Biohybrid Urchin-Like ZnO-Based Microspheres with Tunable Hierarchical Structures and Enhanced Photoelectrocatalytic Properties.

Microorganisms have attracted much attention to act as biotemplates for fabricating micro/nanostructured functional particles. However, it is still challenging to produce tunable hierarchical particles based on microorganisms with intricate architectures and superior stability. Herein, a novel strategy is developed to fabricate biohybrid urchin-like magnetic ZnO microspheres based on Chlorella (Ch.) with tunable hierarchical core-shell structures. Using Ch. cells as microspherical templates, Fe3 O4 nanoparticles and ZnO nanorod (NR) arrays are deposited in sequence to form the final biohybrid heterostructure microspheres (Ch.@Fe3 O4 @ZnO NRs). Ordered growth and structural regulation of 3D ZnO NR arrays are achieved via a facile and controllable manner. Compared with the prepared microspheres with diverse structure configurations of ZnO shells, the Ch.@Fe3 O4 @ZnO NRs possess excellent light absorption and photoelectrocatalysis performance toward tetracycline degradation (normalized apparent rate constant, k = 366.3 h-1 g-1 ), which is significantly larger than that of ZnO nanoflower/nanoparticle loaded types. It also proves that the synergistic enhancement of well-oriented ZnO NR arrays, heterojunction structures, and biomass features is the fundamental reason for outstanding photoelectrocatalytic activity. Due to the remarkable stability and versatility, this work provides abundant opportunities to construct biohybrid multilevel micro/nanostructures with significant potentials for practical applications.

Magnetically Actuated Cell-Robot System: Precise Control, Manipulation, and Multimode Conversion.

Border-nearing microrobots with self-propelling and navigating capabilities have promising applications in micromanipulation and bioengineering, because they can stimulate the surrounding fluid flow for object transportation. However, ensuring the biosafety of microrobots is a concurrent challenge in bioengineering applications. Here, macrophage template-based microrobots (cell robots) that can be controlled individually or in chain-like swarms are proposed, which can transport various objects. The cell robots are constructed using the phagocytic ability of macrophages to load nanomagnetic particles while maintaining their viability. The robots exhibit high position control accuracy and generate a flow field that can be used to transport microspheres and sperm when exposed to an external magnetic field near a wall. The cell robots can also form chain-like swarms to transport a large object (more than 100 times the volume). This new insight into the manipulation of macrophage-based cell robots provides a new concept by converting other biological cells into microrobots for micromanipulation in biomedical applications.

Continuous directional water transport on the peristome surface of Nepenthes alata.

Numerous natural systems contain surfaces or threads that enable directional water transport. This behaviour is usually ascribed to hierarchical structural features at the microscale and nanoscale, with gradients in surface energy and gradients in Laplace pressure thought to be the main driving forces. Here we study the prey-trapping pitcher organs of the carnivorous plant Nepenthes alata. We find that continuous, directional water transport occurs on the surface of the 'peristome'--the rim of the pitcher--because of its multiscale structure, which optimizes and enhances capillary rise in the transport direction, and prevents backflow by pinning in place any water front that is moving in the reverse direction. This results not only in unidirectional flow despite the absence of any surface-energy gradient, but also in a transport speed that is much higher than previously thought. We anticipate that the basic 'design' principles underlying this behaviour could be used to develop artificial fluid-transport systems with practical applications.

Air Bubble Bridge-Based Bioinspired Underwater Adhesion.

Wet adhesion is greatly demanded in fields of wearable devices, wound dressings, and smart robotics. However, reusable, noninvasive and convenient adhesive pads in the liquid environment have remained a challenge. Here, a novel concept of underwater adhesion inspired by the diving beetle, which utilizes the air bubbles as an adhesive to realize nondestructive and repeatable adhesion working across a wide range of scales is shown. The mechanism of underwater bubble adhesion is revealed by the capillarity of air-bubble bridge, of which the property depends on the dynamic bubble contact angles and the gap distance. The design principle of the air bubble-based underwater adhesion is proposed and validated to tune the interfacial acting force by theoretical and experimental results. Finally, a strong, reusable surface adhesive based on air bubble bridges is demonstrated from macro- to microscales in applications of particle manipulation and particle self-assembly. This unique view of underwater bubble adhesion provides new ideas for broader applications.

Precise Control of Customized Macrophage Cell Robot for Targeted Therapy of Solid Tumors with Minimal Invasion.

Injecting micro/nanorobots into the body to kill tumors is one of the ultimate ambitions for medical nanotechnology. However, injecting current micro/nanorobots based on 3D-printed biocompatible materials directly into blood vessels for targeted therapy is often difficult, and mistakes in targeting can cause serious side effects, such as blood clots, oxidative stress, or inflammation. The natural affinity of macrophages to tumors, and their natural phagocytosis and ability to invade tumors, make them outstanding drug delivery vehicles for targeted tumor therapy. Hence, a magnetically controlled cell robot (MCR) based on a macrophage drug carrier is proposed. Here, living macrophages are converted into MCRs through endocytosis of specially-designed magnetic nanoparticles loaded with doxorubicin and indocyanine green. Following this, the MCRs can be transported to tumors through the blood vessels using external magnetic fields, and penetrate the blood vessels into the interior of the tumor due to their deformability. With the MCR's cascaded drug release, targeted killing of tumors in mice is demonstrated, with minimal effects on the normal surrounding tissue. The ability to impart precise drug doses onto natural cells, such as macrophages, and load various functional components into the MCRs, offers an efficient method for precise targeted therapy.

MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide. Recent studies have shown that the polytopic enzyme membrane associated ring-CH-type finger 6 (MARCH6) participates in tumorigenesis, but its function in HCC development needs to be investigated. This study aimed to explore the role of MARCH6 in HCC. METHODS: Expression of MARCH6 in human HCC samples was checked by immunohistochemical staining assay. Clinical relevance of MARCH6 and activating transcription factor 2 (ATF2) was analyzed from TCGA database. CCK-8, EdU staining, colony formation and transwell were performed to assess cell proliferation, growth and migration. Xenografted tumorigenesis was used to examine in vivo role MARCH6. Immunoblotting was applied to detect protein abundance. RESULTS: We found that MARCH6 expression was elevated in human HCC samples. Over-expression of MARCH6 was associated with poor prognosis of HCC patients. Up-expression of MARCH6 promoted cell growth and migration of HCC cells. In contrast, the HCC cell growth and migration were suppressed by MARCH6 knockdown. Furthermore, the DNA synthesis was enhanced by MARCH6. The expression of ATF2 was potentiated by MARCH6 over-expression, while it was suppressed by MARCH6 silencing. TCGA database showed positive correlation between the expression of MARCH6 and ATF2. Importantly, ATF2 expression contributed to the oncogenic function of HCC cells. CONCLUSION: Our findings suggest that MARCH6-mediated ATF2 up-regulation contributes to HCC development. MARCH6 may be a promising target for the diagnosis and treatment of HCC.

The relationship between red blood cell distribution and islet ß-cell function indexes in patients with type 2 diabetes.

BACKGROUND: Red cell distribution width (RDW) is a predicter of infections, cancer and diabetes. However, the relationship between RDW and ß-cell function and insulin resistance remains unclear in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to explore the relationship between RDW and ß-cell function in patients with T2DM. METHODS: A total of 559 T2DM patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and biochemical characteristics such as age, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and lipid profiles were collected. Homeostasis model assessment of insulin resistance (HOMA2IR) and homeostasis model assessment of ß-cell function (HOMA2%B) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCPI). Correlations and multiple linear regressions were performed to explore the association between RDW and islet function indexes in total population and in different gender subgroups. RESULTS: The HOMA2%B gradually increased according to RDW tertiles (lowest, second, highest RDW tertiles; 47.1(32.9-75.4), 54.05(34.1-81), and 57.9(38.65-95.4), respectively; P = 0.036). Correlation analysis indicated that there were significant correlations between RDW and age, diabetes duration, diastolic blood pressure (DBP), triglycerides (TG), aspartate transaminase (AST), FBG, HbA1c and HOMA2%B in all subjects. In male subjects, RDW correlated positively with age, high-density lipoprotein cholesterol (HDL) and AST, and it correlated negatively with body mass index (BMI), DBP and TG. In female subjects, RDW correlated positively with age, duration, serum creatinine (Cr), FCPI and HOMA2%B, and it correlated negatively with alanine transaminase (ALT), FBG and HbA1c. Multiple linear regressions indicated that RDW was significantly correlated with HOMA2%B and HbA1c in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of men for HOMA2%B only and in women for HbA1c only. CONCLUSIONS: RDW is associated with ß-cell function assessed by HOMA2%B after adjusting for covariates in male T2DM patients.

Intramedullary lesion resection as an effective treatment of spinal cord microscopic polyangiitis: a case report.

BACKGROUND: Microscopic polyangiitis (MPA), an autoimmune disease, is a subtype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The lungs and kidneys are the most common targets, whereas spinal cord involvement is rare. METHODS: We reported the clinical manifestations, diagnosis, and management of a patient with spinal cord MPA. RESULTS: The patient showed spinal compression symptoms and was diagnosed with MPA following magnetic resonance imaging (MRI) and histological examination. Spinal compression symptoms were completely relieved after intramedullary lesion resection and postoperative treatment with methylprednisolone. CONCLUSION: The diagnosis of MPA without typical manifestations can be challenging. MRI and histological examination are of great importance in spinal cord MPA diagnosis. Intramedullary lesion resection is an effective treatment for spinal cord MPA. Methylprednisolone is also recommended for postoperative treatment.

Bone formation recovery with gold nanoparticle-induced M2 macrophage polarization in mice.

The prevention of fractures induced by inflammatory bone disease remains a clinical challenge. This is because of a lack of bone formation to fill in the bone defects, which are believed to be due in part to persistent inflammation caused by the imbalance of M1 over M2 macrophages. In this study, gold nanoparticles (AuNPs) were synthesized to shift the balance of macrophages at the site of bone damage to improve osteanagenesis in a mouse model of LPS-induced inflammatory bone erosion. Specifically, the AuNPs treatment improved bone structure and increased bone mineral density (BMD) by ~14% compared with model group. Macrophages recruited by LPS treatment were reduced by ~11% after AuNPs injection. Compared to LPS treatment only, the percentage of M2 macrophages increased threefold by AuNPs, while the proportion of M1 macrophages decreased by 59%. This promoted the regeneration of bone matrix proteins in the bone defect site, which finally leads to increased bone mass and improved bone structure in model mice. These data suggest that AuNPs could be a novel candidate therapeutic for inflammatory bone disease rather than a drug carrier.

In vivo biological safety evaluation of an iron-based bioresorbable drug-eluting stent.

Bioresorbable stents (BRS) are investigated and designed to revascularize occluded arteries. The iron-based bioresorbable stent is a promising device in interventional therapies, although it's corrosion and bioresorption rate remain challenging. In this work, we introduced a novel nitrided iron coronary stent (IBS) with enhanced degradation rate compared with pure iron stent. To evaluate the biosafety of this device, a sub-chronic systemic toxicity study was conducted and a stainless steel stent (Supporter™) served as a control. Here, the bioresorbable stent was first evaluated in rat abdominal aortic implantation model. When subjected to exaggerated exposure dose, no clinical signs of toxicity or mortality were observed in either, the IBS group or the control group. Histopathological examinations showed the corrosion particles of iron were encapsulated by fibrocytes and engulfed by macrophages, indicating that the degradation of iron was in the early stage. Our results demonstrated that the nitrided iron stent did not induce systemic toxicity under the experimental conditions.

The Basic Properties of Gold Nanoparticles and their Applications in Tumor Diagnosis and Treatment.

Gold nanoparticles (AuNPs) have been widely studied and applied in the field of tumor diagnosis and treatment because of their special fundamental properties. In order to make AuNPs more suitable for tumor diagnosis and treatment, their natural properties and the interrelationships between these properties should be systematically and profoundly understood. The natural properties of AuNPs were discussed from two aspects: physical and chemical. Among the physical properties of AuNPs, localized surface plasmon resonance (LSPR), radioactivity and high X-ray absorption coefficient are widely used in the diagnosis and treatment of tumors. As an advantage over many other nanoparticles in chemicals, AuNPs can form stable chemical bonds with S-and N-containing groups. This allows AuNPs to attach to a wide variety of organic ligands or polymers with a specific function. These surface modifications endow AuNPs with outstanding biocompatibility, targeting and drug delivery capabilities. In this review, we systematically summarized the physicochemical properties of AuNPs and their intrinsic relationships. Then the latest research advancements and the developments of basic research and clinical trials using these properties are summarized. Further, the difficulties to be overcome and possible solutions in the process from basic laboratory research to clinical application are discussed. Finally, the possibility of applying the results to clinical trials was estimated. We hope to provide a reference for peer researchers to better utilize the excellent physicochemical properties of gold nanoparticles in oncotherapy.

Ultrafast water harvesting and transport in hierarchical microchannels.

Various natural materials have hierarchical microscale and nanoscale structures that allow for directional water transport. Here we report an ultrafast water transport process in the surface of a Sarracenia trichome, whose transport velocity is about three orders of magnitude faster than those measured in cactus spine and spider silk. The high velocity of water transport is attributed to the unique hierarchical microchannel organization of the trichome. Two types of ribs with different height regularly distribute around the trichome cone, where two neighbouring high ribs form a large channel that contains 1-5 low ribs that define smaller base channels. This results in two successive but distinct modes of water transport. Initially, a rapid thin film of water is formed inside the base channels (Mode I), which is followed by ultrafast water sliding on top of that thin film (Mode II). This two-step ultrafast water transport mechanism is modelled and experimentally tested in bio-inspired microchannels, which demonstrates the potential of this hierarchal design for microfluidic applications.

Study of biodegradable occluder of atrial septal defect in a porcine model.

OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets were divided into two groups: an experimental group (n = 27) and a control group (n = 18). The experimental group underwent percutaneous implantation of a modified PLLA ASD device while the control group underwent percutaneous implantation of a widely used metal ASD device. X-ray imaging, transthoracic echocardiography (TTE), electrocardiogram (ECG), histopathology and electron microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets were all successfully implanted with modified biodegradable and metal ASD devices, respectively. While both devices exhibited very good occluding effects, the modified PLLA ASD devices were completely endothelialized at 3 months after implantation, and the endothelialization appeared to be more complete compared to the control group. Degradation of the PLLA devices was noted at 12 months follow-up with no loss of integrity at the atrial septum. CONCLUSION: This animal model with implanting of the occluders was effective and not associated with complications. The modified PLLA ASD devices are more controllable and practical than our previous devices. The implanted devices demonstrated good endothelialization and degradability in short and moderate term follow-up. Long-term studies are now underway to further evaluate the biodegradability of this novel device.

Three-dimensional assembly of silver nanoparticles spatially confined by cellular structure of Spirulina, from nanospheres to nanosheets.

Three-dimensional (3D) ordered construction of nanoparticles (NPs) has attracted much attention in wide applications, however, techniques with respect to cost effective nanofabrication of well defined functional architectures is still lacking. To address this specific issue, a bio-interface confinement approach is proposed that precisely replicates the complex cellular structural features of microbes and integrates silver NP (SNP) building blocks into their 3D framework in a precise, low cost and mass production way. Herein, the SNPs with nanospheres and nanosheets structure were synthesized by way of electroless deposition using Spirulina as template. Results showed that SNPs were orderly assembled along the cellular structure, and the spatially confinement of cellular texture induced the transformation of SNPs from sphere to flake morphology during their continuous growth. The silver assembly not only shows good antibacterial activity, but also exhibits excellent surface enhanced Raman scattering (SERS) performance with the enhancement factor as high as 5.95 × 108 and good recuperability towards Rhodamine 6G. The fascinating SERS performance can be ascribed to the combined action of nanosheets morphology of SNPs, hierarchical nanostructure of the cellular structure, and the small interparticle spacing. This strategy provides an effective strategy for controllable and ordered 3D assembly of NPs by using the cellular texture.

Bio-inspired Flexible Lateral Line Sensor Based on P(VDF-TrFE)/BTO Nanofiber Mat for Hydrodynamic Perception.

Fish and some amphibians can perform a variety of behaviors in confined and harsh environments by employing an extraordinary mechanosensory organ, the lateral line system (LLS). Inspired by the form-function of the LLS, a hydrodynamic artificial velocity sensor (HAVS) was presented in this paper. The sensors featured a polarized poly (vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)]/barium titanate (BTO) electrospinning nanofiber mat as the sensing layer, a polyimide (PI) film with arrays of circular cavities as the substrate, and a poly(methyl methacrylate) (PMMA) pillar as the cilium. The P(VDF-TrFE)/BTO electrospinning nanofiber mat demonstrated enhanced crystallinity and piezoelectricity compared with the pure P(VDF-TrFE) nanofiber mat. A dipole source was employed to characterize the sensing performance of the fabricated HAVS. The HAVS achieved a velocity detection limit of 0.23 mm/s, superior to the conventional nanofiber mat-based flow sensor. In addition, directivity was feasible for the HAVS, which was in accordance with the simulation results. The proposed bio-inspired flexible lateral line sensor with hydrodynamic perception ability shows promising applications in underwater robotics for real-time flow analysis.

A Novel Bioinspired Continuous Unidirectional Liquid Spreading Surface Structure from the Peristome Surface of Nepenthes alata.

A novel unidirectional liquid spreading surface with an inclined arc pitted groove, inspired by the continuous unidirectional liquid spreading mechanism on the peristome surface of N. alata, is explored and fabricated by two-step UV lithography. Its superior unidirectional liquid spreading capability to that of other surface patterns is demonstrated, and its unidirectional liquid spreading mechanism is investigated.

Development of a Flexible Artificial Lateral Line Canal System for Hydrodynamic Pressure Detection.

Surface mounted 'smart skin' can enhance the situational and environmental awareness of marine vehicles, which requires flexible, reliable, and light-weight hydrodynamic pressure sensors. Inspired by the lateral line canal system in fish, we developed an artificial lateral line (ALL) canal system by integrating cantilevered flow-sensing elements in a polydimethylsiloxane (PDMS) canal. Polypropylene and polyvinylidene fluoride (PVDF) layers were laminated together to form the cantilevered flow-sensing elements. Both the ALL canal system and its superficial counterpart were characterized using a dipole vibration source. Experimental results showed that the peak frequencies of both the canal and superficial sensors were approximately 110 Hz, which was estimated to be the resonance frequency of the cantilevered flow-sensing element. The proposed ALL canal system demonstrated high-pass filtering capabilities to attenuate low-frequency stimulus and a pressure gradient detection limit of approximately 11 Pa/m at a frequency of 115 ± 1 Hz. Because of its structural flexibility and noise immunity, the proposed ALL canal system shows significant potential for underwater robotics applications.

A Novel-Design Poly-L-Lactic Acid Biodegradable Device for Closure of Atrial Septal Defect: Long-Term Results in Swine.

OBJECTIVES: The aim of this study is to evaluate the long-term effectiveness and safety of a self-expandable, double-disk biodegradable device made of poly-L-lactic acid (PLLA) for closure of atrial septal defects (ASDs) in swine. METHODS: ASDs were created by transseptal needle puncture followed by balloon dilatation in 20 piglets. The experimental group comprised 18 animals, while the remaining 2 animals were used as controls. Effectiveness and safety were evaluated by rectal temperature, leukocyte count, chest radiography, electrocardiogram, transthoracic echocardiography (TTE), intracardiac echocardiography (ICE), and histologic studies. Animals were followed up at 1, 3, 6, and 12 months. RESULTS: An ASD model was successfully created in 19 animals; 1 piglet died during the procedure. The ASD diameters that were created ranged from 5 to 6.4 mm. Devices were successfully implanted in 17 animals. No animal died during the follow-up studies. Rectal temperatures and electrocardiograms were normal at follow-up, while leukocyte counts transiently increased from 1 to 6 months. Radiography, TTE, ICE, and macroscopic studies demonstrated that PLLA occluders were positioned well, with no shifting, mural thrombus formation, or atrioventricular valve insufficiency. Histologic evaluations showed that PLLA devices were partially degraded in the follow-up study. CONCLUSIONS: ASD closure with the novel PLLA biodegradable device is safe and effective. Longer-term studies are needed to evaluate long-term biodegradability.

Fabrication of All-SiC Fiber-Optic Pressure Sensors for High-Temperature Applications.

Single-crystal silicon carbide (SiC)-based pressure sensors can be used in harsh environments, as they exhibit stable mechanical and electrical properties at elevated temperatures. A fiber-optic pressure sensor with an all-SiC sensor head was fabricated and is herein proposed. SiC sensor diaphragms were fabricated via an ultrasonic vibration mill-grinding (UVMG) method, which resulted in a small grinding force and low surface roughness. The sensor head was formed by hermetically bonding two layers of SiC using a nickel diffusion bonding method. The pressure sensor illustrated a good linearity in the range of 0.1-0.9 MPa, with a resolution of 0.27% F.S. (full scale) at room temperature.

Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection.

MOTIVATION: Owing to its importance in both basic research (such as molecular evolution and protein attribute prediction) and practical application (such as timely modeling the 3D structures of proteins targeted for drug development), protein remote homology detection has attracted a great deal of interest. It is intriguing to note that the profile-based approach is promising and holds high potential in this regard. To further improve protein remote homology detection, a key step is how to find an optimal means to extract the evolutionary information into the profiles. RESULTS: Here, we propose a novel approach, the so-called profile-based protein representation, to extract the evolutionary information via the frequency profiles. The latter can be calculated from the multiple sequence alignments generated by PSI-BLAST. Three top performing sequence-based kernels (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein representation. Various tests were conducted on a SCOP benchmark dataset that contains 54 families and 23 superfamilies. The results showed that the new approach is promising, and can obviously improve the performance of the three kernels. Furthermore, our approach can also provide useful insights for studying the features of proteins in various families. It has not escaped our notice that the current approach can be easily combined with the existing sequence-based methods so as to improve their performance as well. AVAILABILITY AND IMPLEMENTATION: For users' convenience, the source code of generating the profile-based proteins and the multiple kernel learning was also provided at http://bioinformatics.hitsz.edu.cn/main/~binliu/remote/