Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

Paper-Based Coculture Platform to Evaluate the Effects of Fibroblasts on Estrogen Signaling in ER+ Breast Cancers.

Cell-based assays enable molecular-level studies of cellular responses to drug candidates or potential toxins. Transactivation assays quantify the activation or inhibition of nuclear receptors, key transcriptional regulators of gene targets in mamalian cells. One such assay couples the expression of luciferase to the transcriptional activity of estrogen receptor-alpha (ERα). While this assay is regularly used to screen for agonists and antagonists of the estrogen signaling pathway, the setup relies on monolayer cultures in which cells are plated directly onto the surface of cell-compatible plasticware. The tumor microenvironment is more than a collection of cancerous cells and is profoundly influenced by tissue architecture, the presence of extracellular matrices, and intercellular signaling molecules produced by non-cancerous neighboring cells (e.g., fibroblasts). There exists a need for three-dimensional culture platforms that can be rapidly prototyped to assess new configurations and readily produced in the large numbers needed for translational studies and screening applications. Here, we demonstrate the utility of the paper-based culture platform to probe the effects of intercellular signaling between two cell types. We used paper scaffolds to generate tumor-like environments, forming a defined volume of breast cancer cells suspended in collagen. By placing the paper scaffolds in commercial 96-well plates, we compared monocultures of only breast cancer cells with coculture configurations containing fibroblasts in different locations that mimicked the stages of breast cancer progression. We show that ERα transactivation in the T47D-KBluc cell line is affected by the presence, number, and proximity of fibroblasts, and is a consequence of intercellular signaling molecules. After screening a small library of fibroblast-secreted signaling molecules, we showed that interleukin-6 (IL-6) was the primary driver of reduced estradiol sensitivity. These effects were mitigated in the coculture configurations by the addition of an IL-6 neutralizing antibody. We also assessed estrogen receptor expression and transcriptional regulation, further demonstrating the utility of the paper-based platform for detailed mechanistic studies.

Trace Organic Contaminant Removal from Municipal Wastewater by Styrenic ß-Cyclodextrin Polymers.

Trace organic contaminants (TrOCs) present major removal challenges for wastewater treatment. TrOCs, such as perfluoroalkyl and polyfluoroalkyl substances (PFAS), are associated with chronic toxicity at ng L-1 exposure levels and should be removed from wastewater to enable safe reuse and release of treated effluents. Established adsorbents, such as granular activated carbon (GAC), exhibit variable TrOC removal and fouling by wastewater constituents. These shortcomings motivate the development of selective novel adsorbents that also maintain robust performance in wastewater. Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents with demonstrated TrOC removal efficacy. Here, we report a simplified and potentially scalable synthesis of a porous polymer composed of styrene-linked ß-CD and cationic ammonium groups. Batch adsorption experiments demonstrate that the polymer is a selective adsorbent exhibiting complete removal for six out of 13 contaminants with less adsorption inhibition than GAC in wastewater. The polymer also exhibits faster adsorption kinetics than GAC and ion exchange (IX) resin, higher adsorption affinity for PFAS than GAC, and is regenerable by solvent wash. Rapid small-scale column tests show that the polymer exhibits later breakthrough times compared to GAC and IX resin. These results demonstrate the potential for ß-CD polymers to remediate TrOCs from complex water matrices.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

Antimicrobial activity effects of electrolytically generated hypochlorous acid-treated pathogenic microorganisms by isothermal kinetic simulation.

This study involves isothermal kinetic simulation to evaluate the parameters of inhibition conditions for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of high-risk pathogens. This is because the new type of the 2019 novel coronavirus (2019-nCoV) is continuously spreading and the importance of public health issues. Environmental disinfection and personal wearing of masks have become important epidemic prevention measures. Selection of concentration kinetics could be estimated best for E. coli and S. aureus of pathogens, 2.74 × 104 and 105 and 2.44 × 104 and 105 colony-forming units (CFU mL-1), by isothermal micro-calorimeter (TAM Air) tests, respectively. Comparisons were made of different doses of 0-70 ppm (in 20 mL test ampoule) hypochlorous acid treatment for conducting nth-order and autocatalytic reaction simulation to evaluate the inhibition reaction parameters, which determined the autocatalytic kinetic model that was beneficially applied on the E. coli and S. aureus. We developed the inhibition reaction parameters of the pathogens, which included the activation energy (E a), the natural logarithm of pre-exponential factor (lnk 0), the enthalpy of inhibition microbial growth reaction (∆H), inhibition microbial growth, and the inhibition growth analysis. Overall, we conducted isothermal kinetic simulation to understand the antimicrobial activity effects of electrolytically generated hypochlorous acid-treated pathogenic microorganisms, which will provide reference for public health and medical-related fields for SDG3, and can contribute to ensuring human health and hygiene.

Electroacupuncture Stimulation Suppresses Postoperative Inflammatory Response and Hippocampal Neuronal Injury.

Postoperative cognitive dysfunction (POCD) is consequence of anesthesia and surgery that primarily affects older people. The prevention and treatment of POCD has drawn an increasing attention in recent decades. Here, we established the animal model mimicked POCD after femoral fracture surgery, and analyze the effect of acupuncture stimulation on postoperative cognitive function after femoral fracture surgery. Compared with the mock group, the cognitive function performance was significantly decreased both in the anaesthesia group and the surgery group, between which the symptoms were more severe in the surgery group. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus were observed in the surgery group, but only peripheral inflammation response was detected in the anaesthesia group. These findings indicated the POCD was the synergistic outcome of anaesthesia and surgical stimulation but with different pathogenic mechanism. The surgery with mental tri-needles (surgery+MTN) group outperformed the surgery group in terms of cognitive function performance. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus was significantly reduced by the electroacupuncture stimulation. Our findings indicated the protection of electroacupuncture form POCD after femoral fracture surgery is related to the inhibition of inflammation response and neuron impairment.

Efficient biodegradation of di-(2-ethylhexyl) phthalate by a novel strain Nocardia asteroides LMB-7 isolated from electronic waste soil.

The di-2-ethylhexyl phthalate (DEHP) degrading strain LMB-7 was isolated from electronic waste soil. According to its biophysical/biochemical characteristics and 16S rRNA gene analysis, the strain was identified as Nocardia asteroides. Optimal pH and temperature for DEHP degradation were 8.0 and 30 °C, respectively, and DEHP removal reached 97.11% after cultivation for 24 h at an initial concentration of 400 mg/L. As degradation intermediates, di-butyl phthalates, mono-2-ethylhexyl phthalate and 2-ethylhexanol could be identified, and it could be confirmed that DEHP was completely degraded by strain LMB-7. To our knowledge, this is a new report of DEHP degradation by a strain of Nocardia asteroides, at rates higher than those reported to date. This finding provides a new way for DEHP elimination from environment.

High levels of triglycerides, apolipoprotein B, and the number of colorectal polyps are risk factors for colorectal polyp recurrence after endoscopic resection: a retrospective study.

Background: The recurrence of polyps after endoscopic treatment is a difficult problem and there may be an association between blood lipid levels and colorectal polyps, but this is controversial and the aim of this study is to explore the risk factors for colorectal polyp recurrence. Methods: A total of 357 patients who underwent intestinal polypectomy from January 1, 2019 to June 1, 2020 in Sichuan Provincial People's Hospital were included in this retrospective study to analyze the potential association between blood indices and recurrence risk. Polyp recurrence was defined as the detection of 1 or more polyps at any time after polypectomy, regardless of site. Follow-up was performed through the electronic medical record system. Patients' age, gender, tobacco and alcohol liking, duration of follow-up, body mass index (BMI), polyp size, number, type of pathology, and lipid profiles (triglycerides, cholesterol, apolipoprotein B, and apolipoprotein A) were collected. Results: Triglycerides (1.54±0.95 vs. 1.25±1.01, P=0.036) and apolipoprotein B (0.87±0.26 vs. 0.79±0.16 mL, P=0.001) were significantly different in both the recurrence and non-recurrence groups. Binary logistic regression identified 3 independent risk factors for recurrence: triglycerides [odds ratio (OR): 1.763, 95% confidence interval (CI): 1.003 to 3.098, P=0.049], apolipoprotein B (OR: 5.438, 95% CI: 1.411 to 20.961, P=0.014), and the number of polyps (OR: 2.540, 95% CI: 1.649 to 3.911, P<0.001). Conclusions: High levels of triglycerides, apolipoprotein B, and the number of colorectal polyps are risk factors for colorectal polyp recurrence after endoscopic resection. Therefore, for patients at high risk of polyp recurrence, we recommend aggressive control of triglyceride and apolipoprotein B levels.

A Tunable Porous ß-Cyclodextrin Polymer Platform to Understand and Improve Anionic PFAS Removal.

Cross-linked polymers containing ß-cyclodextrin (ß-CD) are promising adsorbents with demonstrated removal performances for per- and polyfluoroalkyl substances (PFASs) from contaminated water sources. Despite the promising performance of some ß-CD-based adsorbents for PFAS removal, many of these materials are not amenable for rational performance improvement or addressing fundamental questions about the PFAS adsorption mechanisms. These ambiguities arise from the poorly defined structure of the cross-linked polymers, especially with respect to the random substitution patterns of the cyclodextrins as well as side reactions that modify the structures of some cross-linkers. Here, we report a new ß-CD polymer platform in which styrene groups are covalently attached to ß-CD to form a discrete monomer that is amenable to radical polymerization. This monomer was polymerized with styrene and methacrylate comonomers to provide three ß-CD polymers with high specific surface areas and high isolated yields (all >93%). A ß-CD polymer copolymerized with a methacrylate bearing a cationic functional group achieved nearly 100% removal for eight anionic PFASs (initial concentration of 1 µg/L for each compound) in nanopure water at an exceedingly low adsorbent loading of 1 mg L-1, as compared to previous cyclodextrin polymers that required loadings at least 1 order of magnitude higher to achieve an equivalent degree of PFAS removal. Furthermore, when the adsorbents were studied in a challenging salt matrix, we observed that long-chain PFAS adsorption was controlled by a complementary interplay of hydrophobic and electrostatic interactions, whereas short-chain PFASs primarily relied on electrostatic interactions. This approach demonstrates great promise for anionic PFAS removal, and we anticipate that new compositions will be tailored using the versatility of radical polymerization to simultaneously target PFASs and other classes of micropollutants in the future.

Photoinduced Superhydrophilicity of Gd-Doped TiO2 Ellipsoidal Nanoparticles Boosts T1 Contrast Enhancement for Magnetic Resonance Imaging.

The unsatisfactory performance of current gadolinium chelate based T1 contrast agents (CAs) for magnetic resonance imaging (MRI) stimulates the search for better alternatives. Herein, we report a new strategy to substantially improve the capacity of nanoparticle-based T1 CAs by exploiting the photoinduced superhydrophilic assistance (PISA) effect. As a proof of concept, we synthesized citrate-coated Gd-doped TiO2 ellipsoidal nanoparticles (GdTi-SC NPs), whose r1 increases significantly upon UV irradiation. The reduced water contact angle and the increased number of surface hydroxyl groups substantiate the existence of the PISA effect, which considerably promotes the efficiency of paramagnetic relaxation enhancement (PRE) and thus the imaging performance of GdTi-SC NPs. In vivo MRI of SD rats with GdTi-SC NPs further demonstrates that GdTi-SC NPs could serve as a high-performance CA for sensitive imaging of blood vessels and accurate diagnosis of vascular lesions, indicating the success of our strategy.

Reaction-based fluorescence probes for "turn on" sensing fluoride ions.

Introducing a weak covalent bond into an originally highly fluorescent molecule to create a non-fluorescent probe is able to provide a new way to detect some nucleophilic targets with enhanced sensitivity. Herein, this is the first time that a tetraphenylethene (TPE)-based probe (TPEONO2) bearing a p-nitrobenzenesulfonyl moiety for the sensing of F- ions in aqueous solution via a cleavage reaction of the sulfonyl ester bond to induce aggregation-induced emission (AIE) has been reported.

Clinical Impact of Thrombus Aspiration and Interaction With D-Dimer Levels in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Objectives: To evaluate the effect of thrombus aspiration (TA) strategy on the outcomes and its interaction with D-dimer levels in patients with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) in "real-world" settings. Materials and Methods: This study included 1,295 patients with STEMI who had undergone primary PCI with or without TA between January 2013 and June 2017. Patients were first divided into a TA+PCI group and a PCI-only group, and the baseline characteristics and long-term mortality between the two groups were analyzed. Furthermore, we studied the effect of TA on the clinical outcomes of patients grouped according to quartiles of respective D-dimer levels. The primary outcome was all-cause mortality, and the secondary outcomes were new-onset heart failure (HF), rehospitalization, re-PCI, and stroke. Results: In the original cohort, there were no significant differences in all-cause mortality between the TA+PCI and PCI-only groups (hazard ratio, 0.789; 95% confidence interval, 0.556-1.120; p = 0.185). After a mean follow-up of 2.5 years, the all-cause mortality rates of patients in the TA + PCI and PCI-only groups were 8.5 and 16.2%, respectively. Additionally, differences between the two groups in terms of the risk of HF, re-PCI, rehospitalization, and stroke were non-significant. However, after dividing into quartiles, as the D-dimer levels increased, the all-cause mortality rate in the PCI group gradually increased (4.3 vs. 6.0 vs. 7.0 vs. 14.7%, p < 0.001), while the death rate in the TA+PCI group did not significantly differ (4.6 vs. 5.0 vs. 4.0 vs. 3.75%, p = 0.85). Besides, in the quartile 3 (Q3) and quartile 4 (Q4) groups, the PCI-only group was associated with a higher risk of all-cause mortality than that of the TA+PCI group (Q3: 4.0 vs. 7.0%, p = 0.029; Q4: 3.75 vs. 14.7%, p < 0.001). Moreover, the multivariate logistic regression analysis demonstrated that TA is inversely associated with the primary outcome in the Q4 group [odds ratio (OR), 0.395; 95% CI, 0.164-0.949; p = 0.038]. Conclusions: The findings of our real-world study express that routine manual TA during PCI in STEMI did not improve clinical outcomes overall. However, patients with STEMI with a higher concentration of D-dimer might benefit from the use of TA during primary PCI. Large-scale studies are recommended to confirm the efficacy of TA.

Overexpression of Capsular Polysaccharide Biosynthesis Protein in Lactobacillus plantarum P1 to Enhance Capsular Polysaccharide Production for Di-n-butyl Phthalate Adsorption.

Exopolysaccharides (EPSs) such as capsular polysaccharide (CPS) are important bioactive carbohydrate compounds and are often used as bioenrichment agents and bioabsorbers to remove environmental pollutants like di-n-butyl phthalate (DBP). Among the EPS-producing bacteria, lactic acid bacteria (LAB) have gained the most attention. As generally recognized as safe (GRAS) microorganisms, LAB can produce EPSs having many different structures and no health risks. However, EPS production by LAB does not meet the needs of large-scale application on an industrial scale. Here, the capA gene (encoding CPS biosynthesis protein) was overexpressed in Lactobacillus plantarum P1 to improve the production of EPSs and further enhance the DBP adsorption capability. Compared with P1, the CPS production in capA overexpressed strain was increased by 11.3 mg/l, and the EPS thickness was increased from 0.0786 ± 0.0224 µm in P1 to 0.1160 ± 0.0480 µm in P1-capA. These increases caused the DBP adsorption ratio of P1-capA to be doubled. Overall, the findings in this study provide a safe method for the adsorption and removal of DBP.

Key role of exopolysaccharide on di-butyl phthalate adsorbing by Lactobacillus plantarum CGMCC18980.

Plasticizers belong to hormone-like substances existing widely in the environment. According to the Environmental Protection Agency of China, they are considered to be the fourth class of toxic chemicals due to their harmful effects on normal endocrine system in human bodies. In the recent published work of our lab, Lactobacillus plantarum CGMCC18980 (strain P1) could reduce the toxicity of di-butyl phthalate (DBP) in rats effectively. The purpose of this study is to further explore the adsorption mechanism of di-butyl phthalate to L. plantarum CGMCC18980, based on optimizing the adsorption conditions. As a consequence, the adsorption effect of L. plantarum CGMCC18980 attributed to relationships between exopolysaccharide, membrane protein, and the cell wall. Experimental results demonstrated that exopolysaccharide and the cell wall were devoted to DBP binding. An obvious adsorption layer was observed outside of L. plantarum CGMCC18980 through scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) results showed that the functional groups involved in adsorption were mainly C=O, C-N, and C-O, which related to lipids and polysaccharides. Zeta potential analysis indicated that DBP adsorption had no significant relationship with surface charge. These results revealed that exopolysaccharide may be the key factor of strain CGMCC18980 in DBP adsorption. KEY POINTS: • Lactobacillus plantarum CGMCC18980 has the ability to adsorb di-butyl phthalate, reaching to 58.63%. • Exopolysaccharide is considered to play a key role in adsorption process. • Membrane protein, cell wall, and surface charge do not contribute to adsorption.

Metastasis-Specific Gene Expression in Autochthonous and Allograft Mouse Mammary Tumor Models: Stratification and Identification of Targetable Signatures.

Breast cancer metastasis is a leading cause of cancer-related death of women in the United States. A hurdle in advancing metastasis-targeted intervention is the phenotypic heterogeneity between primary and secondary lesions. To identify metastasis-specific gene expression profiles we performed RNA-sequencing of breast cancer mouse models; analyzing metastases from models of various drivers and routes. We contrasted the models and identified common, targetable signatures. Allograft models exhibited more mesenchymal-like gene expression than genetically engineered mouse models (GEMM), and primary culturing of GEMM-derived metastatic tissue induced mesenchymal-like gene expression. In addition, metastasis-specific transcriptomes differed between tail vein and orthotopic injection of the same cell line. Gene expression common to models of spontaneous metastasis included sildenafil response and nicotine degradation pathways. Strikingly, in vivo sildenafil treatment significantly reduced metastasis by 54%, while nicotine significantly increased metastasis by 46%. These data suggest that (i) actionable metastasis-specific pathways can be readily identified, (ii) already available drugs may have great potential to alleviate metastatic incidence, and (iii) metastasis may be influenced greatly by lifestyle choices such as the choice to consume nicotine products. In summary, while mouse models of breast cancer metastasis vary in ways that must not be ignored, there are shared features that can be identified and potentially targeted therapeutically. IMPLICATIONS: The data we present here exposes critical variances between preclinical models of metastatic breast cancer and identifies targetable pathways integral to metastatic spread. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/9/1278/F1.large.jpg.

Characteristics of Hypervirulent Klebsiella pneumoniae: Does Low Expression of rmpA Contribute to the Absence of Hypervirulence?

Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) has been increasingly reported and is now recognized as a significant threat to public health; however, characterization of MDR-hvKP has not been systematically investigated. In the present study, 124 of 428 (28.92%) K. pneumoniae clinical isolates collected from January 2010 to December 2016 were identified with aerobactin and defined as hvKP; these included 94 non-MDR-KP, 20 extended-spectrum ß-lactamase-producing K. pneumoniae (ESBL-KP), and 10 carbapenem-resistant K. pneumoniae (CR-KP) isolates. The remaining 304 isolates without presence of virulence factor aerobactin were defined as classic K. pneumoniae (cKP). The antimicrobial resistance rate of cKP was significantly higher than that of the hvKP isolates in the non-MDR-KP group, but showed no significant differences in the ESBL-KP and CR-KP groups. The detection frequencies of capsular serotype K1 (magA), hypermucoviscosity, sequence type 23 (ST23), and the virulence gene rmpA were significantly higher in the hvKP than cKP isolates in all three groups (P < 0.05). Most of the hypervirulent ESBL-KP and CR-KP isolates were K non-typeable (16/30) and harbored at least one gene for virulence (26/30). The hypervirulent ESBL-KP isolates primarily carried bla CTX-M (12/20, 60%) genes, and the hypervirulent CR-KP isolates mainly carried bla NDM- 1 (8/10, 80%) genes. Moreover, three hypervirulent ESBL-KP and two hypervirulent CR-KP isolates showed resistance to tigecycline but were sensitive to colistin. The transcriptional levels of rmpA in cKP were much lower than that in hvKP isolates in all three groups. Furthermore, overexpression of rmpA in the rmpA-low-expression cKP isolates could enhance bacterial virulence in the mouse infection experiment. In conclusion, our data suggest that the capsular serotype K1 (magA), rmpA, hypermucoviscosity, and ST23 were strongly associated with hvKP in non-MDR-KP, ESBL-KP, and CR-KP groups, and low rmpA expression levels contributed to the absence of hypervirulent phenotype.

Hypoxia differentially regulates estrogen receptor alpha in 2D and 3D culture formats.

Hypoxia is a common feature in solid tumors. Clinical samples show a positive correlation between the expression of the hypoxia-inducible factor HIF-1α and estrogen receptor alpha (ERα) and a negative correlation between HIF-1α and hormone sensitivity. Results from monolayer cultures are in contention with clinical observations, showing that ER (+) cell lines no longer express ERα under hypoxic conditions (1% O2). Here, we compared the impact of hypoxia on the ERα signaling pathway for T47D cells in a 2D and 3D culture format. In the 2D format, the cells were cultured as monolayers. In the 3D format, paper-based scaffolds supported cells suspended in a collagen matrix. Using ELISA, Western blot, and immunofluorescence measurements, we show that hypoxia differentially regulates ERα protein levels in a culture environment-dependent manner. In the 2D format, the protein levels are significantly decreased in hypoxia. In the 3D format, the protein levels are maintained in hypoxia. Hypoxia reduced ERα transcriptional activation in both culture formats. These results highlight the importance of considering tissue dimensionality for in vitro studies. They also show that ERα protein levels in hypoxia are not an accurate indicator of ERα transcriptional activity, and confirm that a positive stain for ERα in a clinical sample may not necessarily indicate hormone sensitivity.