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Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge‐driven treatments. We report the use of camelid single‐domain nanobodies (Nbs) against fungal β‐1,3‐glucanosyltransferases (Gel) involved in β‐1,3‐glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti‐Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for β‐1,3‐glucan remodelling in C. deneoformans survival. These findings add new insight about the role of β‐1,3‐glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases. [ABSTRACT FROM AUTHOR]

Purpose: Bibliometric and scientometric analyses provide a structured approach to large amounts of data, enabling the prediction of research theme trends over time, the detection of shifts in the boundaries of disciplines, and the identification of the most productive countries, institutions and scholars. In the context of prostate-specific membrane antigen (PSMA)-targeted radiotheranostics, no bibliometric or scientometric analysis has been published thus far. Therefore, this study was conducted to identify key contributors to the literature, assess the global scientific production of related research, and possibly predict future development patterns. Methods: Scientometrics and bibliometrics were utilized to analyze the current body of knowledge while tracking its evolution to support scientific decisionmaking comprehensively and systematically. Science mapping techniques were employed to visualize research activities. Two different tools, Tableau and VOSviewer, were utilized, with VOSviewer being deemed the most suitable for the research objectives. The Web of Science (WoS) was used as the principal database for the searches. Results: Through the search process over a period of 30 years (January 1993-January 2023), 694 original studies in the English language were subjected to comprehensive analysis. By employing bibliometric and scientometric methods, multiple networks were created that mapped various concepts, such as publication trends, leading countries, cocitations, coauthorship among researchers and scientists, as well as coauthorship among organizations and funding agencies. This study revealed the evolutionary patterns, trends, outliers, and key players in the PSMA field, which enabled a more nuanced understanding of the research landscape. Conclusion: This research contributes to the enrichment of knowledge on PSMA-targeted radiotheranostics through detailed global bibliometric and scientometric analyses. It stresses the necessity for the development of communication platforms, the establishment of supportive infrastructures, and the implementation of proactive solutions to address emerging challenges. This study offers a significant resource for delineating effective strategies and identifying prominent funding bodies essential for continuous advancements in the field of PSMA-based diagnosis and therapy for prostate cancer. It is vital to sustain this momentum to ensure further progress in this pioneering area. [ABSTRACT FROM AUTHOR]

Candida albicans is an opportunistic fungus that becomes pathogenic and problematic under certain biological conditions. C. albicans may cause painful and uncomfortable symptoms, as well as deaths in immunocompromised patients. Therefore, early detection of C. albicans is essential. However, conventional detection methods are costly, slow, and inaccessible to women in remote or developing areas. To address these concerns, we have developed a wearable and discrete naked-eye detectable colorimetric platform for C. albicans detection. With some modification, this platform is designed to be directly adhered to existing feminine hygiene pads. Our platform is rapid, inexpensive, user-friendly, and disposable and only requires three steps: (i) the addition of vaginal fluid onto sample pads; (ii) the addition of gold nanoparticle gel and running buffer, and (iii) naked eye detection. Our platform is underpinned by selective thiolated aptamer-based recognition of 1,3-β-D glucan molecules—a hallmark of C. albicans cell walls. In the absence of C. albicans, wearable sample pads turn bright pink. In the presence of C. albicans, the wearable pads turn dark blue due to significant nanoparticle target-induced aggregation. We demonstrate naked-eye colorimetric detection of 4.4 × 106 C. albicans cells per ml and nanoparticle stability over a pH range of 3.0–8.0. We believe that this proof-of-concept platform has the potential to have a significant impact on women's health globally. [ABSTRACT FROM AUTHOR]

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

The injudicious usage of antibiotics during infections caused by Gram-negative bacteria leads to the emergence of β-lactamases. Among them, the NDM-1 enzyme poses a serious threat to human health. Developing new antibiotics or inhibiting β-lactamases might become essential to reduce and prevent bacterial infections. Nanobodies (Nbs), the smallest antigen-binding single-domain fragments derived from Camelidae heavy-chain-only antibodies, targeting enzymes, are innovative alternatives to develop effective inhibitors. The biopanning of an immune VHH library after phage display has helped to retrieve recombinant antibody fragments with high inhibitory activity against recombinant-NDM-1 enzyme. Nb02NDM-1, Nb12NDM-1, and Nb17NDM-1 behaved as uncompetitive inhibitors against NDM-1 with Ki values in the nM range. Remarkably, IC50 values of 25.0 nM and 8.5 nM were noted for Nb02NDM-1 and Nb17NDM-1, respectively. The promising inhibition of NDM-1 by Nbs highlights their potential application in combating particular Gram-negative infections. [ABSTRACT FROM AUTHOR]