The emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system (Cas) gene-editing system represents a promising tool for genome manipulation. However, its low ...intracellular delivery efficiency severely compromises its use and potency for clinical applications. Nanocarriers, such as liposomes, polymers, and inorganic nanoparticles, have shown great potential for gene delivery. The remarkable development of nanoparticles as non-viral carriers for the delivery of the CRISPR/Cas9 system has shown great promise for therapeutic applications. In this review, we briefly summarize the delivery components of the CRISPR/Cas9 system and report on the progress of nano-system development for CRISPR/Cas9 delivery. We also compare the advantages of various nano-delivery systems and their applications to deliver CRISPR/Cas9 for disease treatment. Nano-delivery systems can be modified to fulfill the tasks of targeting cells or tissues. We primarily emphasize the novel exosome-based CRISPR/Cas9 delivery system. Overall, we review the challenges, development trends, and application prospects of nanoparticle-based technology for CRISPR/Cas9 delivery.
Articular cartilage repair is a critical issue in osteoarthritis (OA) treatment. The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. IGF-1 is a ...member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. Here, we reviewed the role of IGF-1 in cartilage anabolism and catabolism. Moreover, we discussed the potential role of IGF-1 in OA treatment. Of note, we summarized the recent progress on IGF delivery systems. Optimization of IGF delivery systems will facilitate treatment application in cartilage repair and improve OA treatment efficacy.
We point out that the largest private shareholders can use their information advantage of the industry to influence banks’ industry lending behavior. Using a sample of Chinese city commercial banks, ...we find that increasing of ownership stake of the largest private shareholders leads banks to lend more to their industries. Interestingly, the largest state-owned shareholders do not have this effect. More importantly, we confirmed the channel of the information advantage by analyzing the bank’s industry NPL ratio and the listed company’s maximum loan amount in the bank. Of course, the effect of the largest private shareholders is achieved by intervening in board decisions. In addition, the ownership structure can influence this effect.
Nutrient additions can stimulate petroleum hydrocarbon degradation, but little is known about how these additions affect the microbial community involved in that degradation. A microcosm study was ...conducted to assess the impact of bioaugmentation with Acinetobacter SZ-1 strain KF453955 and biostimulation with nutrients nitrogen and phosphorus on petroleum hydrocarbon degradation efficiency and microbial community dynamics during bioremediation of an oil-contaminated soil. Soils were incubated without shaking at room temperature for 10 weeks, and petroleum hydrocarbon degradation efficiency, catalase activity, petroleum hydrocarbon degrader population, and bacterial community diversity were determined. Results showed biostimulation and bioaugmentation, respectively, promoted 60% and 34% degradation of the total petroleum hydrocarbons (TPH) after six weeks of incubation. A degradation plateau occurred in the seventh week. Catalase activity and the populations of oil degraders in soil were generally greater for biostimulation than for bioaugmentation. The inoculants survived into the seventh week for the bioaugmentation treatment, and bacterial diversity did not increase by biostimulation. The populations of TPH-degraders in soil were positively related to TPH degradation efficiency during bioremediation of petroleum-polluted soils.
•Biostimulation and bioaugmentation achieved 60% and 34% oil hydrocarbon degradation.•Degradation plateau occurred in the seventh week.•Biostimulation with nitrogen and phosphorus enhanced microbial growth and activity.•The inoculants, Acinetobacter SZ-1 strain KF453955, survived in oil-polluted soil.
Traditional culture methods may underestimate the tolerance of microorganisms to disinfectants because of the existence of viable but nonculturable or sublethally injured cells after disinfection. ...The selection of a strict method is crucial for the evaluation of disinfection performance. The actions of 2 typical disinfectants – ultraviolet (UV) and chlorine – on the fecal indicator Escherichia coli were investigated by the detection of culturability, membrane permeability, metabolic activity, deoxyribonucleic acid (DNA), and messenger ribonucleic acid (mRNA). During UV disinfection, the irreversible damages in the cell membrane and cellular adenosine triphosphate (ATP) were negligible at low UV doses (<80mJ/cm2). However, membrane permeability was damaged at low doses of chlorine (<5mg/L), leading to leakage of cellular ATP. Our study showed that a slight lesion in DNA was detected even at high doses of UV (400mJ/cm2) and chlorine (>5mg/L) treatments. The decay of mRNA was more rapid than that of DNA. The degradation level of mRNA depended on the choice of target genes. After exposure to 50mJ/cm2 UV dose or 5mg/L chlorine for 30min, the DNA damage repair function (RecA mRNA) was inhibited. The mRNA involved in the DNA damage repair function can be a potential indicator of bacterial viability.
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The dynamics of glass-forming systems shows a multitude of features that are absent in normal liquids, such as non-exponential relaxation and a strong temperature-dependence of the relaxation time. ...Connecting these dynamic properties to the microscopic structure of the system is challenging because of the presence of the structural disorder. Here we use computer simulations of a metallic glass-former to establish such a connection. By probing the temperature and wave-vector dependence of the intermediate scattering function we find that the relaxation dynamics of the glassy melt is directly related to the local arrangement of icosahedral structures: Isolated icosahedra give rise to a liquid-like stretched exponential relaxation whereas clusters of icosahedra lead to a compressed exponential relaxation that is reminiscent to the one found in a solid. Our results show that in metallic glass-formers these two types of relaxation processes can coexist and give rise to a dynamics that is surprisingly complex.
The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure ...resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.
•We provide the first proteomic analysis of DIV1.•Thirty viral structural proteins are identified by one-dimension electrophoresis coupled with LC-MS/MS.•Twenty-three of the structural proteins are ...confirmed by Western blotting.
Decapod iridescent virus 1 (DIV1) is one of the major pathogens of farmed shrimp. In this study, the structural proteins of DIV1 were analyzed by mass spectrometry. DIV1 virions were purified from the hemolymph of artificially infected Cherax quadricarinatus. The viral proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a total of 28 protein bands were obtained. These protein bands were in-gel digested with trypsin and the resulting tryptic peptide mixtures were subjected to liquid chromatography with tandem mass spectrometry analysis. Thirty virus-encoded proteins were identified. Among them, 6 proteins were predicted to contain transmembrane domains, 3 proteins were predicted to contain an Arg-Gly-Asp motif. Nine proteins showed significant homology with functionally characterized proteins. Antibodies were produced for these candidate proteins and 23 of them were confirmed to be the components of DIV1 virions by Western blotting. This study provides the first proteomic analysis of DIV1, which establishes a foundation for further investigation of viral infection and replication.
Abstract
Despite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main ...types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.
Scanning probe microscopy has been extensively applied to probe interfacial water in many interdisciplinary fields but the disturbance of the probes on the hydrogen-bonding structure of water has ...remained an intractable problem. Here, we report submolecular-resolution imaging of the water clusters on a NaCl(001) surface within the nearly noninvasive region by a qPlus-based noncontact atomic force microscopy. Comparison with theoretical simulations reveals that the key lies in probing the weak high-order electrostatic force between the quadrupole-like CO-terminated tip and the polar water molecules at large tip-water distances. This interaction allows the imaging and structural determination of the weakly bonded water clusters and even of their metastable states with negligible disturbance. This work may open an avenue for studying the intrinsic structure and dynamics of ice or water on surfaces, ion hydration, and biological water with atomic precision.
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