Cross-Linked Polyacrylic-Based Hydrogel Polymer Electrolytes for Flexible Supercapacitors.

Hydrogel polymer electrolytes (GPEs), as an important component of flexible energy storage devices, have gradually received wide attention compared with traditional liquid electrolytes due to their advantages of good mechanical, bending, and safety properties. In this paper, two cross-linked GPEs of poly(acrylic acid-co-acrylamide) or poly(acrylic acid-co-N-methylolacrylamide) with NaNO3 aqueous solution (P(AA-co-AM)/NaNO3 or P(AA-co-HAM)/NaNO3) were successfully prepared using radical polymerization, respectively, using acrylic acid (AA) as the monomer, N-methylolacrylamide (HAM) or acrylamide (AM) as the comonomer, and N, N-methylenebisacrylamide (MBAA) as the cross-linking agent. We investigated the morphology, glass transition temperature (Tg), ionic conductivities, mechanical properties, and thermal stabilities of the two GPEs. By comparison, P(AA-co-HAM)/NaNO3 GPE exhibits a higher ionic conductivity of 2.00 × 10-2 S/cm, lower Tg of 152 °C, and appropriate mechanical properties, which are attributed to the hydrogen bonding between the -COOH and -OH, and moderate cross-linking. The flexible symmetrical supercapacitors were assembled with the two GPEs and two identical activated carbon electrodes, respectively. The results show that the flexible supercapacitor with P(AA-co-HAM)/NaNO3 GPE shows good electrochemical performance with a specific capacitance of 63.9 F g-1 at a current density of 0.2 A g-1 and a capacitance retention of 89.4% after 3000 charge-discharge cycles. Our results provide a simple and practical design strategy of GPEs for flexible supercapacitors with wide application prospects.

VMF-SSD: A Novel V-Space Based Multi-Scale Feature Fusion SSD for Apple Leaf Disease Detection.

Apple leaf diseases seriously affect the quality of apples and may lead to yield losses, detecting apple leaf diseases accurately can prevent diseases from spreading and promote the healthy growth of the industry. However, recent studies cannot achieve accurate detection of leaf diseases with high accuracy because the lesions are of different sizes. So, this paper proposed a novel apple leaf disease detection method called VMF-SSD (V-space-based Multi-scale Feature-fusion SSD), which is designed to extract more reliable multi-scale feature representations for varied sizes of diseased spots and improve the final detection performance. The multi-scale feature extraction is established with multi-scale feature representation to further improve the disease detection performance, especially for small spots. After that, a V-space-based location branch is presented to enhance the texture feature information and help further identify disease spot location. Finally, attention mechanisms are utilized to automatically learn the importance of feature channels at different scales for distinguishing diseased spots of different sizes. Experimental results showed that the VMF-SSD method achieves 83.19% mAP and obtains the detection speed of 27.53 FPS on the test set, which indicates that the proposed VMF-SSD method can achieve competitive performance on apple leaf diseases detection task and satisfy the requirements of agricultural production applications.

Tightly intercalated Ti3C2Tx/MoO3-x/PEDOT:PSS free-standing films with high volumetric/gravimetric performance for flexible solid-state supercapacitors.

Ti3C2Tx-MXenes have extremely promising applications in electrochemistry, but the development of Ti3C2Tx is limited due to severe self-stacking problem. Here, we introduced oxygen vacancy-enriched molybdenum trioxide (MoO3-x) with pseudocapacitive properties as the intercalator of Ti3C2Tx and PEDOT with high electronic conductivity as the co-intercalator and conductive binder of Ti3C2Tx to synthesize Ti3C2Tx/MoO3-x/PEDOT:PSS (TMP) free-standing films by vacuum-assisted filtration and H2SO4 soaking. The tightly intercalated free-standing film structure can effectively improve the self-stacking phenomenon of Ti3C2Tx, expose more active sites and facilitate electron/ion transport, thus making TMP show excellent electrochemical performance. The volumetric and gravimetric capacitance of optimized TMP-2 can reach 1898.5 F cm-3 and 523.0 F g-1 at 1 A g-1 with a rate performance of 90.5% at the current density from 1 A g-1 to 20 A g-1, which is significantly better than those of MXene-based composites reported in the literature. The directly-assembled TMP-2//TMP-2 flexible solid-state supercapacitor displays high energy/power output performances (25.1 W h L-1 at 6383.1 W L-1, 6.9 W h kg-1 at 1758.4 W kg-1) and there is no obvious change after 100 cycles at a bending angle of 180°. As a result, the tightly intercalated TMP-2 free-standing film with high volumetric/gravimetric capacitances is a promising material for flexible energy storage devices.

Targeted-Deletion of a Tiny Sequence via Prime Editing to Restore SMN Expression.

Spinal muscular atrophy (SMA) is a devastating autosomal recessive motor neuron disease associated with mutations in the survival motor neuron 1 (SMN1) gene, the leading genetic cause of infant mortality. A nearly identical copy gene (SMN2) is retained in almost all patients with SMA. However, SMN2 fails to prevent disease development because of its alternative splicing, leading to a lack of exon 7 in the majority of SMN2 transcripts and yielding an unstable truncated protein. Several splicing regulatory elements, including intronic splicing silencer-N1 (ISS-N1) of SMN2 have been described. In this study, targeted-deletion of ISS-N1 was achieved using prime editing (PE) in SMA patient-specific induced pluripotent stem cells (SMA-iPSCs) with a high efficiency of 7/24. FL-SMN expression was restored in the targeted-deletion iPS clones and their derived motor neurons (iMNs). Notably, the apoptosis of the iMNs, caused by the loss of SMN protein that leads to the hyperactivity of endoplasmic reticulum (ER) stress, was alleviated in targeted-deletion iPSCs derived-iMNs. Thus, this is the first study to demonstrate that the targeted-deletion of ISS-N1 via PE for restoring FL-SMN expression holds therapeutic promise for SMA.

An Episomal CRISPR/Cas12a System for Mediating Efficient Gene Editing.

(1) Background: Gene editing technology, as represented by CRISPR is a powerful tool used in biomedical science. However, the editing efficiency of such technologies, especially in induced pluripotent stem cells (iPSCs) and other types of stem cells, is low which hinders its application in regenerative medicine; (2) Methods: A gene-editing system, COE, was designed and constructed based on CRISPR/Cas12a and Orip/EBNA1, and its editing efficiency was evaluated in human embryonic kidney 293T (HEK-293T) cells with flow cytometry and restriction fragment length polymorphism (RFLP) analysis. The COE was nucleofected into iPSCs, then, the editing efficiency was verified by a polymerase chain reaction and Sanger sequencing; (3) Results: With the extension of time, COE enables the generation of up to 90% insertion or deletion rates in HEK-293T cells. Furthermore, the deletion of a 2.5 kb fragment containing Exon 51 of the dystrophin gene (DMD) in iPSCs was achieved with high efficiency; out of 14 clones analyzed, 3 were positive. Additionally, the Exon 51-deleted iPSCs derived from cardiomyocytes had similar expression profiles to those of Duchenne muscular dystrophy (DMD) patient-specific iPSCs. Moreover, there was no residue of each component of the plasmid in the editing cells; (4) Conclusions: In this study, a novel, efficient, and safe gene-editing system, COE, was developed, providing a powerful tool for gene editing.

The clinicopathological and genetic features of ovarian diffuse large B-cell lymphoma.

Ovarian lymphoma, whether a primary or secondary condition, is very rare. Little is known about its genetic aberrations. Here, we reviewed the clinical, morphological and immunohistochemical characteristics of nine ovarian diffuse large B-cell lymphoma (DLBCL) cases and performed fluorescence in situ hybridisation (FISH) analysis to detect MYC, BCL2 and BCL6 translocations. We also performed whole exome sequencing analysis to determine their genomic features compared with those of conventional extranodal DLBCL. The results showed that six of nine cases were bilateral and three cases were left-sided. Histologically, the tumour cells were homogeneous and a starry-sky pattern was very common in ovarian DLBCL (Burkitt-like). Immunohistochemically, most of the cases (7/9) were germinal centre B-cell-like (GCB) subtype, and dual expression of MYC and BCL2 was found in three cases of ovarian DLBCL. A double-hit (involving MYC and BCL6) phenotype was found in one case of ovarian DLBCL (GCB subtype). Sequencing analysis revealed that NOTCH4, NCOR2, BCL10 and CARD11 were frequently mutated both in ovarian DLBCL and conventional extranodal DLBCL. COL27A1, PRKCB, HLA-A, NOTCH3 and HDAC4 mutations were found only in ovarian DLBCL but not in conventional DLBCL, and NOTCH3 and HDAC4 mutations were only identified in the GCB subtype. Furthermore, several signalling pathways including the B-cell receptor, Epstein-Barr virus infection, HTLV-1 infection, Notch, PI3K-AKT and mTOR were found to be involved in ovarian DLBCL. Our results broaden the understanding of the clinicopathological and molecular characteristics of ovarian DLBCL and compare their genetic features to those of conventional extranodal DLBCL for the first time.

Unexpected Polypseudorotaxanes Formed from the Self-assembly of ß-Cyclodextrins with Poly( N-isopropylacrylamide) Homo- and Copolymers.

Compared with polypseudorotaxanes (PPRs) formed from the self-assembly of ß-cyclodextrins (ß-CDs) with poly(propylene glycol) (PPG) and γ-CDs with poly( N-isopropylacrylamide) (PNIPAAm), the ratio of the inner cavity size of ß-CD to the cross-sectional area of PNIPAAm appears not appropriate for their self-assembly. For a better understanding of the possibility of ß-CDs including PNIPAAm and the crystal structure of PPRs formed therefrom, the PNIPAAm homo- and copolymers were subjected to self-assembly with ß-CDs in an aqueous solution at room temperature. The results revealed that when ß-CDs meet thicker PNIPAAms, the self-assembly takes place, not only giving rise to PPRs by a manner of main-chain inclusion complexation but also presenting the PPRs a matched over-fit crystal structure different from those of either a matched tight-fit ß-CD-PPG PPR or a mismatched over-fit γ-CD-PNIPAAm PPR. This is most likely due to the thicker PNIPAAm adapting its unfavorable main-chain cross-sectional area to fit into the cavity of ß-CDs by changing the side-chain conformations. Based on the X-ray diffraction patterns, a monoclinic crystal system was created from these PPRs and the unit cell parameters calculated were as follows: a = 15.3 Å, b = 10.3 Å, and c = 21.2 Å; ß = 110.3°; and space group P2. It suggested that this matched over-fit crystal structure would possess a Mosaic crystal structure rather than a typical channel-like one.

Paired CRISPR/Cas9 Nickases Mediate Efficient Site-Specific Integration of F9 into rDNA Locus of Mouse ESCs.

Hemophilia B (HB) is an X-linked recessive bleeding disorder, caused by F9 gene deficiency. Gene therapy combined with the CRISPR/Cas9 technology offers a potential cure for hemophilia B. Now the Cas9 nickase (Cas9n) shows a great advantage in reducing off-target effect compared with wild-type Cas9. In this study, we found that in the multicopy ribosomal DNA (rDNA) locus, the homology directed recombination (HDR) efficiency induced by sgRNA-Cas9n was much higher than sgRNA-Cas9, meanwhile without off-target in six predicted sites. After co-transfection into mESCs with sgRNA-Cas9n and a non-viral rDNA targeting vector pMrnF9, harboring the homology donor template and the human F9 expression cassette, a recombination efficiency of 66.7% was achieved and all targeted clones were confirmed to be site-specific integration of F9 in the rDNA locus by PCR and southern blotting. Targeted mESCs retained the main pluripotent properties and were then differentiated into hepatic progenitor like cells (HPLCs) and mature hepatocytes, which were characterized by hepatic markers and functional assays. Importantly, the differentiated cells could transcribe exogenous F9 and secrete coagulation factor IX (FIX) proteins, suggesting active transcription and stable inheritance of transgenes in the rDNA locus. After intrasplenical transplantation in severe combined immune deficiency (SCID) mice, targeted HPLCs could survive and migrate from spleen to liver, resulting in secretion of exogenous FIX into blood. In summary, we demonstrate an efficient and site-specific gene targeting strategy in rDNA locus for stem cell-based gene therapy for hemophilia B.

A vascular tissue engineering scaffold with core-shell structured nano-fibers formed by coaxial electrospinning and its biocompatibility evaluation.

In this article, a tubular vascular tissue engineering scaffold with core-shell structured fibers was produced by coaxial electrospinning at an appropriate flow rate ratio between the inner and outer solution. PCL was selected as the core to provide the mechanical property and integrity to the scaffold while collagen was used as the shell to improve the attachment and proliferation of vascular cells due to its excellent biocompatibility. The fine core-shell structured fibers were demonstrated by scanning electron microscope and transmission electron microscope observations. Subsequently, the collagen shell was crosslinked by genipin and further bound with heparin. The crosslinking process was confirmed by the increasing of tensile strength, swelling ratio and thermogravimetric analysis measurements while the surface heparin content was characterized by means of a UV-spectrophotometer and activated partial thromboplastin time tests. Furthermore, the mechanical properties such as stitch strength and bursting pressure of the as-prepared scaffold were measured. Moreover, the biocompatibility of the scaffold was evaluated by cytotoxicity investigation with L929 cells via MTT assay. Endothelial cell adhesion assessments were conducted to reveal the possibility of the formation of an endothelial cell layer on the scaffold surface, while the ability of smooth muscle cell penetration into the scaffold wall was also assessed by confocal laser scanning microscopy. The as-prepared core-shell structured scaffold showed promising potential for use in vascular tissue engineering.

Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

[Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.