An amphiphilic material arginine-arginine-bile acid promotes α-synuclein amyloid formation.

Amyloid generation plays essential roles in various human diseases, biological functions, and nanotechnology. However, developing efficient chemical and biological candidates for regulating amyloid fibrillation remains difficult because information on the molecular actions of modulators is insufficient. Thus, studies are needed to understand how the intermolecular physicochemical properties of the synthesised molecules and amyloid precursors influence amyloidogenesis. In this study, we synthesised a novel amphiphilic sub-nanosized material, arginine-arginine (RR)-bile acid (BA), by conjugating positively charged RR to hydrophobic BA. The effects of RR-BA on amyloid formation were investigated on α-synuclein (αSN) in Parkinson's disease and on K18 and amyloid-ß (1-42) (Aß42) in Alzheimer's disease. RR-BA showed no appreciable effect on the kinetics of K18 and Aß42 amyloid fibrillation because of their weak and non-specific interactions. However, RR-BA specifically bound to αSN with moderate binding affinity through electrostatic interactions between the positively charged RR and the negatively charged cluster in the C-terminus of αSN. In addition, hydrophobic BA in the αSN-RR-BA complex transiently condensed αSN for primary nucleation, thereby accelerating αSN amyloid fibrillation. We propose an electrostatic binding and hydrophobic condensation model of RR-BA-driven amyloid formation of αSN, which will contribute to the rational design and development of molecules for controlling amyloid aggregation in diverse fields.

Bean Extract-Based Gargle for Efficient Diagnosis of Active COVID-19 Infection Using Rapid Antigen Tests.

The antigen-based rapid diagnostic test (Ag-RDT) using saliva specimens is fast, noninvasive, and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing. We evaluated a novel Beanguard gargle (BG)-based virus collection method that can be applied to Ag-RDT as an alternative to the current RT-PCR with an NPS for early diagnosis of COVID-19. This clinical trial comprised 102 COVID-19-positive patients hospitalized after a governmental screening process and 100 healthy individuals. Paired NPS and BG-based saliva specimens from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs, whose diagnostic performance for detecting SARS-CoV-2 was compared. BG-Ag-RDTs showed high sensitivity (97.8%) and specificity (100%) in 45 patients within 6 days of illness and detected all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic active COVID-19 cases, both BG-Ag-RDTs and BG-RT-PCR showed sensitivities and specificities of 100%. Sensitivities of BG-Ag-RDT and BG-RT-PCR toward salivary viral detection were highly concordant, with no discrimination between symptomatic (97.0%), asymptomatic (100%), or SARS-CoV-2 variant (100%) cases. The intermolecular interactions between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from the bean extract (BE), were observed in terms of physicochemical properties. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis. Using BG-based saliva specimens remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables noninvasive, rapid, and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management. IMPORTANCE An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness. The method represents an attractive alternative to nasopharyngeal swabs for the early diagnosis of symptomatic and asymptomatic COVID-19 cases. The evidence suggests that the method could have a potential for mass screening and monitoring of COVID-19 cases.

Treatment outcomes and complications in FIGO stage IIIC and IVB endometrioid endometrial cancer patients presenting as nodal spreads following systematic lymphadenectomy and adjuvant therapy.

OBJECTIVE: To evaluate the treatment outcomes and complications of patients with FIGO stage IIIC and IVB endometrioid endometrial cancer (EC) presenting primarily as nodal spreads following systematic lymphadenectomy and adjuvant therapy. MATERIAL AND METHODS: Forty-four FIGO stage IIIC and IVB endometrioid EC patients between July 2003 and March 2020 received staging procedures including systematic lymphadenectomy. The survival outcomes and late treatment-related complications were compared between adjuvant chemoradiation-based group and chemotherapy-based group. RESULTS: Of the 44 patients, 16 (36.4%) had stage IIIC1, 26 (59.1%) had stage IIIC2, and 2 (4.5%) had stage IVB disease. The median follow-up time was 54 months (range, 10-185 months). There was no statistical difference in mortality between the microscopic and macroscopic nodal groups (6.2% vs 4.3%, p > 0.999). Eleven patients (25.0%) and 33 patients (75.0%) received adjuvant chemoradiation and chemotherapy, respectively. The 5-year disease-free and overall survival rates were not different between the two groups (disease-free survival, 81.8% vs 82.1%, p = 0.743; overall survival, 90.9% vs 95.8%, p = 0.537). The incidence rates of grade 2 lymphedema (36.4% vs 9.1%, p = 0.032) and grade 2/3 gastrointestinal complications (36.4% vs 0.0%, p < 0.001) were higher in the chemoradiation-based group than those in the chemotherapy-based group. CONCLUSIONS: Systematic lymphadenectomy and adjuvant chemotherapy might be the preferred treatment for FIGO stage IIIC and IVB endometrioid EC patients presenting as nodal spreads given that no difference in patient survival was found, but a higher incidence of treatment-related complications was observed in the chemoradiation-based group.

Decreased expression of progesterone receptor membrane component 1 in fetal membranes with chorioamnionitis among women with preterm birth.

PURPOSE: Progesterone receptor membrane component 1 (PGRMC1) have anti-inflammatory and anti-apoptotic properties. This study aimed to determine the expression of PGRMC1 in fetal membranes among women with preterm labor (PTL), preterm premature rupture of membranes (PPROM), and acute histologic chorioamnionitis (HCA) during preterm birth. METHODS: Full thickness fetal membranes were obtained from women with gestational age-matched (32-34 weeks of gestational age), and categorized as PTL without HCA (PTL, n = 10), PPROM without HCA (PPROM, n = 10), PPROM with HCA (HCA, n = 10), and term without labor and HCA (term birth (TB), n = 9). The expression of PGRMC1 was assessed using western blot and Immunohistochemistry (IHC). As CD14 is a component of the innate immune system during inflammation, CD14 was used as inflammatory indicator. Nonparametric statistics were used for analysis. RESULTS: PGRMC1 expression for all of preterm birth was lower than in TB (P = 0.01). In HCA, PGRMC1 expression was significantly decreased compared to that in PTL and PPROM (P = 0.006. P = 0.001, respectively). PGRMC1 expression in PPROM was higher than that in PTL (P = 0.002). There was a negative correlation between PGRMC1 and CD 14/ß-actin ratio (r = - 0.518; P = 0.002). IHC showed that PGRMC1 was predominant in the cytoplasm of cells, these results were consistent with those of the western blot analysis. CONCLUSION: Preterm birth with PTL, PPROM, and especially HCA is associated with a decreased PGRMC1 in fetal membranes and inversely associated with increased CD 14.

8% Efficiency Cu2ZnSn(S,Se)4 (CZTSSe) Thin Film Solar Cells on Flexible and Lightweight Molybdenum Foil Substrates.

The use of flexible and highly conducting molybdenum (Mo) foil as a substrate offers several advantages such as a high thermal stability, smooth surface, and chemical inertness for the fabrication of high-efficiency thin film solar cells (TFSCs) by lowering the manufacturing costs. Here, we report a record preliminary efficiency of ∼8% for sputtered-grown Cu2ZnSn(S,Se)4 (CZTSSe) TFSCs on flexible and lightweight Mo foils. Careful studies were focused on identifying the role of preparative parameters such as annealing temperature, absorber composition, and post-preparative optimization to bridge the obtained record efficiency of ∼8% to a previous record efficiency of 7.04% for Na-incorporated CZTSSe sputter-based TFSCs. Interestingly, the preliminary record efficiency of ∼8% for our CZTSSe device grown via a scalable sputtering method was achieved by optimizing the absorber quality and post-preparative device optimization. While our preliminary results with a record efficiency demonstrate the potential of sputtering method, there is much scope for further improvement in the device efficiency by thoroughly understanding alkali element doping in the absorber layer.

Rhodium(I)-catalyzed one-pot synthesis of dialkyl ketones from methanol and alkenes through directed sp3 C-H bond activation of N-methylamine.

The hydroacylation of methanol with alkenes was developed using a catalytic system consisting of Rh(I), 2-amino-4-picoline and benzoic acid; the reaction is speculated to occur by the initial N-methylation of 2-amino-4-picoline with methanol, and the subsequent dehydrogenation of the resulting N-methylamine, followed by double chelation-assisted hydroimination of alkene with the imine to give dialkyl ketones after hydrolysis.

Ruthenium-catalyzed coupling of aldimines with arylboronates: new synthetic method for aromatic ketones.

Using the chelation strategy, the reaction of aldimines bearing the 3-picolin-2-yl group with various arylboronates in the presence of a ruthenium catalyst furnished the corresponding ketimines in high yields for a short reaction time; the resulting ketimines were readily converted to ketones by hydrolysis.