Mechanisms Of Resistance Research Articles

Discordant results between Xpert MTB/RIF assay and Bactec MGIT 960 culture system regarding the detection of rifampin-resistant Mycobacterium tuberculosis isolates in Wenzhou, China.

This study aimed to assess the possible causes of discordant results between Xpert MTB/RIF (Xpert) and Bactec MGIT 960 Culture System (MGIT960) regarding rifampicin (RIF) susceptibility in Mycobacterium tuberculosis. Patients with previous RIF-resistant tuberculosis who were admitted to Wenzhou Central Hospital from January 2020 to December 2022 were enrolled. The isolates obtained from these patients were subjected to RIF susceptibility tests using Xpert and MGIT960, and the minimum inhibitory concentration (MIC) of RIF was determined by the MYCOTB MIC plate test. Additionally, molecular docking and molecular dynamics (MD) simulations were performed to evaluate the binding efficacy of rpoB and RIF based on rpoB mutations detected in the isolates with discordant RIF susceptibility results. A total of 28 isolates with discordant RIF susceptibility test results were detected, 15 of them were RIF susceptible with MICs ≤ 0.5 µg/mL. Twelve out of 15 isolates contained borderline RIF resistance-associated mutations [L430P (n = 6), H445N (n = 6)], 1 isolate had D435Y and Q429H double mutation, and the remaining 2 isolates had a silent (Q432Q) mutation. Compared with the affinity of RIF toward the wild type (WT) (-45.83 kcal/mol) by MD, its affinity toward L452P (-55.52 kcal/mol), D435Y (-47.39 kcal/mol), L430P (approximately -69.72 kcal/mol), H445N (-49.53 kcal/mol), and Q429H (-55.67 kcal/mol) increased. Borderline RIF resistance-associated mutations were the main cause for the discordant RIF susceptibility results between Xpert and MGIT960, and the mechanisms of the resistance need further investigated.IMPORTANCEThis study is aimed at assessing discordant results between Xpert MTB/RIF (Xpert) assay and Bactec MGIT 960 Culture System (MGIT960) regarding the detection of rifampicin (RIF)-resistant Mycobacterium tuberculosis isolates in Wenzhou, China. The discordant results of RIF between these two assays were mainly caused by borderline RIF resistance-associated mutations, subsequently by silent mutations of rpoB. Borderline RIF resistance- associated mutations detected in our study were demonstrated to not be affected by the affinity of rpoB and RIF by molecular dynamics, and the mechanism of resistance was needed to be clarified. For the discordant results of RIF by Xpert and MGIT960 that occurred, rpoB DNA sequencing was recommended to investigate its association with resistance to RIF.

Reduced stress propagation leads to increased mechanical failure resistance in auxetic materials

Reduced stress propagation leads to increased mechanical failure resistance in auxetic materials

Nanomechanical and Microstructural Characterization of Biocompatible Ti3Au Thin Films Grown on Glass and Ti6Al4V Substrates.

Ti-Au intermetallic-based material systems are being extensively studied as next-generation thin film coatings to extend the lifetime of implant devices. These coatings are being developed for application to the articulating surfaces of total joint implants and, therefore, must have excellent biocompatibility combined with superior mechanical hardness and wear resistance. However, these key characteristics of Ti-Au coatings are heavily dependent upon factors such as the surface properties and temperature of the underlying substrate during thin film deposition. In this work, Ti3Au thin films were deposited by magnetron sputtering on both glass and Ti6Al4V substrates at an ambient and elevated substrate temperature of 275 °C. These films were studied for their mechanical properties by the nanoindentation technique in both variable load and fixed load mode using a Berkovich tip. XRD patterns and cross-sectional SEM images detail the microstructure, while AFM images present the surface morphologies of these Ti3Au thin films. The biocompatibility potential of the films is assessed by cytotoxicity tests in L929 mouse fibroblast cells using Alamar blue assay, while leached ion concentrations in the film extracts are quantified using ICPOEMS. The standard deviation for hardness of films deposited on glass substrates is ∼4 times lower than that on Ti6Al4V substrates and is correlated with a corresponding increase in surface roughness from 2 nm for glass to 40 nm for Ti6Al4V substrates. Elevating substrate temperature leads to an increase in film hardness from 5.1 to 8.9 GPa and is related to the development of a superhard β phase of the Ti3Au intermetallic. The standard deviation of this peak mechanical hardness value is reduced by ∼3 times when measured in fixed load mode compared to the variable load mode due to the effect of nanoindentation tip penetration depth. All tested Ti-Au thin films also exhibit excellent biocompatibility against L929 fibroblast cells, as viability levels are above 95% and leached Ti, Al, V, and Au ion concentrations are below 0.1 ppm. Overall, this work demonstrates a novel Ti3Au thin film system with a unique combination of high hardness and excellent biocompatibility with potential to be developed into a new wear-resistant coating to extend the lifetime of articulating total joint implants.

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde.

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100nM with only 1.36J/cm2 light dose at 415nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50nM of IP-H-OH2+ and just 1.36J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.

Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential.

Lung malignant tumors are a type of cancer with high incidence and mortality rates worldwide. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung malignant tumors, and most patients are diagnosed at advanced stages, leading to poor prognosis. Over the past decades, various oncogenic driver alterations associated with lung cancer have been identified, each of which can potentially serve as a therapeutic target. Rat sarcoma (RAS) genes are the most commonly mutated oncogenes in human cancers, with Kirsten rat sarcoma (KRAS) being the most common subtype. The role of KRAS oncogene in NSCLC is still not fully understood, and its impact on prognosis remains controversial. Despite the significant advancements in targeted therapy and immune checkpoint inhibitors (ICI) that have transformed the treatment landscape of advanced NSCLC in recent years, targeting KRAS (both directly and indirectly) remains challenging and is still under intensive research. In recent years, significant progress has been made in the development of targeted drugs targeting the NSCLC KRASG12C mutant subtype. However, research progress on target drugs for the more common KRASG12D subtype has been slow, and currently, no specific drugs have been approved for clinical use, and many questions remain to be answered, such as the mechanisms of resistance in this subtype of NSCLC, how to better utilize combination strategies with multiple treatment modalities, and whether KRASG12D inhibitors offer substantial efficacy in the treatment of advanced NSCLC patients.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma.

B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 x BCMA bispecific antibody (BsAb), 42% (30/72) of whom had prior BCMA-directed therapy exposure. Malignant plasma cell BCMA expression was present in all BCMA therapy-naïve patients. Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets

Despite the availability of target drugs in the first and second line, only 30% of FLT3mut AMLs are cured. Among the multiple mechanisms of resistance, those of FLT3mut LSC are the most difficult to eradicate because of their metabolic and genomic characteristics. Reactivation of glycogen synthesis, inhibition of the RAS/MAPK pathway, and degradation of FLT3 may be potential aids to fight the resistance of LSC to FLT3i. LSC is also characterized by the expression of a CD34+/CD25+/CD123+/CD99+ immunophenotype. The receptor and ligand of FLT3, the natural killer group 2 member D ligand (NKGD2L), and CD123 are some of the targets of chimeric antigen receptor T cells (CAR-T), bispecific T-cell engager molecules (BiTEs), CAR-NK and nanoparticles recently designed and reported here. The combination of these new therapeutic options, hopefully in a minimal residual disease (MRD)-driven approach, could provide the future answer to the challenge of treating FLT3mut AML.

Macrolide Resistance in the Aerococcus urinae Complex: Implications for Integrative and Conjugative Elements

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China

BackgroundRecently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important.MethodsThe antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR.ResultsAll the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates.ConclusionThe emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

MicroRNA (miRNA) profiling of maize genotypes with differential response to Aspergillus flavus implies zma-miR156–squamosa promoter binding protein (SBP) and zma-miR398/zma-miR394–F -box combinations involved in resistance mechanisms

Maize (Zea mays), a major food crop worldwide, is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite aflatoxin (AF) especially under climate change induced abiotic stressors that favor mold growth. Several studies have used “-omics” approaches to identify genetic elements with potential roles in AF resistance, but there is a lack of research identifying the involvement of small RNAs such as microRNAs (miRNAs) in maize-A. flavus interaction. In this study, we compared the miRNA profiles of three maize lines (resistant TZAR102, moderately resistant MI82, and susceptible Va35) at 8 h, 3 d, and 7 d after A. flavus infection to investigate possible regulatory antifungal role of miRNAs. A total of 316 miRNAs (275 known and 41 putative novel) belonging to 115 miRNA families were identified in response to the fungal infection across all three maize lines. Eighty-two unique miRNAs were significantly differentially expressed with 39 miRNAs exhibiting temporal differential regulation irrespective of the maize genotype, which targeted 544 genes (mRNAs) involved in diverse molecular functions. The two most notable biological processes involved in plant immunity, namely cellular responses to oxidative stress (GO:00345990) and reactive oxygen species (GO:0034614) were significantly enriched in the resistant line TZAR102. Coexpression network analysis identified 34 hubs of miRNA-mRNA pairs where nine hubs had a node in the module connected to their target gene with potentially important roles in resistance/susceptible response of maize to A. flavus. The miRNA hubs in resistance modules (TZAR102 and MI82) were mostly connected to transcription factors and protein kinases. Specifically, the module of miRNA zma-miR156b-nb – squamosa promoter binding protein (SBP), zma-miR398a-3p – SKIP5, and zma-miR394a-5p – F-box protein 6 combinations in the resistance-associated modules were considered important candidates for future functional studies.

Evaluation of KRAS inhibitor-directed therapies for pancreatic cancer treatment

Despite significant advancements in the treatment of other cancers, pancreatic ductal adenocarcinoma (PDAC) remains one of the world’s deadliest cancers. More than 90% of PDAC patients harbor a Kirsten rat sarcoma (KRAS) gene mutation. Although the clinical potential of anti-KRAS therapies has long been realized, all initial efforts to target KRAS were unsuccessful. However, with the recent development of a new generation of KRAS-targeting drugs, multiple KRAS-targeted treatment options for patients with PDAC have entered clinical trials. In this review, we provide an overview of current standard of care treatment, describe RAS signaling and the relevance of KRAS mutations, and discuss RAS isoform- and mutation-specific differences. We also evaluate the clinical efficacy and safety of mutation-selective and multi-selective inhibitors, in the context of PDAC. We then provide a comparison of clinically relevant KRAS inhibitors to second-line PDAC treatment options. Finally, we discuss putative resistance mechanisms that may limit the clinical effectiveness of KRAS-targeted therapies and provide a brief overview of promising therapeutic approaches in development that are focused on mitigating these resistance mechanisms.

Indigenous People Struggle for Damage Repair: Assessing Shadow Networks Resistance and Pursuit of Resilience in the Context of an Industrial Disaster

This study aims to understand the emergence of bottom-up social practices in shadow networks in the context of an industrial disaster. The empirical focus involves the Guarani and Tupinikim indigenous people, victims of the Fundão tailing dam rupture, one of the world’s greatest socio-environmental disasters. We adopted a qualitative approach to identify the indigenous shadow network’s agency, resistance mechanisms, and resilience activation. We interpret indigenous resistance as a way of fighting for their existence, with mechanisms crafted by collective deliberation and community mobilization. We identified the mining industry’s efforts to divide resistance and how the indigenous shadow network rebuilt resistance mechanisms through activating resilience based on indigenous values, interconnected leaderships, and social memory from their ancestral land. We thereby advance in understanding the indigenous shadow network’s agency that allows managers to intervene with on-ground actions to maintain or enhance resistance and resilience in the context of organizational studies.

Bacteriocin diversity, function, discovery and application as antimicrobials.

Bacteriocins are potent antimicrobial peptides that are produced by bacteria. Since their discovery almost a century ago, diverse peptides have been discovered and described, and some are currently used as commercial food preservatives. Many bacteriocins exhibit extensively post-translationally modified structures encoded on complex gene clusters, whereas others have simple linear structures. The molecular structures, mechanisms of action and resistance have been determined for a number of bacteriocins, but most remain incompletely characterized. These gene-encoded peptides are amenable to bioengineering strategies and heterologous expression, enabling metagenomic miningand modification of novel antimicrobials. The ongoing global antimicrobial resistance crisis demands that novel therapeutics be developed to combat infectious pathogens. New compounds that are target-specific and compatible with the resident microbiota would be valuable alternatives to current antimicrobials. As bacteriocins can be broad or narrow spectrum in nature, they are promising tools for this purpose. However, few bacteriocins have gone beyond preclinical trials and none is currently used therapeutically in humans. In this Review, we explore the broad diversity in bacteriocin structure and function, describe identification and optimization methods and discuss the reasons behind the lack of translation beyond the laboratory of these potentially valuable antimicrobials.

PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity.

Overexpression of PDR16 Confers Amphotericin B Resistance in a PMP3-Dependent Manner in Yeast Saccharomyces cerevisiae.

Invasive fungal infections in humans with compromised immune systems are the primary cause of morbidity and mortality, which is becoming more widely acknowledged. Amphotericin B (AmB) is one of the antifungal drugs used to treat such infections. AmB binds with plasma membrane ergosterol, inducing cellular ions to leak and causing cell death. Reduction in ergosterol content and modification of cell walls have been described as AmB resistance mechanisms. In addition, when the sphingolipid level is decreased, the cell becomes more susceptible to AmB. Previously, PDR16, a gene that encodes phosphatidylinositol transfer protein in Saccharomyces cerevisiae, was shown to enhance AmB resistance upon overexpression. However, the mechanism of PDR16-mediated AmB resistance is not clear. Here, in this study, it was discovered that a plasma membrane proteolipid 3 protein encoded by PMP3 is essential for PDR16-mediated AmB resistance. PDR16-mediated AmB resistance does not depend on ergosterol, but a functional sphingolipid biosynthetic pathway is required. Additionally, PMP3-mediated alteration in membrane integrity abolishes PDR16 mediated AmB resistance, confirming the importance of PMP3 in the PDR16 mediated AmB resistance.

Circulating tumour DNA analysis and new uses of anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer

Currently, tumour tissue biopsy to determine RAS/BRAF gene alterations, assess microsatellite instability status, and determine HER‑2/neu gene amplification/hyperexpression is the gold standard of diagnosis and allows the selection of optimal molecularly targeted therapy when considering treatment strategies for patients with metastatic colorectal cancer. However, biopsy does not fully reflect the existing intratumoural heterogeneity and clonal evolution of tumour cells, which can often be the cause of therapeutic failures. In recent years, liquid biopsy has attracted increasing attention as an additional and potentially alternative non-invasive tool for molecular tumour profiling. Assessment of circulating tumour DNA allows changes in the genetic status of the tumour to be monitored and the «burden» of disease to be measured dynamically in real time. Advances in liquid biopsy technology have led to promising new strategies for the management of patients with metastatic colorectal cancer in late-line therapy. The standard drug arsenal in this group of patients is limited to either repeat administration of previously effective therapy or regorafenib and the combination of trifluridine/tipiracil with bevacizumab, which are characterized by limited clinical activity. However, thanks to the discovery of the NeoRAS wild-type phenomenon and the rechallenge strategy of anti-EGFR monoclonal antibodies based on the study of clonal selection and evolution of tumour cells, the administration of epidermal growth factor inhibitors in a molecularly selected by liquid biopsy population is accompanied by good tolerability and efficacy. Numerous clinical studies are ongoing to further understand the mechanisms of tumour resistance and to develop new evidence-based treatment approaches in order to realise the concept of personalised medicine.

Impact of Antimicrobial Resistance in Health and Economic Outcomes: A Review

Background: Antimicrobial resistance (AMR) observed when microorganism adapt and multiply in the presence of drugs to which they are exposed. Antibiotic resistance is a global health problem, with the current trend of inappropriate and overuse of antibiotics predicted to cause 10 million deaths by 2050. However, resistant bacteria are multiplying worldwide, infecting healthy people, animals, and human environment, affecting countries with low- and middle-income countries. Although the discovery of antibiotics has saved many lives in recent years, increasing bacterial resistance to antibiotics threatens clinical and agricultural progress, and even treatable bacterial infections can be life-threatening. Strategies: In the present review we discuss the global burden of social and economic impact of antibiotic resistance, common mechanisms of antibiotic resistance, microbiological health and treatment resistance, patient attitudes, hospital and cancer outcomes. Summarize the impact of AMR. Potential strategies to overcome AMR such as Targeting antimicrobial-resistant enzymes, Targeting antimicrobial-resistant bacteria, Drug delivery systems, Physiochemical methods, Unconventional strategies. Conclusion: The devastating effect of antibiotic resistance is clear by way of the sudden boom inside the quantity of cases in which microorganism are immune to typically prescribed antibiotics in clinical practice. Although the superiority of bacterial resistance is growing, there is limited statistics at the impact of this hassle on the fitness and economic consequences of the clinical network.

Metal cation crosslinked, partially reduced graphene oxide membranes with enhanced stability for high salinity, produced water treatment by pervaporative separation

Graphene oxide (GO)-based membranes hold significant promise for applications ranging from energy storage to protective coatings, to saline water and produced water treatment, owing to their chemical stability and unique barrier properties achieving a high selectivity for water permeation. However, unmodified GO membranes are not stable when submerged in liquid water, creating challenges with their commercial utilization in aqueous filtration and pervaporation applications. To mitigate this, we develop an approach to modify GO membranes through a combination of low temperature thermal reduction and metal cation crosslinking. We demonstrate that Zn2+–rGO and Fe3+–rGO membranes had the highest permeation flux of 8.3 ± 1.5 l m−2 h−1 and 7.0 ± 0.4 l m−2 h−1, for saline water separation, respectively, when thermally reduced after metal cross-linking; These membranes maintained a high flux of 7.5 ± 0.7 l m−2 h−1, and 5.5 ± 0.3 l m−2 h−1 for produced water separation, respectively. All the membranes had a salt rejection higher than 99%. Fe3+ crosslinked membranes presented the highest organic solute rejections for produced water of 69%. Moreover, long term pervaporation testing was done for the Zn2+–rGO membrane for 12 h, and only a minor drop of 6% in permeation flux was observed, while Zn2+–GO had a drop of 24%. Both modifiers significantly enhanced the stability with Fe3+–rGO membranes displaying the highest mechanical abrasion resistance of 95% compared to non-reduced and non-crosslinked GO. Improved stability for all samples also led to higher selectivity to water over organic contaminants and only slightly reduced water flux across the membrane.

Synthesis, crystal structure and properties of YB2C2

ABSTRACT YB2C2 is a novel ultra-high temperature ceramic material with high damage tolerance. In this work, the synthesis mechanism, crystal structure, electronic structure, elastic properties and thermal shock resistance of YB2C2 were systematically investigated through experiments and calculations. It was determined by differential scanning calorimetry with the heating rate of 10°C/min that YB2C2 was formed by the reaction of YB2C and C at about 1202°C, and became the main phase at 1450°C. The space group of YB2C2 was determined to be P4/mbm by X-ray diffraction, transmission electron microscopy, Rietveld refinement and first-principles calculations for the first time. The lattice constants are a = b = 0.5351 nm and c = 0.3561 nm. The atom positions are as follows: Y is located at 2a (0, 0, 0), B is located 4 h (0.133, 0.633, 0.5) and C is located at 4 h (0.662, 0.162, 0.5). The chemical bonding of YB2C2 displayed sharp anisotropy, with strong B-C bond within the B2C2 nets, and weak Y-B/Y-C bond between Y atom layers and B2C2 nets. Additionally, YB2C2 exhibited abnormal thermal shock resistance when the thermal shock temperature exceeded 800°C, with the residual flexural strength at 1300°C being more than 70% of the strength at room temperature.