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Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT) 1-6 . However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD 7-10 . Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD., (© 2024. The Author(s).)

Background: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques., Methods: C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia., Results: Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection., Conclusions: Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques., (© 2023. The Author(s).)

Background: Viruses, the majority of which are uncultivated, are among the most abundant biological entities on Earth. From altering microbial physiology to driving community dynamics, viruses are fundamental members of microbiomes. While the number of studies leveraging viral metagenomics (viromics) for studying uncultivated viruses is growing, standards for viromics research are lacking. Viromics can utilize computational discovery of viruses from total metagenomes of all community members (hereafter metagenomes) or use physical separation of virus-specific fractions (hereafter viromes). However, differences in the recovery and interpretation of viruses from metagenomes and viromes obtained from the same samples remain understudied., Results: Here, we compare viral communities from paired viromes and metagenomes obtained from 60 diverse samples across human gut, soil, freshwater, and marine ecosystems. Overall, viral communities obtained from viromes had greater species richness and total viral genome abundances than those obtained from metagenomes, although there were some exceptions. Despite this, metagenomes still contained many viral genomes not detected in viromes. We also found notable differences in the predicted lytic state of viruses detected in viromes vs metagenomes at the time of sequencing. Other forms of variation observed include genome presence/absence, genome quality, and encoded protein content between viromes and metagenomes, but the magnitude of these differences varied by environment., Conclusions: Overall, our results show that the choice of method can lead to differing interpretations of viral community ecology. We suggest that the choice of whether to target a metagenome or virome to study viral communities should be dependent on the environmental context and ecological questions being asked. However, our overall recommendation to researchers investigating viral ecology and evolution is to pair both approaches to maximize their respective benefits. Video Abstract., (© 2024. The Author(s).)

The color of the tablets and capsules produced by pharmaceutical companies is important from the perspectives of product branding and counterfeiting. According to some studies, light can change tablet color during storage. In this study, tablets comprising amlodipine besylate (AB), a well-known light-sensitive drug, were coated with commonly used coating materials and exposed to light. Compared to the tablets that were not exposed to light, the color of those exposed to light changed over time. In fact, a faster and more pronounced color change was observed in the tablets exposed to light; however, the amount of AB did not decrease significantly in these tablets. The coating materials and their amounts were varied to clarify the materials involved in the color change. Based on the results, titanium dioxide and hypromellose may be involved in the color change process. As titanium dioxide is a photocatalyst, it may induce or promote chemical changes in hypromellose upon light irradiation. Overall, care should be exercised during selection of the coating polymer because titanium dioxide may promote photodegradation of the coatings while protecting the tablet's active ingredient from light., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

In situ characterization of materials in their operational state is a highly active field of research. Investigating the structure and response of materials under stimuli that simulate real working environments for technological applications can provide new insight and unique input to the synthesis and design of novel materials. Over recent decades, experimental setups that allow different stimuli to be applied to a sample inside an electron microscope have been devised, built, and commercialized. In this review, we focus on the in situ investigation of optically active materials using transmission electron microscopy. We illustrate two different approaches for exposing samples to light inside the microscope column, explaining the importance of different aspects of their mechanical construction and choice of light source and materials. We focus on the technical challenges of the setups and provide details of the construction, providing the reader with input on deciding which setup will be more useful for a specific experiment. The use of these setups is illustrated using examples from the literature of relevance to photocatalysis and nanoparticle synthesis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nanoparticles can undergo aging phenomena in sewage treatment systems, which alter their physical and chemical properties. However, the effect of aged nanoparticles on the dewatering performance of activated sludge under long-term low concentrations is yet to be reported in sewage treatment systems. Here, we compared the chronic effects of pristine and aged TiO 2 nanoparticles on the sludge dewatering index, which includes specific resistance to filtration (SRF) and bound water (BW) in a sequencing batch reactor (SBR) at μg/L concentration levels, and analyzed the relevant mechanisms. The results indicated that aging in the sludge supernatant altered the photosensitivity and water stability of nanoparticles, which was mainly due to the changes in the zeta potential and energy band of the particle and was ultimately attributed to the combined effect of particle surface inclusions such as organic matter and inorganic salt. At 10 μg/L, nanoparticles reduced the sludge dewaterability, which observed an improvement at 100 μg/L. This is because 10 μg/L promoted the secretion of extracellular polymeric substances (EPS), which regulated the structure of sludge flora and increased the abundance of secreted quorum sensing-acyl-homoserine lactones (QS-AHL) and EPS genera, while the corresponding exposure results for 100 μg/L were the opposite, owing to the damage and necrosis effects caused by exposure under long-term light, which reduced EPS production and increased sludge density. Interestingly, aging could alleviate the effects of two exposure concentrations on sludge dewatering, mainly because of the decrease in the photoactivity of the nanoparticles. The results of this study show that environmental aging could delay, but not reverse the results of exposure to specific concentrations of nanoparticles. However, the significantly different ecological effects of photosensitive nanoparticles with two environmentally relevant concentration should be refined and confirmed again in freshwater environments to provide a basis for subsequent scientific management and control of photosensitive nanoparticles., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)