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Purpose: To investigate the clinical results of vitrectomy alone as the primary treatment for rhegmatogenous retinal detachment (RD) in patients with atopic dermatitis (AD).Methods: The medical records of patients with AD treated for rhegmatogenous retinal detachment (RD) were retrospectively reviewed. We investigated the characteristics of retinal breaks and detachments, applied surgical methods, and results.Results: Twenty eyes of 14 patients with AD who presented with rhegmatogenous RD and treated by vitrectomy were included in this analysis. Sixteen eyes (80%) were treated with vitrectomy, either alone or in combination with cataract surgery, and the retina was successfully attached to 94% of the eyes. There were four cases in which vitrectomy was combined with encircling. Reoperation was needed in half of the eyes that received vitrectomy with encircling, which presented nearly total detachment, severe proliferative vitreoretinopathy, and pseudophakia.Conclusions: Vitrectomy alone, in combination with cataract surgery, may be sufficient to treat rhegmatogenous RD in patients with AD. Additional encircling or buckling should still be considered in complicated cases.

Primary cilia, antenna-like cellular sensor structures, are generated from the mother centriole in the G0/G1 cell-cycle phase under control by cellular signaling pathways involving Wnt, hedgehog, and platelet-derived growth factor. Although primary ciliary dynamics have been reported to be closely related to ciliopathy and tumorigenesis, the molecular basis for the role of primary cilia in human disease is lacking. To clarify how Wnt3a affects primary ciliogenesis in anticancer drug-resistant cells, we derived specific drug-resistant subcell lines from A549 human lung cancer cells using anticancer drugs doxorubicin, dasatinib, and paclitaxel (A549/Dox, A549/Das, and A549/Pac, respectively). The primary cilia-containing cell population and primary cilia length increased in the A549/Dox and A549/Pac subcell lines under increased MDR1 expression, when compared to those in the parental A549 cells. In the A549/Das subcell line, primary cilia length increased but the cell population was not affected. In addition, Wnt3a increased primary cilia-containing cell population and primary cilia length in A549/Dox, A549/Das, and A549/Pac cells, without change of cell growth. Abnormal shapes of primary cilia were frequently observed by anticancer drug resistance and Wnt3a stimulation. Taken together, our results indicate that anticancer drug resistance and Wnt3a affect primary ciliogenesis synergistically, suggesting a potential new strategy for overcoming anticancer drug resistance.

Upregulation of human enhancer filamentation 1 (HEF1/NEDD9/Cas-L) and Polo-like kinase 1 (Plk1) is closely correlated with metastasis of human cancer. However, the mechanism by which the overexpression of HEF1 or Plk1 stimulates cancer metastasis and induces tumorigenesis remains enigmatic. In addition, the accumulation of HEF1 at the focal adhesion (FA) is known to be an essential event in cancer cell migration, but the mechanism of how HEF1 is targeted to the FA remains yet to be unveiled. This study was performed to elucidate the FA docking mechanism of HEF1 and to determine its effect on tumorigenesis. To confirm the effect of the kinase on HEF1 translocation, various expression-knockdown stable cell lines were generated using a lentivirus system, and the effect of the HEF1-Plk1 complex on tumorigenesis was confirmed using a xenograft mouse model. Here, we show that Wnt5a-dependent Plk1 binding to HEF1 is critically required for HEF1 translocation to the FA. We also confirmed that Plk1 and CK1δ activities essential for HEF1 translocation are induced by Wnt5a. Finally, we confirmed the induction of tumorigenesis by the HEF1-Plk1 complex in the xenograft mouse model. Our data collectively unveil the Wnt5a-CK1δ-HEF1-Plk1-FA remodeling pathway that governs HEF1 transportation to the FA to induce cell migration and tumorigenesis. This study sheds light on a mechanism underlying tumorigenesis and provides new strategies for anticancer therapy.

Protein arginylation is a critical regulator of a variety of biological processes. The ability to uncover the global arginylation pattern and its associated signaling pathways would enable us to identify novel disease targets. Here, we report the development of a tool able to capture the N-terminal arginylome. This tool, termed R-catcher, is based on the ZZ domain of p62, which was previously shown to bind N-terminally arginylated proteins. Mutating the ZZ domain enhanced its binding specificity and affinity for Nt-Arg. R-catcher pulldown coupled to LC–MS/MS led to the identification of 59 known and putative arginylated proteins. Among these were a subgroup of novel ATE1-dependent arginylated ER proteins that are linked to diverse biological pathways, including cellular senescence and vesicle-mediated transport as well as diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. This study presents the first molecular tool that allows the unbiased identification of arginylated proteins, thereby unlocking the arginylome and provide a new path to disease biomarker discovery. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03805-x.

Objective We report the results of pharmacogenomics-based antidepressant treatment (PGXt) results in treating treatment-resistant major depressive disorder (TRD) patients in real practice. Methods Nine patients were prescribed NeuropharmagenⓇ for selection of antidepressants for individual patient and their clinical outcomes were followed. Results After treatment by PGXt results from current antidepressants, substantial reduction of depressive symptoms was observed at some point and maintained during observation period in six patients. Conclusion Our case series potentially shows the clinical utility and benefit of PGXt for treatment of TRD patients.

Research and development of smart vessels has progressed significantly in recent years, and ships have become high-value technology-intensive resources. These ships entail high production costs and long-life cycles. Thus, modernized technical design, professional training, and aggressive maintenance are important factors in the efficient management of ships. With the continuing digital revolution, the industrial shipbuilding applicability of augmented reality (AR) and virtual reality (VR) technologies as well as related 3D system modeling and processes has increased. However, resolving the differences between AR/VR and real-world models remains burdensome. This problem is particularly evident when mapping various texture characteristics to virtual objects. To mitigate the burden and improve the performance of such technologies, it is necessary to directly define various texture characteristics or to express them using expensive equipment. The use of deep-learning-based CycleGAN, however, has gained attention as a method of learning and automatically mapping real-object textures. Thus, we seek to use CycleGAN to improve the immersive capacities of AR/VR models and to reduce production costs for shipbuilding. However, when applying CycleGAN’s textures to pipe structures, the performance is insufficient for direct application to industrial piping networks. Therefore, this study investigates an improved CycleGAN algorithm that can be specifically applied to the shipbuilding industry by combining a modified object-recognition algorithm with a double normalization method. Thus, we demonstrate that basic knowledge on the production of AR industrial pipe models can be applied to virtual models through machine learning to deliver low-cost and high-quality textures. Our results provide an on-ramp for future CycleGAN studies related to the shipbuilding industry.

Objective : To test clinical effectiveness and tolerability of Korean Red Ginseng augmentation (RGA) in major depressive disorder (MDD) patients with difficult-to-treat. Methods Thirty six patients were enrolled in this 6 weeks, prospective, clinical trial. Rating scales were MontgomeryAsberg Depression Rating Scale (MADRS), Patient Health Questionnaire-15, Clinical Global Impression-improvement (CGI-I), and Patient Satisfaction Score. The primary endpoint was a remission rate measured by MADRS score at the end of study (≤ 10). Clinical outcomes and tolerability were assessed at baseline, week 2, and week 6. Results Among 36 patients, 26 patients completed the study and 28 patients had post-baseline visit data. The remission rate by MADRS score was 39.3% (11/28) and 57.1% by CGI-I scores of 1 or 2 at the end of the study. The mean change of MADRS score was significantly decreased by 44.4% from baseline to the end of study. The most frequent adverse events were headache (7/28, 25.0%) during the study. Conclusion Our study indicates the putative effectiveness and tolerability of RGA for treating MDD with difficult-to-treat in clinical practice. However, adequately powered, randomized, controlled trials will be needed to confirm these results.

Objective There has been a lack of data regarding the usefulness and clinical characteristic between patients-treated with and without antidepressants (Pw/Pwo ADs). Methods One hundred and eighty inpatients were recruited and observed for a 6-month. The depressive, cognitive, daily activity, and motor symptoms were evaluated at baseline and tracked at month 6, with the use of rating scales including Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Global Deterioration Scale (GDS), modified Rankin Scale (MRS), modified Barthel Index (MBI), and Berg Balance Scale (BBS). Results Among 178 patients, 84 (47.2%) were treated with ADs. PwAD had numerically or significantly higher depressive cognitive, and motor symptoms along with daily activity impairment (8.3 point higher in BDI score, p < 0.001; 3.6 point lower in MMSE, p = 0.003; 0.8 point higher in GDS score, p = nonsignificant; 8.2 point lower in BBS score, p = 0.053, and 0.4 point higher in MBI score, p = nonsignificant) than PwoAD. Psychiatric consultation was also significantly higher in PwAD than in PwoAD (p < 0.001). The numbers need to treat for good clinical outcomes between PwAD and PwoAD were 5.8, 6.0, and 7.5, respectively, by MRS, MBI, and BBS scores. Conclusion Our findings suggest the potential utility of AD treatment and different clinical parameters between patients- treated with and without ADs. Adequately-powered and well-controlled further studies are mandatory to confirm and fully elaborate such association.

The importance of operations and maintenance (O&M) and piping inspection in shipbuilding and offshore plant industries has significantly increased recently. Therefore, this study proposes a system that uses augmented reality (AR) to support these operations. AR in O&M and inspection systems can increase work comprehension and efficiency by utilizing 3D graphics, instead of drawings, to describe specific work functions. To realize this improvement, the augmented model should correspond to the reality; if accurate registration is not achieved, it can disrupt the work functions. Therefore, marker-based AR is used to generate specific recognition objects and correct the location of the augmented model. However, owing to certain characteristics of the shipbuilding and offshore plant industries, the markers are likely to be damaged, and thus the cameras fail to clearly detect them. In this study, a 3D camera was used to generate a point cloud based on 3D image information. Accordingly, the area around the model to be detected was designated as the region of interest (ROI). Furthermore, it is difficult to support a high-end device environment because it is tested as a portable device that can be used in a working environment; therefore, superfluous data were removed by detecting the 3D edges in the ROI, thereby minimizing data operation. The scalability of this work was enhanced using the computer-aided design (CAD) file information extracted from the CAD tool (used in the shipbuilding industry) and converting it into a point cloud. The proposed system is expected to eliminate the issues related to understanding the O&M work by addressing registration errors that might occur in constrained environments and to improve the torsional phenomenon of the augmented models.

According to the Korea Radioactive Waste Agency’s (KORAD’s) medium and low level radioactive waste management implementation plan, the Domestic 3rd Step Landfill Disposal Facility has planned to accept a total of 104,000 drums (2 trenches) of very low level radioactive waste (VLLW), from the decommissioning site from April 2019 - February 2026 (total budget: 224.6 billion Won). Subsequently, 260,000 drums (5 trenches) will be disposed in a 34,076 m2. Accordingly, KORAD is preparing a waste acceptance criteria (WAC) for this facility. Every disposal facility for VLLW in other countries such as France and Spain, operate their WAC for each VLLW facility with a reasonable application approach, This, paper focuses on analyzing the WAC conditions in VLLW sites in the USA and discusses whether these can be met in domestic VLLW WAC. It also helps in the preparation of WAC for the 3rd Step Landfill Disposal Site in Gyeongju, since the USA has prior experience on decommissioning nuclear waste.

This study aimed to enhance the stability and security of power plant control network systems by developing detectable models using artificial intelligence machine learning techniques. Due to the closed system operation policy of facility manufacturers, it is challenging to detect and respond to security threats using standard security systems. With the increasing digitization of control systems, the risk of external malware penetration is also on the rise. To address this, machine learning techniques were applied to extract patterns from network traffic data produced at an average of 6.5 TB per month, and fingerprinting was used to detect unregistered terminals accessing the control network. By setting a threshold between transmission amounts and attempts using one month of data, an anomaly judgment model was learned to define patterns of data communication between the origin and destination. The hypothesis was tested using machine learning techniques if a new pattern occurred and no traffic occurred. The study confirmed that this method can be applied to not only plant control systems but also closed-structured control networks, where availability is critical, and other industries that use large amounts of traffic data. Experimental results showed that the proposed model outperformed existing models in terms of detection efficiency and processing time.

Background and Objectives: We investigated and compared the efficacy of three and five monthly loading regimens of an intravitreal aflibercept injection (IVA) in patients with diabetic macular edema (DME). Materials and Methods: This was a retrospective study that included patients diagnosed with DME and treated with an either three or five monthly aflibercept loading regimen from July 2018 to March 2022. Information on clinical characteristics and changes in the central retinal thickness (CRT) were obtained from medical records. Results: In total, 44 eyes of 44 patients with DME treated with IVA were included in this study, with 30 eyes treated with 3-monthly loadings (three-loading group) and 14 eyes with 5-monthly loadings (five-loading group). The mean CRT significantly decreased from the baseline one month after loading in both the three-loading and five-loading groups (p < 0.001). Four cases were refractory to treatment in the three-loading group, while there were no cases of refractory DME in the five-loading group. The stability rate was significantly higher in the five-loading group at three months after loading (p = 0.033). Conclusions: Five-monthly loading regimens of IVA might be favorable for DME considering the rate of refractory cases, stable duration, and the importance of early responsiveness to IVA in DME.

Background To investigate the safety of vitrectomy with laser photocoagulation in eyes with small peripheral retinal breaks without air or gas tamponade. Methods Among patients who underwent vitrectomy for various retinal disorders, those with small peripheral retinal breaks treated by laser photocoagulation without air or gas tamponade were included in this study. Their medical records were assessed retrospectively, and we investigated the characteristics of small peripheral retinal breaks and the incidence of postoperative retinal detachment (RD). Results Thirty-one eyes of 31 patients who presented with small peripheral retinal breaks requiring endolaser photocoagulation during vitrectomy were included in this analysis. There were two cases of iatrogenic retinal breaks that occurred during vitrectomy, while others were preexisting lesions, including retinal tears, atrophic retinal holes, and retinal holes with lattice degeneration. There were no cases of RD during the follow-up period of at least 6 months. Conclusions Adequate laser treatment without gas or air tamponade may be sufficient during vitrectomy in cases with small peripheral retinal breaks without concurrent RD, along with complete removal of vitreoretinal traction.

β‐Catenin is a multifunctional protein and participates in numerous processes required for embryonic development, cell proliferation, and homeostasis through various molecular interactions and signaling pathways. To date, however, there is no direct evidence that β‐catenin contributes to cytokinesis. Here, we identify a novel p‐S60 epitope on β‐catenin generated by Plk1 kinase activity, which can be found at the actomyosin contractile ring of early telophase cells and at the midbody of late telophase cells. Depletion of β‐catenin leads to cytokinesis‐defective phenotypes, which eventually result in apoptotic cell death. In addition, phosphorylation of β‐catenin Ser60 by Plk1 is essential for the recruitment of Ect2 to the midbody, activation of RhoA, and interaction between β‐catenin, Plk1, and Ect2. Time‐lapse image analysis confirmed the importance of β‐catenin phospho‐Ser60 in furrow ingression and the completion of cytokinesis. Taken together, we propose that phosphorylation of β‐catenin Ser60 by Plk1 in cooperation with Ect2 is essential for the completion of cytokinesis. These findings may provide fundamental knowledge for the research of cytokinesis failure‐derived human diseases., Phosphorylation of β‐catenin Ser60 by Plk1 in cooperation with Ect2 induces RhoA activation and mediates the progression of furrow ingression and subsequent cytokinesis steps.

The transfer characteristics of the three different CMOS image sensor (CIS) pixel schemes; the vertical transfer gate (VTG) with the front-side deep trench isolation (FDTI), the VTG with the back-side deep trench isolation (BDTI), and the planar transfer gate (PTG) with the BDTI are rigorously studied with 3D TCAD simulation. The electrical potential profiles of photo-diode (PD) region are optimized in terms of full well capacity (FWC) and transfer characteristics for each scheme. The simulated blooming margin potentials are well matched to the experimental blooming signal. According to our TCAD analysis, the VTG with the FDTI scheme showed high full FWC characteristics compared to the PTG with the BDTI and the VTG with the BDTI.

Due to the global economic downturn and low oil prices, orders for offshore plants and vessels have declined. Moreover, the range of regulations has increased and customer requirements have...

We developed a dual pixel with accurate and all-directional auto focus (AF) performance in CMOS image sensor (CIS). The optimized in-pixel deep trench isolation (DTI) provided accurate AF data and good image quality in the entire image area and over whole visible wavelength range. Furthermore, the horizontal-vertical (HV) dual pixel with the slanted in-pixel DTI enabled the acquisition of all-directional AF information by the conventional dual pixel readout method. These technologies were demonstrated in 1.4μm dual pixel and will be applied to the further shrunken pixels.

Upregulation of human enhancer filamentation 1 (HEF1/NEDD9/Cas-L) and Polo-like kinase 1 (Plk1) is closely correlated with metastasis of human cancer. However, the mechanism by which the overexpression of HEF1 or Plk1 stimulates cancer metastasis and induces tumorigenesis remains enigmatic. In addition, the accumulation of HEF1 at the focal adhesion (FA) is known to be an essential event in cancer cell migration, but the mechanism of how HEF1 is targeted to the FA remains yet to be unveiled.This study was performed to elucidate the FA docking mechanism of HEF1 and to determine its effect on tumorigenesis.To confirm the effect of the kinase on HEF1 translocation, various expression-knockdown stable cell lines were generated using a lentivirus system, and the effect of the HEF1-Plk1 complex on tumorigenesis was confirmed using a xenograft mouse model.Here, we show that Wnt5a-dependent Plk1 binding to HEF1 is critically required for HEF1 translocation to the FA. We also confirmed that Plk1 and CK1δ activities essential for HEF1 translocation are induced by Wnt5a. Finally, we confirmed the induction of tumorigenesis by the HEF1-Plk1 complex in the xenograft mouse model.Our data collectively unveil the Wnt5a-CK1δ-HEF1-Plk1-FA remodeling pathway that governs HEF1 transportation to the FA to induce cell migration and tumorigenesis. This study sheds light on a mechanism underlying tumorigenesis and provides new strategies for anticancer therapy.

Background and Objectives: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker used to predict heart failure and evaluate volume status in hemodialysis (HD) patients. However, it is difficult to determine the cutoff value for NT-proBNP in HD patients. In this study, we analyzed whether NT-proBNP helps predict heart function and volume status in HD patients. Materials and Methods: This prospective observational study enrolled 96 end-stage kidney disease patients with HD. All patients underwent echocardiography and bioimpedance spectroscopy (BIS) after an HD session. Overhydration (OH) was measured by BIS. Laboratory data were obtained preHD, while serum NT-proBNP was measured after HD. Interventions for blood pressure control and dry weight control were performed, and NT-proBNP was re-assessed after a month. Results: There was an inverse correlation between NT-proBNP and ejection fraction (EF) (β = −0.34, p = 0.001). OH (β = 0.331, p = 0.001) and diastolic dysfunction (β = 0.226, p = 0.027) were associated with elevated NT-proBNP. In a subgroup analysis of diastolic dysfunction grade, NT-proBNP increased according to dysfunction grade (normal, 4177 pg/mL [2637–10,391]; grade 1, 9736 pg/mL [5471–21,110]; and grades 2–3, 26,237 pg/mL [16,975–49,465]). NT-proBNP showed a tendency toward a decrease in the ‘reduced dry weight’ group and toward an increase in the ‘increased dry weight’ group compared to the control group (ΔNT-proBNP, −210 pg/mL [−12,899 to 3142], p = 0.104; 1575 pg/mL [−113 to 6439], p = 0.118). Conclusions: We confirmed that NT-proBNP is associated with volume status as well as heart function in HD patients.

Incorporating different wavelength (400 to 1000nm) LEDs, photoplethysmography (PPG) sensors allow wearable devices to monitor various health parameters such as heart rate (HR), oxygen saturation (SpO 2 ), and blood pressure (BP). Nowadays, PPG sensing technology at the wrist is well established. To cope with the large degree of motion turbulence presented at the wrist, PPG sensors use Green (Gr) LEDs together with multiple photodiodes (PD), and they are driven by wide-dynamic-range (DR) current-sensing front-ends [1]. It is attractive to use a near-infra-red (nIR) PPG sensor in a True Wireless Stereo (TWS), as the ear provides the best site to measure heart rhythm (more blood flow, constant distance from the heart, and less motion than at the finger or wrist). However, TWS requires a PPG sensor that is more stringent on size and power consumption (shown in Fig. 28.2.1). A promising solution [2, 3] is integrating an array of PDs with an ADC to dramatically reduce power while also providing monolithic integration. However, the limited DR (

Purpose: The objective of this study was to improve the three-dimensional (3D) understanding of optimal lateral cortical hinge in medial open-wedge high tibial osteotomy (MOWHTO) via a computational cadaveric simulation of actual size. Methods: The computed tomography data of 117 adult cadavers were imported into Mimics® software to design 3D models of tibia and fibula. To simulate the MOWTHO, a virtual cutting plane was developed inside the safe zone based on established landmarks. After splitting and distracting through the cutting plane, the 10-mm cylinder (Ø 30 mm; height 10 mm) was placed vertically to be occupied properly in the nonosteotomized lateral cortex. The cross points between the round cylinder and cutting plane represented the anterior and posterior hinge points, which were used to validate the 3D position and direction of cortical hinge. Results: A 10-mm cylinder did not violate the proximal tibiofibular joint (PTFJ) and the protruding segment of the condylar area was less than 2 mm in 115 models. The connecting line between anterior and posterior hinge points was an average of 12.1° (range 0–24.1°, SD 4.64) to the lateral side. In the nonoverlapping anteroposterior projection between proximal fibula and tibia, the posterior hinge point was laid over the PTFJ as close as possible. Based on free 360° rotation and magnification without any tilt, no posterior cortical disruption of PTFJ was observed while securing a minimum width of 10 mm. Conclusion: If the posterior hinge point was placed immediately above the PTFJ without involvement, the nonosteotomized portion carried sufficient width greater than 10 mm, despite lateral rotation at an average hinge direction of 12.1°.

Signal amplification is a key step that determines the sensitivity of molecular assays. Although studies on aptamers have mostly focused on their target-binding ability, taking advantage of the gene-coding function of nucleic acids, we demonstrate here that aptamers can be engineered into diagnostic reagents that can both recognize a target and generate highly amplified detection signals. We developed a strategy that employs a ‘readable’ aptamer that consists of a single-stranded aptamer and a double-stranded reporter gene. After binding to its target via the aptamer region, the reporter gene of the readable aptamer produces amplified number of signal-generating enzymes through a subsequent in vitro expression reaction. In contrast to conventional enzyme-conjugation methods, this method allows the generation of far more amplified detection signals, thereby markedly increasing the sensitivity of detection enough to analyze a target present in aM concentrations.

We developed a simple and rapid method for analyzing nonproteinogenic amino acids that does not require conventional chromatographic equipment. In this technique, nonproteinogenic amino acids were first converted to a proteinogenic amino acid through in vitro metabolism in a cell extract. The proteinogenic amino acid generated from the nonproteinogenic precursors were then incorporated into a reporter protein using a cell-free protein synthesis system. The titers of the nonproteinogenic amino acids could be readily quantified by measuring the activity of reporter proteins. This method, which combines the enzymatic conversion of target amino acids with translational analysis, makes amino acid analysis more accessible while minimizing the cost and time requirements. We anticipate that the same strategy could be extended to the detection of diverse biochemical molecules with clinical and industrial implications.

The primary cilium is a non-motile microtubule-based structure, which functions as an antenna-like cellular sensing organelle. The primary cilium is assembled from the basal body, a mother centriole-based structure, during interphase or a quiescent cell stage, and rapidly disassembles before entering mitosis in a dynamic cycle. Defects in this ciliogenesis dynamics are associated with human diseases such as ciliopathy and cancer, but the molecular mechanisms of the ciliogenesis dynamics are still largely unknown. To date, various cellular signaling pathways associated with primary cilia have been proposed, but the main signaling pathways regulating primary cilia assembly/disassembly remain enigmatic. This review describes recent findings in Wnt-induced primary cilia assembly/disassembly and potential future directions for the study of the cellular signaling related to the primary ciliogenesis dynamics.

Background and Aims Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. Method We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with IgA nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time×group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Results Compared to the MHC group, the MGA and IgAN groups displayed differences in the time×group effects of eGFR (Figure 1), higher mean annual rates of eGFR decline (Table), and higher urinary mtDNA copy numbers (Figure 2); however, these groups did not significantly differ from each other. Conclusion The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

We compared the abilities of several ATP regeneration systems to support the production of soluble proteins in a cell-free synthesis system. While changes in the ATP level in the reaction mixture were variable depending on the ATP regeneration system employed, the yields and solubilities of synthesized proteins did not always correlate with the ATP level. Instead, the efficiency of cell-free protein synthesis was substantially affected by changes in the pH of the reaction mixture. These results suggest that measures to maintain the pH of the reaction mixture should be considered when choosing an energy source for cell-free protein synthesis.

An expression immunoassay is a powerful technique that combines unique features of immunosorbent assays and cell-free protein synthesis. The main advantage of the expression immunoassay is a greatly amplified signal, whereas a conventional enzyme-linked immunosorbent assay (ELISA) employs a single enzyme molecule conjugated to a detection antibody to produce a measurable signal. Expression immunoassays utilize a DNA molecule conjugated to a target-bound antibody to generate multiple enzyme molecules that then produce the signal. To date, expression immunoassays have not been widely adopted due to the limited availability of efficient methods for translating antibody-conjugated DNA. We developed a highly efficient translation module for expression immunoassays using an Escherichia coli extract-based cell-free protein synthesis system. When we used our immunoassay technique to detect α-fetoprotein, we achieved a limit of detection of 7 fM. Given the outstanding sensitivity that can be obtained with only minimal modifications to the procedure of standard ELISA, we believe that this method will open up new possibilities for widespread application of expression immunoassays to ultrasensitive detection and diagnostics.

The objective of the present study is to provide a databank and comprehensible design equations for the shrinkage strain curve of lightweight aggregate concrete (LWAC) by using artificially expanded bottom ash and dredged soil granules. A total of 25 concrete mixtures were prepared with regard to the parameters of the substitution level of natural sand for lightweight fine aggregates and water-to-cement ratios. Based on the experimental observations, the time function, and 91-day shrinkage strain as a specific point were formulated by introducing the parameter of an equivalent porosity of aggregates to rationally evaluate the shrinkage strain curve of LWAC. Test results showed that the amount of shrinkage strain at 28 days ranged between 39% and 55% of that measured at 210 days, indicating that the acceleratory period was delayed due to the internal curing effect of lightweight aggregates. The shrinkage strains of LWAC decreased in proportion to the equivalent porosity ( P eq ) of aggregates, showing that the decreasing rates of the shrinkage strains ranged between 16% and 36% at 3 days, and 21% and 23% at 180 days when P eq value increased from 21.8% to 42.9%. For the proposed equations, the mean and standard deviation of the normalized root-mean-square error values between experiments and predictions are 0.44 and 0.21, respectively, resulting in a better accuracy than the code models (fib 2010 and EC 2) of which comparisons resulted in high overestimation, especially at an early age.

The open nature of cell-free synthesis allows customization of the reaction conditions for given target molecules using diverse biological and non-biological substances. This study demonstrates that non-ionic detergents can be used to enhance translation during the synthesis of peptides in a cell-free system derived from an Escherichia coli extract. The yield of the antimicrobial peptide Cecropin P1 was markedly increased in the presence of detergents. The stimulatory effect of detergents was not limited to the Cecropin P1 peptide, but the detergent also enhanced the translation of other antimicrobial peptides. Furthermore, the enhanced translation rate by detergents was maintained for extended periods by a continuous exchange cell-free synthesis reaction, leading to production of antimicrobial peptides with markedly improved yields.

In this study, we demonstrate the conversion of starch to (R,R)-2,3-butanediol (2,3-BD) in a hybrid cell-free synthesis system containing a mixture of lysates derived from Escherichia coli (E. coli) and cyanobacteria. A sufficient pool of pyruvate required for the synthesis of 2,3-BD was generated by combining metabolic pathways of cyanobacteria and E. coli. Successful synthesis of 2,3-BD was achieved by additional modifications of the hybrid cell-free system with the enzymes required to convert pyruvate to 2,3-BD. The results demonstrate a new approach to harness biological pathways to expand the scope of cell-free metabolic engineering by cross-species combinations of cell lysates.