Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in ...terms of cavity shape and functional group decoration. We report a series of heteroleptic Pd2A2B2 coordination cages that self‐assemble from a library of shape complementary bis‐monodentate ligands in a non‐statistical fashion. Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All‐atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities.
A series of heteroleptic Pd2A2B2 coordination cages was prepared by shape‐complementary assembly (SCA) from a modular set of ligands and screened for binding phosphate guests. All‐atom molecular dynamics simulations reveal that an endohedral hydrogen bond donor site is the decisive but not exclusive factor for binding phosphate diesters inside the cavity in a competitive solvent.
Integrated optics provides a versatile platform for quantum information processing and transceiving with photons1–8. The implementation of quantum protocols requires the capability to generate ...multiple high-quality single photons and process photons with multiple high-fidelity operators9–11. However, previous experimental demonstrations were faced by major challenges in realizing sufficiently high-quality multi-photon sources and multi-qubit operators in a single integrated system4–8, and fully chip-based implementations of multi-qubit quantum tasks remain a significant challenge1–3. Here, we report the demonstration of chip-to-chip quantum teleportation and genuine multipartite entanglement, the core functionalities in quantum technologies, on silicon-photonic circuitry. Four single photons with high purity and indistinguishablity are produced in an array of microresonator sources, without requiring any spectral filtering. Up to four qubits are processed in a reprogrammable linear-optic quantum circuit that facilitates Bell projection and fusion operation. The generation, processing, transceiving and measurement of multi-photon multi-qubit states are all achieved in micrometre-scale silicon chips, fabricated by the complementary metal–oxide–semiconductor process. Our work lays the groundwork for large-scale integrated photonic quantum technologies for communications and computations.Four single-photon states are generated and entangled on a single micrometre-scale silicon chip, and provide the basis for the demonstration of chip-to-chip quantum teleportation.
The influence of the microstructure on mechanical properties of AlSi10Mg fabricated by casting and selective laser melting (SLM) were investigated and contrasted in this work, with an emphasis on ...understanding the forming mechanism. The microstructure, phase structure and mechanical properties were characterized by scanning electron microscopy/field-emission Transmission Electron Microscopy (SEM/TEM), X-Ray Diffraction (XRD), tensile and fatigue tests. The results indicated that the SLM AlSi10Mg exhibited a supersaturated Si network structure precipitated along α-Al cell. Brittle β-Al5FeSi and π-Al8FeMg3Si6 phases were found in the as-cast and SLM AlSi10Mg respectively due to different thermal histories during processing. The SLM AlSi10Mg showed higher tensile strength but lower elongation than the casting, as the result of grain refinement and tortuous crack path. The fatigue results revealed that unmelted powder, oxide inclusion and pores can considerably degrade the fatigue properties for the SLM AlSi10Mg. The SLM process offered a new method for material processing that would avoid harmful Fe-bearing intermetallic compounds and refine the microstructures for enhancing strength.
Scab, frogeye spot, and cedar rust are three common types of apple leaf diseases, and the rapid diagnosis and accurate identification of them play an important role in the development of apple ...production. In this work, an improved model based on VGG16 is proposed to identify apple leaf diseases, in which the global average poling layer is used to replace the fully connected layer to reduce the parameters and a batch normalization layer is added to improve the convergence speed. A transfer learning strategy is used to avoid a long training time. The experimental results show that the overall accuracy of apple leaf classification based on the proposed model can reach 99.01%. Compared with the classical VGG16, the model parameters are reduced by 89%, the recognition accuracy is improved by 6.3%, and the training time is reduced to 0.56% of that of the original model. Therefore, the deep convolutional neural network model proposed in this work provides a better solution for the identification of apple leaf diseases with higher accuracy and a faster convergence speed.
Chinese chives is a popular herb vegetable and medicine in Asian countries. Southwest China is one of the centers of origin, and the mountainous areas in this region are rich in wild germplasm. In ...this study, we collected four samples of germplasm from different altitudes: a land race of cultivated Chinese chives (Allium tuberosum), wide-leaf chives and extra-wide-leaf chives (Allium hookeri), and ovoid-leaf chives (Allium funckiaefolium). Leaf metabolites were detected and compared between A. tuberosum and A. hookeri. A total of 158 differentially accumulated metabolites (DAM) were identified by Gas Chromatography—Mass Spectrometry (GC-MS) and Liquid Chromatography—Mass Spectrometry (LC-MS), among which there was a wide range of garlic odor compounds, free amino acids, and sugars. A. hookeri contains a higher content of fructose, garlic odor compounds, and amino acids than A. tuberosum, which is supported by the higher expression level of biosynthetic genes revealed by transcriptome analysis. A. hookeri accumulates the same garlic odor compound precursors that A. tuberosum does (mainly methiin and alliin). We isolated full-length gene sequences of phytochelatin synthase (PCS), γ-glutamyltranspeptidases (GGT), flavin-containing monooxygenase (FMO), and alliinase (ALN). These sequences showed closer relations in phylogenetic analysis between A. hookeri and A. tuberosum (with sequence identities ranging from 86% to 90%) than with Allium cepa or Allium sativum (which had a lower sequence identity ranging from 76% to 88%). Among these assayed genes, ALN, the critical gene controlling the conversion of odorless precursors into odor compounds, was undetected in leaves, bulbs, and roots of A. tuberosum, which could account for its weaker garlic smell. Moreover, we identified a distinct FMO1 gene in extra-wide-leaf A. hookeri that is due to a CDS-deletion and frameshift mutation. These results above reveal the molecular and metabolomic basis of impressive strong odor in wild Chinese chives.
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary ...to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
Neuroinflammation, which ultimately leads to neuronal loss, is considered to play a crucial role in numerous neurodegenerative diseases. The neuroinflammatory process is characterized by the ...activation of glial cells such as microglia. Endoplasmic reticulum (ER) stress is commonly associated with impairments in neuronal function and cognition, but its relationship and role in neurodegeneration is still controversial. Recently, it was confirmed that nonharmful levels of ER stress protected against experimental Parkinson's disease. Here, we investigated mild ER stress-based regulation of lipopolysaccharide (LPS)-driven neuroinflammation in rats and in primary microglia.
Male Sprague-Dawley (SD) rats received the intracerebroventricular injection of the ER stress activator tunicamycin (TM) with or without intraperitoneal injection of the ER stress stabilizer sodium 4-phenylbutyrate (4-PBA) 1 h before LPS administration. The levels of neuroinflammation and memory dysfunction were assessed 24 h after treatment. In addition, the effect of mild ER stress on microglia was determined in vitro.
Here, we found that low doses of TM led to mild ER stress without cell or organism lethality. We showed that mild ER stress preconditioning reduced microglia activation and neuronal death as well as improved LPS-induced memory impairment in rats. In addition, pre-exposure to nonlethal doses of TM in microglia showed significant protection against LPS-induced proinflammatory cytokine production and M1/2b polarization. However, sodium 4-PBA, a compound that ameliorates ER stress, ablated this protective effect in vivo and in vitro.
Based on our findings, we conclude that the mild ER stress not only limits the accumulation of misfolded proteins but also protects tissues from harmful endotoxemia insults. Therefore, ER stress preconditioning has potential therapeutic value for the treatment of neurodegenerative diseases.
The optofluidic laser has become an important platform for biological sensing and medical diagnosis. To date, fluorescent dyes and proteins have been widely utilized as gain materials for biological ...analysis due to their good biocompatibility, but the limited photostability restricts their reliability and sensitivity. Here, an optofluidic microlaser with an ultralow threshold down to 7.8 µJ cm−2 in the ultrahigh‐Q whispering‐gallery microcavity, which is filled with a biocompatible conjugated polymer, is demonstrated. This conjugated polymer exhibits a significant enhancement in the lasing stability compared with a typical laser dye (Nile red). In the experiment, after 20 min of illumination with the excitation intensity of 23.2 MW cm−2, the lasing intensity of the conjugated polymer experiences a decrease of less than 10%, while the lasing feature of Nile red completely disappears. Additionally, by mechanically stretching the resonator, the lasing frequency can be fine‐tuned with the range of about 2 nm, exceeding the free spectral range of the resonator.
Tunable optofluidic microlasers with an ultralow threshold down to 7.8 μJ cm−2 are demonstrated in an ultrahigh‐Q whispering‐gallery microcavity filled with a biocompatible conjugated polymer. Compared with typical laser dyes, the conjugated polymer exhibits a significant enhancement in lasing stability. This low‐threshold laser with excellent photostability could find widespread use in aqueous environments for biological sensing and medical diagnosis.
Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the ...expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC).
KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model.
KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.
These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.
Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, ...such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.
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