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Background: There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB.Methods: Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers.Results: Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate.Conclusion: FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients’ medical condition when deciding to perform FNABs would be advisable to lower potential complications.

The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin

Hydrogels are promising material for wound dressing and tissue engineering. However, owing to their low tissue adhesion in a moist environment and lack of flexibility, hydrogels are still not widely applied in movable parts, such as joints. Herein, we report a dual-crosslinked hydrogel adhesive using a dopamine-modified and acrylate-terminated crosslinker, tri(ethylene glycol) diacrylate-dopamine crosslinker (TDC). The covalent crosslinking was formed by photopolymerization between acrylic acid (AA) and TDC, and the noncovalent crosslinking was formed by intermolecular dopamine-dopamine and dopamine-AA interactions. Our resultant hydrogel demonstrated strong tissue adhesion in a moist environment (approximately 71 kPa) and high mechanical resilience (approximately 94%) with immediate recovery at a 200% strain rate. Moreover, it accelerated wound healing upon dressing the wound site properly. Our study provides the potential for advanced polymer synthesis by introducing a functional crosslinking agent.

PURPOSE: Clearance of brain waste in the cerebrospinal fluid (CSF) through the meningeal lymphatic vessels (mLV) has been evaluated mostly through the fluorescent imaging which has inherent limitations in the context of animal physiology and clinical translatability. The study aimed to establish molecular imaging for the evaluation of mLV clearance function. METHODS: Radionuclide imaging after intrathecal (IT) injection was acquired in C57BL/6 mice of 2–9 months. The distribution of [(99m)Tc]Tc-diethylenetriamine pentaacetate (DTPA) and [(64)Cu]Cu-human serum albumin (HSA) was comparatively evaluated. Evans Blue and [(64)Cu]Cu-HSA were used to evaluate the distribution of tracer under various speed and volume conditions. RESULTS: [(99m)Tc]Tc-DTPA is not a suitable tracer for evaluation of CSF clearance via mLV as no cervical lymph node uptake was observed while it was cleared from the body. A total volume of 3 to 9 μL at an infusion rate of 300 to 500 nL/min was not sufficient for the tracer to reach the cranial subarachnoid space and clear throughout the mLV. As a result, whole-body positron emission tomography imaging using [(64)Cu]Cu-HSA at 700 nL/min, to deliver 6 μL of injected volume, was set for characterization of the CSF to mLV clearance. Through this protocol, the mean terminal CSF clearance half-life was measured to be 123.6 min (range 117.0–135.0) in normal mice. CONCLUSIONS: We established molecular imaging to evaluate CSF drainage through mLV using [(64)Cu]Cu-HSA. This imaging method is expected to be extended in animal models of dysfunctional meningeal lymphatic clearance and translational research for disease-modifying therapeutic approaches. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13139-022-00746-6.

Background Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes.Results We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®.Conclusion The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.

The conversion efficiency of energy-harvesting devices can be increased by utilizing hot-carriers (HCs). However, due to ultrafast carrier-carrier scattering and the lack of carrier injection dynamics, HC-based devices have low efficiencies. In the present work, we report the effective utilization of HCs at the nanoscale and their transfer dynamics from a non-noble metal to a metal oxide interface by means of real-space photocurrent mapping by using local probe techniques and conducting femtosecond transient absorption (TA) measurements. The photocurrent maps obtained under white light unambiguously show that the HCs are injected into the metal oxide layer from the TiN layer, as also confirmed by conductive atomic force microscopy. In addition, the increased photocurrent in the bilayer structure indicates the injection of HCs from both layers due to the broadband absorption efficiency of TiN layer, passivation of the surface states by the top TiN layer, and smaller barrier height of the interfaces. Furthermore, electrostatic force microscopy and Kelvin probe force microscopy provide direct evidence of charge injection from TiN to the MoOx film at the nanoscale. The TA absorption spectra show a strong photo-bleaching signal over wide spectral range and ultrafast decaying behavior at the picosecond time scale, which indicate efficient electron transfer from TiN to MoOx. Thus, our simple and effective approach can facilitate HC collection under white light, thereby achieving high conversion efficiency for optoelectronic devices.

The physiological crosstalk between glucocorticoid and melatonin maintains neuronal homeostasis in regulating circadian rhythms. However, the stress-inducing level of glucocorticoid triggers mitochondrial dysfunction including defective mitophagy by increasing the activity of glucocorticoid receptors (GRs), leading to neuronal cell death. Melatonin then suppresses glucocorticoid-induced stress-responsive neurodegeneration; however, the regulatory mechanism of melatonin, i.e., associated proteins involved in GR activity, has not been elucidated. Therefore, we investigated how melatonin regulates chaperone proteins related to GR trafficking into the nucleus to suppress glucocorticoid action. In this study, the effects of glucocorticoid on suppressing NIX-mediated mitophagy, followed by mitochondrial dysfunction, neuronal cell apoptosis, and cognitive deficits were reversed by melatonin treatment by inhibiting the nuclear translocation of GRs in both SH-SY5Y cells and mouse hippocampal tissue. Moreover, melatonin selectively suppressed the expression of FKBP prolyl isomerase 4 (FKBP4), which is a co-chaperone protein that works with dynein, to reduce the nuclear translocation of GRs among the chaperone proteins and nuclear trafficking proteins. In both cells and hippocampal tissue, melatonin upregulated melatonin receptor 1 (MT1) bound to Gαq, which triggered the phosphorylation of ERK1. The activated ERK then enhanced DNA methyltransferase 1 (DNMT1)-mediated hypermethylation of FKBP52 promoter, reducing GR-mediated mitochondrial dysfunction and cell apoptosis, the effects of which were reversed by knocking down DNMT1. Taken together, melatonin has a protective effect against glucocorticoid-induced defective mitophagy and neurodegeneration by enhancing DNMT1-mediated FKBP4 downregulation that reduced the nuclear translocation of GRs.

Background Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD1) block tumor growth by reinvigorating the immune system; however, determining their efficacy only by the changes in tumor size may prove inaccurate. As the immune cells including macrophages in the tumor microenvironment (TME) are associated with the response to anti-PD1 therapy, tumor-associated macrophages (TAMs) imaging using nanoparticles can noninvasively provide the immune enrichment status of TME. Herein, the mannosylated-serum albumin (MSA) nanoparticle was labeled with radioactive isotope 68Ga to target the mannose receptors on macrophages for noninvasive monitoring of the TME according to anti-PD1 therapy. Results B16F10-Luc and MC38-Luc tumor-bearing mice were treated with anti-PD1, and the response to anti-PD1 was determined by the tumor volume. According to the flow cytometry, the responders to anti-PD1 showed an increased proportion of TAMs, as well as lymphocytes, and the most enriched immune cell population in the TME was also TAMs. For noninvasive imaging of TAMs as a surrogate of immune cell augmentation in the TME via anti-PD1, we acquired [68Ga] Ga-MSA positron emission tomography. According to the imaging study, an increased number of TAMs in responders at the early phase of anti-PD1 treatment was observed in both B16F10-Luc and MC38-Luc tumor-bearing mice models. Conclusion As representative immune cells in the TME, non-invasive imaging of TAMs using MSA nanoparticles can reflect the immune cell enrichment status in the TME closely associated with the response to anti-PD1. As non-invasive imaging using MSA nanoparticles, this approach shows a potential to monitor and evaluate anti-tumor response to immune checkpoint inhibitors.

Age-related cognitive decline is associated with dysfunctional lymphatic efflux of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. Intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice for the evaluation of lymphatic efflux of CSF and its age-related variation. [64Cu]Cu-albumin PET was done at multiple time points after intrathecal injection of [64Cu]Cu-albumin with the infusion speed of 700 nl/min in the adult and aged mice of 15–25 months old age. CSF clearance and paravertebral lymph nodes were quantified after injection and at later stationary phase. Representing perturbed state by 6 μl (1/7 of CSF volume with twice the production rate for 9 minutes of intrathecal injection) and at the next day of stationary return of CSF dynamics in mice, CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 in adult and 123.3 ± 15.6 minutes in aged mice (p = 0.01). The % injected dose at 4, 6 and 24 hours were higher in aged mice than in the adult mice (p < 0.05) and the visualized paravertebral lymph node activity tended to be lower in the aged, which was different from [64Cu]Cu-NOTA or [64Cu]Cu-ESION PET. [64Cu]Cu-albumin PET enabled quantification of CSF-lymphatic efflux over all the levels of brain spinal cords and visualization with quantifiability of lymph node activity. [64Cu]Cu-albumin PET revealed an age-related decrease in CSF-lymphatic efflux due to less efflux from the subarachnoid space, especially at stationary phase in the aged mice.

Converting mechanical deformation from surrounding environment into detectable electrical signals remains one of the most attractive fields due to its potential applications in sustainable energy harvesting, self-powered sensors, and others. Presently, deformation energy is harvested by generating voltage/current through bending/twisting of piezoelectric materials, but its recyclability is limited in number. In contrast, polarization is generated in all known insulators/semiconductors due to elastic strain gradient, which offers unique electromechanical coupling and in turn, could generate significant potential differences to drive charge transfer. Here, we demonstrate that extremely high direct current with density of 28 × 106 A m−2 is generated without need of any external power supply by applying pointed force using conductive-atomic force microscope (cAFM) tip on multilayer graphene/substrate (SiO2, Si, glass). Further, the ramp-dependent time-resolved current is measured at a localized point, which indicates that pointed force-induced flexoelectric potential differences are the main driving factor to utilize mechanoelectrical coupling and in turn generate high current density. This research work provides a new strategy to utilize the flexoelectric effect to utilize electromechanical coupling to generate giant energy harvesting, which will have a potential impact on the various multiple fields including smart devices, materials, and even a fundamental understanding of physics.

Silk protein is being increasingly introduced as a prospective material for biomedical devices. However, a limited locus to intervene in nature-oriented silk protein makes it challenging to implement on-demand functions to silk. Here, we report how polymorphic transitions are related with molecular structures of artificially synthesized silk protein and design principles to construct a green-lithographic and high-performative protein resist. The repetition number and ratio of two major building blocks in synthesized silk protein are essential to determine the size and content of β-sheet crystallites, and radicals resulting from tyrosine cleavages by the 193 nm laser irradiation induce the β-sheet to α-helix transition. Synthesized silk is designed to exclusively comprise homogeneous building blocks and exhibit high crystallization and tyrosine-richness, thus constituting an excellent basis for developing a high-performance deep-UV photoresist. Additionally, our findings can be conjugated to design an electron-beam resist governed by the different irradiation-protein interaction mechanisms. All synthesis and lithography processes are fully water-based, promising green lithography. Using the engineered silk, a nanopatterned planar color filter showing the reduced angle dependence can be obtained. Our study provides insights into the industrial scale production of silk protein with on-demand functions.

Background Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD1) block tumor growth by reinvigorating the immune system; however, determining their efficacy only by the changes in tumor size may prove inaccurate. As the immune cells including macrophages in the tumor microenvironment (TME) are associated with the response to anti-PD1 therapy, tumor-associated macrophages (TAMs) imaging using nanoparticles can noninvasively provide the immune enrichment status of TME. Herein, the mannosylated-serum albumin (MSA) nanoparticle was labeled with radioactive isotope 68Ga to target the mannose receptors on macrophages for noninvasive monitoring of the TME according to anti-PD1 therapy. Results B16F10 tumor-bearing mice were treated with anti-PD1, and the response to anti-PD1 was determined by the tumor volume. According to the flow cytometry, the responders to anti-PD1 showed an increased proportion of TAMs, as well as lymphocytes, and the most enriched immune cell population in the TME was also TAMs. For noninvasive imaging of TAMs as a surrogate of immune cell augmentation in the TME via anti-PD1, we acquired [68Ga]Ga-MSA positron emission tomography. According to the imaging study, an increased number of TAMs in responders at the early phase of anti-PD1 treatment was observed in both B16F10 and MC38 tumor-bearing mice models. Conclusion As representative immune cells in the TME, non-invasive imaging of TAMs using MSA nanoparticles can reflect the immune cell enrichment status in the TME closely associated with the response to anti-PD1. As non-invasive imaging using MSA nanoparticles, this approach shows a potential to monitor and evaluate anti-tumor response to immune checkpoint inhibitors.

The improvement in the growth yield and control of atomically thin WSe2 flakes by chemical vapor deposition (CVD) using pre-deposited WO3 nanopowders as a W source is demonstrated. WO3 nanopowders are pre-deposited on the growth substrate and utilized as a W source instead of separate W sources in the CVD system. In this way, mostly mono or bilayer WSe2 flakes are grown on the growth substrate with high density and an average size of around 20 μm. The devices based on the as-grown WSe2 flakes show p-type behaviors with a high on/off ratio of ~ 105 and carrier mobility of ~ 0.5 cm2 V− 1 s−1 as well as a large positive photoresponse. The density and size of WSe2 flakes can be controlled by adjusting the amount of pre-deposited WO3 nanopowders. This approach can be used to grow W-based two-dimensional materials as well as their heterostructures with other materials such as graphene and carbon nanotubes.

We investigated the variation of current density–voltage (J–V) characteristics of an organic solar cell (OSC) in the dark and at 9 different light intensities ranging from 0.01 to 1 sun of the AM1.5G spectrum. All three conventional parameters, short-circuit currents (Jsc), open-circuit voltage (Voc), and Fill factor (FF), representing OSC performance evolved systematically in response to light intensity increase. Unlike Jsc that showed quasi-linear monotonic increase, Voc and FF showed distinctive non-monotonic variations. To elucidate the origin of such variations, we performed extensive simulation studies including Shockley–Read–Hall (SRH) recombination losses. Simulation results were sensitive to defect densities, and simultaneous agreement to 10 measured J–V curves was possible only with the defect density of $$5 \times 10^{12} {\text{ cm}}^{ - 3}$$ 5 × 10 12 cm - 3 . Based on analyses of simulation results, we were able to separate current losses into SRH- and bimolecular-recombination components and, moreover, identify that the competition between SRH- and bimolecular-loss currents were responsible for the aforementioned variations in Jsc, Voc, and FF. In particular, we verified that apparent demarcation in Voc, and FF variations, which seemed to appear at different light intensities, originated from the same mechanism of dominance switching between recombination losses.

This study focuses on the changes in wave energy in response to tidal currents in the western sea of Jeju Island where high-energy wave conditions along with strong tidal currents are usual. Here, an ocean-wave coupled modeling system was used to investigate the effect of tidal currents on the wave energy condition. A comparative experiment with and without tidal currents shows that the current largely affects wave energy in terms of the wave spectrum as a response to the relative direction between waves and currents. When the direction of the tidal current is the same as that of wave propagation, the magnitude of wave height is reduced with energy transfer from shorter periods of 7–9 s to longer periods of 10–12 s, resulting in a decrease (increase) of shorter (longer) wave energy. This reaction is reversed when the tidal current flows in a direction opposite to that of wave propagation. The uncoupled model tends to overestimate/underestimate the wave energy during the ebb/flood tides when the waves follow/oppose the currents by approximately 25%. This study demonstrates that ocean-wave coupling is capable of improving model wave conditions, and therefore, this model is useful for estimating potential wave energy resource and candidate sites.

Background Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Methods A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. Results Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. Conclusion The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

Biotin (vitamin B7) is a water-soluble vitamin used as a co-enzyme for carboxylases essential for human metabolism. The high affinity to streptavidin makes biotin an important substance in immunoassays. Excessive biotin intake due to over-the counter supplements has become problematic because of the effects on laboratory test results. There have been no reports of biotin-induced thyroid immunoassay interference in Korea. We report three patients with papillary thyroid cancer who showed false thyrotoxicosis on follow-up laboratory examinations with a literature review. The patients’ medical history should be thoroughly questioned and patients should be informed to curtail consuming biotin before laboratory tests to avoid assay interference. Non-biotinylated assays can be considered if it is impossible to withhold the supplements. These methods will prevent physicians from making incorrect decisions that could result in an inappropriate treatment for their patients.