Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may be due, in part, to alterations that occur in ...the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.e., predisposition due to maternal asthma diagnosis) and hospital-related environmental and clinical factors that alter microbial exposures early in life, we considered a unique cohort of preterm infants born ≤ 34 weeks gestational age from two local level III NICUs, as part of the MAP (Microbiome, Atopic disease, and Prematurity) Study. From MAP participants, we chose a sub-cohort of infants whose mothers had a history of asthma and matched gestational age and sex to infants of mothers without a history of asthma diagnosis (control). We performed a prospective, paired metagenomic and metabolomic analysis of stool and milk feed samples collected at birth, 2 weeks, and 6 weeks postnatal age. Although there were clinical factors associated with shifts in the diversity and composition of stool-associated bacterial communities, maternal asthma diagnosis did not play an observable role in shaping the infant gut microbiome during the study period. There were significant differences, however, in the metabolite profile between the maternal asthma and control groups at 6 weeks postnatal age. The most notable changes occurred in the linoleic acid spectral network, which plays a role in inflammatory and immune pathways, suggesting early metabolomic changes in the gut of preterm infants born to mothers with a history of asthma. Our pilot study suggests that a history of maternal asthma alters a preterm infants' metabolomic pathways in the gut, as early as the first 6 weeks of life.
The test of four rubber concrete filled steel tube (RuCFST) members, one concrete filled steel tube (CFST) member and one empty member were conducted under pure bending. The main parameters were the ...shear span ratio (λ) from 3 to 5, and the rubber replacing ratio (r) from 10% to 20%. The bending moment-strain curves, the bending moment-deflection curves and the bending moment-curvature curves were obtained. The failure modes of core rubber concrete were analyzed. The failure mode of RuCFST members was bending failure from the results. The cracks of rubber concrete were distributed evenly and sparsely, and the filling of rubber in core concrete prevented the development of cracks. The shear span ratio has little effect on the behavior of the tested specimens. While the rubber replacing ratio had little effect on the bending moment capacity, but had some influence on the bending stiffness of the tested specimens. After filling in rubber concrete, the bending moment capacity and the bending stiffness can be improved compared with the empty steel tube specimen.
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•A highly time-resolved PCB profile in the Tibetan Plateau was revealed;•Contributions from atmospheric deposition and lateral remobilization was distinguished;•Remobilization ...dynamics significantly shaped sedimentary PCB record;•PCBs from catchment may serve as a secondary source to the water systems.
Lake sediment cores from remote alpine regions are crucial for investigating historical emissions of persistent organic pollutants (POPs), predominantly transported via long-range atmospheric transport (LRAT), with negligible local contributions. This study emphasized the overlooked aspect of lateral remobilization's impact on POPs deposition history on the Xizang Plateau, distinguishing it from direct atmospheric deposition. Through analyzing vertical profiles and compositional variations of polychlorinated biphenyls (PCBs) in a dated sediment core from the Tibetan lake of Yamzho Yumco, the emission history of PCBs in Asia could be reconstructed, with notably emission peaks in the 1970 s. Importantly, fluctuations in total PCB fluxes during flood events indicated significant lateral remobilization of older PCBs from surrounding soils into the lake, marked by an increased presence of hexa- and hepta-CBs relative to atmospheric deposits. A strong correlation between the ratio of (tri- + tetra- + penta-CBs) to (hexa- + hepta-CBs) and total PCB flux highlighted the critical influence of remobilization on the sediment's PCB profile. Our findings reveal that temporal and compositional PCB variations would align with the both direct contribution of atmospheric deposition and secondary source of lateral remobilization, enhancing the understanding of POPs dynamics in sediment cores.
Asthma is the most common chronic disease within the paediatric population. Although it is multifactorial, its onset may be linked to early-life exposures with subsequent impact on immune system ...development. Microbial and dietary metabolic products have been implicated in the development and exacerbation of paediatric asthma. Linoleic acid is the most common omega-6 polyunsaturated fatty acid in the Western diet. In this review, we summarise the literature regarding the involvement of linoleic acid in the development of and its impact on existing paediatric asthma. First, we summarise the existing knowledge surrounding the relationship between human microbial metabolism and allergic diseases in children. Next, we examine cellular or animal model-based mechanistic studies that investigated the impact of dietary- and microbial-derived linoleic acid metabolites on asthma. Finally, we review the literature investigating the impact of linoleic acid metabolites on the development and exacerbation of childhood asthma. While there is conflicting evidence, there is growing support for a role of linoleic acid in the onset and pathophysiology of asthma. We recommend that additional cellular, animal, and longitudinal studies are performed that target linoleic acid and its metabolites.
Stenotrophomonas maltophilia
has been recognized as an emerging global opportunistic pathogen, and it is intrinsically resistant to most antibiotics, which makes the limited choice for treating
S. ...maltophilia
infections. Bacteriophage with the proper characterization is considered as a promising alternative treatment option to control
S. maltophilia
infections. In this study, we isolated a novel
Siphoviridae
bacteriophage vB_SmaS_BUCT626 with lytic activity against
S. maltophilia
. Phage vB_SmaS_BUCT626 can lysis 10 of 20
S. maltophilia
and was relatively stable at a wide range of temperatures (4–70 °C) and pH values (3.0–13.0) and exhibited good tolerance to chloroform. The genome of phage vB_SmaS_BUCT626 was a 61,662-bp linear double-stranded DNA molecule with a GC content of 56.2%, and contained 100 open-reading frames. It carried no antibiotic resistance, toxin, virulence-related genes, or lysogen-formation gene clusters. Together, these characteristics make phage vB_SmaS_BUCT626, a viable candidate as a biocontrol agent against
S. maltophilia
infection.
Enterobacter hormaechei is an opportunistic pathogen and is found in a large variety of food including animal-derived food. In recent years, bacteria present a severe clinical challenge due to their ...increasing resistance to antibiotics. Bacteriophages have gained attention as a new antibacterial strategy. In this study, we isolated a novel E. hormaechei bacteriophage IME278 from hospital sewage in Beijing, China. Bacteriophage IME278 had a double-stranded linear DNA genome with 40,164 bp and 51.99% GC content. Whole-genome alignments showed IME278 shared 87% homology with other phages in the National Center for Biotechnology Information (NCBI) database. And phylogenetic analysis demonstrated that IME278 was highly similar to bacteriophages belonging to the genus Kayfunavirus, family Autographiviridae, indicating IME278 can be classified as a new member of the Autographiviridae family. Transmission electron microscopy revealed that IME278 had an icosahedral head 51.72 nm in diameter and a tail 151.28 nm in length. Bacteriophage IME278 was able to survive under high temperature (50 °C–70 °C) and its activity decreased significantly above 70 °C and almost completely inactivated at 80 °C. Bacteriophage IME278 could survive in a wide pH range (4.0–11.0) and it was stable in chloroform (up to 5%). The phage was sensitive to UV irradiation. Bacteriophage IME278 had a latent period of 40 min and reached a plateau stage at 150 min and its cleavage was approximately 8.21 × 108/3.66 × 108 = 2.24. The biocontrol potential of bacteriophage IME278 was evaluated in a model that artificially contaminated pork with E. hormaechei 529 and the result revealed that IME278 could effectively control bacterial contamination on pork. The in-depth analysis of the biological characteristics, whole genome sequencing, and bioinformatics of IME278 has laid the foundation for the biocontrol application and the treatment of bacteria using bacteriophages.
•The discovery of E. hormaechei bacteriophage IME278 expand our knowledge of the diversity of phage contingent.•E. hormaechei bacteriophage IME278 shared 87% homology with other phages, indicating IME278 can be classified as a new genus.•E. hormaechei bacteriophage IME278 was similar to bacteriophages belonging to the genus Kayfunavirus, family Autographiviridae.•The biocontrol potential of bacteriophage IME278 revealed that IME278 could effectively control bacterial contamination on pork.
Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated ...in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications-driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.
Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying ...mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.
Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.
