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A major health concern of the 21 st century is the rise of multi-drug resistant pathogenic microbial species. Recent technological advancements have led to considerable opportunities for low-dimensional materials (LDMs) as potential next-generation antimicrobials. LDMs have demonstrated antimicrobial behaviour towards a variety of pathogenic bacterial and fungal cells, due to their unique physicochemical properties. This review provides a critical assessment of current LDMs that have exhibited antimicrobial behaviour and their mechanism of action. Future design considerations and constraints in deploying LDMs for antimicrobial applications are discussed. It is envisioned that this review will guide future design parameters for LDM-based antimicrobial applications. Antimicrobial resistance is a growing global problem and low dimensional materials have emerged as a potential solution. Here, the authors review the progress which has been made on low dimensional antimicrobials looking at the materials synthesis, modes of action and currently applications.

Biofilms are assemblages of microbial cells, extracellular polymeric substances (EPS), and other components extracted from the environment in which they develop. Within biofilms, the spatial distribution of these components can vary. Here we present a fundamental characterization study to show differences between biofilms formed by Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Pseudomonas aeruginosa, and the yeast-type Candida albicans using synchrotron macro attenuated total reflectance-Fourier transform infrared (ATR-FTIR) microspectroscopy. We were able to characterise the pathogenic biofilms’ heterogeneous distribution, which is challenging to do using traditional techniques. Multivariate analyses revealed that the polysaccharides area (1200–950 cm−1) accounted for the most significant variance between biofilm samples, and other spectral regions corresponding to amides, lipids, and polysaccharides all contributed to sample variation. In general, this study will advance our understanding of microbial biofilms and serve as a model for future research on how to use synchrotron source ATR-FTIR microspectroscopy to analyse their variations and spatial arrangements.

Antimicrobial resistance (AMR) poses a global health crisis demanding innovative solutions. Traditional antibiotics, though pivotal over the past century in combating bacterial infections, face diminished efficacy against evolving bacterial defense mechanisms, especially in Gram‐negative strains. This study explores self‐assembled ionizable lipid nanoparticles (LNPs) with the incorporation of two ionizable lipid components (one cationic, one anionic) in nanocarriers for advanced antimicrobial drug delivery of the broad‐spectrum antibiotic Piperacillin (Pip). Incorporating cationic ionizable lipid ALC‐0315, recognized as a functional lipid in the Pfizer‐BioNTech mRNA‐based SARS‐CoV‐2 vaccine, into LNPs allowed mesophase transition, pH responsiveness, and ionization behavior in acidic environments found in sites of bacterial infections, to be studied using synchrotron small angle X‐ray scattering, dynamic light scattering, and a 2‐(p‐toluidino)‐6‐naphthalene sulfonic acid assay. Incorporating another anionic ionizable lipid, oleic acid not only modulates the LNPs’ physicochemical properties, such as size, internal phase nanostructure, and surface charge but also synergistically enhances the antimicrobial potency together with ALC‐0315 with a benefit enhancing permeability and fusion with bacterial membranes. This study introduces a strategy for tailoring ionizable lipid compositions in LNPs, providing a new approach to antimicrobial treatment contributing to the fight against AMR. Lipid cubosomes comprising monoolein, ionizable cationic lipid ALC‐0315, and ionizable anionic oleic acid are developed as an antimicrobial drug delivery system. The synergistic effect of the internal inverse cubic structure and the ionic lipid molecular interactions significantly enhances the membrane permeability of piperacillin‐loaded particles, leading to increased Gram‐negative bacteria growth inhibition.

Deep eutectic solvents (DESs) and ionic liquids (ILs) are highly tailorable solvents that have shown a lot of promise for a variety of applications including cryopreservation, drug delivery, and protein stabilisation. However, to date, there is very limited information on the detailed interactions of these solvents with mammalian cells. In this work, we studied six DESs and one IL that show promise as cryoprotective agents, applying synchrotron macro–ATR–FTIR to examine their effects on key biochemical components of HaCat mammalian cells. These data were paired with resazurin metabolic assays and neutron reflectivity experiments to correlate cellular interactions with cellular toxicity. Stark differences were observed even between solvents that shared similar components. In particular, it was found that solvents that are effective cryoprotective agents consistently showed interactions with cellular membranes, while high toxicity correlated with strong interactions of the DES/IL with nucleic acids and proteins. This work sheds new light on the interactions between novel solvents and cells that may underpin future biomedical applications.

Antimicrobial Agent Delivery Ionizable lipid cubosomes comprising monoolein, ionizable cationic lipid ALC‐0315, and ionizable anionic oleic acid are developed as an antimicrobial drug delivery system. The synergistic effect of the internal inverse cubic structure and the ionic lipid molecular interactions significantly enhances the membrane permeability of piperacillin‐loaded particles, leading to increased Gram‐negative bacteria growth inhibition. More in article number 2400145, Haitao Yu, Calum J. Drummond, Jiali Zhai, and co‐workers.

Several international recommendations address the assessment of graft-versus-host disease (GvHD) after hematopoietic cell transplantation (HCT). This position statement by GvHD experts from the European Society for Blood and Marrow Transplantation (EBMT), the National Institutes of Health (NIH) and the Center for International Blood and Marrow Transplant Research (CIBMTR) reviews the existing guidelines for both acute and chronic GvHD, addresses potential confusions that arise in daily practice and proposes consensus definitions for many key terms. We provide a historical perspective on the currently available guidelines and recommend the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria for acute GvHD and the NIH 2014 criteria for chronic GvHD as the most comprehensive and detailed criteria available. This statement also offers practical guidance for the implementation of these recommendations and a set of consensus definitions for commonly used GvHD terms in order to facilitate future clinical and translational research. To assist the dissemination of these recommendations, a web-application based on this position statement is available ( https://www.uzleuven.be/egvhd ). We believe that adherence to a common set of GvHD assessment criteria is vitally important to improve the quality of data, compare results of retrospective studies and prospective clinical trials, and make therapeutic recommendations based on quality evidence.

Fast radio bursts (FRBs) are highly dispersed millisecond-duration radio flashes probably arriving from far outside the Milky Way1,2. This phenomenon was discovered at radio frequencies near 1.4 gigahertz and so far has been observed in one case3 at as high as 8 gigahertz, but not at below 700 megahertz in spite of substantial searches at low frequencies4,5,6,7. Here we report detections of 13 FRBs at radio frequencies as low as 400 megahertz, on the Canadian Hydrogen Intensity Mapping Experiment (CHIME) using the CHIME/FRB instrument8. They were detected during a telescope pre-commissioning phase, when the sensitivity and field of view were not yet at design specifications. Emission in multiple events is seen down to 400 megahertz, the lowest radio frequency to which the telescope is sensitive. The FRBs show various temporal scattering behaviours, with the majority detectably scattered, and some apparently unscattered to within measurement uncertainty even at our lowest frequencies. Of the 13 reported here, one event has the lowest dispersion measure yet reported, implying that it is among the closest yet known, and another has shown multiple repeat bursts, as described in a companion paper9. The overall scattering properties of our sample suggest that FRBs as a class are preferentially located in environments that scatter radio waves more strongly than in the diffuse interstellar medium in the Milky Way.

There is uncertainty about the effects of treating obstructive sleep apnea on glycemic control in patients with type 2 diabetes. To determine whether treatment of obstructive sleep apnea in patients with type 2 diabetes improves glycemic control. In this trial, we randomized patients with type 2 diabetes and no previous diagnosis of obstructive sleep apnea, with a glycated hemoglobin level of 6.5-8.5%, and an oxygen desaturation index of 15 or more events per hour to positive airway pressure therapy or to usual care. A total of 416 patients met the entry criteria as determined by each site and were randomized. Of the 298 participants who met centrally adjudicated entry criteria, no differences between the study groups were seen for change in glycated hemoglobin. Furthermore, there were no between-group differences when analyses were restricted to those with poorer baseline glycemic control, those with more severe sleep apnea, or those who were adherent to therapy. A greater fall in diastolic blood pressure occurred in the positive airway pressure group than in the usual care group (-3.5 mm Hg vs. -1.5 mm Hg; P = 0.07). This difference was significant in those who were adherent to positive airway pressure therapy (-4.4 mm Hg vs. -1.6 mm Hg; P = 0.02). There was a significant reduction in sleepiness in the positive airway pressure therapy group (P < 0.0001). Quality of life assessment revealed improvements in vitality, mental health, and mental component summary scores in the positive airway pressure therapy group. This trial showed no effect of positive airway pressure therapy on glycemic control in patients with relatively well-controlled type 2 diabetes and obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT00509223).

A suite of offline and real-time gas- and particle-phase measurements was deployed at Look Rock, Tennessee (TN), during the 2013 Southern Oxidant and Aerosol Study (SOAS) to examine the effects of anthropogenic emissions on isoprene-derived secondary organic aerosol (SOA) formation. High- and low-time-resolution PM2.5 samples were collected for analysis of known tracer compounds in isoprene-derived SOA by gas chromatography/electron ionization-mass spectrometry (GC/EI-MS) and ultra performance liquid chromatography/diode array detection-electrospray ionization-high-resolution quadrupole time-of-flight mass spectrometry (UPLC/DAD-ESI-HR-QTOFMS). Source apportionment of the organic aerosol (OA) was determined by positive matrix factorization (PMF) analysis of mass spectrometric data acquired on an Aerodyne Aerosol Chemical Speciation Monitor (ACSM). Campaign average mass concentrations of the sum of quantified isoprene-derived SOA tracers contributed to ~ 9 % (up to 28 %) of the total OA mass, with isoprene-epoxydiol (IEPOX) chemistry accounting for ~ 97 % of the quantified tracers. PMF analysis resolved a factor with a profile similar to the IEPOX-OA factor resolved in an Atlanta study and was therefore designated IEPOX-OA. This factor was strongly correlated (r2 > 0.7) with 2-methyltetrols, C5-alkene triols, IEPOX-derived organosulfates, and dimers of organosulfates, confirming the role of IEPOX chemistry as the source. On average, IEPOX-derived SOA tracer mass was ~ 26 % (up to 49 %) of the IEPOX-OA factor mass, which accounted for 32 % of the total OA. A low-volatility oxygenated organic aerosol (LV-OOA) and an oxidized factor with a profile similar to 91Fac observed in areas where emissions are biogenic-dominated were also resolved by PMF analysis, whereas no primary organic aerosol (POA) sources could be resolved. These findings were consistent with low levels of primary pollutants, such as nitric oxide (NO ~ 0.03 ppb), carbon monoxide (CO ~ 116 ppb), and black carbon (BC ~ 0.2 μg m−3). Particle-phase sulfate is fairly correlated (r2 ~ 0.3) with both methacrylic acid epoxide (MAE)/hydroxymethyl-methyl-α-lactone (HMML)- (henceforth called methacrolein (MACR)-derived SOA tracers) and IEPOX-derived SOA tracers, and more strongly correlated (r2 ~ 0.6) with the IEPOX-OA factor, in sum suggesting an important role of sulfate in isoprene SOA formation. Moderate correlation between the MACR-derived SOA tracer 2-methylglyceric acid with sum of reactive and reservoir nitrogen oxides (NOy; r2 = 0.38) and nitrate (r2 = 0.45) indicates the potential influence of anthropogenic emissions through long-range transport. Despite the lack of a clear association of IEPOX-OA with locally estimated aerosol acidity and liquid water content (LWC), box model calculations of IEPOX uptake using the simpleGAMMA model, accounting for the role of acidity and aerosol water, predicted the abundance of the IEPOX-derived SOA tracers 2-methyltetrols and the corresponding sulfates with good accuracy (r2 ~ 0.5 and ~ 0.7, respectively). The modeling and data combined suggest an anthropogenic influence on isoprene-derived SOA formation through acid-catalyzed heterogeneous chemistry of IEPOX in the southeastern US. However, it appears that this process was not limited by aerosol acidity or LWC at Look Rock during SOAS. Future studies should further explore the extent to which acidity and LWC as well as aerosol viscosity and morphology becomes a limiting factor of IEPOX-derived SOA, and their modulation by anthropogenic emissions.

NRC publication: Yes