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Ultrasensitive, rapid, and reliable biomolecular sensing is essential for biomedical diagnostics, requiring real-time monitoring and detection of trace samples. Optical sensing, particularly plasmonic biosensing, meets these demands through noninvasive, high-sensitivity detection based on the interaction between light and molecules. Here, we present novel plasmonic metamaterial-based sensing strategy, utilizing the circular dichroism (CD) response of grating-coupled surface plasmon resonance (SPR) from chiral nanoparticle grating structure (i.e., 2D helicoid crystal) on gold substrate. Strong chiroptic response of helicoids has been effectively expanded to produce a remarkable CD/ g reflection response in the SPR mode, achieved by spectral coupling of SPR with localized surface plasmon resonance (LSPR) in helicoids. This CD response, derived from the differential of left and right circularly polarized light, corrects optical fluctuations, enhancing sensitivity and reliability. Our SPR-CD-based approach achieves a sensitivity of 379.2 nm/RIU and detection limit of a few mM for d-glucose, offering a new paradigm for high-performance optical biosensors.

All the information essential for life is encoded within our genome and epigenome, which orchestrates diverse cellular states spatially and temporally. In particular, the epigenome interacts with internal and external stimuli, encoding and preserving cellular experiences, and it serves as the regulatory base of the transcriptome across diverse cell types. The emergence of single-cell transcriptomic and epigenomic data collection has revealed unique omics signatures in diverse tissues, highlighting cellular heterogeneity. Recent research has documented age-related epigenetic changes at the single-cell level, alongside the validation of cellular rejuvenation through partial reprogramming, which involves simultaneous epigenetic modifications. These dynamic shifts, primarily fueled by stem cell plasticity, have catalyzed significant interest and cross-disciplinary research endeavors. This review explores the genomic and epigenomic alterations with aging, elucidating their reciprocal interactions. Additionally, it seeks to discuss the evolving landscape of rejuvenation research, with a particular emphasis on dissecting stem cell behavior through the lens of single-cell analysis. Moreover, it proposes potential research methodologies for future studies., Competing Interests: Declaration of Competing Interests The authors have no potential conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Chiral plasmonic nanostructures are in high demand because of their unique optical properties, which are applicable to polarization control, chiral sensing and biomedical applications. An easy and scalable synthesis method for these nanostructures may facilitate their development further. We have reported the synthesis for 432-symmetric chiral plasmonic nanoparticles by using a seed-mediated colloidal method facilitated by a chiral amino acid and peptides. Among those, 432 helicoid III nanoparticles particularly exhibited well-defined chiral morphologies and exceptional chiroptic properties, evidenced by a Kuhn's dissymmetry factor (g-factor) of 0.2, making them valuable for various applications. Here, we detail the synthesis stages, including the synthesis of seed nanoparticles, the verification of each stage outcome and the calibration of synthesis conditions. We further illustrate the troubleshooting section and video-document the stages to facilitate the reliable reproduction of 432 helicoid III nanoparticles. The procedure requires 8 h to complete and can be carried out by users with expertise in chemistry or materials science., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Limited.)

Chiral inorganic nanomaterials hold significant promise for various applications, including enantioselective catalysis, polarization-controlling optical devices, metamaterials, and enantioselective molecular sensors. In our previous work, we presented a method for synthesizing chiral Au 432 helicoid III (Au helicoids) from peptides and amino acids, where helical gaps are intricately arranged with 432 symmetry within single cubic nanoparticles. In this study, we have achieved the fabrication of chiral silica molds through Au etching subsequent to the silica coating of Au helicoids. We demonstrate that these molds serve as geometrically confined reactors capable of producing chiral Ag, Pd, and Pt 432 helicoid III (Ag, Pd, and Pt helicoids). The morphology of the synthesized Ag, Pd, and Pt helicoids closely resembles that of the Au helicoids, exhibiting a superior g-factor compared to other reported chiral structures of each material. Notably, the Ag and Pd helicoids are found to be single-crystalline, with high-index planes exposed within the gaps. We believe that this silica mold-based approach can be generalized to synthesize chiral nanomaterials of various metal and even oxide materials.

Symmetrical lesions in the temporal poles and external capsules on brain MRI are known as radiological markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); however, similar imaging findings have also been reported in neuromyelitis optica spectrum disorder (NMOSD), and this study investigated the frequency of such findings. The study included 55 NMOSD patients who met the 2015 international NMO diagnosis panel (IPND) criteria and were positive for aquaporin-4 antibodies (AQP4-Ab). Images were evaluated based on the consensus of two neuroradiologists, and brain lesions were detected in 33 patients, of whom 2 (6%) had symmetrical lesions in both the temporal poles and external capsules, and 1 (3%) had symmetrical lesions confined to the external capsules. Therefore, when symmetrical lesions in the temporal poles and external capsules are observed on MRI, NMOSD should be considered in the differential diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glioblastoma (GBM) has a fatal prognosis because of its aggressive and invasive characteristics. Understanding the mechanism of invasion necessitates an elucidation of the relationship between tumor cells and the tumor microenvironment. However, there has been a scarcity of suitable models to investigate this. In this study, we established a glioblastoma-cerebral organoid assembloid (GCOA) model by co-culturing patient-derived GBM tumoroids and human cerebral organoids. Tumor cells from the tumoroids infiltrated the cerebral organoids, mimicking the invasive nature of the parental tumors. Using time-lapse imaging, various invasion patterns of cancer cells within cerebral organoids resembling a normal tissue milieu were monitored. Both single- and collective-cell invasion was captured in real-time. We also confirmed the formation of an intercellular tumor network and tumor-normal-cell interactions. Furthermore, the transcriptomic characterization of GCOAs revealed distinct features of invasive tumor cells. Overall, this study established the GCOA as a three-dimensional (3D) in vitro assembloid model to investigate invasion mechanisms and interactions between tumor cells and their microenvironment., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Microglia play a crucial role in synaptic elimination by engulfing dystrophic neurons via triggering receptors expressed on myeloid cells 2 (TREM2). They are also involved in the clearance of beta-amyloid (Aβ) plaques in Alzheimer's disease (AD); nonetheless, the driving force behind TREM2-mediated phagocytosis of beta-amyloid (Aβ) plaques remains unknown. Here, using advanced 2D/3D/4D co-culture systems with loss-of-function mutations in TREM2 (a frameshift mutation engineered in exon 2) brain organoids/microglia/assembloids, it is identified that the clearance of Aβ via TREM2 is accelerated by externalized phosphatidylserine (ePtdSer) generated from dystrophic neurons surrounding the Aβ plaques. Moreover, it is investigated whether microglia from both sporadic (CRISPR-Cas9-based APOE4 lines) and familial (APP NL-G-F /MAPT double knock-in mice) AD models show reduced levels of TREM2 and lack of phagocytic activity toward ePtdSer-positive Aβ plaques. Herein new insight is provided into TREM2-dependent microglial phagocytosis of Aβ plaques in the context of the presence of ePtdSer during AD progression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two major demyelinating diseases affecting the central nervous system (CNS). The objective of this study is to evaluate the prevalence of pontine trigeminal nerve lesions in patients diagnosed with MS and NMOSD using MRI., Methods: This retrospective study included patients diagnosed with MS or NMOSD between July 2018 and July 2023. MS patients were clinically diagnosed using the 2017 McDonald criteria, while NMOSD patients were those who met the 2015 International Panel for NMO Diagnosis (IPND) criteria and were positive for Aquaporin-4 Antibody (AQP4-Ab)., Results: The study included a total of 90 patients, with 45 diagnosed with MS and another 45 with NMOSD. Pontine trigeminal nerve lesions were observed in both MS and NMOSD, but were more prevalent in MS patients (20 % vs. 2 %, p = 0.008). Root entry zone (REZ) lesions were found in 4 of 45 MS patients, accounting for 9 % (95 % CI: 3 %-17 %), and were absent in the NMOSD group; however, there was no significant difference between the two groups (p = 0.12). Of the MS patients with pontine trigeminal nerve lesions, 6 out of 9 (63 %; 95 % CI, 36 %-98 %) exhibited bilateral lesions, which was significantly more prevalent compared to the NMOSD group (13 % vs. 0 %, p = 0.03)., Conclusions: The presence of pontine trigeminal nerve lesions, particularly when bilateral, are significantly more prevalent in MS patients than in those with NMOSD, suggesting their utility as a distinctive marker and potential diagnostic indicator specifically for MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Genome-wide association studies (GWAS) of metabolic syndrome (MetS) have predominantly focused on non-Asian populations, with limited representation from East Asian cohorts. Moreover, previous GWAS analyses have primarily emphasized the significance of top single nucleotide polymorphisms (SNPs), poorly explaining other SNP signals in linkage disequilibrium. This study aimed to reveal the interaction between rs651821 and rs2266788, the principal variants of apolipoprotein A5 (APOA5), within the most significant loci identified through GWAS on MetS., Methods: GWAS on MetS and its components was conducted using the data from the Korean Genome and Epidemiology Study (KoGES) city cohort comprising 58,600 individuals with available biochemical, demographic, lifestyle factors, and the most significant APOA5 locus was analyzed further in depth., Results: According to GWAS of MetS and its diagnostic components, a significant association between the APOA5 SNPs rs651821/rs2266788 and MetS/triglycerides/high-density lipoprotein phenotypes was revealed. However, a conditional analysis employing rs651821 unveiled a reversal in the odds ratio for rs2266788. Therefore, rs651821 and rs2266788 emerged as independent and opposing signals in the extended GWAS analysis, i.e., the multilayered effects. Further gene-environment interaction analyses regarding lifestyle factors such as smoking, alcohol consumption, and physical activity underscored these multilayered effects., Conclusion: This study unveils the intricate interplay between rs651821 and rs2266788 derived from MetS GWAS. Removing the influence of lead SNP reveals an independent protective signal associated with rs2266788, suggesting a multilayered effect between these SNPs. These findings underline the need for novel perspectives in future MetS GWAS., (© 2024. The Author(s).)

Background: Detection of a common channel outside the duodenal wall is important in diagnosing pancreaticobiliary maljunction (PBM). The present study evaluated the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in diagnosing PBM., Methods: This single-center retrospective study enrolled 45 patients who were diagnosed with PBM or high confluence of pancreatobiliary ducts (HCPBD) between January 2007 and December 2021. The diagnostic sensitivities of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI), and CH-EUS for diagnosing PBM were analyzed. Imaging findings were evaluated by two reviewers blinded to the clinicopathological results., Results: Based on diagnostic criteria, 33 patients were diagnosed with PBM and 12 with HCPBD. Compared with the patients with HCPBD, those with PBM had significantly longer common channel (12.5 mm vs. 8.1 mm, P = 0.018) and common bile duct (13.0 mm vs. 8.6 mm, P = 0.049) lengths. The κ-coefficients for differentiating PBM and HCPBD were 0.871 between CE-CT and MRI, 0.330 between CE-CT and CH-EUS, and 0.611 between MRI and CH-EUS. The diagnostic sensitivity of CH-EUS (95.2%) was higher than that of CE-CT (83.3%) and MRI (82.8%), although the differences were not statistically significant., Conclusion: CH-EUS may be useful for the diagnosis of PBM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Homochirality is an important feature in biological systems and occurs even in inorganic nanoparticles. However, the mechanism of chirality formation and the key steps during growth are not fully understood. Here we identify two distinguishable pathways from achiral to chiral morphologies in gold nanoparticles by training an artificial neural network of cellular automata according to experimental results. We find that the chirality is initially determined by the nature of the asymmetric growth along the boundaries of enantiomeric high-index planes. The deep learning-based interpretation of chiral morphogenesis provides a theoretical understanding but also allows us to predict an unprecedented crossover pathway and the resulting morphology., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC., Methods: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed., Results: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported., Conclusions: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Enzymes in nature efficiently catalyze chiral organic molecules by elaborately tuning the geometrical arrangement of atoms in the active site. However, enantioselective oxidation of organic molecules by heterogeneous electrocatalysts is challenging because of the difficulty in controlling the asymmetric structures of the active sites on the electrodes. Here, we show that the distribution of chiral kink atoms on high-index facets can be precisely manipulated even on single gold nanoparticles; and this enabled stereoselective oxidation of hydroxyl groups on various sugar molecules. We characterized the crystallographic orientation and the density of kink atoms and investigated their specific interactions with the glucose molecule due to the geometrical structure and surface electrostatic potential.

The water oxidation reaction, the most important reaction for hydrogen production and other sustainable chemistry, is efficiently catalyzed by the Mn 4 CaO 5 cluster in biological photosystem II. However, synthetic Mn-based heterogeneous electrocatalysts exhibit inferior catalytic activity at neutral pH under mild conditions. Symmetry-broken Mn atoms and their cooperative mechanism through efficient oxidative charge accumulation in biological clusters are important lessons but synthesis strategies for heterogeneous electrocatalysts have not been successfully developed. Here, we report a crystallographically distorted Mn-oxide nanocatalyst, in which Ir atoms break the space group symmetry from I 4 1 / amd to P1. Tetrahedral Mn(II) in spinel is partially replaced by Ir, surprisingly resulting in an unprecedented crystal structure. We analyzed the distorted crystal structure of manganese oxide using TEM and investigated how the charge accumulation of Mn atoms is facilitated by the presence of a small amount of Ir.

Background and Aim: A multicenter, open-label randomized Phase II trial was conducted to determine whether low-dose gemcitabine plus nab-paclitaxel (GnP) could improve tolerability and show equivalent efficacy to the standard-dose GnP for elderly patients with metastatic pancreatic cancer., Methods: Consecutive patients aged ≥65 years with metastatic pancreatic cancer who presented at one of four Japanese referral centers between November 2016 and January 2021 were enrolled. The 60 patients were randomly assigned to low- or standard-dose groups with a 1:1 ratio. Patients in the low-dose GnP group received gemcitabine at a dose of 250 mg/m 2 and nab-paclitaxel at 125 mg/m 2 ., Results: Low-dose GnP significantly decreased the rate of cases requiring dose reduction (16.7% vs 63.3%). The response rate (36.7% vs 33.3%) and progression-free survival (7.3 vs 8 months) were comparable between the low- and standard-dose groups as determined by independent review. The difference in the median overall survival between the two groups was not significant (7.9 vs 12 months). The proportion of patients with hematologic and non-hematologic treatment-related adverse events was comparable between the two groups., Conclusion: Low-dose GnP had an equivalent efficacy to conventional therapy; however, it did not reduce adverse events., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Underrepresentation of non-European (EUR) populations hinders growth of global precision medicine. Resources such as imputation reference panels that match the study population are necessary to find low-frequency variants with substantial effects. We created a reference panel consisting of 14,393 whole-genome sequences including more than 11,000 Asian individuals. Genome-wide association studies were conducted using the reference panel and a population-specific genotype array of 72,298 subjects for eight phenotypes. This panel yields improved imputation accuracy of rare and low-frequency variants within East Asian populations compared with the largest reference panel. Thirty-nine previously unidentified associations were found, and more than half of the variants were East Asian specific. We discovered genes with rare protein-altering variants, including LTBP1 for height and GPR75 for body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type-specific effects. We suggest that this dataset will add to the potential value of Asian precision medicine.

Syneilesis palmata (SP) is a traditional medicinal plant. SP has been reported to have anti-inflammatory, anticancer, and anti-human immunodeficiency virus (HIV) activities. However, there is currently no research available on the immunostimulatory activity of SP. Therefore, in this study, we report that S. palmata leaves (SPL) activate macrophages. Increased secretion of both immunostimulatory mediators and phagocytic activity was observed in SPL-treated RAW264.7 cells. However, this effect was reversed by the inhibition of TLR2/4. In addition, inhibition of p38 decreased the secretion of immunostimulatory mediators induced by SPL, and inhibition of TLR2/4 decreased the phosphorylation of p38 induced by SPL. SPL augmented p62/SQSTM1 and LC3-II expression. The increase in protein levels of p62/SQSTM1 and LC3-II induced by SPL was decreased by the inhibition of TLR2/4. The results obtained from this study suggest that SPL activates macrophages via TLR2/4-dependent p38 activation and induces autophagy in macrophages via TLR2/4 stimulation.

Hovenia dulcis has been reported to have various pharmacological activities, but most studies were done with its fruits. However, from an economic point of view, the use of discarded leaves and branches as by-products is very valuable. In this study, the in vitro and in vivo anti-obesity activities of Hovenia dulcis branch extract (HDB) were investigated to evaluate the applicability of HDB as an anti-obesity agent. In differentiated 3T3-L1 cells, HDB inhibited lipid droplet accumulation. And HDB downregulated CEBPα, PPARγ, and perilipin-1, and upregulated ATGL, p-HSL, HSL, p-AMPK, UCP-1, PGC-1α, PRDM16, LC3-II, and p62/SQSTM1. In addition, HDB increased free glycerol content. In HFD-induced obese mice, HDB reduced body weight and total fat weight. In addition, HDB decreased blood LDL-cholesterol, blood total cholesterol, and blood triglyceride. These results indicate that HDB has anti-obesity activity and HDB can be used as a healthy functional food agent for weight reduction.

Identifying the three-dimensional (3D) crystal plane and strain-field distributions of nanocrystals is essential for optical, catalytic, and electronic applications. However, it remains a challenge to image concave surfaces of nanoparticles. Here, we develop a methodology for visualizing the 3D information of chiral gold nanoparticles ≈ 200 nm in size with concave gap structures by Bragg coherent X-ray diffraction imaging. The distribution of the high-Miller-index planes constituting the concave chiral gap is precisely determined. The highly strained region adjacent to the chiral gaps is resolved, which was correlated to the 432-symmetric morphology of the nanoparticles and its corresponding plasmonic properties are numerically predicted from the atomically defined structures. This approach can serve as a comprehensive characterization platform for visualizing the 3D crystallographic and strain distributions of nanoparticles with a few hundred nanometers, especially for applications where structural complexity and local heterogeneity are major determinants, as exemplified in plasmonics., (© 2023. The Author(s).)

The present study investigated the immunostimulatory activity and anti-obesity activity of Adenocaulon himalaicum leaf extracts (AHL) in RAW264.7 cells and 3T3-L1 cells. AHL increased the production of immunostimulatory factors, such as NO, inducible nitric oxide synthase (iNOS), IL-1β, IL-6 and TNF-α and activated the phagocytotic activity in RAW264.7 cells. Inhibition of Toll-like receptor 4 (TLR4) attenuated the AHL-mediated production of immunostimulatory factors and activation of phagocytic activity in RAW264.7 cells. Inhibition of p38 and JNK blocked the AHL-mediated production of immunostimulatory factors, whereas inhibition of TLR4 suppressed the AHL-mediated phosphorylation of p38 and JNK. Additionally, AHL blocked the lipid accumulation in 3T3-L1 cells. AHL downregulated proliferator-activated receptor γ, CCAAT enhancer binding protein α and perilipin-1 levels, while upregulating adipose triglyceride lipase, phosphorylated (p-)hormone-sensitive lipase, p-adenosine monophosphate activated protein kinase, uncoupling protein 1, peroxisome-proliferator-activated receptor-γ coactivator-1 α and PR domain containing 16 levels in 3T3-L1 cells. These findings suggested that AHL may exert immunostimulatory activity through macrophages via TLR4-mediated activation of p38 and JNK and anti-obesity activity by blocking lipid accumulation via the inhibition of adipogenesis and induction of lipolysis and browning of white adipocytes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Choi et al.)

Aims: This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL., Conclusion: Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD., Clinical Trial Registration: ClinicalTrials.gov, Identifier:NCT03044665., Competing Interests: Conflict of interest: S.C.Y. is a chief technical officer of PHI Digital Healthcare and has received consulting fee from IQVIA; B.-K.K. has received speaker’s fees from Medtronic and Abbott Vascular; M.-K.H. has received speaker’s fees from Medtronic, Abbott Vascular, and Pfizer, Y.J. has received institutional research grants from Biotronik and Hanmi, and J.-S.K. has received proctoring fees from Abbott Vascular. All other authors declare no competing interests., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Craniopharyngioma is a benign tumor classified as grade 1 by the World Health Organization Classification of Tumors of the Central Nervous System. We present a rare case of a high-18F-FDG-avidity papillary craniopharyngioma of the third ventricle. A 65-year-old man underwent CT and MRI examinations for gait disturbance, lower-limb weakness, and urinary incontinence, and an oval solid tumor that extended from the suprasellar region to the third ventricle was identified. 18F-FDG PET/CT showed high accumulation (SUVmax, 22.3) in the tumor. A transventricular endoscopic tumor biopsy led to the diagnosis of papillary craniopharyngioma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Quantitative analysis of chiral molecules in various solvents is essential. However, there are still many challenges to enhancing the sensitivity in precisely determining both concentration and chirality. Here, we built an algorithmic methodology to predict and optimally design the chiroptical response of chiral plasmonic sensors for a specific target chiral analyte with the aid of deep learning. Based upon the analytic and intuitive understanding of the Born-Kuhn type plasmonic nanodimer, we designed and trained the neural networks that can successfully predict the chiroptical properties and further inversely design the plasmonic structure to achieve the intended circular dichroism. The developed algorithm could identify the optimum structure exhibiting the maximum sensitivity for the given specific analytes. Surprisingly, we discovered that sensitivity strongly depends on the various conditions of analytes and can be finely tuned with the structural parameters of plasmonic nanodimers. We envision that this study can provide a general platform to develop ultrasensitive chiral plasmonic sensors whose structure and sensitivity have been evolved algorithmically for adoption in specific applications.

Quantitative determination and in situ monitoring of molecular chirality at extremely low concentrations is still challenging with simple optics because of the molecular-scale mismatch with the incident light wavelength. Advances in spectroscopy 1-4 and nanophotonics have successfully lowered the detection limit in enantioselective sensing, as it can bring the microscopic chiral characteristics of molecules into the macroscopic scale 5-7 or squeeze the chiral light into the subwavelength scale 8-17 . Conventional nanophotonic approaches depend mainly on the optical helicity density 8,9 by localized resonances within an individual structure, such as localized surface plasmon resonances (LSPRs) 10-16 or dielectric Mie resonances 17 . These approaches use the local chiral hotspots in the immediate vicinity of the structure, whereas the handedness of these hotspots varies spatially. As such, these localized resonance modes tend to be error-prone to the stochasticity of the target molecular orientations, vibrations and local concentrations 18,19 . Here we identified enantioselective characteristics of collective resonances (CRs) 20 arising from assembled 2D crystals of isotropic, 432-symmetric chiral gold nanoparticles (helicoids) 21,22 . The CRs exhibit a strong and uniform chiral near field over a large volume above the 2D crystal plane, resulting from the collectively spinning, optically induced dipoles at each helicoid. Thus, energy redistribution by molecular back action on the chiral near field shifts the CRs in opposite directions, depending on the handedness of the analyte, maximizing the modulation of the collective circular dichroism (CD)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We aimed to examine the accuracy of tumor staging of intrahepatic cholangiocarcinoma (ICC) by using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT). From January 2001 to December 2021, 202 patients underwent PET-CT, CT, and MRI for the initial staging of ICC in two institutions. Among them, 102 patients had undergone surgical treatment. Ninety patients who had a histopathological diagnosis of ICC were retrospectively reviewed. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. Ninety patients with histologically diagnosed ICC were included. PET-CT demonstrated no statistically significant advantage over CT and MR in the diagnosis of multiple tumors and macrovascular invasion, and bile duct invasion. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET-CT in lymph node metastases were 84%, 86%, 91%, 84%, and 86%, respectively. PET-CT revealed a significantly higher accuracy compared to CT or MRI (86%, 67%, and 76%, p < 0.01, respectively) in the diagnosis of regional lymph node metastases. The accuracy of tumor staging by PET-CT was higher than that by CT/MRI (PET-CT vs. CT vs. MRI: 68/90 vs. 47/90 vs. 51/90, p < 0.05). 18F-FDG PET-CT had sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion similar to those of CT or MRI; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. 18F-FDG PET-CT exhibited higher tumor staging accuracy than that of CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients ( n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

Precise control over the morphology and facets of Pd nanomaterials has great importance in catalytic and sensing applications. In this study, we synthesized Pd nanoparticles with multiple types of low-Miller-index-faceted morphologies by systematically defining the synthesis conditions of the seed-mediated colloidal preparation method. We discovered the morphological evolution of Pd nanoparticles by following the trajectory of the surface Miller indices, which were determined by the cooperative effects of cetyltrimethylammonium bromide and ascorbic acid. By precise control of the morphological trajectory, Pd nanoparticles with a new cuborhombicube morphology, composed of 36 facets and concave edges, were discovered. This study provides important insight into the design of the surface Miller indices and morphologies of functional nanomaterials.

Precise control of morphology and optical response of 3-dimensional chiral nanoparticles remain as a significant challenge. This work demonstrates chiral gold nanoparticle synthesis using single-stranded oligonucleotide as a chiral shape modifier. The homo-oligonucleotide composed of Adenine nucleobase specifically show a distinct chirality development with a dissymmetric factor up to g ~ 0.04 at visible wavelength, whereas other nucleobases show no development of chirality. The synthesized nanoparticle shows a counter-clockwise rotation of generated chiral arms with approximately 200 nm edge length. The molecular dynamics and density functional theory simulations reveal that Adenine shows the highest enantioselective interaction with Au(321) R/S facet in terms of binding orientation and affinity. This is attributed to the formation of sequence-specific intra-strand hydrogen bonding between nucleobases. We also found that different sequence programming of Adenine-and Cytosine-based oligomers result in chiral gold nanoparticles' morphological and optical change. These results extend our understanding of the biomolecule-directed synthesis of chiral gold nanoparticles to sequence programmable deoxyribonucleic acid and provides a foundation for programmable synthesis of chiral gold nanoparticles., (© 2022. The Author(s).)

Anal abscesses and fistulas are potential complications of Crohn’s disease (CD). Chronic immunosuppression, loose stools, and poor wound healing in this population present challenges to the management of perianal diseases. The purpose of the study was to determine the predominant bacterial species found in specimens from perianal lesions causing anal abscess and/or fistula drainage in hospitalized patients, and to compare the number and type of microorganisms isolated from samples taken from patients undergoing biological therapy or traditionally treated. The outcomes of studies of patients treated for anal abscesses or fistulas from 2017 to 2019 were evaluated. Data obtained from medical records included culture and antibiotic sensitivity results of swabs from perianal lesions of isolated microorganisms. A total of 373 swabs were collected from perianal lesions during the analysis period, including 51 (49 positive samples) from patients with CD. The predominant pathogen was Escherichia coli (55%, p < 0.001), the second most common microorganism was Staphylococcus aureus (14.3%, p < 0.001). In vitro susceptibility testing showed E. coli, ESBL (strain with Extended Spectrum Beta-Lactamase) in five cases, S. aureus, MRSA (methicillin-resistant S. aureus -resistant to all beta-lactam antibiotics: penicillins with inhibitors, cephalosporins, monobactams, carbapenems, except for ceftaroline) in one sample. Biologic therapy does not affect the type of microorganisms isolated from perianal abscesses in patients with CD.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non-small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs., Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening., Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs., Conclusion: Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

In manufacturing C-N bond-containing compounds, it is an important challenge to alternate the conventional methodologies that utilize reactive substrates, toxic reagents, and organic solvents. In this study, we developed an electrochemical method to synthesize a C-N bond-containing molecule avoiding the use of cyanides and amines by harnessing nitrate (NO 3 - ) as a nitrogen source in an aqueous electrolyte. In addition, we utilized oxalic acid as a carbon source, which can be obtained from electrochemical conversion of CO 2. Thus, our approach can provide a route for the utilization of anthropogenic CO 2 and nitrate wastes, which cause serious environmental problems including global warming and eutrophication. Interestingly, the coreduction of oxalic acid and nitrate generated reactive intermediates, which led to C-N bond formation followed by further reduction to an amino acid, namely, glycine. By carefully controlling this multireduction process with a fabricated Cu-Hg electrode, we demonstrated the efficient production of glycine with a faradaic efficiency (F.E.) of up to 43.1 % at -1.4 V vs. Ag/AgCl (current density≈90 mA cm -2 )., (© 2021 Wiley-VCH GmbH.)

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).

Ischemic preconditioning (IPC) significantly reduces ischemia-reperfusion injury in the brain by inducing ischemic tolerance. Although emerging evidence suggests that microRNAs (miRNAs) contribute to the pathogenesis of brain ischemia and IPC-induced neuroprotection, the role of miRNAs and their underlying mechanisms are still unclear. IPC was induced in male C57BL/6 mice by brief bilateral common carotid artery occlusion. After 24 h, mice underwent transient middle cerebral artery occlusion followed by 3 h of reperfusion. Expression levels of messenger RNAs (mRNAs) and proteins were examined in the ipsilateral cortex, and mimics and inhibitors of selective miRNAs were transfected into Neuro-2a cells before oxygen-glucose deprivation (OGD). Post-IPC miRNA expression profiling identified neuroprotection-associated changes in miRNA expression in the ipsilateral cortex after ischemic stroke. Among them, miR-33-5p and miR-135b-5p were significantly downregulated by IPC. Inhibition of miR-33-5p and miR-135b-5p expression protected Neuro-2a cells from OGD-induced apoptosis. Inhibition of these two miRNAs significantly increased mRNA and protein levels of ATP-binding cassette subfamily A member 1 (ABCA1), and a binding assay showed that these two miRNAs showed specificity for Abca1 mRNA. Overexpression of ABCA1 decreased the Bax/Bcl2 mRNA ratio and activation of caspase-9 and caspase-3, whereas knockdown of ABCA1 expression increased the Bax/Bcl2 mRNA ratio and the percentage of Neuro-2a cells with a loss of mitochondrial membrane potential after OGD-treatment. In conclusion, ABCA1 expression is regulated by miR-33-5p and miR-135b-5p. Increased ABCA1 expression following IPC exerts a protective influence against cerebral ischemia via suppression of a mitochondria-dependent apoptosis pathway.

Chiral inorganic nanomaterials have revealed opportunities in various fields owing to their strong light-matter interactions. In particular, chiral metal oxide nanomaterials that can control light and biochemical reactions have been highlighted due to their catalytic activity and biocompatibility. In this study, we present the synthesis of chiral cobalt oxide nanoparticles with a g -factor of 0.01 in the UV-visible region using l- and d-Tyr-Tyr-Cys ligands. The conformation of the Tyr-Tyr-Cys peptide on the nanoparticle surfaces was identified by 2D NMR spectroscopy analysis. In addition, the sequence effect of Tyr-Tyr-Cys developing chiral nanoparticles was analyzed. The revealed peptide structure, along with the experimental results, demonstrate the important role of the thiol group and carboxyl group of the Tyr-Tyr-Cys ligand in chirality evolution. Importantly, due to the magnetic properties of chiral cobalt oxide nanoparticles and their strong absorption in the UV region, the circular dichroism (CD) responses can be dramatically modulated under an external magnetic field.

Background: Pulmonary sarcomatoid carcinoma (PSC) is rare with a poor outcome and is resistant to conventional cytotoxic chemotherapy. The efficacy and safety of durvalumab and tremelimumab for treating recurrent or metastatic PSCs were assessed by a nonrandomized, open-label, phase II study., Methods: A total of 18 patients with recurrent or metastatic PSC received 1500 mg of durvalumab and 75 mg of tremelimumab every four weeks, followed by 750 mg of durvalumab every two weeks until the disease progressed, or an unacceptable toxicity level was reached. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. Genomic profiling of PSC by next-generation sequencing (NGS) and determination of peripheral blood lymphocyte subsets using flow cytometry were performed for exploratory analysis., Results: A total of 15 out of 18 patients were evaluated for the analysis of the primary endpoint. At the data cutoff point, the ORR of 26.7% (95% confidence interval [CI]: 7.8-55.1) was achieved with the median follow-up duration of 12.0 months (range, 8.4-16.1). Median PFS and OS were 5.9 months (95% CI: 1.1-11.9) and 15.4 months (95% CI: 11.1-not reached), respectively. Treatment-related adverse events (AEs) of any grade were reported in 16 patients; the most common AEs were pruritus (n = 5), pneumonitis (n = 4), and rash (n = 4). Treatment was discontinued in two patients due to AEs of grade ≥ 3., Conclusions: Durvalumab and tremelimumab demonstrated clinical benefit with a prolonged survival and manageable toxicity profile in patients with recurrent or metastatic PSC., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Chirality is a basic property of nature and has great importance in photonics, biochemistry, medicine, and catalysis. This importance has led to the emergence of the chiral inorganic nanostructure field in the last two decades, providing opportunities to control the chirality of light and biochemical reactions. While the facile production of 3D nanostructures has remained a major challenge, recent advances in nanocrystal synthesis have provided a new pathway for efficient control of chirality at the nanoscale by transferring molecular chirality to the geometry of nanocrystals. Interestingly, this discovery stems from a purely crystallographic outcome: chirality can be generated on high-Miller-index surfaces, even for highly symmetric metal crystals. This is the starting point herein, with an overview of the scientific history and a summary of the crystallographic definition. With the advance of nanomaterial synthesis technology, high-Miller-index planes can be selectively exposed on metallic nanoparticles. The enantioselective interaction of chiral molecules and high-Miller-index facets can break the mirror symmetry of the metal nanocrystals. Herein, the fundamental principle of chirality evolution is emphasized and it is shown how chiral surfaces can be directly correlated with chiral morphologies, thus serving as a guide for researchers in chiral catalysts, chiral plasmonics, chiral metamaterials, and photonic devices., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Osteoporotic fractures comprise a deadly disease which has ascending epidemiology in the 21st century. Cha-racterized by inadequate force impulses which cause breaks of bone tissue in key places for traumatology: proximal femur, spine. This is a severe economic, social, and health problem. The first condition for recovery after fracture is obtaining proper qualification for surgical treatment. Next the surgery must be made as fast as possible in order to provide internal diagnostics, while simultaneously maintaining the patient&apos;s safety. It&apos;s very important to create optimal conditions for bone healing. The essence of the problem &quot;osteoporotic fractures&quot; is low bone mineral density (BMD). It was found that in research &apos;in vivo&apos;, it is possible to reach a higher value of this factor via supplementation with ossein-hydroxyapatite complex (OHC) as compared to standard Calcium Salts.

Background: Pediatric thyroid cancer has characteristics that are distinct from adulthood thyroid cancer. Due to its very low prevalence, little is known about the genetic characteristics of pediatric follicular thyroid cancer (FTC). Methods: We investigated genetic alterations in tumor tissues from 15 patients aged <20 years (median: 14.3 years; range: 2.4 - 19.0 years) using multifaceted approaches. Whole-exome sequencing, targeted next-generation sequencing using a cancer gene panel, and Sanger sequencing of the major exons of the H/K/N-RAS and DICER1 genes and the promoter region of the TERT gene were performed. Normal tissues or blood of patients with DICER1- or PTEN -positive tumors was also evaluated to determine whether the variant is germ line. Results: The median tumor size was 3.1 cm (range: 0.6 - 6.4 cm). Four patients exhibited angioinvasion and one extensive capsular invasion; none showed evidence of disease over a median of 8.1 years. Eight patients (53.3%) had DICER1 variants, including four with DICER1 syndrome (three patients were <10 years of age). One patient had a germ line PTEN frameshift variant with the diagnosis of PTEN hamartoma tumor syndrome. One patient had a PAX8/PPARγ rearrangement, and two patients had no genetic driver alteration other than multiple loss of heterozygosity with or without copy number alterations in their tumors. No RAS or TERT variants were found. Nodular hyperplasia and follicular adenoma (FA) coexisted in DICER1 variant-positive FTCs more frequently than variant-negative FTCs ( p  = 0.026). All DICER1 variant-positive FTCs had a somatic missense variant at metal binding sites (six at codon p.E1813 and two at codon p.D1709) within the RNase IIIb domain; seven had other missense, nonsense, or frameshift variants in the DICER1 gene. Six coexisting FAs of two patients with DICER1 syndrome (three of each) had additional somatic variants at metal binding sites within the RNase IIIb domain (codon p.E1705, p.D1709, p.D1810, or p.E1813), different from each other and from the indexed FTC tumor. Conclusions: Pediatric FTCs have distinct genomic alterations and pathogenesis compared with adults, particularly those characterized by DICER1 variants. The DICER1 variant should be considered in pediatric FTCs, especially in cases <10 years of age. In all DICER1 variant-positive FTCs and FAs, recurrent hotspot variants were found at metal binding sites within the RNase IIIb domain, suggesting they impact tumorigenesis.

Chiral optical metamaterials with delicate structures are in high demand in various fields because of their strong light-matter interactions. Recently, a scalable strategy for the synthesis of chiral plasmonic nanoparticles (NPs) using amino acids and peptides has been reported. Reported herein, 3D chiral gold NPs were synthesized using dipeptide γ-Glu-Cys and Cys-Gly and analyzed crystallographically. The γ-Glu-Cys-directed NPs present a cube-like outline with a protruding chiral wing. In comparison, the NPs synthesized with Cys-Gly exhibited a rhombic dodecahedron-like outline with curved edges and elliptical cavities on each face. Morphology analysis of intermediates indicated that γ-Glu-Cys generated an intermediate concave hexoctahedron morphology, while Cys-Gly formed a concave rhombic dodecahedron. NPs synthesized with Cys-Gly are named 432 helicoid V because of their unique morphology and growth pathway., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The increase in genetic alterations targeted by specific chemotherapy in lung cancer has led to the need for universal use of more comprehensive genetic testing, which has highlighted the development of a lung cancer diagnostic panel using next-generation sequencing., Objective: We developed a hybridization capture-based massively parallel sequencing assay named Friendly, Integrated, Research-based, Smart and Trustworthy (FIRST)-lung cancer panel (LCP), and evaluated its performance., Methods: FIRST-LCP comprises 64 lung cancer-related genes to test for various kinds of genetic alterations including single nucleotide variations (SNVs), insertions and deletions (indels), copy number variations (CNVs), and structural variations. To assess the performance of FIRST-LCP, we compiled test sets using HapMap samples or tumor cell lines with disclosed genetic information, and also tested our clinical lung cancer samples whose genetic alterations were known by conventional methods., Results: FIRST-LCP accomplished high sensitivity (99.4%) and specificity (100%) of the detection of SNVs. High precision was also achieved, with intra- or inter-run concordance rate of 0.99, respectively. FIRST-LCP detected indels and CNVs close to the expected allele frequency and magnitude, respectively. Tests with samples from lung cancer patients also identified all SNVs, indels and fusions., Conclusion: Based on the current state of the art, continuous application of the panel design and analysis pipeline following up-to-date knowledge could ensure precision medicine for lung cancer patients.

The electrochemical reduction of carbon dioxide (CO 2 ) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO 2 to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO 2 to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO 2 in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Prolonged hyperuricemia is a cause of gout and an independent risk factor for chronic health conditions including diabetes and chronic kidney diseases. Genome-wide association studies (GWASs) for serum uric acid (SUA) concentrations have repeatedly confirmed genetic loci including those encoding uric acid transporters such as ABCG2 and SLC9A2. However, many single nucleotide polymorphisms (SNPs) found in GWASs have been common variants with small effects and unknown functions. In addition, there is still much heritability to be explained. To identify the causative genetic variants for SUA concentrations in Korean subjects, we conducted a GWAS (1902 males) and validation study (2912 males and females) and found four genetic loci reaching genome-wide significance on chromosomes 4 (ABCG2) and 11 (FRMD8, EIF1AD and SLC22A12-NRXN2). Three loci on chromosome 11 were distributed within a distance of 1.3 megabases and they were in weak or moderate linkage disequilibrium (LD) states (r2 = 0.02-0.68). In a subsequent association analysis on the GWAS loci of chromosome 11 using closely positioned markers derived from whole genome sequencing data, the most significant variant to be linked with the nearby GWAS signal was rs121907892 (c.774G>A, p.W258*) of the SLC22A12 gene. This variant, and each of the three GWAS SNPs, were in LD (r2 = 0.06-0.32). The strength of association of SNPs with SUA concentration (negative logarithm of P-values) and the genetic distance (r2 of LD) between rs121907892 and the surrounding SNPs showed a quantitative correlation. This variant has been found only in Korean and Japanese subjects and is known to lower the SUA concentration in the general population. Thus, this low-frequency variant, rs121907892, known to regulate SUA concentrations in previous studies, is responsible for the nearby GWAS signals., Competing Interests: The authors have declared that no competing interests exist.

Synthesis of chiral plasmonic materials has been highlighted for the last decades with their optical properties and versatile potential applications. Recently reported aqueous-based amino acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles with 432 point-group symmetry shows exceptionally high chiroptic response within 100 nm scales. Despite its already excellent chiroptic response, a single-nanoparticle dark field scattering study revealed that full chiroptic potential of chiral gold nanoparticle is limited with its overall synthetic uniformity. Based on this knowledge, we present a multi-chirality-evolution step synthesis method for the enhancement of chiroptic response through an increase in particle uniformity. Detailed time variant study and interrelationship study of reaction parameters allowed the systematic construction of design principles for chiral nanoparticles with exceptional chiroptic response. With the application of precisely controlled growth kinetic to two distinct growth regimes, modified chiral gold nanoparticles showed significantly improved uniformity, achieving an improved dissymmetry factor of g = 0.31. We expect that our strategy will aid in precise morphology and property control for chiral nanomaterials, which can be used in various plasmonic metamaterial applications.

The processes of biological photosynthesis provide inspiration and valuable lessons for artificial energy collection, transfer, and conversion systems. The extraordinary efficiency of each sequential process of light to biomass conversion originates from the unique architecture and mechanism of photosynthetic proteins. Near 100% quantum efficiency of energy transfer in biological photosystems is achieved by the chlorophyll assemblies in antenna complexes, which also exhibit a significant degree of light polarization. The three-dimensional chiral assembly of chlorophylls is an optimized biological architecture that enables maximum energy transfer efficiency with precisely designed coupling between chlorophylls. In this review, we summarize the key lessons from the photosynthetic processes in biological photosystems, and move our focus to energy transfer mechanisms and the chiral structure of the chlorophyll assembly. Then, we introduce recent approaches and possible implications to realize the biological energy transfer processes on bioinspired scaffold-based artificial antenna systems.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age., Competing Interests: The authors declare no potential conflicts of interest.

Chiral plasmonic nanostructures have opened up unprecedented opportunities in optical applications. We present chirality evolution in nanoparticles focusing on the crystallographic aspects and elucidate key parameters for chiral structure formation. From a detailed understanding of chirality formation, we achieved a morphology (432 Helicoid IV) of three-dimensionally controlled chiral plasmonic nanoparticles based on the rhombic dodecahedral shape. The role of the synthesis parameters, seed, cysteine, cetyltrimethylammonium bromide and ascorbic acid on chiral formation are studied, and based on this understanding, the systematic control of the chiral structure is presented. The relation between the modulated chiral structure factors and optical response is further elucidated by electromagnetic simulation. Importantly, a new optical response is achieved by assembling chiral nanoparticles into a film. This comprehensive study of chiral nanoparticles will provide valuable insight for the further development of diverse chiral plasmonic nanostructures with fascinating properties.

Plasmonic metamaterials are artificially designed materials which exhibit optical properties that cannot be found in nature. They have unique and special abilities related to electromagnetic wave control, including strong field enhancement in the vicinity of the surfaces. Over the years, scientists have succeeded in dramatically improving the detection limit of molecular chirality utilizing a variety of plasmonic metamaterial platforms. In this mini-review, we will discuss the principles of most recent issues in chiral sensing applications of plasmonic metamaterials, including suggested formulas for signal enhancement of chiroptical plasmonic sensors, and studies on various platforms that employ different sensing mechanisms.

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: 6 were adults (mean age, 43.0 years [range, 23-56 years]) and 1 was a child (age, 10 years). The most common symptoms were seizures (n = 4) and headache (n = 2). The tumors were supratentorial (temporal, 5; frontal lobes, 2) in origin as reported. Vacuolated tumor cells were robustly positive for α-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N, nestin and CD34. GFAP and vimentin were expressed in reactive astrocytes but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAF V600E , H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%), and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No IDH1/IDH2 and BRAF V600E mutations were found upon direct sequencing. Whole-exome sequencing revealed FGFR2-ZMYND11 gene fusion in 1 case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average period of 68 months (range, 23-101 months). The analysis of 7 typical cases of MVNT suggested that these lesions may be clonal tumors because FGFR2-ZMYND11 fusion was found (1 case)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Context: Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown., Objective: To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer., Design and Setting: We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data., Results: The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues., Conclusions: To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.