Steroid-associated hip joint collapse in bipedal emus

In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients

Luminescent and Magnetic α‑Fe₂O₃@Y₂O₃:Eu³⁺ Bifunctional Hollow Microspheres for Drug Delivery

Fluorescent and magnetic bifunctional nanomaterials have found several applications in life sciences, including biological labeling, magnetic resonance imaging, gene therapy, and nanodrug delivery. In this work, we develop a facile route that combines the assisted-template approach with a homogeneous co-precipitation method and a high-temperature calcination process, allowing the successful preparation of fluorescent–magnetic α-Fe₂O₃@Y₂O₃:Eu³⁺ bifunctional hollow microspheres (BHMs) with mesoporous shells and hollow-core structures. Scanning electron microscopy, transmission electron microscopy, emission spectroscopy, magnetic testing, and N₂ adsorption techniques were employed to characterize the fluorescent–magnetic α-Fe₂O₃@Y₂O₃:Eu³⁺ BHMs. The results showed that the resulting BHMs exhibited uniformly spherical morphologies with mesoporous shells and hollow-core structures and were characterized by good dispersibility, photofluorescence, and magnetic responsiveness in solution. Ibuprofen loading and drug-release simulation experiments showed that the BHMs exhibited a high drug-loading capacity (126 mg/g) and a sustained drug-release profile, which would allow them to be employed as nanodrug carriers for the therapeutic treatment of malignant tumors

Fabrication of Ultrasensitive Field-Effect Transistor DNA Biosensors by a Directional Transfer Technique Based on CVD-Grown Graphene

Most graphene field-effect transistor (G-FET) biosensors are fabricated through a routine process, in which graphene is transferred onto a Si/SiO₂ substrate and then devices are subsequently produced by micromanufacture processes. However, such a fabrication approach can introduce contamination onto the graphene surface during the lithographic process, resulting in interference for the subsequent biosensing. In this work, we have developed a novel directional transfer technique to fabricate G-FET biosensors based on chemical-vapor-deposition- (CVD-) grown single-layer graphene (SLG) and applied this biosensor for the sensitive detection of DNA. A FET device with six individual array sensors was first fabricated, and SLG obtained by the CVD-growth method was transferred onto the sensor surface in a directional manner. Afterward, peptide nucleic acid (PNA) was covalently immobilized on the graphene surface, and DNA detection was realized by applying specific target DNA to the PNA-functionalized G-FET biosensor. The developed G-FET biosensor was able to detect target DNA at concentrations as low as 10 fM, which is 1 order of magnitude lower than those reported in a previous work. In addition, the biosensor was capable of distinguishing the complementary DNA from one-base-mismatched DNA and noncomplementary DNA. The directional transfer technique for the fabrication of G-FET biosensors is simple, and the as-constructed G-FET DNA biosensor shows ultrasensitivity and high specificity, indicating its potential application in disease diagnostics as a point-of-care tool

Defect-Induced Ultrafast Nonadiabatic Electron–Hole Recombination Process in PtSe₂ Monolayer

Defects are inevitable in two-dimensional materials due to the growth condition, which results in many unexpected changes in materials’ properties. Here, we have mainly discussed the nonradiative recombination dynamics of PtSe2 monolayer without/with native point defects. Based on first-principles calculations, a shallow p-type defect state is introduced by a Se antisite, and three n-type defect states with a double-degenerate shallow defect state and a deep defect state are introduced by a Se vacancy. Significantly, these defect states couple strongly to the pristine valence band maximum and lead to the enhancement of the in-plane vibrational Eg mode. Both factors appreciably increase the nonadiabatic coupling, accelerating the electron–hole recombination process. An explanation of PtSe2-based photodetectors with the slow response, compared to conventional devices, is provided by studying this nonradiative transitions process

Microcavity-Integrated Carbon Nanotube Photodetectors

Carbon nanotubes (CNTs) are considered to be highly promising nanomaterials for multiwavelength, room-temperature infrared detection applications. Here, we demonstrate a single-tube diode photodetector monolithically integrated with a Fabry–Pérot microcavity. A ∼6-fold enhanced optical absorption can be achieved, because of the confined effect of the designed optical mode. Furthermore, taking advantage of Van-Hove-singularity band structures in CNTs, we open the possibility of developing chirality-specific (<i>n</i>,<i>m</i>) CNT-film-based signal detectors. Utilizing a concept of the “resonance and off-resonance” cavity, we achieved cavity-integrated chirality-sorted CNT-film detectors working at zero bias and resonance-allowed mode, for specific target signal detection. The detectors exhibited a higher suppression ratio until a power density of 0.07 W cm^–2 and photocurrent of 5 pA, and the spectral full width at half-maximum is ∼33 nm at a signal wavelength of 1200 nm. Further, with multiple array detectors aiming at different target signals integrated on a chip, a multiwavelength signal detector system can be expected to have applications in the fields of monitoring, biosensing, color imaging, signal capture, and on-chip or space information transfers. The approach can also bring other nanomaterials into on-chip or information optoelectronics, regardless of the available doping polarity

Anti-Ambipolar Field-Effect Transistors Based On Few-Layer 2D Transition Metal Dichalcogenides

Two-dimensional (2D) materials and their related van der Waals heterostructures have attracted considerable interest for their fascinating new properties. There are still many challenges in realizing the potential of 2D semiconductors in practical (opto)­electronics such as signal transmission and logic circuit, etc. Herein, we report the gate-tunable anti-ambipolar devices on the basis of few-layer transition metal dichalcogenides (TMDs) heterostructures to gain higher information storage density. Our study shows that carrier concentration regulated by the gate voltage plays a major role in the “anti-ambipolar” behavior, where the drain-source current can only pass through in specific range of gate voltage (<i>V</i>_g) and it will be restrained if the <i>V</i>_g goes beyond the range. Several improved strategies were theoretically discussed and experimentally adopted to obtain higher current on/off ratio for the anti-ambipolar devices, such as choosing suitable <i>p</i>-/<i>n</i>-pair, increasing carrier concentration by using thicker-layer TMDs, and so on. The modified SnS₂/WSe₂ device with the current on/off ratio exceeding 200 and on-state <i>V</i>_g ranging from −20 to 0 V was successfully achieved. On the basis of the anti-ambipolar field-effect transistors (FETs), we also reveal the potential of three-channel device unit for signal processing and information storage. With the equal quantity <i>N</i> of device units, 3^<i>N</i> digital signals can be obtained from such three-channel devices, which are much larger than 2^<i>N</i> ones obtained from traditional two-channel complementary metal oxide semiconductors (CMOS)

Placenta-restricted gene expression in <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> transgenic mice.

<p>Pregnant mice were sacrificed on gestation day 16.5 and placentas, multiple organs and embryos were collected. (<b>A</b>) Copy number of transgenes was determined by qPCR analysis in <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> transgenic founders. Genotyping analysis (<b>B</b>, <b>D</b>) of <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> transgenes by PCR and expression pattern of <i>Cre</i> mRNA (<b>C</b>, <b>E</b>) analyzed by RT-qPCR in placenta, fetus and multiple maternal organs from female transgenic mice (derived from Tg 5 founder) mated with wild type FVB male mice. β-actin was used as an internal control. Tg placental RNA is used as positive control. nd, not detectable; P, Positive control; N, Negative control. (<b>F</b>) Immunochemistry staining of Cre recombinase using anti-Cre antibody in the placentas of pregnant <i>Tpbpa</i>r<i>/Ada</i>f<i>-Ada</i>P<i>-Cre</i> females mated with wild type FVB males. Placentas with <i>Tpbpa</i>r<i>/Ada</i>f-<i>Ada</i>P-<i>Cre</i> transgenes (Cr⁺(Tg)) expressed Cre protein in giant cells (indicated by long arrow), spongiotrophoblast cells (indicated by short arrow) and cells in the labyrinthine zone (indiated by arrow head)of placentas, with highest expression in the spongiotrophoblast zone. Panel <b>F</b> (inset) showed nuclear localization of Cre in trophoblast cells. Placentas lacking <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-Cre transgenes (Cre⁻, panel <b>F</b>) and multiple organs from pregnant transgenic dams (<b>G</b>) showed no Cre immunostaining. Endogenous ADA immunostaining was performed in placentas with or without <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-Cre transgenes using anti-ADA antibody (panel <b>F</b>). Scale bar, 100 µm (placenta) or 50 µm (inset) and 500 µm for maternal organs.</p

Synthesis and Transport Properties of Large-Scale Alloy Co_0.16Mo_0.84S₂ Bilayer Nanosheets

Synthesis of large-scale highly crystalline two-dimensional alloys is significant for revealing properties. Here, we have investigated the vapor growth process of high-quality bilayer Co_<i>x</i>Mo_1–<i>x</i>S₂ (<i>x</i> = 0.16) hexagonal nanosheets systematically. As the initial loading of the sulfur increases, the morphology of the Co_<i>x</i>Mo_1–<i>x</i>S₂ (0 < <i>x</i> ≤ 1) nanosheets becomes hexagons from David stars step by step at 680 °C. We find that Co atoms mainly distribute at the edge of nanosheets. When the temperature increases from 680 to 750 °C, high-quality cubic pyrite-type crystal structure CoS₂ grows on the surface of Co_<i>x</i>Mo_1–<i>x</i>S₂ nanosheet gradually and forms hexagonal film induced by the nanosheet. Electrical transport measurements reveal that the Co_<i>x</i>Mo_1–<i>x</i>S₂ nanosheets and CoS₂ films exhibit n-type semiconducting transport behavior and half-metallic behavior, respectively. Theoretical calculations of their band structures agree well with the experimental results

Generation of <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> chimeric expression vector and <i>in vitro</i> analysis of its Cre recombinase activity in human trophoblast cells.

<p>(<b>A</b>) Structure of p<i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> construct. <i>Tpbpa</i>r/<i>Ada</i>f chimeric enhancer and <i>Ada</i> basal promoter (<i>Ada</i>P) were ligated to the sequence encoding Cre cDNA containing a nuclear localization signal (NLS). (<b>B</b>) Schematic representation of pCAG-CATZ vector. The PCR primers, primer pair 1 (AG and Z3) were used to monitor Cre-mediated loxP-dependent DNA recombination (2100 bp for parental DNA, 690 bp for the recombined DNA). Primer pair 2 (CAT2 and CAT3) were internal primers used to detect pCAG-CATZ. (<b>C</b>) PCR analysis: pCAG-CATZ was transfected alone or together with CMV-Cre or different amounts of <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> into human trophoblast cells (HTR). DNA was isolated 48 h after transfection and assayed for the presence of the recombination-dependent 690 bp fragment. In the absence of Cre, only the 2100 bp precursor PCR fragment was observed. However, in the presence of Cre, both the 2100 bp precursorand the 690 bp product PCR fragments were detected. The amount of 690 bp PCR fragment observed increased with additional <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> transfected to the cells. The 320 bp PCR fragment was used to determine that pCAG-CATZ was transfected into the cells. (<b>D</b>) Schematic representation of AdMA19 vector. Spacer interposed between the <i>loxP</i> sites precludes efficient lucifearse expression in the absence of the Cre recombinase. (<b>E</b>) Luciferase analysis. AdMA19 vector was transfected with CMV-<i>Cre (CMV-Cre/AdMA19</i>,1∶1), different amounts of <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre</i> (<i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre/AdMA19,1∶1 or 5∶1</i>) or alone. Cellular extracts were isolated 48 h after transfection and luciferase activity was measured. All data are expressed as mean ± SEM. n = 6. * <i>P</i><0.05 versus cells transfected with AdMA19 construct only. **<i>P<0.05 versus Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P-<i>Cre/AdMA19,1∶1</i>.</p

Random assembly of placental specific enhancers and <i>in vitro</i> analysis of their ability to activate the basal promoter of the <i>Ada</i> gene in multiple cell types.

<p>(<b>A</b>) Schematic illustrations of the constructs. (<b>B</b>) Luciferase activity in human trophoblast (HTR) cells transfected with each construct. (<b>C</b>) Luciferase activity driven by <i>Tpbpa</i>r/<i>Ada</i>f-<i>Ada</i>P chimeric enhancer in multiple cell lines. Data are expressed as mean ± SEM. n = 4–6. * <i>P</i><0.05 versus cells transfected with <i>Ada</i>f-<i>Ada</i>P construct.</p