We propose a bacteria-based microrobot (bacteriobot) based on a new fusion paradigm for theranostic activities against solid tumors. We develop a bacteriobot using the strong attachment of bacteria to Cy5.5-coated polystyrene microbeads due to the high-affinity interaction between biotin and streptavidin. The chemotactic responses of the bacteria and the bacteriobots to the concentration gradients of lysates or spheroids of solid tumors can be detected as the migration of the bacteria and/or the bacteriobots out of the central region toward the side regions in a chemotactic microfluidic chamber. The bacteriobots showed higher migration velocity toward tumor cell lysates or spheroids than toward normal cells. In addition, when only the bacteriobots were injected to the CT-26 tumor mouse model, Cy5.5 signal was detected from the tumor site of the mouse model. In-vitro and in-vivo tests verified that the bacteriobots had chemotactic motility and tumor targeting ability. The new microrobot paradigm in which bacteria act as microactuators and microsensors to deliver microstructures to tumors can be considered a new theranostic methodology for targeting and treating solid tumors.

ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

No abstract

We fabricated a homogeneous thin film by blending a hole-transporting organic molecule having long alkyl chains, N,N′-bis(3-methylphenyl)-N,N′-bis(phenyl)-9,9-dioctylfluorene (DOFL-TPD), with InP/ZnSe/ZnS quantum dots (QDs) and used it as an emissive layer (EML) in a light-emitting diode (LED). The blended QD EML-based device exhibited an external quantum efficiency of 18.6% and a maximum luminance of 128 577 cd/m 2 . Additionally, its operational lifetime significantly increased in comparison to that of the control devices without DOFL-TPD. We found that the uniform distribution of DOFL-TPD in the blended QD EML without any phase separation facilitated hole injection into the EML and energy transfer to QDs. Moreover, it was newly discovered that the blended QD EML suppressed electron injection into the hole transport/injection layers, thereby preventing structural degradation of the device. The homogeneously blended QD layer with an efficient charge transport material shows a strong potential to develop efficient and stable optoelectronic devices with balanced charge density.

A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber.

The influence of the morphology of quantum dot (QD)‐semiconducting polymer hybrid emission layers on the performance of quantum dot‐based light emitting diodes (QLEDs) is systematically investigated. Chemically grafted QD‐semiconducting polymer hybrids are fabricated by the ligand exchange procedure between CdSe/CdxZn1−xS QDs and a new block copolymer consisting of a carbazole‐based electroactive block with a low highest occupied molecular orbital level and a disulfide‐based anchor block. The performance of QLEDs with hybrid emission layers is compared with QLEDs utilizing QD‐only and physically mixed QD/polymer emission layers. It is shown that only in the emission layers formed by chemically grafted hybrids QDs are evenly distributed throughout the semiconducting polymer matrix. This leads to improved charge transport balance and suppressed photoluminescence quenching of QDs. As a result, hybrid QLEDs with the peak external quantum efficiency of 5.6% and the peak luminance of 21 707 cd m−2 which outperform the conventional devices with QD‐only emission layers are fabricated.

We have investigated the possibility of fabricating quantum dot light‐emitting diodes (QLEDs) using inkjet printing technology, which is the most attractive method for the full‐color patterning of QLED displays. By controlling the quantum dot (QD) ink formulation and inkjet printing condition, we successfully patterned QLED pixels in the 60‐in ultrahigh definition TV format, which has a resolution of 73 pixels per inch. The inkjet‐printed QLEDs exhibited a maximum luminance of 2500 cd/m2. Although the performance of inkjet‐printed QLEDs is low compared with that of QLEDs fabricated using the spin‐coating process, our results clearly indicate that the inkjet printing technology is suitable for patterning QD emissive layers to realize high‐resolution, full‐color QLED displays.

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.