Multi‐valued logic (MVL) technology that utilizes more than two logic states has recently been reconsidered because of the demand for greater power saving in current binary logic systems. Extensive ...efforts have been invested in developing MVL devices with multiple threshold voltages by adopting negative differential transconductance and resistance. In this study, a reconfigurable, multiple negative‐differential‐resistance (m‐NDR) device with an electric‐field‐induced tunability of multiple threshold voltages is reported, which comprises a BP/ReS2 heterojunction and a ReS2/h‐BN/metal capacitor. Tunability for the m‐NDR phenomenon is achieved via the resistance modulation of the ReS2 layer by electrical pulses applied to the capacitor region. Reconfigurability is verified in terms of the function of an MVL circuit composed of a reconfigurable m‐NDR device and a load transistor, wherein staggered‐type and broken‐type double peak‐NDR device operations are adopted for ternary inverter and latch circuits, respectively.
A reconfigurable, multiple negative‐differential‐resistance device with an electric‐field‐induced tunability of multiple threshold voltages is proposed. Following the successful verification of the tunability of multiple negative‐differential‐resistance phenomenon, the reconfigurability in terms of the function of multi‐valued logic circuits, from ternary inverter to latch circuit, is demonstrated.
In free flap operation, temporary hyperemia of the transferred flaps can often be encountered in the early postoperative period, appearing reddish and rapid capillary refilling time, which mimics ...venous congestion. This study aimed to investigate the factors associated with the development of hyperemia and evaluate clinical course. Consecutive patients who underwent free flap-based reconstruction between December 2019 and October 2021 were reviewed. Independent risk factors associated with its development were assessed. Flap showing initial hyperemic features were assessed using flap blood glucose measurement (BGM). If it showed over 60 mg/dL, they were closely observed without management. Their clinical outcomes were evaluated. In total, 204 cases were analyzed, of which 35 (17.2%) showed initial hyperemia. Multivariable analyses showed that using thoracodorsal artery perforator flaps and muscle containing flaps (musculocutaneous/muscle-chimeric flaps) and conducting end-to-end arterial anastomosis (vs. end-to-side) were independent predictors. All cases with initial hyperemia showed over 60 mg/dL in BGM. The phenomenon resolved spontaneously within 6.9 h averagely. Overall perfusion-related complications developed in 10 (4.9%) cases, which rate did not differ between the two groups. Several factors might be associated with the development of initial hyperemia after free flap surgery. With proper assessment, this condition can be successfully managed without unnecessary intervention.
Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia‐inducible factor (HIF‐1) protein leads to ...angiogenesis, metastasis, apoptosis resistance, and many other pro‐tumorigenic responses in cancer development. HIF‐1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia‐sensitive, a target‐specific HIF‐1 inhibitor may be a better clinical candidate in cancer drug discovery. Though no HIF‐1 inhibitor is clinically available to date, a lot of effort has been applied during the last decade in search of potent HIF‐1 inhibitors. In this review, we will summarize the structure–activity relationship of ten different chemotypes reported to be HIF‐1 inhibitors in the last decade (2007–2016), their mechanisms of action for HIF‐1 inhibition, progress in the way of target‐specific inhibitors, and problems associated with current inhibitors. It is anticipated that the results of these research on the medicinal chemistry of HIF‐1 inhibitors will provide decent information in the design and development of future inhibitors.
This study was designed to evaluate the effects of graded levels of arachidonic acid (ARA) in low fish meal diets (30% fish meal, 30% plant protein blends) on growth, feed utilization, and immunity ...of olive flounder (Paralichthys olivaceus). The control diet was formulated with 3% fish oil and 5.1% soybean oil (ARA0.0). Five other diets were formulated incorporating different levels of ARA into the ARA0.0 diet at the expense of soybean oil; that is, 0.3, 0.6, 0.9, 1.2, and 1.5% ARA (ARA0.3, ARA0.6, ARA0.9, ARA1.2, and ARA1.5), respectively. Three replicate groups of fish (88.24 ± 0.06 g) were placed into 18 polyvinyl circular tanks (215 L), with 24 fish each and fed an experimental diet twice a day for nine weeks. Overall, significantly improved growth performance was observed in the ARA0.6 group. Liver C18:2n-6 was significantly reduced, and liver ARA content was significantly increased with the increase in dietary ARA levels. Nitroblue tetrazolium activity was significantly higher in the ARA0.6 group, and significantly higher superoxide dismutase and myeloperoxidase activities were observed in the ARA0.9 group. Further, immunoglobulin level and lysozyme activity were significantly improved in the ARA0.3 group, antiprotease activity was increased in the ARA0.6 and ARA0.9 groups, and the ARA0.3 group showed lower liver lipid content than the ARA0.0 group. Serum prostaglandin E2 level was significantly increased with 1.5% ARA inclusion. Pro-inflammatory gene expressions of interleukin (IL)-6, IL-8, IL-10, perforin, and tumor necrosis factor in the intestine were significantly downregulated, and anti-inflammatory gene expression of transforming growth factor-β2 gene expression was significantly upregulated with higher dietary ARA supplementation (0.9–1.5%). These results indicate that 0.3–0.9% supplemented ARA may improve the growth, immune, and hematological parameters of olive flounder.
•The optimum dietary arachidonic acid level for olive flounder's growth was 5.8 g/kg.•0.3–0.9% dietary ARA improved the antioxidant capacity and innate immune parameters.•0.9–1.5% dietary ARA downregulated the intestinal pro-inflammatory gene expression.•Dietary ARA improved the intestinal structure and reduced liver lipid deposition.
Plasmonic metal nanoparticles have great potential for chemical and biological sensor applications, due to their sensitive spectral response to the local environment of the nanoparticle surface and ...ease of monitoring the light signal due to their strong scattering or absorption. In this work, we investigated the dependence of the sensitivity of the surface plasmon resonance (frequency and bandwidth) response to changes in their surrounding environment and the relative contribution of optical scattering to the total extinction, on the size and shape of nanorods and the type of metal, that is, Au vs Ag. Theoretical consideration on the surface plasmon resonance condition revealed that the spectral sensitivity, defined as the relative shift in resonance wavelength with respect to the refractive index change of surrounding materials, has two controlling factors: first the bulk plasma wavelength, a property dependent on the metal type, and second on the aspect ratio of the nanorods which is a geometrical parameter. It is found that the sensitivity is linearly proportional to both these factors. To quantitatively examine the dependence of the spectral sensitivity on the nanorod metal composition and the aspect ratio, the discrete dipole approximation method was used for the calculation of optical spectra of Ag−Au alloy metal nanorods as a function of Ag concentration. It is observed that the sensitivity does not depend on the type of the metal but depends largely on the aspect ratio of nanorods. The direct dependence of the sensitivity on the aspect ratio becomes more prominent as the size of nanorods becomes larger. However, the use of larger nanoparticles may induce an excessive broadening of the resonance spectrum due to an increase in the contribution of multipolar excitations. This restricts the sensing resolution. The insensitivity of the plasmon response to the metal composition is attributable to the fact that the bulk plasma frequency of the metal, which determines the spectral dispersion of the real dielectric function of metals and the surface plasmon resonance condition, has a similar value for the noble metals. On the other hand, nanorods with higher Ag concentration show a great enhancement in magnitude and sharpness of the plasmon resonance band, which gives better sensing resolution despite similar plasmon response. Furthermore, Ag nanorods have an additional advantage as better scatterers compared with Au nanorods of the same size.
Choosing reliable recipient vessels is crucial for successful free flap reconstruction of lower extremity defects, especially in patients with ischemic vasculopathy. This report describes our ...experience with the intraoperative use of indocyanine green angiography (ICGA) for selecting recipient vessels in lower extremity free flap reconstruction cases. Three patients with lower extremity defects and ischemic vasculopathy underwent free flap reconstruction. Intraoperatively, the candidate vessels were evaluated using ICGA. In the first case, a 10 × 6 cm defect on the anterior side of the lower third of the leg caused by minor trauma and associated with peripheral arterial occlusive disease was reconstructed using a super-thin anterolateral thigh flap based on one perforator. In the second case, a 12 × 8 cm defect on the posterior side of the right lower leg caused by a dog bite and associated with severe atherosclerosis throughout all three major vessels in the lower leg was reconstructed using a muscle-sparing latissimus dorsi myocutaneous flap. In the third case, a 13.5 × 5.5 cm defect on the right lateral malleolar region, where the peroneus longus tendon was exposed due to Buerger's disease, was reconstructed using a one perforator-based super-thin anterolateral thigh flap. In all cases, ICGA was used to evaluate the functionality of the candidate recipient vessels. In two cases, the candidate vessels showed acceptable blood flow, and the operations proceeded as planned. In the third case, the planned vessels of posterior tibial vessels were not identified to have sufficient blood flow, and one of their branches showing enhancement in ICGA was selected and used as a recipient vessel. All flaps survived completely. No adverse events occurred during the follow-up period of postoperative 3 months. Our results suggest that ICGA may be a valuable diagnostic tool for evaluating the quality of candidate recipient vessels in cases where their functionality cannot be guaranteed with conventional imaging modalities.
Background
With the growing demand for the use of thin perforator flaps, obtaining knowledge on the superficial anatomy of perforators is imperative for stable flap elevation. Conventional modalities ...for perforator mapping fall short in providing such information. High‐frequency ultrasound (HFUS), known for visualizing the superficially located anatomic structures, may potentially fill this void. This study aimed to evaluate the effectiveness of HFUS in the outcome of anterolateral thigh (ALT) and superficial circumflex iliac artery perforator (SCIP) flap‐based reconstructions.
Methods
Consecutive patients who underwent free ALT or SCIP flap‐based reconstruction from January 2021 to November 2022 were retrospectively reviewed. Perforator mapping was conducted using a handheld Doppler during the first year, while HFUS was used in the latter part. The two techniques were compared in terms of flap harvesting time and perfusion‐related complication rates while considering the flap elevation plane.
Results
In total, 123 cases were analyzed, including 82 ALT flaps (41 in each group) and 41 SCIP flaps (16 in the Doppler and 25 in the HFUS group). The time required for flap elevation exhibited a tendency to decrease in the HFUS group, with a significant difference observed in cases involving thin flap elevation (super‐thin ALT flaps and pure‐skin‐perforator SCIP flaps). Compared with the Doppler group, the HFUS group demonstrated significantly lower rates of PRCs, particularly partial flap necrosis. This difference remained significant in multivariable analyses.
Conclusion
Our results suggest that HFUS might be an appealing modality for perforator mapping in cases requiring thin ALT and SCIP flap.
We investigated whether human serum albumin (HSA) in suspended human hepatocytes would affect the uptake clearance of anionic drugs with high binding to HSA and improve the extrapolation of in vivo ...hepatic clearance from in vitro uptake clearance by the hepatocytes via the "albumin-mediated" hepatic uptake mechanism. The uptake clearances for total forms (
) and for unbound forms (
) of 11 anionic drugs all of which were organic anion-transporting polypeptide (OATP) substrates were determined with suspended human hepatocytes in varying concentrations of HSA. The fraction of unbound drugs (
) was determined using an equilibrium dialysis at the various HSA concentrations. The
values decreased with increasing concentrations of HSA, whereas the unbound uptake clearances (
(+) =
/
) in the presence of HSA increased substantially, thus demonstrating the "albumin-mediated" hepatic uptake mechanism. The relationships between
and HSA concentration were well described by the previously proposed facilitated-dissociation model, in which the drug-albumin complex interacts with the cell surface, enhancing the dissociation of the complex and providing unbound drug for hepatic uptake. Furthermore, the
(+) values in in vivo conditions (at 5% HSA) were predicted from those obtained in isolated hepatocytes on the basis of the facilitated-dissociation model, revealing compatibility with the overall hepatic intrinsic clearance in vivo. We conclude that the "facilitated-dissociation" model is useful for describing the "albumin-mediated" hepatic uptake phenomenon of OATP drugs and to predict hepatic uptake clearance in vivo.
Donor site defects following the radial forearm flap (RFF) harvest have been usually covered with skin grafting, which often lead to suboptimal outcomes and donor morbidities, including delayed ...healing and scar contractures. The present report aimed to evaluate the outcomes of using another free flap, the domino flap, for coverage of donor site defects following RFFF harvest.
Five patients (two males and three females) who underwent coverage of donor defects of RFFF using another free flap between 2019 and 2021 were reviewed. Their mean age was 74 years and the mean dimension of the defect of the RFF donor site was 8.7 × 5.6 cm. Four patients used an anterolateral thigh flap and one used a superficial circumflex iliac artery perforator flap.
The mean size of the domino flaps were 12.2 × 5.8 cm. Distal stumps of radial vessels adopting retrograde flow were used as recipients in four cases, and proximal ones adopting anterograde in one. The donor site of the domino flaps was primarily closed. All patients recovered well without any postoperative complications. Aesthetically pleasing outcomes with no functional impairment related to scar contractures were observed in the donor site of RFF during the mean follow-up of 15.7 months.
Use of another free flap for coverage of RFFF donor defects may provide rapid wound healing and satisfactory outcomes, and may be considered an alternative option in cases with large-sized defects that are expected to take a long time to achieve complete healing with skin grafting.
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