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Colistin is one of the last-line treatments for multi-drug resistant Gram-negative bacterial infections. The emergence of mobile colistin resistance genes has driven global concern and triggered the need for surveillance. Our report reveals the identification of mcr-9.1 and mcr-10.1 in Ecuador by employing a proximity ligation technique.

The present study describes the synthesis of various bioactive compounds, including bis‐coumarins, bis‐lawsones, bis‐dimedones, and bis‐indolylmethanes, using a novel catalytic system called "Brønsted acid saponin combined catalyst" (BASapC). The BASapC was formed by combining p‐toluenesulfonic acid (PTSA) and saponin in an aqueous medium. The prepared BASapC proved to be effective in facilitating cascade‐type Knoevenagel–Michael addition reactions between various aromatic aldehydes with 4‐hydroxycoumarin, lawsone, dimedone, or indole at 80 °C. In the BASapC system, PTSA acted as a powerful Brønsted acid, activating reactants, whereas saponin served as a natural surfactant, enhancing the solubility of organic compounds in water. This catalytic approach established a straightforwardness and robustness of diversity‐oriented synthesis (DoS), delivering the desired products with good to excellent yields. Additionally, the BASapC exhibited recyclability for at least four cycles without significant loss of activity. [ABSTRACT FROM AUTHOR]

Sandstorms pose a substantial hurdle to image clearness, affecting visibility, detail representation, and color quality. In this study, a novel algorithm named multistep color reparation (MCR) is constructed, particularly for the enhancement of images impacted by sandstorms. MCR includes a thorough procedure comprising five distinct phases. The first phase focuses on enhancing color indemnity by effectively compensating the missing color information, assuring that the enhanced images appear with better true-to-life colors. Next, a statistics-based intensity redistribution is employed as a second phase to emphasize tonality, ensuring better perceptual quality. The third phase applies an optimized intuitionistic fuzzy model, leveraging the fuzzy model's undiscovered abilities to remove the dust veil. Following this, a color deviation correction phase is executed to rectify the emerging color shifts and inaccuracies, applying corrective measures to enliven accurate color representation. Finally, a fast visibility restoration approach is implemented to improve the visibility and provide better saturation. To evaluate the efficacy of MCR, thorough experiments were performed comparing it with eight state-of-the-art algorithms. Quality assessments were carried out using six high-level image evaluation metrics alongside the processing times. The findings exhibited that MCR outperforms all competing algorithms, and it efficaciously addressed the challenges posed by sandstorm-induced degradation, presenting substantial enhancements in perceptual fidelity and quality. [ABSTRACT FROM AUTHOR]

The National Park of Hainan Tropical Rainforest (NPHTR) plays the crucial role of an ecological barrier for Hainan Island. It also serves as a valuable repository of tropical biological heritage for the world. The scientific establishment of an ecological security pattern (ESP) for the NPHTR is therefore essential for ensuring the robustness and stability of this regional ecosystem, safeguarding tropical biodiversity, and promoting sustainable development. This study integrates ecosystem service functions (ESFs) and ecological sensitivity to identify ecological sources (ESs) so that regional integrity is promoted and ecological security is ensured. Ecological corridors (ECs) are established on the basis of a minimum cumulative resistance (MCR) model and circuit theory. We integrate ESs, nodes, and corridors to construct the ESP of the NPHTR. The areas of extreme importance and sensitivity in the NPHTR account for 25.17% and 25.47% of its overall area, respectively, and are predominantly situated in the higher elevations of its eastern and central regions. Further, the ESs are mainly distributed in its western region, specifically Ba Wangling (BWL), Jian Fengling (JFL), and Ying Geling (YGL), covering an area of 1624.67 km2 (38.06% of the total area) of the NPHTR. After correction, 47 ECs with a distance of 870.9 km have been established, with BWL and YGL serving as the core areas. The ecological pinch- and barrier points in the NPHTR cover areas of 11.49 km2 and 16.35 km2, respectively, primarily consisting of man-made landscapes such as farmlands and buildings. These areas are significantly disturbed by human activities. The NPHTR has an ESP of "one screen, one district, three belts, multiple points, and multiple corridors". BWL and YGL, which contain numerous sources and corridors, are crucial ecological functional zones. To ensure the horizontal connectivity of rare wildlife, such as of Nomascus hainanus and Cervus eldii hainanus, the NPHTR should establish buffer or development zones. These findings offer valuable insights for the development and planning of ecological civilization on Hainan Island, as well as for the establishment and management of the ESP of other national parks and nature reserves. [ABSTRACT FROM AUTHOR]

Background: Wastewaters are considered as important players in the spread of antimicrobial resistance, thus affecting the health of humans and animals. Here, we focused on wastewaters as a possible source of carbapenemase-producing Enterobacterales for the environment. Methods: A total of 180 presumptive coliforms from hospital and municipal wastewaters, and a river in the Czech Republic were obtained by selective cultivation on meropenem-supplemented media and tested for presence of carbapenemase-encoding genes by PCR. Strains carrying genes of interest were characterized by testing antimicrobial susceptibility, carbapenemase production and combination of short- and long- read whole-genome sequencing. The phylogenetic tree including publicly available genomes of Enterobacter asburiae was conducted using Prokka, Roary and RAxML. Results: Three VIM-producing Enterobacter asburiae isolates, members of the Enterobacter cloacae complex, were detected from hospital and municipal wastewaters, and the river. The blaVIM−1 gene was located within a class 1 integron that was carried by different F-type plasmids and one non-typeable plasmid. Furthermore, one of the isolates carried plasmid-borne colistin-resistance gene mcr-10, while in another isolate chromosomally located mcr-9 without colistin resistance phenotype was detected. In addition, the analysis of 685 publicly available E. asburiae genomes showed they frequently carry carbapenemase genes, highlighting the importance of this species in the emergence of resistance to last-line antibiotics. Conclusion: Our findings pointed out the important contribution of hospital and community wastewaters in transmission of multi-drug resistant pathogens. [ABSTRACT FROM AUTHOR]

Colistin resistance poses a major therapeutic challenge and resistant strains have now been reported worldwide. However, the occurrence of such bacteria in aquatic environments is considerably less understood. This study aimed to isolate and characterize colistin-resistant strains from water and plastic litter collected in an urban recreational estuary. Altogether, 64 strains with acquired colistin resistance were identified, mainly Acinetobacter spp. and Enterobacter spp. From these, 40.6% were positive for at least one mcr variant (1–9), 26.5% harbored, extended-spectrum beta-lactamases, 23.4% harbored, sulfonamide resistance genes, and 9.3% harbored, quinolone resistance genes. merA , encoding mercury resistance, was detected in 10.5% of these strains, most of which were also strong biofilm producers. The minimum inhibitory concentration toward colistin was determined for the mcr -positive strains and ranged from 2 to ≥512 µg ml−1. Our findings suggest that Gram-negative bacteria highly resistant to a last-resort antimicrobial can be found in recreational waters and plastic litter, thereby evidencing the urgency of the One Health approach to mitigate the antimicrobial resistance crisis. [ABSTRACT FROM AUTHOR]

Abstract Background Wastewaters are considered as important players in the spread of antimicrobial resistance, thus affecting the health of humans and animals. Here, we focused on wastewaters as a possible source of carbapenemase-producing Enterobacterales for the environment. Methods A total of 180 presumptive coliforms from hospital and municipal wastewaters, and a river in the Czech Republic were obtained by selective cultivation on meropenem-supplemented media and tested for presence of carbapenemase-encoding genes by PCR. Strains carrying genes of interest were characterized by testing antimicrobial susceptibility, carbapenemase production and combination of short- and long- read whole-genome sequencing. The phylogenetic tree including publicly available genomes of Enterobacter asburiae was conducted using Prokka, Roary and RAxML. Results Three VIM-producing Enterobacter asburiae isolates, members of the Enterobacter cloacae complex, were detected from hospital and municipal wastewaters, and the river. The bla VIM−1 gene was located within a class 1 integron that was carried by different F-type plasmids and one non-typeable plasmid. Furthermore, one of the isolates carried plasmid-borne colistin-resistance gene mcr-10, while in another isolate chromosomally located mcr-9 without colistin resistance phenotype was detected. In addition, the analysis of 685 publicly available E. asburiae genomes showed they frequently carry carbapenemase genes, highlighting the importance of this species in the emergence of resistance to last-line antibiotics. Conclusion Our findings pointed out the important contribution of hospital and community wastewaters in transmission of multi-drug resistant pathogens.

Isotopic labeling is an attractive modality that has been widely used in many aspects of chemistry, the life sciences, and medical research; especially deuterated drugs and radioactive molecules have been used in the diagnosis and treatment of cancer and neurodegenerative diseases. The widespread application and rapid development of isotopically labeled molecules has led to an increased demand for new isotopic labeling chemical methods to synthesize highly specific molecules bearing defined nuclides. Multicomponent reactions (MCRs) are modular build-up approaches for the rapid generation of complex molecules often containing biologically relevant scaffold structures. There is great potential to use MCRs to construct isotopically labeled molecules because assembly speed and reaction diversity are key advantages of MCR. In this review, we provide an overview of the recent literature on this topic that can provide insight into the application of MCRs in the field of isotopic labeling. [ABSTRACT FROM AUTHOR]

Abstract Background Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia. Methods Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors. Results The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050–3.024), hypertension (Adj OR = 1.725; 95% CI:1.094–2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103–3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319–16.823), were predictors for MCR incidence. Conclusions Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults.

The renewable 5‐hydroxymethylfurfural (5‐HMF) has gained a wide interest from the chemistry community as a valuable biobased platform opening the way to many applications. Despite an impressive number of publications reporting either its preparation or its functionalization, its direct use in fine chemistry, and especially in multi‐component reaction (MCR), is less reported. Here, we report a complete study of the use of 5‐HMF in the Hantzsch dihydropyridines synthesis. The strategy was applied to a scope of β‐dicarbonyl molecules (including β‐ketoesters and 1,3‐diketones) in a 3‐component procedure leading to a series of symmetrical 1,4‐dihydropyridines derived from 5‐HMF in excellent yields. The study was extended to the 4‐component protocol using one equivalent of a β‐ketoester and one equivalent of 5,5‐dimethyl‐1,3‐cyclohexanedione (dimedone), which efficiently provided the corresponding unsymmetrical dihydropyridines. [ABSTRACT FROM AUTHOR]

Background: Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia. Methods: Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors. Results: The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050–3.024), hypertension (Adj OR = 1.725; 95% CI:1.094–2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103–3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319–16.823), were predictors for MCR incidence. Conclusions: Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults. [ABSTRACT FROM AUTHOR]

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam. [ABSTRACT FROM AUTHOR]

Starting compound 1 was synthesized according to reference.1 Benzylidene thiazole pyrimidin-3(5H)-ones were synthesized reactions of 1 with bromoacetic acid and various aryl-aldehydes in the same vessel via one-step, unlike studies in the literature. Quantum chemical parameters and full geometry optimizations for all compounds were computed using DFT based on B3LYP. Cytotoxic action potential of synthesized compounds was evaluated using trypan blue dye exclusion and MTT assays in different cell lines including adenocarcinoma alveolar basal epithelial-like adherent A549 cells, the colon adenocarcinoma HT-29 cells, prostate adenocarcinoma DU-145 cells, and diploid ARPE-19 retinal pigment epithelial cells. Embryotoxicity and genotoxicity assessments were performed on pluripotent human embryonal carcinoma NT2 and human lymphocyte cells, respectively. Compound A1 exhibited good anticancer activity on A549 and DU-145 cell lines, and the compounds including A3, 4, 6, and 9 induced cytotoxicity on A549 cells. The compounds A1-10 also showed a good biosafety profile at relatively lower concentrations. [ABSTRACT FROM AUTHOR]

Colistin (CT) is the last-resort of antibiotic against multidrug-resistance (MDR) Acinetobacter baumannii (A. baumannii) infection. However, colistin resistance is increasingly reported in A. baumannii isolates partially due to the global emergence and dissemination of plasmid-borne mobile colistin resistance (mcr) gene and is a threat to human health. Thus, available treatment strategies urgently required in the fight against colistin-resistant A. baumannii. Here, we showed that mcr confers damaged outer membrane (OM) permeability in A. baumannii, which could compromise the viability of A. baumannii. Consistently, A. baumannii with colistin resistance exhibits increased susceptibility to macromolecular antibiotics such as rifampicin (RIF) and erythromycin (ERY). Moreover, the combination therapy of colistin and rifampicin demonstrates efficacy against colistin-resistant A. baumannii, regardless of the presence of mcr. Altogether, our data suggest that the synergy of colistin in combination with macromolecular hydrophobic antibiotics poses a promising therapeutic alternative for colistin-resistant A. baumannii.

Mobile colistin resistance (MCR) is the primary mechanism for colistin resistance and has been disseminated worldwide; this has gained substantial attention and led to policy changes for the use of colistin in food animals in many countries. The global spread of mcr was attributed to the high selective pressure of colistin used in livestock, and the acquisition of mcr by low-copy-number and highly conjugative plasmids. The dramatic decrease of mcr after the colistin-banning policy could be associated with the fitness cost mediated by MCR. Besides mediating resistance to both polymyxins and antimicrobial peptides, MCR is thought to enhance the virulence of bacteria and affect the host immune response. To combat colistin-resistant bacteria, MCR inhibitors have been developed based on the structure of MCR, and other strategies targeting mcr -positive plasmids/strains have also been exploited. Colistin is regarded as a last-line drug against serious infections caused by multidrug-resistant Gram-negative bacterial pathogens. Therefore, the emergence of mobile colistin resistance (mcr) genes has attracted global concern and led to policy changes for the use of colistin in food animals across many countries. Currently, the distribution, function, mechanism of action, transmission vehicles, origin of mcr , and new treatment strategies against MCR-producing pathogens have been extensively studied. Here we review the prevalence, structure and function of mcr , the fitness cost and persistence of mcr -carrying plasmids, the impact of MCR on host immune response, as well as the control strategies to combat mcr -mediated colistin resistance. Colistin is regarded as a last-line drug against serious infections caused by multidrug-resistant (MDR) Gram-negative bacterial pathogens. Therefore, the emergence of mobile colistin resistance (mcr) genes has attracted global concern and led to policy changes for the use of colistin in food animals across many countries. Currently, the distribution, function, mechanism of action, transmission vehicles, origin of mcr , and new treatment strategies against MCR-producing pathogens have been extensively studied. Here we review the prevalence, structure, and function of mcr , the fitness cost and persistence of mcr -carrying plasmids, the impact of MCR on host immune response, as well as the control strategies to combat mcr -mediated colistin resistance. [ABSTRACT FROM AUTHOR]

As the hot spot and key topic in landscape ecology, the construction of ecological security pattern strives to maintain the integrity of landscape patterns and the continuity of the ecological process, and achieve sustainable development of the region. Taking Hefei City in China as a study area, according to the basal ecological features of Hefei City, the InVEST model was used to select three key indicators of ecosystem service importance (biodiversity, water yield, and carbon storage) to identify ecological sources; the resistance surface based on land use types was modified by the nighttime light (NTL) data; the potential ecological corridors were identified using minimal cumulative resistance model; lastly, the key ecological corridors were extracted using the gravity model. The results showed that: By combining 14 ecological sources, 91 potential ecological corridors, 16 key corridors, and ecological nodes, the ecological security pattern of Hefei City was constructed. Hefei's ecological source area is 1911.7 km2, accounting for 16.68% of the city's total area. It was dominated by water and woodland, which was distributed in the city's eastern and southern regions. The potential ecological corridor was 926.71 km long, while the key ecological corridor was 56.7 km long. Finally, A "One vertical and three horizontal" Hefei City ecological security pattern was built on this foundation. Our research results had important guiding significance for the sustainable utilization of ecological resources in Hefei City and could provide theoretical basis and technical support for ecological protection in Hefei City. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia (E.) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples (n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli. In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The blaTEM group was most frequently detected (97.02%), followed by blaCTX m (45.5%), blaSHV (9.9%), and blaOXA-2 (0.9%). However, mcr genes and blaNDM, blaKPC, blaVIM, and blaOXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the blaTEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms. [ABSTRACT FROM AUTHOR]

In recent years, landscape fragmentation has become increasingly serious due to the impact of human activities. The ecological network can ensure the ecological function of the region through linearly connecting ecological corridors and effectively solving the problem of landscape fragmentation that occurs in the evolution of landscape patterns. Based on MSPA and MCR models, the article analyses the distribution and changes of landscape types in the Haihe River basin and constructs an ecological network in the study area by combining the local ecological characteristics of the basin. The network structure is optimized in the end by selecting three large stepping stones, constructing 69 internal ecological stepping stones, identifying 212 fracture points, and adding seven ecological corridors to build a point–line surface network structure with an internal and external double‐loop structure. The connectivity of the network structure is evaluated by using complex network method. It is calculated that the network connectivity performance is improved by 13.95% after optimization, which means the species exchange in the study area is closer. [ABSTRACT FROM AUTHOR]

Introduction: Motoric cognitive risk syndrome (MCR), characterized by subjective cognitive complaints and slow gait in older populations, is associated with sleep duration. However, the association between MCR and daytime nap duration has not been thoroughly explored. Methods: Baseline data from the China Health and Retirement Longitudinal Study (CHARLS) were used in this study. MCR was defined as the coexistence of subjective cognitive complaints and objective slow gait speed without a history of dementia or mobility disability. Daytime nap duration was categorized into four groups: no napping, short napping (

Abstract In the field of world heritage conservation, there has been broad consensus on carrying out heritage conservation research on the basis of spatial integration and interregional and international cooperation. However, there are still many deficiencies in the integration of culture with the environment, regional economic and social development, and the regional, holistic and multimodal conservation and utilization of cultural heritage sites. In China, the Dongjiang-Hanjiang River Basin is a representative area of substantial cultural and ecological value for both Guangdong Province and the whole country. This paper uses the morphological spatial pattern analysis and the minimum cumulative resistance model to integrate cultural ecology sources and establish a cross-regional and large-scale cultural ecology network system that includes 1 main corridor, 22 important corridors and 17 secondary corridors. In addition, based on identified cultural landscape nodes and cultural ecology services, the economy of the cultural ecology corridor could be developed with large-scale co-construction, co-governance and shared working mechanisms to overcome administrative limits and realize the conservation and utilization of multimodal and large-scale heritage sites. This approach has strong theoretical and practical significance for innovative methods in cultural ecology research, as well as for new content in the research of Lingnan culture, ecosystem restoration, and the economic and social development of towns and villages. This article supplements unilateral studies of regional culture and ecology and demonstrates an in-depth application of cultural ecology theory.

Abstract Background Colistin is an antibiotic used as a last-resort to treat multidrug-resistant Gram-negative bacterial infections. Colistin had been used for a long time in veterinary medicine for disease control and as a growth promoter in food-producing animals. This excessive use of colistin in food animals causes an increase in colistin resistance. This study aimed to determine molecular characteristics of colistin-resistant Escherichia coli in broiler chicken and chicken farm environments. Results Four hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia. E. coli was isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detect mcr genes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize the E. coli isolates. Out of the 425 (94%; 425/453) E. coli isolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of the mcr positive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 μg/ml. The most prominent mcr gene detected was mcr-1 (47.9%; 23/48), followed by mcr-8 (18.8%; 9/48), mcr-7 (14.5%; 7/48), mcr-6 (12.5%; 6/48), mcr-4 (2.1%; 1/48), mcr-5 (2.1%; 1/48), and mcr-9 (2.1%; 1/48) genes. One E. coli isolate originating from the fecal sample was found to harbor both mcr-4 and mcr-6 genes and another isolate from the drinking water sample was carrying mcr-1 and mcr-8 genes. The majority of the mcr positive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of the mcr positive E. coli isolates were multidrug resistant. The most frequently detected virulence genes among mcr positive E. coli isolates were ast (38%; 18/48) followed by iss (23%; 11/48). This is the first research to report the prevalence of mcr-4, mcr-5, mcr-6, mcr-7, and mcr-8 genes in E. coli from broiler chickens and farm environments in Malaysia. Conclusion Our findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistant E. coli, posing a risk to public health and food safety.

The National Park of Hainan Tropical Rainforest (NPHTR) plays the crucial role of an ecological barrier for Hainan Island. It also serves as a valuable repository of tropical biological heritage for the world. The scientific establishment of an ecological security pattern (ESP) for the NPHTR is therefore essential for ensuring the robustness and stability of this regional ecosystem, safeguarding tropical biodiversity, and promoting sustainable development. This study integrates ecosystem service functions (ESFs) and ecological sensitivity to identify ecological sources (ESs) so that regional integrity is promoted and ecological security is ensured. Ecological corridors (ECs) are established on the basis of a minimum cumulative resistance (MCR) model and circuit theory. We integrate ESs, nodes, and corridors to construct the ESP of the NPHTR. The areas of extreme importance and sensitivity in the NPHTR account for 25.17% and 25.47% of its overall area, respectively, and are predominantly situated in the higher elevations of its eastern and central regions. Further, the ESs are mainly distributed in its western region, specifically Ba Wangling (BWL), Jian Fengling (JFL), and Ying Geling (YGL), covering an area of 1624.67 km2 (38.06% of the total area) of the NPHTR. After correction, 47 ECs with a distance of 870.9 km have been established, with BWL and YGL serving as the core areas. The ecological pinch- and barrier points in the NPHTR cover areas of 11.49 km2 and 16.35 km2, respectively, primarily consisting of man-made landscapes such as farmlands and buildings. These areas are significantly disturbed by human activities. The NPHTR has an ESP of “one screen, one district, three belts, multiple points, and multiple corridors”. BWL and YGL, which contain numerous sources and corridors, are crucial ecological functional zones. To ensure the horizontal connectivity of rare wildlife, such as of Nomascus hainanus and Cervus eldii hainanus, the NPHTR should establish buffer or development zones. These findings offer valuable insights for the development and planning of ecological civilization on Hainan Island, as well as for the establishment and management of the ESP of other national parks and nature reserves.

Tetramic acids exhibit intriguing biological activity and are particularly attractive scaffolds for drug design. In this paper, we present a convenient approach based on the Dieckmann cyclization of Ugi adducts of malonic monoesters to afford a series of medically important polysubstituted tetramic acid derivatives. This simple and versatile method tolerates various substituents in both the amine, aldehyde and isocyanide moieties allowing the use of α‐substituted malonic acid monoesters. Examples of further functionalization of the free methylene group in the synthesized compounds have been presented. [ABSTRACT FROM AUTHOR]

Multicomponent reactions provide an excellent approach toward quaternary carbon centres utilizing convergent chemical reactions in a highly selective manner under one‐pot conditions. The reactivity of substrates and metal catalysts is carefully controlled, precluding the formation of side‐products. In this context, transition metal catalyzed reactions of onium ylides generated via diazo precursors and nucleophiles with a third component (an electrophile) have garnered significant attention. Using an allylic precursor as the electrophilic partner provides opportunities to construct all‐carbon quaternary centres. Furthermore, the presence of an allyl fragment in the multicomponent product serves as a pivotal handle for carrying out subsequent modifications. Several recent studies have employed Rh, Pd, and dual Rh/Pd catalytic systems in multicomponent reactions involving allylic alkylation that proceed via a synergistic or relay pathway. Although not significantly successful, in a few cases, asymmetric induction is achieved through chiral phosphoric acids or chiral phosphine ligands. Limited substrate and catalyst scope and the underlying mechanistic complexities have posed formidable challenges, slowing the advancement of asymmetric reactions. This review provides details of multicomponent reactions using readily available substrates like diazo compounds, allylic carbonates, and nucleophiles (R‐OH, R‐NH2,,etc.) forming complex organic compounds. Our primary objective is to discuss the mechanistic issues that may facilitate the progress in asymmetric reactions in this field. [ABSTRACT FROM AUTHOR]

In the field of world heritage conservation, there has been broad consensus on carrying out heritage conservation research on the basis of spatial integration and interregional and international cooperation. However, there are still many deficiencies in the integration of culture with the environment, regional economic and social development, and the regional, holistic and multimodal conservation and utilization of cultural heritage sites. In China, the Dongjiang-Hanjiang River Basin is a representative area of substantial cultural and ecological value for both Guangdong Province and the whole country. This paper uses the morphological spatial pattern analysis and the minimum cumulative resistance model to integrate cultural ecology sources and establish a cross-regional and large-scale cultural ecology network system that includes 1 main corridor, 22 important corridors and 17 secondary corridors. In addition, based on identified cultural landscape nodes and cultural ecology services, the economy of the cultural ecology corridor could be developed with large-scale co-construction, co-governance and shared working mechanisms to overcome administrative limits and realize the conservation and utilization of multimodal and large-scale heritage sites. This approach has strong theoretical and practical significance for innovative methods in cultural ecology research, as well as for new content in the research of Lingnan culture, ecosystem restoration, and the economic and social development of towns and villages. This article supplements unilateral studies of regional culture and ecology and demonstrates an in-depth application of cultural ecology theory. [ABSTRACT FROM AUTHOR]

Background: Colistin is an antibiotic used as a last-resort to treat multidrug-resistant Gram-negative bacterial infections. Colistin had been used for a long time in veterinary medicine for disease control and as a growth promoter in food-producing animals. This excessive use of colistin in food animals causes an increase in colistin resistance. This study aimed to determine molecular characteristics of colistin-resistant Escherichia coli in broiler chicken and chicken farm environments. Results: Four hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia. E. coli was isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detect mcr genes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize the E. coli isolates. Out of the 425 (94%; 425/453) E. coli isolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of the mcr positive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 μg/ml. The most prominent mcr gene detected was mcr-1 (47.9%; 23/48), followed by mcr-8 (18.8%; 9/48), mcr-7 (14.5%; 7/48), mcr-6 (12.5%; 6/48), mcr-4 (2.1%; 1/48), mcr-5 (2.1%; 1/48), and mcr-9 (2.1%; 1/48) genes. One E. coli isolate originating from the fecal sample was found to harbor both mcr-4 and mcr-6 genes and another isolate from the drinking water sample was carrying mcr-1 and mcr-8 genes. The majority of the mcr positive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of the mcr positive E. coli isolates were multidrug resistant. The most frequently detected virulence genes among mcr positive E. coli isolates were ast (38%; 18/48) followed by iss (23%; 11/48). This is the first research to report the prevalence of mcr-4, mcr-5, mcr-6, mcr-7, and mcr-8 genes in E. coli from broiler chickens and farm environments in Malaysia. Conclusion: Our findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistant E. coli, posing a risk to public health and food safety. [ABSTRACT FROM AUTHOR]

Background: The black fungus, mucormycosis, is on the list of lethal complications reported in recent times in COVID patients. Methodology: This cross-sectional study included all cases of post-COVID-19 mucormycosis. Patients' demographics, clinical presentations, and general health information were collected using a pre-designed form. Results: The study included 171 participants with the mean (SD) age as 49 (10) years with the sex distribution as 71% (122/171) male and 29% (49/122) females. About half of the admitted patients (47%) were known cases of Diabetes Mellitus type II with a median (IQR) Glycosylated Haemoglobin (HbA1c) of 9.1% (7–11.1%). Only 28% (48/171) had received the first COVID vaccination, and 2.9% (5/171) were fully vaccinated with two doses. During COVID-19, 76% (130/171) required hospitalisation for a mean (SD) stay of 11 (6.4) days. Eighty percent of the patients (136/171) received steroids during therapy, while 87% (150/171) and 51% (88/171) received antibiotics and antivirals, respectively. Oxygen was administered to 71% of hospitalised patients (120/171), with 39.1% (47/120) receiving it for more than 7 days. About the development of the first symptoms of mucormycosis (headache, nasal congestion, black crusts in the nose, facial pain, swelling in cheeks and eyes, and loss of vision) after being diagnosed with COVID-19, 16% (28/171) reported it within 7 days, 75% (127/171) between 8 and 30th days and 9% (16/171) after a month. On examination, 20% of mucor patients had hard palate findings, eschars, fistulas, and perforations, 38% had periodontal abscesses, and 5% reported tenderness to percussion. Conclusion: Generally, oral manifestations involved the palate and included varying degrees of mucosal discolouration, swelling, ulcers, superficial necrotic areas, and bone exposure and necrosis with dark eschars. [ABSTRACT FROM AUTHOR]

The presence of methicillin-resistant or -susceptible S. aureus in pig nostrils has been known for a long time, but the occurrence of extended-spectrum beta-lactamase (ESBL)-producing E. coli has hardly been investigated. Here, we collected 25 E. coli recovered from nasal samples of 40 pigs/10 farmers of four farms. Nine ESBL-producing isolates belonging to ST48, ST117, ST847, ST5440, ST14914 and ST10 were retrieved from seven pigs. All blaESBL genes (blaCTX-M-32, blaCTX-M-14, blaCTX-M-1, blaCTX-M-65, and blaSHV-12) were horizontally transferable by conjugation through plasmids belonging to IncI1 (n=3), IncX1 (n=3) and IncHI2 (n=1) types. IncI1-plasmids displayed different genetic environments: i) IS26-blaSHV-12-deoR-IS26, ii) wbuC-blaCTX-M-32-ISKpn26 (IS5), and iii) IS930-blaCTX-M-14-IS26. The IncHI2-plasmid contained the genetic environment IS903-blaCTX-M-65-fipA with multiple resistance genes associated either to: a) Tn21-like transposon harbouring genes conferring aminoglycosides/beta-lactams/chloramphenicol/macrolides resistance located on two atypical class 1 integrons with an embedded ΔTn5393; or b) Tn1721-derived transposon displaying an atypical class 1 integron harbouring aadA2-arr3-cmlA5-blaOXA-10-aadA24-dfrA14, preceding the genetic platform IS26-blaTEM-95-tet(A)-lysR-floR-virD2-ISVsa3-IS3075-IS26-qnrS1, as well as the tellurite resistance module. Other plasmids harbouring clinically relevant genes were detected, such as a ColE-type plasmid carrying the mcr-4.5 gene. Chromosomally encoded genes (fosA7) or integrons (intI1-dfrA1-aadA1-qacE-sul1/intI1-IS15-dfrA1-aadA2) were also identified. Finally, an IncY plasmid harbouring a class 2 integron (intI2-dfrA1-sat2-aadA1-qacL-IS406-sul3) was detected but not associated with a blaESBL gene. Our results evidence that pig nostrils might favour the spread of ESBL-E. coli and mcr-mediated colistin-resistance. Therefore, enhanced monitoring should be considered, especially in a sector where close contact between animals in intensive farming increases the risk of spreading antimicrobial resistance.

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

ABSTRACT: Objectives: The horizontal transfer of antibiotic resistance genes in Gram-negative bacteria, mainly through plasmids, is one of the greatest concerns for health systems worldwide and has been a growing threat in hospitals related to healthcare-associated infections by multidrug-resistant bacteria. Here we present phenotypic and genomic characterization of a KPC-2 and MCR-1.27-producing Klebsiella pneumoniae strain isolated from a paediatric patient at an oncologic hospital in Belém, Pará State, Brazilian Amazon region. Methods: Antibiotic susceptibility test, whole genome sequencing, and in silico analysis were used to characterize the bacterial isolate (IEC48020) received in the Evandro Chagas Institute. Results: The isolate was resistant to carbapenems, colistin, polymyxin B, and several other antimicrobials and was susceptible in vitro just to tigecycline, classified as an extensively drug-resistant phenotype. Genomic analysis revealed IEC48020 strain belonged to sequence type 11, clonal complex 258 high-risk clone and the presence of eight plasmids, two of them harbouring mcr-1.27 and blaKPC-2 genes, and the presence of virulence-related genes encoding yersiniabactin, phospholipase D, and traT genes. Conclusions: The presence and dissemination of high-risk clone bacteria with high disseminating plasmids containing antibiotic resistance genes for last resource antibiotics treatment options is a threat to the healthcare system and demands efforts in surveillance and epidemiological research for better knowledge of the actual situation of antibiotic resistance in the healthcare system, especially in the Amazon region, Brazil.

The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, Acinetobacter stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including naxD, lpxACD, and stkR gene deletion. On the other hand, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of mcr genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules. [ABSTRACT FROM AUTHOR]

Introduction: Within the 2007-2014 programme for the surveillance of antimicrobial resistance (AMR) in livestock in France, mcr-1 prevalence average in commensal Escherichia coli was found to be 5.9% in turkeys and 1.8% in broilers, indicating that mobile colistin resistance had spread in farm animals. In 2017, the French national Ecoantibio2 plan was established to tackle AMR in veterinary medicine, with the objective of a 50% reduction in exposure to colistin in farm animals within 5 years (from 2014-2015 to 2020). Our objective was to update data concerning the prevalence and molecular epidemiology of colistin resistance, in consideration of colistin sales in poultry production in France. Methods: Antimicrobial susceptibility of commensal E. coli isolated from broilers and turkeys at slaughterhouse was determined by broth micro-dilution. The mcr genes were screened by polymerase chain reaction (PCR). Whole genome sequencing (WGS) was used to investigate the genetic diversity of colistinresistant isolates. Transformation experiments enabled identification of the mcrbearing plasmid replicon types. The correlation between prevalence of colistin resistance and colistin usage data was explored statistically. Results and discussion: In 2020, in France, the resistance prevalence to colistin in poultry production was 3% in turkeys and 1% in broilers, showing a significant highly positive correlation with a -68% decrease of poultry exposure to colistin since 2014. Only the mcr-1 gene was detected among the colistin-resistant E. coli. More than 80% of isolates are multi-drug resistant with 40% of isolates originating from turkeys and 44% originating from broilers co-resistant to the critically important antimicrobial ciprofloxacin. Most of the strains had no clonal relationship. The mcr gene was located in different plasmid types, carrying various other AMR genes. The decrease in colistin resistance among poultry in France can be considered a positive outcome of the national action plans for reduced colistin usage. [ABSTRACT FROM AUTHOR]

The emergence and prevalence of mobile colistin resistance gene mcr have dramatically compromised the clinical efficacy of colistin, a cyclopeptide antibiotic considered to be the last option for treating different-to-treat infections. The combination strategy provides a productive and cost-effective strategy to expand the lifespan of existing antibiotics. Structural-activity relationship analysis of polymyxins indicates that the fatty acyl chain plays an indispensable role in their antibacterial activity. Herein, it is revealed that three saturated fatty acids (SFAs), especially sodium caprate (SC), substantially potentiate the antibacterial activity of colistin against mcr-positive bacteria. The combination of SFAs and colistin effectively inhibits biofilm formation and eliminates matured biofilms, and is capable of preventing the emergence and spread of mobile colistin resistance. Mechanistically, the addition of SFAs reduces lipopolysaccharide (LPS) modification by simultaneously promoting LPS biosynthesis and inhibiting the activity of MCR enzyme, enhance bacterial membrane damage, and impair the proton motive force-dependent efflux pump, thereby boosting the action of colistin. In three animal models of infection by mcr-positive pathogens, SC combined with colistin exhibit an excellent therapeutic effect. These findings indicate the therapeutic potential of SFAs as novel antibiotic adjuvants for the treatment of infections caused by multidrug-resistant bacteria in combination with colistin. [ABSTRACT FROM AUTHOR]

Salmonella is one of the most important zoonotic pathogens and a major cause of foodborne illnesses, posing a serious global public health hazard. The emergence of plasmid-mediated mcr genes in Salmonella has greatly reduced the clinical choice of salmonellosis treatment. The aim of this study was to investigate the plasmid characteristics of mcr-positive Salmonella identified from patients in Sichuan, China during 2014 to 2017 by whole genomes sequencing. In this study, a total of 12 mcr-positive isolates (1.15%,; mcr-1, n=10; mcr-3, n=2) were identified from 1046 Salmonella isolates using PCR. Further characterization of these isolates was performed through antimicrobial susceptibility testing, conjugation assays, whole genome sequencing, and bioinformatics analysis. The mcr-1 gene in these isolates were carried by three types of typical mcr-1-bearing plasmids widely distributed in Enterobacteriaceae (IncX4, IncI2 and IncHI2). Of note, two mcr-1-harboring IncHI2 plasmids were integrated into chromosomes by insertion sequences. Two mcr-3-bearing plasmids were IncC and IncFIB broad-host-range plasmids respectively. Genetic context analysis found that mcr-1 was mainly located in Tn6330 or truncated Tn6300, and mcr-3 shared a common genetic structure tnpA-mcr-3-dgkA-ISKpn40. Overall, we found that mcr gene in clinical Salmonella were commonly carried by broad-host plasmids and have potential to transfer into other bacteria by these plasmids. Continuous surveillance of MDR Salmonella in humans and investigation the underlying transmission mechanisms of ARGs are vital to curb the current severe AMR concern. [ABSTRACT FROM AUTHOR]

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia (E.) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples (n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli. In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The blaTEM group was most frequently detected (97.02%), followed by blaCTX m (45.5%), blaSHV (9.9%), and blaOXA-2 (0.9%). However, mcr genes and blaNDM, blaKPC, blaVIM, and blaOXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the blaTEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms.

ABSTRACT The aim of this study was to determine the occurrence of plasmid-mediated colistin resistance in domestic and imported meat and slaughter animals in the Czech Republic during 2020–2021 by using selective cultivation and direct PCR testing. A total of 111 colistin-resistant Escherichia coli isolates with mcr-1 gene were obtained from 65 (9.9%, n = 659) samples and subjected to whole-genome sequencing. Isolates with mcr were frequently found in fresh meat from domestic production (14.2%) as well as from import (28.8%). The mcr-1-positive E. coli isolates predominantly originated from meat samples (16.6%), mainly poultry (27.1%), and only minor part of the isolates came from the cecum (1.7%). In contrast to selective cultivation, 205 (31.1%) samples of whole-community DNA were positive for at least one mcr variant, and other genes besides mcr-1 were detected. Analysis of whole-genome data of sequenced E. coli isolates revealed diverse sequence types (STs) including pathogenic lineages and dominance of ST1011 (15.6%) and ST162 (12.8%). Most isolates showed multidrug-resistant profile, and 9% of isolates produced clinically important beta-lactamases. The mcr-1 gene was predominantly located on one of three conjugative plasmids of IncX4 (83.5%), IncI2 (7.3%), and IncHI2 (7.3%) groups. Seventy-two percent isolates of several STs carried ColV plasmids. The study revealed high prevalence of mcr genes in fresh meat of slaughter animals. Our results confirmed previous assumptions that the livestock, especially poultry production, is an important source of colistin-resistant E. coli with the potential of transfer to humans via the food chain. IMPORTANCE We present the first data on nation-wide surveillance of plasmid-mediated colistin resistance in the Czech Republic. High occurrence of plasmid-mediated colistin resistance was found in meat samples, especially in poultry from both domestic production and import, while the presence of mcr genes was lower in the gut of slaughter animals. In contrast to culture-based approach, testing of whole-community DNA showed higher prevalence of mcr and presence of various mcr variants. Our results support the importance of combining cultivation methods with direct culture-independent techniques and highlight the need for harmonized surveillance of plasmid-mediated colistin resistance. Our study confirmed the importance of livestock as a major reservoir of plasmid-mediated colistin resistance and pointed out the risks of poultry meat for the transmission of mcr genes toward humans. We identified several mcr-associated prevalent STs, especially ST1011, which should be monitored further as they represent zoonotic bacteria circulating between different environments.

IntroductionWithin the 2007–2014 programme for the surveillance of antimicrobial resistance (AMR) in livestock in France, mcr-1 prevalence average in commensal Escherichia coli was found to be 5.9% in turkeys and 1.8% in broilers, indicating that mobile colistin resistance had spread in farm animals. In 2017, the French national Ecoantibio2 plan was established to tackle AMR in veterinary medicine, with the objective of a 50% reduction in exposure to colistin in farm animals within 5 years (from 2014–2015 to 2020). Our objective was to update data concerning the prevalence and molecular epidemiology of colistin resistance, in consideration of colistin sales in poultry production in France.MethodsAntimicrobial susceptibility of commensal E. coli isolated from broilers and turkeys at slaughterhouse was determined by broth micro-dilution. The mcr genes were screened by polymerase chain reaction (PCR). Whole genome sequencing (WGS) was used to investigate the genetic diversity of colistin-resistant isolates. Transformation experiments enabled identification of the mcr-bearing plasmid replicon types. The correlation between prevalence of colistin resistance and colistin usage data was explored statistically.Results and discussionIn 2020, in France, the resistance prevalence to colistin in poultry production was 3% in turkeys and 1% in broilers, showing a significant highly positive correlation with a −68% decrease of poultry exposure to colistin since 2014. Only the mcr-1 gene was detected among the colistin-resistant E. coli. More than 80% of isolates are multi-drug resistant with 40% of isolates originating from turkeys and 44% originating from broilers co-resistant to the critically important antimicrobial ciprofloxacin. Most of the strains had no clonal relationship. The mcr gene was located in different plasmid types, carrying various other AMR genes. The decrease in colistin resistance among poultry in France can be considered a positive outcome of the national action plans for reduced colistin usage.

Limited attention has been given to improving carbon storage by identifying ecological conservation and restoration areas (ECRAs). In this research, we proposed a new framework for identifying ECRAs by incorporating future carbon storage changes into ecological security patterns (ESPs), including several models of the Patch-generating Land Use Simulation (PLUS), Integrated Valuation of Ecosystem Service and Tradeoffs (InVEST), Minimum Cumulative Resistance (MCR) and circuit theory. This new framework was applied in Jiangsu Yangtze River Economic Belt, East China. To evaluate the effectiveness of this new framework, we compared two scenarios: an ecological priority scenario (EPS) where future carbon storage change was not considered and an ecosystem carbon sequestration scenario (ECSS) where future carbon storage change was explicitly incorporated. Under the EPS, ecological conservation areas and ecological restoration areas were 11169.87 km2 and 221.11 km2, respectively. Under the ECSS, the ecological conservation areas and ecological restoration areas were 14768.76 km2 and 244.89 km2, respectively. Carbon storage will be most likely to increase around lakes and the Yangtze River, and the identified key areas under the ECSS will be more adaptable to future environmental changes than the EPS. This new framework can effectively enhance both ecological function and carbon sequestration, providing effective support for policymakers in landscape management and low-carbon development in other regions facing similar challenges. In the meantime, more caution is needed for the possible limitations, such as without adequate consideration of uncertainties of changes in population, land use, and economy in the future.

The advent of antimicrobials-resistant (AMR), including colistin-resistant bacteria, poses a significant challenge to animal and human health, food safety, socioeconomic growth, and the global environment. This study aimed to ascertain the colistin resistance prevalence and molecular mechanisms of colistin resistance in Enterobacteriaceae. The colistin resistance was determined using broth microdilution assay, PCR; and Sanger sequencing of mcr genes responsible for colistin resistance in Enterobacteriaceae (n  =  627), including Escherichia coli (436), Salmonella spp. (n  =  140), and Klebsiella pneumoniae (n  =  51), obtained from chicken and chicken meats. Out of 627 Enterobacteriaceae, 8.6% of isolates exhibited colistin resistance phenotypically. Among these colistin resistant isolates, 9.3% (n  =  37) were isolated from chicken meat, 7.2% (n  =  11) from the cloacal swab of chicken and 7.9% (n  =  6) from the litter samples. Overall, 12.96% of colistin-resistant isolates were positive with mcr genes, in which mcr-1 and mcr-5 genes were determined in 11.11% and 1.85% of colistin-resistant isolates, respectively. The E. coli isolates obtained from chicken meats, cloacal swabs and litter samples were found positive for mcr-1, and Salmonella spp. originated from the chicken meat sample was observed with mcr-5, whereas no mcr genes were observed in K. pneumoniae strains isolated from any of the collected samples. The other colistin resistance genes, including mcr-2, mcr-3, mcr-4, mcr-6, mcr7, mcr-8, mcr-9, and mcr-10 were not detected in the studied samples. The mcr1 and mcr-5 genes were sequenced and found to be 100% identical to the mcr-1 and mcr-5 gene sequences available in the NCBI database. This is the first report of colistin resistance mcr-5 gene in Malaysia which could portend the emergence of mcr-5 harboring bacterial strains for infection. Further studies are needed to characterize the mr-5 harbouring bacteria for the determination of plasmid associated with mcr-5 gene. [ABSTRACT FROM AUTHOR]

Ecological corridors can improve the connectivity between different habitat regions, ultimately halting the loss of biodiversity and habitat fragmentation. Building ecological corridors is a crucial step in protecting biodiversity. Ecological corridors had previously been built primarily on nature reserves, ignoring ecosystem services. In this study, a novel approach to building ecological corridors is put forth that takes into account a variety of ecosystem services, morphological spatial pattern analysis (MSPA), and connectivity methodologies to identify significant ecological sources. Ecological corridors and significant strategic nodes are created based on the minimum cumulative resistance model (MCR) and circuit theory in order to construct the Yangtze River Delta's ecological security pattern. The research found that: (1) the identified ecological sources are 90,821.84 km2, and the total length of ecological corridors is 4704.03 km. (2) In total, 141 ecological restoration areas are identified, with a total area of 2302.77 km2; 151 ecological protection areas are identified, with a total area of 5303.43 km2. This study can provide valuable insights into the establishment of ecological patterns and the construction of priority restoration and protection areas in the ecological restoration of the Yangtze River Delta. [ABSTRACT FROM AUTHOR]

The emergence of colistin resistance is one of the most serious future issues since it is a last‐resort antibiotic used to treat infections caused by multidrug‐resistant (MDR) gram‐negative bacteria, particularly those resistant to carbapenems. The aquatic environment acts as a reservoir for the emergence and spread of colistin resistant pathogens. The emergence and transmission of a plasmid mediated mcr gene is one of the most important mechanism of colistin resistance in gram negative bacteria. Several mcr variants have been identified in zoonotic pathogens of aquatic origin that may easily transmit this gene to human pathogens. Currently, very few studies have been conducted to test colistin susceptibility in aquaculture associated bacteria. This may be attributed to a limited technical resource for screening colistin‐resistant microorganisms. As a result, to reduce the emergence and spread of colistin resistance in human and animal health, as well as in the environment, the One Health strategy and laboratory methodologies must be expanded. [ABSTRACT FROM AUTHOR]

A revision of the Energy Efficiency Design Index (EEDI) formulation was previously proposed to be useful for inland ships of Bangladesh. The study incorporated the shallow water effect using Schlichting's method which has been developed in 1934 based on a large number of ship model tests to show how a ship's resistance in shallow water deviates from that in deep water. However, the evaluation and presentation of Schlichting's results did not cover all range of ship parameters. This reanalysis has considered the shallow water effect by actual measurement of 15 inland ships of Bangladesh. Later, the results of Schlichting's method were compared with (a) actual investigation, (b) an improved version of Schlichting's method proposed by Lackenby in 1963, and (c) a new method proposed by C B Barrass in 2004. It was found that the deviations of Schlichting's results are much higher than Lackenby and Barrass's methods in comparison to the investigated results. In a previous analysis of the inland ships of Bangladesh, the Maximum Continuous Rating (MCR) of the main engine was considered by using the Holtrop-Mennen method. As this method requires too much ship data, that analysis had assumed some unknown required ship data. This reanalysis has overcome that problem by the physical investigations of the same 15 inland ships of Bangladesh. The average MCR for inland cargo ships and oil tankers of Bangladesh are measured as 70% by the investigations, whereas it is 80% for passenger ships. [ABSTRACT FROM AUTHOR]

This study aimed to establish a comprehensive and sustainable approach to the conservation of historical districts through the "Cultural Landscape Security Pattern" (CLSP) theory. Deploying this theory can penetrate limitations posed by physical and social-emotional factors, enabling a resilient framework which can coordinate long-term heritage protection with urbanization in a more sustainable manner. Chaozong Street in Changsha City, China, was taken as the locus of study, which was initiated by quantitatively analyzing and evaluating the cultural landscape. The ArcGIS spatial analysis and the minimum cumulative resistance (MCR) model were then considered to model different levels of CLSP. It was on this basis that corresponding regulations and development strategies were then proposed. The results from the study demonstrate that implementing CLSP in historic districts can construct a protective network over the districts, which can then guide the recovery of fragmented historical built environments, as well as ensure continuity of historical consciousness and integrity. In addition, in comparison with conventional protection planning methods, this method features greater flexibility and adaptability when considering and accounting for complex spatial issues in historic districts and provides a novel approach for similar studies. [ABSTRACT FROM AUTHOR]

Mobilized colistin resistance genes (mcr) may confer resistance to the last-resort antimicrobial colistin and can often be transmitted horizontally. mcr encode phosphoethanolamine transferases (PET), which are closely related to chromosomally encoded, intrinsic lipid modification PET (i-PET; e.g., EptA, EptB, CptA). To gain insight into the evolution of mcr within the context of i- PET, we identified 69,814 MCR-like proteins present across 256 bacterial genera (obtained by querying known MCR family representatives against the National Center for Biotechnology Information [NCBI] non-redundant protein database via protein BLAST). We subsequently identified 125 putative novel mcr-like genes, which were located on the same contig as (i) ≥1 plasmid replicon and (ii) ≥1 additional antimicrobial resistance gene (obtained by querying the PlasmidFinder database and NCBI’s National Database of Antibiotic Resistant Organisms, respectively, via nucleotide BLAST). At 80% amino acid identity, these putative novel MCR-like proteins formed 13 clusters, five of which represented putative novel MCR families. Sequence similarity and a maximum likelihood phylogeny of mcr, putative novel mcr-like, and ipet genes indicated that sequence similarity was insufficient to discriminate mcr from ipet genes. A mixed-effect model of evolution (MEME) indicated that site- and branch-specific positive selection played a role in the evolution of alleles within the mcr-2 and mcr-9 families. MEME suggested that positive selection played a role in the diversification of several residues in structurally important regions, including (i) a bridging region that connects the membrane-bound and catalytic periplasmic domains, and (ii) a periplasmic loop juxtaposing the substrate entry tunnel. Moreover, eptA and mcr were localized within different genomic contexts. Canonical eptA genes were typically chromosomally encoded in an operon with a two-component regulatory system or adjacent to a TetR-type regulator. Conversely, mcr were represented by single-gene operons or adjacent to pap2 and dgkA, which encode a PAP2 family lipid A phosphatase and diacylglycerol kinase, respectively. Our data suggest that eptA can give rise to “colistin resistance genes” through various mechanisms, including mobilization, selection, and diversification of genomic context and regulatory pathways. These mechanisms likely altered gene expression levels and enzyme activity, allowing bona fide eptA to evolve to function in colistin resistance. [ABSTRACT FROM AUTHOR]

The uncontrolled usage of antibiotics, especially colistin as growth promoter in poultry and the manures utilized as fertilizers in vegetable farming serve as the fundamental causes of mobilized colistin resistance (mcr) gene emergence in Escherichia coli (E. coli). This study was conducted to determine the prevalence, antibiotic susceptibility profile and phylogroups of colistin resistant E. coli isolated from poultry farm (217 chicken cloacal swab), 200 raw chicken meat and 100 vegetables samples from markets in Kelantan, Malaysia. The samples were processed using routine microbiological method, polymerase chain reaction (PCR) to detect colistin resistant E. coli isolates, disk diffusion antimicrobial susceptibility tests with 13 antibiotics, colistin minimum inhibitory concentration (MIC) test and PCR based phylogroups detection. The overall E. coli prevalence was 71.0% (367/517) and 3.9% (20/517) isolates harboured multiple mcr-genes (mcr-1, mcr-3, mcr-6, mcr-8 and mcr-9) from chicken origin only, while no mcr detected was in vegetables. The findings revealed that 89 – 100% E. coli isolates from chickens were resistant towards tetracycline, ampicillin, amoxicillin, and chloramphenicol with multiple antibiotic resistance index score of more than 0.2 yet the vegetable isolates were showing higher sensitivity towards these antibiotics. The ten mcr-harbouring isolates exhibited phenotypic colistin resistance at MIC ≥ 4 µg/ml. Meanwhile, phylogroup A (45.1%) and phylogroup B1 (20%) were predominating in chicken whereas phylogroup A (59.4%) was highlighted in vegetable origin isolates. These findings underscore the emerging threat of multidrug resistance and increasing trends of mcr in E. coli, mainly in food animals in Malaysia. [ABSTRACT FROM AUTHOR]

The co-existence of the colistin resistance (mcr) gene with multiple drug-resistance genes has raised concerns about the possibility of the development of pan-drug-resistant bacteria that will complicate treatment. This study aimed to investigate the antibiotic resistance profiles and co-existence of antibiotic resistance genes among the colistin-resistant Enterobacteriaceae isolates recovered from poultry and poultry meats. The antibiotic susceptibility to various classes of antibiotics was performed using the Kirby-Bauer disk diffusion method and selected antimicrobial resistance genes were detected using PCR in a total of 54 colistin-resistant Enterobacteriaceae isolates including Escherichia coli (E. coli) (n = 32), Salmonella spp. (n = 16) and Klebsiella pneumoniae (K. pneumoniae) (n = 6) isolates. Most of the isolates had multi-drug resistance (MDR), with antibiotic resistance against up to seven classes of antibiotics. All mcr-harbouring, colistin-resistant Enterobacteriaceae isolates showed this MDR (100%) phenotype. The mcr-1 harbouring E. coli isolates were co-harbouring multiple antibiotic resistance genes. The seven most commonly identified resistance genes (blaTEM, tetA, floR, aac-3-IV, aadA1, fosA, aac(6_)-lb) were detected in an mcr-1-harbouring E. coli isolate recovered from a cloacal swab. The mcr-5 harbouring Salmonella spp. isolate recovered from poultry meats was positive for blaTEM, tetA, floR, aac-3-IV, fosA and aac(6_)-lb genes. In conclusion, the colistin-resistant Enterobacteriaceae with mcr genes co-existing multiple clinically important antimicrobial resistance genes in poultry and poultry meats may cause potential future threats to infection treatment choices in humans and animals. [ABSTRACT FROM AUTHOR]

CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs). e-CHACRs can be inserted at various genomic locations and carry two or more gRNAs, the first copying the e-CHACR and the second mutating and inactivating the cas9 transgene. Alternatively, ERACRs are inserted at the same genomic location as a gene drive, carrying two gRNAs that cut on either side of the gene drive to excise it. e-CHACRs efficiently inactivate Cas9 and can drive to completion in cage experiments. Similarly, ERACRs, particularly those carrying a recoded cDNA-restoring endogenous gene activity, can drive reliably to fully replace a gene drive. We compare the strengths of these two systems.