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To realize RNA interference (RNAi) therapeutics, it is necessary to deliver therapeutic RNAs (such as small interfering RNA or siRNA) into cell cytoplasm. A major challenge of RNAi therapeutics is the endosomal entrapment of the delivered siRNA. In this study, we developed a family of delivery vehicles called Janus base nanopieces (NPs). They are rod-shaped nanoparticles formed by bundles of Janus base nanotubes (JBNTs) with RNA cargoes incorporated inside via charge interactions. JBNTs are formed by noncovalent interactions of small molecules consisting of a base component mimicking DNA bases and an amino acid side chain. NPs presented many advantages over conventional delivery materials. NPs efficiently entered cells via macropinocytosis similar to lipid nanoparticles while presenting much better endosomal escape ability than lipid nanoparticles; NPs escaped from endosomes via a “proton sponge” effect similar to cationic polymers while presenting significant lower cytotoxicity compared to polymers and lipids due to their noncovalent structures and DNA-mimicking chemistry. In a proof-of-concept experiment, we have shown that NPs are promising candidates for antiviral delivery applications, which may be used for conditions such as COVID-19 in the future.

Over the last two decades, lipid nanoparticles (LNPs) have evolved as an effective biocompatible and biodegradable RNA delivery platform in the fields of nanomedicine, biotechnology, and drug delivery. They are novel bionanomaterials that can be used to encapsulate a wide range of biomolecules, such as mRNA, as demonstrated by the current successes of COVID‐19 mRNA vaccines. Therefore, it is important to provide a perspective on LNPs for RNA delivery, which further offers useful guidance for researchers who want to work in the RNA‐based LNP field. This perspective first summarizes the approaches for the preparation of LNPs, followed by the introduction of the key characterization parameters. Then, the in vitro cell experiments to study LNP performance, including cell selection, cell viability, cellular association/uptake, endosomal escape, and their efficacy, were summarized. Finally, the in vivo animal experiments in the aspects of animal selection, administration, dosing and safety, and their therapeutic efficacy were discussed. The authors hope this perspective can offer valuable guidance to researchers who enter the field of RNA‐based LNPs and help them understand the crucial parameters that RNA‐based LNPs demand. This perspective summarizes the approaches for the preparation of lipid nanoparticles (LNPs), the key characterization parameters, in vitro cell experiments, and in vivo animal experiments. The authors hope this perspective can offer valuable guidance to researchers who enter the field of RNA‐based LNPs and help them understand the crucial parameters that RNA‐based LNPs demand.

As China’s first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight -HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.

Fungi represent an important source of bioactive secondary metabolites (SMs), which have wide applications in many fields, including medicine, agriculture, human health, and many other industries. The genes involved in SM biosynthesis are usually clustered adjacent to each other into a region known as a biosynthetic gene cluster (BGC). The recent advent of a diversity of genetic and genomic technologies has facilitated the identification of many cryptic or uncharacterized BGCs and their associated SMs. However, there are still many challenges that hamper the broader exploration of industrially important secondary metabolites. The recent advanced CRISPR/Cas system has revolutionized fungal genetic engineering and enabled the discovery of novel bioactive compounds. In this review, we firstly introduce fungal BGCs and their relationships with associated SMs, followed by a brief summary of the conventional strategies for fungal genetic engineering. Next, we introduce a range of state-of-the-art CRISPR/Cas-based tools that have been developed and review recent applications of these methods in fungi for research on the biosynthesis of SMs. Finally, the challenges and limitations of these CRISPR/Cas-based systems are discussed and directions for future research are proposed in order to expand their applications and improve efficiency for fungal genetic engineering.

BackgroundCaliche nodules, the product of the leaching and deposition of calcium carbonate in the soil, are widely distributed in loessial profiles on the Loess Plateau in China. Their presence leads to complex interactions between plant roots and the soil.Aims and MethodsWe studied the interactions between caliche-nodule and water content and their effects on the biomass, morphology and vertical distribution of roots of Caragana (Caragana korshinskii Kom.) for two years using a soil-column experiment. Four root parameters (biomass, diameter, length density and surface-area density) in various diameter classes were compared and analyzed.ResultsWater and caliche-nodule contents significantly affected root biomass and morphology. Both coarse- and fine-root biomasses were highest at a nodule content of 30%, did not differ significantly from those in fine earth (nodule-free) but were significantly higher than at the other two nodule contents. The nodules affected fine-root biomass when water content was <60% of field capacity. Higher water content corresponded to higher biomass. Roots become thick and short in loess containing nodules. High contents of nodules (50%) negatively affected root biomass at every depth and caused larger percentage of fine roots to concentrate in the shallower layers.ConclusionOur results demonstrate that plants growing in the loess containing caliche nodules show some degree of adaptability in root morphology. High nodule content is adverse to accumulation of root biomass. Caliche nodules should be given more consideration when investigating the dynamics and habits of plant growth on the Loess Plateau.

Unique membrane structures endow membranes with controlled ion transport properties in both biological and artificial systems, and they have shown broad application prospects from industrial production to biological interfaces. Herein, current advances in nanochannel‐structured membranes for manipulating ion transport are reviewed from the perspective of membrane structures. First, the controllability of ion transport through ion selectivity, ion gating, ion rectification, and ion storage is introduced. Second, nanochannel‐structured membranes are highlighted according to the nanochannel dimensions, including single‐dimensional nanochannels (i.e., 1D, 2D, and 3D) functioning by the controllable geometrical parameters of 1D nanochannels, the adjustable interlayer spacing of 2D nanochannels, and the interconnected ion diffusion pathways of 3D nanochannels, and mixed‐dimensional nanochannels (i.e., 1D/1D, 1D/2D, 1D/3D, 2D/2D, 2D/3D, and 3D/3D) tuned through asymmetric factors (e.g., components, geometric parameters, and interface properties). Then, ultrathin membranes with short ion transport distances and sandwich‐like membranes with more delicate nanochannels and combination structures are reviewed, and stimulus‐responsive nanochannels are discussed. Construction methods for nanochannel‐structured membranes are briefly introduced, and a variety of applications of these membranes are summarized. Finally, future perspectives to developing nanochannel‐structured membranes with unique structures (e.g., combinations of external macro/micro/nanostructures and the internal nanochannel arrangement) for mediating ion transport are presented. Unique membrane structures endow membranes with controlled ion transport properties in both biological and artificial systems, showing broad application prospects in different fields. In this review, current advances in nanochannel‐structured membranes for manipulating ion transport are reviewed from the perspective of membrane structures, followed by a discussion of stimulus responsiveness, construction methods, and applications. Finally, future perspectives for developing membranes with unique structures for mediating ion transport are presented.

Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as proteins, peptides, and nucleic acids. Among them, proteins have shown a series of advantages and potential in various therapeutic applications, such as introducing therapeutic proteins due to genetic defects, or used as nanocarriers for anticancer agents to decelerate tumor growth or control metastasis. This review discusses the existing nanoparticle delivery systems, introducing design strategies, advantages of using each system, and possible limitations. Moreover, we will examine the intracellular delivery of different protein therapeutics, such as antibodies, antigens, and gene editing proteins into the host cells to achieve anticancer effects and cancer vaccines. Finally, we explore the current applications of protein delivery in anticancer treatments.

This paper presents a graphene-Au coated photonic crystal fiber (PCF) sensor in the visible regime. Designing a side-polish D-shaped plane over the PCF’s defect of the periodic air holes can effectively enhance the evanescent field. Graphene on gold can enhance the sensor’s sensitivity because it can stably adsorb biomolecules and increase the propagation constant of the surface plasmon polariton (SPP). Using the finite element method (FEM), we demonstrated that the sensing performance is greatly improved by optimizing the PCF’s geometric structural parameter. The proposed PCF sensor exhibited high performance with a maximum wavelength sensitivity of 4200 nm/RIU, maximum amplitude sensitivity of 450 RIU−1, and refractive index resolution of 2.3 × 10−5 RIU in the sensing range 1.32–1.41. This research provides a potential application for the design a new generation of highly sensitive biosensors.

Renal tubular epithelial cells (TECs) can initiate an adaptive response to completely recover from mild acute kidney injury (AKI), whereas severe injury often leads to persistence of maladaptive repair and progression to kidney fibrosis. Through profiling of active DNA regulatory elements by ATAC-seq, we reveal widespread, dynamic changes in the chromatin accessibility of TECs after ischemia–reperfusion injury. We show that injury-specific domains of regulatory chromatin become accessible prior to gene activation, creating poised chromatin states to activate the consequent gene expression program and injury response. We further identify RXRα as a key transcription factor in promoting adaptive repair. Activation of RXRα by bexarotene, an FDA-approved RXRα agonist, restores the chromatin state and gene expression program to protect TECs against severe kidney injury. Together, our findings elucidate a chromatin-mediated mechanism underlying differential responses of TECs to varying injuries and identify RXRα as a therapeutic target of acute kidney injury. Renal tubular epithelial cells (TECs) can initiate an adaptive or maladaptive response after injuries of different severity. Here, the authors elucidate a chromatin-mediated mechanism underlying the responses of TECs to varying kidney injuries.

Inflammation is the common pathogenesis of coronary atherosclerosis disease (CAD) and rheumatoid arthritis (RA). Although it is established that RA increases the risk of CAD, the underlining mechanism remained indefinite. This study seeks to explore the molecular mechanisms of RA linked CAD and identify potential target gene for early prediction of CAD in RA patients. The study utilized five raw datasets: GSE55235, GSE55457, GSE12021 for RA patients, and GSE42148 and GSE20680 for CAD patients. Gene Set Enrichment Analysis (GSEA) was used to investigate common signaling pathways associated with RA and CAD. Then, weighted gene co-expression network analysis (WGCNA) was performed on RA and CAD training datasets to identify gene modules related to single-sample GSEA (ssGSEA) scores. Overlapping module genes and differentially expressed genes (DEGs) were considered as co-susceptible genes for both diseases. Three hub genes were screened using a protein-protein interaction (PPI) network analysis via Cytoscape plug-ins. The signaling pathways, immune infiltration, and transcription factors associated with these hub genes were analyzed to explore the underlying mechanism connecting both diseases. Immunohistochemistry and qRT-PCR were conducted to validate the expression of the key candidate gene, PPARG, in macrophages of synovial tissue and arterial walls from RA and CAD patients. The study found that Fc-gamma receptor-mediated endocytosis is a common signaling pathway for both RA and CAD. A total of 25 genes were screened by WGCNA and DEGs, which are involved in inflammation-related ligand-receptor interactions, cytoskeleton, and endocytosis signaling pathways. The principal component analysis(PCA) and support vector machine (SVM) and receiver-operator characteristic (ROC) analysis demonstrate that 25 DEGs can effectively distinguish RA and CAD groups from normal groups. Three hub genes TUBB2A, FKBP5, and PPARG were further identified by the Cytoscape software. Both FKBP5 and PPARG were downregulated in synovial tissue of RA and upregulated in the peripheral blood of CAD patients and differential mRNAexpreesion between normal and disease groups in both diseases were validated by qRT-PCR.Association of PPARG with monocyte was demonstrated across both training and validation datasets in CAD. PPARG expression is observed in control synovial epithelial cells and foamy macrophages of arterial walls, but was decreased in synovial epithelium of RA patients. Its expression in foamy macrophages of atherosclerotic vascular walls exhibits a positive correlation (r = 0.6276, p = 0.0002) with CD68. Our findings suggest that PPARG may serve as a potentially predictive marker for CAD in RA patients, which provides new insights into the molecular mechanism underling RA linked CAD.