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An on-site activated aptasensing platform is constructed for highly reliable ATP monitoring in cancer cells both in vitro and in vivo by combining tumor-specific activatable MnO2 with the stimuli-responsive cascade DNA amplifier.

DNA-based nanoprobes have attracted extensive interest in the field of bioanalysis. Notably, engineered DNA nanoprobes that can respond to multiple pathological parameters are desirable to detect targets precisely. Here we design a split aptamer/DNAzyme (aptazyme)-based DNA probe for fluorescence detection of ATP and further develop a cooperatively activatable DNA nanoprobe for tumor-specific imaging of ATP in vivo. The DNA nanoprobes comprising split aptazyme-coated MnO2 nanovectors have high stability and are synergistically activated by multiple biomarkers, GSH and ATP. Upon stimuli by overexpressed GSH in tumor cells, this DNA nanoprobe can release the aptazyme and self-supply cofactor Mn2+ of the DNAzyme. Sequentially, intracellular ATP induces the proper folding of the split ATP aptamer and Mn2+-dependent DNAzyme, which activates the specific cleavage of substrate and generates the optical readout signal. This nanoprobe exhibits remarkable resistance to enzymatic degradation, satisfactory biosafety, identifies ATP specifically within cancer cells, and selectively lights up solid tumors. Our research provides a reliable method for ATP imaging in cancer cells and opens a new avenue for biochemical research and highly accurate disease diagnosis.

On e-learning platforms, most e-learners didn’t complete the course successfully. It means that reducing dropout is a critical problem for the sustainability of e-learning. This paper aims to estab...

Basal cells are multipotent stem cells of a variety of organs, including the respiratory tract, where they are major components of the airway epithelium. However, it remains unclear how diverse basal cells are and how distinct subpopulations respond to airway challenges. Using single cell RNA-sequencing and functional approaches, we report a significant and previously underappreciated degree of heterogeneity in the basal cell pool, leading to identification of six subpopulations in the adult murine trachea. Among these, we found two major subpopulations, collectively comprising the most uncommitted of all the pools, but with distinct gene expression signatures. Notably, these occupy distinct ventral and dorsal tracheal niches and differ in their ability to self-renew and initiate a program of differentiation in response to environmental perturbations in primary cultures and in mouse injury models in vivo. We found that such heterogeneity is acquired prenatally, when the basal cell pool and local niches are still being established, and depends on the integrity of these niches, as supported by the altered basal cell phenotype of tracheal cartilage-deficient mouse mutants. Finally, we show that features that distinguish these progenitor subpopulations in murine airways are conserved in humans. Together, the data provide novel insights into the origin and impact of basal cell heterogeneity on the establishment of regionally distinct responses of the airway epithelium during injury-repair and in disease conditions.

Effective adjuvants that enhance immune responses have great potential for vaccine development and disease prevention. A major challenge is the effective delivery of vaccine component to specific c...

Photodynamic therapy (PDT) has extraordinary promise for the treatment of many cancers. However, its clinical progress is impaired by the intrinsic hypoxic tumor microenvironment that limits PDT efficacy and the safety concern associated with biological specificity of photosensitizers or vehicles. Now it is demonstrated that rationally designed DNA nanosponges can load and delivery photosensitizer effectively, target tumor precisely, and relieve hypoxia-associated resistance remarkably to enhance the efficacy of PDT. Specifically, the approach exhibits a facile assembly process, provides programmable and versatile nanocarriers, and enables robust in vitro and in vivo anti-cancer efficacy with excellent biosafety. These findings represent a practical and safe approach by designer DNA nanoassemblies to combat cancer effectively and suggest a powerful strategy for broad biomedical application of PDT.

Business failure is an important issue for companies in the 21st century, and green business is of global concern. Therefore, it is of vital importance to reveal the critical factors that could lead to green business failure. Nevertheless, existing research has not fully addressed this yet. This study adopts the company life cycle theory to identify such critical factors. The Decision Making Trial and Evaluation Laboratory (DEMATEL) method is applied to convert the expert opinion into quantifiable data, and grey relational analysis is used to take the imprecise information into account in order to improve the validity of the results. Research frameworks constructed from company life cycle is able to reflect the critical factors that lead to green business failure at different development phases. Meanwhile, the adoption of Grey DEMATEL improves the accuracy of assessment, and the result of assessment provides feasible and practical suggestions for decision-making.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H2O2 overexpressed in TME and generation of O2. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.

Wind characteristics (e.g., mean wind speed, gust factor, turbulence intensity and integral scale, etc.) are quite scattered in different measurement conditions, especially during typhoon and/or hurricane processes, which results in the structural engineer ambiguously determining the wind parameters in wind-resistant design of buildings and structures in cyclone-prone regions. In tropical cyclones (including typhoons and hurricanes), the inconsistent wind characteristics may be in part ascribed to the complex flow structure with the coexistence of both mechanical and convective turbulence in the boundary layer of tropical cyclones. Another significant contribution to the scattered wind characteristics is due to various measurement conditions (e.g., terrain exposure and height) and data processing schemes (e.g., averaging time). The removal of the inconsistency in the field-measurement system may offer a more rational comparison of measured wind data from various observation platforms, and hence facilitates a better identification scheme of the wind characteristics to guide the urban planning design and wind-resistant design of buildings and structures. In this study, an analytical framework was firstly proposed to eliminate the potential observation-related effects in wind characteristics and then the wind characteristics of seven field measured tropical cyclones (four typhoons and three hurricanes) were comparatively investigated. Specifically, field measurements of wind characteristics were converted to a standard reference station with a roughness length of 0.03 m, observation duration of 10 min for mean wind and averaging time of 3 s for gusty wind at a 10 m height. The differences of the measured wind characteristics between the typhoons and hurricanes were highlighted. The standardized turbulent wind characteristics under the analytical framework for typhoons and hurricanes were compared with the corresponding recommendations in standard of American Society of Civil Engineers (ASCE 7-10) and Architectural Institute of Japan Recommendations for Loads on Buildings (AIJ-RLB-2004).

Cdt1 is a novel kinetochore–microtubule binding protein. The middle and the C-terminal winged-helix domains of Cdt1 are involved in microtubule binding. Aurora B kinase phosphorylation of Cdt1 influences its microtubule binding in vitro and is necessary for kinetochore–microtubule stability and mitotic progression in cells., Robust kinetochore–microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex–dependent manner leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores. Deletion mapping of Cdt1 revealed that the regions comprising the middle and C-terminal winged-helix domains but lacking the N-terminal unstructured region were required for efficient MT binding. Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B–phosphomimetic Cdt1 exhibited attenuated MT binding, and its cellular expression induced defective kMT attachments with a concomitant delay in mitotic progression. Thus we provide mechanistic insight into how Cdt1 affects overall kMT stability in an Aurora B kinase phosphorylation-dependent manner; which is envisioned to augment the MT-binding of the Ndc80 complex.

Hypoxia-induced resistance to tumor treatment restricts further development of photodynamic therapy. Instead of simple reoxygenation to relieve hypoxia in traditional therapeutic approaches, a mitochondria-targeted reactive oxygen species (ROS) amplifier is constructed to reverse hypoxia resistance and enhance tumor sensitivity to hypoxia-resistant photodynamic therapy. Mesoporous silica nanoparticles are modified with triphenylphosphine to enhance its blood circulation and endow it with mitochondria-targeted specificity. α-Tocopherol succinate and indocyanine green are loaded in mitochondria-targeted mesoporous silica nanoparticles to reduce innate oxygen consumption by blocking mitochondrial respiration chain, leading to endogenous mitochondrial ROS burst and imaging-guided photodynamic therapy. This mitochondria-targeted oxidative stress amplifier not only disrupts mitochondrial redox homeostasis and triggers long-term high oxidative stress but also makes tumor more sensitive to hypoxia-resistant photodynamic therapy. The imaging-guided ROS amplifier confirms the feasibility and effectiveness of both in vitro and in vivo anticancer performance, suggesting a promising clinical strategy in hypoxia-related tumor treatment.

Lightweight and thermal insulative cementitious materials with large porous structures for improving energy efficiency have rapid development currently. However, the design of cementitious materials for energy-efficient building system in terms of low thermal conductivity, excellent mechanical properties and lightweight remains a crucial challenge in construction & building fields. Recently, the polymer-based lattice-inspired structures fabricated by 3D printing technology (3DPT) show a rapid development that achieves a balance of thermal and mechanical properties due to their ordered and large-scale cellular architecture. In this work, a novel category of lattice-inspired cementitious lattice materials was first proposed for applying in the energy-efficient building systems by integrating the 3DPT and traditional casting technology. Taking face-centered cubic (FCC) lattice as an example, the advantages of the proposed fabrication technology and FCLMs are follows: (i) ultralight weight; (ii) enhanced ductility of brittle cementitious materials; (iii) low thermal conductivity. Through the structural and material design, the proposed fabrication technology could effectively overcome the current issues of 3DPT, such as the weakness of interlayer performance and low accuracy (Extrusion-based 3DPT) as well as limited feasible materials (Powder-bed-based 3DPT), in the civil engineering. Statement of Significance How to design cementitious materials for energy-efficient building system in terms of thermal conductivity, mechanical properties and lightweight requirement remains a crucial challenge in construction & building fields. Inspired by the low thermal conductivity and lightweight structure of metamaterials in the previous researches (Song et al., Materials & Design, 2019. 173: 107773-86; Nicholas et al. Nano letter, 2018. 18: 4755-61), here a novel category of lattice-inspired cementitious materials with ordered porous structures has been proposed for energy-efficient building materials with lightweight, low thermal conductivity and good mechanical properties characteristics. Additionally, recently there is increased interest to use 3D concrete printing technology (3DCPT) to automatically manufacture complicated and customized structure. However, currently, 3DCPT encounters many sticky issues, involving that (i) weak interlayer performance induced by cold joints between layers; (ii) deformation under self-weight due to the low yield stress of fresh mix; (iii) probable shrinkage under the low water/cement ratios typically used in printed mortars; (iv) geometrical instability owing to creating suspended structures. It is not a trivial to directly print cementitious porous materials, and therefore this work also achieved a breakthrough in developing cementitious porous materials combining advanced SLA 3D printing and traditional casting technology for the first time. It is worth mention that compared to Extrusion-based 3DCPT and Powder-bed-based 3DCPT, the advantages of the manufacture technology include that (i) automatically printing 3D complex structure; (ii) Optional cementitious materials; (iii) Good interlayer performances of prepared materials. We expect that the proposed design idea and novel manufacture strategy could serve as the guideline to develop material-structural-functional integrated energy-efficient building materials combining 3D printing technology, advanced structure design and high-performance cementitious materials.

After 30 years of development, 3D printing technology (3DPT) is becoming increasingly popular in civil engineering field. However, weak interlayer performance and lack of reinforcement significantly limit its application. Nowadays, structural-functional integrated energy-efficient building materials, theoretically requiring a balance of mechanical properties and thermal resistance, are an emerging interdisciplinary research area in civil engineering field. This work proposed a novel digital cement-based manufacture technology by integrating 3D printing technology with casting technology. By incorporating tension-resistant polymeric truss network (PTN), a category of 3D face-centered cubic-inspired cement-based hybrid composites (FCHCs) is proposed. Results show the printed PTN can effectively improve the tension-resistant capacity of cement mortar. The FCHCs not only exhibit a multiple cracking damage characteristic but also a low thermal conductivity compared to traditional cement-based materials. A building energy simulation program was performed to evaluate the effectiveness of FCHCs on the energy savings. It is found that 34% heating energy could be saved for FCHCs building.

TiO 2 -graphene aerogel (TiO 2 -GA) 3D hybrids were directly assembled via a one-pot hydrothermal process followed by freeze-drying without using any structure-directing agent. The hybrids with a hierarchical structure exhibited large surface area (S BET = 283.6 m 2 g −1 ) and high pore volume (V p = 0.278 cm 3 g −1 ), in which the ultradispersed TiO 2 nanoparticles were in a single crystal phase of anatase. When used as the anodes for lithium ion battery, the TiO 2 -GA hybrids exhibited higher reversible capacity, more stable cycling performance and better rate-capability than TiO 2 ascribed to the unique 3D nanoporous structure and the synergistic interaction of GA and TiO 2 .

Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner, leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores. Deletion mapping of Cdt1 revealed that the regions comprising the middle and C-terminal winged-helix domains but lacking the N-terminal unstructured region was required for efficient MT-binding. Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B-phosphomimetic Cdt1 exhibited attenuated MT-binding and its cellular expression induced defective kMT attachments with a concomitant delay in mitotic progression. Thus we provide mechanistic insight into how Cdt1 affects overall kMT stability in an Aurora B kinase phosphorylation-dependent manner; which is envisioned to augment the MT-binding of the Ndc80 complex.eTOC summary• Cdt1 binds to microtubules• The middle and the C-terminal winged-helix domains of Cdt1 are involved in MT-binding• Aurora B Kinase phosphorylates Cdt1 and influences its MT-binding• Aurora B-mediated Cdt1 phosphorylation is necessary for kMT stability and mitotic progression

Ciliogenesis requires the removal of CP110 from the mother centriole; actin dynamics also influence ciliation, at least partly by affecting the centrosomal accumulation of ciliogenic membrane vesicles. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in vertebrates, controlled cilia biogenesis in cultured cells by concomitantly downregulating CP110 and repressing branched F-actin formation. Blocking miR-129-3p inhibited serum-starvation-induced ciliogenesis, whereas its overexpression potently induced ciliation in proliferating cells and also promoted cilia elongation. Gene expression analysis further identified ARP2, TOCA1, ABLIM1 and ABLIM3 as its targets in ciliation-related actin dynamics. Moreover, miR-129-3p inhibition in zebrafish embryos suppressed ciliation in Kupffer's vesicle and the pronephros, and induced developmental abnormalities including a curved body, pericardial oedema and defective left-right asymmetry. Therefore, our results reveal a mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly through microRNA-mediated post-transcriptional regulation.

Nanog, Sox2, and Oct4 are key transcription factors critical for the pluripotency and self-renewal of embryonic stem (ES) cells. Their downregulations lead to differentiation, accompanied with changes in cell motility. Whether these factors impact cell motility directly, however, is not clear. Here we addressed this question by initially assessing their effect in non-stem cells. We found that the ectopic expression of Nanog, Sox2, or Oct4 markedly inhibited ECV304 cell migration. Detailed examinations revealed that Nanog induced disorganizations of the actin cytoskeleton and peripheral localizations of focal adhesions. These effects required its DNA-binding domain and are thus transcription dependent. Furthermore, thymosin β4 and Rnd3 were identified as its downstream targets. Their depletions in ECV304 cells by RNAi phenocopied the ectopic expression of Nanog in both cell motility and actin organization, whereas their ectopic expressions rescued the migration defect of Nanog overexpression. Both proteins were upregulated during mouse ES cell differentiation. Their levels in the pluripotent mouse P19 cells also increased upon Nanog ablation, coincident with an increase in cell motility. Moreover, persistent expression of Nanog in zebrafish embryos suppressed gastrulation and cell migration. These results indeed suggest a dual role of certain transcription factors in the orchestration of differentiation and motility.