Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research

The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein(Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases(CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.

Efficacy and safety of Nafamostat mesylate in patients with endstage renal failure

BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.

Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study

AIM To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME. criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2: 1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 degrees C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.

Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration

Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.

Circulating exosomal lncRNA contributes to the pathogenesis of spinal cord injury in rats

Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury.Thus,the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions.To this end,we established a rat model of spinal cord hemisection.Circulating exosomes were extracted from blood samples from spinal cord injury and control(sham)rats and further identified through Western blotting and electron microscopy.RNA was isolated from the exosomes and sequenced.The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes,as well as their cellular locations and molecular functions.Furthermore,quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908,XR_590093,XR_591455,XR_360081,and XR_346933––was increased,whereas the expression of XR_351404,XR_591426,XR_353833,XR_590076,and XR_590719 was decreased.Of note,these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network,which also included 198 mRNAs and 41 miRNAs.Taken together,our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury,suggesting that they may be involved in spinal cord injury pathology and pathogenesis.These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.

Real-time dynamics in strongly correlated quantum-dot systems

We investigate the real-time dynamical properties of Rabi-type oscillation through strongly correlated quantum-dot systems by means of accurate hierarchical equations of motion.It is an extension of the hierarchical Liouville-space approach for addressing strongly correlated quantum-dot systems.We study two paradigmatic models,the single quantum-dot system,and serial coupling double quantum-dot system.We calculate accurately the time-dependent occupancy of quantum-dot systems subject to a sudden change of gate voltage.The Rabi-type oscillation of the occupancy and distinct relaxation time of the quantum-dot systems with different factors are described.This is helpful to understand dissipation and decoherence in real-time dynamics through nanodevices and provides a theoretical frame to experimental investigation and manipulation of molecular electronic devices.

高海拔地区汉、藏、回3个民族上颌窦底与上颌后牙的CBCT位置测量分析

目的通过锥体束CT(CBCT)检查分析高海拔地区汉、藏、回3个民族上颌窦与上颌后牙的位置关系,为拔牙、口腔外科手术、种植和植骨手术提供统计学依据。方法随机收集汉、藏、回3个民族各110例(男女各55例,左右共110侧),共330例上颌窦的CBCT扫描数据,对其双侧上颌窦底至上颌后牙根尖和牙槽嵴顶距离的测量数据进行统计和对比分析。结果男性和女性上颌窦底至上颌第2前磨牙根尖的平均距离为:汉族(5.52±1.47)和(4.46±1.82)mm,藏族(6.65±1.72)和(6.19±1.71)mm,回族(5.45±2.04)和(4.07±1.74)mm;上颌窦底至上颌第1磨牙根尖的平均距离为:汉族(4.09±1.74)和(2.74±1.59)mm,藏族(5.05±1.62)和(4.25±1.68)mm,回族(4.23±1.71)和(2.72±1.67)mm;上颌窦底至上颌第2磨牙根尖的平均距离为:汉族(3.66±1.79)和(2.55±1.58)mm,藏族(5.29±1.67)和(4.14±1.71)mm,回族(3.49±1.76)和(2.45±1.66)mm;上颌窦底至上颌后磨牙槽嵴顶的平均距离为:汉族(12.82±1.69)和(11.83±1.67)mm,藏族(13.70±1.79)和(13.14±1.59)mm,回族(13.25±1.62)和(11.14±1.58)mm。结论高海拔地区汉、藏、回3个民族的上颌窦与上颌后牙的位置关系存在差异;上颌窦底至上颌第2前磨牙、第1磨牙、第2磨牙牙根距离的平均值:汉族和回族均低于藏族;上颌窦底至上颌后牙牙槽嵴顶的平均距离:男性:藏族>回族>汉族,女性:藏族>汉族>回族。

Computational Study on Thermodynamic Properties of Fischer-Tropsch Synthesis Process

Using the highly accurate G4 method, we computed the thermodynamic data of 1287 possible reaction products under a wide range of reaction conditions in the Fischer-Tropcsh synthesis (FTS) process. These accurate thermodynamic data provide basic thermodynamic quantities for the actual chemical engineering process and are useful in analyzing product distribution because FTS demonstrates many features of an equilibrium-controlled system. Our results show that the number of thermodynamically allowed products to increase when lowering temperature, raising pressure, and raising H2/CO ratio. At low temperature, high pressure and high H2/CO ratio, many products are thermodynamically allowed and the selectivity of product has to be controlled by kinetic factors. On the other hand, high selectivity of lighter products can be realized in thermodynamics by raising temperature and lowering pressure. We found that the equilibrium product yield will reach a maximum and remain unchanged when lowering temperature, raising pressure, and raising H2/CO ratio to some limits, implying that optimizing reaction conditions has no effect on equilibrium product yields beyond these limits. The thermodynamic analysis is also useful in designing and evaluating FTS reaction mechanisms. We found that reaction pathways through formaldehyde should be discarded because of its extremely low equilibrium yield. Recently, in the FTS process using metal-oxide-zeolite catalysts for the highly selective production of C2-C4 olefins and aromatic hydrocarbons, there are several guesses on the possible reaction intermediates entering the zeolite channel. Our results show that ketene, methanol, and dimethyl ether are three possible reaction intermediates.

Mg acceptor activation mechanism and hole transport characteristics in highly Mg-doped AlGaN alloys

The Mg acceptor activation mechanism and hole transport characteristics in AlGaN alloy with Mg doping concentration(~ 1020 cm-3) grown by metal–organic chemical vapor deposition(MOCVD) are systematically studied through optical and electrical properties. Emission lines of shallow oxygen donors and(VⅢ complex)1- as well as VN3+ and neutral Mg acceptors are observed, which indicate that self-compensation is occurred in Mg-doped AlGaN at highly doping levels. The fitting of the temperature-dependent Hall effect data shows that the acceptor activation energy values in Mgdoped AlxGa1-xN(x = 0.23, 0.35) are 172 meV and 242 meV, and the hole concentrations at room temperature are 1.2×1018 cm-3 and 3.3× 1017 cm-3, respectively. Therefore, it is believed that there exists the combined effect of the Coulomb potentials of the dopants and screening of the Coulomb potentials by a high hole concentration. Moreover, due to the high ionized acceptors’ concentration and compensation ratio, the impurity conduction becomes more prominent and the valence band mobility drops sharply at low temperature.

Plasma assisted molecular beam epitaxial growth of GaN with low growth rates and their properties

A systematic investigation on PA-MBE grown GaN with low growth rates(less than 0.2μm/h)has been conducted in a wide growth temperature range,in order to guide future growth of sophisticated fine structures for quantum device applications.Similar to usual growths with higher growth rates,three growth regions have been revealed,namely,Ga droplets,slightly Ga-rich and N-rich 3D growth regions.The slightly Ga-rich region is preferred,in which GaN epilayers demonstrate optimal crystalline quality,which has been demonstrated by streaky RHEED patterns,atomic smooth surface morphology,and very low defect related yellow and blue luminescence bands.The growth temperature is a critical parameter to obtain high quality materials and the optimal growth temperature window(~700-760℃)has been identified.The growth rate shows a strong dependence on growth temperatures in the optimal temperature window,and attention must be paid when growing fine structures at a low growth rate.Mg and Si doped GaN were also studied,and both p-and n-type materials were obtained.

Broadband Terahertz Transmission Modulation Based on Hybrid Graphene-Metal Metamaterial

A novel patterned metamaterial,composed of graphene layer and metal periodic array of split ring resonators （SRRs） and cross-shapedresonators （CSRs）, with broadband terahertz （THz） wave modulation was proposed and theoretically studied. It demonstrated that a broad passband high transmission of over 96.1% in the frequency range from 1.02 THz to 1.66 THz and two narrow band resonance frequencies f1 and f2 could be generated. The modulation depth of transmission was 29.2% when the graphene layer was covered on the metal metamaterial surface, and the modulation depth could be further increased by increasing the Fermi energy of graphene layer and reached approximately 79.5% at 1.0 eV in a broadband THz frequency range. The resonance frequencies of f1 and f2 were blue-shifted, and their modulation depths reached about 63.2% and 18%, respectively. These results show that the ultrathin graphene-metal metamaterial exhibits potential to achieve highperformance active THz devices and may offer widespread applications.

Zero-energy modes in serially coupled double quantum dots

We investigate symmetrically coupled double quantum dots via the hierarchical equations of motion method and propose a novel zero-energy mode(ZEM) at a temperature above the spin singlet–triplet transition temperature. Owing to the resonance of electron quasi-particle and hole quasi-particle, ZEM has a peak at ω = 0 in the spectral density function.We further examine the effect of the magnetic field on the ZEM, where an entanglement of spin and charge has been determined;therefore, the magnetic field can split the ZEM in the spectra.

Ferromagnetism in High-Surface-Area ZnO Nanosheets Prepared by a Template-Assisted Hydrothermal Method

High-surface-area ZnO nanosheets are prepared using a template-assisted hydrothermal method.A saturation moment as high as 0.02 emu/g is obtained for the ZnO nanosheets.Both photoluminescence spectroscopy and x-ray photoelectron spectroscopy demonstrate the existence of abundant oxygen vacancies on the surfaces of the nanosheets.In addition,the oxygen vacancy concentration increases with an increasing nanosheet surface area.The results show that the origin of the room-temperature ferromagnetism is closely related with a large surface area and oxygen vacancies of the nanosheets.This finding suggests that the high-surface-area ZnO nanosheets are promising to be applied to spintronic devices.

One-step selective dehydrogenation of cyclic hemiacetal sugars toward to their chiral lactones

Chiral glycosyl lactone is an important class of bioactive compound and pharmaceutical intermediate in nature, especially for chiral lactones with 4 carbon atoms, which are very useful building blocks for synthesis of biologically interesting compounds. Herein, a selective dehydrogenation and solvent matched catalytic system under oxygen-free conditions was developed to try to achieve the one-step direct conversion of cyclic hemiacetal sugars toward their chiral glycosyl lactones. During the process, the inherent structural characteristics of sugar was efficiently utilized, and the transfer of its chiral centers was realized. Under the optimum condition, the corresponding lactones were successfully prepared from C_(4)-C6sugars with cyclic hemiacetal structure in acetonitrile. The reaction mechanism in acetonitrile was explored by the first principle density functional theory calculations and tracking reaction process. It was found that the high lactone yield in acetonitrile was due to the high proportion of α-conformation form among multiple tautomers in it. This selective dehydrogenation process may further extend the possibility of the preparation of chiral synthons from carbohydrates directly.

Ethnopharmacological Investigation and Rapid Authentication of Mongolian Patent Medicines Digeda

Objective To investigate Mongolian medicinal plants called Digeda and the prescriptions in Inner Mongolia region and to establish a molecular method for authentication of Digeda Mongolian patent medicines （MPMs）. Methods A field investigation was conducted on traditional uses of Digeda. After interviewed traditional healers in Mongolian, ethnopharmacological information of Digeda prescriptions was recorded in detail, including names, compositions, and traditional uses. And the total DNA from 10 MPMs has been amplified by three pairs of specific primers. Specific PCR products were further identified by sequence alignment with the known sequences already submitted in GenBank or own sequences. Results Fifteen Digeda plants and 29 Digeda prescriptions with their ethnopharmacological knowledge were collected. Ten MPM samples containing Lomatogonium rotatum, Viola philippica, and Corydalis bungeana were successfully evidenced by PCR with specific bands as raw materials. Conclusion Digeda should be further investigated in ethnopharmacology, which is a fundamental step toward developing efficacious natural drugs for various diseases. PCR amplification of specific allele is an easy and economical method, which can be used to identify highly processed MPMs and will assist in monitoring their qualities and legalities.

Influence of Oxide Morphologies on Galvanizability of Third Generation Automotive Steel

Focusing on improving the galvanizability of the third generation automotive steel, the effect of surface ox ide morphologies on the galvanizability was studied. The results show that the surface oxide types of sample steels by X ray photoelectron spectroscopy （XPS） analysis after annealing in different conditions are the same. Only MnO, MnO2 and Cr2O3 were detected and no complex oxide exists on the surface. Morphologies of surface oxides can greatly influence the galvanizability of the third generation automotive steel. Nodule-like oxide surface can contribute to better wettability and inhibition layer than vitreous film like oxide surface. Galvanized panels of nodule-like oxide surface steels only show pinhole sized bare spots, while panels galvanized from vitreous film-like oxide surface steels reveal larger areas of bare spots and uncoated areas. Inhibition layer observed in galvanized panels of nodule-like oxide surface steels is compact but not homogeneous; some inhibition layer grains are fine, and others are coarse, while the inhibition layer grains of panels galvanized from vitreous film-like oxide surface steels have a non-compact morphology with some particularly fine equiaxed crystals which developed deficiently.

Lewis Acid Enables Ketone Phosphorylation:Synthesis of Alkenyl Phosphonates

Main observation and conclusion An efficient Lewis acid enabled ketones phosphonylation to synthesize vinylphosphonates has been developed.This method relays on ketone hydrophosphonylation/α-hydroxy phosphonates unimolecular elimination(E1)dehydration cascade reaction sequence.