Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder.

Variants of the Diaphanous-Related Formin 1 (DIAPH-1) gene have recently been reported causing inherited macrothrombocytopenia. The essential/"diagnostic" characteristics associated with the disorder are emerging; however, robust and complete criteria are not established. Here, we report the first cases of DIAPH1-related disorder in Australia caused by the autosomal dominant gain-of-function DIAPH1 R1213X variant formed by truncation of the protein within the diaphanous auto-regulatory domain (DAD) with loss of regulatory motifs responsible for autoinhibitory interactions within the DIAPH1 protein. We affirm phenotypic changes induced by the DIAPH1 R1213X variant to include macrothrombocytopenia, early-onset progressive sensorineural hearing loss, and mild asymptomatic neutropenia. High-resolution microscopy confirms perturbations of cytoskeletal dynamics caused by the DIAPH1 variant and we extend the repertoire of changes generated by this variant to include alteration of procoagulant platelet formation and possible dental anomalies.

Ultralight Multifunctional Carbon-Based Aerogels by Combining Graphene Oxide and Bacterial Cellulose.

Nanostructured carbon aerogels with outstanding physicochemical properties have exhibited great application potentials in widespread fields and therefore attracted extensive attentions recently. It is still a challenge so far to develop flexible and economical routes to fabricate high-performance nanocarbon aerogels, preferably based on renewable resources. Here, ultralight and multifunctional reduced graphene oxide/carbon nanofiber (RGO/CNF) aerogels are fabricated from graphene oxide and low-cost, industrially produced bacterial cellulose by a three-step process of freeze-casting, freeze-drying, and pyrolysis. The prepared RGO/CNF aerogel possesses a very low apparent density in the range of 0.7-10.2 mg cm-3 and a high porosity up to 99%, as well as a mechanically robust and electrically conductive 3D network structure, which makes it to be an excellent candidate as absorber for oil clean-up and an ideal platform for constructing flexible and stretchable conductors.

Bacterial Cellulose: A Robust Platform for Design of Three Dimensional Carbon-Based Functional Nanomaterials.

Three dimensional (3D) carbon nanomaterials exhibit great application potential in environmental protection, electrochemical energy storage and conversion, catalysis, polymer science, and advanced sensors fields. Current methods for preparing 3D carbon nanomaterials, for example, carbonization of organogels, chemical vapor deposition, and self-assembly of nanocarbon building blocks, inevitably involve some drawbacks, such as expensive and toxic precursors, complex equipment and technological requirements, and low production ability. From the viewpoint of practical application, it is highly desirable to develop a simple, cheap, and environmentally friendly way for fabricating 3D carbon nanomaterials in large scale. On the other hand, in order to extend the application scope and improve the performance of 3D carbon nanomaterials, we should explore efficient strategies to prepare diverse functional nanomaterials based on their 3D carbon structure. Recently, many researchers tend to fabricate high-performance 3D carbon-based nanomaterials from biomass, which is low cost, easy to obtain, and nontoxic to humans. Bacterial cellulose (BC), a typical biomass material, has long been used as the raw material of nata-de-coco (an indigenous dessert food of the Philippines). It consists of a polysaccharide with a ß-1,4-glycosidic linkage and has a interconnected 3D porous network structure. Interestingly, the network is made up of a random assembly of cellulose nanofibers, which have a high aspect ratio with a diameter of 20-100 nm. As a result, BC has a high specific surface area. Additionally, BC hydrogels can be produced on an industrial scale via a microbial fermentation process at a very low price. Thus, it can be an ideal platform for design of 3D carbon-based functional nanomaterials. Before our work, no systematic work and summary on this topic had been reported. This Account presents the concepts and strategies of our studies on BC in the past few years, that is, converting cheap biomass into high value-added 3D carbon nanomaterials and designing diverse functional materials on 3D carbon structure. We first briefly introduce the history, constituent, and microstructure features of BC and discuss its advantages as a raw material for preparing the CNF aerogels. Then, we summarize the methods and strategies for preparing various 3D carbon-based nanomaterials from BC. In addition, the potential applications of the developed CNF aerogel based functional materials are also highlighted in this Account, including stretchable conductors, oxygen reduction reaction catalysts, supercapacitors, lithium-ion battery, and oil cleanup. Finally, we give some prospects on the future challenges in this emerging research area of designing CNF aerogel based functional nanomaterials from BC.

Phase diagrams guide synthesis of highly ordered intermetallic electrocatalysts: separating alloying and ordering stages.

Supported platinum intermetallic compound catalysts have attracted considerable attention owing to their remarkable activities and durability for the oxygen reduction reaction in proton-exchange membrane fuel cells. However, the synthesis of highly ordered intermetallic compound catalysts remains a challenge owing to the limited understanding of their formation mechanism under high-temperature conditions. In this study, we perform in-situ high-temperature X-ray diffraction studies to investigate the structural evolution in the impregnation synthesis of carbon-supported intermetallic catalysts. We identify the phase-transition-temperature (TPT)-dependent evolution process that involve concurrent (for alloys with high TPT) or separate (for alloys with low TPT) alloying/ordering stages. Accordingly, we realize the synthesis of highly ordered intermetallic catalysts by adopting a separate annealing protocol with a high-temperature alloying stage and a low-temperature ordering stage, which display a high mass activity of 0.96 A mgPt-1 at 0.9 V in H2-O2 fuel cells and a remarkable durability.

Nuclear-targeted carbon quantum dot mediated CRISPR/Cas9 delivery for fluorescence visualization and efficient editing.

Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs-PEI-PEG conjugate (CQDs-PP) with an ultra-small size and positive surface charge. Here we show that CQDs-PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs-PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs-PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs-PEI (CQDs-P). Thus, the nuclear-targeted CQDs-PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.

Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.

The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.

Comparing transfection efficiency and safety for antisense oligodeoxyribonucleotide between phospholipids-based microbubbles and liposomes.

OBJECTIVE: To compare transfection efficiency and safety for antisense oligodeoxynucleotides (AS-ODNs) between two type of phospholipids-based vectors. METHODS: An AS-ODNs sequence HA824 combined with luciferase reporter plasmid was used. Under low intensity ultrasound (US), a breast cancer cell line SK-BR-3 was exposed to different concentration of microbubbles and liposomes. Transfection efficiency was detected by fluorescence microscopy. Cell viability was verified by propidium iodide assay. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the inhibitory effect of HA824 on HER-2 expression at mRNA level. Atomic force microscopy (AFM) scanning techniques was employed to observe the change of membrane pore size. RESULTS: AS-ODNs transfection efficiency showed an increasing tend with microbubble concentration, but not with liposome concentration. Maximum transfection efficiency with minimum cell viability was achieved under 2% microbubble concentration. Too strong sonoporation activity would enlarge membrane pores significantly and cause low cell viability. CONCLUSION: US-mediated AS-ODNs transfection enhanced by phospholipids-based microbubbles represents an effective and safe avenue.

Pluronic block copolymers: novel functions in ultrasound-mediated gene transfer and against cell damage.

Pluronics have been investigated as vectors for drug and gene delivery in vitro and in vivo and were demonstrated to have high efficiency for gene transfer in vivo. However, they alone do not enhance gene transfer in vitro. We examined three pluronics, F127, L61 and P85, for their effects on ultrasound (US)-mediated gene transfer in three cell lines, 3T3-MDEI, C2C12 and CHO. The polymers showed differential effects on cell viability and transfection efficiency in a dose-dependent manner. All the polymers were unable to facilitate gene transfer when used alone, but enhanced US-mediated gene transfer significantly at concentrations around the critical micelle concentration in the three cell lines. F127 showed no significant toxicity at any concentration and protected the cells against US-mediated damage at a high concentration. L61 decreased cell viability significantly in a dose-dependent manner, whereas P85 showed mild toxicity when its concentration was at or above 0.05%.

Self-interconnecting Pt nanowire network electrode for electrochemical amperometric biosensor.

One-dimensional Pt nanostructures are of considerable interest for the development of highly stable and sensitive electrochemical sensors. This paper describes a self-interconnecting Pt nanowire network electrode (PtNNE) for the detection of hydrogen peroxide (H2O2) and glucose with ultrahigh sensitivity and stability. The as-prepared PtNNE consists of polycrystalline nanowires with high-index facets along the side surface which provides more active surface atoms on kinks and steps, those ultralong nanowires being interconnected with each other to form a free-standing network membrane. The excellent structural features of the PtNNE promoted its performance as a Pt-based electrochemical sensor both in terms of electrocatalytic activity and stability. Amperometric measurements towards hydrogen peroxide were performed; the PtNNE sensor showed an extremely high sensitivity of 1360 µA mM(-1) cm(-2). This excellent sensitivity is mainly attributed to the high-index facets of the nanowires resulting in their superior electrocatalytic activity towards H2O2, and the interconnected nanowire network forming an "electron freeway" transport model, which could provide multiple electron pathways and fast electron transport on the electrode, leading to rapid reaction and sensitive signal detection. The as-prepared PtNNE also holds promise as an oxidase-based biosensor. As a proof of concept, a PtNNE-based glucose biosensor also showed an outstanding sensitivity as high as 114 µA mM(-1) cm(-2), a low detection limit of 1.5 µM, and an impressive detection range from 5 µM to 30 mM.

The efficacy and safety of telaprevir-based regimens for treating chronic hepatitis C virus genotype 1 infection: a meta-analysis of randomized trials.

OBJECTIVE: Previous studies have reported that telaprevir is effective for treating chronic hepatitis C virus (HCV) genotype 1 infection; however, the efficacy and safety of telaprevir-based regimens remain uncertain. METHODS: To assess the efficacy and safety of telaprevir in patients with chronic HCV genotype 1 infection, we conducted a meta-analysis of all available randomized controlled trials (RCT) comparing the efficacy and safety of the addition of telaprevir to a standard regimen (combination of telaprevir with peginterferon and ribavirin, TPR group) with the standard regimen alone (peginterferon and ribavirin, PR group). RESULTS: Ultimately, six RCTs involving a total of 2,759 patients with chronic HCV genotype 1 infection were included in this meta-analysis. The outcomes showed that the sustained virologic response (SVR) rate was significantly higher in the TPR group (1,284/1,932, 66.5%) than in the PR group (296/827, 35.8%) with a pooled odds ratio (OR) [3.81, 95% confidence interval (CI) 2.43-5.96, p<0.001]. The results also showed that the relapse rate was significantly lower in the TPR group (190/1,484, 12.8%) than in the PR group (140/425, 32.9%) with a pooled risk ratio (RR) (0.40; 95% CI 0.24-0.66, p<0.001). However, there was an increased risk of serious adverse events in the TPR group (RR=1.45, 95% CI 1.12-1.87, p=0.005). CONCLUSION: Telaprevir-based regimens can significantly increase the SVR rate and reduce the relapse rate in patients with chronic HCV genotype 1 infection. However, the safety of telaprevir-based regimens still requires further study.

Quantitative ultrasonic computed tomography using phase-insensitive pyroelectric detectors.

The principle of using ultrasonic computed tomography (UCT) clinically for mapping tissue acoustic properties was suggested almost 40 years ago. Despite strong research activity, UCT been unable to rival its x-ray counterpart in terms of the ability to distinguish tissue pathologies. Conventional piezoelectric detectors deployed in UCT are termed phase-sensitive (PS) and it is well established that this property can lead to artefacts related to refraction and phase-cancellation that mask true tissue structure, particularly for reconstructions involving attenuation. Equally, it has long been known that phase-insensitive (PI) detectors are more immune to this effect, although sufficiently sensitive devices for clinical use have not been available. This paper explores the application of novel PI detectors to UCT. Their operating principle is based on exploiting the pyroelectric properties of the piezoelectric polymer polyvinylidene difluoride. An important detector performance characteristic which makes it particularly suited to UCT, is the lack of directionality of the PI response, relative to the PS detector mode of operation. The performance of the detectors is compared to conventional PS detection methods, for quantitatively assessing the attenuation distribution within various test objects, including a two-phase polyurethane phantom. UCT images are presented for a range of single detector apertures; tomographic reconstruction images being compared with the known structure of phantoms containing inserts as small as 3 mm, which were readily imaged. For larger diameter inserts (>10 mm), the transmitter-detector combination was able to establish the attenuation coefficient of the insert to within ±10% of values determined separately from plane-wave measurements on representative material plaques. The research has demonstrated that the new PI detectors are significantly less susceptible to refraction and phase-cancellation artefacts, generating realistic images in situations where conventionally-employed through-transmission PS detection techniques were unable to do so. The implications of the study to the potential screening of breast disease are discussed.

Bacterial-cellulose-derived carbon nanofiber@MnO2 and nitrogen-doped carbon nanofiber electrode materials: an asymmetric supercapacitor with high energy and power density.

A new kind of high-performance asymmetric supercapacitor is designed with pyrolyzed bacterial cellulose (p-BC)-coated MnO2 as a positive electrode material and nitrogen-doped p-BC as a negative electrode material via an easy, efficient, large-scale, and green fabrication approach. The optimal asymmetric device possesses an excellent supercapacitive behavior with quite high energy and power density.

Bio-inspired fabrication of hierarchical FeOOH nanostructure array films at the air-water interface, their hydrophobicity and application for water treatment.

Hierarchical FeOOH nanostructure array films constructed by different nanosized building blocks can be synthesized at the air-water interface via a bio-inspired gas-liquid diffusion method. In this approach, poly(acrylic acid) (PAA) as a crystal growth modifier plays a crucial role in mediating the morphology and polymorph of FeOOH crystals. With the increase of PAA concentration, the shape of the building blocks assembling into FeOOH films can be tailored from nanosheets, to rice spikes, then to branched fibers, and finally to nanowires. What is more, a low concentration of PAA will induce the formation of α-FeOOH, while a high one could stabilize FeOOH in the form of the γ-FeOOH phase. After being modified with a thin layer of polydimethylsiloxane (PDMS), the as-prepared FeOOH films exhibited strong hydrophobicity with water contact angles (CA) from 134° to 148° or even superhydrophobicity with a CA of 164° in the sample constructed by nanosheets. When the FeOOH nanostructures were dispersed in water by ultrasound, they displayed quite promising adsorption performance of heavy metal ions for water treatment, where the highest adsorption capacity can reach 77.2 mg·g⁻¹ in the sample constructed by nanowires. This bio-inspired approach may open up the possibilities for the fabrication of other functional nanostructure thin films with unique properties.

[Ecological risk evaluation of heavy metals of the typical dredged mud in Shanghai].

In order to discuss the potential ecological risk of heavy metals of the typical dredged mud in Shanghai, the Hakanson potential ecological risks method was used to analyse and assess the potential ecological risks of heavy metals, including Hg, Cd, Cu, Pb, As,Cr and Zn in dredged mud from the following three areas-the dock apron of Huangpu River, the mouth of the Yangtze River and inland waterways. The results showed that the mean values of ecological risk index (Er(i)) of the seven heavy metals are 20.05, 17.49, 8.82, 5.71, 4.68, 1.74 and 1.13, respectively, all of which belonged to the low ecological risk; Cd (one location in inland waterways) and Hg (three locations in the mouth of the Yangtze River and one location in inland waterways) are the most hazardous elements, with the Er(i) > 40, which belonged to the medium ecological risk or the high ecological risk, and other elements belonged to the low ecological risk. From the results of ecological risk indices(ERI) of the heavy metals in Shanghai dredged mud, the risk of the heavy metals belonged to the low ecological risk. The ERI of inland waterways, the mouth of the Yangtze River and the dock apron of the Huangpu River were 81.4, 57.7 and 52.5, respectively, which all belong to the low ecological risk.

[Retrospective study on volume of bone cement injection for concurrent of fracture after thoracolumbar vertebraes kyphoplasty].

OBJECTIVE: To explore relationship between volume of bone cement injection and concurrent of fracture after thoracolumbar osteoporotic vertebral fracture treated by percutaneous kyphoplasty (PKP). METHODS: From January 2006 to December 2008,68 patients with thoracolumbar osteoporotic vertebral fracture treated by PKP were retrospectively analyzed. Among them, 30 patients with less than 3 ml bone cement injection (mean 2.5 ml, low group), including 11 males and 19 females, with an average age of (85.0 +/- 8.5) years (ranging for 60 to 91); 38 cases with over 4 ml bone cement injection (mean 4.5 ml, large group), including 15 males and 23 females,with an average age of (86.0 +/- 9.2) years (ranging for 60 to 93). Factors of concurrent vertebral fractures were observed during follow-up. RESULTS: All patients were followed up from 3.4 to 5.1 years with an average of 3.8 years. Thirteen patients (43.3%) co-occurred fracture in low group,among which strengthened concurrent vertebral fracture occurred in 1 case,upper and lower section adjacent vertebral fracture in 8 cases,distal segment of vertebral fracture in 4 cases; while 18 patients (47.3%) co-occurred fracture in large group,among which strengthened concurrent vertebral fracture occurred in 2 cases, upper and lower section adjacent vertebral fracture in 10 cases,distal segment of vertebral fracture in 6 cases. No significant difference between two groups (P > 0.05). CONCLUSION: Bone cement injection is not main influence factors for treating concurrent of fracture after thoracolumbar osteoporotic vertebral fracture by PKP. Concurrent fracture mainly relates with progress of osteoporosis, the volume of injection volume may appropriately over the volume of balloon.

Highly active carbonaceous nanofibers: a versatile scaffold for constructing multifunctional free-standing membranes.

Translating the unique characteristics of individual nanoscale components into macroscopic materials such as membranes or sheets still remains a challenge, as the engineering of these structures often compromises their intrinsic properties. Here, we demonstrate that the highly active carbonaceous nanofibers (CNFs), which are prepared through a template-directed hydrothermal carbonization process, can be used as a versatile nanoscale scaffold for constructing macroscopic multifunctional membranes. In order to demonstrate the broad applicability of the CNF scaffold, we fabricate a variety of CNF-based composite nanofibers, including CNFs-Fe(3)O(4), CNFs-TiO(2), CNFs-Ag, and CNFs-Au through various chemical routes. Importantly, all of them inherit unique dimensionality (high aspect ratio) and mechanical properties (flexibility) of the original CNF scaffolds and thus can be assembled into macroscopic free-standing membranes through a simple casting process. We also demonstrate the wide application potentials of these multifunctional composite membranes in magnetic actuation, antibiofouling filtration, and continuous-flow catalysis.

Carbonaceous nanofiber membrane functionalized by beta-cyclodextrins for molecular filtration.

In this paper, we report the fabrication of carbonaceous nanofiber (CNF) membranes functionalized by beta-cyclodextrins (CNF-ß-CD membrane) and their application for molecular filtration. The chemically synthesized carbonaceous nanofibers were first functionalized by ß-CD, and the free-standing CNF membrane can be prepared by a simple filtration process. The membrane shows a remarkable capability to function as an ideal molecular filter through complexation of phenolphthalein molecules with the cyclodextrin molecules grafted on the CNFs. As a typical dye pollutant, fuchsin acid can also be effectively removed from the solution through such a membrane. Engineering the surface of this carbonaceous nanofiber membrane may allow it to be used for other applications such as chiral separation and drug delivery.

[Clinical observation of effects and complications of the mid-stage in treating osteoporotic vertebral compression fracture with percutaneous kyphoplasty].

OBJECTIVE: To observe the clinical effects and complications in treating osteoporotic vertebral fractures with percutaneous kyphoplasty (PKP) and in order to found the cause and countermeasures of the complications. METHODS: From March 2006 to March 2007, 31 patients with osteoporotic vertebral fractures were treated with unilateral percutaneous kyphoplasty. There were 11 males and 20 females, ranging in age from 54 to 91 years with the mean of 81 years. All patients were followed up for more than three years. At pre-treatment and postoperatively immediately, 1, 2, 3 years after PKP, the height of anterior vertebral body and thoracic-lumbar and back pain were respectively analyzed by imaging data and VAS scoring. RESULTS: At pre-treatment and postoperatively immediately, 1, 2, 3 years after PKP, the height of anterior vertebral body were (0.9 +/- 0.2), (2.6 +/- 0.3), (2.6 +/- 0.2), (2.5 +/- 0.7), (2.5 +/- 0.4) cm, respectively; the VAS soring were (7.6 +/- 1.4), (2.3 +/- 0.7), (2.4 +/- 0.5), (2.8 +/- 0.3), (3.1 +/- 0.2) scores, respectively. The height of anterior vertebral body recoveried obviously after PKP (P < 0.05); following prolongation of time, the height of anterior vertebral body gradually reduced (P > 0.05). The thoracic-lumbar and back pain relieved obviously after PKP (P < 0.05); following prolongation of time, the pain gradually aggratated, but there was no significant difference (P > 0.05). At final follow up, reinforced vertebral re-fractures was found in 2 cases, adjacent vertebral fractures in 6 cases, distal vertebral fractures in 2 cases, asymptomatic degeneration of adjacent intervertebral in 5 cases. CONCLUSION: PKP have definite and early effects in treating osteoporotic vertebral fractures. But in mid-stage after PKP, the height of anterior vertebral body reduce and the pain aggravate gradually, especially degenerative adjacent vertebral fracture advent. Strict choosing the candidate of the precedure, improvement of materials of perfusion and reducing of volume of bone cement maybe can decrease incidence rate of complications.