Flowmicro in-Line Analysis-Driven Design of Reactions Mediated by Unstable Intermediates: Flash Monitoring Approach.

Invited for the cover of this issue is the group of Aiichiro Nagaki, Yosuke Ashikari and co-workers at Hokkaido University. The image depicts flash monitoring of reactive intermediate in a flow microreactor. Read the full text of the article at 10.1002/chem.202303774.

Flowmicro In-Line Analysis-Driven Design of Reactions Mediated by Unstable Intermediates: Flash Monitoring Approach.

The direct observation of reactive intermediates is an important issue for organic synthesis. However, intermediates with an extreme instability are hard to be monitored by common spectroscopic methods such as FTIR. We have developed synthetic method utilizing flow microreactors, which enables a generation and reactions of unstable intermediates. Herein we report that, based on our flowmicro techniques, we developed an in-line analysis method for reactive intermediates in increments of milliseconds. We demonstrated the direct observation of the living and dead species of the anionic polymerization of alkyl methacrylates. The direct information of the living species enabled the anionic polymerization and copolymerization of oligo(ethylene glycol) methyl ether methacrylates, which is the important but difficult reaction in the conventional method.

Enhanced Light Harvesting in Photovoltaic Devices Using an Edge-Located One-Dimensional Grating Polydimethylsiloxane Membrane.

In streamlined multipurpose applications for light management and protection, encapsulants are merged with photonic crystal structures into solar modules. We present an edge-located 1D grating, attachable polymer on the top of a photovoltaic module to provide a strategy for capturing solar light and improving cell efficiency. Large-area solar arrays suffer from space utilization problems due to nonactive area. The introduction of periodically patterned gratings with specific geometric range is highly preferred to redirect the light toward photovoltaic active areas. To realize optimized broadband light diffraction for solar devices, the theoretical analysis of one-dimensional line patterned diffraction gratings was performed through wave-optic-based simulation. Based on the experimental results, the replica molding-based patterning method was adopted to fabricate the grating polymer for low-cost thin-film production. Also, we demonstrated enhanced light collection by grating patterned encapsulants with improved current density in comparison to the performance of a flat surface.

Toward the Synthesis of Yuzurimine-Type Alkaloids: Stereoselective Construction of the Heterocyclic Portions of Deoxyyuzurimine and Macrodaphnine.

The heterocyclic portions of yuzurimine-type alkaloids, such as deoxyyuzurimine and macrodaphnine, were synthesized by using a stereoselective hydroboration-oxidation reaction to install the C20 methyl group, the intramolecular Mitsunobu reaction to construct the E-ring portion, and the intramolecular SN2 reaction to construct the F-ring portion as key steps.

Reflective color filter with precise control of the color coordinate achieved by stacking silicon nanowire arrays onto ultrathin optical coatings.

The engineering of structural colors is currently a promising, rapidly emerging research field because structural colors of outstanding spatial resolution and durability can be generated using a sustainable production method. However, the restricted and saturated color range in micro/nano-fabricated structural 'pigments' has hindered the dissemination of structural color printing. Here, this article presents a spectral mixing color filter (SMCF), which is the concept of fine-tunable color systems, capable of addressing the current issues in structural color engineering, by stacking a vertical silicon nanowire array embedded in a transparent polymer onto ultrathin optical coating layers. These two photonic structures enable independent tuning the optical resonance of each structure, depending on geometrical parameters, such as the diameter of nanowires and thickness of absorbing medium. Hence, the SMCF facilitates the linear combination of two resonant spectra, thereby enabling fine-tuning and widening of the color gamut. Theoretical studies and experimental results reveal the detailed working mechanisms and extraordinary mechanical feature of the SMCF. Based on the analyses, the concept of flexible optical device, e.g., a reflective anti-counterfeiting sticker, is demonstrated. Successful characterization demonstrates that the proposed strategy can promote the color controllability/purity of structural color and the applicability as flexible optical device.

Enlarged Color Gamut Representation Enabled by Transferable Silicon Nanowire Arrays on Metal-Insulator-Metal Films.

Artificial structural colors arising from nanosized materials have drawn much attention because of ultrahigh resolution, durability, and versatile utilizations compared to conventional pigments and dyes. However, the limited color range with current approaches has interrupted the supply for upcoming structural colorimetric applications. Here, we suggest a strategy for the widening of the color gamut by linear combination of two different resonance modes originating from silicon nanowire arrays (Si NWAs) and metal-insulator-metal nanoresonators. The enlarged color gamut representations are simply demonstrated by transferring Si NWAs embedded in a flexible polymer layer without additional treatment/fabrication. Optical simulation is used to verify the additive creation of a new resonance dip, without disturbing the original mode, and provides "predictable" color reproduction. Furthermore, we prove that the proposed structures are applicable to well-known semiconductor materials for various flexible optical devices and other colorant applications.

Thermo-optic control of the longitudinal radiation angle in a silicon-based optical phased array.

We demonstrate longitudinal beam-steering with a 1×16 silicon optical phased array (OPA) using a monochromatic light source and thermo-optic control of the refractive index in the grating radiator region. The refractive index is controlled by forming a series of n-i-n heaters, placing i-regions in each radiator of the OPA. When the biased voltage in the heaters is increased, the refractive index of the radiator region is increased by the thermo-optic effect, and the longitudinal radiation angle is changed according to the Bragg condition. The transversal beam-steering is accomplished by phase control with the phase shifters, which are devised with a p-i-n diode using the electro-optic effect. With these electro-optic p-i-n phase shifters and n-i-n thermo-optic radiators, we achieve a relatively wide 2D beam-steering in a range of 10.0°/45.4° in the longitudinal/transversal directions with a 1.55 µm light source. The tuning efficiency is 0.016°/mW in the longitudinal beam-steering.

Fabrication of Flexible, Redoxable, and Conductive Nanopillar Arrays with Enhanced Electrochemical Performance.

Highly ordered and flexible nanopillar arrays have received considerable interest for many applications of electrochemical devices because of their unique mechanical and structural properties. Here, we report on highly ordered polyoxometalate (POM)-doped polypyrrole (Ppy) nanopillar arrays produced by soft lithography and subsequent electrodeposition. As-prepared POM-Ppy/nanopillar films show superior electrochemical performances for pseudocapacitor and enzymeless electrochemical sensor applications and good mechanical properties, which allowed them to be easily bent and twisted. Regarding electrochemical characteristics for pseudocapacitive electrodes, the POM-Ppy/nanopillar electrodes are capable of delivering high areal capacitance of 77.0 mF cm(-2), high rate performance, and good cycle life of ∼100% retention over 3500 cycles even when bent. Moreover, the study suggests that the POM-Ppy/nanopillar electrodes have an excellent electrocatalytic activity toward hydrogen.

Moth-Eye TiO2 Layer for Improving Light Harvesting Efficiency in Perovskite Solar Cells.

A moth-eye nanostructured mp-TiO2 film using conventional lithography, nano-imprinting and polydimethyl-siloxane (PDMS) stamping methods is demonstrated for the first time. Power conversion efficiency of the moth-eye patterned perovskite solar cell is improved by ≈11%, which mainly results from increasing light harvesting efficiency by structural optical property.

Nanopillar films with polyoxometalate-doped polyaniline for electrochemical detection of hydrogen peroxide.

Design and fabrication of electrodes is key in the development of electrochemical sensors with superior electrochemical performances. Herein, an enzymeless electrochemical sensor is developed for detection of hydrogen peroxide based on the use of highly ordered polyoxometalate (POM)-doped polyaniline (PANI) nanopillar films. The electrodeposition technique enables the entrapment of POMs into PANI during electropolymerization to produce thin coatings of POM-PANI. Electrochemical investigations of the POM-PANI/nanopillar electrode showed well-defined multiple pairs of redox peaks and rapid electron transfer. The nanopillar structure facilitated the diffusion of the electrolyte and thus, enhanced the redox reaction. In particular, the POM-PANI/nanopillar electrode was incorporated into a flow injection biosensor and it demonstrates its electrocatalytic activity to detect hydrogen peroxide with high sensitivity, rapid response time, and low detection limit.

Sagittal abdominal diameter is an independent predictor of all-cause and cardiovascular mortality in incident peritoneal dialysis patients.

BACKGROUNDS AND AIMS: Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients. METHODS: We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients. RESULTS: The mean SAD was 24.5 ± 4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514-7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005-1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994-32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007-1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥ 24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m(2)). CONCLUSIONS: SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.

High throughput ultralong (20 cm) nanowire fabrication using a wafer-scale nanograting template.

Nanowires are being actively explored as promising nanostructured materials for high performance flexible electronics, biochemical sensors, photonic applications, solar cells, and secondary batteries. In particular, ultralong (centimeter-long) nanowires are highly attractive from the perspective of electronic performance, device throughput (or productivity), and the possibility of novel applications. However, most previous works on ultralong nanowires have issues related to limited length, productivity, difficult alignment, and deploying onto the planar substrate complying with well-matured device fabrication technologies. Here, we demonstrate a highly ordered ultralong (up to 20 cm) nanowire array, with a diameter of 50 nm (aspect ratio of up to 4,000,000:1), in an unprecedented large (8 in.) scale (2,000,000 strands on a wafer). We first devised a perfectly connected ultralong nanograting master template on the whole area of an 8 in. substrate using a top-down approach, with a density equivalent to that achieved with e-beam lithography (100 nm). Using this large-area, ultralong, high-density nanograting template, we developed a fast and effective method for fabricating up to 20 cm long nanowire arrays on a plastic substrate, composed of metal, dielectric, oxide, and ferroelectric materials. As a suggestion of practical application, a prototype of a large-area aluminum wire grid polarizer was demonstrated.

Leptin/adiponectin ratio is an independent predictor of mortality in nondiabetic peritoneal dialysis patients.

BACKGROUND: The leptin/adiponectin (L/A) ratio has been suggested to be an atherosclerotic index for diabetic patients and a useful marker of insulin resistance in patients with and without diabetes. Even though end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) are well characterized by abnormal adipocytokine metabolism, the significance of alterations in the L/A ratio is largely unexplored in these patients. In this prospective study, we investigated the associations of leptin, adiponectin, and the L/A ratio with clinical outcomes in nondiabetic PD patients. METHODS: The study included 131 stable nondiabetic ESRD patients who had been on PD for more than 3 months. Serum leptin and adiponectin levels were determined at baseline. Mortality was evaluated over a 5-year follow-up period. RESULTS: During the follow-up period, 22 patients died (16.8%), including 10 (45.5%) as a result of cardiovascular disease. The L/A ratio showed a significant positive correlation with body mass index [BMI (r = 0.47, p < 0.001)], high-sensitivity C-reactive protein (r = 0.32, p < 0.001), and triglycerides (r = 0.43, p < 0.001). In addition, we observed significant inverse correlations between the L/A ratio and percentage lean body mass (r = -0.30, p = 0.001) and high-density lipoprotein cholesterol (r = -0.31, p = 0.001). In contrast to individual leptin and adiponectin levels, the L/A ratio was found to be independently associated with an increased mortality risk (relative risk: 1.15; 95% confidence interval: 1.05 to 1.27; p = 0.003) even after adjustments for age and BMI. CONCLUSIONS: The L/A ratio might be better related to patient outcomes than adipocytokines are individually in nondiabetic patients undergoing PD.

Progression of aortic arch calcification over 1 year is an independent predictor of mortality in incident peritoneal dialysis patients.

BACKGROUNDS AND AIMS: The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients. METHODS: We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients. RESULTS: Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336-3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577-8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150-5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079-14.890, P = 0.038) in patients with AoAC at baseline. CONCLUSIONS: The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.

Clinical outcomes, when matched at presentation, do not vary between adult-onset Henöch-Schönlein purpura nephritis and IgA nephropathy.

Henöch-Schönlein purpura nephritis (HSPN) is considered a systemic form of immunoglobulin A nephropathy (IgAN). Although these are different pictures of a single disease, there are no studies directly comparing long-term outcomes of these two clinical entities. To clarify this, we studied 120 patients with biopsy-proven HSPN and 1070 patients with IgAN. The primary outcome was the composite of a doubling of baseline serum creatinine, end-stage renal disease, or death. Secondary outcomes included the individual renal outcomes or the rate of decline in estimated glomerular filtration rate. In the unmatched cohort, patients with HSPN had more vasculitic symptoms, more favorable histologic features, and were more commonly treated with steroids than patients with IgAN. The risk of reaching the primary outcome was significantly lower in HSPN patients than patients with IgAN (hazard ratio, 0.67). The 1:2 propensity score matching gave matched pairs of 89 patients with HSPN and 178 patients with IgAN, resulting in no differences in baseline conditions. In this matched cohort, there were no significant differences in reaching the primary and secondary outcomes between the two groups. Thus, after adjustment by propensity score matching, clinical outcomes did not differ between HSPN and IgAN, suggesting the two forms of the same disease have a similar prognosis.

Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy.

BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr). RESULTS: Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04). CONCLUSIONS: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.

Removal of kidney stones by extracorporeal shock wave lithotripsy is associated with delayed progression of chronic kidney disease.

PURPOSE: This study aimed to elucidate whether stone removal by extracorporeal shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease (CKD) progression. MATERIALS AND METHODS: We conducted a retrospective analysis of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline clinical and laboratory data, kidney stone characteristics, and history of receiving ESWL. We classified study patients into two groups according to whether they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with those of ESWL group before undergoing ESWL. In the next step, we sought to compare annual eGFR changes in the same patients before and after ESWL. Finally, we compared annual eGFR changes between success and failure groups among patients undergoing ESWL. RESULTS: The mean age of the patients was 62 years and 72.5% were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL group before undergoing ESWL showed similar annual eGFR changes (-1.75±6.5 vs. -1.63±7.2 mL/min/1.73 m²/year, p=0.425). However, eGFR declined slower after undergoing ESWL than before ESWL (annual eGFR changes, -0.29±6.1 vs. -1.63±7.2 mL/min/1.73 m²/year, p<0.05). In addition, among patients in ESWL group, eGFR declined faster in the failure group than in the success group (annual eGFR change, -1.01±4.7 vs. -0.05±5.2 mL/min/1.73 m²/year, p<0.05). CONCLUSION: Our results suggest that stone removal by ESWL is associated with delayed deterioration of renal function in CKD patients with nephrolithiasis.

Low circulating adiponectin levels are associated with insulin resistance in non-obese peritoneal dialysis patients.

In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m(2). IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m(2). When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR ≤1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (γ = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (γ = -0.250, P = 0.050) and positively correlated with age (γ = 0.334, P = 0.008) and triglyceride (γ = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (ß = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD.

Electrocardiographic left ventricular hypertrophy and outcome in hemodialysis patients.

BACKGROUND AND AIMS: Electrocardiography (ECG) is the most widely used initial screening test for the assessment of left ventricular hypertrophy (LVH), an independent predictor of cardiovascular mortality in patients with end-stage renal disease (ESRD). However, traditional ECG criteria based only on voltage to detect LVH have limited clinical utility for the detection of LVH because of their poor sensitivity. METHODS: This prospective observational study was undertaken to compare the prognostic significance of commonly used ECG criteria for LVH, namely Sokolow-Lyon voltage (SV) or voltage-duration product (SP) and Cornell voltage (CV) or voltage-duration product (CP) criteria, and to investigate the association between echocardiographic LV mass index (LVMI) and ECG-LVH criteria in ESRD patients, who consecutively started maintenance hemodialysis (HD) between January 2006 and December 2008. RESULTS: A total of 317 patients, who underwent both ECG and echocardiography, were included. Compared to SV and CV criteria, SP and CP criteria, respectively, correlated more closely with LVMI. In addition, CP criteria provided the highest positive predictive value for echocardiographic LVH. The 5-year cardiovascular survival rates were significantly lower in patients with ECG-LVH by each criterion. In multivariate analyses, echocardiographic LVH [adjusted hazard ratio (HR): 11.71; 95% confidence interval (CI): 1.57-87.18; P = 0.016] and ECG-LVH by SP (HR: 3.43; 95% CI: 1.32-8.92; P = 0.011) and CP (HR: 3.07; 95% CI: 1.16-8.11; P = 0.024) criteria, but not SV and CV criteria, were significantly associated with cardiovascular mortality. CONCLUSIONS: The product of QRS voltage and duration is helpful in identifying the presence of LVH and predicting cardiovascular mortality in incident HD patients.

Immunoglobulin A nephropathy associated with Plasmodium falciparum malaria.

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.