and-go" separation model, tiny water-in-oil droplets can be separated into pure water and oil droplets through "go-in-opposite ways" on curved peristome-mimetic surfaces, in milliseconds, without energy input. More importantly, this overflow controlled method can be applied to handle oil-in-oil droplets with surface tension differences as low as 14.7â mN m-1 and viscous liquids with viscosities as high as hundreds centipoises, which markedly increases the range of applicable liquids for micro-scaled separation. Furthermore, the curved peristome-mimetic surface guides the separated drops in different directions with high efficiency.
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We have investigated the propagation dynamics of super-Gaussian optical beams in fractional Schrödinger equation. We have identified the difference between the propagation dynamics of super-Gaussian beams and that of Gaussian beams. We show that, the linear propagation dynamics of the super-Gaussian beams with order m > 1 undergo an initial compression phase before they split into two sub-beams. The sub-beams with saddle shape separate each other and their interval increases linearly with propagation distance. In the nonlinear regime, the super-Gaussian beams evolve to become a single soliton, breathing soliton or soliton pair depending on the order of super-Gaussian beams, nonlinearity, as well as the Lévy index. In two dimensions, the linear evolution of super-Gaussian beams is similar to that for one dimension case, but the initial compression of the input super-Gaussian beams and the diffraction of the splitting beams are much stronger than that for one dimension case. While the nonlinear propagation of the super-Gaussian beams becomes much more unstable compared with that for the case of one dimension. Our results show the nonlinear effects can be tuned by varying the Lévy index in the fractional Schrödinger equation for a fixed input power.
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Liquid uni-directional transport on solid surface without energy input would advance a variety of applications, such as in bio-fluidic devices, self-lubrication, and high-resolution printing. Inspired by the liquid uni-directional transportation on the peristome surface of Nepenthesâ alata, here, we fabricated a peristome-mimicking surface through high-resolution stereo-lithography and demonstrated the detailed uni-directional transportation mechanism from a micro-scaled view visualized through X-ray microscopy. Significantly, an overflow-controlled liquid uni-directional transportation mechanism is proposed and demonstrated. Unlike the canonical predictions for completely wetting liquids spreading symmetrically on a high-energy surface, liquids with varied surface tensions and viscosities can spontaneously propagate in a single preferred direction and pin in all others. The fundamental understanding gained from this robust system enabled us to tailor advanced micro-computerized tomography scanning and stereo-lithography fabrication to mimic natural creatures and construct a wide variety of fluidic machines out of traditional materials.
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Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mø@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mø@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies.
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Neoplasias , Camundongos , Animais , Neoplasias/patologia , Macrófagos , Transferência Adotiva , Bactérias , Microambiente Tumoral , ImunoterapiaRESUMO
Liquid entrainment with a solid architecture passing through the fluid-fluid interface is ubiquitous and widely used in industrial processes as a liquid transfer method. Besides liquid properties, solid structures play a core role in entrainment. Although the influence of its macroscopic curvatures and microscale roughness has attracted years of research, the effect and potential of the commonly seen millimetric structures have not been sufficiently explored and exploited. Here, we demonstrate enhanced liquid entrainment on the millimetric structured surface by the co-effect of viscosity and capillarity for sustained liquid transfer of small deviation, including high-quantity uptake and practically operational drainage with small and relatively uniform droplet dripping time of varied liquid viscosities. With the overall process of viscous-capillary entrainment, we achieve stable cyclical arrayed liquid transport, showing its potential for sustained liquid transfer in intractable situations in laboratory, industry, and even daily life.
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Morphology tuning is a potent strategy to modulate physiological effects of synthetic biomaterials, but it is rarely explored in microbe-based biochemicals due to the lack of artificial adjustability. Inspired by the interesting phenomenon of microbial transformation, Escherichia coli is rationally adjusted into filamentous morphology-adjusted bacteria (MABac) via chemical stimulation to prepare a bacteria-based vaccine adjuvant/carrier. Inactivated MABac display stronger immunogenicity and special delivery patterns (phagosome escape and cytoplasmic retention) that are sharply distinct from the short rod-shaped bacteria parent (Bac). Transcriptomic study further offers solid evidence for deeply understanding the in vivo activity of MABac-based vaccine, which more effectively motivates multiple cytosolic immune pathways (such as NOD-like receptors and STING) and induces pleiotropic immune responses in comparison with Bac. Harnessing the special functions caused by morphology tuning, the MABac-based adjuvant/carrier significantly improves the immunogenicity and delivery profile of cancer antigens in vivo, thus boosting cancer-specific immunity against the melanoma challenge. This study validates the feasibility of tuning bacterial morphology to improve their biological effects, establishing a facile engineering strategy that upgrades bacterial properties and functions without complex procedures like gene editing.
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Adjuvantes Imunológicos , Vacinação , Adjuvantes Imunológicos/farmacologia , Escherichia coli/genética , BactériasRESUMO
Reactive oxygen species (ROS) are closely related to the antiviral immune response of plants, while virus can regulate ROS through various pathways to facilitate their own infection or replication. Citrus yellow vein clearing virus (CYVCV) is one of the most devastating viruses affecting lemon (Citrus limon) industry worldwide. However, the pathogenesis of CYVCV remains poorly understood. In this study, direct interaction between the coat protein (CP) of CYVCV and the ascorbate peroxidase 1 of lemon (ClAPX1) was confirmed for the first time by yeast two-hybrid, Bimolecular Fluorescence Complementation, and Co-immunoprecipitation assays. Transient expression of CP in lemon and Nicotiana benthamiana significantly enhanced the enzyme activity of the ClAPX1, and then inhibited the accumulation of H2O2. In addition, overexpression of ClAPX1 in lemon by transgene significantly promoted CYVCV accumulation and depressed the expression of most genes involved in jasmonic acid (JA) signaling pathway. Correspondingly, ClAPX1 silencing by RNA interference inhibited CYVCV accumulation and increased the expression of most genes involved in JA signaling pathway. To our knowledge, this is the first report that viruses regulate ROS by targeting APX directly, thereby suppressing host immune response and promoting viral accumulation, which may be mediated by JA signaling pathway.