Phenotypic and genomic characterization of a multidrug-resistant Salmonella enterica serovar Kentucky ST198 isolated from a patient in China.

OBJECTIVES: The objective of this study was to investigate the resistance mechanisms of a multidrug-resistant Salmonella Kentucky ST198 FJ-2064 isolated from a patient in China. METHODS: The antimicrobial susceptibility of FJ-2064 was determined by the standard disc dilution and broth microdilution methods. The complete genome of FJ-2064 was sequenced using PacBio and Illumina MiSeq platforms. Polymerase chain reaction (PCR) and S1-PFGE were utilized to confirm the mutation sites and the genomic plasmids, respectively. RESULTS: Isolate FJ-2064 belongs to sequence type ST198 and harboured no visible large plasmids, but was concurrent resistant to 22 detected antimicrobial agents including cefotaxime, ciprofloxacin, and azithromycin. The complete genome sequence identified 20 acquired antibiotic resistance genes (ARGs) and five chromosomal mutations in the gyrA and parC genes of the quinolone resistance determining regions (QRDRs) in FJ-2064. In addition, PCR sequencing confirmed that most of the ARGs were clustered on one multidrug-resistant region and a variant of SGI1-K. In particular, the bla-TEM-1 and bla-CTX-M-55, qnrS1, mph(A) genes, which confer resistance to cephalosporins, quinolones, and macrolides respectively, were all located on the multidrug-resistant region. CONCLUSIONS: We have demonstrated one multidrug-resistant region and a variant of SGI1-K in a Salmonella Kentucky ST198 that is co-resistant to cefotaxime, ciprofloxacin, and azithromycin.

Bergenin alleviates proliferative arterial diseases by modulating glucose metabolism in vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and phenotypic switching are key mechanisms in the development of proliferative arterial diseases. Notably, reprogramming of the glucose metabolism pattern in VSMCs plays an important role in this process. PURPOSE: The aim of this study is to investigate the therapeutic potential and the mechanism underlying the effect of bergenin, an active compound found in Bergenia, in proliferative arterial diseases. METHODS: The effect of bergenin on proliferative arterial disease was evaluated using platelet-derived growth factor (PDGF)-stimulated VSMCs and a mouse model of carotid artery ligation. VSMC proliferation and phenotypic switching were evaluated in vitro using cell counting kit-8, 5-ethynyl-2-deoxyuridine incorporation, scratch, and transwell assays. Carotid artery neointimal hyperplasia was evaluated in vivo using hematoxylin and eosin staining and immunofluorescence. The expression of proliferation and VSMC contractile phenotype markers was evaluated using PCR and western blotting. RESULTS: Bergenin treatment inhibited PDGF-induced VSMC proliferation and phenotypic switching and reduced neointimal hyperplasia in the carotid artery ligation model. Additionally, bergenin partially reversed the PDGF-induced Warburg-like glucose metabolism pattern in VSMCs. RNA-sequencing data revealed that bergenin treatment significantly upregulated Ndufs2, an essential subunit of mitochondrial complex I. Ndufs2 knockdown attenuated the inhibitory effect of bergenin on PDGF-induced VSMC proliferation and phenotypic switching, and suppressed neointimal hyperplasia in vivo. Conversely, Ndufs2 overexpression enhanced the protective effect of bergenin. Moreover, Ndufs2 knockdown abrogated the effects of bergenin on the regulation of glucose metabolism in VSMCs. CONCLUSION: These findings suggest that bergenin is effective in alleviating proliferative arterial diseases. The reversal of the Warburg-like glucose metabolism pattern in VSMCs during proliferation and phenotypic switching may underlie this therapeutic mechanism.

Biosafety Risk Control Strategies in Laboratory Animal Research.

To understand biosafety's current situation in laboratory animal research and risk factors affecting occupational health. Compliance surveys were conducted by questionnaire via Questionnaire Star (an application app on the Internet) in Chinese. Thirty-nine anonymous questionnaires were collected. The surveyed institution has established 24 types of ABSL (Animal Biosafety Laboratory) and biosafety management organizations and systems equipped with safety equipment. Our study also suggests that the principal of the laboratory establishment fails to perform supervision and inspection responsibilities, the inappropriate design of the animal biosafety laboratory, non-standardized personnel training and health management, non-strict waste management, and insufficient emergency management. The administrative department and work units should address certain safety and occupational health risks in laboratory animal research. The author proposes control strategies based on organizational guarantee, personnel management, emergency management, etc., to help prevent risks and ensure occupational health. Due to regional limitations and small sample size, the results may not be generalisable to all parts of the world. However, some of the key common issues may also be present in other regions, so we believe that this research still has some relevance.

Progress and application of adipose-derived stem cells in the treatment of diabetes and its complications.

Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.

Adaptive Ion Channels Formed in Ultrathin and Semicrystalline Polymer Interphases for Stable Aqueous Batteries.

Aqueous Zn batteries have recently emerged as promising candidates for large-scale energy storage, driven by the need for a safe and cost-effective technology with sufficient energy density and readily accessible electrode materials. However, the energy density and cycle life of Zn batteries have been limited by inherent chemical, morphological, and mechanical instabilities at the electrode-electrolyte interface where uncontrolled reactions occur. To suppress the uncontrolled reactions, we designed a crystalline polymer interphase for both electrodes, which simultaneously promotes electrode reversibility via fast and selective Zn transport through the adaptive formation of ion channels. The interphase comprises an ultrathin layer of crystalline poly(1H,1H,2H,2H-perfluorodecyl acrylate), synthesized and applied as a conformal coating in a single step using initiated chemical vapor deposition (iCVD). Crystallinity is optimized to improve interphase stability and Zn-ion transport. The optimized interphase enables a cycle life of 9500 for Zn symmetric cells and over 11,000 for Zn-MnO2 full-cell batteries. We further demonstrate the generalizability of this interphase design using Cu and Li as examples, improving their stability and achieving reversible cycling in both. The iCVD method and molecular design unlock the potential of highly reversible and cost-effective aqueous batteries using earth-abundant Zn anode materials, pointing to grid-scale energy storage.

Mediating role of anxiety and impulsivity in the association between child maltreatment and lifetime non-suicidal self-injury with and without suicidal self-injury.

BACKGROUND: Child maltreatment can increase the risk of lifetime non-suicidal self-injury (NSSI) and suicidal self-injury (SSI), but there is limited knowledge regarding the differences of potentially psychological mechanisms between NSSI with and without SSI. METHODS: Participants, 3918 community-based Chinese young men aged 18-34 years in Chengdu, were included in this study. We investigated the association between depression, anxiety, psychosis, child maltreatment, adulthood traumatic events, impulsivity, alcohol dependence, drug abuse, and lifetime of NSSI among participants with and without SSI. Parallel mediation analysis was utilized to explore the mediators for the relation between child maltreatment and NSSI. RESULTS: The prevalence of lifetime NSSI was 6.1 % (95 % CI: 5.4 %-6.9 %) among young men. Anxiety and impulsivity partially mediated the effect of child maltreatment on NSSI either with (indirect effect: 51.2 %) or without SSI (indirect effect: 34.3 %). Depression was independently and significantly associated with only NSSI but not with NSSI+SSI. Alcohol dependence and psychosis were independently and significantly associated with NSSI+SSI and mediated the effect of child maltreatment on NSSI+SSI. LIMITATIONS: The cross-sectional survey data limits the robustness of the proof to the causal relationships. CONCLUSIONS: Anxiety and impulsivity are associated with NSSI either with or without SSI and partially mediate the effect of child maltreatment on NSSI. Depression is associated with only NSSI, while alcohol dependence and psychosis are only associated with NSSI+SSI. It could be crucial to improve treatment and recovery of alcohol dependence and psychosis for preventing young men engaged in NSSI from attempting SSI.

Cross-sectional study on dysphagia evaluation in community-dwelling older adults using the Eating Assessment Tool (EAT) -10, EAT-2, and Water Swallow Test.

BACKGROUND: Dysphagia is a health concern that causes severe complications and affects the life quality of the older population. This study aimed to determine the diagnostic performance of the Eating Assessment Tool (EAT)-2 compared with the EAT-10 and the Water Swallow Test (WST) in screening for dysphagia. METHODS: A cross-sectional study was conducted among 5,090 community-dwelling older adults. Dysphagia was evaluated using both a subjective measure, the 10-item EAT (EAT-10) and an objective measure, the WST. The kappa index in pairs were analyzed. The validity and reliability of EAT-2 were also assessed. RESULTS: The sensitivity and specificity of the EAT-2 were 96.3 % and 94.8 %, respectively. The kappa index between the EAT-2 and EAT-10 was 0.64, whereas it was 0.11 between the EAT-10 and WST. CONCLUSIONS: The EAT-2 was a simpler screening tool for dysphagia. Combining the subjective questionnaire (EAT-10 or EAT-2) and the objective test (WST) is recommended.

Structure Revision of Type B Polycyclic Polyprenylated Acylphloroglucinols Fused to a Partly Reduced Furan Ring.

Four previous papers reported the isolation and structural determination of 10 polycyclic polyprenylated acylphloroglucinols (PPAPs), uraliones F, G, K, and O, attenuatumiones E and F, and scabrumiones A-D, from Hypericum species. Their structures were identified as type B PPAPs that featured not only the characteristic acyl group at C-3 of the bicyclo[3.3.1]nonane core but also a partly reduced furan ring fused to the C-1-C-2-O-2 atoms of the core. However, the 1D and 2D NMR data of these compounds were more consistent with type A PPAPs that featured not only the acyl group at C-1 but also a partially reduced furan ring fused to the C-3-C-2-O-2 atoms of the core. Now we revise these 10 previously proposed structures to the corresponding type A PPAPs via NMR analysis. Additionally, we propose a rule that uses NMR data to determine whether a particular PPAP that is fused to a partly reduced furan ring at C-3-C-2-O-2 or C-1-C-2-O-2 is type A or type B, respectively. We also propose a rule to assign the relative configurations of corresponding type A PPAPs at C-18 and revise the configurations of sampsonione N, hypericumoxides A-C, and hyperscabin G.

Association between health literacy and dysphagia in the community-dwelling older population: a cross-sectional study.

BACKGROUND: Dysphagia, or swallowing disorders, has become a growing concern due to the aging population, and health literacy plays a crucial role in active aging. However, the relationship between them remains unclear. AIMS: To investigate the association between health literacy and dysphagia among community-dwelling older adults in China. METHODS: A survey was conducted on 4462 older adults aged 65 and above in a community in Yiwu City, China, from May 2021 to January 2022. Swallowing problems were assessed using a 30 ml water swallowing test (WST) and the Eating Assessment Tool-10 questionnaire (EAT-10). The participants' health literacy was evaluated using the Chinese Health Literacy Scale (CHLS). Logistic regression and t tests were employed to measure the association between them. RESULTS: The prevalence of dysphagia was 5.70% and 7.85% as determined by EAT-10 and 30 ml-WST, respectively. The health literacy level of community-dwelling older adults was 24.4 ± 4.93 (9-45). Participants with dysphagia exhibited lower levels of health literacy (p < 0.05). The logistic regression model demonstrated an inverse association between health literacy and dysphagia (OR = 0.94, 95%CI = 0.91-0.96 for EAT-10, and OR = 0.93, 95%CI = 0.92-0.95 for WST). Moreover, this association remained significant even after adjusting for covariates. DISCUSSION: Older adults with dysphagia have lower levels of health literacy, particularly in terms of their ability to seek medical advice, acquire and evaluate medical information, and access social support resources. CONCLUSIONS: Health literacy is associated with dysphagia among community-dwelling older adults. Effective interventions should be implemented to provide support in terms of both medical services and social support for this population.

Absolute quantification of viable Vibrio cholerae in seawater samples using multiplex droplet digital PCR combined with propidium monoazide.

Introduction: Toxigenic Vibrio cholerae serogroup O1 and O139 are the pathogens responsible for the global cholera epidemic. V. cholerae can settle in the water and spread via the fecal-oral route. Rapid and accurate monitoring of live V. cholerae in environmental water has become an important strategy to prevent and control cholera transmission. Conventional plate counting is widely used to detect viable bacteria but requires time and effort. Methods: This study aims to develop a new assay that combines triplex droplet digital PCR (ddPCR) with propidium monoazide (PMA) treatment for quantitatively detecting live V. cholerae O1/O139 and cholera enterotoxin. Specific primers and probes were designed according to the conserved regions of gene rfb O1, rfb O139, and ctxA. The amplification procedures and PMA treatment conditions were optimized. The specificity, sensitivity, and ability of PMA-ddPCR to detect viable bacteria-derived DNA were evaluated in simulated seawater samples. Results and Discussion: The results revealed that the optimal primer concentrations of rfb O1, rfb O139, and ctxA were 1 µM, while the concentrations of the three probes were 0.25, 0.25, and 0.4 µM, respectively. The best annealing temperature was 58°C to obtain the most accurate results. The optimal strategy for distinguishing dead and live bacteria from PMA treatment was incubation at the concentration of 20 µM for 15 min, followed by exposure to a 650-W halogen lamp for 20 min. In pure culture solutions, the limit of detection (LODs) of V. cholerae O1 and O139, and ctxA were 127.91, 120.23 CFU/mL, and 1.5 copies/reaction in PMA-triplex ddPCR, respectively, while the LODs of the three targets were 150.66, 147.57 CFU/mL, and 2 copies/reaction in seawater samples. The PMA-ddPCR sensitivity was about 10 times higher than that of PMA-qPCR. When detecting spiked seawater samples with live bacterial concentrations of 1.53 × 102 and 1.53 × 105 CFU/mL, the assay presented a higher sensitivity (100%, 16/16) than qPCR (50.00%, 8/16) and a perfect specificity (100%, 9/9). These results indicate that the developed PMA-triplex ddPCR is superior to the qPCR regarding sensitivity and specificity and can be used to rapidly detect viable toxigenic V. cholerae O1 and O139 in suspicious seawater samples.

The motivation and pleasure deficits but not expressivity affects social functioning through cognitive function in male patients with schizophrenia: A structural equation model.

OBJECTIVE: This study aims to compare cognitive function and social functioning in male schizophrenia patients with deficit syndrome (DS) and non-DS, and to explore the associations among two different dimensions of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits), cognitive function and social functioning base on a Structural Equation Model (SEM). METHODS: The current study enrolled 161 male schizophrenia patients and 120 age- and education- matched healthy controls. The DS and non-DS group were categorized by the Chinese version of Schedule for the Deficit Syndrome (SDS). The psychotic and negative symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS). The Social functioning was measured by Scale of Social function in Psychosis Inpatients (SSPI). A battery of classical neurocognitive tests was used for assessing cognition including sustained vigilance/attention, cognitive flexibility, ideation fluency and visuospatial memory. RESULTS: Our study indicated that DS patients performed worser in cognitive function and social functioning than non-DS patients. The SEM model demonstrated that MAP significantly affected social functioning through direct influence and mediation of cognitive function. However, our results found that EXP had little influence on cognitive function and social function. CONCLUSION: Our findings provided evidence supporting that DS may represent as a subtype of schizophrenia, and the MAP factor play a pivotal role to influence the cognitive and social functioning in schizophrenia patients.

Status of mandatory treatment of mentally ill offenders without criminal responsibility in China: Information from 5,262 mandatory treatment judgments.

Background: To avoid public health risks, all governments ensure monitoring and treatment of mentally ill persons if they offend and assess their level of criminal responsibility. The Criminal Procedure Law of the People's Republic of China (2013) instituted special procedures. However, there are few articles in English which explain the implementation of mandatory treatment procedures in China. Methods: We collected 5,262 qualified documents from 2013 to 2021 from the China Judgments Documents Online. We analyzed social demographic characteristics, trial-related information as well as the mandatory treatment-related content, to investigate the mandatory treatment of China's mentally ill offenders without criminal responsibility, from 2013 to 2021. Simple descriptive statistics and chi-square tests were used to compare differences among several types of documents. Results: There was an overall change trend of the number of documents: increasing year by year from 2013 to 2019 after the implementation of the new law, but with sharp decrease in 2020 and 2021 during covid-19 pandemic. From 2013 to 2021, a total of 3,854 people had applications made for mandatory treatment, of whom 3,747 (97.2%) were given mandatory treatment, 107 (2.8%) had applications rejected. "Schizophrenia and other psychotic disorders" was the most common diagnosis in both groups and all offenders receiving mandatory treatment (3,747, 100.0%) were considered to have no criminal responsibility. A total of 1,294 patients had applications made for relief of mandatory treatment, of whom 827 (63.9%) were subsequently approved for relief, 467 (36.1%) were rejected. A total of 118 patients had applications for relief two or more times, and 56 (47.5%) were finally relieved. Conclusion: Our study presents the Chinese model of a criminal mandatory treatment system to the international community which has been in operation since the implementation of the new law. Legislatory changes and covid-19 pandemic can have effect on the number of mandatory treatment cases. Patients, their close relatives and mandatory treatment institutions have the right to apply for relief from mandatory treatment, but the final decision in China is taken by the court.

Prenylated acylphloroglucinols from the fruits of Garcinia xanthochymus.

Our continuous study of the dry fruits of Garcinia xanthochymus led to the isolation and structural characterization of four new prenylated acylphloroglucinols, xanthochymusones J-M (1-4), together with the known polycyclic polyprenylated acylphloroglucinols, garciniagifolone A (5) and garcinialiptone A (6). Their structures were elucidated by interpretation of NMR and MS spectroscopic data. Compound 1 bearing a similar core to that of hulupinic acid should be derived via oxidization and ring contraction of prenylated acylphloroglucinol. The inhibitory activities of all the compounds against three human hepatocellular carcinoma cell lines Huh-7, Hep 3B, and Hep G2 were evaluated, and compounds 4 and 5/6 exhibited moderate cytotoxic activities against Hep G2 cells with IC50 values10.4 and 8.8 µM.

Polycyclic Polyprenylated Acylphloroglucinols Bearing a Lavandulyl-Derived Substituent from Garcinia xanthochymus Fruits.

Many type B polycyclic polyprenylated acylphloroglucinols (PPAPs) bear a lavandulyl-derived substituent, and the configurational assignment of this side chain can be difficult and sometimes leads to erroneous conclusions. In this study, 21 PPAPs, including the new xanthochymusones A-I (1-9), have been isolated from the fruits of Garcinia xanthochymus and structurally characterized. The relative configuration of the C-30 stereocenter was assigned by a combination of chemical transformations, 1H-1H coupling constants, conformational analysis, and NOE experiments. The configurational assignment of compound 7 indicates that the relative configuration at C-30 of PPAPs is not always the same. The absolute configurations of the new compounds were assigned by ECD and X-ray diffraction data, as well as by biosynthetic considerations. Analysis of NMR data enabled the configurational revision of garcicowins C and D. All the isolated PPAPs were tested for antiproliferative activity against three human hepatocellular carcinoma cell lines, including Huh-7, Hep 3B, and HepG2. Compounds 5 and 6, 7-epi-isogarcinol (16), and coccinone C (17) exhibited moderate antiproliferative activity. Compounds 6 and 16 induced apoptosis and inhibited cell migration in Huh-7 cells, probably through downregulating the STAT3 signaling pathway. This study provides effective methods for configurational assignments of type B PPAPs.

Zwitterionic Polymer Gradient Interphases for Reversible Zinc Electrochemistry in Aqueous Alkaline Electrolytes.

Aqueous alkaline zinc batteries are of scientific and technological interest because of the potential they offer for cost-effective and safe storage of electrical energy. Poor electrochemical reversibility and shape change of the Zn anode, propensity of Zn to become passivated by surface oxides and hydroxide films upon prolonged exposure to the electrolyte, and electroreduction of water are well-studied but remain unsolved challenges. Here, we create and study electrochemical and transport properties of precise, spatially tunable zwitterionic polymer interphases grown directly on Zn using an initiated-chemical vapor deposition polymerization methodology. In aqueous alkaline media, spatial gradients in composition─from the polymer-electrolyte interface to the solid-polymer interface─promote highly reversible redox reactions at high current density (20 mA cm-2) and high areal capacity (10 mAh cm-2). Via molecular dynamics and experimental analyses, we conclude that the interphases function by regulating the distribution and activity of interfacial water molecules, which simultaneously enables fast ion transport and suppression of surface passivation and the hydrogen evolution reaction. To illustrate the practical relevance of our findings, we study aqueous Zn||NiOOH and Zn||air batteries and observe that zwitterionic polymer interphases produce extended life at high currents and high areal capacity.

Oncolytic Vaccinia Virus Harboring Aphrocallistes vastus Lectin Inhibits the Growth of Hepatocellular Carcinoma Cells.

Oncolytic vaccinia virus has been developed as a novel cancer therapeutic drug in recent years. Our previous studies demonstrated that the antitumor effect of oncolytic vaccina virus harboring Aphrocallistes vastus lectin (oncoVV-AVL) was significantly enhanced in several cancer cells. In the present study, we investigated the underlying mechanisms of AVL that affect virus replication and promote the antitumor efficacy of oncolytic virus in hepatocellular carcinoma (HCC). Our results showed that oncoVV-AVL markedly exhibited antitumor effects in both hepatocellular carcinoma cell lines and a xenograft mouse model. Further investigation illustrated that oncoVV-AVL could activate tumor immunity by upregulating the expression of type I interferons and enhance virus replication by inhibiting ISRE mediated viral defense response. In addition, we inferred that AVL promoted the ability of virus replication by regulating the PI3K/Akt, MAPK/ERK, and Hippo/MST pathways through cross-talk Raf-1, as well as metabolism-related pathways. These findings provide a novel perspective for the exploitation of marine lectins in oncolytic therapy.

Global Genomic Characterization of Salmonella enterica Serovar Telelkebir.

Non-typhoidal Salmonella (NTS) is a common cause for self-limiting gastroenteritis, representing a public health concern globally. NTS is one of the leading causes of foodborne illnesses in China; however, the invasive infection caused by NTS is largely underappreciated. Here, we reported an NTS invasive infection caused by an infrequently reported serovar Telelkebir (13,23:d:e,n,z15) strain FJ001 in China, which carries antimicrobial-resistant genes [fosA7 and aac(6')-Iaa] and typhoid-toxin genes (cdtB, pltA, and pltB). By conducting the whole genomic sequencing, we also investigated the relatedness of this strain with an additional 120 global contextual Salmonella enterica serovar Telelkebir (S. Telelkebir) isolates, and assessed the antimicrobial-resistant determinants and key virulence factors using the available genomic dataset. Notably, all 121 (100%) of the S. Telelkebir strains possessed the typhoid toxin genes cdtB, pltA, and pltB, and 58.67% (71/121) of S. Telelkebir harbored antimicrobial-resistant gene fosaA7. The study by core genome multilocus sequence typing (cgMLST) and core single-nucleotide polymorphism (SNP)-based phylogenomic analysis demonstrated that the S. Telelkebir isolates from different sources and locations clustered together. This suggests that regular international travels might increase the likelihood of rapid and extensive transmissions of potentially pathogenic bacteria. For the first time, our study revealed the antimicrobial resistance, virulence patterns, and genetic diversity of the serovar S. Telelkebir isolate in humans and similar isolates over the world. The present study also suggests that genomic investigation can facilitate surveillance and could offer added knowledge of a previously unknown threat with the unique combination of virulent and antimicrobial-resistant determinants.

Three-dimensional line edge roughness in pre- and post-dry etch line and space patterns of block copolymer lithography.

In this work, we employ large-scale coarse-grained molecular dynamics (CGMD) simulations to study the three-dimensional line edge roughness associated with line and space patterns of chemo-epitaxially directed symmetric block copolymers (BCPs) on a flat substrate. The di-block copolymer chain length and interaction parameters are validated with the experimental BCP period, L0 and corresponding molecular weight. Defect-free lamellae are formed, after which the system is quenched below the glass transition temperature before selectively dry-etching off one of the BCP phases. The effect of varying etch-selectivity on post-etch resist domain morphology was studied. The roughness of the polymer domain was evaluated over three process stages: annealing, pre-etching, and post-etching. Power spectral density plots were then generated to elucidate the contributions of low and high frequency roughness for the three process stages. The roughness results obtained from simulations are shown to be in close agreement with the roughness result obtained from analyzing experimental SEM images. Parameters like the Hurtz roughness exponent and correlation length inherent to the process and the BCP were also revealed from the experimental study.

Modulating Toll-like receptor mediated signaling by (1-->3)-beta-D-glucan rapidly induces cardioprotection.

OBJECTIVE: Immune and inflammatory signaling pathways, initiated by the innate response, are involved in myocardial ischemia/reperfusion (I/R) injury. Toll-like receptor (TLR) mediated MyD88-dependent NFkappaB pathways play a role in the induction of innate immunity. We have reported that glucan phosphate (GP) improved survival in experimental sepsis, which correlated with decreased tissue NFkappaB activation. In the present study, we report that GP rapidly induced cardioprotection against I/R injury in vivo. METHODS: Sprague-Dawley rats were pretreated with GP (40 mg/kg, i.p) 1 h before 45 min of ligation of the left anterior descending coronary followed by reperfusion for 4 and 24 h. Infarction size was examined by triphenyltetrazolium chloride (TTC) staining. NFkappaB activation was analyzed by electrophoretic mobility shift assay (EMSA). IkappaB kinase-beta (IKKbeta), IL-1 receptor-associated kinase (IRAK) and Phosphoinositide 3-kinase (PI3K) activities were determined by kinase assay with appropriate substrates. Association of TLR4 with MyD88 or with PI3K p85 was assessed by immunoprecipitation with anti-TLR4 followed by immunoblotting with anti-MyD88 or anti-p85. RESULTS: GP treatment reduced infarct size by 47% in rat hearts subjected to reperfusion for 4 h and by 50% following reperfusion for 24 h. The same protective effect was observed when GP was administrated 5 min after initiation of ischemia. The mechanisms of GP induced cardioprotection involve decreased association of TLR4 with MyD88, inhibition of I/R induced IRAK and IKKbeta activity and decreased NFkappaB activity. In addition, GP increased TLR4 phosphotyrosine, resulting in increasing PI3K/Akt activity in the myocardium, which correlated with decreased cardiac myocyte apoptosis following I/R. CONCLUSION: The results suggest that activation of the TLR mediated MyD88-dependent NFkappaB signaling pathway may play an important role in myocardial I/R injury, while stimulation of the PI3K/Akt signaling could serve a protective role. The data indicates that GP treatment shifts the TLR mediated activation signal in I/R from a predominantly NFkappaB pathway to a predominant PI3K/Akt signaling pathway.