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ObjectiveTo analyze the differences in the expressions of the total and phosphorylated proteins in human colon cancer HCT116 cells after the knockout (KO) of retinoic acid-induced protein 16 (RAI16) and explore the possible mechanism and related signaling pathways affecting its protein function in HCT116 cells. MethodsHCT116 KO and WT cell proteins were collected and extracted, and the protein extraction efficiency was detected via a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) experiment. After protein digestion, the peptides were labeled with TMT and analyzed via mass spectrometry. We used bioinformatics methods to analyze the identified differential proteins and differentially phosphorylated proteins by using GO, KEGG, and STRING databases. ResultsThe results of SDS-PAGE showed no evident protein degradation. In addition, some key bands were significantly different between the experimental and control groups. A total of 147 up-regulated and 230 down-regulated differential proteins were screened in accordance with the conditions of Foldchange≥1.5 or Foldchange≤1/1.5 and P

The study examined the functional properties of lactic yeast-fermented Tartary buckwheat sprout with passion and pineapple juice (Tatary buckwheat sprout juice). Pineapple and passion fruit were included during fermentation to improve the sensory and nutritional quality of the juice. We initially created a juice with Tartary buckwheat sprouts, and then fermented it with Lactobacillus plantarum and yeast (Saccharomyces cerevisiae) to produce a novel fermented sprout juice. Our results indicated that the best organoleptic quality was achieved when the inoculum of Lactobacillus plantarum was 2%, the inoculum of yeast was 1%, and the fermentation time was 30 hours. The results showed that fermentation resulted in a 1.55-fold increase in the total amino acid content, with fresh sweet amino acids increasing by 1.75-fold and sour-bitter amino acids increasing by 1.33-fold. Additionally, the levels of acetic acid, lactic acid, citric acid, and tartaric acid in the buckwheat sprout juice increased by 12.31%, 11.45%, 4.22%, and 3.88%, respectively. GC-MS analysis revealed a significant increase of volatile flavoring substances, such as alcohols and esters, by more than 24.7% in the fermentation products. From the results, yeast-Lactobacillus fermentation process may effectively improve the nutritional values of Tartary buckwheat sprout juice.

Abstract Motor imagery is a higher-order cognitive brain function that mentally simulates movements without performing the actual physical one. Although motor imagery has attracted the interest of many researchers, and mental practice utilizing motor imagery has been widely used in sports training and post-stroke rehabilitation, neural bases that determine individual differences in motor imagery ability are not well understood. In this study, using controllability of motor imagery (CMI) test that can objectively evaluate individual ability to manipulate one’s imaginary postures, we examined structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, by analyzing T1-weighted structural MRI data obtained from 89 participants and functional MRI data obtained from 28 of 89 participants. The higher CMI test scorers had larger volume in the bilateral superior frontoparietal white matter regions. The CMI test activated the bilateral dorsal premotor cortex (PMD) and superior parietal lobule (SPL); specifically, the left PMD and/or the right SPL enhanced functional coupling with the visual body, somatosensory, and motor/kinesthetic areas in the higher scorers. Hence, controllability of motor imagery is higher for those who well-develop superior frontoparietal network, and for those whose this network accesses these sensory areas to predict the expected multisensory experiences during motor imagery. This study elucidated for the first time the structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, and advanced understanding of individual differences in motor imagery ability.

The observation of spinon excitations in the S = 1 2 triangular antiferromagnet Ca3ReO5Cl2 reveals a quasi-one-dimensional (1D) nature of magnetic correlations, in spite of the nominally 2D magnetic structure. This phenomenon is known as frustration-induced dimensional reduction. Here, we present high-field electron spin resonance spectroscopy and magnetization studies of Ca3ReO5Cl2, allowing us not only to refine spin-Hamiltonian parameters, but also to investigate peculiarities of its low-energy spin dynamics. We argue that the presence of the uniform Dzyaloshinskii-Moriya interaction (DMI) shifts the spinon continuum in momentum space and, as a result, opens a zero-field gap at the Γ point. We observed this gap directly. The shift is found to be consistent with the structural modulation in the ordered state, suggesting this material as a perfect model triangular-lattice system, where a pure DMI-spiral ground state can be realized. Frustration-induced dimensional reduction is manifested in lower dimensionality of magnetic correlations compared to that of the magnetic structure. Here the authors demonstrate the role of the uniform Dzyaloshinskii-Moriya interaction in the recently synthesized material Ca3ReO5Cl2 exhibiting dimensional reduction. [ABSTRACT FROM AUTHOR]

In the context of telecommunication networks, the network terminals involve certain constraints that are either related with the performance of the corresponding network or with the availability of some classes of devices. In this paper, we discuss a tree-like telecommunication network design problem with the constraint limiting the number of terminals. First, this problem is formulated as a leaf-constrained minimum spanning tree (lc-MST). Then we develop a tree-based genetic representation to encode the candidate solutions of the lc-MST problem. Compared with the existing heuristic algorithm, the numerical results show the high effectiveness of the proposed GA approach on this problem. Keywords: genetic algorithms; network design; minimum spanning tree; telecommunication

Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.

Abstract Most of life’s vast diversity of species and phenotypes is often attributed to adaptive radiation. Yet its contribution to species and phenotypic diversity of a major group has not been examined. Two key questions remain unresolved. First, what proportion of clades show macroevolutionary dynamics similar to adaptive radiations? Second, what proportion of overall species richness and phenotypic diversity do these adaptive-radiation-like clades contain? We address these questions with phylogenetic and morphological data for 1226 frog species across 43 families (which represent >99% of all species). Less than half of frog families resembled adaptive radiations (with rapid diversification and morphological evolution). Yet, these adaptive-radiation-like clades encompassed ~75% of both morphological and species diversity, despite rapid rates in other clades (e.g., non-adaptive radiations). Overall, we support the importance of adaptive-radiation-like evolution for explaining diversity patterns and provide a framework for characterizing macroevolutionary dynamics and diversity patterns in other groups.

Abstract Background No effective treatment for NAION with strong evidence has been established till date. The aim of this investigator-led, prospective, non-randomized, open-label, uncontrolled multi-center exploratory clinical trial is to evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with NAION. Methods Five patients with monocular NAION underwent TdES (10-ms biphasic pulses, 1.0 mA, 20 Hz, 30 min) of the affected eye six times at 2-week intervals. The primary endpoint was the logarithm of the mini-mum angle of resolution (logMAR) visual acuity at 12 weeks compared with 0 weeks. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, and mean deviation (MD) of the Humphrey field analyzer (HFA) 10–2 and HFA Esterman test scores. Additionally, the safety of TdES was evaluated. Results LogMAR visual acuity improved by ≥ 0.1 in two eyes, and ETDRS visual acu-ity improved by ≥ 5 characters in one eye. The mean change in logMAR visual acuity from week 0 showed an increasing trend. The mean MD of HFA 10–2 showed no obvious change, while HFA Esterman score improved in four eyes. All patients completed the study according to the protocol, and no treatment-related adverse events were observed. Conclusions TdES treatment may have improved visual acuity and visual field in some patients. Further sham-controlled study in larger cohort is needed on its effectiveness. Trial registration UMIN, UMIN000036220. Registered 15 March, 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041261 .

Abstract Mosquitoes have profoundly affected human history and continue to threaten human health through the transmission of a diverse array of pathogens. The phylogeny of mosquitoes has remained poorly characterized due to difficulty in taxonomic sampling and limited availability of genomic data beyond the most important vector species. Here, we used phylogenomic analysis of 709 single copy ortholog groups from 256 mosquito species to produce a strongly supported phylogeny that resolves the position of the major disease vector species and the major mosquito lineages. Our analyses support an origin of mosquitoes in the early Triassic (217 MYA [highest posterior density region: 188–250 MYA]), considerably older than previous estimates. Moreover, we utilize an extensive database of host associations for mosquitoes to show that mosquitoes have shifted to feeding upon the blood of mammals numerous times, and that mosquito diversification and host-use patterns within major lineages appear to coincide in earth history both with major continental drift events and with the diversification of vertebrate classes.

Abstract The ubiquitin‒proteasome system (UPS) and autophagy are the two primary cellular pathways of misfolded or damaged protein degradation that maintain cellular proteostasis. When the proteasome is dysfunctional, cells compensate for impaired protein clearance by activating aggrephagy, a type of selective autophagy, to eliminate ubiquitinated protein aggregates; however, the molecular mechanisms by which impaired proteasome function activates aggrephagy remain poorly understood. Here, we demonstrate that activation of aggrephagy is transcriptionally induced by the transcription factor NRF1 (NFE2L1) in response to proteasome dysfunction. Although NRF1 has been previously shown to induce the expression of proteasome genes after proteasome inhibition (i.e., the proteasome bounce-back response), our genome-wide transcriptome analyses identified autophagy-related p62/SQSTM1 and GABARAPL1 as genes directly targeted by NRF1. Intriguingly, NRF1 was also found to be indispensable for the formation of p62-positive puncta and their colocalization with ULK1 and TBK1, which play roles in p62 activation via phosphorylation. Consistently, NRF1 knockdown substantially reduced the phosphorylation rate of Ser403 in p62. Finally, NRF1 selectively upregulated the expression of GABARAPL1, an ATG8 family gene, to induce the clearance of ubiquitinated proteins. Our findings highlight the discovery of an activation mechanism underlying NRF1-mediated aggrephagy through gene regulation when proteasome activity is impaired.

Background: Eurotium cristatum (E. cristatum) is the probiotic fungus in Fu-brick tea, with which fermentation brings a unique flavor and taste and health-promoting effects. Tartary buckwheat leaves are rich in functional active substances such as flavonoids and phenolic compounds, yet are not effectively utilized. Methods: Tartary buckwheat leaves were processed into raw green tea first and subsequently fermented with E. cristatum to develop a novel fermented leaf tea. The tea quality was evaluated by the aspects of the sensory scores by E-tongue, the volatile compounds by HS-SPME-GC-MS, the non-volatile profile by biochemical and UPLC-MS/MS methods and the antioxidant activity by the colorimetric assay. Results: Fermented leaf tea displayed a golden yellow color, a unique “flower” aroma and a dark-tea taste, with an improved sensory acceptability. Fermentation raised the content of volatile heterocyclic and aromatic compounds, alkenes and other aromatic components, which produced a unique floral flavor. The proportion of sour, bitter and astringency accounting non-volatile compounds such as phenolic acids and amino acids decreased, while the proportion of umami and sweet accounting substances such as responsible amino acids increased. Fermented leaf tea displayed a relative stronger total antioxidant activity against ABTS. Conclusion: E. cristatum fermentation exerted positive effects on Tartary buckwheat leaf tea quality.

Incorporation of a silicon fillet self-aligned contact (SIFT) process in the super self-aligned half micron BiCMOS technology facilitates high speed operations in ECL and CMOS bipolar circuits. The compatibility of bipolar and CMOS devices helps simplify the integrated process flow in the circuit with the SIFT process reducing CMOS drain and device source capacitance. Gate delay values for bipolar and CMOS circuits are 24 ps and 50 ps, respectively, on 0.6-micrometer-thick gate ring oscillators. The operation of this technology in a single phase decision circuit and a static frequency divider proves the technology's validity.

This is a retrospective, consecutive, noncomparative case series of 6 eyes of 5 retinitis pigmentosa (RP) patients who had undergone pars plana vitrectomy (PPV) and intraocular lens (IOL) implantation. The aim of this case series was to report the long-term outcomes of PPV with IOL implantation in patients with RP). The surgical procedures, visual function, refractive error, corneal endothelial cell density, intraocular pressure, and retinal morphology were evaluated before and 3 years after the surgery. Six eyes of 5 RP patients that had undergone PPV and IOL implantation with or without suturing for lens dislocation were studied. The visual acuity was maintained or improved at 3 years after surgery in all 6 eyes. No intraoperative complications occurred in any of the cases. The mean deviation of the Humphrey Field Analyzer 10–2 program and the retinal morphology evaluated by optical coherence tomography did not show any abnormal changes before and after surgery. In two eyes, the postoperative refractive error was more myopic than the attempted refractive error. In conclusion, PPV with IOL implantation can be performed safely in RP patients, and the long-term visual acuity can be maintained.

Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 μg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance. The power of kainic acid (KA)-induced network oscillation in the ACC Cg1 region slice preparation increased in LPS-treated mice. Notably, histamine, which was added in vitro, increased the oscillation power in the brain slices from LPS-untreated mice; for the LPS-treated mice, however, the effect of histamine was suppressive. In the open field test, frequency of entries into the center area showed a negative correlation with the power of network oscillation (0.3 μM of KA, theta band (3-8 Hz); 3.0 μM of KA, high-gamma band (50-80 Hz)). These results suggest that LPS-induced systemic inflammation results in increased network oscillation and a drastic change in histamine sensitivity in the ACC, accompanied by the robust production of systemic pro-inflammatory cytokines in the periphery, and that these alterations in the network oscillation and animal behavior as an acute phase reaction relate with each other. We suggest that our experimental setting has a distinct advantage in obtaining mechanistic insights into inflammatory cognitive impairment through comprehensive analyses of hormonal molecules and neuronal functions.

Three-dimensional (3D) photoacoustic imaging (PAI) can provide rich information content and has gained increasingly more attention in various biomedical applications. However, current 3D PAI methods either involves pointwise scanning of the 3D volume using a single-element transducer, which can be time-consuming, or requires an array of transducers, which is known to be complex and expensive. By utilizing a 3D encoder and compressed sensing techniques, we develop a new imaging modality that is capable of single-shot 3D PAI using a single-element transducer. The proposed method is validated with phantom study, which demonstrates single-shot 3D imaging of different objects and 3D tracking of a moving object. After one-time calibration, while the system could perform single-shot 3D imaging for different objects, the calibration could remain effective over 7 days, which is highly beneficial for practical translation. Overall, the experimental results showcase the potential of this technique for both scientific research and clinical applications.

Understanding the process underlying the spatial gradients in biodiversity is a fundamental issue in ecology. Altitudinal gradients are ideal systems for examining the community assembly process because they represent rapid changes in environmental conditions over relatively short distances. The functional and phylogenetic approaches allow a deeper mechanistic understanding of the underlying assembly process. However, whether community assembly from montane to alpine zones is driven more by ecological constraints or human settlement patterns is not fully resolved and may vary by system. Here, we examined the phylogenetic and trait-based functional structures from the montane to alpine zones and clarified the effects of natural environmental factors and human-induced landscape transformation on the breeding bird assemblage on Mount Norikura, central Japan. Breeding birds from 700 to 3026 m a.s.l. were surveyed in 2016–2017. Bird community structures were examined based on species richness, functional and phylogenetic structures. A null modelling approach was performed to examine functional and phylogenetic cluster/overdispersion structures; clustering and overdispersion imply species elimination by environmental filters and limiting similarity as a corollary of competitive exclusion of species, respectively. Furthermore, we examined the relative effect of natural environments and human disturbance. Bird species richness was high in the mountain base to mid-elevation, then decreased with elevation. We found a contrasting pattern in the phylogenetic and functional structures in the alpine zone: phylogenetic overdispersion and functional clustering. In contrast, the functional and phylogenetic structures were clustered in the upper parts of the subalpine zone. The functional and phylogenetic clusterings in the lower parts of the subalpine and montane zones were negligible with the weak effects of the environmental filtering. Single-trait analysis showed that the high abiotic tolerance and foraging or nesting capabilities in treeless environments were clustered in the alpine zone, and mobility was clustered in the subalpine zones. Natural environments strongly affected bird community structures, but human disturbance added species to assemblages in the mountain base to mid-elevation and changed the functional and phylogenetic structures. Our findings highlight that filtering by severe natural environments is a fundamental community assembly process in high mountain regions, whereas filtering effects can be weaker at lower elevations. Furthermore, the filtering effect should differ between the alpine and the upper parts of the subalpine zones because of different combinations of clustered traits. Climate change and landscape transformation pressures may strongly impact biodiversity in the alpine and subalpine zones, respectively.

Background/purpose: The SimEx is dental training system that applies new technology in a computerized dental simulator. The purpose of this study was to understand the usability satisfaction of the SimEx dental education and evaluation system by dental students and dentists at Tohoku University. Materials and methods: In this study, the Tohoku University IRB execution number was 2020-3-33. The number of subjects accepted was 59 at Tohoku University and divided into 4 groups based on years of clinical experience (Group A: 0 years; Group B: 1–2 years; Group C: 2–5 years; Group D: at least 5 years), and a total of 58 usability questionnaires were collected. Subjects completed the SimEx Usability Satisfaction Questionnaire after operating the SimEx (EPED Inc., Kaohsiung, Taiwan) course, which contained 16 questions. Results: Among the 58 questionnaires collected by Tohoku University, there were 19 undergraduate students (4th∼6th grade), 12 post-graduate students, 14 residents, and 13 dentists. Significant differences between Group A and Group B, and between Group A and Group D were found (P

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Key Clinical Message This report presents the clinical findings and prognosis of a healthy male patient who developed acute macular neuroretinopathy after COVID‐19 vaccination. Abnormal findings improved about 1 month after the onset and disappeared 3 months later. The subjective symptoms disappeared in 3 months, and no recurrence was observed for 1 year.

Photoacoustic (PA) theranostics is a new emerging field that uniquely combines diagnosis and treatment in one modality. However, its current status is compromised by the indispensable dependence on nonreversible phase-change nanoprobes that provides one-time-only action. Here, we demonstrate a picosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics, guaranteeing sustained PA cavitation by using non-phase-change nanoprobes. Theoretical simulations validate that, when compressing the excitation laser pulse width to hundred-picosecond, the thermal confinement effects of a conventional nanoprobe will induce transient heating of the extremely thin surrounding liquid layer of the nanoprobes beyond its cavitation point in a localized area at nanoscale, resulting in intense cavitation and PA shockwaves by the environment rather than the nanoprobes. Both cellular and mouse model experiments have demonstrated the highly effective anti-tumor effects. This method provides a sustainable, reproducible, and highly effective strategy for PA theranostics, prefiguring great potential for the clinical applications.

Abstract Background Previous studies have identified noninvasive methods for predicting atrial fibrillation (AF) recurrence after catheter ablation (CA). We assessed the association between AF recurrence and atrial late potentials (ALPs), which were measured using P‐wave signal‐averaged electrocardiography (P‐SAECG). Methods Consecutive patients with paroxysmal AF who underwent their first CA at our institution between August 2015 and August 2019 were enrolled. P‐SAECG was performed before CA. Two ALP parameters were evaluated: the root‐mean‐square voltage during the terminal 20 ms (RMS20) and the P‐wave duration (PWD). Positive ALPs were defined as an RMS20 115 ms. Patients were allocated to either the recurrence or nonrecurrence group based on the presence of AF recurrence at the 1‐year follow‐up post‐CA. Results Of the 190 patients (age: 65 ± 11 years, 37% women) enrolled in this study, 21 (11%) had AF recurrence. The positive ALP rate was significantly higher in the recurrence group than in the nonrecurrence group (86% vs. 64%, p = .04), despite the absence of differences in other baseline characteristics between the two groups. In the multivariate analysis, positive ALP was an independent predictor of AF recurrence (odds ratio: 3.83, 95% confidence interval: 1.05–14.1, p = .04). Conclusions Positive ALP on pre‐CA P‐SAECG is associated with AF recurrence after CA.

ABSTRACT Aims/Introduction We aimed to clarify the real‐world risk of lower‐limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium–glucose cotransporter 2 inhibitors (SGLT2is). Materials and Methods We carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower‐limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents. Results Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80–2.24). However, female sex (HR 2.78, 95% CI 1.12–6.94) and use of strong statins (HR 2.68; 95% CI 1.18–8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group. Conclusions SGLT2is might not be related to an increased risk of lower‐limb amputation in patients with type 2 diabetes in real‐world clinical practice. The possible increased risk of SGLT2is‐associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable.