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OBJECTIVE: P-glycoprotein (P-gp) of membrane transporters leads to drug resistance by the exclusion of intracellular drugs, including corticosteroids. Some patients with highly active systemic lupus erythematosus (SLE) show poor response to corticosteroids; however, the mechanisms of steroid resistance remain unclear. The aim of this study was to elucidate the clinical relevance of P-gp expression on lymphocytes to steroid resistance in patients with active SLE. METHODS: Flow cytometric analyses of the expression of P-gp on peripheral blood lymphocytes from 20 normal volunteers and 80 SLE patients were performed. Steroid-exclusion analysis of peripheral blood mononuclear cells (PBMCs) was conducted by using radioisotope-labeled dexamethasone. RESULTS: P-gp was expressed at significantly high levels on most of the peripheral blood lymphocytes from SLE patients, whereas normal lymphocytes had only marginal expression. The quantity of P-gp on SLE lymphocytes correlated with the disease activity in each patient, as estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Furthermore, in SLE patients whose SLEDAI scores were >12 despite taking >0.5 mg/kg/day of prednisolone, P-gp expression on lymphocytes was markedly increased, and intracellular dexamethasone in their PBMCs was significantly decreased. However, intensive immunosuppressive treatment in these SLE patients resulted in successful control of disease activity, which occurred in parallel with a marked reduction of P-gp on lymphocytes. CONCLUSION: The overexpression of P-gp on lymphocytes might lead to exclusion of corticosteroids from lymphocytes, resulting in steroid resistance in patients with highly active SLE. Reduction of P-gp expression achieved by intensive immunosuppressive treatment overcame the steroid resistance. We therefore propose that measurement of P-gp expression on lymphocytes is useful in the assessment of steroid resistance and is a good marker for indicating the need for intensive immunosuppressive treatment in patients with highly active SLE. [ABSTRACT FROM AUTHOR]

An abstract of the article "Development of Cyanobacterial Blooms With Special Reference to the Role of Overwintering Population," by S. Tsujimura is presented.

The development of nonfullerene acceptors (NFAs), represented by ITIC, has contributed to improving the power conversion efficiency (PCE) of organic solar cells (OSCs). Although tuning the electronic structures to reduce the exciton binding energy (E b ) is considered to promote photocharge generation, a rational molecular design for NFAs has not been established. In this study, we designed and developed two ITIC-based NFAs bearing spiro-substituted bithiophene or biphenyl units (named SpiroT-DCI and SpiroF-DCI) to tune the frontier molecular orbital (FMO) distribution of NFAs. While the highest occupied molecular orbitals (HOMOs) of SpiroF-DCI and ITIC are delocalized in the main π-conjugated framework, the HOMO of SpiroT-DCI is distributed on the bithiophene unit. Reflecting this difference, SpiroT-DCI exhibits a smaller E b than either SpiroF-DCI or ITIC, and exhibits greater external quantum efficiency in single-component OSCs. Furthermore, SpiroT-DCI shows improved PCEs for bulk-heterojunction OSCs with a donor of PBDB-T, compared with that of either SpiroT-DCI or ITIC. Time-resolved spectroscopy measurements show that the photo-induced intermolecular charge separation is effective even in pristine SpiroT-DCI films. This study highlights the introduction of spiro-substituted bithiophene units that are effective in tuning the FMOs of ITIC, which is desirable for reducing the E b and improving the PCE in OSCs., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Enzyme-mediator bioconjugation is emerging as a building block for designing electrode platforms for the construction of biosensors and biofuel cells. Here, we report a one-pot bioconjugation technique for flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) and thionine (TH) using a series of cross-linkers, including epoxy, N -hydroxysuccinimide (NHS), and aldehydes. In this technique, FAD-GDH and thionine are conjugated through an amine cross-linking reaction to generate a redox network, which has been successfully employed for the oxidation of glucose. The bioconjugation chemistry of cross-linkers with the amino groups on FAD-GDH and thionine plays a vital role in generating distinct network structures. The epoxy-type cross-linker reacts with the primary and secondary amines of thionine at room temperature, thereby producing an FAD-GDH-TH-FAD-GDH hyperbranched bioconjugate network, the aldehyde undergoes a rapid cross-linking reaction to produce a network of FAD-GDH-FAD-GDH, while the NHS-based cross-linker can react with the primary amines of both FAD-GDH and thionine, forming an FAD-GDH-cross-linker-TH polymeric network. This reaction has the potential to enable the conjugation of a redox mediator with a FAD-GDH network, which is particularly essential when designing an enzyme electrode platform. The data demonstrated that the polymeric cross-linked network based on the NHS cross-linker exhibited a considerable increase in electron transport while producing a catalytic current of 830 μA cm -2 . The cross-linker spacer arm length also affects the overall electrochemical function of the network and its performance; an adequate spacer length containing a cross-linker is required, resulting in a faster electron transfer. Finally, a leaching test confirmed that the stability of the enzyme electrode was improved when the electrode was tested using the redox probe. This study elucidates the relationship between cross-linking chemistry and redox network structure and enhances the high performance of enzyme electrode platforms for the oxidation of glucose.

Perspiration plays a pivotal role not only in thermoregulation but also in reflecting the body's internal state and its response to external stimuli. The up-to-date skin-based wearable platforms have facilitated the monitoring and simultaneous analysis of sweat, offering valuable physiological insights. Unlike conventional passive sweating, dynamic normal perspiration, which occurs during various activities and rest periods, necessitates a more reliable method of collection to accurately capture its real-time fluctuations. An innovative microfluidic patch incorporating a hierarchical superhydrophilic biosponge, poise to significantly improve the efficiency capture of dynamic sweat is introduced. The seamlessly integrated biosponge microchannel showcases exceptional absorption capabilities, efficiently capturing non-sensitive sweat exuding from the skin surface, mitigating sample loss and minimizing sweat volatilization. Furthermore, the incorporation of sweat-rate sensors alongside a suite of functional electrochemical sensors endows the patch of uninterrupted monitoring and analysis of dynamic sweat during various activities, stress events, high-energy intake, and other scenarios., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The power conversion efficiency (PCE) of organic photovoltaics (OPVs) has reached more than 19% due to the rapid development of non-fullerene acceptors (NFAs). To compete with the PCEs (26%) of commercialized silicon-based inorganic photovoltaics, the drawback of OPVs should be minimized. This drawback is the intrinsic large loss of open-circuit voltage; however, a general approach to this issue remains elusive. Here, we report a discovery regarding highly efficient NFAs, specifically ITIC. We found that charge-transfer (CT) and charge dissociation (CD) can occur even in a neat ITIC film without the donor layer. This is surprising, as these processes were previously believed to take place exclusively at donor/acceptor heterojunctions. Femtosecond time-resolved visible to mid-infrared measurements revealed that in the neat ITIC layers, the intermolecular CT immediately proceeds after photoirradiation (<0.1 ps) to form weakly-bound excitons with a binding energy of 0.3 eV, which are further dissociated into free electrons and holes with a time-constant of 56 ps. Theoretical calculations indicate that stacking faults in ITIC ( i.e. , V-type molecular stacking) induce instantaneous intermolecular CT and CD in the neat ITIC layer. In contrast, J-type stacking does not support such CT and CD. This previously unknown pathway is triggered by the larger dipole moment change on the excited state generated at the lower symmetric V-type molecular stacking of ITIC. This is in sharp contrast with the need of sufficient energy offset for CT and CD at the donor-acceptor heterojunction, leading to the significant voltage loss in conventional OPVs. These results demonstrate that the rational molecular design of NFAs can increase the local dipole moment change on the excited state within the NFA layer. This finding paves the way for a groundbreaking route toward the commercialization of OPVs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)