Surface Roughness Gradients Reveal Topography‐Specific Mechanosensitive Responses in Human Mesenchymal Stem Cells

The topographic features of an implant, which mechanically regulate cell behaviors and functions, are critical for the clinical success in tissue regeneration. How cells sense and respond to the topographical cues, e.g., interfacial roughness, is yet to be fully understood and even debatable. Here, the mechanotransduction and fate determination of human mesenchymal stem cells (MSCs) on surface roughness gradients are systematically studied. The broad range of topographical scales and high‐throughput imaging is achieved based on a catecholic polyglycerol coating fabricated by a one‐step‐tilted dip‐coating approach. It is revealed that the adhesion of MSCs is biphasically regulated by interfacial roughness. The cell mechanotransduction is investigated from focal adhesion to transcriptional activity, which explains that cellular response to interfacial roughness undergoes a direct force‐dependent mechanism. Moreover, the optimized roughness for promoting cell fate specification is explored

Determinants of L-Aspartate and IMP Recognition in Escherichia coli Adenylosuccinate Synthetase

Adenylosuccinate synthetase governs the first committed step in the de novo synthesis of AMP. Mutations of conserved residues in the synthetase fromEscherichia coli reveal significant roles for Val273 and Thr300 in the recognition ofL-aspartate, even though these residues do not or cannot hydrogen bond with the substrate. The mutation of Thr300 to alanine increases the K m forL-aspartate by 30-fold. In contrast, its mutation to valine causes no more than a 4-fold increase in the K m forL-aspartate, while increasing k catby 3-fold. Mutations of Val273 to alanine, threonine, or asparagine increase the K m forL-aspartate from 15- to 40-fold, and concomitantly decrease the K ifor dicarboxylate analogues ofL-aspartate by up to 40-fold. The above perturbations are comparable with those resulting from the elimination of a hydrogen bond between the enzyme and substrate: alanine mutations of Thr128 and Thr129 increase theK m for IMP by up to 30-fold and the alanine mutation of Thr301 abolishes catalysis supported byL-aspartate, but has no effect on catalysis supported by hydroxylamine. Structure-based mechanisms, by which the above residues influence substrate recognition, are presented

Acidochromic organic photovoltaic integrated device

Tremendous efforts have been devoted to boosting the power conversion efficiency (PCE) of organic solar cells (OSCs) via the introduction of cathode interlayers (CILs). However, CIL materials have limited diversity and the development of multifunctional devices is largely neglected. Herein, an acidochromic organic photovoltaic integrated device is firstly proposed by introducing an acid-sensitive stimulating-reaction organic molecule as both the CIL of OSCs and the sensor of monitoring environmental acidity. The oxazolidine unit of acidochromic molecule can form a ring-opening structure after acid treatment, resulting in the remarkable color change with the direct reflection of pH value of ecological environment. The additive-free PM6:Y6 OSCs using the acidochromic molecule as the CIL achieve an excellent PCE of above 15.29 %, which is 47 % higher than that of the control device. The PCE can even maintain above 92 % after treating CIL with various strong acids (pH = 1). Moreover, the color of acidified films and the degraded performance of acidified OSCs can be easily restored by alkaline treatment. The successful application of CIL in other highly efficient photovoltaic systems proves its good universality. This work triggers the promising application of acidochromic molecules in solar cells as CIL with the additional function of recognition of acid environment

13.4 % Efficiency from All-Small-Molecule Organic Solar Cells Based on a Crystalline Donor with Chlorine and Trialkylsilyl Substitutions

How to simultaneously achieve both high open-circuit voltage (Voc) and high short-circuit current density (Jsc) is a big challenge for realising high power conversion efficiency (PCE) in all-small-molecule organic solar cells (all-SM OSCs). Herein, a novel small molecule (SM)-donor, namely FYSM−SiCl, with trialkylsilyl and chlorine substitutions was designed and synthesized. Compared to the original SM-donor FYSM−H, FYSM−Si with trialkylsilyl substitution showed a decreased crystallinity and lower highest occupied molecular orbital (HOMO) level, while FYSM−SiCl had an improved crystallinity, more ordered packing arrangement, significantly lower HOMO level, and predominant “face-on” orientation. Matched with a SM-acceptor Y6, the FYSM−SiCl-based all-SM OSCs exhibited both high Voc of 0.85 V and high Jsc of 23.7 mA cm−2, which is rare for all-SM OSCs and could be attributed to the low HOMO level of FYSM−SiCl donor and the delicate balance between high crystallinity and suitable blend morphology. As a result, FYSM−SiCl achieved a high PCE of 13.4 % in all-SM OSCs, which was much higher than those of the FYSM−H- (10.9 %) and FYSM−Si-based devices (12.2 %). This work demonstrated a promising method for the design of efficient SM-donors by a side-chain engineering strategy via the introduction of trialkylsilyl and chlorine substitutions

10.13% Efficiency All-Polymer Solar Cells Enabled by Improving the Optical Absorption of Polymer Acceptors

The limited light absorption capacity for most polymer acceptors hinders the improvement of the power conversion efficiency (PCE) of all-polymer solar cells (all-PSCs). Herein, by simultaneously increasing the conjugation of the acceptor unit and enhancing the electron-donating ability of the donor unit, a novel narrow-bandgap polymer acceptor PF3-DTCO based on an A–D–A-structured acceptor unit ITIC16 and a carbon–oxygen (C–O)-bridged donor unit DTCO is developed. The extended conjugation of the acceptor units from IDIC16 to ITIC16 results in a red-shifted absorption spectrum and improved absorption coefficient without significant reduction of the lowest unoccupied molecular orbital energy level. Moreover, in addition to further broadening the absorption spectrum by the enhanced intramolecular charge transfer effect, the introduction of C–O bridges into the donor unit improves the absorption coefficient and electron mobility, as well as optimizes the morphology and molecular order of active layers. As a result, the PF3-DTCO achieves a higher PCE of 10.13% with a higher short-circuit current density (Jsc) of 15.75 mA cm−2 in all-PSCs compared with its original polymer acceptor PF2-DTC (PCE = 8.95% and Jsc = 13.82 mA cm−2). Herein, a promising method is provided to construct high-performance polymer acceptors with excellent optical absorption for efficient all-PSCs

Solid polymer electrolytes: Ion conduction mechanisms and enhancement strategies

Solid polymer electrolytes (SPEs) possess comprehensive advantages such as high flexibility, low interfacial resistance with the electrodes, excellent film-forming ability, and low price, however, their applications in solid-state batteries are mainly hindered by the insufficient ionic conductivity especially below the melting temperatures, etc. To improve the ion conduction capability and other properties, a variety of modification strategies have been exploited. In this review article, we scrutinize the structure characteristics and the ion transfer behaviors of the SPEs (and their composites) and then disclose the ion conduction mechanisms. The ion transport involves the ion hopping and the polymer segmental motion, and the improvement in the ionic conductivity is mainly attributed to the increase of the concentration and mobility of the charge carriers and the construction of fast-ion pathways. Furthermore, the recent advances on the modification strategies of the SPEs to enhance the ion conduction from copolymer structure design to lithium salt exploitation, additive engineering, and electrolyte micromorphology adjustion are summarized. This article intends to give a comprehensive, systemic, and profound understanding of the ion conduction and enhancement mechanisms of the SPEs for their viable applications in solid-state batteries with high safety and energy density

MicroRNA clusters integrate evolutionary constraints on expression and target affinities : the miR-6/5/4/286/3/309 cluster in Drosophila

This research was supported by the Hong Kong Research Grant Council GRF Grant (14103516), The Chinese University of Hong Kong Direct Grant (4053248), and TUYF Charitable Trust (6903957) (JHLH).A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs.PostprintPeer reviewe

Tubular basement membrane deposits after allogeneic hematopoietic stem cell transplantation

Abstract Background Extraglomerular immune complex deposition is rare and only a few membranous nephropathy cases with tubular basement membrane deposits have been reported following allogeneic hematopoietic stem cell transplantation. Case presentation We reported a 56-year-old man with increased serum creatinine after allogeneic hematopoietic stem cell transplantation who underwent a renal biopsy. Tubular interstitial nephritis was identified on light microscope. The unique histologic features were diffuse tubular basement membrane immune complex deposition detected by both immunofluorescence and electron microscopy, while the glomerular involvement was inconspicuous. The differential diagnosis from other forms of tubular basement membrane deposition is discussed. Conclusion Diffuse granular tubular basement membrane immune complex deposition with minimal glomerular involvement is also a manifestation of renal complication in hematopoietic stem cell transplantation recipient. However, the exact mechanism and target antigen remains unknown

CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells

MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host’s innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF-κB. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses