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.
Designer DNA nanosponges relieve hypoxia‐associated resistance and enhance photodynamic therapy (PDT). The facile assembly process, robust in vitro and in vivo therapeutic efficacy, and good biosafety demonstrate a practical platform of PDT for biomedical applications. This approach also suggests that DNA nanotechnology has great potential for advanced therapeutics.
In wireless sensor networks, energy saving is a crucial aspect. To address the issue of declining network energy consumption, we propose a clustering algorithm based on data sensing and a similarity ...clustering collection strategy. In the clustering process, we consider node similarity, residual energy, and define two weighting functions for incoming and competing cluster heads. In the node similarity measurement, we define two improved similarity judgment models to complement each other, and propose the corresponding data estimation methods. In the data collection process, we propose a data collection strategy based on representative (R) nodes. In this strategy, we use length-compressed coding, and improve the sleep scheduling algorithm to achieve the effect of adaptively changing the spatial sampling rate. In order to evaluate the effectiveness of our proposed strategy, we conduct experiments comparing it with more advanced energy-saving algorithms in four key performance parameters: data reduction ratio, data accuracy, network lifetime and network energy consumption. The results demonstrate that our proposed energy-saving algorithm can effectively eliminate data redundancy and extend network lifetime.
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.
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.
The dynamics of medical resource demand during public health crises pose significant challenges to emergency supply chain management, particularly within an evolving and complex social environment. ...To explore this, the interactive effects of information diffusion and virus spreading on medical resource demand are investigated using a novel three-layer coevolution “information–epidemic–resource” model through Markov process simulations. The study firstly identifies eight factors influencing demand fluctuations in terms of some city characteristics, such as media exposure, consistency of public opinion, self-protection level, and restrictive protection level, while categorizing resources into individual holdings and centralized storage. Then, extensive simulations are examined to elucidate the impact of these factors. The results reveal that various city characteristics can affect fluctuation in demand for both individual holdings and centralized storage. Inaccurate media information tends to inflate fluctuations, while higher public opinion consistency can reduce it. Reinforcing self-protection decreases the demand fluctuations of individuals, and effective restrictive protections can reduce fluctuations in centralized resource storage. Moreover, an analytical simulation of various city scenarios, underpinned by statistical data from selected Chinese and German cities, demonstrates that distinct city characteristics significantly influence medical resource demand changes during epidemics. This underscores the importance of tailoring emergency medical supply strategies to the specific developmental traits of different countries and cities. This study provides valuable insights to researchers, governments, and enterprises, enhancing their preparedness and response for emergency supply chain disruptions.
Achieving complete and precise genome duplication requires that each genomic segment be replicated only once per cell division cycle. Protecting large eukaryotic genomes from re-replication requires ...an overlapping set of molecular mechanisms that prevent the first DNA replication step, the DNA loading of MCM helicase complexes to license replication origins, after S phase begins. Previous reports have defined many such origin licensing inhibition mechanisms, but the temporal relationships among them are not clear, particularly with respect to preventing re-replication in G2 and M phases. Using a combination of mutagenesis, biochemistry, and single cell analyses in human cells, we define a new mechanism that prevents re-replication through hyperphosphorylation of the essential MCM loading protein, Cdt1. We demonstrate that Cyclin A/CDK1 can hyperphosphorylate Cdt1 to inhibit MCM re-loading in G2 phase. The mechanism of inhibition is to block Cdt1 binding to MCM independently of other known Cdt1 inactivation mechanisms such as Cdt1 degradation during S phase or Geminin binding. Moreover, our findings suggest that Cdt1 dephosphorylation at the mitosis-to-G1 phase transition re-activates Cdt1. We propose that multiple distinct, non-redundant licensing inhibition mechanisms act in a series of sequential relays through each cell cycle phase to ensure precise genome duplication.
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.
In order to control the epidemic and complete the supervision of increasing population, we devised a kind of face detection system. This system detected face with MTCNN and then it detect whether the ...person wears the mask with MobileNet. Also we added non-standardized samples in the model training so that it can detect pedestrians who are not properly worn. The experimental results showed that the system can effectively identify the wearing of masks.
Cdc42GAP promotes inactivation of Cdc42, a small GTPase whose activation at the leading edge by guanine nucleotide exchange factors is critical for cell migration. How Cdc42GAP is regulated to ensure ...proper levels of active Cdc42 is poorly understood. Here we show that Nudel, a cytoplasmic dynein regulator, competes with Cdc42 for binding Cdc42GAP. Consequently, Nudel can inhibit Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Both Nudel and Cdc42GAP exhibit leading-edge localization in migrating cells. The localization of Nudel requires its phosphorylation by Erk1/2. Depleting Nudel by RNAi or overexpression of a nonphosphorylatable mutant abolishes Cdc42 activation and cell migration. Our data thus uncover Nudel as a regulator of Cdc42 during cell migration. Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel.
WSNs have various uses across numerous industries and are one of the essential technologies of modern life. Energy consumption is the issue that has drawn the greatest attention and still has to be ...resolved because the nodes that comprise WSNs have a limited amount of energy. Numerous factors influence energy consumption, and our algorithm design considerations are centered on extending the network lifetime and energy efficiency through the resolution of imbalance and hotspot issues related to WSNs clustering. Because of this, we suggest a partitioned uneven cluster routing algorithm based on gray wolf optimization. To find the ideal cluster head, we first divide the network into areas with distinct important influence factors, then we improve the final cluster head election function and the candidate cluster head competition radius. Subsequently, to reduce the energy consumption resulting from multiple rounds of clustering, similarity determination is introduced. Finally, the optimal transmission path in the multi-hop process is obtained by combining the Gray Wolf optimization algorithm with the relay node selection function. Simulation results show that the network lifetime of the proposed algorithm is extended by 54.6 %, 46.2 %, 58.6 %, and 18.5 % compared to LEACH, DEBUC, LEACH-EDP, and LEACH-IM, respectively. The energy efficiency of the proposed algorithm is extended by 40.8 %, 7.1 %, 22.7 %, and 34.0 %, respectively. The proposed algorithm significantly extends the network lifetime and improves the energy efficiency of the network.
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