Low G+C Gram-positive Firmicutes, such as the clinically important pathogens Staphylococcus aureus and Bacillus cereus, use the low-molecular weight thiol bacillithiol (BSH) as a defense mechanism to buffer the intracellular redox environment and counteract oxidative stress encountered by human neutrophils during infections. The protein YpdA has recently been shown to function as an essential NADPH-dependent reductase of oxidized bacillithiol disulfide (BSSB) resulting from stress responses and is crucial for maintaining the reduced pool of BSH and cellular redox balance. In this work, we present the first crystallographic structures of YpdAs, namely, those from S. aureus and B. cereus. Our analyses reveal a uniquely organized biological tetramer; however, the structure of the monomeric subunit is highly similar to those of other flavoprotein disulfide reductases. The absence of a redox active cysteine in the vicinity of the FAD isoalloxazine ring implies a new direct disulfide reduction mechanism, which is backed by the presence of a potentially gated channel, serving as a putative binding site for BSSB in the proximity of the FAD cofactor. We also report enzymatic activities for both YpdAs, which along with the structures presented in this work provide important structural and functional insight into a new class of FAD-containing NADPH-dependent oxidoreductases, related to the emerging fight against pathogenic bacteria.Intranasal vaccines offer key advantages over traditional needle-based vaccines. They are simple to administer and painless and establish local immunity at mucosal surfaces. Owing to these advantages, they are particularly attractive for use in resource-limited locations of the world.  https://www.selleckchem.com/products/MLN8237.html  Subunit vaccines also have advantages for global distribution, as they can be engineered to be more stable to fluctuations in environmental conditions than live-attenuated or inactivated vaccines, but they tend to be poorly immunogenic intranasally. Toward realizing the potential of intranasal subunit vaccination, biomaterial-based technologies are emerging. This review provides an overview of recent progress in the preclinical development of biomaterial-based intranasal vaccines against subunit antigens and should serve as an effective introduction to the current state of this exciting field. We provide a brief overview of the obstacles facing intranasal vaccine development and identify key design criteria for consideration when designing biomaterials for intranasal subunit vaccine delivery. Promising strategies are discussed across a wide array of biomaterial classes, with a focus on selected exemplary works that highlight the considerable potential of intranasal vaccines and the biomaterial-based technologies that enable them.Due to the complexity and limited availability of human brain tissues, for decades, pathologists have sought to maximize information gained from individual samples, based on which (patho)physiological processes could be inferred. Recently, new understandings of chemical and physical properties of biological tissues and multiple chemical profiling have given rise to the development of scalable tissue clearing methods allowing superior optical clearing of across-the-scale samples. In the past decade, tissue clearing techniques, molecular labeling methods, advanced laser scanning microscopes, and data visualization and analysis have become commonplace. Combined, they have made 3D visualization of brain tissues with unprecedented resolution and depth widely accessible. To facilitate further advancements and applications, here we provide a critical appraisal of these techniques. We propose a classification system of current tissue clearing and expansion methods that allows users to judge the applicability of individual ones to their questions, followed by a review of the current progress in molecular labeling, optical imaging, and data processing to demonstrate the whole 3D imaging pipeline based on tissue clearing and downstream techniques for visualizing the brain. We also raise the path forward of tissue-clearing-based imaging technology, that is, integrating with state-of-the-art techniques, such as multiplexing protein imaging, in situ signal amplification, RNA detection and sequencing, super-resolution imaging techniques, multiomics studies, and deep learning, for drawing the complete atlas of the human brain and building a 3D pathology platform for central nervous system disorders.We report the first systematic experimental and theoretical study of the relationship between the linker functionalization and the thermodynamic stability of metal-organic frameworks (MOFs) using a model set of eight isostructural zeolitic imidazolate frameworks (ZIFs) based on 2-substituted imidazolate linkers. The frameworks exhibit a significant (30 kJ·mol-1) variation in the enthalpy of formation depending on the choice of substituent, which is accompanied by only a small change in molar volume. These energetics were readily reproduced by density functional theory (DFT) calculations. We show that these variations in the enthalpy of MOF formation are in linear correlation to the readily accessible properties of the linker substituent, such as the Hammett σ-constant or electrostatic surface potential. These results provide the first quantifiable relationship between the MOF thermodynamics and the linker structure, suggesting a route to design and tune MOF stability.Until now, an electrochemical lateral flow assay (eLFA) capable of detecting nucleic acids has remained a challenge and has been scarcely explored because of its complicated multistep nature. Here, we report an automated paper-based eLFA device for the quantitative detection of the hepatitis B virus (HBV)-the major cause of liver cirrhosis and hepatocellular carcinoma (HCC). Using a time-delayed microfluidic strategy fabricated on paper, an automated and precisely sequenced solution transfer was enabled by single sample loading. A gold metallization strategy was employed for the signal-on electrochemical detection of the target DNA. Furthermore, a pyrrolidinyl peptide nucleic acid (so-called "acpcPNA") was used as a probe in this study because it offers higher specificity and yields lower background currents than those of traditional probes. Under optimal conditions, a broad dynamic range (10 pM to 2 μM) with an excellent detection limit (down to 7.23 pM) was achieved. The overall operation can be completed within 7 min of sample loading.