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The upper Tarim River basin is supporting approximately 50 million people by melting the glaciers and snow, which are highly vulnerable and sensitive to climate change. Therefore, assessing the relative effects of climate change on the runoff of this region is essential not only for understanding the mechanism of hydrological response over the mountainous areas in Southern Xinjiang but also for local water resource management. This study quantitatively investigated the climate change in the mountainous area of the upper Tarim River basin, using the up-to-date “ground-truth” precipitation and temperature data, the Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE, 1961–2010, 0.25°) data; analyzed the potential connections between runoff data, observed at Alar station, and the key climatological variables; and discussed the regression models on simulating the runoff based on precipitation and temperature data. The main findings of this study were as follows—(1) both annual precipitation and temperature generally increase at rates of 0.85 mm/year and 0.25 °C/10a, respectively, while the runoff data measured at the Alar station shows fluctuating decreasing trends. (2) There are significant spatial differences in the temporal trends of precipitation; for example, the larger increasing rates of precipitation occur in the Karakoram mountains, while the larger decreasing rates happen in the northwestern Kashgar county. (3) The decreasing trends of temperature mainly occur in Kashgar county and its surrounding areas in summer. (4) Seasonal correlations in precipitation and temperature trends are more significant than those on a monthly and annual scale. (5) The regression model in simulating the runoff in the upper Tarim River basin based on radial basis function (RBF) is better than that based on the least-squares method, with the predictive values based on RBF models significantly better (correlation coefficient, CC ∼ 0.85) than those by least-squares models (CC ∼ 0.75). These findings will provide valuable information to inform environmental scientists and planners on the climate change issues in the upper Tarim River basin of Southern Xinjiang, China, under a semiarid-arid climate.

A facile sol–gel spin coating method has been proposed for the synthesis of spin-coated ZnO nanofilms on ITO substrates. The as-prepared ZnO-nanofilm-based W/ZnO/ITO memory cell showed forming-free and tunable nonvolatile multilevel resistive switching behaviors with a high resistance ratio of about two orders of magnitude, which can be maintained for over 103 s and without evident deterioration. The tunable nonvolatile multilevel resistive switching phenomena were achieved by modulating the different set voltages of the W/ZnO/ITO memory cell. In addition, the tunable nonvolatile resistive switching behaviors of the ZnO-nanofilm-based W/ZnO/ITO memory cell can be interpreted by the partial formation and rupture of conductive nanofilaments modified by the oxygen vacancies. This work demonstrates that the ZnO-nanofilm-based W/ZnO/ITO memory cell may be a potential candidate for future high-density, nonvolatile, memory applications.

Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation ( Myo6 C442Y/+ ) mouse model that recapitulated the phenotypes of human dominant-inherited deafness. We first screened several variants of Cas13-based RNA base editors and guide RNAs (gRNAs) targeting Myo6 C442Y in cultured cells and found that mini dCas13X.1-based adenosine base editor (mxABE), composed of truncated Cas13X.1 and the RNA editing enzyme adenosine deaminase acting on RNA 2 deaminase domain variant (ADAR2dd E488Q ), exhibited both high efficiency of A > G conversion and low frequency of off-target edits. Single adeno-associated virus (AAV)–mediated delivery of mxABE in the cochlea corrected the mutated Myo6 C442Y to Myo6 WT allele in homozygous Myo6 C442Y/C442Y mice and resulted in increased Myo6 WT allele in the injected cochlea of Myo6 C442Y/+ mice. The treatment rescued auditory function, including auditory brainstem response and distortion product otoacoustic emission up to 3 months after AAV-mxABE- Myo6 injection in Myo6 C442Y/+ mice. We also observed increased survival rate of hair cells and decreased degeneration of hair bundle morphology in the treated compared to untreated control ears. These findings provide a proof-of-concept study for RNA editing tools as a therapeutic treatment for various semidominant forms of hearing loss and other diseases.

Competitive coevolution between microbes and viruses has led to the diversification of CRISPR-Cas defense systems against infectious agents. By analyzing metagenomic terabase datasets, we identified two compact families (775 to 803 amino acids (aa)) of CRISPR-Cas ribonucleases from hypersaline samples, named Cas13X and Cas13Y. We engineered Cas13X.1 (775 aa) for RNA interference experiments in mammalian cell lines. We found Cas13X.1 could tolerate single-nucleotide mismatches in RNA recognition, facilitating prophylactic RNA virus inhibition. Moreover, a minimal RNA base editor, composed of engineered deaminase (385 aa) and truncated Cas13X.1 (445 aa), exhibited robust editing efficiency and high specificity to induce RNA base conversions. Our results suggest that there exist untapped bacterial defense systems in natural microbes that can function efficiently in mammalian cells, and thus potentially are useful for RNA-editing-based research.

The electronic structures and optical properties of intrinsic Mg2Si and Nd-incorporated Mg2Si were studied by first principles. The result demonstrates that the Fermi energy level of Nd-incorporated Mg2Si is located in the conduction band and it is n-type conduction. The absorption peak intensity of Nd-incorporated Mg2Si is slightly smaller than that of the intrinsic Mg2Si, but the absorption span is longer than that of the intrinsic Mg2Si. The intrinsic Mg2Si barely absorbs photons with energy lower than 0.5 eV, but Nd-incorporated Mg2Si still has a large absorption. In addition, with the increase of Nd incorporating concentration, the absorption coefficient of Nd-incorporated Mg54Si27 increased gradually in far ultraviolet light. The results suggest that Nd incorporating can improve the absorption of Mg2Si in the infrared and far ultraviolet region. It supplies a theoretical basis for preparing the photoelectric devices of rare earth incorporated Mg2Si.

Detection of endogenous signals and precise control of genetic circuits in the natural context are essential to understand biological processes. However, the tools to process endogenous information are limited. Here we developed a generalizable endogenous transcription-gated switch that releases single-guide RNAs in the presence of an endogenous promoter. When the endogenous transcription-gated switch is coupled with the highly sensitive CRISPR-activator-associated reporter we developed, we can reliably detect the activity of endogenous genes, including genes with very low expression (

Graphene has long been considered to have a wide application perspective in many fields, such as electronic information, chemical industry and aerospace. However, the actual graphene materials contain a variety of defects that affect their properties. Accurate and rapid identification of defect structure types is of great significance for the application of graphene. First, the image preprocessing technology is used to improve the classification precision. Next, use the convolutional neural network to classify the type of vacancy defect and perform rapid analytical tasks to accurately identify graphene defect structures. This study aims to contribute to this growing area of research in graphene to classify and count the vacancy defects automatically and quickly in monitoring its surface structures.

CRISPR-Cas13 systems have recently been employed for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has imposed a major barrier for their in vivo applications. We designed a dual-fluorescent reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells. Among over 200 engineered variants, several Cas13 variants (including Cas13d and Cas13X) exhibit efficient on-target activity but markedly reduced collateral activity. Furthermore, transcriptome-wide off-targets and cell growth arrest induced by Cas13 are absent for these variants. Importantly, high-fidelity Cas13 variants show comparable RNA knockdown activity with wild-type Cas13 but no detectable collateral damage in transgenic mice and adeno-associated virus-mediated somatic cell targeting. Thus, high-fidelity Cas13 variants with minimal collateral effect are now available for targeted degradation of RNAs in basic research and therapeutic applications.

Presently, there has been increasing attention on TiAl3, which is commonly used for fabricating power aviation devices owing to its good oxidation resistance and outstanding mechanical properties in high-temperature. As the microstructures determine the macroscopic properties of a material, we investigated the connectivity of icosahedral central atoms in TiAl3 using conventional methods in this study. The topologically close-packed (TCP) structures are present in supercooled liquids, metallic glasses, and metallic liquids. They are intrinsic to liquid metals and are an essential character of the structure in metallic glasses (MGs). However, because of the lack of the concept of connectivity of the TCP structures, we investigated connectivity from the icosahedral central atoms to TCP structures, and a formula was proposed to calculate the connectivity of the TCP structures. Based on the results, low temperatures and cooling rates are conducive to generate high connectivity between icosahedral central atoms and TCP structures. The proposed formula can characterize the connectivity of the TCP structures. These findings open new opportunities for conducting research on the connectivity of clusters in binary alloys.

As a wide-bandgap semiconductor material with small dielectric constant and good thermal stability, aluminium nitride (AlN) can theoretically emit light in the deep ultraviolet wavelength region, so it is important in expanding the response of AlN in the visible region. In order to study the influences of La doping on the photoelectric properties of wurtzite AlN crystal, the first-principle plane-wave pseudopotential method and generalized gradient approximation were used to study the lattice constants, electronic structure and optical properties of undoped and La-doped AlN. The calculation results indicate that the intrinsic AlN is a direct-bandgap semiconductor material which both conduction band bottom and valence band top being at the G point, but La-doped AlN forms an indirect-bandgap semiconductor in which the conduction band bottom is at the G point and the valence band top is at the F point. The peak of the density of states is reduced near Fermi energy, and the electronic localization features are significantly diminished. The La doping makes the forbidden band width of AlN narrow, which reduces the photon energy needed for the electron transition, and shows a red shift phenomenon, which expands the influence on visible light. Therefore, this provides a theoretical basis for the study of the photoelectric properties of rare-earth-metal La-doped AlN.

Recently emerging SARS-CoV-2 virus has caused a global pandemic, with millions of infections and over 200, 000 deaths1. However, development of effective anti-coronavirus treatments has lagged behind. Competitive co-evolution between microbes and viruses has led to the diversification of microbe’s CRISPR/Cas defense systems against infectious viruses2,3. Among class-2 single effector systems, Cas13 is effective in combating RNA phages4. Previous studies have discovered novel Cas9 and Cas12 systems from metagenomic sequence of natural microbes5-7. Here we report the identification of two additional compact Cas13 families from natural microbes that are effective in degrading RNA viruses in mammalian cells. Using metagenomic terabase data sets, we searched for previously uncharacterized Cas13 genes proximal to the CRISPR array with a customized computational pipeline, and identified two most compact families (775 to 803 amino acids) of CRISPR-Cas ribonucleases, named hereafter as CRISPR/Cas type VI-E and VI-F. Out of seven Cas13 proteins, we found that Cas13e.1 was the smallest and could be engineered for efficient RNA interference and base editing in cultured mammalian cell lines. Moreover, Cas13e.1 has a high activity for degrading SARS-CoV-2 sequences and the genome of live influenza A virus (IAV). Together with a minimal pool of 10 crRNAs, Cas13e.1 could target over 99% of all known 3,137 coronavirus genomes for achieving antiviral defense. Overall, our results demonstrated there exist untapped bacterial defense systems in natural microbes that can function efficiently in mammalian cells, thus potentially useful for preventing viral infection in humans such as COVID-19.

Acetone is flammable and harmful to human health and environment. It is urgent and significant to develop high sensitivity and efficiency sensors for acetone gas detecting. Herein, a novel nanoscale hollow–shell structure of CeO2 with high stability, sensitivity and selectivity for acetone gas detecting was designed. The as-developed nanoscale hollow–shell CeO2 sensor presents 270% sensing response, and the corresponding response and recovery are 6 s and 11 s when detecting 100 ppm acetone gas at 260 ℃. Remarkably, this sensor exhibits excellent stability in continual detection of 100 ppm acetone gas in 60 days. Furthermore, the developed nanoscale hollow–shell CeO2 sensor presents an outstanding selectivity to acetone gas among ethanol, methanol, xylene, ammonia, formaldehyde and ethylene glycol gases. DFT further reveals that there are 0.66 electrons of acetone molecule transferred to CeO2, which will decease CeO2 band gap from 2.74 eV to 1.91 eV, and consequently the conductivity enhanced after absorbing acetone gas. This developed CeO2 nanoscale hollow–shell sensor can be used as matrix sensor material for VOCs detection.

The Al-doped Mg2Si thin films were fabricated on sapphire substrates by magnetron sputtering technique, and the influences of different Al doping contents on the Raman scattering and room-temperature (RT) photoluminescence (PL) of Mg2Si thin films were investigated. The crystal structure, morphology, composition, Raman scattering and PL property of the thin film were examined using X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM) equipped with energy dispersive X-ray spectroscopy (EDS) and Raman spectroscopy, respectively. XRD results indicate that the intensity of diffraction peaks of Al-doped Mg2Si thin films are higher than that of undoped Mg2Si thin film, and decrease with increasing Al doping content. The FESEM image shows a few cavities in the surface of the film. The EDS results show that the thin films have the Al content of 0, (1.17 ± 0.1) at.%, (1.53 ± 0.1) at.%, (1.86 ± 0.08) at.% and (2.76 ± 0.11) at.%, respectively. The results of Raman scattering measurement reveal that all samples have the characteristic peak of Mg2Si. And Al dopant-induced Raman peak centered at 441 cm−1 was detected. Room-temperature photoluminescence of the Mg2Si:Al film was observed for the first time. Two visible light luminescence peaks center about 580 nm (2.14 eV) and 630 nm (1.97 eV), respectively, which originate from the different energy levels transition at the interface between crystalline Mg2Si and MgO surface layer. With decreasing excitation power, the position of the maximum of PL has no obvious change and the intensity drops significantly.

Gallium nitride (GaN) is a promising material for high-frequency and high-power electronics owing to its high thermal stability, wide bandgap, and high breakdown voltage. Monocrystalline GaN films are usually produced by metal organic chemical vapor phase deposition using Si, SiC, or Al2O3 as the substrate. However, the difference in lattice constants and thermal expansion coefficients causes many defects in GaN epilayers. In particular, the formation of twins will strongly influence the electronic properties of GaN-based devices. In this study, the solidification process of GaN was simulated by molecular dynamics at a cooling rate of 1012 K/s, and the twin structures in GaN were discussed. The results of this simulation showed two types of twins, including coherent twin and rotating twin, which were analyzed by visualization technology. The formation of twins was related to the coexistence of zinc blende and wurtzite phases. Furthermore, the types of twins were closely associated to the stacking ways of zinc blende and wurtzite structures. In general, it is essential to study the microstructure and the structural evolution of twin GaN, in order to give references to experiments about the growth and characteristics of twins.

To understand the photoluminescence mechanisms and optimize the design of Mg 2 Si-based light-emitting devices, Mg 2 Si films were fabricated on silicon (111) and glass substrates by magnetron sputtering technique, and the influences of different substrates on the photoelectric properties of Mg 2 Si films were investigated systematically. The crystal structure, cross-sectional morphology, composition ratios and temperature-dependent photoluminescence (PL) of the Mg 2 Si films were examined using X-ray diffraction (XRD), Scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS) and PL measurement system, respectively. XRD results indicate that the Mg 2 Si film on Si (111) displays polycrystalline structure, whereas Mg 2 Si film on glass substrate is of like-monocrystalline structure.SEM results show that Mg 2 Si film on glass substrate is very compact with a typical dense columnar structure, and the film on Si substrate represents slight delamination phenomenon. EDS results suggest that the stoichiometry of Mg and Si is approximately 2:1. Photoluminescence (PL) of Mg 2 Si films was observed for the first time. The PL emission wavelengths of Mg 2 Si are almost independence on temperature in the range of 77–300 K. The PL intensity decreases gradually with increasing temperature. The PL intensity of Mg 2 Si films on glass substrate is much larger than that of Mg 2 Si film on Si (111) substrate. The activation energy of 18 meV is determined from the quenching of major luminescence peak(1342 nm) as a function of temperature in the Mg 2 Si film grown on Si (111) substrate, which is much smaller than that deduced in the sample grown on glass substrate (about 25meV). The small activation energy can be attributed to the additional nonradiative centers originated from relatively poor crystal quality.The physical mechanism responsible for the measured ∼1342 nm and other three longer wavelengths emissions may be respectively result from strong Mg i donor level to valence band transitions and other defect-related radiative recombination occurred in the Mg 2 Si films.

A detailed theoretical study on the influence of lattice vacancy on structural and optical properties of the magnesium silicide Mg2Si has been performed based on the first-principles pseudopotential method. The results show that Mg2Si has changed from indirect band gap semiconductor to direct band gap semiconductor because of Mg vacancy. Compared with the dielectric function, absorption coefficient, refractive index, reflectivity and photon conductivity of Mg2Si, those peaks of Mg15Si8 appear from 0 to 1.8 eV. And the loss function’s biggest peak of Mg15Si8 moves to the direction of high energy.

Summary Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Muller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson’s disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction. Electronic supplementary material The online version of this article (10.1186/s13059-019-1703-6) contains supplementary material, which is available to authorized users.

Supplementary methods. (DOCX 26 kb)