Rise In Resistance Research Articles

Cu2O-SnO2-PDA heterozygous nanozyme doped hydrogel mediated conglutinant microenvironment regulation for wound healing therapy

Bacterial infection significantly hinders the wound healing process. Overuse of antibiotics has led to the rise of drug resistance in bacteria, making the development of smart medical dressings that promote wound healing without antibiotics, a critical need. In this study, Cu₂O-SnO₂-PDA (PCS) nanoenzymes with Fenton-like activity and high photothermal conversion efficiency were developed. These nanoenzymes were then incorporated into a hydrogel through cross-linking of acrylamide (AM) and N-[Tris-(hydroxymethyl)methyl] acrylamide (THMA), forming a tough, highly-adhesive, and self-healing composite hydrogel (AT/PCS) with antimicrobial properties. The AT/PCS hydrogel exhibits excellent mechanical strength and adhesion, facilitating increased oxygen levels and strong adherence to the wound site. Moreover, it effectively regulates the wound microenvironment by combining synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT) for antibacterial treatment. The AT/PCS hydrogel enhances collagen deposition and expedites wound healing in a rat model, largely due to its potent antibacterial properties.

Experience oExperience of an antimicrobial stewardship programme in a tertiary care hospital in Sri Lankaf an Antimicrobial stewardship programme in a tertiary care hospital in Sri Lanka

Introduction: Hospital-based antibiotic stewardship programmes are helpful to optimise the treatment of infectious diseases and to prevent the development of antibiotic resistance. The rise in multi-drug resistance in Sri Lankan hospitals including carbapenem-resistant organisms emphasises the need for implementation of effective AMS programmes and planned in national strategic plan to combat antimicrobial resistance. A sustainable approach towards an effective AMS pro-gramme is continuously needed. The data on experience in implementing AMS programmes in Sri Lanka is scares.Objective: To share the experiences and challenges faced while implementing an AMS programme in a hospital,.d. Guidelines on empirical and prophylactic use of anti-microbials and common infections were distributed to each unit. A list of antimicrobials prepared according to WHO AwaRe classification and drug chart designed for documentation of optimal prescribing.Results: There was a 27.3% reduction in mean carba-penem consumption after initial implementation and the consumption is gradually rising. 36% decrease in carbapenem resistance rate in Acinetobacter species, 33% reduction in carbapenem-resistant Pseudomonas species was observed. The point prevalence of anti-microbial use was found to be 45.5% and 49% in 2023 and 2024 respectively. The commonest indication for antimicrobial use in prescriptions was community-acquired infections. There was a reduction in continuing antibiotics for surgical prophylaxis after implementation of AMS programme.Conclusion: For successful implementation of an AMS programme in community acquired drug resistance also should be addressed. In hospital setting continuation of surgical prophylaxis is an area which can be improved easily. Adequate staff and time allocated for AMS activities will be beneficial for sustainable programmes.

Experiments on High-Temperature Irradiation of Li2ZrO3/MgLi2ZrO4 Ceramics by He2+ Ions

The key objective of this study is to determine the effect of interphase boundaries, the formation of which is caused by the variation of Li2ZrO3/MgLi2ZrO4 phases in lithium-containing ceramics based on lithium metazirconate, on the resistance to near-surface layer destruction processes associated with irradiation with He2+ ions. During the observation of the deformation effects that have an adverse impact on the volumetric swelling of the near-surface layers of ceramics, the thermal expansion factor caused by high-temperature irradiation was considered, simulating conditions as close as possible to the operating conditions of these materials as blankets for tritium propagation. During the studies conducted, it was established that an elevation in the contribution of MgLi2ZrO4 in the composition of ceramics leads to a rise in resistance to deformation swelling caused by structural distortions of the crystal lattice, due to a decrease in the effect of thermal expansion, alongside the presence of interphase boundaries. The established dependencies of the change in the hardness of the near-surface layer of the studied ceramics made it possible to establish the kinetics of softening caused by the deformation distortion of the crystalline structure, as well as to determine the relationship between volumetric swelling and softening (change in hardness) and a decrease in crack resistance (change in the value of resistance to single compression).

Health system interventions and responses to anti-microbial resistance: A scoping review of evidence from 15 African countries.

The global rise in antimicrobial resistance (AMR) is claiming the lives of more than 1.2 million people each year. According to the World Health Organization (WHO) this global health crisis is particularly acute in Africa, largely due to fragile and underfunded health systems. Efforts to combat this public health threat have led to the implementation of health system interventions worldwide aimed at managing and containing the spread of AMR. However, the literature on the real time impacts and the barriers that hinder the implementation of these interventions in the African context is limited. The objective of this scoping review was to identify AMR interventions in African health systems, their impact, and the challenges of the implementation. Drawing on Muka and colleague's 24 step approach for scoping reviews, two major public health databases (PubMed and Global Health) were searched for articles in accordance with the PRISMA guidelines resulting in 4,783 records. Screening and retrieval of articles was done using Rayyan software based on specified inclusion criteria and 36 articles included in the final list. These articles were synthesized after extracting specific data on AMR interventions and their impact on African health systems. The review identified four broad impacts of AMR interventions including 1. Reduction in antibiotics use, 2. Increased adherence to guidelines and protocols, 3. Enhanced laboratory-based AMR surveillance, 4. Development of antimicrobial stewardship (AMS) Action Plans and Teams. However, challenges such as poor laboratory infrastructure, logistical challenges, poor financial commitment and inadequate education and training were identified as challenges impeding the successful implementation of AMR interventions in Africa. Our findings reveal a range of successful AMR interventions in African health systems although infrastructural and financial challenges remain. Better standardization and reporting of AMR diagnosis while leveraging the available information is needed to improve the optimization of treatment guidelines across Africa.

Pharmacies and use of antibiotics: a cross sectional study in 19 Arab countries

BackgroundThe rise of antimicrobial resistance, which is partially attributed to the overuse and/or misuse of antibiotics in health care, is one of the world’s largest public health challenges. The distribution of antibiotics in absence of a prescription in pharmacies is a significant contributor to the growing global public health crisis of antibiotic resistance. A pharmacist’s clinical and lawful knowledge of antibiotic provide has an impact on the proper way to dispense medication. There are few novel studies assessing pharmacists comprehension and experience in prescribing antibiotics in low- and middle-income countries, including those in the Arabian region.Objectives(I) assess pharmacy team members Knowledge about antibiotics as reported by individuals themselves and their behavior in dispensing antimicrobial without a prescription and (ii) find potential influences on this behavior.SettingPharmacists were chosen from various regions in Algeria, Bahrain, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen, based on their convenience and ease of access.MethodsA descriptive cross-sectional assessment among a random sample (n = 2833) of community pharmacists was conducted Utilizing a structured, validated, and questionnaire that underwent pilot testing, a comprehensive survey with four distinct sections covering biography, knowledge, practice, and attitude domains was employed.The main outcomeMeasures were knowledge, attitude, and practice toward dispensing antibiotics without prescription.ResultsOf the 3100 pharmacists reached, 2833 completed and return the questionnaires (response rate 91.3%). Most of the respondents were male (57.4%). Aged between 19 and 31 years old (76.2%). Most of them held a B.Sc. Degree (78.5%). Worked as staff pharmacists (73.2%). During the survey, it was discovered that there were gaps in their knowledge regarding antibiotic usage. A total of 45.7% of the respondents were unaware that antibiotics can be used as prophylaxis, while 33.3% did not recognize the consequences of making incorrect antibiotic choices. Regarding their practice patterns, 53.8% of the pharmacists admitted that they did not consistently adhere to guidelines when dispensing antibiotics. In terms of attitudes toward antibiotic usage, 36.8% disagreed with the guidelines of not supply antibiotics without a prescription, suggesting some variation in opinions among pharmacists on this matter. Additionally, a significant percentage (75%) believed that community pharmacists had qualifications to prescribe antibiotics for infections.ConclusionThe recent survey has shed light on the differences among pharmacists in regard to dispensing antibiotics without prescriptions and their understanding of resistance. The findings are concerning, indicating a deficient in of knowledge as regards the use of antibiotics. It is crucial to implement regulations and enhance education efforts to tackle the growing problem of resistance. Collaboration between healthcare professionals and awareness campaigns is essential in addressing this issue.

Gaps in knowledge and recurrent urinary tract infections in women.

The focus of this review is to present recent literature and gaps in knowledge (GIKs) surrounding the current and future treatment and prevention of uncomplicated recurrent urinary tract infections (rUTIs) in women. Recurrent urinary tract infections are common, significantly reduce quality of life, and create a substantial economic burden to the healthcare system. They are disproportionately affecting the postmenopausal women. Antibiotics, which are used for the treatment and prophylaxis of uncomplicated rUTI, have become problematic, as there is a global rise in allergy and resistance to these agents and their use is associated with further antimicrobial resistance. Thus, in recent decades, several alternative, nonantibiotic approaches have been evaluated. There is a critical need for a concerted and standardized methodology for diagnosing, treating, and monitoring women with rUTIs. Additionally, novel nonantibiotic alternative treatment and preventive measures for UTIs are desperately required to address the global issue of antibiotic recalcitrance in all age groups, and specifically older women. Research efforts have sought to develop alternative and more effective techniques; many of which appear to be promising, but require additional evaluation and validation through clinical trials.

In vitro and In silico Antibacterial Evaluation of N-Methyl-2-phenylmaleimides

Background: Novel antibiotics are needed to stem the rise of antimicrobial resistance. N-Methyl-2-phenylmaleimide (NMP) compounds previously synthesised by our research group are structural analogues of 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones found by others to have antibacterial activity. Objectives: This study aims to explain the significance of NMPs and their antibacterial activity. The antibacterial activity of the NMPs was determined against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The partition coefficient of the NMPs and a pharmacophore model were used to explain their antibacterial activity. Methods: The Kirby Bauer Disc diffusion method was used to screen the NMPs for activity, while the broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the active NMPs. Using the in vitro antibacterial activity of 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones, a common feature pharmacophore model was constructed and validated. The rank score, fit value, enrichment factor (EF20%), and receiver operating characteristic area under the curve (ROC-AUC) were used as validation metrics. Results: The NMPs were only active against S. aureus, with compound 3 (4 µg/ml) being the most active. The majority of NMPs were bacteriostatic. A common feature pharmacophore model was validated (rank score: 120.5; fit value: 4; EF20%: 4.3; ROC-AUC: 0.9 ± 0.03) and showed that three hydrogen bond acceptors and a ring aromatic region are important for activity. Comparing the partition coefficient of the NMPs to their MIC a statistically significant correlation was found. Conclusion: NMPs can be used as lead compounds in future studies. The validated pharmacophore model and partition coefficient can be used to develop more active compounds.

Superhydrophobic Dressing for Singlet Oxygen Delivery in Antimicrobial Photodynamic Therapy against Multidrug-Resistant Bacterial Biofilms.

The rise of antimicrobial resistance poses a critical public health threat worldwide. While antimicrobial photodynamic therapy (aPDT) has demonstrated efficacy against multidrug-resistant (MDR) bacteria, its effectiveness can be limited by several factors, including the delivery of the photosensitizer (PS) to the site of interest and the development of bacterial resistance to PS uptake. There is a need for alternative methods, one of which is superhydrophobic antimicrobial photodynamic therapy (SH-aPDT), which we report here. SH-aPDT is a technique that isolates the PS on a superhydrophobic (SH) membrane, generating airborne singlet oxygen (1O2) that can diffuse up to 1 mm away from the membrane. In this study, we developed a SH polydimethylsiloxane dressing coated with PS verteporfin. These dressings contain air channels called a plastron for supplying oxygen for aPDT and are designed so that there is no direct contact of the PS with the tissue. Our investigation focuses on the efficacy of SH-aPDT on biofilms formed by drug-sensitive and MDR strains of Gram-positive (Staphylococcus aureus and S. aureus methicillin-resistant) and Gram-negative bacteria (Pseudomonas aeruginosa and P. aeruginosa carbapenem-resistant). SH-aPDT reduces bacterial biofilms by approximately 3 log with a concomitant decrease in their metabolism as measured by MTT. Additionally, the treatment disrupted extracellular polymeric substances, leading to a decrease in biomass and biofilm thickness. This innovative SH-aPDT approach holds great potential for combating antimicrobial resistance, offering an effective strategy to address the challenges posed by drug-resistant wound infections.

Novel Modified Piperacillin Inhibitors of Penicillin-Binding Protein 3 (PBP3) and Their Intermolecular Interactions.

<b>Background and Objective:</b> Despite the rise of antibiotic resistance, penicillin and the broader group of β-lactams have continued to be the most crucial class of antibiotics. Penicillin-Binding Protein 3 (PBP3) in <i>Pseudomonas aeruginosa</i> is the specific molecule that β-lactam-based medicines target. The objective is to design and study several piperacillin derivatives to create novel antibacterial agents. <b>Materials and Methods:</b> Piperacillin derivatives were drawn using chem sketch and prepared using AutoDock 4.2.6 Tools. Molecular docking simulations were conducted on novel piperacillin derivatives and piperacillin (Control) against the 6r3x.PDB protein. The AutoDock log files were analyzed to determine the lowest energy of binding (LEB) values for each ligand. Consequently, the conformer with the most favorable binding energy may be identified. <b>Results:</b> All of the proposed piperacillin derivatives displayed improved binding energies when compared to the reference chemical piperacillin. This suggests the potential for stronger interactions between derivatives and proteins, resulting in an enhanced likelihood of biological effects. Compounds b, e and j, when used alongside piperacillin, showed similar binding sites inside the active site and have the potential for additional characterization. <b>Conclusion:</b> Compounds b, e and j are highly likely to exhibit inhibitory activity, indicating that they should be synthesized and tested for biological activity.

Advances in Artemisinin Resistance: Mechanisms, Detection, and Novel Therapeutic Approaches

Artemisinin-based combination therapies (ACTs) have been instrumental in reducing global malaria mortality over the past two decades. However, the rise of artemisinin resistance, particularly in Southeast Asia and parts of Africa, threatened these gains. Artemisinin resistance was characterized by delayed parasite clearance and is primarily driven by mutations in the kelch13 (K13) gene, which reduce the drug’s efficacy. This review explored the mechanisms behind artemisinin resistance, including genetic mutations, parasite stress responses, and reduced ring-stage sensitivity. Detection strategies, such as the use of molecular markers like K13 mutations and in vitro phenotypic assays, were discussed in detail. To combat resistance, novel therapeutic approaches were emerging, including the optimization of ACTs, the use of triple-drug regimens, host-directed therapies, and gene-editing technologies. The article highlighted the need for new antimalarial drugs, improved diagnostic tools, and global collaboration to address this growing challenge. We conducted the review by analyzing recent literature and summarizing advances in both resistance mechanisms and therapeutic strategies. Finally, future directions were outlined, emphasizing the importance of research, regulatory frameworks, and investment to mitigate the spread of resistance and ensure effective malaria control. Keywords: Artemisinin resistance, K13 mutations, malaria treatment, combination therapies, gene editing, host-directed therapies.

Green and energy-saving tread rubber by constructing chemical cross-linking interface between graphene oxide and natural rubber

The dispersibility of fillers and interfacial interaction are crucial for polymer nanocomposites. Developing a simple, efficient and green method to simultaneously reduce and functionalize graphene oxide (GO) for preparing graphene/rubber composites with excellent dispersibility and enhanced interfacial interactions remains one of the main trends in developing and expanding the application of graphene in the rubber industry. In this work, VOC (volatile organic compound) -free and environmentally friendly L-methionine (L-Met) was selected as the functional modifier of GO. Then, L-Met-modified GO (MGO) was blended with natural rubber (NR) in an aqueous phase to prepare MGO/NR composites. The amphiphilic property of L-Met not only reduced GO but also endowed it with less agglomeration and excellent water dispersibility, which was a prerequisite for achieving uniform dispersion of GO in the NR matrix. In addition, the amino acids on the surface of MGO enhanced the compatibility between GO and the protein-phospholipid layer on the outer layer of NR latex particles. Meanwhile, L-Met containing sulfur bonds promoted rubber vulcanization, resulting in the formation of a cross-linked network between the modified GO and NR molecular chains. Compared to unmodified GO/NR composites, MGO/NR composites exhibited excellent mechanical properties and low heat build-up. More importantly, the solid tire prepared by using L-Met as the interface modifier for GO filled rubber showed lower rolling resistance and temperature rise, and the energy saving efficiency was improved. This strategy is expected to provide a new insight into the green production of organically modified graphene and the preparation of low-energy-consumption green graphene tires.

Adjuvant-dependent impacts on vaccine-induced humoral responses and protection in preclinical models of nasal and genital colonization by pathogenic Neisseria.

Neisseria gonorrhoeae, which causes the sexually transmitted infection gonorrhea and N. meningitidis, a leading cause of bacterial meningitis and septicemia, are closely related human-restricted pathogens that inhabit distinct primary mucosal niches. While successful vaccines against invasive meningococcal disease have been available for decades, the rapid rise in antibiotic resistance has led to an urgent need to develop an effective gonococcal vaccine. Several surface antigens are shared among these two pathogens, making cross-species protection an exciting prospect. However, the type of vaccine-mediated immune response required to achieve protection against respiratory versus genital infection remains ill defined. In this study, we utilize well established mouse models of female lower genital tract colonization by N. gonorrhoeae and upper respiratory tract colonization by N. meningitidis to examine the performance of transferrin binding protein B (TbpB) vaccines formulated with immunologically distinct vaccine adjuvants. We demonstrate that vaccine-mediated protection is influenced by the choice of adjuvant, with Th1/2-balanced adjuvants performing optimally against N. gonorrhoeae, and both Th1/2-balanced and Th2-skewing adjuvants leading to a significant reduction in N. meningitidis burden. We further establish a lack of correlation between protection status and the humoral response or bactericidal titre. Combined, this work provides supports the feasibility for a single vaccine formulation to achieve pan-neisserial coverage.

Blocking HXA3-mediated neutrophil elastase release during S. pneumoniae lung infection limits pulmonary epithelial barrier disruption and bacteremia.

Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant threefold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin, triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased the release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier-disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.IMPORTANCEStreptococcus pneumoniae (Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses to Sp. Excessive polymorphonuclear leukocyte (PMN) infiltration into Sp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflect bona fide lung epithelium, we identified eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment for Sp lung infection.

Pharmacophore-based approach for the identification of potent inhibitors against LpxC Enzyme from Salmonella Typhi

Antimicrobial resistance (AMR) is currently a global health concern, mostly caused by microorganisms like bacteria, viruses, parasites, and fungi that acquire resistance to antimicrobial drugs. Salmonella is responsible for a variety of diseases but mainly cause typhoid. The primary concern is the rise in resistance in both non-typhoid and typhoid strains of this species. To address this issue, it is necessary to identify novel targets and strategies for the development of new antibacterial drugs. Lipid A, a strong bacterial endotoxin that modulates the immune system in human, is a key component of the virulence factor generated during the salmonella infection. Lipid A is synthesized in case of Gram-negative bacteria by cascade of nine enzyme pathway. The second step in case of Lipid A biosynthesis, catalysed by LpxC, a Zn+ dependent metallo-amidase considered as rate limiting step. In this manuscript we have used protein-ligand interaction fingerprint (PLIF)–derived pharmacophore models to screen small molecules (natural products library from Zinc database, Asinex database, Thiophene analogues) against Salmonella typhi LpxC (StLpxC). Further top hit molecules were subjected to MD-simulation and ADMET studies. We identified three optimal compounds, s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8, that exhibit strong binding affinity towards the LpxC active site.

Time-resolved multi-omics reveals diverse metabolic strategies of Salmonella during diet-induced inflammation.

With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on Salmonella ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.IMPORTANCEIdentifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.

Self-assembled ROS-triggered Bletilla striata polysaccharide-releasing hydrogel dressing for inflammation-regulation and enhanced tissue-healing

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.

Preparation and arc erosion mechanism of Ni skeleton reinforced Ag-based contact materials with CuO-coated SnO2

The Ag-SnO2 contact material is widely regarded as the most promising environmental friendly electrical contact material. However, during the make and break operations, SnO2 particles rising to the surface can cause increased contact resistance and temperature rise, which affects the service life of the contact material. In this study, a three-dimensional (3D) Ni skeleton reinforced Ag-based contact material with CuO-coated SnO2 are successfully fabricated via powder metallurgy technology. The basic physical properties of the novel contact material were tested and the microstructures and arc erosion morphologies were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The research demonstrated that the hardness and electrical conductivity of the novel contact material are 128.9 HV and 46 %IACS, respectively. It can be observed that the SnO2-rich phase is uniformly distributed in the Ag matrix without significant upward after arc erosion, which indicates that the SnO2@CuO core-shell structure effectively enhances the wettability between Ag and SnO2. Meanwhile, the study revealed that the Ni phase uniformly distributed at the interface of the Ag phase during the arc erosion process, indicating that the 3D Ni skeleton structure effectively impedes the expansion of the Ag molten pool and improves the anti-arc erosion performance.

Mutations in the efflux regulator gene oqxR provide a simple genetic switch for antimicrobial resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae is a pathogen of major concern in the global rise of antimicrobial resistance and has been implicated as a reservoir for the transfer of resistance genes between species. The upregulation of efflux pumps is a particularly concerning mechanism of resistance acquisition as, in many instances, a single point mutation can simultaneously provide resistance to a range of antimicrobials and biocides. The current study investigated mutations in oqxR, which encodes a negative regulator of the RND-family efflux pump genes, oqxAB, natively found in the chromosome of K. pneumoniae. Resistant mutants in four K. pneumoniae strains (KP6870155, NTUH-K2044, SGH10, and ATCC43816) were selected from single exposures to 30 µg/mL chloramphenicol and 12 mutants were selected for whole genome sequencing to identify mutations associated with resistance. Resistant mutants generated by single exposures to chloramphenicol, tetracycline, or ciprofloxacin at ≥4 X MIC were replica plated onto all three antibiotics to observe simultaneous cross-resistance to all compounds, indicative of a multidrug resistance phenotype. A variety of novel mutations, including single point mutations, deletions, and insertions, were found to disrupt oqxR leading to significant and simultaneous increases in resistance to chloramphenicol, tetracycline, and ciprofloxacin. The oqxAB-oqxR locus has been mobilized and dispersed on plasmids in many Enterobacteriaceae species and the diversity of these loci was examined to evaluate the evolutionary pressures acting on these genes. Comparison of the promoter regions of oqxR in plasmid-borne copies of the oqxR-oqxAB operon indicated that some constructs may produce truncated versions of the oqxR transcript, which may impact on oqxAB regulation and expression. In some instances, co-carriage of chromosomal and plasmid encoded oqxAB-oqxR was found in K. pneumoniae, implying that there is selective pressure to maintain and expand the efflux pump. Given that OqxR is a repressor of oqxAB, any mutation affecting its expression or function can lead to multidrug resistance. This is in contrast to antibiotic target site mutations that must occur in limited sequence space to be effective and not impact the fitness of the cell. Therefore, oqxR may act as a simple genetic switch to facilitate resistance via OqxAB mediated efflux.

Facile synthesis of silver nanoparticles using Calotropis procera leaves: unraveling biological and electrochemical potentials

The alarming rise of pathogen antibiotic resistance presents a major global health challenge and demands a novel way to control the microbial infections. Simultaneously, nanotechnology has found numerous uses in electrical as well as electronic systems, including timing, filtering, power factor adaptation, and capacitors for energy storage. This work investigates the synthesis and characterization of a silver nanoparticle (AgNPs) utilizing Calotropis procera (CPL) leaf extract. The optimization of synthesis process and the reduction of nanoparticles (NPs) were validated by UV–visible spectroscopy. AgNPs' was exhaustively characterized for morphology, crystallinity, zeta-potential, and structural properties. The produced NPs demonstrated a wide range of characteristics, such as antioxidant, antidiabetic, antibacterial, and antifungal effects. Furthermore, remarkable electrochemical performance was indicated by the CPL-AgNPs electrode, which has mesoporous, clustered sphere-shaped particles onto a flexible stainless-steel substrate. This highlights the electrode's potential in energy storage applications. Copper monosulfide served as the anode and CPL-AgNPs as the cathode electrode in tested hybrid supercapacitor devices, which proved remarkable specific capacitances, high specific energy, and exceptionally high specific power. In order to address the twin challenges of antimicrobial resistance alongside advanced energy storage, this study provides a novel and thorough analysis of the basic electrochemistry as well biological properties of AgNPs, clarifying their potential storage of charges mechanisms and biomedical applications.Graphical abstract

Treatment 'cultures', sexually transmitted infections and the rise of antimicrobial resistance.

In this article, we examine the current management of sexually transmitted infections (STIs), in the context of rising antimicrobial resistance (AMR), through the lens of 'treatment cultures'. Prevailing treatment cultures-including the prominence of syndromic care for STIs-foster certain possibilities and foreclose others, with important consequences for countering AMR. Drawing on qualitative interviews with STI professionals, experts and industry representatives, we unpack these stakeholders' accounts of STI treatment cultures, drawing out the importance of socio-historical (i.e. taboo and stigma), political-economic (i.e. perceptions of significance, profit-making and prioritisation) and subjective (i.e. patient contexts and reflexivity) dimensions therein. In developing this critical account of how treatment cultures are formed, reproduced and indeed resisted, we reveal how such discourses and practices render the reining in of AMR and shifting antibiotic use difficult, and yet, how productive engagement remains key to any proposed solutions. As such, the article contributes to our understanding of AMR as a highly diversified field, through our exploration of the bio-social dimensions of resistance as they relate to the case of STIs.