Search

The first round of comprehensive evaluation of majors in Jiangxi Province has achieved positive results.Scientific summary and analysis of the comprehensive evaluation of majors is conductive to improving the enthusiasm of universities to participate in the next round of comprehensive evaluation of majors, and the reasonable use of comprehensive evaluation results of majors is conducive to promoting the participating universities to improve the level of major construction,so as to promote the overall quality of higher education in Jiangxi Province.After statistical analysis of the first round of comprehensive evaluation results of majors in Jiangxi Province,the only participating majors in the province,were excluded,and the ranking results of comprehensive evaluation of different universities of the same majors are assigned points.Then,the average of the scores of all participating majors of each university was taken as the basis of university ranking to rank each university,and the ranking data were reliable,comparable in connotation and reliable in evaluation.From the ranking results,it can be concluded that more majors do not necessarily bring about better ranking,and some new undergraduate institutions are not sustainable due to the insufficient number of participating majors.The unsustainability of the ranking is affected by the insufficient number of majors participating in the comprehensive evaluation in some new undergraduate institutions.

DNA nanotechnology has been widely employed in the construction of various functional nanostructures. However, most DNA nanostructures rely on hybridization between multiple single-stranded DNAs. Herein, we report a general strategy for the construction of a double-stranded DNA-ribonucleoprotein (RNP) hybrid nanostructure by folding double-stranded DNA with a covalently bivalent clustered regularly interspaced short palindromic repeats (CRISPR)/nuclease-dead CRISPR-associated protein (dCas) system. In our design, dCas9 and dCas12a can be efficiently fused together through a flexible and stimuli-responsive peptide linker. After activation by guide RNAs, the covalently bivalent dCas9-12a RNPs (staples) can precisely recognize their target sequences in the double-stranded DNA scaffold and pull them together to construct a series of double-stranded DNA-RNP hybrid nanostructures. The genetically encoded hybrid nanostructure can protect genetic information in the folded state, similar to the natural DNA-protein hybrids present in chromosomes, and elicit efficient stimuli-responsive gene transcription in the unfolded form. This rationally developed double-stranded DNA folding and unfolding strategy presents a new avenue for the development of DNA nanotechnology.

Based on complementary base pairing, nucleic acid molecules have acted as engineerable building blocks to prepare versatile nanostructures with unique shapes and sizes. Benefiting from excellent programmability and biocompatibility, rationally designed nucleic acid nanostructures have been widely employed in biomedical applications. With the development of the chemical biology of nucleic acids, various stimuli-responsive nucleic acid nanostructures have been constructed by tailored chemical modification with multifunctional components. In this minireview, we summarize the representative and latest research about the employment of stimuli-responsive nucleic acid nanostructures for drug delivery in response to endogenous and exogenous stimuli (redox gradient, pH, nuclease, biomacromolecule, and light). We also discuss the broad prospects and remaining challenges of nucleic acid nanotechnology in biomedical applications.

Given a graph $G$ and an odd prime $p$, for a mapping $f: E(G) \to {\mathbb Z}_p\setminus\{0\}$ and a ${\mathbb Z}_p$-boundary $b$ of $G$, an orientation $\tau$ is called an $(f,b;p)$-orientation if the net out $f$-flow is the same as $b(v)$ in ${\mathbb Z}_p$ at each vertex $v\in V(G)$ under orientation $D$. This concept was introduced by Esperet et al. (2018), generalizing mod $p$-orientations and closely related to Tutte's nowhere zero 3-flow conjecture. They proved that $(6p^2 - 14p + 8)$-edge-connected graphs have all possible $(f,b;p)$-orientations. In this paper, the framework of such orientations is extended to signed graph through additive bases. We also study the $(f,b;p)$-orientation problem for some (signed) graphs families including complete graphs, chordal graphs, series-parallel graphs and bipartite graphs, indicating that much lower edge-connectivity bound still guarantees the existence of such orientations for those graph families.

DNA-based nanogels have attracted much attention in the biomedical research field. Herein, we report a universal strategy for the fabrication of an aptamer-modified DNA tetrahedron (TET)-based nanogel for combined chemo/gene therapy of multidrug-resistant tumors. In our design, terminal extended antisense oligonucleotides (ASOs) are employed as the linker to co-assemble with two kinds of three-vertex extended TETs for the efficient construction of the DNA-based nanogel. With the incorporation of an active cell-targeting group (aptamer in one vertex of TET) and a controlled-release element (disulfide bridges in the terminals of ASOs), the functional DNA-based nanogel can achieve targeted cellular internalization and stimuli-responsive release of embedded ASOs. After loading with the chemodrug (doxorubicin (DOX), an intercalator of double-stranded DNA), the multifunctional DOX/Nanogel elicits efficient chemo/gene therapy of human MCF-7 breast tumor cells with DOX resistance (MCF-7R). This aptamer-modified DNA tetrahedron-based nanogel provides another strategy for intelligent drug delivery and combined tumor therapy.

Background Circular RNAs (circRNAs) are known to play a crucial role in a variety of malignancies. However, the precise role of circRNAs in cervical squamous cell carcinoma (CSCC) remains largely unknown. Methods The expression of circ0001955 was determined by real-time quantitative PCR and fluorescence in situ hybridization. To examine the effects of circ0001955 on CSCC metastasis and growth, functional experiments were conducted in vitro and in vivo. Mechanistically, nucleocytoplasmic separation, dual luciferase reporter assay, RNA antisense purification experiments, and rescue experiments were performed to confirm the interaction between circ0001955, miR-188-3p, and NCAPG2 in CSCC. Results Here, we demonstrated that a circRNA derived from the CSNK1G1 gene (circ0001955) is significantly upregulated in CSCC. The overexpression of circ0001955 promotes tumor proliferation and metastasis, whereas the knockdown of circ0001955 exerts the opposite effects. Mechanistically, circ0001955 competitively binds miR-188-3p and prevents miR-188-3p from reducing the levels of NCAPG2, activating the AKT/mTOR signaling pathway to induce epithelial mesenchymal transformation. Notably, the application of an inhibitor of mTOR significantly antagonized circ0001955-mediated CSCC tumorigenesis. Conclusion circ0001955 promotes CSCC tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis which would provide an opportunity to search new therapeutic targets for CSCC. Graphical Abstract

Targeted delivery of therapeutic drugs is essential for precise treatment of various diseases to reduce possible serious side-effects. A screened DNA aptamer has been widely developed for active targeting delivery. Herein, we report a facile strategy for the construction of a branched DNA aptamer cluster-based nanoplatform for efficiently targeted drug delivery. In our design, the terminal-modified DNA aptamer can be covalently conjugated to form a branched aptamer cluster by click reaction easily. The branched aptamer cluster-modified DNA tetrahedron (TET) demonstrates highly targeted cellular uptake with the modification of only one site. After loading the chemotherapeutic drug (doxorubicin, DOX), the DNA aptamer cluster-based nanoplatform elicits a remarkable and selective inhibition of tumor cell proliferation by much-enhanced targeted delivery. This covalently conjugated branched DNA aptamer cluster-based nanoplatform provides a new strategy for the development of targeted drug delivery.

DC voltage detection of sub-modules is very important for the stability of cascaded multilevel converters. Operation and maintenance personnel need a detection algorithm to supplement the uncertainty and risk caused by the traditional redundancy scheme. This paper presented a DC voltage indirect estimation method based on current transformer. The method uses the AC side current value, as well as the sub-module equivalent circuit model and switching state to estimate the DC voltage of the sub-module of the cascade system. The estimation models are established and can be used to the sub-modules of three topologies, i.e., half-bridge, H bridge topology and clamp double sub-module. Simulation and experimental systems are built to testify the proposed method. The results showed that, when [Formula: see text] or 12, the indirect detection model based on AC current met the requirements of detection accuracy within 1% under different calculation steps, and the sampling error had little influence on it. The indirect estimation method could reduce the use of DC transformers and improve equipment reliability and maintainability.

Nucleic acid nanostructures with structural programmability, spatial addressability and excellent biocompatibility have drawn much attention in various biomedical applications, such as bioimaging, biosensing and drug delivery. In this review, we summarize the recent research progress in the field of bioimaging based on nucleic acid nanostructures with different imaging models, including fluorescent imaging(FI), magnetic resonance imaging(MRI), photoacoustic imaging(PAI) and positron emission tomography/computed tomography(PET/CT) imaging. We also discuss the remaining challenges and further opportunities involved in the bioimaging research based on nucleic acid nanostructures.

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA ‘locking strands’ outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge. A DNA nanodevice vaccine has been developed and utilized to stimulate a tumour-specific cytotoxic T lymphocyte response in vivo, leading to the inhibition of tumour growth as well as prevention of metastasis.

DNA nanostructures have garnered considerable interest as research tools in the field of cell biology and pathology. Herein, we develop an addressable double-bundle DNA tetrahedron with distinct modification sites to load multiple functional components for efficient regulation of gene expression. In our tailored nanoplatform, nucleic acid drugs (antisense for gene therapy) and protein drugs (KillerRed for photodynamic therapy) are precisely organized in the chemically well-defined DNA tetrahedron. With the attachment of active targeting groups, this functional DNA nanocarrier can efficiently penetrate into the cell membrane and subsequently transport drugs to the target subcellular organelles (mitochondrion and nucleus) for inducing synergistic cell behavior regulation to start the endogenous apoptotic process. This tailored DNA nanocarrier provides unprecedented opportunities for intelligent drug delivery and cell biology research.

The purpose of this study was to explore the association of fibrin/fibrinogen degradation products (FDP) levels with the risk of macrosomia, and determine whether FDP, either alone or combined with traditional factors in late pregnancy, could be used to predict macrosomia at birth in healthy pregnancies.A total of 9464 health pregnant women with singleton pregnancy were recruited in this retrospective cohort study. Maternal plasma FDP levels at hospital admission and birth outcomes were obtained from laboratory system and hospital records, respectively.FDP levels in late pregnancy were significant higher in women who delivered macrosomia than those who delivered infants with normal weight [median (interquartile range, IQR): 8.2 (5.8-11.9) vs. 6.6 (4.7-9.6) mg/L; P 0.001]. Multivariable logistic regression analysis demonstrated that FDP levels were independently associated with macrosomia risk. Pregnant women in the highest quartile of FDP had a 2.99-fold higher risk of delivering macrosomia compared with those in the lowest (adjusted OR: 2.99; 95% CI: 2.27-3.93). In addition, the incorporation of FDP into the crude prediction model significantly improved the area under curve (AUC) for predicting macrosomia (0.774 vs. 0.787; P 0.001).Our findings suggest that maternal plasma FDP levels in late pregnancy are independently and significantly associated with risk of macrosomia. Combination of FDP levels and traditional risk factors could promote the prediction of macrosomia.

A versatile DNA bipyramid nanostructure is assembled as a tumor-targeted, dual-modal nanoprobe for in vivo imaging. Magnetic resonance contrast agents (Gd-DOTA), fluorescence imaging molecules (Dyl...

A versatile DNA bipyramid nanostructure is assembled as a tumor-targeted, dual-modal nanoprobe for

Chondrocyte mechanotransduction is not well understood, but recently, it has been proposed that mechanically activated ion channels such as transient receptor potential vanilloid 4 (TRPV4), Piezo1, and Piezo2 are of functional importance in chondrocyte mechanotransduction. The aim of this study was to distinguish the potential contributions of TRPV4, Piezo1, and Piezo2 in transducing different intensities of repetitive mechanical stimulus in chondrocytes. To study this, TRPV4-, Piezo1-, or Piezo2-specific siRNAs were transfected into cultured primary chondrocytes to knock down (KD) TRPV4, Piezo1, or Piezo2 expression, designated TRPV4-KD, Piezo1-KD, or Piezo2-KD cells. Then we used Flexcell® Tension System to apply cyclic tensile strains (CTS) of 3% to 18% at 0.5 Hz for 8 h to the knockdown and control siRNA-treated cells. Finally, using a Ca2+ imaging system, stretch-evoked intracellular Ca2+ ([Ca2+] i) influx in chondrocytes was examined to investigate the roles of TRPV4, Piezo1, and Piezo2 in Ca2+ signaling in response to different intensities of repetitive mechanical stretch stimulation. The characteristics of [Ca2+] i in chondrocytes evoked by stretch stimulation were stretch intensity dependent when comparing unstretched cells. In addition, stretch-evoked [Ca2+] i changes were significantly suppressed in TRPV4-KD, Piezo1-KD, or Piezo2-KD cells compared with control siRNA-treated cells, indicating that any channel essential for Ca2+ signaling induced by stretch stimulation in chondrocytes. Of note, they played different roles in calcium oscillation induced by different intensities of stretch stimulation. More specifically, TRPV4-mediated Ca2+ signaling played a central role in the response of chondrocytes to physiologic levels of strain (3% and 8% of strain), while Piezo2-mediated Ca2+ signaling played a central role in the response of chondrocytes to injurious levels of strain (18% of strain). These results provide a basis for further examination of mechanotransduction in cartilage and raise a possibility of therapeutically targeting Piezo2-mediated mechanotransduction for the treatment of cartilage disease induced by repetitive mechanical forces. Impact statement Chondrocytes in cartilage are constantly subjected to load-induced stimuli and regulate their metabolic activities in order to maintain cartilage homeostasis. Therefore, mechanotransduction is important in chondrocytes and is vital for their role in cartilage function. Our results indicate that chondrocytes might sense and distinguish the different intensities of repetitive mechanical stimulus by using different mechanosensitive ion channels. Specifically, TRPV4 is mainly responsible for sensing physiologic levels of repetitive CTS stimulus, while Piezo2 mainly contributes to chondrocyte sensing noxious levels of repetitive CTS loading. These results provide a basis for further examination of mechanotransduction in cartilage and raise the possibility of therapeutically targeting Piezo2-mediated mechanotransduction for the treatment of OA which is induced by injurious and repetitive mechanical stimulation.

The purpose of this study was to analyze the chemical characterization of Tianshan green tea polysaccharides (TSPS), and evaluate its antioxidant activity by chemical-based and cellular-based antioxidant models in vitro. The results showed that the TSPS were composed of mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose with a molar ratio of 14.5:33.5:10.5:6.5:111.5:22.3:59.5:51: 1.0, and an average molecular weight of 19.49 kDa. TSPS exhibited excellent antioxidant ability to DPPH radical, hydroxyl radical, and ABTS radical, and enhanced the ferric-reducing power (FRAP). The antioxidation model of LO2 and HepG2 cells was established, and found that TSPS had no significant toxicity to either of the two cells at the range of 0.1-5 mg/mL, but clearly protected cells from H2 O2 -induced apoptosis and significantly reduced intracellular ROS level. In addition, the activities of antioxidant-associated enzymes were detected in LO2 cells, which suggested that TSPS could significantly improve the activities of SOD and CAT enzyme when the concentration was higher than 0.5 mg/mL. Furthermore, TSPS activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway by promoting Nrf2 nuclear translocation and inhibited the expression of Kelch-like ECH-associated protein 1 (Keap-1) and enhanced the expression of heme oxygenase-1 (HO-1). PRACTICAL APPLICATIONS: Tianshan green tea, a local variety in Fujian Province, belongs to unfermented tea. Polysaccharide is considered as the most promising component in Tianshan green tea. This study showed that TSPS had excellent antioxidant activity and had no significant toxicity to cells, which provides a scientific foundation and new idea for its further development and application in functional foods.

DNA origami technique provides a programmable way to construct nanostructures with arbitrary shapes. The dimension of assembled DNA origami, however, is usually limited by the length of the scaffold strand. Herein, we report a general strategy to efficiently organize multiple DNA origami tiles to form super-DNA origami using a flexible and covalent-bound branched DNA structure. In our design, the branched DNA structures (Bn: with a certain number of 2-6 branches) are synthesized by a copper-free click reaction. Equilateral triangular DNA origamis with different numbers of capture strands (Tn: T1, T2, and T3) are constructed as the coassembly tiles. After hybridization with the branched DNA structures, the super-DNA origami (up to 13 tiles) can be efficiently ordered in the predesigned patterns. Compared with traditional DNA junctions (Jn: J2-J6, as control groups) assembled by base pairing between several DNA strands, a higher yield and more compact structures are obtained using our strategy. The highly ordered and discrete DNA origamis can further precisely organize gold nanoparticles into different patterns. This rationally developed DNA origami ordering strategy based on the flexible and covalent-bound branched DNA structure presents a new avenue for the construction of sophisticated DNA architectures with larger molecular weights.

Remotely controlled on-demand functional healing is vital to components that are difficult to access and repair in distance such as satellites and unmanned cruising aircrafts. Compared with other stimuli, a blue laser is a better choice to input energy to the damaged area in distance because of its high energy density and low dissipation through the air. Herein, diselenide-containing polyurethane (PUSe) is first employed to fabricate visible light-responsive stretchable conductive composites with multiwalled carbon nanotubes (MWCNTs). Then, laser-induced remote healing was realized based on the characteristics of long-distance propagation of lasers and the dynamic properties of diselenide bonds. Moreover, the PUSe/MWCNT composite film can be used to transfer an electrical signal in the circuit containing a signal generator. This laser-induced remote healing of conductivity paves the way for developing healing conductors which are difficult to access and repair.

Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid "origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.

Feng Zhang,1 Wei Long,1 Qin Zhou,1 Jing Wang,1 Ye Shi,1 Jianbing Liu,1,* Qiuwei Wang2,* 1Department of Medical Genetics, Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Clinical Laboratory, Changzhou Children’s Hospital Affiliated to Nantong Medical University, Changzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianbing LiuDepartment of Medical Genetics, Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaTel +86 0519-88581983Email liujb2222@126.comQiuwei WangClinical Laboratory, Changzhou Children ’ s Hospital Affiliated to Nantong Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaTel +86 0519-69808280Email qiuwei_wang@ntu.edu.cnPurpose: This study aimed to explore the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal isolated nasal bone absence (INBA) or isolated nasal bone hypoplasia (INBH). We hope to provide additional relevant information for clinical counseling.Patients and Methods: From November 1, 2018, to March 1, 2020, 55 pregnant women with isolated nasal bone dysplasia were admitted to the Changzhou Maternity and Child Health Care Hospital. Based on the degree of abnormality, the patients were divided into two groups: INBA and INBH. CMA was performed on all patients. The clinical data and prenatal genetic diagnoses of the two groups were retrospectively analyzed. According to the requirements of WES for samples, 12 cases with negative CMA results were selected for the WES test.Results: A total of 55 cases with INBA or INBH met the inclusion criteria. In 35INBA fetuses, there was one case of trisomy 21 and one case of 10q11.22 deletion (5.7Mb), and the abnormality rate was 5.71% (2/35). Compared with INBA fetuses, the abnormality rate was increased in the fetuses with INBH [15.00% (3/20)] (15.00% vs 5.71%); there was one case of 1q21.1 duplication (1.3Mb), one case of Xp22.31 duplication (1.67Mb), and one case of 4p deletion (7.6Mb). In a later retrospective study, two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively.Conclusion: A preliminary study confirmed that molecular prenatal diagnosis should be performed in fetuses with INBA or INBH. CMA followed by WES is an effective method.Keywords: chromosomal microarray, whole exome sequencing, isolated nasal bone absence, isolated nasal bone hypoplasia