Dissemination and characteristics of high-level erythromycin-resistant Enterococcus faecalis from bulk tank milk of dairy companies in Korea.

Enterococci are environmental pathogens that can cause bovine mastitis, which is treated with macrolides, one of which is erythromycin (ERY). The aim of this study was to compare the characteristics of high-level erythromycin-resistant (HLER) Enterococcus faecalis (E. faecalis) isolates from bulk tank milk of 4 dairy companies, identified as A to D, in order to assess the threat to public health. Although isolates from company D showed the highest prevalence of E. faecalis, the prevalence of HLER E. faecalis in isolates from company A showed a significant difference. A total of 149 of the 301 HLER E. faecalis isolates showed the highest rate of resistance to tetracycline. In the distribution of antimicrobial resistance genes, 147 isolates carried the ermB gene alone and 2 isolates carried both ermA and ermB genes. Also, 72 and 60 isolates carried both tetM and tetL genes and the tetM gene alone, respectively, and 38 isolates carried the optrA gene. The prevalence of both aac(6')Ie-aph(2″)-la and ant(6')-Ia genes was the highest and 104 isolates harbored the Int-Tn gene carrying the Tn916/1545-like transposon. Although the distribution of the e rmB gene showed no significant difference among dairy companies, the prevalence of other resistance genes and transposons showed significant differences among dairy companies. Virulence genes were highly conserved in the HLER E. faecalis isolates. Our results indicated that there were significant differences in phenotypic and genotypic characteristics of HLER E. faecalis isolates in milk from 4 different dairy companies. A structured management protocol by companies and constant monitoring are therefore necessary to minimize public health hazards.

Les entérocoques sont des agents pathogènes environnementaux qui peuvent causer la mammite bovine, qui est traitée avec des macrolides, dont l'érythromycine (ERY). Le but de cette étude était de comparer les caractéristiques des isolats d'Enterococcus f aecalis (E. faecalis) hautement résistants à l'érythromycine (HLER) provenant du lait de réservoir en vrac de quatre entreprises laitières, identifiées comme A à D, afin d'évaluer la menace pour santé publique. Bien que les isolats de la société D aient montré la prévalence la plus élevée d'E. faecalis, la prévalence d'E. faecalis HLER dans les isolats de la société A montrait une différence significative. Un total de 149 des 301 isolats d'E. faecalis HLER ont montré le taux le plus élevé de résistance à la tétracycline. Dans la distribution des gènes de résistance aux antimicrobiens, 147 isolats portaient le gène ermB seul et deux isolats portaient à la fois les gènes ermA et ermB. En outre, 72 et 60 isolats portaient à la fois les gènes tetM et tetL et le gène tetM seul, respectivement, et 38 isolats portaient le gène optrA. La prévalence des gènes aac(6')Ie-aph(2″)-la et ant(6')-Ia était la plus élevée et 104 isolats portaient le gène Int-Tn portant le transposon de type Tn916/1545. Bien que la distribution du gène ermB n'ait montré aucune différence significative entre les entreprises laitières, la prévalence d'autres gènes de résistance et transposons a montré des différences significatives entre les entreprises laitières. Les gènes de virulence étaient hautement conservés dans les isolats d'E. faecalis HLER. Nos résultats ont indiqué qu'il y avait des différences significatives dans les caractéristiques phénotypiques et génotypiques des isolats d'E. faecalis HLER dans le lait de quatre entreprises laitières différentes. Un protocole de gestion structuré par les entreprises et une surveillance constante sont donc nécessaires pour minimiser les risques pour la santé publique.(Traduit par Docteur Serge Messier).

Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models.

BACKGROUND: Aggregated amyloid-ß (Aß) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aß is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aß aggregates. METHODS: The dissociative activity of aryloxypropanolamine derivatives against Aß aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. RESULTS: Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against ß-sheet-rich Aß aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular ß-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aß. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aß and tau. CONCLUSIONS: Collectively, our results evince the potential of chemical-driven dissociation of Aß aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

Effect of Breast Silicone Implant Topography on Bacterial Attachment and Growth: An In Vitro Study.

BACKGROUND/AIM: The mechanisms underlying capsular contracture remain unclear. Emerging evidence supports the inflammation hypothesis, according to which bacteria from an adherent biofilm cause chronic inflammation and collagen deposition on the implant and trigger capsular contracture. Our goal was to evaluate the effect of different types of breast implants on the growth of Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa, which are commonly found in biofilms in infection. MATERIALS AND METHODS: Bacteria were grown in tryptic soy broth at 37°C for 2, 6, and 24 h and subsequently incubated for 24 h on 12 shell sections of smooth, nano-, and macrotextured breast implants. After incubation, the solutions were ultrasonicated and bacterial numbers were determined by serial dilution. S. aureus were fixed, washed with phosphate-buffered saline, dehydrated in ethanol, and coated with a platinum film to visualize the presence of biofilms by scanning electron microscopy. RESULTS: The numbers of S. aureus and S. epidermidis attached to the smooth and nanotextured surface implants were significantly lower than those on the macrotextured surface for all incubation times, whereas the number of P. aeruginosa was non-significantly lowest on the nanotextured surface after 24h incubation. Biofilms on smooth and nanotextured implant surfaces showed patchy patterns on scanning electron microscopy in contrast to the continuous pattern detected on macrotextured implants. CONCLUSION: Nanotextured breast implants may limit bacterial growth and thus prevent capsular contracture.

Relationship between CRISPR sequence type and antimicrobial resistance in avian pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) is a primary cause of extraintestinal disease and respiratory infections in chickens; therefore, various antimicrobials applied via mass medication in farms to control APEC in Korea. In this study, we analyzed the relationship between CRISPR sequence type and antimicrobial resistance (AMR) in APEC isolates. Based on spacer distribution, a total of 103 CRISPR-positive APEC isolates were classified into 25 E. coli sequence types (ESTs), largely into two clusters that were correlated with phylogenetic groups: isolates appearing to have CRISPR 1 and/or 2 (93.2 %) and those having CRISPR 3 and 4 (6.8 %). Moreover, ESTs were divided into three AMR pattern-based groups: cephems-resistant group, non-cephems-resistant group, and antimicrobial sensitive group. There were significant differences among the groups (p < 0.05). Sixteen of the 25 ESTs had a significantly higher distribution of multidrug-resistant (MDR) isolates than the other ESTs (p < 0.05), and the ratio of MDR isolates was significantly higher than that of non-MDR isolates in the CRISPR 1 and 2 arrays (p < 0.05). A total of 9 protospacers were identified with protospacer, with protospacer 1 in CRISPR 1 being the most prevalent among the isolates (41.7 %). The protospacers of CRISPR 1 and 2 loci were associated with protection against external invaders such as bacteriophage or endogenous gene regulation. However, each protospacer of the CRISPR 3 and 4 loci originated from genes associated with AMR plasmids. These results indicate that CRISPR sequence type can improve AMR bacteria and enhance strategies for tackling the complexity of AMR in bacterial pathogens.

Comparison of antimicrobial resistance and molecular characterization of Escherichia coli isolates from layer breeder farms in Korea.

In Korea, 4 big layer companies that possess one grandparent and 3 parent stocks are in charge of 100% of the layer chicken industry. In this study, we investigated the antimicrobial resistance of commensal 578 E. coli isolated from 20 flocks of 4-layer breeder farms (A, B, C, and D), moreover, compared the characteristics of their resistance and virulence genes. Isolates from farms B and D showed significantly higher resistance to the ß-lactam antimicrobials (amoxicillin, ampicillin, and 1st-, 2nd-, and 3rd-generation cephalosporins). However, resistance to ciprofloxacin, nalidixic acid, and tetracycline was significantly higher in the isolates from farm A (P < 0.05). Interestingly, the isolates from farm C showed significantly lower resistance to most antimicrobials tested in this study. The isolates from farms B, C, and D showed the high multiple resistance to the 3 antimicrobial classes. Furthermore, the isolates from farm A showed the highest multiple resistance against the 5 classes. Among the 412 ß-lactam-resistant isolates, 123 (29.9%) carried blaTEM-1, but the distribution was significantly different among the farms from 17.5% to 51.4% (P < 0.05). Similarly, the most prevalent tetracycline resistance gene in the isolates from farms B, C, and D was tetA (50.0-77.0%); however, the isolates from farm A showed the highest prevalence in tetB (70.6%). The distribution of quinolone (qnrB, qnrD, and qnrS) and sulfonamide (su12)-resistant genes were also significantly different among the farms but that of chloramphenicol (catA1)- and aminoglycoside (aac [3]-II, and aac [6']-Ib)-resistant genes possessed no significant difference among the farms. Moreover, the isolates from farm C showed significantly higher prevalence in virulence genes (iroN, ompT, hlyF, and iss) than the other 3 farms (P < 0.05). Furthermore, the phenotypic and genotypic characteristics of E. coli isolates were significantly different among the farms, and improved management protocols are required to control of horizontal and vertical transmission of avian disease, including the dissemination of resistant bacteria in breeder flocks.

Comparative analysis of genetic characterization of ß-lactam-resistant Escherichia coli from bulk tank milk in Korea.

BACKGROUND: This study was conducted to analyze the genetic characteristics of 41 ß-lactam-resistant Escherichia coli isolates, which are one of the common causes of environmental mastitis, isolated from the bulk tank milk of 290 dairy farms in five factories operated by three dairy companies in Korea. RESULTS: Analysis of the phenotypic and genotypic characteristics of ß-lactam-resistant E. coli isolates revealed differences between factories even within the same company. Isolates from factory A1 and C1 showed high resistance to cephalothin (76.9 and 100%, respectively), which is a first-generation cephalosporins, whereas resistance to tetracycline was showed by only the isolates from factories B1 (60.0%), C2 (66.7%), and C3 (100%). Although all the 41 ß-lactam-resistant E. coli isolates were positive for blaOXA-1, blaTEM-1 was highly prevalent in isolates from factories C2 (100%) and C3 (100%). Among 17 isolates resistant to both ß-lactams and aminoglycosides, the most common multilocus sequence type was ST399 (13isolates, 76.5%). Furthermore, 2 (11.8%) and 12 (70.6%) isolates belonged to the phylogenetic groups B2 and D, respectively, which are invasive strains that cause intestinal infections, respectively. The predominant serogroup was O15 (70.6%), which is a globally distributed extraintestinal pathogen. Interestingly, one isolate from factory A1 belonged to O157 and carried six virulence genes, simultaneously. CONCLUSIONS: Although E. coli isolates were isolated from bulk tank milk, and not the clinical mastitis samples, the presence of the phylogenetic groups B2 and D, and the serogroups O15 and O157, which harbor antimicrobial resistance genes and virulence factors, can pose a threat to public health.

Comparative Analysis of Chloramphenicol-Resistant Enterococcus faecalis Isolated from Dairy Companies in Korea.

Although chloramphenicol is currently banned from use in livestock, other phenicols, such as florfenicol and thiamphenicol, have been used for the treatment of bacterial infections in domestic cattle in Korea. This study compares the characteristics of chloramphenicol-resistant Enterococcus faecalis isolated from the bulk tank milk of four major dairy companies in Korea. Although the distribution of multidrug resistance patterns showed no significant differences between the four companies, 85 chloramphenicol-resistant Enterococcus faecalis isolates showed a significantly high number of resistances against five or six antimicrobial classes (37.6%, respectively) (p < 0.05). When analyzing the distribution of phenicol resistance genes, 31 (36.5%) isolates only carried the catA gene, and two (6.3%) isolates from company A only carried the cfr gene. No isolates carried the catB or fexA genes. Regarding the distribution of other resistance genes, both the tetL and tetM (45.9%), ermB (82.4%), and both aac(6″)-Ie-aph(2″)-la and ant(6')-Ia genes (30.6%) showed a high prevalence, and the optrA and poxtA genes were observed separately, each in only two (2.4%) isolates. Our results confirm that the dissemination of chloramphenicol-resistant Enterococcus faecalis and some antimicrobial resistance genes show significant differences between dairy companies. Therefore, our results support that each dairy company should undertake effective surveillance programs to better understand and minimize the emergence of resistance on a multidisciplinary level.

Characteristics of High-Level Aminoglycoside-Resistant Enterococcus faecalis Isolated from Bulk Tank Milk in Korea.

Enterococci, which are considered environmental mastitis-causing pathogens, have easily acquired aminoglycoside-resistant genes that encode various aminoglycoside-modifying enzymes (AME). Therefore, this study was conducted to compare the distribution of high-level aminoglycoside-resistant (HLAR) and multidrug-resistant (MDR) Enterococcus faecalis (E. faecalis) bacteria isolated from bulk tank milk in four dairy companies in Korea. Moreover, it analyzed the characteristics of their antimicrobial resistance genes and virulence factors. Among the 301 E. faecalis bacteria studied, 185 (61.5%) showed HLAR with no significant differences among the dairy companies. Furthermore, 129 (69.7%) of the 185 HLAR E. faecalis showed MDR without significant differences among companies. In contrast, HLAR E. faecalis from companies A, B, and C were significantly higher in resistance to the four classes than those in company D, which had the highest MDR ability against the three antimicrobial classes (p < 0.05). In addition, in the distribution of AME genes, 72 (38.9%) and 36 (19.5%) of the isolates carried both aac(6')Ie-aph(2″)-la and ant(6)-Ia genes, and the ant (6)-Ia gene alone, respectively, with significant differences among the companies (p < 0.05). In the distribution of virulence genes, the ace (99.5%), efa A (98.9%), and cad 1 (98.4%) genes were significantly prevalent (p < 0.05). Thus, our results support that an advanced management program by companies is required to minimize the dissemination of antimicrobial resistance and virulence factors.

Prediction of suspicious ankle instability using the calcaneofibular ligament cross-sectional area.

BACKGROUND: An injured calcaneofibular ligament (CFL) is a major cause of ankle instability (AI). Previous research has demonstrated that the thickness of the calcaneofibular ligament (CFLT) is correlated with higher-grade sprains and ankle instability. However, inflammatory hypertrophy is distinct from ligament thickness; accordingly, we considered that the calcaneofibular ligament cross-sectional area (CFLCSA) as a potential morphological parameter to analyze inflammatory CFL. We hypothesized that the CFLCSA was a key morphologic parameter in AI diagnosis. METHODS: We gathered the CFL data of 26 AI patients and 25 control subjects who had undergone ankle magnetic resonance imaging (A-MRI), and it had revealed no evidence of AI. Ankle level T1-weighted coronal A-MRI images were acquired. Using our image analysis program (INFINITT PACS), we analyzed the CFLT and CFLCSA at the CFL on the A-MRI. The CFLCSA was measured as the whole ligament cross-sectional area of the CFL that was most hypertrophied in the transverse A-MR images. The CFLT was measured at the thickest level of CFL. RESULTS: The mean CFLT was 3.49±0.82 mm in the control group, and 4.82±0.76 mm in the AI group. The mean CFLCSA was 33.31±7.02 mm2 in the control group, and 65.33±20.91 mm2 in the AI group. The AI patients had significantly greater CFLT (P<0.001) and CFLCSA (P<0.001) than the control group participants. A receiver operating characteristic (ROC) curve analysis in the evaluation of the diagnostic tests showed that the optimal cut-off score of the CFLT was 4.06 mm, with 76.9% sensitivity, 76.0% specificity, and an area under the curve (AUC) of 0.89 (95% CI, 0.79-0.99). The optimal cut-off threshold of the CFLCSA was 43.85 mm2, with 92.3% sensitivity, 92.0% specificity, and AUC of 0.94 (95% CI, 0.86-1.00). CONCLUSIONS: Even though the CFLT and CFLCSA were both significantly associated with AI, the CFLCSA was a more sensitive diagnostic test.

Virulence Variation of Salmonella Gallinarum Isolates through SpvB by CRISPR Sequence Subtyping, 2014 to 2018.

Salmonella Gallinarum is a Gram-negative bacteria that causes fowl typhoid, a septicemic disease with high morbidity and mortality that affects all ages of chickens. Although vaccines and antimicrobials have been used nationwide to eradicate the disease, the malady is still prevalent in Korea. In this study, we investigated the virulence and genetic variation of 116 S. Gallinarum isolates from laying hens between 2014 and 2018. A total of 116 isolates were divided into five Gallinarum Sequence Types (GST) through clustered regularly interspaced short palindromic repeats (CRISPR) subtyping method. The GSTs displayed changes over time. The 116 isolates showed no difference in virulence gene distribution, but the polyproline linker (PPL) length of the SpvB, one of the virulence factors of Salmonella spp., served as an indicator of S. Gallinarum pathogenicity. The most prevalent PPL length was 22 prolines (37.9%). The shortest PPL length (19 prolines) was found only in isolates from 2014 and 2015. However, the longest PPL length of 24 prolines appeared in 2018. This study indicates that PPLs of S. Gallinarum in Korea tend to lengthen over time, so the pathogenic potency of the bacteria is increasing. Moreover, the transition of GST was associated with PPL length extension over time. These results indicate that surveillance of changing GST and PPL length are necessary in the monitoring of S. Gallinarum isolates.

Reactive oxygen species-induced activation of Yes-associated protein-1 through the c-Myc pathway is a therapeutic target in hepatocellular carcinoma.

BACKGROUND: The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1 (YAP-1). Dysregulation in Hippo pathway has been proposed as one of the therapeutic targets in hepatocarcinogenesis. The levels of reactive oxygen species (ROS) increase during the progression from early to advanced hepatocellular carcinoma (HCC). AIM: To study the activation of YAP-1 by ROS-induced damage in HCC and the involved signaling pathway. METHODS: The expression of YAP-1 in HCC cells (Huh-7, HepG2, and SNU-761) was quantified using real-time polymerase chain reaction and immunoblotting. Human HCC cells were treated with H2O2, which is a major component of ROS in living organisms, and with either YAP-1 small interfering RNA (siRNA) or control siRNA. To investigate the role of YAP-1 in HCC cells under oxidative stress, MTS assays were performed. Immunoblotting was performed to evaluate the signaling pathway responsible for the activation of YAP-1. Eighty-eight surgically resected frozen HCC tissue samples and 88 nontumor liver tissue samples were used for gene expression analyses. RESULTS: H2O2 treatment increased the mRNA and protein expression of YAP-1 in HCC cells (Huh-7, HepG2, and SNU-761). Suppression of YAP-1 using siRNA transfection resulted in a significant decrease in tumor proliferation during H2O2 treatment both in vitro and in vivo (both P < 0.05). The oncogenic action of YAP-1 occurred via the activation of the c-Myc pathway, leading to the upregulation of components of the unfolded protein response (UPR), including 78-kDa glucose-regulated protein and activating transcription factor-6 (ATF-6). The YAP-1 mRNA levels in human HCC tissues were upregulated by 2.6-fold compared with those in nontumor tissues (P < 0.05) and were positively correlated with the ATF-6 Levels (Pearson's coefficient = 0.299; P < 0.05). CONCLUSION: This study shows a novel connection between YAP-1 and the UPR through the c-Myc pathway during oxidative stress in HCC. The ROS-induced activation of YAP-1 via the c-Myc pathway, which leads to the activation of the UPR pathway, might be a therapeutic target in HCC.

The predictive role of the posterior tibial tendon cross-sectional area in early diagnosing posterior tibial tendon dysfunction.

A hypertrophied posterior tibial tendon (PTT) has been considered to be an important morphologic parameter of PTT dysfunction (PTTD). Previous research has demonstrated that the PTT thickness (PTTT) is correlated with early signs of PTTD. However, the thickness is different from hypertrophy. Thus, we devised the PTT cross-sectional area (PTTCSA) as a new predictive parameter for diagnosing the PTTD.The PTT data were acquired from 14 patients with PTTD and from 20 normal individuals who underwent ankle magnetic resonance imaging. We measured the PTTT and PTTCSA at the PTT on the ankle magnetic resonance imaging.The mean PTTT was 2.43 ±â€Š0.39 mm in the normal group and 3.40 ±â€Š0.42 mm in the PTTD group. The average PTTCSA was 16.10 ±â€Š4.27 mm in the normal group and 26.93 ±â€Š4.38 mm in the PTTD group. The receiver operator characteristic analysis curve demonstrated that the highest predictive value of the PTTT was 3.07 mm, with 85.7% sensitivity, 85.0% specificity. The highest predictive value of the PTTCSA was 22.54 mm, with 92.9% sensitivity, 90.0% specificity.Our findings suggest that the PTTCSA was a more valid predictor of PTTD, even though the PTTT and PTTCSA were both significantly associated with PTTD.

Hematological factors predicting mortality in patients with traumatic epidural or subdural hematoma undergoing emergency surgical evacuation: A retrospective cohort study.

Hematological abnormalities at admission are common after traumatic brain injuries and are associated with poor outcomes. The objective of this study was to identify the predictive factors of mortality among patients who underwent emergency surgery for the evacuation of epidural hematoma (EDH) or subdural hematoma (SDH).This was a single-center retrospective cohort study of 200 patients who underwent emergency surgical evacuation of EDH or SDH between September 2010 and December 2018. Data on hematological parameters and clinical and intraoperative features were collected. The primary end-point was 1-year mortality after surgery. Univariate and multivariate analysis were performed, and the receiver operating characteristic (ROC) curves were assessed.Of the 200 patients included in this study, 102 (51%) patients died within 1 year of emergency surgery. Lymphocyte count at admission, creatinine levels, activated partial thromboplastin time (aPTT), age, intraoperative epinephrine use, and Glasgow Coma Scale (GCS) score were significantly associated with mortality in the multivariate analysis. The areas under the ROC curve for the GCS score, aPTT, and lymphocyte counts were 0.677 (95% confidence interval [CI] 0.602-0.753), 0.644 (95% CI 0.567-0.721), and 0.576 (95% CI 0.496-0.656), respectively.Patients with elevated lymphocyte counts on admission showed a higher rate of 1-year mortality following emergency craniectomy for EDH or SDH. In addition, prolonged aPTT and a lower GCS score were also related to poor survival.

Dual-Functional Electrolyte Additives toward Long-Cycling Lithium-Ion Batteries: Ecofriendly Designed Carbonate Derivatives.

Long-term stability of the solid electrolyte interphase (SEI) and cathode-electrolyte interface (CEI) layers formed on anodes and cathodes is imperative to mitigate the interfacial degradation of electrodes and enhance the cycle life of lithium-ion batteries (LIBs). However, the SEI on the anode and CEI on the cathode are vulnerable to the reactive species of PF5 and HF produced by the decomposition and hydrolysis of the conventional LiPF6 electrolyte in a battery inevitably containing a trace amount of water. Here, we report a new class of cyclic carbonate-based electrolyte additives to preserve the integrity of SEI and CEI in LIBs. This new class of additives is designed and synthesized by an ecofriendly approach that involves fixing CO2 with functional epoxides bearing various reactive side chains. It was found that the cyclic carbonates of 3-(1-ethoxyethoxy)-1,2-propylene carbonate and 3-trimethoxysilylpropyloxy-1,2-propylene carbonate, possessing high capability for the stabilization of Lewis-acidic PF5, exhibit a capacity retention of 79.0% after 1000 cycles, which is superior to that of the pristine electrolyte of 54.7%. Moreover, TMSPC has HF-scavenging capability, which, along with PF5 stabilization, results in enhanced rate capability of commercial LiNi0.6Mn0.2Co0.2O2 (NCM622)/graphite full cells, posing a significant potential for high-energy-density LIBs with long cycle stability.

Tumor-Stroma Crosstalk Enhances REG3A Expressions that Drive the Progression of Hepatocellular Carcinoma.

BACKGROUND: Crosstalk between tumors and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). However, there is little existing information about the key signaling molecule that modulates tumor-stroma crosstalk. METHODS: Complementary DNA (cDNA) microarray analysis was performed to identify the key molecule in tumor-stroma crosstalk. Subcutaneous xenograft in vivo murine model, immunoblotting, immunofluorescence, and real-time polymerase chain reaction using HCC cells and tissues were performed. RESULTS: The key molecule, regenerating gene protein-3A (REG3A), was most significantly enhanced when coculturing HCC cells and activated human hepatic stellate cells (HSCs) (+8.2 log) compared with monoculturing HCC cells using cDNA microarray analysis. Downregulation of REG3A using small interfering RNA significantly decreased the proliferation of HSC-cocultured HCC cells in vitro and in vivo, and enhanced deoxycholic acid-induced HCC cell apoptosis. Crosstalk-induced REG3A upregulation was modulated by platelet-derived growth factor ßß (PDGF-ßß) in p42/44-dependent manner. REG3A mRNA levels in human HCC tissues were upregulated 1.8-fold compared with non-tumor tissues and positively correlated with PDGF-ßß levels. CONCLUSIONS: REG3A/p42/44 pathway/PDGF-ßß signaling plays a significant role in hepatocarcinogenesis via tumor-stroma crosstalk. Targeting REG3A is a potential novel therapeutic target for the management of HCCs by inhibiting crosstalk between HCC cells and HSCs.

Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an Aß1-40-injected mouse model of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) is associated with an increased inflammatory response via activated microglia and astrocytes. In the present study, we investigated whether treatment with the anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody adalimumab can improve cognitive function and reduce AD pathology in Aß1-40-injected animal models of AD, as well as the mechanisms underlying the effects of treatment. Aß1-40-injected mice treated with adalimumab exhibited significant improvements in memory relative to mice injected with Aß1-40 alone, as well as decreases in beta secretase-1 (BACE1) protein expression and Aß1-40 plaques. In addition, adalimumab treatment significantly attenuated neuronal damage and neuroinflammation in Aß1-40-injected mice. Aß1-40-induced decreases in brain-derived neurotrophic factor (BDNF) expression were also attenuated by treatment with adalimumab. Our experiments further verified that the effects of adalimumab are mediated by nuclear factor kappa B (NF-κB) p65 signalling. Serine 536 residues of NF-κB p65, which is phosphorylated by TNF-α, increased along with the degradation of inhibitor of κB (IκB) in the hippocampus of Aß-injected mice, although these effects were again attenuated by adalimumab. Furthermore, Aß1-40-induced increases in TNF-α and interleukin (IL)-6 expression were decreased by treatment with adalimumab. Our results indicate that adalimumab may be clinically useful in human patients with AD.

Scavenging Materials to Stabilize LiPF6 -Containing Carbonate-Based Electrolytes for Li-Ion Batteries.

In conjunction with electrolyte additives used for tuning the interfacial structures of electrodes, functional materials that eliminate or deactivate reactive substances generated by the degradation of LiPF6 -containing electrolytes in lithium-ion batteries offer a wide range of electrolyte formulation opportunities. Herein, the recent advancements in the development of: (i) scavengers with high selectivity and affinity toward unwanted species and (ii) promoters of ion-paired LiPF6 dissociation are highlighted, showing that the utilization of the above additives can effectively mitigate the problem of electrolyte instability that commonly results in battery performance degradation and lifetime shortening. A deep mechanistic understanding of LiPF6 -containing electrolyte failure and the action of currently developed additives is demonstrated to enable the rational design of effective scavenging materials and thus allow the fabrication of highly reliable batteries.

Fluoroethylene Carbonate-Based Electrolyte with 1 M Sodium Bis(fluorosulfonyl)imide Enables High-Performance Sodium Metal Electrodes.

Sodium (Na) metal anodes with stable electrochemical cycling have attracted widespread attention because of their highest specific capacity and lowest potential among anode materials for Na batteries. The main challenges associated with Na metal anodes are dendritic formation and the low density of deposited Na during electrochemical plating. Here, we demonstrate a fluoroethylene carbonate (FEC)-based electrolyte with 1 M sodium bis(fluorosulfonyl)imide (NaFSI) salt for the stable and dense deposition of the Na metal during electrochemical cycling. The novel electrolyte combination developed here circumvents the dendritic Na deposition that is one of the primary concerns for battery safety and constructs the uniform ionic interlayer achieving highly reversible Na plating/stripping reactions. The FEC-NaFSI constructs the mechanically strong and ion-permeable interlayer containing NaF and ionic compounds such as Na2CO3 and sodium alkylcarbonates.

Molecular Engineered Safer Organic Battery through the Incorporation of Flame Retarding Organophosphonate Moiety.

Here, we report the first electrochemical assessment of organophosphonate-based compound as a safe electrode material for lithium-ion batteries, which highlights the reversible redox activity and inherent flame retarding property. Dinickel 1,4-benzenediphosphonate delivers a high reversible capacity of 585 mA h g-1 with stable cycle performance. It expands the scope of organic batteries, which have been mainly dominated by the organic carbonyl family to date. The redox chemistry is elucidated by X-ray absorption spectroscopy and solid-state 31P NMR investigations. Differential scanning calorimetry profiles of the lithiated electrode material exhibit suppressed heat release, delayed onset temperature, and endothermic behavior in the elevated temperature zone.

Synergistic Effect of Partially Fluorinated Ether and Fluoroethylene Carbonate for High-Voltage Lithium-Ion Batteries with Rapid Chargeability and Dischargeability.

The roles of a partially fluorinated ether (PFE) based on a mixture of 1,1,1,2,2,3,3,4,4-nonafluoro-4-methoxybutane and 2-(difluoro(methoxy)methyl)-1,1,1,2,3,3,3-heptafluoropropane on the oxidative durability of an electrolyte under high-voltage conditions, the rate capability of the graphite and 5 V-class LiNi0.4Mn1.6O4 (LNMO) electrodes, and the cycling performance of graphite/LNMO full cells are examined. Our findings indicate that the use of PFE as a cosolvent in the electrolyte yields thermally stable electrolytes with self-extinguishing ability. Electrochemical tests confirm that the PFE combined with fluoroethylene carbonate (FEC) effectively alleviates the oxidative decomposition of the electrolyte at the high-voltage LNMO cathode and enables reversible electrochemical reactions of the graphite anodes and LNMO cathodes at high rates. Moreover, the combination of PFE, which mitigates electrolyte decomposition at high voltages, and FEC, which stabilizes the anode-electrolyte interface, enables the reversible cycling of high-voltage full cells (graphite/LNMO) with a capacity retention of 70.3% and a high Coulombic efficiency of 99.7% after 100 cycles at 1C rate at 30 °C.