CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway.

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application

PSO-FNN-Based Vertical Handoff Decision Algorithm in Heterogeneous Wireless Networks

AbstractAiming at working out the problem that fuzzy logic and neural network based vertical handoff algorithm didn’t consider the load state reasonably in heterogeneous wireless networks, a PSO-FNN-based vertical handoff decision algorithm is proposed. The algorithm executes factors reinforcement learning for the fuzzy neural network (FNN) with the objective of the equal blocking probability to adapt for load state dynamically, and combined with particle swarm optimization (PSO) algorithm with global optimization capability to set initial parameters in order to improve the precision of parameter learning. The simulation results show that the PSO-FNN algorithm can balance the load of heterogeneous wireless networks effectively and decrease the blocking probability as well as handoff call blocking probability compared to sum-received signal strength (S-RSS) algorithm

Sr\u3csub\u3e2\u3c/sub\u3eFe\u3csub\u3e1.5\u3c/sub\u3eMo\u3csub\u3e0.5\u3c/sub\u3eO\u3csub\u3e6-δ\u3c/sub\u3e – Sm\u3csub\u3e0.2\u3c/sub\u3eCe\u3csub\u3e0.8\u3c/sub\u3eO\u3csub\u3e1.9\u3c/sub\u3e Composite Anodes for Intermediate-Temperature Solid Oxide Fuel Cells

Sr2Fe1.5Mo0.5O6−δ (SFM) perovskite is carefully investigated as an anode material for solid oxide fuel cells with LaGaO3-based electrolytes. Its electronic conductivity under anodic atmosphere is measured with four-probe method while its ionic conductivity is determined with oxygen permeation measurement. Samaria doped ceria (SDC) is incorporated into SFM electrode to improve the anodic performance. A strong relation is observed between SDC addition and polarization losses, suggesting that the internal SFM-SDC contacts are active for H2 oxidation. The best electrode performance is achieved for the composite with 30 wt% SDC addition, resulting in an interfacial polarization resistance of 0.258 Ω cm2 at 700◦C for La0.8Sr0.2Ga0.8Mg0.2O3−δ supported single cells. Electrochemical impedance spectroscopy analysis indicates that the high performance of SFM-SDC composite anodes is likely due to the high ionic conductivity and electro-catalytic activity of SDC by promoting the ionic exchange processes. Redox cycle treatment shows that SDC addition can even improve the redox tolerance of SFM anodes

Ferroelectric memristor based on Pt/BiFeO3/Nb-doped SrTiO3 heterostructure

We report a continuously tunable resistive switching behavior in Pt/BiFeO₃/Nb-doped SrTiO₃ heterostructure for ferroelectric memristor application. The resistance of this memristor can be tuned up to 5 × 10⁵% by applying voltage pulses at room temperature, which exhibits excellent retention and anti-fatigue characteristics. The observed memristive behavior is attributed to the modulation effect of the ferroelectric polarization reversal on the width of depletion region and the height of potential barrier of the p-n junction formed at the BiFeO₃/Nb-doped SrTiO₃ interface.This work was supported by the National Natural Science Foundation of China (Grant Nos. 11074193 and 51132001). Q.L. and Y.L. acknowledge the support of the Australian Research Council (ARC) in the form of ARC Discovery Grants

Modulating the Verwey Transition of Epitaxial Magnetite Thin Films by Ionic Gating

Understanding the Verwey transition in magnetite (Fe3O4), a strongly correlated magnetic oxide, is a one-century-old topic that recaptures great attention because of the recent spectroscopy studies revealing its orbital details. Here, the modulation of the Verwey transition by tuning the orbital configurations with ionic gating is reported. In epitaxial magnetite thin films, the insulating Verwey state can be tuned continuously to be metallic showing that the low-temperature trimeron states can be controllably metalized by both the gate-induced oxygen vacancies and proton doping. The ionic gating can also reverse the sign of the anomalous Hall coefficient, indicating that the metallization is associated with the presence of a new type of carrier with competing spin. The variable spin orientation associated with the sign reversal is originated from the structural distortions driven by the gate-induced oxygen vacancies

Ruminal microbiota and muscle metabolome characteristics of Tibetan plateau yaks fed different dietary protein levels

IntroductionThe dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels.MethodsIn this study, 36 yaks were randomly assigned to three groups (n = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration).Results16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed_species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group (P < 0.05). At the genus level, the relative abundance of Christensenellaceae_R-7_group in the HP group was notably greater than that in the LP and MP groups (P < 0.05). Conversely, the relative abundance of Rikenellaceae_RC9_gut_group displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group (P < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group (P < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group (P < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group (P < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of NK4A214_group was negatively correlated with Orlistat concentration; the relative abundance of Christensenellaceae_R-7_group was positively correlated with D-(-)-Glutamine and L-arginine concentrations.DiscussionOur findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels

Optical studies of structural phase transition in the vanadium-based kagome metal ScV6Sn6

In condensed matter physics, materials with kagome lattice exhibit exotic emergent quantum states, including charge density wave (CDW), superconductivity and magnetism. Very recently, hexagonal kagome metal ScV6Sn6 was found to undergo fascinating first-order structural phase transition at around 92 K and a 3x3x3 CDW modulation. The bulk electronic band properties are enlightened for comprehending the origin of the structural phase transition. Here, we perform a optical spectroscopy study on the monocrystalline compound across the transition temperature. The structural transition gives rise to the abrupt changes of optical spectra without observing gap development behavior. The optical measurements revealed a sudden reconstruction of the band structure after transition. We emphasize that the phase transition is of the first order and distinctly different from the conventional density-wave type condensation. Our results provide insight into the origin of the structural phase transition in the new kagome metal compound.Comment: 7 pages, 4 figure

Pump-induced terahertz conductivity response and peculiar bound state in Mn3Si2Te6

We report the significant enhancement on ultrafast terahertz optical conductivity and the unexpected formation of a polaronic-like state in semiconductor Mn3Si2Te6 at room temperature. With the absorption of pump photons, the low-frequency terahertz photoconductivity spectrum exhibits a significant rise, quickly forming a broad peak and subsequently shifting to higher energy. The short-lived nature of the broad peak, as well as the distribution of optical constants, strongly points towards a transient polaron mechanism. Our study not only provides profound insights into the remarkable photoelectric response of Mn3Si2Te6 but also highlights its significant potential for future photoelectric applications