Multiscale embedded printing of engineered human tissue and organ equivalents.

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.

Real-Time Detection of Multiple Intracellular MicroRNAs using an Ultrasound-Propelled Nanomotor-Based Dynamic Fluorescent Probe.

Multiple intracellular microRNA (miRNA) detection is essential for disease diagnosis and management. Nonetheless, the real-time detection of multiple intracellular miRNAs has remained challenging. Herein, we have developed an ultrasound (US)-powered nanomotor-based dynamic fluorescent probe for the real-time OFF-ON fluorescent determination of multiple intracellular miRNAs. The new probe relies on the utilization of multicolored quantum dot (QD)-labeled single-stranded DNA (ssDNA)/graphene oxide (GO)-coated US-powered gold nanowire (AuNW) nanomotors. The fluorescence of QDs is quenched due to π-π interactions with the GO. Upon binding to target miRNAs, the QDs-ssDNA is now distant from the AuNWs, resulting in effective OFF-ON QD fluorescence switching. Compared with conventional passive probes, the dynamic fluorescent probe enhances probe-target interactions by using the US-propelled nanomotor, resulting in exceptionally efficient and prompt hybridization. Simultaneous quantitative analysis of miR-10b and miR-21 in vitro can be achieved within 15 min with high sensitivity and specificity. Additionally, multicolor QDs provide strong signal intensity and multiplexed detection, enabling one-step real-time discrimination between cancer cells (A549) and normal cells (L02). The obtained results are in good agreement with those from qRT-PCR. This dynamic fluorescent probe based on a nanomotor and QDs enables rapid "on the move" specific detection of multiple intracellular miRNAs in intact cells, facilitating real-time monitoring of diverse intracellular miRNA expression, and it could pave the way for novel applications of nanomotors in biodetection.

Correction: A poly(thymine)-templated fluorescent copper nanoparticle hydrogel-based visual and portable strategy for an organophosphorus pesticide assay.

Correction for 'A poly(thymine)-templated fluorescent copper nanoparticle hydrogel-based visual and portable strategy for an organophosphorus pesticide assay' by Jihua Chen et al., Analyst, 2019, 144, 2423-2429, https://doi.org/10.1039/C9AN00017H.

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota.

INTRODUCTION: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. METHODS: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. RESULTS: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1ß and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. CONCLUSION: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Construction of a novel digital method for quantitative analysis of occlusal contact and force.

BACKGROUND: Occlusal analysis is essential in the dental clinical practice. However, the traditional occlusal analysis performed on the two-dimensional level can not directly correspond to the tooth surface with three-dimensional profile, therefore the clinical guidance value is limited. METHODS: By combining the 3D digital dental models and quantitative data from 2D occlusal contact analysis, this study constructed a novel digital occlusal analysis method. The validity and reliability of DP and SA were verified by comparing the results of occlusal analysis of 22 participants. ICC values for occlusal contact area (OCA) and occlusal contact number (OCN) were tested. RESULTS: Results confirmed the reliability of the two occlusal analysis methods with ICC values of 0.909 for SAOCA, 0.906 for DPOCA, 0.929 for SAOCN and 0.904 for DPOCN. The Bland-Altman plot, paired t-test (tOCN = 0.691, P > 0.05) and Pearson correlation analysis results (R = 0.68, p < 0.001) verified the validity between SA and DP. Then a novel digital occlusal analysis method was constructed, which not only can locate the occlusion contact and provide the quantitative analysis, but also provide a comprehensive description of the resultant force of each tooth and the component forces on the x-, y- and z-axis. CONCLUSIONS: This new occlusal analysis method can obtain quantitative analysis of occlusal contact including contact area and force information simultaneously, which will provide new impetus and greater help for clinical dental treatment and scientific research.

Autoimmune glial fibrillary acidic protein astrocytopathy presented as isolated area postrema symdrome: a case report.

BACKGROUND: Area postrema syndrome (APS) as the isolated manifestation in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been rarely reported. CASE PRESENTATION: A 61-year-old male patient presented with intractable hiccup. He was first admitted to the department of Gastroenterology because he had no symptoms other than hiccup. Then he was diagnosed with possible digestive system disease and started on treatment. 2 weeks later, his symptom didn't improve at all. After consultation, the patient was referred to our department. Cerebrospinal fluid (CSF) analysis revealed lymphocytes pleocytosis, elevated protein level. Cell-based assays demonstrated GFAP antibodies in blood and CSF. His symptom improved with steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone. Three months after the initial presentation, he showed no relapses. CONCLUSIONS: We report atypical manifestation of autoimmune GFAP astrocytopathy which presented as APS, suggesting that autoimmune GFAP astrocytopathy should be added to the list of possible cause of APS.

Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder.

Microcystin-LR (MC-LR), a potent hepatotoxin can cause liver damages. However, research on hepatic lipid metabolism caused by long-term exposure to environmental concentrations MC-LR is limited. In the current study, mice were exposed to various low concentrations of MC-LR (0, 1, 30, 60, 90, 120 µg/L in the drinking water) for 9 months. The general parameters, serum and liver lipids, liver tissue pathology, lipid metabolism-related genes and proteins of liver were investigated. The results show that chronic MC-LR exposure had increased the levels of triglyceride (TG) and total cholesterol (TC) in serum and liver. In addition, histological observation revealed that hepatic lobules were disordered with obvious inflammatory cell infiltration and lipid droplets. More importantly, the mRNA and proteins expression levels of lipid synthesis-related nuclear sterol regulatory element binding protein-1c (nSREBP-1c), SREBP-1c, cluster of differentiation 36 (CD36), acetyl-CoA-carboxylase1 (ACC1), stearoyl-CoA desaturase1 (SCD1) and fatty acid synthase (FASN) were increased in MC-LR treated groups, the expression levels of fatty acids ß-oxidation related genes peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) was decreased after exposure to 60-120 µg/L MC-LR. Furthermore, the inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were higher than that in the control group. All the findings indicated that mice were exposed to chronic low concentrations MC-LR caused liver inflammation and hepatic lipid metabolism disorder .

Optimal Mapping of Spiking Neural Network to Neuromorphic Hardware for Edge-AI.

Neuromorphic hardware, the new generation of non-von Neumann computing system, implements spiking neurons and synapses to spiking neural network (SNN)-based applications. The energy-efficient property makes the neuromorphic hardware suitable for power-constrained environments where sensors and edge nodes of the internet of things (IoT) work. The mapping of SNNs onto neuromorphic hardware is challenging because a non-optimized mapping may result in a high network-on-chip (NoC) latency and energy consumption. In this paper, we propose NeuMap, a simple and fast toolchain, to map SNNs onto the multicore neuromorphic hardware. NeuMap first obtains the communication patterns of an SNN by calculation that simplifies the mapping process. Then, NeuMap exploits localized connections, divides the adjacent layers into a sub-network, and partitions each sub-network into multiple clusters while meeting the hardware resource constraints. Finally, we employ a meta-heuristics algorithm to search for the best cluster-to-core mapping scheme in the reduced searching space. We conduct experiments using six realistic SNN-based applications to evaluate NeuMap and two prior works (SpiNeMap and SNEAP). The experimental results show that, compared to SpiNeMap and SNEAP, NeuMap reduces the average energy consumption by 84% and 17% and has 55% and 12% lower spike latency, respectively.

Use of a digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery.

A digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery is presented. This technique integrates bone reduction and implant placement information into a dual-function surgical template and introduces a digital approach to fabricating immediate interim implant-supported fixed dental prostheses with the same occlusal relationship as the one evaluated with diagnostic removable prostheses.

Synthesis of Poly(ionic Liquid)s-block-poly(methyl Methacrylate) Copolymer-Grafted Silica Particle Brushes with Enhanced CO2 Permeability and Mechanical Performance.

Poly(ionic liquid) (PIL)-based block copolymers are of particular interest as they combine the specific properties of PILs with the self-assembling behaviors of block copolymers, broadening the range of potential applications for PIL-based materials. In this work, three particle brushes: SiO2-g-poly(methyl methacrylate) (PMMA), SiO2-g-PIL, and SiO2-g-PMMA-b-PIL were prepared through surface-initiated atom transfer radical polymerization. Unlike the homogeneous homopolymer particle brushes, the block copolymer particle brush SiO2-g-PMMA-b-PIL exhibited a bimodal chain architecture and unique phase-separated morphology, which were confirmed by size-exclusion chromatography and transmission electron microscopy. In addition, the influence of the introduction of the PMMA segment on the gas separation and mechanical performance of the PIL-containing block copolymer particle brushes were investigated. A significant improvement of Young's modulus was observed in the SiO2-g-PMMA-b-PIL compared to the SiO2-g-PIL bulk films; meanwhile, their gas separation performances (CO2 permeability and CO2/N2 selectivity) were the same, which demonstrates the possibility of improving the mechanical properties of PIL-based particle brushes without compromising their gas separation performance.

Biotin exposure-based immunomagnetic separation coupled with sodium dodecyl sulfate, propidium monoazide, and multiplex real-time PCR for rapid detection of viable Salmonella Typhimurium, Staphylococcus aureus, and Listeria monocytogenes in milk.

In this study, we established a rapid and sensitive method for the detection of viable Salmonella Typhimurium, Staphylococcus aureus, and Listeria monocytogenes in milk using biotin-exposure-based immunomagnetic separation (IMS) combined with sodium dodecyl sulfate (SDS), propidium monoazide (PMA), and multiplex real-time PCR (mRT-PCR). We used IMS to lessen the assay time for isolation of target bacteria. We then optimized the coupling conditions and immunomagnetic capture process. The immunoreaction and incubation times for 5 µg of mAb coupled with 500 µg of streptavidin-functionalized magnetic beads using a streptavidin-biotin system were 90 and 30 min, respectively. Treatment with SDS-PMA before mRT-PCR amplification eliminated false-positive outcomes from dead bacteria and identified viable target bacteria with good sensitivity and specificity. The limit of detection of IMS combined with the SDS-PMA-mRT-PCR assay for the detection of viable Salmonella Typhimurium, Staph. aureus, and L. monocytogenes in spiked milk matrix samples was 10 cfu/mL and remained significant even in the appearance of 106 cfu/mL of nontarget bacteria. The entire detection process was able to identify viable bacteria within 9 h. The combination of biotin-exposure-mediated IMS and SDS-PMA-mRT-PCR has potential value for the rapid and sensitive detection of foodborne pathogens.

MBP-activated autoimmunity plays a role in arsenic-induced peripheral neuropathy and the potential protective effect of mecobalamin.

Intake excessive arsenic (As) is related to the occurrence of peripheral neuropathy. However, both the underlying mechanism and the preventive approach remain largely unknown. In the present study, As treatment significantly decreased the mechanical withdrawal threshold and increased the titer of anti-myelin basic protein antibody in rats, accompanied with damaged BNB. The levels of inflammatory cytokines and proteolytic enzymes were also significantly upregulated. However, administration of MeCbl in As-treated rats significantly reversed the decline in hindfoot mechanical withdrawal threshold, as well as BNB failure and sciatic nerve inflammation. Repeated As treatment in athymic nude mice indicated that sciatic nerve inflammation and mechanical hyperalgesia were T cell-dependent. These data implicated that MBP-activated autoimmunity and the related neuroinflammation probably contributed to As-induced mechanical hyperalgesia and MeCbl exerted a protective role probably via maintenance the integrity of BNB and inhibition of neuroinflammation.

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management.

Rheumatoid arthritis (RA) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and bone damage as well as progressive disability. Synovial inflammation is promoted through the infiltration of mononuclear immune cells, dominated by CD4+ T cells, macrophages and dendritic cells (DCs), together with fibroblast-like synoviocytes (FLS), into the synovial compartment. Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly attributed to immunomodulatory and anti-inflammatory effects. Several lines of experimental study have recently investigated the therapeutic potential of berberine and its underlying mechanisms in treating RA condition. The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/ß-catenin, AMPK/lipogenesis and LPA/LPA1 /ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. Importantly, these molecular targets may explore new therapeutic targets for RA treatment.

Dynamic Precipitation, Dynamic Recrystallization, and Texture Evolution of Mg-5Zn Alloy Sheets with Trace Ca and Sr Additions.

The effects of trace Ca and Sr addition on dynamic precipitates, dynamic recrystallization (DRX) behavior, and texture evolution of Mg­5Zn alloy sheets fabricated by high strain rate rolling (HSRR) were investigated by electron backscattered diffraction (EBSD), transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and X-ray diffraction (XRD). The Zn-rich precipitates formed with plate shapes, short-rod shapes, and near-spherical shapes, indicating that the most important function of adding Ca and Sr is to promote the precipitation process. The precipitate density increases, but the precipitate size and DRX volume fraction decrease with the addition of the alloying elements. It is concluded that the effects of combined Ca/Sr addition on promoting precipitation and refining precipitate size are more effective than that of single Ca addition, and the reduction in DRX volume fraction can be attributed to the inhibition of fine precipitation on the nucleation and growth of DRX. Moreover, the macro-texture intensity is mainly related to DRX as the DRX grains are much more randomly oriented than deformed grains. In addition, the texture intensity in DRX regions is primarily associated with the precipitates, which can inhibit DRX grain rotation due to their pinning effect on the grain boundaries.

Polymer additive controlled morphology for high performance organic thin film transistors.

Solution-crystallizable small-molecule organic semiconductors, such as 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene), 5,11-bis(triethylgermylethynyl)anthradithiophene (diF-TEG-ADT), 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT), and N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDIF-CN2), demonstrate various practical advantages including high mobility, air stability and solution processibility. In this article, we review various polymer additive based approaches to control the crystal morphology and the resultant charge transport of some bench-mark, high performance, solution crystallizable, small-molecule organic semiconductors. The polymer additives are discussed under the categories of non-conjugated polymers and conjugated polymers. The approaches and structure-performance correlations that we discussed here may be applied far beyond the examples shown in this review and have important implications for high performance organic semiconductors in general.

Associations among gastroesophageal reflux disease, mental disorders, sleep and chronic temporomandibular disorder: a case-control study.

BACKGROUND: Temporomandibular disorders (TMDs) are a family of pain-related disorders associated with impaired function in the jaw, temporomandibular joint and muscles of mastication. Our objectives were to evaluate the association between chronic TMD and gastresophageal reflux disease (GERD) and to determine whether mental disorders or undermined sleep mediates this association. METHODS: We conducted a case-control study involving 1522 consecutive adult patients with chronic TMD and 1522 matched controls from 2 hospitals in China. All participants were aged between 18 and 70 years and were recruited from July 2017 to April 2018 Chronic TMD was diagnosed by trained dentists using the criteria in the Orofacial Pain Prospective Evaluation and Risk Assessment Study. Trained gastroenterologists made blinded diagnoses of GERD according to the Montreal definition and classification (at least 2 d of mild symptoms, or 1 d of moderate or severe symptoms per week). We used validated questionnaires to evaluate psychological status and sleep quality. RESULTS: Of the study participants, we identified 132 patients and 61 controls with GERD. Using conditional logistic regression analysis, we identified GERD as a risk factor for TMD (odds ratio 2.74, 95% confidence interval 1.88 to 3.98). Mediation analyses identified that somatization, anxiety and undermined sleep moderately mediated the relation between TMD and GERD. INTERPRETATION: Our study suggests that symptomatic GERD is associated with chronic, painful TMD, and somatization, anxiety and undermined sleep mediate this association to a certain extent. Due consideration should be given to the evaluation and management of gastrointestinal symptoms and mental disorders in the combined therapy for painful TMD.

A poly(thymine)-templated fluorescent copper nanoparticle hydrogel-based visual and portable strategy for an organophosphorus pesticide assay.

Since fluorescence assays with high sensitivity for organophosphorus pesticides (OPs) are urgently required to protect the ecosystem and prevent disease, an environmentally friendly and label-free fluorescent probe is desirable. Herein, a poly-thymine30 DNA-templated copper nanoparticle (poly T30-Cu NPs) hydrogel fluorescent probe was explored for the construction of an OPs sensing platform via tyrosinase (TYR) enzyme-controlled quenching. Initially, TYR can efficiently quench the fluorescence of poly T30-Cu NPs; however, when OPs are mixed with a certain amount of TYR, the fluorescence of poly T30-Cu NPs can be recovered. Based on this phenomenon, we designed a functionalized hydrogel based on poly T30-Cu NPs for portable and visible detection of OPs with high sensitivity and selectivity. This proposed fluorescent platform was demonstrated to enable rapid detection of OPs (paraoxon as the model analyte) and provide excellent sensitivity with a detection limit of 3.33 × 10-5 ng µL-1 and a linear range of 1.0 × 10-4-1.0 ng µL-1. The fluorescent probe does not require a sophisticated synthesis and labeling process; in addition, it is environmentally friendly because of the presence of a biotemplate of DNA and biocompatible copper. Moreover, the functional hydrogel combines the features of portability, visualization, fast signal response and environmental anti-interference that make the proposed strategy more feasible in complex practical detection.

Solvent-Free Synthesis of CuO/HKUST-1 Composite and Its Photocatalytic Application.

A metal-organic framework (MOF) is one kind of crystalline microporous material and is increasingly used as a host of catalytically active guests. Nanostructured materials supported on MOFs have presented enhanced catalytic activity and stability. Templates or several steps are essential to the synthesis of MOF composites. Simple and effective MOF synthesis methods are still challenging. Nanosized copper oxide particles in MOF composites, described as nanosized CuO@HKUST-1, were prepared by a facile solvent-free reaction. These series of CuO@HKUST-1 composites exhibited excellent photocatalytic activity for production of hydrogen and methylene blue (MB) degradation under visible light. This synthesis method provides an effective way to fabricate MOF-related nanocomposite catalysts.

An Ionomeric Renewable Thermoplastic from Lignin-Reinforced Rubber.

An ionomeric, leathery thermoplastic with high mechanical strength is prepared by a new thermal processing method from a soft, melt-processable rubber. Compositions made by incorporation of equal-mass lignin, a renewable oligomeric feedstock, in an acrylonitrile-butadiene rubber often yield weak rubbers with large lignin domains (1-2 µm). The addition of zinc chloride (ZnCl2 ) in such a composition based on sinapyl alcohol-rich lignin during a solvent-free synthesis induces a strong interfacial crosslinking between lignin and rubber phases. This compositional modification results in finely interspersed lignin domains (<100 nm) that essentially reinforce the rubbery matrix with a 10-22 °C rise in the glassy-to-rubbery transition temperature. The ion-modified polymer blends also show improved materials properties, like a 100% increase in ultimate tensile strength and an order of magnitude rise in Young's modulus. Coarse-grained molecular dynamics (MD) simulations verify the morphology and dynamics of the ionomeric material. The computed result also confirms that the ionomers have glassy characteristics.

Effects of microcystins-LR on genotoxic responses in human intestinal epithelial cells (NCM460).

Microcystin-LR (MC-LR), a cyclic heptapeptide toxin produced by cyanobacteria, was found to induce genotoxic actions in various types of cells. Some investigators reported that microcystin-LR acted as tumor initiator in the observed genotoxic action mediated by this cyanotoxin. However, the underlying mechanisms underlying MC-induced DNA damage in the human intestine epithelium cell line (NCM460) are not known. The purpose of this study was to examine the influence of 24 hr exposure to 5 or 10 µM MC-LR on intestinal DNA damage using NCM460 intestine cell line as a model. Data showed that MC-LR increased Olive tail moment (OTM) as evidenced by the comet assay, inhibited protein phosphatase 2A (PP2A) activity, elevated reactive oxygen species levels (ROS) and enhanced γ-H2AX and p-p53 protein expression levels. Results indicated that MC-LR produced intestinal DNA damage by inhibiting PP2A activity, activating p53 protein and subsequently initiating excess generation of ROS. These observations suggest that MC-LR-induced intestinal DNA damage involves a complex series of events that include oxidant stress, PP2A enzymic inhibition and activation of p53 protein.