Mycobiome analyses of critically ill COVID-19 patients.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and colonization. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality.

Aspergillus-mediated allergic airway inflammation is triggered by dendritic cell recognition of a defined spore morphotype.

Background: Exposure to fungi, especially Aspergillus fumigatus, can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs) initiate allergic inflammatory responses to allergic stimuli. However, it is unclear if Af spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required.

Impact of N-acetyl-L-cysteine on spindle morphology and reactive oxygen species in vitrified/warmed in vitro matured bovine oocytes.

Low developmental potential of vitrified in vitro matured (IVM) bovine oocytes is frequently attributed to high levels of reactive oxygen species (ROS) and abnormal spindle assembly. This study aimed to evaluate the efficacy of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, added to IVM medium in reducing ROS and preserving spindle configuration of vitrified/warmed IVM bovine oocytes. Oocytes collected from abattoir ovaries were either cultured in IVM medium or in IVM medium supplemented with 1 mM NAC for the initial 8 h of IVM.

Lanthanide-Based Organic Salts: Synthesis, Characterization, and Cytotoxicity Studies.

The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C.

A phylogenetic approach to explore the conidial surface-associated proteome and its role in pathogenesis.

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of , two closely related non-pathogenic species, and , and the cryptic pathogen . After identifying 62 proteins uniquely expressed on the conidial surface, we assessed null mutants for 42 genes encoding conidial proteins.

In Vitro Antimicrobial Studies of Mesoporous Silica Nanoparticles Comprising Anionic Ciprofloxacin Ionic Liquids and Organic Salts.

The combination of active pharmaceutical ingredients in the form of ionic liquids or organic salts (API-OSILs) with mesoporous silica nanoparticles (MSNs) as drug carriers can provide a useful tool in enhancing the capabilities of current antibiotics, especially against resistant strains of bacteria. In this publication, the preparation of a set of three nanomaterials based on the modification of a MSN surface with cholinium ([MSN-Chol][Cip]), 1-methylimidazolium ([MSN-1-MiM][Cip]) and 3-picolinium ([MSN-3-Pic][Cip]) ionic liquids coupled with anionic ciprofloxacin have been reported. All ionic liquids and functionalized nanomaterials were prepared through sustainable protocols, using microwave-assisted heating as an alternative to conventional methods.

Functional analysis of the kinome reveals a DYRK kinase involved in septal plugging is a novel antifungal drug target.

More than 10 million people suffer from lung diseases caused by the pathogenic fungus . The azole class of antifungals represent first line therapeutics for most of these infections however resistance is rising. Identification of novel antifungal targets that, when inhibited, synergise with the azoles will aid the development of agents that can improve therapeutic outcomes and supress the emergence of resistance.

Aneuploidy Is Associated with Azole Resistance in Aspergillus fumigatus.

Azole resistance in Aspergillus fumigatus is on the rise. Nontarget-mediated mechanisms are a common cause of azole resistance in chronic pulmonary aspergillosis (CPA). Here, we investigate resistance mechanisms using whole-genome sequencing.

COVID-19-Associated Pulmonary Aspergillosis Isolates Are Genomically Diverse but Similar to Each Other in Their Responses to Infection-Relevant Stresses.

Secondary infections caused by the pulmonary fungal pathogen Aspergillus fumigatus are a significant cause of mortality in patients with severe coronavirus disease 19 (COVID-19). Even though epithelial cell damage and aberrant cytokine responses have been linked to susceptibility to COVID-19-associated pulmonary aspergillosis (CAPA), little is known about the mechanisms underpinning copathogenicity. Here, we analyzed the genomes of 11 A.

Pathogenicity and virulence of .

Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.

Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells.

COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, therapeutics that can help manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease.

Differential Proinflammatory Responses to by Airway Epithelial Cells In Vitro Are Protease Dependent.

is an important human respiratory mould pathogen. In addition to a barrier function, airway epithelium elicits a robust defence against inhaled by initiating an immune response. The manner by which initiates this response and the reasons for the immunological heterogeneity with different isolates are unclear.

Characterisation of Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy.

The precise characterization of the mechanisms modulating survival within airway epithelial cells has been impaired by the lack of live-cell imaging technologies and user-friendly quantification approaches. Here we described the use of an automated image analysis pipeline to estimate the proportion of spores taken up by airway epithelial cells, those contained within phagolysosomes or acidified phagosomes, along with the fungal factors contributing to these processes. Coupling the use of fluorescent strains and fluorescent epithelial probes targeting lysosomes, acidified compartments and cell membrane, we found that both the efficacy of lysosome recruitment to phagosomes and phagosome acidification determines the capacity of airway epithelial cells to contain growth.

Tranexamic acid use in severely injured patients, is it always appropriate?

Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.

Mesoporous silica nanoparticles with manganese and lanthanide salts: synthesis, characterization and cytotoxicity studies.

Several organic salts based on the combination of two different choline derivative cations and MnCl3-, GdCl4- and TbCl4- as anions were immobilized in mesoporous silica nanoparticles (MSNs) by a two-step synthetic method. Firstly, MSNs were functionalized with choline derivative cations with chloride anions and then the metals were incorporated by the reaction of the chloride with the respective metal chloride salts. These nanomaterials were fully characterized by different characterization techniques such as 1H-NMR, FT-IR, elemental analysis, TEM, TGA, N2 adsorption, XRD and DLS.

Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.

Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed "aspergilloses," in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host-pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A.

Boosting Antimicrobial Activity of Ciprofloxacin by Functionalization of Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) are very promising nanomaterials for treating bacterial infections when combined with pharmaceutical drugs. Herein, we report the preparation of two nanomaterials based on the immobilization of ciprofloxacin in mesoporous silica nanoparticles, either as the counter-ion of the choline derivative cation (MSN-[Ch][Cip]) or via anchoring on the surface of amino-group modified MSNs via an amide bond (MSN-Cip). Both nanomaterials were characterized by TEM, FTIR and solution H NMR spectroscopies, elemental analysis, XRD and N adsorption at 77 K in order to provide the desired structures.