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The modification of carborane anion monocarba-closo-dodecaborate (1) with perfluoroalkyl groups enhances its solubility in fluorinated ethers. This novel approach achieves a degree of solubility that is unattainable by using traditional lipophilic modifications or boro–vertex functionalizations of 1. A spectroscopic analysis in combination with DFT calculations confirmed that these new anions retain their weakly coordinating nature and exhibit moderate chemical stability.

Abstract We demonstrate long-range enhancement of fluorescence and Raman scattering using a dense random array of Ag nanoislands (AgNIs) coated with column-structured silica (CSS) overlayer of over 100 nm thickness, namely, remote plasmonic-like enhancement (RPE). The CSS layer provides physical and chemical protection, reducing the impact between analyte molecules and metal nanostructures. RPE plates are fabricated with high productivity using sputtering and chemical immersion in gold(I)/halide solution. The RPE plate significantly enhances Raman scattering and fluorescence, even without proximity between analyte molecules and metal nanostructures. The maximum enhancement factors are 107-fold for Raman scattering and 102-fold for fluorescence. RPE is successfully applied to enhance fluorescence biosensing of intracellular signalling dynamics in HeLa cells and Raman histological imaging of oesophagus tissues. Our findings present an interesting deviation from the conventional near-field enhancement theory, as they cannot be readily explained within its framework. However, based on the phenomenological aspects we have demonstrated, the observed enhancement is likely associated with the remote resonant coupling between the localised surface plasmon of AgNIs and the molecular transition dipole of the analyte, facilitated through the CSS structure. Although further investigation is warranted to fully understand the underlying mechanisms, the RPE plate offers practical advantages, such as high productivity and biocompatibility, making it a valuable tool for biosensing and biomolecular analysis in chemistry, biology, and medicine. We anticipate that RPE will advance as a versatile analytical tool for enhanced biosensing using Raman and fluorescence analysis in various biological contexts.

Objectives Inhaled nitric oxide (iNO) is a known treatment for pulmonary hypertension (PH) associated with bronchopulmonary dysplasia in preterm infants after 7 days of age (postacute phase). However, a consensus regarding the optimal criteria for initiating iNO therapy in this population in the postacute phase is currently lacking. This study, therefore, aimed to identify the criteria for initiating iNO therapy, alongside the associated clinical and echocardiographic findings, in this population.Design We performed a scoping review using the population-concept-context framework following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.Data sources PubMed, Embase and the Japanese database ‘Ichushi’ were systematically searched for relevant articles published between January 2003 and August 2023.Eligibility criteria This study included randomised controlled trials, prospective and retrospective cohort studies, case–control studies and case series on iNO therapy in the postacute phase for preterm infants born before 34 gestational weeks, written in English or Japanese.Data extraction and synthesis Data screening, extraction and charting were performed independently, with the characteristics and findings of the included studies subsequently summarised.Results We included 10 reports that analysed the data from 10 separate studies. The use of iNO therapy was categorised as prophylactic and rescue purposes. While randomised controlled trials (RCTs) and retrospective analyses indicated the safety of iNO during the postacute phase, the latter highlighted poor prognoses associated with severe cases requiring rescue iNO therapy. Additionally, although echocardiography is currently the primary diagnostic tool for identifying PH in preterm infants, standardised diagnostic criteria are lacking. Further, reports of complications and side effects associated with iNO are rare.Conclusion Our exploration of the initiation criteria for iNO revealed that definitive guidelines have not been established. Nonetheless, iNO administration during the postacute phase appeared to be safe and devoid of complications.Trial registration number UMIN000051498.

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Abstract Background Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. Methods Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. Results Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. Conclusion Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

Introduction Inhaled nitric oxide (iNO) use is recommended for persistent pulmonary hypertension of the newborn in term and late preterm infants. Recently, iNO therapy to prevent bronchopulmonary dysplasia (BPD) or rescue for hypoxic respiratory failure and pulmonary hypertension secondary to BPD has increasingly been used in preterm infants after 7 days of postnatal age (in the postacute phase), despite its off-label use. However, the initiation criteria of iNO therapy for preterm infants in the postacute phase are varied. The aim of this scoping review is to identify the clinical and/or echo findings at the initiation of iNO therapy in preterm infants in the postacute phase.Methods and analysis We will search PubMed, Embase and the Japanese database ‘Ichushi.’ The following studies will be included in the review: randomised controlled trials, prospective/retrospective cohort studies, case–control studies and case series on iNO therapy for preterm infants in the postacute phase; studies published between January 2003 and August 2023; studies conducted in developed countries and studies written in English or Japanese. We will independently screen, extract and chart data using the population–concept–context framework following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We will summarise the characteristics and findings of the included studies.Ethics and dissemination Obtaining an institutional review board approval is not required because of the nature of this review. A final report of review findings will be published and disseminated through a peer-reviewed journal and presentation at relevant conferences.Trial registration number UMIN000051498.

Collided ribosomes are marked by ubiquitination to induce quality control mechanisms. Here, authors show that mammalian disomes form a distinct structural interface, in which uS10 K63-linked polyubiquitination is critical for ribosome dissociation.

Fatty acids salts exert bactericidal and bacteriostatic effects that inhibit bacterial growth and survival. However, bacteria can overcome these effects and adapt to their environment. Bacterial efflux systems are associated with resistance to different toxic compounds. Here, several bacterial efflux systems were examined to determine their influence on fatty acid salt resistance in Escherichia coli. Both acrAB and tolC E. coli deletion strains were susceptible to fatty acid salts, while plasmids carrying acrAB, acrEF, mdtABC, or emrAB conferred drug resistance to the ΔacrAB mutant, which indicated complementary roles for these multidrug efflux pumps. Our data exemplify the importance of bacterial efflux systems in E. coli resistance to fatty acid salts.

Hailey-Hailey disease (HHD) is a rare autosomal dominant acantholytic dermatosis clinically characterized by recurrent erythematous plaques and erosions mainly on the intertriginous regions. Although HHD seriously affects quality of life, conventional treatments often fail to provide long-term relief for most patients. The effectiveness of apremilast, a phosphodiesterase-4 inhibitor, against severe HHD was first reported in 2018, and after further testing, this agent is currently expected to be established as an efficacious and safe therapeutic option. Here we report two cases of HHD treated with apremilast which showed opposite outcomes. Although the case with extremely severe symptoms showed remarkable and long-lasting improvement with apremilast used after acute treatment with oral corticosteroid, the other case, with milder symptoms treated only with apremilast, showed no improvement. Our transcriptome analysis using skin samples collected prior to apremilast administration revealed the involvement of the NF-κB signaling pathway, which is related to the responses to bacteria and other organisms. However, this pathway was more strongly activated in case 2 than in case 1, suggesting that the steroid treatment preceding apremilast may have been effective and supportive in the apremilast-responding case. One of the two cases highlights the potential of apremilast as a treatment option for HHD, but the other underlines the difficulties in managing HHD and the complexity of the disease background. The accumulation of cases and larger clinical studies are expected to precisely evaluate the safety and efficacy of apremilast, and the potential for therapies in combination with conventional treatments.

Feral horses form relatively stable harems over time that are characterized by long-lasting bonds among their members, a characteristic that makes them an exceptional case of a social system among terrestrial ungulates. Their social system has been described as uniform despite the wide differences in their environment and demography. Horse populations subjected to human interference often show higher levels of population instability that can ultimately compromise their reproductive success. In this article, we describe demographic and dynamic changes of a Portuguese population of Garranos in Serra d’Arga (SA), which is impacted by human and predation pressures, over six breeding seasons. Furthermore, we tested several hypotheses related to the impact of anthropogenic disturbance on the structure and dynamics of this population. Our results revealed that the SA population had relatively little human interference at the start of the project in 2016. This was supported by the natural composition of the herd (total number of individuals, 206), which consisted of several single- and multi-male harems (n = 17 and 7, respectively) and bachelor males (n = 9). However, from 2017 to 2021, SA’s Garrano population suffered a drastic decline. Approximately two-thirds of the individuals and all bachelor males disappeared, and 76% of adult female transfers occurred after the death or disappearance of the harem male. Predatory pressures and poor management of the population, which allowed illegal human interference, contributed to this population crisis. A low population growth rate, reduced birth and foal survival rates, in addition to a delayed primiparous age were observed in this population and exacerbated after its drastic decline; suggesting the viability and survival of this Garrano population were compromised. Investigating the population demographic changes and their causes and consequences can provide guidelines for managing populations and help fight the extinction of horse breeds.

Maternal aging has negative influences on the development and racing performance of their offspring in racehorses. However, the mechanism by which pregnancy at old age reduces the race performance of the offspring is unknown. Here, two hypotheses were posited: 1) Foals born to older mares are more likely to have muscular, skeletal, and cognitive disadvantages (direct effects). 2) Foals born to older mares are more likely to be affected by non-physiological factors correlating with the mare's age, such as the quality of sires (e.g. low-quality sires are likely to be chosen as partners of older broodmares). To test these hypotheses, the effect of the broodmare's age on the offspring's racing performance was examined, while controlling for the effects of the stallion's quality, age, and ID, offspring's sex, trainer, and the location of the training center. Information of racehorses registered to the Japan Racing Association were collected from the Japan Bloodhorse Breeders' Association website. Overall, results showed that the racing performance of horses born from older mares was lower than that of horses born from younger mares. However, generalized linear mixed models (GLMM) indicated that the quality of sires was significantly associated with the offspring's racing performance, rather than the broodmare's age itself. Furthermore, the age of broodmares was negatively correlated with the quality of sires, although the variance inflation factor was low. Therefore, the effect of maternal aging was negligible or only limited, and rather, the sire's quality had an important influence on the offspring's racing performance. Low quality sires, or cheap stallions in other words, are likely to be chosen as partners of older blood-mares, which may have reproductive risks such as lower fertility and higher rate of miscarriages. The present study suggests that the conventional belief that racehorses born from older mares show lower performance may not always be accurate.

According to recent social demands for sustainable developments, the value of biomass as feedstocks for chemical industry is increasing. With the aid of metabolic engineering and genome editing, microbial fermentation has been developed for producing value-added chemicals from biomass feedstocks, while further improvements are desired for producing more diverse chemicals and increasing the production efficiency. The major intrinsic limitation in conventional fermentation technologies is associated with the need for balancing the net redox equivalents between substrates and products, resulting in limited repertories of fermentation products. One solution for this limitation would be “electro-fermentation (EF)” that utilizes bioelectrochemical systems for modifying the intracellular redox state of electrochemically active bacteria, thereby overcoming the redox constraint of fermentation. Recent studies have attempted the production of chemicals based on the concept of EF, while its utility has not been sufficiently demonstrated in terms of low production efficiencies. Here we discuss EF in terms of its concept, current status and future directions, which help us develop its practical applications to sustainable chemical industries.

Ultramicrobacteria (UMB) that can pass through a 0.22 µm filter are attractive because of their novelty and diversity. However, isolating UMB has been difficult because of their symbiotic or parasitic lifestyles in the environment. Some UMB have extracellular electron transfer (EET)-related genes, suggesting that these symbionts may grow on an electrode surface independently. Here, we attempted to culture from soil samples bacteria that passed through a 0.22 µm filter poised with +0.2 V vs. Ag/AgCl and isolated Cellulomonas sp. strain NTE-D12 from the electrochemical reactor. A phylogenetic analysis of the 16S rRNA showed 97.9% similarity to the closest related species, Cellulomonas algicola, indicating that the strain NTE-D12 is a novel species. Electrochemical and genomic analyses showed that the strain NTE-D12 generated the highest current density compared to that in the three related species, indicating the presence of a unique electron transfer system in the strain. Therefore, the present study provides a new isolation scheme for cultivating and isolating novel UMB potentially with a symbiotic relationship associated with interspecies electron transfer.

Acropora pruinosa is a threatened zooxanthellate scleractinian coral that is distributed in the temperate areas along the coastline of Japan and the northern area of the South China Sea. Since A. pruinosa propagates both asexually and sexually, assessing clonal diversity and genetic connectivity among populations is important for conservation. In addition, high morphological variations in the field create confusion during species identification. To examine the existence of hidden genetic lineages, clonality, and genetic connectivity of A. pruinosa for conservation, we applied microsatellite analysis. Clustering analysis indicated two distinct geographically separated genetic lineages: one is distributed in the west, and the other is distributed in the east. The two lineages co-existed in Nishidomari, Kochi. There was no obvious difference in morphological characteristics between the two lineages. Although the factors influencing the observed distribution patterns remain unknown, there is a possibility that the two lineages might have diverged somewhere in the north-western Kyushu and north-eastern Pacific coast habitats in the past, and then periodically colonized the current habitats. A low clonal diversity was observed in most of the populations, indicating a high rate of asexual reproduction associated with their branching morphologies. In addition, there are strong genetic structuring in this species, indicating weak connectivity among populations. These results indicated a low larval dispersal potential among populations and that populations are basically sustained by a high rate of clone propagation and self-seeding. The existence of cryptic lineages and genetically isolated populations with high clonality emphasized the importance of conservation of A. pruinosa.

Methanogens capable of accepting electrons from Fe0 cause severe corrosion in anoxic conditions. In previous studies, all iron-corrosive methanogenic isolates were obtained from marine environments. However, the presence of methanogens with corrosion ability using Fe0 as an electron donor and their contribution to corrosion in freshwater systems is unknown. Therefore, to understand the role of methanogens in corrosion under anoxic conditions in a freshwater environment, we investigated the corrosion activities of methanogens in samples collected from groundwater and rivers. We enriched microorganisms that can grow with CO2/NaHCO3 and Fe0 as the sole carbon source and electron donor, respectively, in ground freshwater. Methanobacterium sp. TO1, which induces iron corrosion, was isolated from freshwater. Electrochemical analysis revealed that strain TO1 can uptake electrons from the cathode at lower than −0.61 V vs SHE and has a redox-active component with electrochemical potential different from those of other previously reported methanogens with extracellular electron transfer ability. This study indicated the corrosion risk by methanogens capable of taking up electrons from Fe0 in anoxic freshwater environments and the necessity of understanding the corrosion mechanism to contribute to risk diagnosis.

Abstract Background Acute gastroenteritis (AGE) is a major reason for presentation to pediatric primary emergency medical centers. Because rotavirus vaccines were introduced in November 2011 for voluntary vaccination in Japan, we analyzed the changes in the numbers of AGE patients. Methods The number and proportion of patients visiting Kobe children’s primary emergency medical center from January 2011 to February 2015 due to AGE, out of all visiting children, were investigated retrospectively. The rotavirus and norovirus epidemic periods were defined as the periods from March to June and from November to February, respectively, based on their disease prevalence. Results In patients ≤2 years of age, the numbers and proportions of patients with AGE were significantly decreased from 2464/14098 (17%) in 2011 to 1888/12321 (15%) in 2014 (p

BackgroundSpinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants.MethodsUC-MSCs were isolated from 16 control infants delivered at 22–40 weeks of gestation and SMA fetus aborted at 19 weeks of gestation (UC-MSC-Control and UC-MSC-SMA). FBs were isolated from control volunteer and SMA patient (FB-Control and FB-SMA). SMN mRNA and protein expression in UC-MSCs and FBs was determined by RT-qPCR and Western blot.ResultsUC-MSC-Control and UC-MSC-SMA expressed the comparable level of MSC markers on their cell surface and were able to differentiate into adipocytes, osteocytes, and chondrocytes. At steady state, SMN mRNA and protein expression was decreased in UC-MSC-SMA compared to UC-MSC-Control, as observed in FB-SMA and FB-Control. In response to histone deacetylase inhibitor valproic acid, SMN mRNA and protein expression in UC-MSC-SMA and FB-SMA was increased. During perinatal development from 22 to 40 weeks of gestation, SMN mRNA and protein expression in UC-MSC-Control was positively correlated with gestational age.ConclusionUC-MSCs isolated from 17 fetus/infant of 19–40 weeks of gestation are expressed functional SMN mRNA and protein. SMN mRNA and protein expression in UC-MSCs is increased with gestational age during perinatal development.

Abstract Congenital candidiasis, which presents with a variety of clinical symptoms, is very rare in both term and preterm infants, and less than 100 neonatal cases have been reported in the medical literature. We describe the case of an extremely premature infant with congenital candidiasis, who was successfully treated and survived without major sequelae. A male infant was born at 25 weeks' gestation (weight, 834 g). He exhibited diffuse erythematous papules. Samples of his skin, pharyngeal mucus, gastric fluid, and tracheal aspirate were found to be Candida albicans—positive while blood cultures were negative. Further histopathological examinations revealed that Candida albicans mycelia had invaded the umbilical cord. After prompt antifungal therapy, the patient's skin lesions improved markedly, and he was discharged from hospital without any major complications. This report highlights the importance of characteristic skin lesions for the early diagnosis of Candida infections, especially in extremely premature infants.

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

The Internet of Things (IoT) paradigm is gradually finding its way in virtually every industry; however, beyond adding more sensors and measuring and controlling previously inaccessible domains, it is also about transforming ‘legacy’ approaches to control systems, such as those used in Building Management Systems (BMS), by leveraging on the advantages brought by Cyber Physical Systems (CPS). The purpose of this paper is to address several issues gradually emerging in the process of applying the CPS and IoT paradigms to revolutionise BMS. The results of this on-going research aim to help avoid potential pitfalls and provide a sound platform for taking advantage of the benefits brought by this technology in a feasible, effective and controlled manner. More specifically, the paper will address i) the changing meaning of interoperability in the context of the explosion in the number of IoT devices, ii) the need for guidance in adopting sustainable CPS and IoT platforms supporting BMS, based on appropriate non-functional and viable systems principles, iii) emerging issues in the BMS ‘cloudification’ endeavour and iv) the lack of data sources’ correlation resulting in sub-optimal data quality and detail in using Big Data technologies to enable effective analytics for prompt BMS decision-making.

Abstract Background Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessive disorder of immune regulation that leads to a hyperinflammatory syndrome. Fetal onset FHL is extremely rare and is considered to be the most severe form of FHL. Case We report a preterm case of FHL that presented as hydrops fetalis. The infant was treated with a chemotherapy regimen based on the HLH-2004 protocol from the third day of life. However, he had persistent cytopenia and died on the 18th day of life due to bacteremia. The detection of defective perforin expression in the patient's natural killer cells and mutations in the PRF1 gene resulted in a molecular diagnosis of FHL. Conclusion We suggest that early diagnosis and the development of an appropriate immunosuppressive strategy that can induce and maintain remission until hematopoietic stem cell transplantation can be performed are required to improve the outcomes of fetal onset FHL.

Optical functions of organic dyes, e.g., fluorescence or photochromism, tend to degrade by light irradiation, which causes a short lifetime of photonic devices. Self-healing of optical functions is attainable by metabolizing bleached molecules with nonirradiated ones. A polydimethylsiloxane elastomer provides a useful matrix for dye molecules, since its flexible structure with nano-sized intermolecular spaces allows dye diffusion from a reservoir to an operation region. Swelling the elastomer with a suitable solvent promotes both dissolution and diffusion of dye molecules. This self-healing function was demonstrated by an experiment in which a photochromic elastomer exhibited improved durability against a repeated coloring-decoloring process.