Ferroportin expression and regulation in human placenta/fetal membranes: Implications for ferroptosis and adverse pregnancy outcomes.

Iron overload is associated with pregnancy complications. Ferroportin (FPN) is the only known iron exporter in mammalian cells. We hypothesize that FPN is functionally important in ferrotopsis, a process of iron-dependent non-apoptotic programmed cell death, and may have a critical role to play in pregnancy success. We investigated the expression of FPN in placenta/fetal membranes by immunohistochemistry in tissues collected from pregnancies with/without preeclampsia (PE) and spontaneous preterm birth (SPTB). FPN was highly expressed in both trophoblasts and decidual cells found in placenta/fetal membranes. Staining was significantly reduced in fetal membranes from SPTB versus healthy pregnancies (P = 0.046). FPN expression in immortalized human endometrial stromal cells (HESC) increased with in vitro decidualization induction using 1 µM of medroxyprogesterone acetate and 0.5 mM of dibutyryl-cAMP. In addition, both HESC cells and immortalized extravillous trophoblast SW71 cells with FPN knockdown showed significant sensitivity to ferroptosis inducer, erastin (P < 0.001 and P = 0.009, respectively). The survival of both HESC and SW71 cells was not negatively affected by iron supplementation with ferric ammonium citrate in the medium. However, SW71 cells were more sensitive than HESC cells to physiologic iron in the presence of a non-lethal dose of erastin (P < 0.001). Taken together, our data demonstrating increased sensitivity of FPN knockdown HESC and SW71 cells to erastin and increased sensitivity of trophoblasts to iron overload under ferroptotic stress support the hypothesis that FPN protects against ferroptosis during pregnancy.

Photolithographic Patterning of Organic Color-Centers.

Organic color-centers (OCCs) have emerged as promising single-photon emitters for solid-state quantum technologies, chemically specific sensing, and near-infrared bioimaging. However, these quantum light sources are currently synthesized in bulk solution, lacking the spatial control required for on-chip integration. The ability to pattern OCCs on solid substrates with high spatial precision and molecularly defined structure is essential to interface electronics and advance their quantum applications. Herein, a lithographic generation of OCCs on solid-state semiconducting single-walled carbon nanotube films at spatially defined locations is presented. By using light-driven diazoether chemistry, it is possible to directly pattern p-nitroaryl OCCs, which demonstrate chemically specific spectral signatures at programmed positions as confirmed by Raman mapping and hyperspectral photoluminescence imaging. This light-driven technique enables the fabrication of OCC arrays on solid films that fluoresce in the shortwave infrared and presents an important step toward the direct writing of quantum emitters and other functionalities at the molecular level.

Channeling Excitons to Emissive Defect Sites in Carbon Nanotube Semiconductors beyond the Dilute Regime.

The exciton photoluminescence of carbon nanotube semiconductors has been intensively exploited for bioimaging, anticounterfeiting, photodetection, and quantum information science. However, at high concentrations, photoluminescence is lost to self-quenching because of the nearly complete overlap of the absorption and emissive states (∼10 meV Stokes shift). Here we show that by introducing sparse fluorescent quantum defects via covalent chemistry, self-quenching can be efficiently bypassed by means of the new emission route. The defect photoluminescence is significantly red-shifted by 190 meV for p-nitroaryl tailored (6,5)-single-walled carbon nanotubes (SWCNTs) from the native emission of the nanotube. Notably, the defect photoluminescence is more than 34 times brighter than the native photoluminescence of unfunctionalized SWCNTs in the most concentrated nanotube solution tested (2.7 × 1014 nanotubes/mL). Moreover, we show that defect photoluminescence is more resistant to self-quenching than the native state in a dense film, which is the upper limit of concentration. Our findings open opportunities to harness nanotube excitons in highly concentrated systems for applications where photoluminescence brightness and light-collecting efficiency are mutually important.

Laser Lithography of a Tube-in-a-Tube Nanostructure.

Carbon nanotubes hold vast potential for device innovations because their optical and electronic properties can be synthetically tailored at a length scale unattainable by lithographic techniques. However, lithographic patterning of carbon nanotubes with electronic-type control remains one of the major problems for the integration of these nanomaterials for practical device applications. In this work, we propose a laser lithography method for direct-write patterning of devices on thin films of outer wall selectively functionalized double-walled carbon nanotubes (Tube^2). This method is enabled by the reversible removal of surface functional groups with a laser tuned into resonance with the inner tube of Tube^2. We show that it is possible to directly create patterned dot arrays and conductive pathways and circuits on insulating Tube^2 thin films by tuning the resonance of the direct-writing laser with the electronic type of the inner tube (i.e., metallic or semiconducting). The successful patterning was unambiguously confirmed with in situ Raman spectral imaging and electrical characterization. This work suggests the possibility of developing a nanostructure-specific nanofabrication technology reminiscent of thermal printing.

Chemical Gating of a Synthetic Tube-in-a-Tube Semiconductor.

A critical challenge to translating field effect transistors into biochemical sensor platforms is the requirement of a gate electrode, which imposes restrictions on sensor device architectures and results in added expense, poorer scalability, and electrical noise. Here we show that it is possible to eliminate the need of the physical gate electrode and dielectrics altogether using a synthetic tube-in-a-tube (Tube∧2) semiconductor. Composed of a semiconducting single-walled carbon nanotube nested in a charged, impermeable covalent functional shell, Tube∧2 allows the semiconducting conduction pathway to be modulated solely by surface functional groups in a chemically gated-all-around configuration. The removal of physical gates significantly simplifies the device architecture and enables photolithography-free, highly scalable fabrication of transistor sensors in nonconventional configurations that are otherwise impossible. We show that concomitant FET sensitivity and single-mismatch selectivity can be achieved with Tube∧2 even in a two-terminal, thin film transistor device configuration that is as simple as a chemiresistor. Miniaturized two-terminal field effect point sensors can also be fabricated, using a straightforward dice-and-dip procedure, for the detection of tuberculosis biomarkers.

Graphene as a functional layer for semiconducting carbon nanotube transistor sensors.

Single-walled carbon nanotubes (SWCNTs) hold vast potential for future electronic devices due to their outstanding properties, however covalent functionalization often destroys the intrinsic properties of SWCNTs, thus limiting their full potential. Here, we demonstrate the fabrication of a functionalized graphene/semiconducting SWCNT (T@fG) heterostructured thin film transistor as a chemical sensor. In this structural configuration, graphene acts as an atom-thick, impermeable layer that can be covalently functionalized via facile diazonium chemistry to afford a high density of surface functional groups while protecting the underlying SWCNT network from chemical modification, even during a covalent chemical reaction. As a result, the highly functionalized carbon-based hybrid structure exhibits excellent transistor properties with a carrier mobility and ON/OFF ratio as high as 64 cm2/Vs and 5400, respectively. To demonstrate its use in potential applications, T@fG thin films were fabricated as aqueous ammonium sensors exhibiting a detection limit of 0.25 µM in a millimolar ionic strength solution, which is comparable with state-of-the-art aqueous ammonium nanosensors.

Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma.

Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis.

Selective breakdown of metallic pathways in double-walled carbon nanotube networks.

Covalently functionalized, semiconducting double-walled carbon nanotubes exhibit remarkable properties and can outperform their single-walled carbon nanotube counterparts. In order to harness their potential for electronic applications, metallic double-walled carbon nanotubes must be separated from the semiconductors. However, the inner wall is inaccessible to current separation techniques which rely on the surface properties. Here, the first approach to address this challenge through electrical breakdown of metallic double-walled carbon nanotubes, both inner and outer walls, within networks of mixed electronic types is described. The intact semiconductors demonstrate a ∼62% retention of the ON-state conductance in thin film transistors in response to covalent functionalization. The selective elimination of the metallic pathways improves the ON/OFF ratio, by more than 360 times, to as high as 40 700, while simultaneously retaining high ON-state conductance.

An in vitro investigation of gastrointestinal Na(+) uptake mechanisms in freshwater rainbow trout.

In vitro gut-sac preparations of all four sections (stomach, anterior, mid, and posterior intestine) of the gastrointestinal tract (GIT) of freshwater rainbow trout, together with radiotracer ((22)Na) techniques, were used to study unidirectional Na(+) uptake rates (UR, mucosal â†’ blood space) and net absorptive fluid transport rates (FTR) under isosmotic conditions (mucosal = serosal osmolality). On an area-specific basis, unidirectional Na(+) UR was highest in the mid-intestine, but when total gut area was taken into account, the three intestinal sections contributed equally, with very low rates in the stomach. The theoretical capacity for Na(+) uptake across the whole GIT is sufficient to supply all of the animal's nutritive requirements for Na(+). Transport occurs by low affinity systems with apparent K m values 2-3 orders of magnitude higher than those in the gills, in accord with comparably higher Na(+) concentrations in chyme versus fresh water. Fluid transport appeared to be Na(+)-dependent, such that treatments which altered unidirectional Na(+) UR generally altered FTR in a comparable fashion. Pharmacological trials (amiloride, EIPA, phenamil, bafilomycin, furosemide, hydrochlorothiazide) conducted at a mucosal Na(+) concentration of 50 mmol L(-1) indicated that GIT Na(+) uptake occurs by a variety of apical mechanisms (NHE, Na(+) channel/H(+) ATPase, NCC, NKCC) with relative contributions varying among sections. However, at a mucosal Na(+) concentration of 10 mmol L(-1), EIPA, phenamil, bafilomycin, and hydrochlorothiazide were no longer effective in inhibiting unidirectional Na(+) UR or FTR, suggesting the contribution of unidentified mechanisms under low Na(+) conditions. A preliminary model is presented.

Covalently functionalized double-walled carbon nanotubes combine high sensitivity and selectivity in the electrical detection of small molecules.

Atom-thick materials such as single-walled carbon nanotubes (SWCNTs) and graphene exhibit ultrahigh sensitivity to chemical perturbation partly because all of the constituent atoms are surface atoms. However, low selectivity due to nonspecific binding on the graphitic surface is a challenging issue to many applications including chemical sensing. Here, we demonstrated simultaneous attainment of high sensitivity and selectivity in thin-film field effect transistors (TFTs) based on outer-wall selectively functionalized double-walled carbon nanotubes (DWCNTs). With carboxylic acid functionalized DWCNT TFTs, we obtained excellent gate modulation (on/off ratio as high as 4000) with relatively high ON currents at a CNT areal density as low as 35 ng/cm(2). The devices displayed an NH(3) sensitivity of 60 nM (or ~1 ppb), which is comparable to small molecule aqueous solution detection using state-of-the-art SWCNT TFT sensors while concomitantly achieving 6000 times higher chemical selectivity toward a variety of amine-containing analyte molecules over that of other small molecules. These results highlight the potential of using covalently functionalized double-walled carbon nanotubes for simultaneous ultrahigh selective and sensitive detection of chemicals and illustrate some of the structural advantages of this double-wall materials strategy to nanoelectronics.