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The carbapenem-resistance genes bla
are widely disseminated in Pseudomonas, and frequently harbored within class 1 integrons that reside within various mobile genetic elements (MGEs). However, there are few reports on detailed genetic dissection of bla
-carrying MGEs in Pseudomonas.
This study presented the complete sequences of five bla
-carrying MGEs, including two plasmids, two chromosomal integrative and mobilizable elements (IMEs), and one chromosomal integrative and conjugative element (ICE) from five different Pseudomonas isolates.
The two plasmids were assigned to a novel incompatibility (Inc) group Inc
, which included only seven available plasmids with determined complete sequences and could be further divided into three subgroups Inc
-1/2/3. A detailed sequence comparison was then applied to a collection of 15 MGEs belonging to four different groups three representative Inc
plasmids, two Tn6916-related IMEs, two Tn6918-related IMEs, and eight Tn6417-related ICEs and ten of these 15 MGd transfer between Pseudomonas isolates, which resulted in the accumulation and spread of blaVIM among Pseudomonas and thus was helpful for the bacteria to survival from the stress of antibiotics. Data presented here provided a deeper insight into the genetic diversification and evolution of VIM-encoding MGEs in Pseudomonas.
Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury.
By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode.
MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.
MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.
Uterine adenomyosis is a common gynecologic disease in premenopausal women, the pathological mechanism of which remains largely unknown. The aim of this study was to identify metabolic biomarkers significantly altered in the myometrium of adenomyosis patients.
The comprehensive metabolomic profiles of 17 myometrium specimens from adenomyosis patients and 25 control specimens were analyzed using untargeted approach by combination of gas chromatography-mass spectrometry and high performance liquid chromatography-mass spectrometry. Metabolic data were filtered using orthogonal partial least square-discriminant analysis and univariate statistics.
We firstly demonstrated that the myometrial metabolome of women with adenomyosis is distinct from that of women without adenomyosis. A total of 106 metabolites, mainly including nucleosides, lipids (including acylcarnitines), amino acids, organic acids and carbohydrates, were found to be differentially expressed in myometrium of uteri with adenomyosis compared to the control subjects. Functional inferences of these perturbed metabolites indicated that inflammation, oxidative stress, cell proliferation and apoptosis, and energy metabolism appeared to be involved in the progress of adenomyosis.
This study firstly described the integrated metabolic signatures of the adenomyosis uterus, which provided novel insights for the pathogenesis study of this disease.
This study firstly described the integrated metabolic signatures of the adenomyosis uterus, which provided novel insights for the pathogenesis study of this disease.
Aseptic Loosening (AL) following periprosthetic osteolysis is the main long-term complication after total joint arthroplasty (TJA). However, there is rare effective treatment except for revision surgery, which is costly and painful to the patients. In recent years, the ketone body β-hydroxybutyrate (BHB) has attracted much attention and has been proved to be beneficial in many chronic diseases. With respect to the studies on the ketone body β-hydroxybutyrate (BHB), its anti-inflammatory ability has been widely investigated. Although the ketone body β-hydroxybutyrate has been applied in many inflammatory diseases and has achieved considerable therapeutic efficacy, its effect on wear particles induced osteolysis is still unknown.
In this work, we confirmed that the anti-inflammatory action of β-hydroxybutyrate (BHB) could be reappeared in CoCrMo alloy particles induced osteolysis. Mechanistically, the ketone body β-hydroxybutyrate (BHB) deactivated the activation of NLRP3 inflammasome triggered by CoCrMo alloy particles. Of note, this inhibitory action was independent of Gpr109a receptor as well as histone deacetylase (HDAC) suppression. check details Furthermore, given that butyrate, one kind of short chainfatty acid (SCFA) structurally related to β-hydroxybutyrate (BHB), has been reported to be an inhibitor of osteoclast, thus we also investigate the effect of β-hydroxybutyrate (BHB) on osteoclast, which was contributed to bone resorption. It was found that β-hydroxybutyrate (BHB) did not only affect osteoclast differentiation, but also inhibit its function. Unlike the inflammasome, the effect of β-hydroxybutyrate (BHB) on osteoclast may mainly rely on histone deacetylase (HDAC) suppression.
In general, our study showed that the alleviation of osteolysis may owe to the effect of β-hydroxybutyrate (BHB) on inflammasome deactivation and osteoclast.
In general, our study showed that the alleviation of osteolysis may owe to the effect of β-hydroxybutyrate (BHB) on inflammasome deactivation and osteoclast.
Governance processes play an important role in shaping the formulation and implementation of policy measures such as restrictions on marketing of ultra-processed foods. However, there is limited analysis of the factors that affect governance for nutrition, especially in low- and middle-income countries such as Thailand and the Southeast Asia region. This study aimed to examine governance factors that create opportunities and challenges for the introduction of policy to restrict food marketing in Thailand, in line with the WHO recommendations to restrict food marketing to children.
A qualitative study design was used. Interviews were conducted with 20 actors with experience and in depth knowledge of food marketing in Thailand, including government, civil society, industry and international organisations. Open questions were asked about experiences and perceptions of the governance processes related to policies for restricting food marketing in Thailand. Themes were derived from the 3-i Framework which relanisms to promote multisectoral coordination across diverse actors reinforced barriers to policy change.
The findings highlight ongoing challenges to the government's aim to strengthen policy to restrict food marketing which, without greater coordination in governance mechanisms, will hinder effective regulation and the achievement of public health goals. This analysis suggests that the Government should prioritise the development of a holistic, multisectoral approach to improve governance for better nutrition outcomes by overcoming policy silos.
The findings highlight ongoing challenges to the government's aim to strengthen policy to restrict food marketing which, without greater coordination in governance mechanisms, will hinder effective regulation and the achievement of public health goals. This analysis suggests that the Government should prioritise the development of a holistic, multisectoral approach to improve governance for better nutrition outcomes by overcoming policy silos.Optically active nanostructures consisting of organic compounds and metallic support have shown great promise in phototherapy due to their increased light absorption capacity and high energy conversion. Herein, we conjugated chlorophyll (Chl) to vanadium carbide (V2C) nanosheets for combined photodynamic/photothermal therapy (PDT/PTT), which reserves the advantages of each modality while minimizing the side effects to achieve an improved therapeutic effect. In this system, the Chl from Leptolyngbya JSC-1 extracts acted as an efficient light-harvest antenna in a wide NIR range and photosensitizers (PSs) for oxygen self-generation hypoxia-relief PDT. The available large surface of two-dimensional (2D) V2C showed high Chl loading efficiency, and the interaction between organic Chl and metallic V2C led to energy conversion efficiency high to 78%. Thus, the Chl/ V2C nanostructure showed advanced performance in vitro cell line killing and completely ablated tumors in vivo with 100% survival rate under a single NIR irradiation. Our results suggest that the artificial optical Chl/V2C nanostructure will benefit photocatalytic tumor eradication clinic application.
Wearing facemasks is of proven efficacy as a public health protective measure against COVID-19. Currently there are no observational data concerning the wearing of facemasks and the adherence to guidelines concerning their handling.
Registration of the way passers-by were wearing facemasks at 26 different locations of five major cities in Greece. The results were correlated with the rate of COVID-19 deaths in the region.
In total, 119,433 passers-by were registered, 57,043 females (47.8%) and 62,390 males (52.2%). From the total sample, 81.1% were wearing the mask properly, 10.8% had their nose out, 6.2% were wearing it under the jaw, and 1.9% had no mask at all . There was a significant difference between males and females concerning any use of mask. Inappropriate use of was correlated with COVID-19 death rate in the studied region.
Our findings suggest that under conditions of mandatory wearing and in central locations of major cities, during walking, proper use of masks is suboptimal, but still contributes with some protection. Fear and risk perception seem to be strong factors contributing to adherence to proper mask wearing.
Our findings suggest that under conditions of mandatory wearing and in central locations of major cities, during walking, proper use of masks is suboptimal, but still contributes with some protection. Fear and risk perception seem to be strong factors contributing to adherence to proper mask wearing.
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