Softening implantable bioelectronics: Material designs, applications, and future directions.

Implantable bioelectronics, integrated directly within the body, represent a potent biomedical solution for monitoring and treating a range of medical conditions, including chronic diseases, neural disorders, and cardiac conditions, through personalized medical interventions. Nevertheless, contemporary implantable bioelectronics rely heavily on rigid materials (e.g., inorganic materials and metals), leading to inflammatory responses and tissue damage due to a mechanical mismatch with biological tissues. Recently, soft electronics with mechanical properties comparable to those of biological tissues have been introduced to alleviate fatal immune responses and improve tissue conformity. Despite their myriad advantages, substantial challenges persist in surgical handling and precise positioning due to their high compliance. To surmount these obstacles, softening implantable bioelectronics has garnered significant attention as it embraces the benefits of both rigid and soft bioelectronics. These devices are rigid for easy standalone implantation, transitioning to a soft state in vivo in response to environmental stimuli, which effectively overcomes functional/biological problems inherent in the static mechanical properties of conventional implants. This article reviews recent research and development in softening materials and designs for implantable bioelectronics. Examples featuring tissue-penetrating and conformal softening devices highlight the promising potential of these approaches in biomedical applications. A concluding section delves into current challenges and outlines future directions for softening implantable device technologies, underscoring their pivotal role in propelling the evolution of next-generation bioelectronics.

Polarization Inverted Ultrasound Transducer Based on Composite Structure for Tissue Harmonic and Frequency Compound Imaging.

Ultrasound transducer with polarization inversion technique (PIT) can provide dual-frequency feature for tissue harmonic imaging (THI) and frequency compound imaging (FCI). However, in the conventional PIT, the ultrasound intensity is reduced due to the multiple resonance characteristics of the combined piezoelectric element, and it is challenging to handle the thin piezoelectric layer required to make a PIT-based acoustic stack. In this study, an improved PIT using a piezo-composite layer was proposed to compensate for those problems simultaneously. The novel PIT-based acoustic stack also consists of two piezoelectric layers with opposite poling directions, in which the piezo-composite layer is located on the front side and the bulk-type piezoelectric layer is located on the back side. The thickness ratio between two piezoelectric layers is 0.5:0.5, but unlike a typical PIT model, it can generate dual-frequency spectrum. A finite element analysis (FEA) simulation was conducted, and subsequently, the prototype transducer was fabricated for performance demonstration. In the simulation and experiment, the intensity was increased by 56.76% and 30.88% compared to the conventional PIT model with the thickness ratio of 0.3:0.7. Thus, the proposed PIT-based transducer is expected to be useful in implementation of THI and FCI.

An Intraocular Pressure Measurement Technique Based on Acoustic Radiation Force Using an Ultrasound Transducer: A Feasibility Study.

High intraocular pressure (IOP) is one of the major risk factors for glaucoma, and thus accurate IOP measurements should be performed to diagnose and treat glaucoma early. In this study, a novel technique for measuring the IOP based on acoustic radiation force was proposed, and its potential was experimentally demonstrated. The proposed technique uses the acoustic radiation force to generate axial displacement on the ocular surface while simultaneously measuring the degree of deformation. In order to verify that the ocular displacement induced by the acoustic radiation force is related to the IOP, the experiment was conducted by fabricating a 5 MHz single element transducer and gelatin phantoms with different stiffness values. Our experimental results show that there is a close relationship between the ocular displacement by the acoustic radiation force and the IOP obtained by a commercial tonometer. Therefore, the proposed acoustic radiation force technique can be a promising candidate for measuring the IOP.

Interleaved Array Transducer with Polarization Inversion Technique to Implement Ultrasound Tissue Harmonic Imaging.

In ultrasound tissue harmonic imaging (THI), it is preferred that the bandwidth of the array transducer covers at least the fundamental frequency f0 for transmission and the second harmonic frequency 2f0 for reception. However, it is challenging to develop an array transducer with a broad bandwidth due to the single resonance characteristics of piezoelectric materials. In this study, we present an improved interleaved array transducer suitable for THI and a dedicated transducer fabrication scheme. The proposed array transducer has a novel structure in which conventional elements exhibiting f0 resonant frequency and polarization-inverted elements exhibiting 2f0 resonant frequency are alternately located, and the thicknesses of all piezoelectric elements are identical. The performance of the proposed method was demonstrated by finite element analysis (FEA) simulations and experiments using a fabricated prototype array transducer. Using the proposed technique, f0 and 2f0 frequency ultrasounds can be efficiently transmitted and received, respectively, resulting in a 90% broad bandwidth feature of the transducer. Thus, the proposed technique can be one of the potential ways to implement high resolution THI.

Intravascular Ultrasound Transducer by Using Polarization Inversion Technique for Tissue Harmonic Imaging: Modeling and Experiments.

Intravascular ultrasound (IVUS) tissue harmonic imaging (THI) is a useful vessel imaging technique that can provide deep penetration depth as well as high spatial and contrast resolution. Typically, a high-frequency IVUS transducer for THI requires a broad bandwidth or dual-frequency bandwidth. However, it is very difficult to make an IVUS transducer with a frequency bandwidth covering from the fundamental frequency to the second harmonic or a dual-peak at the desired frequency. To solve this problem, in this study, we applied the polarization inversion technique (PIT) to the IVUS transducer for THI. The PIT makes it relatively easy to design IVUS transducers with suitable frequency characteristics for THI depending on the inversion ratio of the piezoelectric layer and specifications of the passive materials. In this study, two types of IVUS transducers based on the PIT were developed for THI. One is a front-side inversion layer (FSIL) transducer with a broad bandwidth, and the other is a back-side inversion layer (BSIL) transducer with a dual-frequency bandwidth. These transducers were designed using finite element analysis (FEA)-based simulation, and the prototype transducers were fabricated. Subsequently, the performance was evaluated by not only electrical impedance and pulse-echo response tests but also B-mode imaging tests with a 25 µm tungsten wire and tissue-mimicking gelatin phantoms. The FEA simulation and experimental results show that the proposed scheme can successfully implement the tissue harmonic IVUS image, and thus it can be one of the promising techniques for developing IVUS transducers for THI.

A Phase-Canceled Backing Layer for Ultrasound Linear Array Transducer: Modeling and Experimental Verification.

In this study, a phase-canceled backing layer for ultrasound linear array transducer is presented. The proposed backing layer is composed of multiple blocks operated by a phase inversion technique. Inside the proposed backing layer, the phase of the reflected signals can be canceled by adjusting acoustic impedance, piezoelectric layer contact area, and thickness of each block constituting the backing layer. Therefore, the total thickness of the backing layer can be significantly reduced while maintaining the performance. Using finite element analysis (FEA) simulation, its performance was verified based on an 8-MHz linear array transducer. Two types of bulk-type backing layers with different thicknesses were also simulated to compare the performance of the proposed method. In the case of a narrow bandwidth signal without the matching layers, the 10-mm-thick bulk-type backing layer yielded a -6-dB bandwidth of 37.2%. When its thickness was reduced to 2 mm, the -6-dB bandwidth was decreased to 17.3% due to the reflected back-wall signals. However, the -6-dB bandwidth of the proposed backing layer with 2-mm thickness was 39.5%, which is similar to the thick bulk-type backing layer. In the case of broad bandwidth signal with the matching layers, the proposed transducer also exhibits similar performance compared with the thick bulk-type backing layer. The narrow bandwidth signal was experimentally implemented by using a prototype array transducer with the proposed technique, and the performance was similar to the simulation. Thus, the proposed method can reduce the thickness of the backing layer of various array transducers.

Computer-aided diagnosis system for thyroid nodules on ultrasonography: diagnostic performance and reproducibility based on the experience level of operators.

PURPOSE: To evaluate the diagnostic performance and reproducibility of a computer-aided diagnosis (CAD) system for thyroid cancer diagnosis using ultrasonography (US) based on the operator's experience. MATERIALS AND METHODS: Between July 2016 and October 2016, 76 consecutive patients with 100 thyroid nodules (≥ 1.0 cm) were prospectively included. An experienced radiologist performed the US examinations with a real-time CAD system integrated into the US machine, and three operators with different levels of US experience (0-5 years) independently applied the CAD system. We compared the diagnostic performance of the CAD system based on the operators' experience and calculated the interobserver agreement for cancer diagnosis and in terms of each US descriptor. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 88.6, 83.9, 81.3, 90.4, and 86.0%, respectively. The sensitivity and accuracy of the CAD system were not significantly different from those of the radiologist (p > 0.05), while the specificity was higher for the experienced radiologist (p = 0.016). For the less-experienced operators, the sensitivity was 68.8-73.8%, specificity 74.1-88.5%, PPV 68.9-73.3%, NPV 72.7-80.0%, and accuracy 71.0-75.0%. The less-experienced operators showed lower sensitivity and accuracy than those for the experienced radiologist. The interobserver agreement was substantial for the final diagnosis and each US descriptor, and moderate for the margin and composition. CONCLUSIONS: The CAD system may have a potential role in the thyroid cancer diagnosis. However, operator dependency still remains and needs improvement. KEY POINTS: • The sensitivity and accuracy of the CAD system did not differ significantly from those of the experienced radiologist (88.6% vs. 84.1%, p = 0.687; 86.0% vs. 91.0%, p = 0.267) while the specificity was significantly higher for the experienced radiologist (83.9% vs. 96.4%, p = 0.016). • However, the diagnostic performance varied according to the operator's experience (sensitivity 70.5-88.6%, accuracy 72.0-86.0%) and they were lower for the less-experienced operators than for the experienced radiologist. • The interobserver agreement was substantial for the final diagnosis and each US descriptor and moderate for the margin and composition.

Comparison of three immunoassays for determination of immunity to rubella virus in healthcare workers.

Rubella virus is a critical infectious pathogen to healthcare workers but is preventable by vaccination. In this study, we used three immunoassays - LIAISON Rubella IgG, ARCHITECT Rubella IgG, and AtheNA Multi-Lyte MMRV IgG - to detect rubella virus IgG and tested 182 serum specimens. The percentage of positives with the three Rubella tests were as follows: LIAISON, 71.9%; ARCHITECT, 83.5%; and AtheNA, 99.5%. The three assays showed an overall agreement rate of 71.9%. The rates of seropositive detection with LIAISON, ARCHITECT, and AtheNA among healthcare workers with and without self-reporting history of past infection or vaccination were 70.7% and 90.9%, 83.6% and 81.8%, and 99.4% and 100%, respectively. The three immunoassays showed a low agreement rate for rubella virus IgG. Therefore, choosing accurate and appropriate IgG assay methods is very important for effective infection control and prevention.

AKIN10 delays flowering by inactivating IDD8 transcription factor through protein phosphorylation in Arabidopsis.

BACKGROUND: Sugar plays a central role as a source of carbon metabolism and energy production and a signaling molecule in diverse growth and developmental processes and environmental adaptation in plants. It is known that sugar metabolism and allocation between different physiological functions is intimately associated with flowering transition in many plant species. The INDETERMINATE DOMAIN (IDD)-containing transcription factor IDD8 regulates flowering time by modulating sugar metabolism and transport under sugar-limiting conditions in Arabidopsis. Meanwhile, it has been reported that SUCROSE NONFERMENTING-1-RELATED PROTEIN KINASE 1 (SnRK1), which acts as a sensor of cellular energy metabolism, is activated by sugar deprivation. Notably, SnRK1-overexpressing plants and IDD8-deficient mutants exhibit similar phenotypes, including delayed flowering, suggesting that SnRK1 is involved in the IDD8-mediated metabolic control of flowering. RESULTS: We examined whether the sugar deprivation-sensing SnRK1 is functionally associated with IDD8 in flowering time control through biochemical and molecular genetic approaches. Overproduction of AKIN10, the catalytic subunit of SnRK1, delayed flowering in Arabidopsis, as was observed in IDD8-deficient idd8-3 mutant. We found that AKIN10 interacts with IDD8 in the nucleus. Consequently, AKIN10 phosphorylates IDD8 primarily at two serine (Ser) residues, Ser-178 and Ser-182, which reside in the fourth zinc finger (ZF) domain that mediates DNA binding and protein-protein interactions. AKIN10-mediated phosphorylation did not affect the subcellular localization and DNA-binding property of IDD8. Instead, the transcriptional activation activity of the phosphorylated IDD8 was significantly reduced. Together, these observations indicate that AKIN10 antagonizes the IDD8 function in flowering time control, a notion that is consistent with the delayed flowering phenotypes of AKIN10-overexpressing plants and idd8-3 mutant. CONCLUSION: Our data show that SnRK1 and its substrate IDD8 constitute a sugar metabolic pathway that mediates the timing of flowering under sugar deprivation conditions. In this signaling scheme, the SnRK1 signals are directly integrated into the IDD8-mediated gene regulatory network that governs flowering transition in response to fluctuations in sugar metabolism, further supporting the metabolic control of flowering.

Glutamine protects against cisplatin-induced nephrotoxicity by decreasing cisplatin accumulation.

Cisplatin is a chemotherapeutic drug but induces acute kidney injury (AKI). Cisplatin-induced AKI depends on several signaling pathways leading to apoptosis in tubular epithelial cells. Glutamine is a substrate for the synthesis of glutathione, the most abundant intracellular thiol and antioxidant, and plays an important role in protecting cells from apoptosis induced by different stimuli. In the present study, we investigated the protective effect of glutamine on cisplatin-induced AKI. Rats were divided into control, glutamine, cisplatin, and cisplatin plus glutamine groups. Glutamine ameliorated renal dysfunction, tissue injury, and cisplatin-induced apoptosis. Cisplatin increased cell death, caspase-3 cleavage, activation of MAPKs and p53, oxidative stress, and mRNA expression of TNF-α and TNFR1 in HK-2 cells. Glutamine treatment reduced cisplatin-induced these changes in HK-2 cells. Notably, glutamine reduced the cisplatin-induced expression of organic cation transporter 2 (OCT2) and cisplatin accumulation. Our results suggest that the protective effect of glutamine on cisplatin is specific for proximal tubular cells and the initial effects may be related to attenuation of cisplatin uptake. Thus, glutamine administration might represent a new strategy for the treatment of cisplatin-induced AKI.

Enhancement of IGF-2-induced neurite outgrowth by IGF-binding protein-2 and osteoglycin in SH-SY5Y human neuroblastoma cells.

A previous study using a mouse model of depression showed that chronic immobilization stress (CIS) reduces levels of insulin-like growth factor (IGF)-2, IGF binding protein 2 (IGFBP2), osteoglycin, and fibromodulin in the amygdala. Here, using human neuroblastoma cells, we tested whether these four proteins cooperatively modulate neuronal plasticity. We found that IGF-2 and IGFBP2 synergistically increased neurite outgrowth via enhanced early signaling through the IGF type 1 receptor. Furthermore, we found that osteoglycin, a small leucine-rich proteoglycan, significantly increased IGF-2/IGFPB2-induced neurite outgrowth, but fibromodulin had no effect. We also found that central amygdala neurons of CIS-induced depressive mouse showed a decreased total dendritic length. These findings suggest that CIS-responsive proteins modulate neuronal morphology during chronic stress.

Targeted inactivation of transcription factors by overexpression of their truncated forms in plants.

Transcription factors are central constituents of gene regulatory networks that control diverse aspects of plant development and environmental adaptability. Therefore they have been explored for decades as primary targets for agricultural biotechnology. A gene of interest can readily be introduced into many crop plants, whereas targeted gene inactivation is practically difficult in many cases. Here, we developed an artificial small interfering peptide (a-siPEP) approach, which is based on overexpression of specific protein domains, and evaluated its application for the targeted inactivation of transcription factors in the dicot model, Arabidopsis, and monocot model, Brachypodium. We designed potential a-siPEPs of two representative MADS box transcription factors, SUPPRESSOR OF OVEREXPRESSOR OF CONSTANS 1 (SOC1) and AGAMOUS (AG), and a MYB transcription factor, LATE ELONGATED HYPOCOTYL (LHY). Transgenic plants overproducing the a-siPEPs displayed phenotypes comparable to those of gene-deficient mutants. The a-siPEPs attenuate nuclear import and DNA-binding of target transcription factors. Our data demonstrate that the a-siPEP tool is an efficient genetic means of inactivating specific transcription factors in plants.

trans-1,2-Diaminocyclohexane mesoporous silica for asymmetric catalysis: enhancement of chirality through confinement space by the plug effect.

trans-1,2-Diaminocyclohexane functionalized mesoporous silica was applied as an ideal catalyst for asymmetric Michael addition of various nitroalkane derivatives. Short channels and plugs in the pore structure offered chiral enhancement in Michael addition.

Food protective effects of Periploca sepium oil and its active component against stored food mites.

The aim of this study was to examine the acaricidal activity of Periploca sepium oil and its active component against Tyrophagus putrescentiae. Based on its 50% lethal dose (LD(50) ) value, P. sepium oil (8.45 µg/cm(2)) was highly active against T. putrescentiae. The active constituent of P. sepium was isolated by chromatographic techniques and identified as 2-hydroxy-4-methoxybenzaldehyde. In the comparison with synthetic acaricides, the acaricidal activity of 2-hydroxy-4-methoxybenzaldehyde (0.94 µg/cm(2)) against T. putrescentiae was 12.2- and 31.2-fold greater than those of benzyl benzoate (11.45 µg/cm(2)) and N,N-diethyl-m-toluamide (29.33 µg/cm(2)), respectively. To establish structure-activity relationships, the acaricidal activities of 2-hydroxy-4-methoxybenzaldehyde and its derivatives against T. putrescentiae were determined by using an impregnated fabric disk bioassay. On the basis of LD(50) values, 4-methoxybenzaldehyde (0.48 µg/cm(2)) was the most effective against T. putrescentiae, followed by 3-methoxybenzaldehyde (0.82 µg/cm(2)), 2-hydroxy-5-methoxybenzaldehyde (0.92 µg/cm(2)), 2-methoxybenzaldehyde (0.95 µg/cm(2)), 2-hydroxybenzaldehyde (0.97 µg/cm(2)), and 2-hydroxy-3-methoxybenzaldehyde (2.35 µg/cm(2)). These results indicate that the introduction of a hydroxyl and/or methoxy group into the benzaldehyde skeleton increased the acaricidal activity. Therefore, 2-hydroxy-4-methoxybenzaldehyde and its derivatives could potentially be used as potent mite control agents.

Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain.

Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule.

Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism.

Alternative splicing of primary gene transcripts provides eukaryotic cells, with a critical scheme for enriching transcriptome and proteome diversity. Here we report that alternative splicing of the Arabidopsis INDERMINATE DOMAIN 14 (IDD14) transcription factor gene generates a competitive inhibitor in regulating starch metabolism. An alternatively spliced IDD14 form (IDD14ß), which is produced predominantly under cold conditions, lacks functional DNA-binding domain but is able to form heterodimers with the functional IDD14 form (IDD14α). IDD14α-IDD14ß heterodimers have reduced binding activity to the promoter of Qua-Quine Starch (QQS) gene that regulates starch accumulation. Transgenic Arabidopsis plants overproducing IDD14α (35S:IDD14α) exhibited retarded growth with pale green leaves as appeared on QQS-overexpressing plants. Notably, IDD14ß overproduction rescued the 35S:IDD14α phenotypes. We propose that alternative splicing of the IDD14 gene generates a self-controlled regulatory loop that may modulate starch accumulation in response to cold.

Direct synthesis of plugged SBA-15 type mesoporous silica using alcoholamines.

Plugged mesoporous SBA-15 having a 2-D hexagonal pore structure could be directly synthesized under acidic conditions using P123 as a supramolecular template, sodium metasilicate and alcoholamines. The use of alcoholamines seemed to play roles as capturing agents for silica sources that could form internal porous plugs.

Removal of Cu(II) from water by tetrakis(4-carboxyphenyl) porphyrin-functionalized mesoporous silica.

Various adsorbents are available for the removal of heavy and toxic metals, silica-based materials have been the most popular. Recently, there has been considerable interest for the modification of organic moieties and mesostructured materials to enable their use as efficient adsorbent for metal removal. In this study, here we are reporting successful incorporation of tetrakis(4-carboxyphenyl)porphyrin (TCPP) in mesoporous silica by the post-synthetic method. TCPP-SBA-15 has been found to be an effective material for the removal of Cu(II) from aqueous solution due to the chelating nature of the porphyrin-bridging group. A comparative study on adsorption of copper(II) ion over NH(2)-SBA-15 silica and TCPP-SBA-15 was performed. The results show that TCPP-SBA-15 material has higher adsorption capacity than NH(2)-SBA-15 silica and it reaches the adsorption maxima around 13 mmol g(-1).

An Analysis of the Correlation between Alopecia and Chief Complaints.

OBJECTIVES: In this study, we measured the extent of ten levels of classified symptoms by 300 (male and female) patients visiting the hair loss clinics of "S" hospitals in Gangbuk and Gangnam between January 2009 and June 2011 by analyzing the patients' chief complaints. METHODS: The method of measurement was based on a symptom questionnaire possessing 51 categories. Through the statistical analysis of data mining techniques, decision trees, and logistic regression, we derived a logistic regression model and decision tree model that improved both the response rate and significant hair loss-related characteristics of the questionnaire. RESULTS: The results of this study indicate that dry hair, seborrheic scalps and skin, tobacco and/or coffee addiction, anxiety, nausea, indigestion, and facial flushing correlate to hair loss. CONCLUSIONS: We anticipate that the subjective symptoms of hair loss can provide a foundation for preventing secondary diseases and provide clinical data information during the period of treatment. This can contribute to the improvement of patient satisfaction after customized treatment.

Acute stress responsive RGS proteins in the mouse brain.

Regulator of G-protein signaling (RGS) proteins play an important role in G-protein coupled receptor (GPCR) signaling and the activity of some GPCRs is modulated via RGS protein levels during stress response. The aim of this study was to investigate changes in RGS protein mRNA expressions in the mouse brain after 2h restraint stress. The mRNA level of 19 RGS proteins was analyzed using real-time PCR in six brain regions, which included the prefrontal cortex, amygdala, hippocampus, hypothalamus, striatum, and pituitary gland, from control and stressed mouse. We found that the level of mRNA of each RGS varied according to brain region and that two to eight RGS proteins exhibited changes in mRNA levels in each brain region by restraint stress. It was also revealed that RGS4 protein amount was consistent with mRNA level, indicating RGS4 protein may have regulatory roles in the acute stress response.