Sustainable alginate-polyionene interpolymeric complex was developed by incorporating poly-cationic polyimidazolium (PIM) salts into alginate solutions or absorbing them into alginate sheets. The multifunctional PIM acts both as a crosslinker, forming the alginate structure and as an antimicrobial agent, which can be gradually released from the material. Here, we explored the potential applications of alginate-PIM materials, such as antimicrobial coatings, wound dressings, and solid sheets with durable antimicrobial activity.

Semiconductor photocatalysts, such as TiO2 and ZnO, have garnered significant attention for their ability to generate hydroxyl radicals, offering various practical applications. However, the reliance on UV light to facilitate electron-hole separation for hydroxyl radical production poses limitations. In this study, a novel approach is presented utilizing Zn@Fe core/shell particles capable of generating hydroxyl radicals without external energy input. The generation process involves electron donation from Zn to O2, resulting in the formation of radical species .O2-/H2O2, followed by Fe-catalyzed conversion of H2O2 into hydroxyl radicals through the Fenton reaction. The release of .OH imparts good antimicrobial and antiviral properties to the Zn@Fe particles. Furthermore, the inclusion of Fe confers magnetic properties to the material. This dual functionality holds promise for diverse potential applications for the Zn@Fe particles. Magnetic Zn@Fe particles with self-promoted hydroxyl radical generation properties demonstrate excellent antimicrobial activities. They are successfully applied as self-disinfecting paints, with no irritation or toxicity to the skin. image

Oxidized halogen antimicrobials, such as hypochlorous acid, have been widely used for microbial control, successfully eliminating waterborne diseases like cholera, typhoid, dysentery, and hepatitis A in developed countries. During the COVID-19 pandemic, these acids were used extensively for air and surface disinfection. However, they require repeated applications as they only offer one-time disinfection. To address this issue, we have developed Cu nanoparticles decorated Zn and Zn@ZnO (denoted as Zn@Cu and Zn@ZnO/Cu), mimicking the neutrophils NADPH oxidase (NOX) system. This novel system utilizes zinc metal to produce H2O2, and a catalytic copper shell to convert H2O2 and Cl-/Br-/I- to hypohalous acid, which has good antimicrobial and antiviral properties along with enhanced durability. The addition of Zn@Cu onto painted surfaces shows good disinfection properties. The application of Zn@ZnO/Cu in diabetic wound healing yields superior outcomes to the conventional silver-based commercial products.

Antimicrobial materials are a crucial component in eradicating and managing the spread of infectious diseases. They are expected to act on a broad spectrum of microbes, including emerging pathogens which could cause the next Disease X. Herein, we reassessed a series of antimicrobial imidazolium polymers on our shelves and uncovered extended functionality through dual modes of action. By redesigning their structures, a truly broad-spectrum antimicrobial material with optimized activity against bacteria (G + ve, G -ve) and fungi, as well as enveloped and non-enveloped viruses was developed. We demonstrated that the imidazolium polymer exhibits dual modes of function against microbes: targeting the microbial membrane and binding DNA. The latter DNA binding affinity was found to be key against non-enveloped viruses. With this insight, we designed small molecule compounds that exhibited optimum broad spectrum antimicrobial activity and excellent efficacy against ESKAPE group of pathogens that are responsible for some of the deadliest nosocomial infections worldwide. Our results could also shed light on the design of broad-spectrum antimicrobial compounds against Disease X.

Invited for this month ' s cover is the group of Ning Yan at the National University of Singapore. The image shows the production of modified oligosaccharides from marine biomass as powerful antimicrobial 'weapon' through the 'booster' made of formaldehyde. The Research Article itself is available at 10.1002/cssc.202300591.

The Front Cover shows chitin-derived oligosaccharides from marine biomass as powerful antimicrobial ‘weapon’ through the ‘booster’ containing formaldehyde. The one-pot reaction of chitin with formaldehyde, an inexpensive bulk chemical, as methylation and reduction reagent converts chitin to N,N-dimethyl chitosan oligosaccharide (DMCOS), dramatically boosting its ‘damage output’ against fungus. The conversion within the ‘booster’ is a three-step tandem process, with critical involvement of adjacent hydroxyl groups. More information can be found in the Research Article by J. Cheng et al.

The rapid development of antimicrobial resistance (AMR) among infectious pathogens has become a major threat and challenge in healthcare systems globally. A strategy distinct from minimizing the overuse of antimicrobials involves the development of novel antimicrobials with a mode of action that prevents the development of AMR microbial strains. Reactive oxygen species (ROS) are formed as a natural byproduct of the cellular aerobic metabolism. However, it becomes pathological when ROS is produced at excessive levels. Exploiting this phenomenon, research on redox-active bactericides has been demonstrated to be beneficial. Materials that release ROS via photodynamic, thermodynamic, and photocatalytic interventions have been developed as nanomedicines and are used in various applications. However, these materials require external stimuli for ROS release to be effective as biocides. In this paper, we report novel zinc-based metal organic framework (Zn@MOF) particles that promote the spontaneous release of active ROS species. The synthesized Zn@MOF spontaneously releases superoxide anions and hydrogen peroxide, exhibiting a potent antimicrobial efficacy against various microbes. Zn@MOF-incorporated plastic films and coatings show excellent, long-lasting antimicrobial potency even under continuous microbial challenge and an aging process. These disinfecting surfaces maintain their antimicrobial properties even after 500× surface wipes. Zn@MOF is also biocompatible and safe on the skin, illustrating its broad potential applications in medical technology and consumer care applications.

Hand or surface sanitizers are all liquid-based products which can be mainly categorized as alcohol or non-alcohol based. The constant release of highly persistent disinfectants and chemicals is hazardous to the environment and human health. Herein, a new concept of solid elastomer sanitizer with inherent fast-killing antimicrobial property is described. Silicone (PDMS) was chosen as the elastomer where the active antimicrobial component of imidazolium polymer (PIM) was carefully modified and incorporated into the PDMS matrix through strong covalent bonds. This chemically bonded antimicrobial component within PDMS acts via release-on-demand model which allows for the long-term reusability of the material. The resulting material can serve as a reusable solid sanitizer that is toxic-free and skin-friendly with fast-killing property. It was proven to sanitize our hands or surfaces and kill microbes within 30-60 s of contact, including ESKAPE pathogens, bacteria, fungi and MS2 bacteriophage. This new concept of solid sanitizer methodology will provide an interesting insight and infinite possibilities for extending to other types of elastomers with suitable or tunable antimicrobial components. This also helps to provide a safer and greener sanitizing model which can dramatically reduce the usage and/or release of disinfectants or harmful chemicals to the environment. The possibilities of extending to other elastomers also widen its potential applications.

Catheters are the most widely used medical device and on the same note, catheter associated infections are also prevalent in health and medical care, globally. Among them, urinary catheters associated infections (CAUTI) predominates the nosocomial infections. Antimicrobial/antifouling catheter innovations to overcome infections has escalated exponentially in recent years. Imidazolium-based polymer antimicrobial (PIM45) is a potent broadspectrum antimicrobial and incorporation of PIM45 in PDMS matrix (PDMS-PIM45 biomaterial) proved to produce a robust, long-lasting antimicrobial biomaterial and could be recycled up to 45 days. Thus, exhibiting beneficial potential for development of medical devices that display inherent antimicrobial propensity. In this study, using a continuous flow model of artificial urine, we proved that PDMS-PIM45 could eradicate the CAUTI causative pathogens, Escherichia coli, Klebsiella pneumoniae, Vancomycin-Resistant Enterococcus sp , completely at 106 CFU/ml loading. Though colonization was not inhibited, lower rate of infection and absence of biofilm development was observed for Methicillin-Resistant Staphylococcus aureus, a newly emerging CAUTI pathogen. Importantly, we have also shown that PDMS-PIM45 could prevent encrustation following Proteus mirabilis infection, and maintain the low pH of artificial urine over 7 days in continuous flow model.

Surface antimicrobial materials are of interest as they can combat the critical threat of microbial contamination without contributing to issues of environmental contamination and the development drug resistance. Most nanostructured surfaces are prepared by post fabrication modifications and actively release antimicrobial agents. These properties limit the potential applications of nanostructured materials on flexible surfaces. Here, we report on an easily synthesized plastic material with inherent antimicrobial activity, demonstrating excellent microbicidal properties against common bacteria and fungus. The plastic material did not release antimicrobial components as they were anchored to the polymer chains via strong covalent bonds. Time-kill kinetics studies have shown that bactericidal effects take place when bacteria come into contact with a material for a prolonged period, resulting in the deformation and rupture of bacteria cells. A scanning probe microscopy analysis revealed soft nanostructures on the submicron scale, for which the formation is thought to occur via surface phase separation. These soft nanostructures allow for polyionic antimicrobial components to be present on the surface, where they freely interact with and kill microbes. Overall, the new green and sustainable plastic is easily synthesized and demonstrates inherent and long-lasting activity without toxic chemical leaching.

In the search for a fast contact-killing antimicrobial surface to break the transmission pathway of lethal pathogens, nanostructured copper surfaces were found to exhibit the desired antimicrobial properties. Compared with plain copper, these nanostructured copper surfaces with Cu(OH)2 nano-sword or CuO nano-foam were found to completely eliminate pathogens at a fast rate, including clinically isolated drug resistant species. Additionally these nanostructured copper surfaces demonstrated potential antiviral properties when assessed against bacteriophages, as a viral surrogate, and murine hepatitis virus, a surrogate for SARS-CoV-2. The multiple modes of killing, physical killing and copper ion mediated killing contribute to the superior and fast kinetics of antimicrobial action against common microbes, and ESKAPE pathogens. Prototypes for air and water cleaning with current nanostructured copper surface have also been demonstrated.

Abstract Background In addition to the widespread use of antibiotics in healthcare settings, the current COVID-19 pandemic has escalated the emergence of antibiotic resistance. Nosocomial infections among hospitalized patients is a leading site for such resistant microbial colonization due to prolonged use of invasive devices and antibiotics in therapies. Invasive medical devices, especially catheters, are prone to infections that could accelerate the development of resistant microbes. Often, catheters - particularly urinary catheters - are prone to high infection rates. Antibiotic-coated catheters can reduce infection rates and although commercially available, are limited in efficacy and choices. Methods Herein, a novel and facile method to fabricate PMDS-based biomaterial for the development of antimicrobial eluting catheters is presented. Silicone based organic polymer polydimethylsiloxane (PDMS) was used to prepare a biomaterial containing novel polymeric imidazolium antimicrobial compound. Results It was found that the PDMS-based biomaterials could eradicate microbial colonization even after 60 days in culture with continuous microbial challenge, be recycled over multiple uses, stored at room temperature for long-term usage and importantly is biocompatible. Conclusion The PDMS-based biomaterial displayed biocidal functionality on microbes of clinical origin, which form major threats in hospital acquired infections. Graphical Abstract

Antimicrobial resistance poses an increasingly serious global health threat. Hence, new antimicrobials with low propensity toward inducing resistance in bacteria are being developed to combat this threat. In this work, a series of imidazolium tetramers have been synthesized by modulating the linkers between imidazoliums or the length of the end groups within the structures of oligomers in order to optimize the activity, selectivity, and biocompatibility of the compounds. These new materials possess high biocompatibility, Gram selectivity, and high efficacy against the selected bacterium as well as clinically isolated methicillin-resistant Staphylococcus aureus species without inducing drug resistance. Therefore, we believe that these compounds can potentially be used to mitigate resistance as highly effective disinfectants in healthcare products or as antimicrobial therapies specifically for Gram-positive bacterial infections.

Antibiotic resistance has become one of the major, deadly threats to public health worldwide. This paper highlights several recent works, which may initiate the development of comprehensive approaches to mitigate antibiotic resistance. The new strategies demonstrate efficiency and efficacy, with very little probability of inducing drug resistance, paving the way for further breakthroughs in drug discovery for infection control.

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.

RATIONALE:Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets.OBJECTIVE:We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo.METHODS AND RESULTS:Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats. A progressive increase of miR-31 (up to 91.4±11.3 fold) was detected in the infarcted myocardium by quantitative real-time PCR. Following target prediction analysis, reporter gene assays confirmed that miR-31 targets the 3´UTR of cardiac troponin-T (Tnnt2), E2F transcription factor 6 (E2f6), mineralocorticoid receptor (Nr3c2) and metalloproteinase inhibitor 4 (Timp4) mRNAs. In vitro, hypoxia and oxidative stress up-regulated miR-31 and suppressed target genes in cardiac cell cultures, whereas LNA-based oligonucleotide inhibition of miR-31 (miR-31i) reversed its repressive effect on target mRNAs. Therapeutic post-ischemic administration of miR-31i in rats silenced cardiac miR-31 and enhanced expression of target genes, while preserving cardiac structure and function at 2 and 4weeks post-MI. Left ventricular ejection fraction (EF) improved by 10% (from day 2 to 30 post-MI) in miR-31i-treated rats, whereas controls receiving scrambled LNA inhibitor or placebo incurred a 17% deterioration in EF. miR-31i decreased end-diastolic pressure and infarct size; attenuated interstitial fibrosis in the remote myocardium and enhanced cardiac output.CONCLUSION:miR-31 induction after MI is deleterious to cardiac function while its therapeutic inhibition in vivo ameliorates cardiac dysfunction and prevents the development of post-ischemic adverse remodeling.

Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

The regulatory roles for non-coding RNAs, the long non-coding RNAs and microRNAs, are emerging as crucial determinants of central nervous system development and function. Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule that has been shown to play an important role in neurite outgrowth during neuronal development. Precise expression of the Negr1 gene is crucial for proper brain development and is dysregulated during brain injury. Hence, we attempted to elucidate the non-coding RNAs that control Negr1 gene expression. A long non-coding RNA, BC048612, transcribed from the bidirectional GC-rich Negr1 gene promoter was found to influence Negr1 mRNA expression. In vitro knockdown of the long non-coding RNA resulted in significant down-regulation of Negr1 mRNA expression, NEGR1 protein levels and neurite length whereas over-expression enhanced Negr1 mRNA expression, NEGR1 protein levels and increased neurite length. Meanwhile, another non-coding RNA, microRNA-203, was found to target the 3' untranslated region of the Negr1 mRNA. Inhibition of microRNA-203 led to increased expression of Negr1 mRNA, elevated NEGR1 protein levels and increased neurite length. Conversely, microRNA-203 over-expression decreased the level of Negr1 mRNA, NEGR1 protein and neurite length. Neither microRNA-203 nor the long non-coding RNA, BC048612 could influence each other's expression. Hence, the long non-coding RNA, BC048612, and microRNA-203 were determined to be positive and negative regulators of Negr1 gene expression respectively. These processes have a direct effect on NEGR1 protein levels and neurite length, thus highlighting the importance of the regulatory non-coding RNAs in modulating Negr1 gene expression for precise neuronal development.

Long non-coding RNAs and microRNAs control gene expression to determine central nervous system development and function. Neuronal growth regulator 1 (NEGRI) is a cell adhesion molecule that plays an important role in neurite outgrowth during neuronal development and its precise expression is crucial for correct brain development. The data described here is related to the research article titled "A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of Neuronal growth regulator 1 (NEGRI) adhesion protein" W. This data article contains detailed bioinformatics analysis of genetic signatures at the Negri gene locus retrieved from the UCSC genome browser. This approach could be adopted to identify putative regulatory non coding RNAs in other tissues and diseases. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/40).

Background Dengue is the most common arboviral illness worldwide. While most infected patients recover, a proportion of them develop severe complications or fatality. Nevertheless, the pathophysiological mechanisms which distinguish the disease severity and associated complications are not clearly understood. We studied blood profiles of dengue patients in order to identify microRNAs that could play a role in these pathophysiological mechanisms. Methods Blood samples from 26 dengue-infected patients were collected within 0–14 days of infection. Together with samples obtained from six healthy individuals, microRNA profiles were generated to identify significantly altered microRNAs upon dengue infection. Profiles of patients with influenza were also used to determine the disease specificity of these altered microRNAs. Their discriminative power to distinguish dengue from influenza was then tested statistically. Results Several significantly altered microRNAs were identified in patients with dengue. Twelve microRNAs were specifically altered upon acute dengue whereas 14 microRNAs exhibited similar expression between dengue and influenza. Seventeen microRNAs which could potentially distinguish dengue-related complications were also identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation. Conclusions We identified two panels of microRNAs – one specific for dengue and the other common to dengue and influenza. We also report on the differentially expressed microRNAs in patients with mild versus severe dengue, which could be the basis for the complications seen in them.