First report of konjac mosaic virus in Spuriopimpinella brachycarpa in Korea.

Spuriopimpinella brachycarpa Nakai (Common name, Chamnamul; family Apiaceae) is a plant whose leaves are consumed as a vegetable and used as a folk medicine in Korea (Kim et al., 2020). In February 2020, seven samples of S. brachycarpa leaf showing virus symptoms including yellowing, vein chlorosis, chlorotic lesions, and severe mottling were collected from a greenhouse in Busan, South Korea, to diagnose the potential disease (Fig. S1a, b). The disease incidence rate in the greenhouse was >10% (2,970 m2). To identify the causal virus, we analyzed leaf dip preparation and thin sections of the symptomatic leaves by transmission electron microscopy. Filamentous virus particles and pinwheel structures were observed, indicating the presence of a potyvirus (Fig. S1c, d). To confirm these results, the symptomatic leaf samples were further analyzed by reverse-transcription polymerase chain reaction (RT-PCR) using potyvirus universal primers (Table S2) and direct sequencing of the PCR products. All samples were positive for konjac mosaic virus (KoMV). To exclude the possibility of infection by multiple viruses, we performed high-throughput sequencing (HTS) on an Illumina NovaSeq 6000 system (Macrogen Inc., Seoul, South Korea). There were two contigs (9,267 and 2,851 nt) mapping to KoMV sequences. A large contig (9,267 nt; 705,967 mapped reads; mean read coverage of 11,351.4x) showed about 80% identity (93% coverage) with KoMV-F (GenBank accession no. NC_007913) isolated from Amorphophallus konjac in Japan (Nishiguchi et al., 2006). To isolate KoMV from S. brachycarpa, we mechanically inoculated leaf extracts from symptomatic samples onto Chenopodium quinoa as an assay host via three single-lesion passages, followed by propagation in Nicotiana benthamiana. In a bioassay of the KoMV isolate (KoMV-BS), we mechanically inoculated sap from infected N. benthamiana onto 31 indicator plants including Cryptotaenia japonica (Apiaceae), which is similar to S. brachycarpa (Table S3). KoMV-BS systemically induced vein chlorosis and/or leaf mottling in four Nicotiana species and C. japonica, and chlorotic local lesions in upper leaves of C. quinoa; no symptoms were observed in 25 other indicator plants. These results were confirmed by RT-PCR. Next, we obtained the complete genome sequence of KoMV-BS using HTS and 5' and 3' rapid amplification of cDNA ends, with newly designed primers (Table S2). The assembled full-length KoMV-BS genome sequence was 9,392 nt in length, excluding the poly(A) tail, and encoded a polyprotein composed of 3,060 amino acids. The sequence was deposited in GenBank (accession no. OR001914). BLAST analysis showed 84~88% and 90~98% identities at CP nucleotide and amino acid levels, respectively with the reported KoMV isolates, confirming the virus to be an isolate of KoMV (synonym; Japanese hornwort mosaic virus, zantedeschia mosaic virus) (Adams et al., 2005; Nishiguchi et al., 2006). KoMV infection was first reported in A. konjac from Japan (Shimoyama et al. 1992) and has been spread worldwide as one of the major causal agents of viral diseases in calla lily (Liao et al., 2020). To the best of our knowledge, this is the first report of KoMV infection in S. brachycarpa. To date, cucumber mosaic virus and tobacco mosaic virus have been reported to infect S. brachycarpa in Korea (Yoon et al., 2016; 2017). Our findings will be helpful for developing virus-management strategies to prevent yield and quality loss in S. brachycarpa.

Fat graft survival requires metabolic reprogramming toward the glycolytic pathway.

BACKGROUND: Fat grafts are widely used as natural fillers in reconstructive and cosmetic surgery. However, the mechanisms underlying fat graft survival are poorly understood. Here, we performed an unbiased transcriptomic analysis in a mouse fat graft model to determine the molecular mechanism underlying free fat graft survival. METHODS: We conducted RNA-sequencing (RNA-seq) analysis in a mouse free subcutaneous fat graft model on days 3 and 7 following grafting (n = 5). High-throughput sequencing was performed on paired-end reads using NovaSeq6000. The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heatmap generation, and gene set enrichment analysis. RESULTS: PCA and heatmap data revealed global differences in the transcriptomes of the fat graft model and the non-grafted control. The top meaningful upregulated gene sets in the fat graft model were related to the epithelial-mesenchymal transition, hypoxia on day 3, and angiogenesis on day 7. Mechanistically, the glycolytic pathway was upregulated in the fat graft model at days 3 (FDR q = 0.012) and 7 (FDR q = 0.084). In subsequent experiments, pharmacological inhibition of the glycolytic pathway in mouse fat grafts with 2-deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n = 5). CONCLUSIONS: Free adipose tissue grafts undergo metabolic reprogramming toward the glycolytic pathway. Future studies should examine whether targeting this pathway can enhance the graft survival rate.

Non-Hermitian chiral degeneracy of gated graphene metasurfaces.

Non-Hermitian degeneracies, also known as exceptional points (EPs), have been the focus of much attention due to their singular eigenvalue surface structure. Nevertheless, as pertaining to a non-Hermitian metasurface platform, the reduction of an eigenspace dimensionality at the EP has been investigated mostly in a passive repetitive manner. Here, we propose an electrical and spectral way of resolving chiral EPs and clarifying the consequences of chiral mode collapsing of a non-Hermitian gated graphene metasurface. More specifically, the measured non-Hermitian Jones matrix in parameter space enables the quantification of nonorthogonality of polarisation eigenstates and half-integer topological charges associated with a chiral EP. Interestingly, the output polarisation state can be made orthogonal to the coalesced polarisation eigenstate of the metasurface, revealing the missing dimension at the chiral EP. In addition, the maximal nonorthogonality at the chiral EP leads to a blocking of one of the cross-polarised transmission pathways and, consequently, the observation of enhanced asymmetric polarisation conversion. We anticipate that electrically controllable non-Hermitian metasurface platforms can serve as an interesting framework for the investigation of rich non-Hermitian polarisation dynamics around chiral EPs.

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria.

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

Revealing non-Hermitian band structure of photonic Floquet media.

Periodically driven systems are ubiquitously found in both classical and quantum regimes. In the field of photonics, these Floquet systems have begun to provide insight into how time periodicity can extend the concept of spatially periodic photonic crystals and metamaterials to the time domain. However, despite the necessity arising from the presence of nonreciprocal coupling between states in a photonic Floquet medium, a unified non-Hermitian band structure description remains elusive. We experimentally reveal the unique Bloch-Floquet and non-Bloch band structures of a photonic Floquet medium emulated in the microwave regime with a one-dimensional array of time-periodically driven resonators. These non-Hermitian band structures are shown to be two measurable distinct subsets of complex eigenfrequency surfaces of the photonic Floquet medium defined in complex momentum space.

Optimal flickering light stimulation for entraining gamma rhythms in older adults.

With aging, optimal parameters of flickering light stimulation (FLS) for gamma entrainment may change in the eyes and brain. We investigated the optimal FLS parameters for gamma entrainment in 35 cognitively normal old adults by comparing event-related synchronization (ERS) and spectral Granger causality (sGC) of entrained gamma rhythms between different luminance intensities, colors, and flickering frequencies of FLSs. ERS entrained by 700 cd/m2 FLS and 32 Hz or 34 Hz FLSs was stronger than that entrained by 400 cd/m2 at Pz (p < 0.01) and 38 Hz or 40 Hz FLSs, respectively, at both Pz (p < 0.05) and Fz (p < 0.01). Parieto-occipital-to-frontotemporal connectivities of gamma rhythm entrained by 700 cd/m2 FLS and 32 Hz or 34 Hz FLSs were also stronger than those entrained by 400 cd/m2 at Pz (p < 0.01) and 38 Hz or 40 Hz FLSs, respectively (p < 0.001). ERS and parieto-occipital-to-frontotemporal connectivities of entrained gamma rhythms did not show significant difference between white and red lights. Adverse effects were comparable between different parameters. In older adults, 700 cd/m2 FLS at 32 Hz or 34 Hz can entrain a strong gamma rhythm in the whole brain with tolerable adverse effects.

Identifying the course of the greater palatine artery using intraoral ultrasonography: cohort study.

AIMS: The greater palatine artery (GPA) is one of the most important anatomical structure for free gingival grafts or connective-tissue grafts during soft tissue surgery for dental implants. Several studies have identified the approximate location of the GPA, but it is impossible to detect its exact location during surgery due to large variability between individuals. The authors, therefore, investigated the course of the GPA using intraoral ultrasonography to determine the feasibility of using real-time nonionizing ultrasonography for implant surgery. MATERIALS AND METHODS: This study included 40 healthy young participants. The courses of the GPA were identified using intraoral ultrasound probes from the first premolar to the second molar. The distance from the gingival margin to the GPA (GM-GPA) and the depth of the palatal gingiva from the GPA (PG-GPA) were measured by two independent examiners. Measurements were analyzed statistically, and interexaminer reliability was determined. RESULTS: The distance of the GM-GPA and the mean depth of the PG-GPA were 14.8 ± 1.6 mm and 4.10 ± 0.51 mm (mean ± SD), respectively. GM-GPA decreased when the GPA ran from the second molar to the first molar, and GM-GPA was significantly shorter in females (P < 0.05). PG-GPA increased when the GPA ran to the posterior teeth. Interexaminer measurement agreements were excellent, with intraclass correlation coefficient values of 0.983 and 0.918 for GM-GPA and PG-GPA, respectively. CONCLUSIONS: Using an intraoral ultrasound probe, real-time GPA tracking is possible, which is expected to help reduce the possibility of bleeding during surgery.

Thyroid Hormone Ameliorates Lymphedema by Suppressing Adipogenesis in a Murine Lymphedema Model.

Background: Exogenous supplementation of thyroid hormone could inhibit excessive fat deposition in lymphedema tissue by suppressing adipogenesis. Methods and Results: Cell viability, adipogenic differentiation, and mRNA expression were measured in 3T3-L1 preadipocytes treated with L-thyroxine. Twelve mice were divided into control and L-thyroxine groups. Two weeks after lymphedema was surgically induced, the experimental mice were fed L-thyroxine for 4 weeks. Tail volume and body weight were measured, and 6 weeks after the surgery, tail skin and subcutaneous tissue were harvested for histopathologic examination and protein isolation. In 3T3-L1 cells, treatment with 10-500 µM L-thyroxine did not affect cell viability. Eight days after induction of adipogenic differentiation, lipid accumulation decreased significantly in the 50 and 100 µM L-thyroxine groups (p < 0.001). mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4) decreased significantly in the 100 µM L-thyroxine group compared with the control group (p = 0.017). Lymphedema tails treated with L-thyroxine exhibited decreased volume (p = 0.028) and thickness of dermal and subcutaneous tissue (p = 0.01) and increased vascular endothelial growth factor-C protein expression (p = 0.017) compared with the control. Conclusion: Thyroid hormone therapy inhibits the adipogenesis of 3T3-L1 cells in vitro and decreases the volume of murine lymphedema tail in vivo. These findings suggest that thyroid hormone therapy could be used to treat lymphedema.

Optimal flickering light stimulation for entraining gamma waves in the human brain.

Although light flickering at 40 Hz reduced Alzheimer's disease (AD) pathologies in mice by entraining gamma waves, it failed to reduce cerebral amyloid burden in a study on six patients with AD or mild cognitive impairment. We investigated the optimal color, intensity, and frequency of the flickering light stimulus for entraining gamma waves in young adults. We compared the event-related synchronization (ERS) values of entrained gamma waves between four different light colors (white, red, green, and blue) in the first experiment and four different luminance intensities in the second experiment. In both experiments, we compared the ERS values of entrained gamma waves between 10 different flickering frequencies from 32 to 50 Hz. We also examined the severity of six adverse effects in both experiments. We compared the propagation of gamma waves in the visual cortex to other brain regions between different luminance intensities and flickering frequencies. We found that red light entrained gamma waves most effectively, followed by white light. Lights of higher luminance intensities (700 and 400 cd/m2) entrained stronger gamma waves than those of lower luminance intensities (100 and 10 cd/m2). Lights flickering at 34-38 Hz entrained stronger and more widely spread beyond the visual cortex than those flickering at 40-50 Hz. Light of 700 cd/m2 resulted in more moderate-to-severe adverse effects than those of other luminance intensities. In humans, 400 cd/m2 white light flickering at 34-38 Hz was most optimal for gamma entrainment.

Outcomes of open versus single-incision laparoscopic totally extraperitoneal inguinal hernia repair using propensity score matching: A single institution experience.

PURPOSE: The aim of the current study was to compare the outcomes between open and single-incision laparoscopic totally extraperitoneal (SILTEP) inguinal hernia repair. METHODS: To compare the outcomes between the open and SILTEP groups, we performed propensity score matching to adjust for significant differences in patient characteristics. The outcomes were compared between the matched groups. RESULTS: Record review identified 477 patients who had undergone inguinal hernia repair from November 2016 to November 2018. Seventy-one patients were excluded from the propensity score matching because of age <18, femoral hernia, conventional 3-port laparoscopic repair, incarcerated hernia, and combined operation. SILTEP in 142 and open repair in 264 patients were identified. After propensity score matching, these individuals were grouped into 82 pairs. Spinal anesthesia was administered more often in the open group than in the SILTEP group. Operation time was significantly longer in the SILTEP group than in the open group (49.6 ± 17.4 vs. 64.8 ± 28.4 min, p < 0.001). However, urinary retention rates of the open group were significantly higher than that of the SILTEP group (11.0% vs. 0%, p = 0.003). The SILTEP group showed significantly lower pain scores at postoperative 6, 12, and 24 hours, and significantly lower rates of intravenous analgesic requirements through postoperative day 1 (30.5% vs. 13.4%, p = 0.008) compared with the open group. CONCLUSION: The outcomes of SILTEP repair were comparable to those of open repair. SILTEP repair may have advantages over open repair for reducing immediate postoperative pain (≤24 hours).

Pre-attentive Visual Processing in Alzheimer's Disease: An Event-related Potential Study.

INTRODUCTION: While identifying Alzheimer's Disease (AD) in its early stages is crucial, traditional neuropsychological tests tend to lack sensitivity and specificity for its diagnosis. Neuropsychological studies have reported visual processing deficits of AD, and event-related potentials (ERPs) are suitable to investigate pre-attentive processing with superior temporal resolution. OBJECTIVE: This study aimed to investigate visual attentional characteristics of adults with AD, from pre-attentive to attentive processing, using a visual oddball task and ERPs. METHODS: Cognitively normal elderly controls (CN) and patients with probable AD (AD) were recruited. Participants performed a three-stimulus visual oddball task and were asked to press a designated button in response to the target stimuli. The amplitudes of 4 ERPs were analyzed. Mismatchnegativity (vMMN) was analyzed around the parieto-occipital and temporo-occipital regions. P3a was analyzed around the fronto-central regions, whereas P3b was analyzed around the centro-parietal regions. RESULTS: Late vMMN amplitudes of the AD group were significantly smaller than those of the CN group, while early vMMN amplitudes were comparable. Compared to the CN group, P3a amplitudes of the AD group were significantly smaller for the infrequent deviant stimuli, but the amplitudes for the standard stimuli were comparable. Lastly, the AD group had significantly smaller P3b amplitudes for the target stimuli compared to the CN group. CONCLUSION: Our findings imply that AD patients exhibit pre-attentive visual processing deficits, known to affect later higher-order brain functions. In a clinical setting, the visual oddball paradigm could be used to provide helpful diagnostic information since pre-attentive ERPs can be induced by passive exposure to infrequent stimuli.

Electrical control of terahertz frequency conversion from time-varying surfaces.

We investigate the electrical control of frequency conversion from a time-varying interdigitated photo-conductive antenna (IPCA) and time-varying metasurface in the terahertz (THz) frequency range. Ultrafast near-infrared (NIR) optical pulses rapidly modify the conductivities of the IPCA and metasurface; however, external voltages can retard this conductivity transition. Thus, external voltages can be used to control the frequency conversion process based on the interaction between the THz waves and the time-varying surfaces. In the IPCA, both frequency up- and down-conversion processes are suppressed by external voltages. However, in the metasurface, the down-conversion is dramatically suppressed by external voltages, whereas the suppression on the up-conversion is less effective.

Regional Beta Index of Electroencephalography May Differentiate Alzheimer's Disease from Depression.

Differentiating early Alzheimer's disease (AD) from depression with cognitive impairment is challenging in the elderly. To develop a model for differentiating these two conditions using electroencephalography (EEG), we enrolled 11 patients with early probable AD and 11 age- and cognitive function-matched patients with major depressive disorder (MDD) and compared the EEG relative powers of 9 scalp regions. Compared to the MDD group, the AD group had a higher global theta relative power (p=0.021). In the MDD group, beta relative power was higher in the mid-central region than in the left or right central regions (p<0.01). The prediction model that included global theta relative power and regional beta index was able to discriminate AD from MDD (AUC=0.893, p=0.002). A combination of global theta relative power and intra-individual regional differences in beta may differentiate early AD from MDD with cognitive impairment.

Control of terahertz nonlinear transmission with electrically gated graphene metadevices.

Graphene, which is a two-dimensional crystal of carbon atoms arranged in a hexagonal lattice, has attracted a great amount of attention due to its outstanding mechanical, thermal and electronic properties. Moreover, graphene shows an exceptionally strong tunable light-matter interaction that depends on the Fermi level - a function of chemical doping and external gate voltage - and the electromagnetic resonance provided by intentionally engineered structures. In the optical regime, the nonlinearities of graphene originated from the Pauli blocking have already been exploited for mode-locking device applications in ultrafast laser technology, whereas nonlinearities in the terahertz regime, which arise from a reduction in conductivity due to carrier heating, have only recently been confirmed experimentally. Here, we investigated two key factors for controlling nonlinear interactions of graphene with an intense terahertz field. The induced transparencies of graphene can be controlled effectively by engineering meta-atoms and/or changing the number of charge carriers through electrical gating. Additionally, nonlinear phase changes of the transmitted terahertz field can be observed by introducing the resonances of the meta-atoms.

Long-term clinical outcomes of Remote Ischemic Preconditioning and Postconditioning Outcome (RISPO) trial in patients undergoing cardiac surgery.

BACKGROUND: Remote ischemic conditioning has been shown to confer myocardial protection. However, there is still no sufficient data on its long-term clinical outcomes. We analyzed the long-term results of the Remote Ischemic Preconditioning and Postconditioning Outcome (RISPO) trial in cardiac surgery patients. METHODS: In the RISPO trial, 1280 patients were randomized to receive remote ischemic preconditioning (RIPC) with postconditioning (RIPostC, upper arm ischemia by four cycles of 5-min inflation followed by 5-min deflation of a pneumatic cuff, N=644) or sham (N=636) during cardiac surgery. Patient follow-up data were collected by review of medical records, telephone interviews, and from the National Statistical Office. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE; a composite of all-cause mortality, myocardial infarction (MI), stroke, and revascularization), and the secondary endpoints were the individual components of the primary endpoint. RESULTS: At completion of follow-up (mean 44months), there was no difference in MACCE between the groups (90 [14.0%] versus 101 [15.9%] in the RIPC with RIPostC versus control groups; hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.672-1.187; P=0.435). However, MI was reduced to half in the RIPC with RIPostC group (10 [1.6%] versus 23 [3.6%]; HR, 0.468; 95% CI, 0.222-0.984; P=0.045). CONCLUSIONS: Remote ischemic preconditioning with RIPostC did not improve long-term MACCE after cardiac surgery. However, MI was reduced in the RIPC with RIPostC group compared with the control group during the follow-up period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00997217.

Terahertz polarization spectroscopy in the near-field zone of a sub-wavelength-scale metal slit.

Time-domain spectroscopy is used to probe the polarization dependence of the terahertz-frequency absorption of α-lactose molecules in the near-field vicinity of a sub-wavelength-scale metal slit. The experimental result finds that the 0.53-THz absorption of this material has an unexpected polarization dependence, strongly coupled to the slit orientation; in particular, the electric wave in parallel polarization exhibits even complete vanishing of the otherwise resonant strong absorption. The physics behind this phenomena may be explained based on the Bethe's sub-wavelength diffraction: the electric field that is measured in the far field, but diffracted from a sub-wavelength-scale metal aperture, originates from solely magnetic dipole radiation and not from the electric dipole radiation, thus showing no electrically-coupled material response.

Graphene-ferroelectric metadevices for nonvolatile memory and reconfigurable logic-gate operations.

Memory metamaterials are artificial media that sustain transformed electromagnetic properties without persistent external stimuli. Previous memory metamaterials were realized with phase-change materials, such as vanadium dioxide or chalcogenide glasses, which exhibit memory behaviour with respect to electrically/optically induced thermal stimuli. However, they require a thermally isolated environment for longer retention or strong optical pump for phase-change. Here we demonstrate electrically programmable nonvolatile memory metadevices realised by the hybridization of graphene, a ferroelectric and meta-atoms/meta-molecules, and extend the concept further to establish reconfigurable logic-gate metadevices. For a memory metadevice having a single electrical input, amplitude, phase and even the polarization multi-states were clearly distinguishable with a retention time of over 10 years at room temperature. Furthermore, logic-gate functionalities were demonstrated with reconfigurable logic-gate metadevices having two electrical inputs, with each connected to separate ferroelectric layers that act as the multi-level controller for the doping level of the sandwiched graphene layer.

Denosumab-related osteonecrosis of the jaw: a case report and management based on pharmacokinetics.

Denosumab, a monoclonal antibody against the receptor activator for nuclear factor-kappa B ligand (RANKL), is a recently approved antiresorptive drug that suppresses osteoclast formation by targeting preosteclasts, in contrast to the traditional antiresorptive bisphosphonates that target mature osteoclasts. Osteonecrosis of the jaw (ONJ) is a well-known, if rare, side effect of bisphosphonate therapy; however, cases of ONJ have also been reported since 2010 in patients taking denosumab. We describe here a patient who developed ONJ while receiving denosumab; the pharmacokinetics of denosumab and bisphosphonates are discussed in the context of ONJ management.

THz near-field spectral encoding imaging using a rainbow metasurface.

We demonstrate a fast image acquisition technique in the terahertz range via spectral encoding using a metasurface. The metasurface is composed of spatially varying units of mesh filters that exhibit bandpass features. Each mesh filter is arranged such that the centre frequencies of the mesh filters are proportional to their position within the metasurface, similar to a rainbow. For imaging, the object is placed in front of the rainbow metasurface, and the image is reconstructed by measuring the transmitted broadband THz pulses through both the metasurface and the object. The 1D image information regarding the object is linearly mapped into the spectrum of the transmitted wave of the rainbow metasurface. Thus, 2D images can be successfully reconstructed using simple 1D data acquisition processes.