O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.

Wnt signaling is an important target for anabolic therapies in osteoporosis. A sclerostin-neutralizing antibody (Scl-Ab), that blocks the Wnt signaling inhibitor (sclerostin), has been shown to promote bone mass in animal models and clinical studies. However, the cellular mechanisms by which Wnt signaling promotes osteogenesis remain to be further investigated. O-GlcNAcylation, a dynamic post-translational modification of proteins, controls multiple critical biological processes including transcription, translation, and cell fate determination. Here, we report that Wnt3a either induces O-GlcNAcylation rapidly via the Ca2+-PKA-Gfat1 axis, or increases it in a Wnt-ß-catenin-dependent manner following prolonged stimulation. Importantly, we find O-GlcNAcylation indispensable for osteoblastogenesis both in vivo and in vitro. Genetic ablation of O-GlcNAcylation in the osteoblast-lineage diminishes bone formation and delays bone fracture healing in response to Wnt stimulation in vivo. Mechanistically, Wnt3a induces O-GlcNAcylation at Serine 174 of PDK1 to stabilize the protein, resulting in increased glycolysis and osteogenesis. These findings highlight O-GlcNAcylation as an important mechanism regulating Wnt-induced glucose metabolism and bone anabolism.

In vivo multi-contrast depth-resolved choroidal imaging of a mouse using polarization-diversity optical coherence tomography.

The results of depth-resolved multi-contrast in vivo mouse choroidal imaging using a polarization-diversity optical coherence tomography (PD-OCT) system are presented. A selectively chosen depth of focus that was fine-tuned with a sensorless adaptive optics technique and a simple segmentation based on the degree of polarization uniformity signal visualizes the detailed features of a mouse choroid from the OCT angiography images. A comprehensive image analysis of the choroid revealed the distinctive pathological characteristics of the laser-induced choroidal neovascularization mouse.

Cucurbit[7]uril-Modified Nano SiO2 for Efficient Separation of Crude Oil Emulsions: Properties and Demulsification Mechanism.

Demulsification of crude oil emulsion is an obvious problem in the whole of petroleum engineering, which needs to be dealt with urgently. In this paper, a supramolecular material Cucurbit[7]uril-SiO2 (CB-SiO2) synthesized with excellent demulsification efficiency (DE) on O/W emulsion was synthesized by a simple thermal synthesis method. The microscopic morphology and structure were investigated through modern characterization techniques. Furthermore, its stability, dynamic interfacial tension (IFT), and wettability (three-phase contact angle (CA)) were systematically investigated, and the demulsification efficiency of different conditions on crude oil emulsion was also investigated. Reassuringly, these results showed that when the temperature was 70 °C, the demulsification dosage was close to 600 mg/L and remained unchanged for 90 min; the demulsification efficiency is 2.2 times compared with the unmodified material, up to 93.63%. In addition, a plausible demulsification mechanism was proposed, which is that CB-SiO2 can adsorb and disrupt the oil-water interface, leading to oil-water separation and promoting demulsification. It is a promising demulsification material for the oil industry demulsification.

The interaction between the costimulatory molecules CD80/86 and CD28 contributed to CD4+ T lymphocyte activation in flounder (Paralichthys olivaceus).

CD28 and CD80/86 are crucial co-stimulatory molecules for the T cell activation. Previous study illustrated that CD28 and CD80/86 present on T cells and antigen-presenting cells in flounder (Paralichthys olivaceus), respectively. The co-stimulatory molecules were closely associated with cell immunity. In this paper, recombinant protein of flounder CD80/86 (rCD80/86) and phytohemagglutinin (PHA) were added to peripheral blood leukocytes (PBLs) in vitro. Lymphocytes were significantly proliferated with CFSE staining, and the proportion of CD4+ and CD28+ lymphocytes significantly increased. In the meantime, genes related to the CD28-CD80/86 signaling pathway or T cell markers were significantly upregulated (p < 0.05). For further study, the interaction between CD80/86 and CD28 was confirmed. The plasmid of CD28 (pCD28-FLAG and pVN-CD28) or CD80/86 (pVC-CD80/86) was successfully constructed. In addition, pVN-ΔCD28 without the conserved motif "TFPPPF" was constructed. The results showed that bands of pCD28-FLAG bound to rCD80/86 were detected by both anti-FLAG and anti-CD80/86. pVN-CD28 complemented to pVC-CD80/86 showing positive fluorescent signals, and pVN-ΔCD28 failed to combine with pVC-CD80/86. The motif "TFPPPF" in CD28 played a crucial role in this linkage. These results indicate that CD28 and CD80/86 molecules interact with each other, and their binding may modulate T lymphocytes immune response in flounder. This study proved the existence of CD28-CD80/86 signaling pathway in flounder.

Short-term and long-term efficacy of accelerated transcranial magnetic stimulation for depression: a systematic review and meta-analysis.

BACKGROUND: In recent years, accelerated transcranial magnetic stimulation (aTMS) has been developed, which has a shortened treatment period. The aim of this study was to evaluate the efficacy and long-term maintenance effects of aTMS in patients with major depressive disorder (MDD). METHODS: We systematically searched online databases for aTMS studies in patients with MDD published before February 2023 and performed a meta-analysis on the extracted data. RESULTS: Four randomized controlled trials (RCTs) and 10 before-and-after controlled studies were included. The findings showed that depression scores significantly decreased following the intervention (SMD = 1.80, 95% CI (1.31, 2.30), p < 0.00001). There was no significant difference in antidepressant effectiveness between aTMS and standard TMS (SMD = -0.67, 95% CI (-1.62, 0.27), p = 0.16). Depression scores at follow-up were lower than those directly after the intervention based on the depression rating scale (SMD = 0.22, 95% CI (0.06, 0.37), p = 0.006), suggesting a potential long-term maintenance effect of aTMS. Subgroup meta-analysis results indicated that different modes of aTMS may have diverse long-term effects. At the end of treatment with the accelerated repetitive transcranial magnetic stimulation (arTMS) mode, depressive symptoms may continue to improve (SMD = 0.29, 95% CI (0.10, 0.49), I2 = 22%, p = 0.003), while the accelerated intermittent theta burst stimulation (aiTBS) mode only maintains posttreatment effects (SMD = 0.01, 95% CI (-0.45, 0.47), I2 = 66%, p = 0.98). CONCLUSIONS: Compared with standard TMS, aTMS can rapidly improve depressive symptoms, but there is no significant difference in efficacy. aTMS may also have long-term maintenance effects, but longer follow-up periods are needed to assess this possibility. TRIAL REGISTRATION: This article is original and not under simultaneous consideration for publication. The study was registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) (number: CRD42023406590).

Fast and high-accuracy collinear reflection Mueller imaging polarimeter implemented with the compound calibration method.

The collinear reflection Mueller matrix imaging polarimeter is suitable for characterizing thick samples with high-scattering depolarization such as biological tissues or in-situ living organs. Achieving fast detection and high measurement accuracy is vital to prevent artifacts and accurately assess polarization characteristics in these applications. This paper demonstrates a fast collinear reflection imaging polarimeter based on liquid crystal variable retarders (LCVRs-CRMMIP). We propose a novel compound calibration method (CCM), to the best of our knowledge, which enhances measurement accuracy through light intensity correction and an improved equivalent calibration sample model. This method surpasses the double-pass eigenvalue calibration method (dp-ECM), enhancing accuracy by over 23 times. Performance evaluations with standard samples, including mirrors, linear polarizers, and wave plates, reveal that the LCVRs-CRMMIP achieves rapid measurements (about 3 s) and high accuracy with an error of less than 0.0017.

P-glycoprotein-mediated herb-drug interaction evaluation between Tenacissoside G and paclitaxel.

P-glycoprotein (P-gp)-mediated herb-drug interactions (HDIs) may impact drug efficacy and safety. Tenacissoside G (Tsd-G), a major active component of Marsdenia tenacissima, exhibits anticancer activity. To analyze the effect of Tsd-G on the pharmacokinetics of paclitaxel (PTX), researchers selected 30 Sprague-Dawley (SD) rats, randomized into a solvent control group, a verapamil positive control group, and 20, 40, and 60 mg/kg Tsd-G groups. After seven consecutive days of intraperitoneal injection of verapamil or Tsd-G, a single dose of 6 mg/kg PTX was injected intravenously. Plasma samples were collected at different time points, and proteins were precipitated using a methanol-acetonitrile solution. An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was developed, with docetaxel as an internal standard, and quantified using positive ion multiple reaction monitoring (MRM) mode. This analytical method's specificity, accuracy, precision, recovery, matrix effect, and sample stability meet the requirements for biological sample determination. After Tsd-G administration in rats, the mean residence time of PTX was significantly prolonged. And Tsd-G can stably bind to P-gp by forming hydrogen bonds and inhibiting the expression of P-gp in rat liver. Although the metabolites of PTX were not detected in this study, the above results still indicate the existence of HDIs between Tsd-G and PTX, and P-gp may be the main target to mediate HDIs.

Gate-Tunable Spin Seebeck Effect and Pure Spin Current Generation in Molecular Junctions Based on Bipolar Magnetic Molecules.

Generating pure spin currents is very desirable in spintronics, as it provides a promising way to substantially reduce Joule heating and achieve ultrahigh integration density. However, to date, most spintronic devices exhibit spin currents that are accompanied by charge currents. The generation of pure spin currents on the nanoscale, particularly at the single-molecule level, remains challenging. Here, we propose that by exploiting our recently reported bipolar magnetic molecules (BMMs) as the core component of single-molecule devices, where the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) come from different spin channels, the generation of pure spin currents can be easily realized via the spin Seebeck effect (SSE) with applied temperature gradient. Moreover, the spin Seebeck coefficient can be modulated over a wide range by applying an external gate voltage. The proposal is verified through first-principles calculations on two BMM-based molecular junctions.

Comprehensive analysis of risk factors for postoperative wound infection following radical mastectomy in breast cancer patients.

Surgical site infections (SSIs) following radical mastectomy in breast cancer patients can significantly affect patient recovery and healthcare resources. Identifying and understanding the risk factors for postoperative wound infections (PWIs) are crucial for improving surgical outcomes. This retrospective study was conducted from June 2020 to June 2023, including 23 breast cancer patients who developed PWIs post-radical mastectomy and a control group of 46 patients without such infections. Comprehensive patient data, including variables such as intraoperative blood loss, hospital stay duration, body mass index (BMI), operation time, anaemia, drainage time, diabetes mellitus, cancer stage, white blood cell (WBC) count, serum albumin levels and preoperative neoadjuvant chemotherapy, were meticulously gathered. Statistical analyses, including univariate and multivariate logistic regression, were performed using SPSS software (Version 27.0). The univariate analysis identified several factors significantly associated with an increased risk of PWIs, including preoperative neoadjuvant chemotherapy, low serum albumin levels, advanced cancer stage, diabetes mellitus and reduced WBC count. Multivariate logistic regression highlighted anaemia, prolonged drainage time, diabetes mellitus, advanced cancer stage, reduced WBC count, hypoalbuminemia and preoperative neoadjuvant chemotherapy as significant contributors to the increased risk of PWIs. Anaemia, extended drainage time, diabetes mellitus, advanced cancer stage, low WBC count, hypoalbuminemia and preoperative neoadjuvant chemotherapy are key risk factors for SSIs post-radical mastectomy. Early identification and proactive management of these factors are imperative to reduce the incidence of postoperative infections and enhance recovery outcomes in breast cancer patients.

[Mechanism of Huachansu Injection against colorectal cancer based on network pharmacology and cellular experimental].

This study aimed to elucidate the mechanism of Huachansu Injection(HCSI) against colorectal cancer(CRC) using network pharmacology, molecular docking technology, and cellular experimental. This research group initially used LC-MS/MS to detect the content of 16 bufadienolides in HCSI. Ten bufadienolide components were selected based on a content threshold of greater than 10 ng·mL~(-1). Their potential targets were further predicted using the SwissTargetPrediction database. CRC-related targets were obtained through GeneCards, OMIM, TTD, and PharmGKB databases. The intersection targets of HCSI in the treatment of CRC were obtained through Venny. The "active component-target-disease" network and target protein-protein interaction(PPI) network were constructed via Cytoscape software. Core targets were screened based on the degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on these key targets. Molecular docking was conducted using AutoDock software on major bufadienolide active components and key targets. Different concentrations of HCSI, psi-bufarenogin(BUF), and bufotalin(BFT) were tested for their effects on cell viability, migration, and apoptosis rates in CRC HCT116 cells. Western blot was conducted to detect the expression of proteins related to the PI3K/Akt/mTOR signaling pathway in HCT116 cells. Eight main active components of HCSI, including arenobufagin, BUF, and BFT, as well as 20 key targets of HCSI in combating CRC, such as EGFR, IL6, and mTOR, were identified. Based on KEGG pathway enrichment and molecular docking results, the PI3K/Akt/mTOR signaling pathway was selected for further verification. Cellular experimental demonstrated that HCSI, BUF, and BFT significantly inhibited the proliferation and migration abilities of HCT116 cells, induced apoptosis in these cells, and downregulated the expression of PI3K/Akt/mTOR pathway-related proteins. This result suggests that HCSI, BUF, and BFT may exert their anti-CRC effects by regulating the PI3K/Akt/mTOR signaling pathway through targets such as mTOR and PIK3CA. This study provides theoretical evidence for exploring the active ingredients and mechanism of HCSI against CRC.

MiR-181c-5p ameliorates learning and memory in sleep-deprived mice via HMGB1/TLR4/NF-κB pathway.

Sleep deprivation (SD) can lead to cognitive impairment caused by neuroinflammation. MiR-181c-5p/HMGB1 axis plays a part in anti-inflammation effects. However, the mechanism that miR-181c-5p facilitates learning and memory in SD mice remains unclear. So we investigated the role of miR-181c-5p in learning and memory impairment induced by SD. We overexpressed miR-181c-5p in the mice hippocampus by injecting lentivirus vector-miR-181c-5p (LV-miR-181c-5p) particles. Mice were divided into four groups: control (Ctrl), SD, SD + miR-181c-5p and SD + vector. We found that mice in the third group showed ameliorated learning and memory compared with the fourth group. The content of ionized calcium binding adaptor molecule 1 (IBA-1) in the third group was decreased compared with the fourth group. Moreover, the expression levels of HMGB1, TLR4 and p-NF-κB in the hippocampus of overexpressed miR-181c-5p mice were reduced. In total, miR-181c-5p ameliorated learning and memory in SD mice via the HMGB1/TLR4/NF-κB pathway.

Uncertainty quantification of CO2 emissions from China's civil aviation industry to 2050.

To mitigate aviation's carbon emissions of the aviation industry, the following steps are vital: accurately quantifying the carbon emission path by considering uncertainty factors, including transportation demand in the post-COVID-19 pandemic period; identifying gaps between this path and emission reduction targets; and providing mitigation measures. Some mitigation measures that can be employed by China's civil aviation industry include the gradual realization of large-scale production of sustainable aviation fuels and transition to 100% sustainable and low-carbon sources of energy. This study identified the key driving factors of carbon emissions by using the Delphi Method and set scenarios that consider uncertainty, such as aviation development and emission reduction policies. A backpropagation neural network and Monte Carlo simulation were used to quantify the carbon emission path. The study results show that China's civil aviation industry can effectively help the country achieve its carbon peak and carbon neutrality goals. However, to achieve the net-zero carbon emissions goal of global aviation, China needs to reduce its emissions by approximately 82%-91% based on the optimal emission scenario. Thus, under the international net-zero target, China's civil aviation industry will face significant pressure to reduce its emissions. The use of sustainable aviation fuels is the best way to reduce aviation emissions by 2050. Moreover, in addition to the application of sustainable aviation fuel, it will be necessary to develop a new generation of aircraft introducing new materials and upgrading technology, implement additional carbon absorption measures, and make use of carbon trading markets to facilitate China's civil aviation industry's contribution to reduce climate change.

[Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification].

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12ß-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Resilience and fragmentation in healthcare coalitions: The link between resource contributions and centrality in health-related interorganizational networks.

Interorganizational coalitions or collaboratives in healthcare are essential to address the health challenges of local communities, particularly during crises such as the Covid-19 pandemic. However, few studies use large-scale data to systematically assess the network structure of these collaboratives and understand their potential to be resilient or fragment in the face of structural changes. This paper analyzes data collected in 2009-2017 about 817 organizations (nodes) in 42 healthcare collaboratives (networks) throughout Florida, the third-largest U.S. state by population, including information about interorganizational ties and organizations' resource contributions to their coalitions. Social network methods are used to characterize the resilience of these collaboratives, including identification of key players through various centrality metrics, analyses of fragmentation centrality and core/periphery structure, and Exponential Random Graph Models to examine how resource contributions facilitate interorganizational ties. Results show that the most significant resource contributions are made by key players identified through fragmentation centrality and by members of the network core. Departure or removal of these organizations would both strongly disrupt network structure and sever essential resource contributions, undermining the overall resilience of a collaborative. Furthermore, one-third of collaboratives are highly susceptible to disruption if any fragmentation-central organization is removed. More fragmented networks are also associated with poorer health-system outcomes in domains such as education, health policy, and services. ERGMs reveal that two types of resource contributions - community connections and in-kind resource sharing - are especially important to facilitate the formation of interorganizational ties in these coalitions.

Environmental impact assessment of second life and recycling for LiFePO4 power batteries in China.

The number of spent lithium-ion batteries (LIBs) will increase exponentially in the coming decade with the retirement of electric vehicles (EVs). There is a knowledge gap in assessing the environmental impact of different terminal disposal paths for EV LIBs in China. Here, we take representative lithium iron phosphate (LFP) power batteries as example and carry out a bottom-up life cycle assessment (LCA). The life cycle stages of battery manufacturing, use, second life and battery recycling are considered to conduct a cradle-to-grave environmental impact analysis. To investigate the environmental benefits of end-of-life (EoL) stage for LFP batteries, two EoL management scenarios are considered in this study. The first one combines second life application with battery recycling, and the second recycles the retired batteries directly after EV use. The result shows that the secondary application of retired LFP batteries in energy storage systems (ESSs) can effectively reduce the net environmental impact of LIB life cycle, especially for fossil fuel depletion. When the service life of secondary use is increased from 1 year to 10 years, the environmental benefits of different impact categories will increase by 0.24-4.62 times. For direct recycle scenario, recycling retired LFP batteries can save more than 30% of metal resources. By comparison, we find that recycling lithium nickel manganese cobalt oxide (NCM) batteries has greater environmental benefits than recycling LFP batteries for all impact categories. When considering the environmental benefits at the EoL stage, most life cycle environmental impact is likely to be offset or even show positive benefits if more than 50% of power batteries can be reused in ESSs after retirement.

MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling.

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

Bipolar Magnetic Molecules for Spin-Polarized Electric Current in Molecular Junctions.

Electrical control of spin transport at single molecule level is highly desired for molecular nanospintronics. By exploiting magnetic bistability of spin crossover complexes, the magnitude of spin polarization can be modulated. However, efficiently controlling the direction of spin polarization at single molecule level is still challenging. Here, we propose a general method to flip the transport electron spin simply by electrical gating in single molecule devices based on bipolar magnetic molecules (BMMs), of which the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) come from different spin channels. Thus, when the device's Fermi level is reversibly adjusted approaching either HOMO or LUMO by changing the polarity of the applied voltage gate, a 100 % spin polarized current with switchable spin direction is achievable. The proposed method is verified by the calculated electronic and transport properties of 9 potential transition metal coordination BMMs.

Emergence of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, carrying a novel mcr-1.19 variant cultured from egg in China.

OBJECTIVES: This study aimed to characterize the genomic features of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, which carried a novel mcr-1 variant, designated as mcr-1.19, mapped to an ESBL-encoding IncHI2 plasmid. METHODS: Antimicrobial susceptibility assays as well as WGS were carried out on isolate CFSA629. The complete closed genome was obtained and then explored to obtain genomic features. Plasmid sequence comparison was performed for pCFSA629 with similar plasmids and the mcr-1 genetic environment was analysed. RESULTS: S. Typhimurium ST34 CFSA629 expressed an MDR phenotype to six classes of compound and consisted of a single circular chromosome and one plasmid. It possessed 11 resistance genes including 2 ESBL genes that mapped to the chromosome and the plasmid; an IS26-flanked composite-like transposon was identified. A novel mcr-1 variant (mcr-1.19) was identified, which had a unique SNP (G1534A) that gave rise to a novel MCR-1 protein containing a Val512Ile amino acid substitution. Plasmid pCFSA629 possessed a conjugative plasmid transfer gene cluster as well as an antimicrobial resistance-encoding gene cluster-containing region that contained two IS26 composite-like transposonal modules, but was devoid of any plasmid-mediated quinolone resistance genes. The background of mcr-1.19 consisted of an ISApl1-mcr-1-PAP2-ter module. CONCLUSIONS: We report on an MDR S. Typhimurium ST34 CFSA629 isolate cultured from egg in China, harbouring an mcr-1.19 variant mapped to an IncHI2 plasmid. This highlights the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella. Improved surveillance is important for tackling the dissemination of mcr genes among foodborne Salmonella around the world.

Klebsiella pneumoniae: Prevalence, Reservoirs, Antimicrobial Resistance, Pathogenicity, and Infection: A Hitherto Unrecognized Zoonotic Bacterium.

Klebsiella pneumoniae is considered an opportunistic pathogen, constituting an ongoing health concern for immunocompromised patients, the elderly, and neonates. Reports on the isolation of K. pneumoniae from other sources are increasing, many of which express multidrug-resistant (MDR) phenotypes. Three phylogroups were identified based on nucleotide differences. Niche environments, including plants, animals, and humans appear to be colonized by different phylogroups, among which KpI (K. pneumoniae) is commonly associated with human infection. Infections with K. pneumoniae can be transmitted through contaminated food or water and can be associated with community-acquired infections or between persons and animals involved in hospital-acquired infections. Increasing reports are describing detections along the food chain, suggesting the possibility exists that this could be a hitherto unexplored reservoir for this opportunistic bacterial pathogen. Expression of MDR phenotypes elaborated by these bacteria is due to the nature of various plasmids carrying antimicrobial resistance (AMR)-encoding genes, and is a challenge to animal, environmental, and human health alike. Raman spectroscopy has the potential to provide for the rapid identification and screening of antimicrobial susceptibility of Klebsiella isolates. Moreover, hypervirulent isolates linked with extraintestinal infections express phenotypes that may support their niche adaptation. In this review, the prevalence, reservoirs, AMR, Raman spectroscopy detection, and pathogenicity of K. pneumoniae are summarized and various extraintestinal infection pathways are further narrated to extend our understanding of its adaptation and survival ability in reservoirs, and associated disease risks.

Epidemiological Study on Prevalence, Serovar Diversity, Multidrug Resistance, and CTX-M-Type Extended-Spectrum ß-Lactamases of Salmonella spp. from Patients with Diarrhea, Food of Animal Origin, and Pets in Several Provinces of China.

A total of 2,283 Salmonella isolates were recovered from 18,334 samples, including samples from patients with diarrhea, food of animal origin, and pets, across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Salmonella enterica serovars Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistance to ≥1 antimicrobial, and 56.4% were multidrug resistant (MDR). A total of 222 isolates harbored extended-spectrum ß-lactamases (ESBLs), and 200 of these were of the CTX-M type and were mostly detected in isolates from chicken meat and turtle fecal samples. Overall, eight blaCTX-M genes were identified, with blaCTX-M-65, blaCTX-M-123, blaCTX-M-14, blaCTX-M-79, and blaCTX-M-130 being the most prevalent. In total, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (S80I), while the plasmid-mediated quinolone resistance (PMQR)-encoding genes oqxA, oqxB, qepA, qnrB, and qnrS were detected in almost all isolates. Of the 15 sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in number of isolates. Our study revealed considerable serovar diversity and a high prevalence of the co-occurrence of MDR determinants, including CTX-M-type ESBLs, quinolone resistance-determining region (QRDR) mutations, and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDR mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M-type ESBL-harboring Salmonella isolates.