Search

Secondary abiotic (SAB) IL-10−/− mice constitute a valuable Campylobacter jejuni-induced enterocolitis model. Given that the host-specific gut microbiota plays a key role in susceptibility of the vertebrate host towards or resistance against enteropathogenic infection, we surveyed immunopathological sequelae of C. jejuni infection in human microbiota associated (hma) and SAB IL-10−/− mice. Following oral challenge, C. jejuni readily colonized the gastrointestinal tract of hma and SAB mice, but with lower numbers in the former versus the latter. Whereas hma mice were clinically less severely compromised, both, macroscopic and microscopic inflammatory sequelae of C. jejuni infection including histopathological and apoptotic cell responses in the colon of IL-10−/− mice were comparably pronounced in the presence and absence of a human gut microbiota at day 6 post-infection. Furthermore, C. jejuni infection of hma and SAB mice resulted in similarly enhanced immune cell responses in the colon and in differential pro-inflammatory mediator secretion in the intestinal tract, which also held true for extra-intestinal including systemic compartments. Notably, C. jeuni infection of hma mice was associated with distinct gut microbiota shifts. In conclusion, hma IL-10−/− mice represent a reliable C. jejuni-induced enterocolitis model to dissect the interactions of the enteropathogen, vertebrate host immunity and human gut microbiota.

The measurement of long noncoding RNAs (lncRNAs) is essential to diagnosis and treatment of various diseases such as cancers. Herein, we develop a simple method to simultaneously detect multiple lncRNAs using programmable ligation-transcription circuit-driven cascade amplification and single-molecule counting. The presence of targets lncRNA HOTAIR and lncRNA MALAT1 activates the ligation-transcription circuits to produce two corresponding functional RNAs. The functional RNAs then cyclically initiate the digestion of signal probes by duplex-specific nuclease to liberate Cy5 and Cy3 molecules. After magnetic separation, the liberated Cy5 and Cy3 molecules are measured by single-molecule counting. In this assay, a single lncRNA can activate ligation-transcription circuit to generate abundant functional RNAs, endowing this assay with high sensitivity. Integration of single-molecule counting ensures the high sensitivity. This method shows extremely high sensitivity with a limit of detection (LOD) of 0.043 aM for HOX gene antisense intergenic RNA (lncRNA HOTAIR) and 0.126 aM for mammalian metastasis-related lung adenocarcinoma transcript 1 (lncRNA MALAT1). Importantly, this method enables simultaneous measurement of multiple endogenous lncRNAs at the single-cell level, and it may discriminate the expressions of various lncRNA in lung tumor tissues of nonsmall cell lung cancer (NSCLC) patients and their corresponding healthy adjacent tissues, offering a promising platform for clinical diagnosis and biomedical research.

Based on image moment theory, an approach for space-variant Shack-Hartmann wavefront reconstruction is presented in this article. The relation between the moment of a pair of subimages and the local transformation coefficients is derived. The square guide 'star' is used to obtain a special solution from this relation. The moment-based wavefront reconstruction has a reduced computational complexity compared to the iteration-based algorithm. Image restorations are executed by the tiling strategy with 5 $\times$ 5 PSFs as well as the conventional strategy with a global average PSF. Visual and quantitative evaluations support our approach., This paper has been accepted for publication in the journal Optics Communications on April 12th, 2023

The occlusion of dentinal tubules has become a rapid and effective method for treating dentin hypersensitivity. Accurate evaluation of dentin occlusion is critical to illustrate the efficacy of oral care products and to optimize dental therapy in the clinics, which is limited by the conventional two-dimensional (2-D) characterization methods. Here, we demonstrate the visualization of the dentin occlusion via three-dimensional (3-D) characterization using a focused ion beam-scanning electron microscopy (FIB-SEM) tomography. Using the “Slice and View” approach, the material used for occluding dentin tubules is imaged with a very high-resolution voxel (10 nm × 10 nm × 20 nm) from 2-D SEM images and then reconstructed into a 3-D volume, which presents the mode of action of toothpaste for treating dentin hypersensitivity. Meanwhile, quantitative analysis of the depth of occlusion is successfully obtained. This work validates the feasibility of FIB-SEM tomography in the analysis of dentin occlusion within the complicated networks of dentine tubules at the nanoscale, and provides a novel approach to facilitate the research and development of oral care products.

Apoferritin can act as a scaffold for functionalization in the inner and outer surfaces. However, traditional covalent modification methods have a risk of disrupting the structure and physicochemical properties of apoferritin. Herein, we report a method for designing versatile apoferritin-based nanosystems through noncovalent interaction between a PEGylated [FeFe]-hydrogenase mimic (FeFe-PEG-N

Mitochondrial oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). Recently, antioxidant therapy has been considered an effective strategy for the treatment of AD. Our previous work discovered that rhein relieved mitochondrial oxidative stress in β-amyloid (Aβ) oligomer-induced primary neurons by improving the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha- (PGC-1α-) regulated mitochondrial biogenesis. While encouraging results have been provided, mechanisms underlying the beneficial effect of rhein on AD are yet to be elucidated in vivo. In this study, we evaluated the therapeutic effect of rhein on an APP/PS1 transgenic (APP/PS1) mouse model of AD and explored its antioxidant mechanisms. As a result, rhein significantly reduced Aβ burden and neuroinflammation and eventually ameliorated cognitive impairment in APP/PS1 mice. Moreover, rhein reversed oxidative stress in the brain of APP/PS1 mice and protected neurons from oxidative stress-associated apoptosis. Further study revealed that rhein promoted mitochondrial biogenesis against oxidative stress by upregulating SIRT1 and its downstream PGC-1α as well as nuclear respiratory factor 1. Improved mitochondrial biogenesis not only increased the activity of superoxide dismutase to scavenge excess reactive oxygen species (ROS) but also repaired mitochondria by mitochondrial fusion to inhibit the production of ROS from the electron transport chain. Notably, the exposure of rhein in the brain analyzed by tissue distribution study indicated that rhein could permeate into the brain to exert its therapeutic effects. In conclusion, these findings drive rhein to serve as a promising therapeutic antioxidant for the treatment of AD. Our research highlights the therapeutic efficacy for AD through regulating mitochondrial biogenesis via the SIRT1/PGC-1α pathway.

TTE is used to regulate the Li+-solvation sheath structure in the low-concentration electrolyte (LCE). This work demonstrates the decisive role of Li+-solvation sheath structure in stabilizing the interfaces between the LCEs and cathodes.

We design mismatched fluorescent probes to directly monitor the long noncoding RNA (lncRNA) in living cells. The introduction of mismatched bases in the fluorescent probe greatly enhances the strand displacement reaction rate toward the target lncRNA. These mismatched probes can monitor the intracellular lncRNA expression level in various cell lines and discriminate cancer cells from normal cells, holding great potential in fundamental biomedical research and clinical disease diagnosis.

Herein, the introduction of hexagonal LaNiO3 on the surface of LiNi0.8Co0.15Al0.05O2 provides a protective and adaptable ultrathin layer to stabilize the microstructure of Ni-rich layered cathode materials, enhancing the electrochemical and thermal stability.

Efficient separation of blood cells and plasma is key for numerous molecular diagnosis and therapeutics applications. Despite various microfluidics-based separation strategies have been developed, a simple, reliable, and multiplexing separation device that can process a large volume of blood is still missing. Here we show a microbead packed deformable microfluidic system that can efficiently separate highly purified plasma from whole blood as well as retrieve blocked blood cells from the device. Combining microscope imaging, optical tomography scanning, and computational fluidic modeling, a highly accurate model is constructed to understand the link between the mechanical properties of the microfluidics, flow rate, and microbeads packing/leaking, which supports and rationalizes the experimental observations. This deformable nano-sieve device establishes a key technology for centrifuge-free diagnosis and treatment of bloodborne diseases and may be important for the design of next-generation deformable microfluidics for separation applications.

The transport, distribution, and mixing of microfluidics often require additional instruments, such as pumps and valves, which are not feasible when operated in point-of-care (POC) settings. Here, we present a simple microfluidic pathogen detection system known as Rotation-Chip that transfers the reagents between wells by manually rotating two concentric layers without using external instruments. The Rotation-Chip is fabricated by a simple computer numerical control (CNC) machining process and is capable of carrying out 60 multiplexed reactions with a simple 30-degree or 60-degree rotation. Leveraging superhydrophobic coating, a high fluid transport efficiency of 92.78% is achieved without observable leaking. Integrated with an intracellular fluorescent assay, an on-chip detection limit of 1.8×106CFU/mL is achieved for ampicillin-resistantEscherichia coli (E. coli), which is similar to our off-chip results. We also develop a computer vision method to automatically distinguish positive and negative samples on the chip, showing 100% accuracy. Our Rotation-Chip is simple, low-cost, high-throughput, and can display test results with a single chip image, ideal for various multiplexing POC applications in resource-limited settings.

An O3 type Li0.6[Li0.2Mn0.8]O2 lithium-rich material has a high reversible capacity due to the synergistic oxidation and reduction of anion and cation. However, the anion oxidation reaction that compensates the charge leads to a partial release of oxygen and the collapse of the structure inevitably. Here, we improve the structural stability of Li0.6[Li0.2Mn0.8]O2 by simultaneously introducing Al ions and B ions. Al ions and B ions randomly occupy octahedral and tetrahedral positions, hindering the migration of Mn ions and expanding the unit cell, resulting in a stable structure and promoting Li+ migration. The co-doped sample has better electrochemical performance than the bare material, and the capacity retention increases from 62.48% to 82.48% after 80 cycles at 0.1C rate, and still provides a capacity of 226 mAh g−1 between 2 and 4.8 V.

Temozolomide (TMZ) is a prodrug of 5-(3-methyltriazene-1-yl)imidazole-4-carboxamide (MTIC, short-lived) and used as a first-line therapy drug for glioblastoma multiforme (GBM). However, little progress has been made in regulating the kinetics of TMZ to MTIC degradation to improve the therapeutic effect, particularly in the case of TMZ-resistant GBM. In this work, we introduced a strategy to cage MTIC by N-acylation of the triazene moiety to boost the MTIC stability, designed a diblock copolymer-based MTIC prodrug installed with a disulfide linkage, and achieved self-assembled polymer micelles without the concern of MTIC leakage under physiological conditions. Polymer micelles could be induced to disassemble by stimuli factors such as glutathione (GSH) and visible light irradiation through thiol/sulfide exchange and homolytic sulfide scission mechanisms, which contributed to MTIC release in GSH-dependent and GSH-independent pathways. The in vitro results demonstrated that microenvironment-responsive polymeric micelles benefited the suppression of both TMZ-sensitive and TMZ-resistant GBM cells. The chemistry of polymer-MTIC prodrug provided a new option for TMZ-based glioma treatment.

LiMn2 O4 (LMO) cathodes suffer from limited cycle life, resulting from Mn dissolution and side reactions between electrode and electrolyte. In this study, Sr-modified LMO is prepared by using a simple strategy. The nature and position of large-radius Sr ions are investigated, alongside their influence on the structural stability of the bulk. SrMnO3 (SMO) is found to be enriched at grain boundaries of LMO, with Mn-O-Sr bonds forming at the SMO/LMO interface. Furthermore, stable SMO alleviates the migration of Mn ions in LMO associated with structural integrity and suppresses side reactions between the electrode and electrolyte. The modified LMO cathodes maintain their structural integrity and display improved rate performance and cycling stability under harsh conditions. Remarkably, the discharge capacity of a Sr-modified LMO||Li half-cell maintains 94.8 % at 25 °C and 79.6 % at 55 °C after 500 cycles. Consequently, enrichment of strontium at grain boundaries presents a promising strategy for developing cathodes for long-term use.

Floor systems constructed from slabs and beams are critical structural elements of reinforced concrete (RC) frame structures, allowing them to resist progressive collapse. To elucidate the complex effects of the slab and its thickness on the progressive-collapse resistance of RC spatial frame structures, three 1/3-scale 2 × 2 span substructure specimens, including one three-dimensional (3D) skeletal frame substructure and two 3D frame–slab substructures with different slab thicknesses, were tested in a middle-column-removal scenario. The test results indicated that the frame–slab substructure exhibited two resisting progressive-collapse stages: a primary mechanism stage, with small deformations, and a secondary mechanism stage, with large deformations. The slab contributions were separated from the floor system and quantified by comparing the results for the skeletal frame substructure and frame–slab substructure. Although there were no in-plane confinements, the slab also significantly improved the resistance against progressive collapse, owing to the compressive and tensile membrane action in the primary and secondary mechanism stages, respectively. Increasing the slab thickness increased the compressive membrane action of the slab, which significantly enhanced the progressive-collapse resistance under small deformations. However, under large deformations, the beam and slab did not work synergistically, which limited the development of secondary mechanisms against progressive collapse.

The copper/graphene (Cu/Gr) composites made of Gr/Cu/Gr foils with a thickness of 25 μm were prepared using spark plasma sintering diffusion bonding (SPS) and hot press diffusion bonding (HP) in an Ar atmosphere at 900 °C for 20 min under a pressure of 50 MPa. The electrical conductivity of the prepared Cu/Gr composites was measured by the van der Pauw method, the microstructure was characterized using Raman spectroscopy, scanning electron microscope and transmission electron microscope, and the corresponding mechanism was analyzed by employing the first-principles calculations. The result indicates that, SPS process reduces the interfacial impurities of Cu/Gr composites, rendering a much higher electrical conductivity (108.6% IACS) than that prepared by using HP (98.8% IACS). This finding is correlated to the reduced oxygen (O) impurities on Gr/Gr interface, which is attributed to the high temperature plasma sputtering effect of SPS. In the prepared Cu/Gr composites, the impurity-free Gr/Gr interface has an ideal spacing of ∼3.3 A wherein carbon (C) across the interface do not bond. Despite the generated C–C covalent bonding within the same Gr layer bounds some of the electrons, the remaining electrons of the p orbital on each C atom are free electrons, leading to the excellent electrical conductivity. In contrast, absorption of O impurities on the Gr/Gr interface increases the spacing between the Gr layers to ∼3.8 A, and generates covalent C–O–C bonding across the interface due to p orbital hybridization. This reduces the free electron concentration and the corresponding electrical conductivity.

The global outbreak of the monkeypox virus (MPXV) highlights the need for rapid and cost-effective MPXV detection tools to effectively monitor and control the monkeypox disease. Herein, we demonstrated a portable CRISPR-Cas-based system for naked-eye detection of MPXV. The system harnesses the high selectivity of CRISPR-Cas12 and the isothermal nucleic acid amplification potential of recombinase polymerase amplification. It can detect both the current circulating MPXV clade and the original clades. We reached a limit of detection (LoD) of 22.4 aM (13.5 copies/µl) using a microtiter plate reader, while the visual LoD of the system is 75 aM (45 copies/µl) in a two-step assay, which is further reduced to 25 aM (15 copies/µl) in a one-pot system. We compared our results with quantitative polymerase chain reaction and obtained satisfactory consistency. For clinical application, we demonstrated a sensitive and precise visual detection method with attomolar sensitivity and a sample-to-answer time of 35 min.