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The emergence of carbapenem-resistant bacteria especially carbapenem-resistant Escherichia coli (CREC) in food animals poses a serious threat to food safety and public health. Reports about the dissemination of carbapenem-resistant bacteria along the food animal production chain are scattered and mainly focus on swine and chicken. Abuse of antibiotics in duck farms is common especially in China which has the largest duck production industry, however, the CREC transmission between farmed ducks and slaughtered meats remains unclear and the role of slaughterhouse in disseminating CREC among duck meats remains largely unknown. Herein, we collected 251 fecal samples from five typical duck farms along with 125 slaughtered meat samples (25 from each farm) in the corresponding slaughterhouse in Anhui Province, China, in December 2018. All samples were screened for CREC isolates which were analyzed for the presence of carbapenemase genes and colistin resistance gene mcr. The resistance profiles, transferability, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing and phylogenetic analysis of the CREC isolates from both ducks and meats were further characterized. This is the first report presenting the high prevalence of bla NDM -positive CREC isolates in ducks from duck farms (57.8 %) and slaughtered meats (33.6 %) in the corresponding slaughterhouse. Among the 203 bla NDM -positive CREC isolates obtained in this study, 19.2 % harbored mcr-1 and all CREC isolates showed resistance to nearly all currently available antibiotics (except tigecycline). Of note, mcr-1 was found in 17.8 % of the meat-derived CREC carrying bla NDM . Based on the PFGE analysis, clonal spread of bla NDM -positive CREC including some also carrying mcr-1 was found between farmed ducks and slaughtered duck meats even from different farms. Special attention should be paid to the clonal dissemination of meat-derived CREC within the slaughterhouse, which contributed to the high prevalence of bla NDM in slaughtered meats. Additionally, horizontal transmission mainly mediated by transferable bla NDM-5 -bearing IncX3 plasmids, untypable bla NDM-1 -bearing plasmids and mcr-1-bearing IncHI2 plasmids further facilitated the rapid spread of such multidrug-resistant strains. Notably, the bla NDM -bearing plasmids and mcr-1-bearing plasmids in CREC from meats were highly similar to those from animals and humans. More worryingly, the phylogenomic analysis showed that CREC isolates from both ducks and corresponding meats clustered with previously reported human CREC isolates carrying mcr-1 in different geographical areas including China. These findings further prove that the CREC and resistance plasmids in farmed ducks could transmit to meats even from different farms via the slaughterhouse and then trigger infections in humans. The high prevalence and clonal transmission of CREC isolates including those also carrying mcr-1 between ducks and meats are alarming, and urgent control measures are required to reduce the dissemination of such organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The etiology of pneumoconiosis is relatively clear, but the pathogenic mechanism is not fully understood, and there is no effective cure for pneumoconiosis. Clarifying the pathogenesis of pneumoconiosis and exploring relevant markers can help screen high-risk groups of dust exposure, and relevant markers can also be used as targets to intervene in the process of pulmonary fibrosis. The in-depth development of genomics, transcriptomics and proteomics has provided a new way to discover more potential markers of pneumoconiosis. In the future, the combination of multi-omics and multi-stage interactive analysis can systematically and comprehensively identify key genes (proteins) , metabolites and metabolic pathways in the occurrence and development of pneumoconiosis, build a core regulatory network, and then screen out sensitive markers related to early diagnosis and treatment of pneumoconiosis. This article summarizes the research progress of pneumoconiosis markers from the perspective of multi-omics, hoping to provide more basic data for the early prevention and diagnosis of pneumoconiosis, pathogenesis research, and therapeutic intervention.

In situ aerobic cometabolism of groundwater contaminants has been demonstrated to be a valuable bioremediation technology to treat many legacy and emerging contaminants in dilute plumes. Several well-designed and documented field studies have shown that this technology can concurrently treat multiple contaminants and reach very low cleanup goals. Fundamentally different from metabolism-based biodegradation of contaminants, microorganisms that cometabolically degrade contaminants do not obtain sufficient carbon and energy from the degradation process to support their growth and require an exogenous growth supporting primary substrate. Successful applications of aerobic cometabolic treatment therefore require special considerations beyond conventional in situ bioremediation, such as competitive inhibition between growth-supporting primary substrate(s) and contaminant non-growth substrates, toxic effects resulting from contaminant degradation, and differences in microbial population dynamics exhibited by biostimulated indigenous consortia versus bioaugmentation cultures. This article first provides a general review of microbiological factors that are likely to affect the rate of aerobic cometabolic biodegradation. We subsequently review fourteen well documented field-scale aerobic cometabolic bioremediation studies and summarize the underlying microbiological factors that may affect the performance observed in these field studies. The combination of microbiological and engineering principles gained from field testing leads to insights and recommendations on planning, design, and operation of an in situ aerobic cometabolic treatment system. With a vision of more aerobic cometabolic treatments being considered to tackle large, dilute plumes, we present several novel topics and future research directions that can potentially enhance technology development and foster success in implementing this technology for environmental restoration., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier B.V.)

Toxoplasma gondii is an opportunistic pathogenic protozoan that can infect all nucleated cells in almost all warm-blooded animals, including humans. T. gondii infection has been reported in many food animals worldwide. However, the prevalence and genotypes of T. gondii in chickens from farmers' markets in Fujian province in southeastern China remain unreported. In the present study, four tissue samples from each of the 577 chickens (namely, the heart, liver, lungs, and muscles) were collected from farmers' markets in five regions of Fujian province (Zhangzhou, Sanming, Quanzhou, Fuzhou, and Longyan). We first analyzed the prevalence and genotypes of T. gondii using PCR targeting of the B1 gene of T. gondii . Of the 577 chickens, thirty-two (5.5%) tested positive for the B1 gene. Among the five regions, Sanming had the highest infection rate (16.8%, 16/95), followed by Quanzhou (8.0%, 8/100), Longyan (5.0%, 5/100), Zhangzhou (1.1%, 2/182), and Fuzhou (1.0%, 1/100). Among these thirty-two T. gondii -positive chickens, the infection rates of the lungs, heart, liver, and muscles were 68.8% (22/32), 34.4% (11/32), 28.1% (9/32), and 9.4% (3/32), respectively. Significant differences in prevalence were found among the different regions ( χ 2 = 35.164, p < 0.05) and tissues ( χ 2 = 25.874, p < 0.05). A total of 128 tissue and organ samples of the thirty-two T. gondii -positive chickens from the different regions were analyzed using PCR-restriction fragment length polymorphism (PCR-RFLP) on the basis of 10 genetic markers. Seven tissue samples (lung samples from five chickens, heart samples from one chicken, and liver samples from one chicken) underwent successful amplification at all the genetic markers, and all the T. gondii genotypes were identified as genotype I (ToxoDB #10). These findings serve as a foundation for evaluating the risk of T. gondii contamination in chicken products intended for human consumption and offer insight into preventing the transmission of the parasite from chickens to humans.

To probe signal propagation and genetic actuation in microbial consortia, we have coopted the components of both redox and quorum sensing (QS) signaling into a communication network for guiding composition by "programming" cell lysis. Here, we use an electrode to generate hydrogen peroxide as a redox cue that determines consortia composition. The oxidative stress regulon of Escherichia coli, OxyR, is employed to receive and transform this signal into a QS signal that coordinates the lysis of a subpopulation of cells. We examine a suite of information transfer modalities including "monoculture" and "transmitter-receiver" models, as well as a series of genetic circuits that introduce time-delays for altering information relay, thereby expanding design space. A simple mathematical model aids in developing communication schemes that accommodate the transient nature of redox signals and the "collective" attributes of QS signals. We suggest this platform methodology will be useful in understanding and controlling synthetic microbial consortia for a variety of applications, including biomanufacturing and biocontainment., (© 2023 Wiley Periodicals LLC.)

Pyrrole-imidazole alkaloids (PIAs) constitute a highly diverse and densely functionalized subclass of marine natural products. Among them, the uncommon dimeric PIAs with ornate molecular architectures, attractive biological properties and interesting biosynthetic origin have spurred a considerable interest of chemists and biologists. The present review comprehensively summarized 84 dimeric PIAs discovered during the period from 1981 to September 2022, covering their source organisms, chemical structures, biological activities as well as biosynthesis. For a better understanding, these structurally intricate PIA dimers are firstly classified and presented according to their carbon skeleton features as well as biosynthesis pathways. Furthermore, relevant summaries focusing on the source organisms and the associated bioactivities of these compounds belonging to different chemical classes are also provided, which will help elucidate the fascinating chemistry and biology of these unusual PIA dimers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Giardia duodenalis is a common intestinal protozoan that can cause diarrhea and intestinal disease in animals and in humans. However, the prevalence and assemblages of G. duodenalis in pigs from Guangxi Zhuang Autonomous Region have not been reported. In this study, a total of 724 fecal samples (201 from nursery pigs, 183 from piglets, 175 from breeding pigs, and 165 from fattening pigs) were obtained in four areas of the region (Nanning, Yulin, Hezhou, and Guigang). The gene of the small subunit ribosomal RNA (SSU rRNA) of G. duodenalis was amplified by nested PCR. The results show that the prevalence of G. duodenalis in pigs was 3.59% (26/724), of which 14 samples belonged to assemblage A (53.85%) and 12 samples belonged to assemblage E (46.15%). The infection rates of G. duodenalis in Hezhou, Yulin, Nanning, and Guigang were 0%, 0.7%, 10.8% and 1.1%, respectively (χ 2  = 45.616, p < 0.01); whereas 5.1% of breeding pigs, 6.0% of piglets, 2.4% of fattening pigs, and 1.0% of nursery pigs were infected with G. duodenalis (χ 2  = 8.874, p < 0.05). The SSU rRNA-positive samples were amplified by PCR based on the β-giardin (bg), glutamate dehydrogenase (gdh), and triphosphate isomerase (tpi) genes. Ten, eight and seven positive samples were detected, respectively. Based on phylogenetic analysis of the three genetic loci sequences, a multilocus genotyping A1 was found. The findings of this study provide basic data for the development of prevention and control of G. duodenalis infections in pigs and humans in the Guangxi Zhuang Autonomous Region., (© Y.-F. Song et al., published by EDP Sciences, 2023.)

As one of the most common marine sponges in tropical and subtropical oceans, the sponges of the genus Agelas , have emerged as unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities. The present review highlights the chemical structure and biological activity of 355 compounds that have been isolated and characterized from the members of Agelas sponges, over the period of about five decades (from 1971 to November 2021). For a better understanding, these numerous compounds are firstly classified and presented according to their carbon skeleton as well as their biosynthetic origins. Relevant summaries focusing on the source organism and the associated bioactivity of these compounds belonging to different chemical classes are also provided. This review highlights sponges of the genus Agelas as exciting source for discovery of intriguing natural compounds., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China., Methods: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff ) was used to estimate the transmission interaction in different age groups., Results: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff  = 4.28), followed by group 2 to 3 (R eff  = 2.61), and group 2 to 4 (R eff  = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old., Conclusions: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China., (© 2021. The Author(s).)

Objective: Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer. Methods: Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer. Results: A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P <0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR =1.33, 95% CI :1.01-1.74, P =0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR =0.71, 95% CI :0.52-0.96, P =0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR =1.53, 95% CI : 1.01-2.32, P =0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR =0.83, 95% CI : 0.69-0.98, P =0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR =3.35,95% CI :2.10-5.34, P <0.001). Conclusion: There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

Background: Rhopressa (netarsudil) has recently been added to the arsenal of treatment for open-angle glaucoma. It is an effective norepinephrine transporter and Rho-associated protein kinase (ROCK) inhibitor used to decrease intraocular pressure (IOP), with the most common side effect being conjunctival hyperemia., Case Presentation: We report a unique case of Rhopressa-induced corneal edema in a 79-year-old African-American woman, which resolved after discontinuation. She had a history of smoking one cigarette per day and did not consume alcohol. She had no history of corneal edema or uveitis., Conclusions: Previous case reports have documented patients with Rhopressa-induced corneal edema; however, they have all had a preexisting history of corneal edema or uveitis. We believe that this is a unique case of Rhopressa-induced corneal edema in a relatively healthy eye. While Rhopressa is effective in managing glaucoma, there may be effects of treatment that are still unknown. We will discuss clinical findings of our case, along with a review of previous literature on Rhopressa and novel ROCK inhibitors. We hope that we can add to the existing body of literature and invite further investigation of Rhopressa and ROCK inhibitors and their effects on the cornea.

Background: Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow., Objective: To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients., Design: Randomized community intervention trial., Participants: The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China., Main Measures: Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention., Key Results: BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P < 0.001). Along with the duration of the follow-up period, systolic and diastolic BP decreased rapidly in the early stages and then gradually after 6 months in the intervention group (P < 0.001). In the intervention group, drug therapy adherence was increased by 39.5% (from 48.1% at 1 month to 87.6% at 1 year) (P < 0.001), more in women (45.6%) than in men (31.2%; P < 0.001). The net effect of the lifestyle intervention improved the rate of BP control by 56.1% (70.8% for men and 44.7% for women). For all physiological and biochemical factors, such as body mass index, waist circumference, lipid metabolism, and glucose control, improvements were more significant in the behavioral intervention group than those in the control group (all P < 0.001)., Conclusion: The addition of lifestyle intervention by physicians or nurses helps control BP effectively and lowers BP better than usual care with antihypertensive drug therapy alone.

Background: Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscript m) and female (subscript f) individuals using a newly developed sex-based model., Methods: The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017. A sex-based Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model was applied to explore the dataset, and a sex-age-based SEIAR model was applied in 2010 to explore the sex- and age-specific transmissions., Results: From 2005 to 2017, 130 770 shigellosis cases (including 73 981 male and 56 789 female cases) were reported in Hubei Province. The SEIAR model exhibited a significant fitting effect with the shigellosis data (P <  0.001). The median values of the shigellosis transmission were 2.3225 × 10 8 for SAR mm (secondary attack rate from male to male), 2.5729 × 10 8 for SAR mf , 2.7630 × 10 -8 for SAR fm , and 2.1061 × 10 -8 for SAR ff . The top five mean values of the transmission relative rate in 2010 (where the subscript 1 was defined as male and age ≤ 5 years, 2 was male and age 6 to 59 years, 3 was male and age ≥ 60 years, 4 was female and age ≤ 5 years, 5 was female and age 6 to 59 years, and 6 was male and age ≥ 60 years) were 5.76 × 10 -8 for β 61 , 5.32 × 10 -8 for β 31 , 4.01 × 10 -8 for β 34 , 7.52 × 10 -9 for β 62 , and 6.04 × 10 -9 for β 64 ., Conclusions: The transmissibility of shigellosis differed among male and female individuals. The transmissibility between the genders was higher than that within the genders, particularly female-to-male transmission. The most important route in children (age ≤ 5 years) was transmission from the elderly (age ≥ 60 years). Therefore, the greatest interventions should be applied in females and the elderly.

Due to the importance of proanthocyanidin bioactivity and its relationship with chemical structure, ultrasound-assisted extraction and purification schemes were proposed to evaluate the proanthocyanidin content and analyze the structural composition and potential bioactivities of different proanthocyanidin fractions from Chinese wild rice ( Zizania latifolia ). Following an optimized extraction procedure, the crude wild rice proanthocyanidins (WRPs) were purified using n-butanol extraction, chromatography on macroporous resins, and further fractionation on Sephadex LH-20 to yield six specific fractions (WRPs-1-WRPs-6) containing proanthocyanidin levels exceeding 524.19 ± 3.56 mg/g extract. Structurally, (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin were present as both terminal and extension units, and (-)-epicatechin was the major extension unit, in each fraction. This is the first preparation of WRP fractions with a different mean degree of polymerization (mDP), ranging from 2.66 ± 0.04 to 10.30 ± 0.46. A comparison of the bioactivities of these fractions revealed that fractions WRPs-1-WRPs-5 had significant DPPH radical scavenging activities, whereas fraction WRPs-6 with a high mDP showed better α-glucosidase and pancreatic lipase inhibitory effects. These findings should help define possible applications of WRPs to functional foods or nutraceuticals.

To develop new antibacterial agents, a series of novel triazole-containing pyrazole ester derivatives were designed and synthesized and their biological activities were evaluated as potential topoisomerase II inhibitors. Compound 4d exhibited the most potent antibacterial activity with Minimum inhibitory concentration (MIC) alues of 4 µg/mL, 2 µg/mL, 4 µg/mL, and 0.5 µg/mL against Staphylococcus aureus , Listeria monocytogenes , Escherichia coli , and Salmonella gallinarum , respectively. The in vivo enzyme inhibition assay 4d displayed the most potent topoisomerase II (IC 50 = 13.5 µg/mL) and topoisomerase IV (IC 50 = 24.2 µg/mL) inhibitory activity. Molecular docking was performed to position compound 4d into the topoisomerase II active site to determine the probable binding conformation. In summary, compound 4d may serve as potential topoisomerase II inhibitor.

Five new oxygenated sesquiterpenes, molestins A⁻D ( 1 , 3 ⁻ 5 ) and epi -gibberodione ( 2 ), three new cyclopentenone derivatives, ent -sinulolides C, D, and F ((+)- 9 ⁻(+)- 11 ), one new butenolide derivative, ent -sinulolide H ((+)- 13 ), and one new cembranolide, molestin E ( 14 ), together with 14 known related metabolites ( 6 ⁻ 8 , (⁻)- 9 ⁻(⁻)- 11 , (±)- 12 , (⁻)- 13 , 15 ⁻ 19 ) were isolated from the Paracel Islands soft coral Sinularia cf. molesta . The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia . Molestin E ( 14 ) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC 50 values of 5.26 and 8.37 μM, respectively. Compounds 4 , 5 , and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC 50 values of 218, 344, and 1.24 μM, respectively.

To provide further insights into the potential health-promoting antioxidants from wild rice ( Zizania latifolia ), which is an abundant but underutilized whole grain resource in East Asia, a partial purification based on D101 macroporous resin was carried out for the purification and enrichment of the antioxidants from the bioactive ethanol extracts of wild rice. On that basis, 34 phenolic compounds in the antioxidant fractions were identified by a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MS n ). The results suggested that phenolic acids could be enriched in the 10% ethanol-eluted fraction whereas flavonoids (including procyanidins and flavonoid glycosides) could be enriched in 20⁻30% ethanol-eluted fractions. A quantitative analysis determined by the multiple reaction monitoring mode of the ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UPLC-QqQ-MS/MS) revealed a high content of procyanidins in wild rice. Compared with phenolic acids, flavonoids may contribute more to the potent antioxidant activity of wild rice. This is the first study on the antioxidants from wild rice Z. latifolia. These findings provide novel information on the functional components of wild rice, and will be of value to further research and development on Z. latifolia .

The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella. The selected compounds (8III-k, 8V-c and 8V-k) exhibit potent inhibition against Topo II and Topo IV with IC 50 values (9.4-25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Topo II inhibiting bactericides., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic.The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01&#95;AE and CRF07&#95;BC among antiretroviral therapy (ART)-naïve MSM recently infected with HIV-1 in Jiangsu Province.We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015. We collected information on demographics and sexual behaviors and a blood sample for HIV genome RNA extraction, RT-PCR amplification, and DNA sequencing. Multiple alignments were made using Gene Cutter, with the selected reference sequences of various subtypes/recombinants from the Los Alamos HIV-1 database. Phylogenetic and Bayesian evolutionary analysis was performed by MEGA version 6.0, Fasttree v2.1.7. and BEAST v1.6.2. Categorical variables were analyzed using χ test (or Fisher exact test where necessary). χ test with trend was used to assess the evolution of HIV-1 subtype distribution over time. All data were analyzed using SPSS20.0 software package (IBM Company, New York, NY).HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01&#95;AE (60.06%), CRF07&#95;BC (22.29%), subtype B (5.88%), CRF67&#95;01B (5.26%), CRF68&#95;01B (2.79%), CRF55&#95;01B (1.55%), CRF59&#95;01B (0.93%), and CRF08&#95;BC (0.62%). Two unique recombination forms (URFs) (0.62%) were also detected. Four epidemic clusters and 1 major cluster in CRF01&#95;AE and CRF07&#95;BC were identified. The introduction of CRF01&#95;AE strain (2001) was earlier than CRF07&#95;BC strain (2004) into MSM resided in Jiangsu based on the time of the most recent common ancestor.Our study demonstrated HIV-1 subtype diversity among ART-naïve MSM recently infected with HIV-1 in Jiangsu. We first depicted the spatiotemporal dynamics, traced the dates of origin for the HIV-1 CRF01&#95;AE/07&#95;BC strains and made inference for the effective population size among newly infected ART-naïve MSM in Jiangsu from 2012 to 2015. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster would be of great value to the monitoring of the epidemic and control of transmission, improvement of antiretroviral therapy strategies, and design of vaccines.

Zijuan tea is a special cultivar of Yunnan broad-leaf tea (Camellia sinensis var. assamica) with purple buds, leaves, and stems. Phytochemical study on this tea led to the discovery of three hydroxycinnamoylated catechins (HCCs) (1-3), seven other catechins (4-10), three proanthocyanidins (11-13), five flavones and flavone glycosides (14-18), two alkaloids (19, 20), one steroid (21), and one phenylpropanoid glycoside (22). The isolation and structural elucidation of the caffeoylated catechin (1) by means of spectroscopic techniques were described. We also provide the first evidence that 1 is synthesized via a two-step pathway in tea plant. The three HCCs (1-3) were investigated on their bioactivity through molecular modeling simulation and biochemical experiments. Our results show that they bind acetylcholinesterase (AChE) tightly and have strong AChE inhibitory activity with IC 50 value at 2.49, 11.41, 62.26μM, respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the relationship between IL-1 gene polymorphisms and coal workers' pneumoconiosis and silicosis susceptibility. Methods: We searched published full-text from PubMed, Web of Science, CNKI, VIP and Wanfang to collect case-control study on IL-1 gene polymorphisms with coal workers' pneumoconiosis and silicosis susceptibility. Eight articles, including 10 case-control studies were included in our study. All analyses were performed using the Stata version 12.0 software. Results: The IL-1RA (+2018) TC or CC variant genotypes were associated with coal workers' pneumoconiosis and silicosis risk ( OR =1.65, 95% CI : 1.11-2.46) . In further stratified analyses, the IL-1RA (+2018) TC or CC variant genotypes were associated with an increased silicosis risk ( OR =2.07, 95% CI : 1.45-2.95) , which were also associated with increased coal workers' pneumoconiosis and silicosis risk in Caucasians ( OR =1.74, 95% CI : 1.22-2.47) . No significant association between IL-1β (+3953) , IL-1β (-511) , IL-1α (+4845) and coal workers' pneumoconiosis and silicosis risk was found either in the overall study or in the stratified analysis. Conclusion: These findings suggested that IL-1RA (+2018) may modify coal workers' pneumoconiosis and silicosis susceptibility. Further replication studies with large sample sizes are warranted to re-evaluate the relationship between IL-1RA (+2018) and coal workers' pneumoconiosis and silicosis risk.

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia p aracaseolaris , yielding five new triterpenoid paracaseolins A-E ( 1 - 4 , and 11 ) together with twelve known analogues ( 5 - 10 , 12 - 17 ). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC 50 value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC 50 value of 28.4 µg/mL. A preliminary structure activity relationship was discussed., Competing Interests: There are no conflict of interest and no controversy among all authors concerning the publication of the manuscript.

Background: Succinate dehydrogenase (SDH) plays an important role in the Krebs cycle, which is considered as an attractive target for development of succinate dehydrogenase inhibitors (SDHIs) based on antifungal agents. Thus, in order to discover novel molecules with high antifungal activities, SDH as the target for a series of novel nicotinamide derivatives bearing substituted pyrazole moieties were designed and synthesised via a one-pot reaction., Results: The biological assay data showed that compound 3 l displayed the most potent antifungal activity with EC 50 values of 33.5 and 21.4 µm against Helminthosporium maydis and Rhizoctonia cerealis, respectively. Moreover, 3 l exhibited the best inhibitory ability against SDH enzymes. The results of docking simulation showed that 3 l was deeply embedded into the SDH binding pocket, and the binding model was stabilised by a cation-π interaction with Arg 43, Tyr 58 and an H-bond with Trp 173., Conclusion: The study suggests that the pyrazole nicotinamide derivative 3 l may serve as a potential SDHI that can be used as a novel antifungal agent, and provides valuable clues for the further design and optimisation of SDH inhibitors. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC 50 values of 12.4, 16.0, and 19.8 μm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml)., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Acetylcholinesterase (AChE) is a key enzyme which present in the central nervous system of living organisms. Organophosphorus pesticides (OPs) that serve as insecticides are AChE inhibitors which have been used widely in agriculture. A series of novel OPs containing pyrazole moiety have been designed and synthesized. The biological evaluation indicated compound 4e appeared 81% larvicidal activity against Plutella xylostella at the concentration of 0.1 mg/L and the inhibition of AChE by compound 4e was distinctly enhanced with the increasing doses. Molecular docking of compound 4e into the three dimensional X-ray structure of the Drosophila melanogaster AChE (DmAChE, PDB code: 1QO9) was carried out utilizating the Discovery Studio (DS), the binding model revealed that the title structure was tightly embedded in the binding sites of DmAChE. Therefore, we suggest that compound 4e may serve as a novel AChE inhibitor that can be utilized as a new insecticidal drug.

Mitogen activated protein kinase (MAPK) signal transduction pathway has been proved to play an important role in tumorigenesis and cancer development. MEK inhibitor has been demonstrated significant clinical benefit for blocking MAPK pathway activation and possibly could block reactivation of the MAPK pathway at the time of BRAF inhibitor resistance. Twenty N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives have been designed and synthesized as MEK inhibitors, and their biological activities were evaluated. Among these compounds, compound 7b showed the most potent inhibitory activity with IC50 of 91nM for MEK1 and GI50 value of 0.26μM for A549 cells. The SAR analysis and docking simulation were performed to provide crucial pharmacophore clues that could be used in further structure optimization., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI)., Methods: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured., Results: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities., Conclusion: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 = 1.18 μM for lymph node cells and IC50 = 0.28 μM for PI3Kγ), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China., Methods: The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed., Results: Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids., Conclusions: Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are developed to reduce prevalence of metabolic syndrome and its components in rural Chinese populations.

Background: There is increasing need to expand availability of donor liver grafts, including steatotic livers. Steatotic liver is associated with poor outcome post-transplantation but with conflicting results in the literature. The aim of this systematic review was to evaluate the impact of steatotic livers on liver transplantation outcomes., Methods: An electronic search of OVID Medline and Embase databases was performed to identify clinical studies that reported outcomes of steatotic livers in liver transplantation. Data were extracted, and basic descriptive statistics were used to summarise data pooled from individual clinical studies., Results: Ninety-two articles were identified, of which 34 met the inclusion criteria, and stratified analysis were performed. There was a lack of standardised definition of primary non-function or impaired primary function amongst the studies and description of type of steatosis. Severely (>60%) steatotic grafts are associated with increased risk of poor graft function, whilst moderate-severe (>30%) steatotic grafts are associated with decreased graft survival., Conclusions: Available evidence showed increased risk of poor graft outcome in moderate-severe steatotic livers. A large prospective multi-centred trial will be required to identify the true risks of steatotic livers. Consistent definition of primary non-function/impaired primary function and description of type of steatosis is also required.

Background: Agarwood, a heartwood derived from Aquilaria trees, is a valuable commodity that has seen prevalent use among many cultures. In particular, it is widely used in herbal medicine and many compounds in agarwood are known to exhibit medicinal properties. Although there exists much research into medicinal herbs and extraction of high value compounds, few have focused on increasing the quantity of target compounds through stimulation of its related pathways in this species., Results: In this study, we observed that cucurbitacin yield can be increased through the use of different light conditions to stimulate related pathways and conducted three types of high-throughput sequencing experiments in order to study the effect of light conditions on secondary metabolism in agarwood. We constructed genome-wide profiles of RNA expression, small RNA, and DNA methylation under red light and far-red light conditions. With these profiles, we identified a set of small RNA which potentially regulates gene expression via the RNA-directed DNA methylation pathway., Conclusions: We demonstrate that light conditions can be used to stimulate pathways related to secondary metabolism, increasing the yield of cucurbitacins. The genome-wide expression and methylation profiles from our study provide insight into the effect of light on gene expression for secondary metabolism in agarwood and provide compelling new candidates towards the study of functional secondary metabolic components.

Steatotic livers are susceptible to cold ischemia, which is thought to be secondary to mitochondrial dysfunction. Ischemic preconditioning (IPC) has been reported to improve liver function in the setting of warm ischemia/reperfusion injury, but the effect of IPC on steatotic liver mitochondrial function (MF) with cold ischemia has not been previously evaluated. We aimed to evaluate MF with various severities of hepatic steatosis after various durations of cold ischemia storage with or without IPC. Male Sprague-Dawley rats were fed a normal diet or a high-fat/high-sucrose diet for 1, 2, or 4 weeks to induce mild (<30%), moderate (30%-60%), or severe (>60%) macrovesicular steatosis, respectively. Liver MF was tested with high-resolution respirometry after 1.5, 4, 8, 12, 18, and 24 hours of cold ischemia. Rats in each group (n = 10) underwent 10 minutes of IPC or no IPC before cold ischemia. The baseline (time 0) respiration was similar for lean and severely steatotic livers despite decreased mitochondrial complex I (C-I) activity in severely steatotic livers. Hepatic steatosis was associated with increased C-I-mediated leaks and decreased respiratory control ratios (RCRs) after cold ischemia. Mildly, moderately, and severely steatotic livers showed significantly lower RCRs after 8, 1.5, and 1.5 hours of cold ischemia, respectively, in comparison with lean livers. IPC restored RCRs in mildly steatotic livers to levels comparable to those in lean livers for up to 24 hours of cold ischemia via the attenuation of C-I-mediated leaks, but it had no beneficial effect on moderately and severely steatotic livers. In conclusion, steatotic livers exhibited apparent mitochondrial dysfunction through an alteration in C-I activity, and this made them more susceptible to prolonged cold ischemia. The clinically based IPC protocol used here restored MF in cases of mild hepatic steatosis by attenuating C-I-mediated leaks after prolonged cold ischemia, but it did work not in livers with moderate or severe steatosis., (© 2015 American Association for the Study of Liver Diseases.)

Background: Evacuatory dysfunction after distal colorectal resection varies from incontinence to obstructed defaecation and is termed anterior resection syndrome. The aim of this study was to identify risk factors for the development of anterior resection syndrome., Methods: All anterior resections undertaken at Auckland Hospital from 2002 to 2012 were retrospectively evaluated. An assortment of patient and peri-operative variables were recorded. Cases were stratified by the occurrence of anterior resection syndrome symptoms from 1 to 5 years post-operatively., Results: A total of 277 patients were identified. Prevalence of anterior resection syndrome decreased progressively from 61 % at 1 year to 43 % at 5 years. Univariate analysis identified anastomotic height, surgeon, pT stage, procedure year and temporary diversion ileostomy as recurring significant correlates (p < 0.05). Logistic regression identified lower anastomotic height (odds ratio (OR) 2.11, 95 % confidence interval (CI) 1.05-4.27; p = 0.04) and obstructive presenting symptoms (OR 6.71, 95 % CI 1.00-44.80; p = 0.05) as independent predictors at 1 and 2 years, respectively. Post-operative chemotherapy was a predictor at 1 year (OR 1.93, 95 % CI 1.04-3.57; p = 0.03). Temporary diverting ileostomy was an independent predictor at 2 (OR 2.49, 95 % CI 1.04-5.95; p = 0.04), 3 (OR 4.17, 95 % CI 1.04-16.78; p = 0.04), 4 (OR 8.05, 95 % CI 1.21-53.6; p = 0.03), and 5 years (OR 49.60, 95 % CI 2.17-1134.71; p = 0.02) after adjusting for anastomotic height., Conclusions: Anastomotic height, post-operative chemotherapy and obstructive presenting symptoms were independent predictors at 1 and 2 years. Temporary diversion ileostomy was an independent predictor for the occurrence of anterior resection syndrome at 2, 3, 4 and 5 years even after correcting for anastomotic height. Prospective assessment is required to facilitate more accurate risk factor analysis.

A series of novel pyrazole amide derivatives 3a-3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV) with different in vivo and in vitro modes at 500 μg/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV) compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3).

Background: Steatotic livers are vulnerable to the deleterious effects of ischaemia-reperfusion injury (IRI) that occur after hepatic surgery. Ischaemic preconditioning (IPC) has been shown to abrogate the effects of IRI in patients undergoing hepatic surgery. Experimental studies have suggested that IPC may be beneficial in steatotic livers subjected to IRI., Objective: The aim of this systematic review was to evaluate the effects of IPC on steatotic livers following hepatic IRI in experimental models., Methods: An electronic search of the OVID Medline and EMBASE databases was performed to identify studies that reported clinically relevant outcomes in animal models of hepatic steatosis subjected to IPC and IRI., Results: A total of 1093 articles were identified, of which 18 met the inclusion criteria. There was considerable heterogeneity in the type of animal model, and duration and type of IRI. Increased macrovesicular steatosis (> 30%) was associated with a poor outcome following IRI. Ischaemic preconditioning was found to be beneficial in > 30% steatotic livers and provided for decreased histological damage, improved liver function findings and increased survival., Conclusions: Experimental evidence supports the use of IPC in steatotic livers undergoing IRI. These findings may be applicable to patients undergoing liver surgery. However, clinical studies are required to validate the efficacy of IPC in this setting., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery., Methods: An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies., Results: 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection., Conclusions: Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC.

In this research, we prepared composite films via covalent coupling of CdSe quantum dots (QDs) to graphene through the direct binding of aryl radicals to the graphene surface. To compare the carrier transport with the CdSe aryl binding graphene film, we prepared CdSe pyridine capping graphene films through the pi-pi interactions of noncovalent bonds between the graphene and pyridine molecules. The photovoltaic devices were fabricated from the two hybrid films using the electrophoretic deposition method on flexible substrates. Even though the two hybrid films have the same amount of QDs and graphene, time-resolved fluorescence emission decay results show that the emission lifetime of the CdSe aryl group binding graphene film is significantly shorter than that of the pyridine capping CdSe-graphene. The quantum efficiency and photocurrent density of the device fabricated from CdSe aryl binding graphene were also higher than those of the device fabricated from pyridine capping CdSe-graphene. These results indicated that the carrier transport of the QD-graphene system is not related to the additive effect from the CdSe and graphene components but rather is a result of the unique interactions between the graphene and QDs. We could expect that these results can be useful in designing QD-graphene composite materials, which are applied in photovoltaic devices.

Background: Agarwood is derived from Aquilaria trees, the trade of which has come under strict control with a listing in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Many secondary metabolites of agarwood are known to have medicinal value to humans, including compounds that have been shown to elicit sedative effects and exhibit anti-cancer properties. However, little is known about the genome, transcriptome, and the biosynthetic pathways responsible for producing such secondary metabolites in agarwood., Results: In this study, we present a draft genome and a putative pathway for cucurbitacin E and I, compounds with known medicinal value, from in vitro Aquilaria agallocha agarwood. DNA and RNA data are utilized to annotate many genes and protein functions in the draft genome. The expression changes for cucurbitacin E and I are shown to be consistent with known responses of A. agallocha to biotic stress and a set of homologous genes in Arabidopsis thaliana related to cucurbitacin bio-synthesis is presented and validated through qRT-PCR., Conclusions: This study is the first attempt to identify cucurbitacin E and I from in vitro agarwood and the first draft genome for any species of Aquilaria. The results of this study will aid in future investigations of secondary metabolite pathways in Aquilaria and other non-model medicinal plants.

Background: Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation., Methods: Livers from 10-week old leptin-deficient obese (ob/ob, n = 9) and lean C57 mice (n = 9) were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity., Results: Ob/ob and lean mice livers showed severe (>60%) macrovesicular and mild (<30%) microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP) levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers., Conclusions: Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in steatotic donor livers.

Backgrounds and Aim: Current assessment of pre-operative liver function relies upon biochemical blood tests and histology but these only indirectly measure liver function. Mitochondrial function (MF) analysis allows direct measurement of cellular metabolic function and may provide an additional index of hepatic health. Conventional MF analysis requires substantial tissue samples (>100 mg) obtained at open surgery. Here we report a method to assess MF using <3 mg of tissue obtained by a Tru-cut® biopsy needle making it suitable for percutaneous application., Methods: An 18G Bard® Max-core® biopsy instrument was used to collect samples. The optimal Tru-cut® sample weight, stability in ice-cold University of Wisconsin solution, reproducibility and protocol utility was initially evaluated in Wistar rat livers then confirmed in human samples. MF was measured in saponin-permeabilized samples using high-resolution respirometry., Results: The average mass of a single rat and human liver Tru-cut® biopsy was 5.60±0.30 and 5.16±0.15 mg, respectively (mean; standard error of mean). Two milligram of sample was found the lowest feasible mass for the MF assay. Tissue MF declined after 1 hour of cold storage. Six replicate measurements within rats and humans (n = 6 each) showed low coefficient of variation (<10%) in measurements of State-III respiration, electron transport chain (ETC) capacity and respiratory control ratio (RCR). Ischemic rat and human liver samples consistently showed lower State-III respiration, ETC capacity and RCR, compared to normal perfused liver samples., Conclusion: Consistent measurement of liver MF and detection of derangement in a disease state was successfully demonstrated using less than half the tissue from a single Tru-cut® biopsy. Using this technique outpatient assessment of liver MF is now feasible, providing a new assay for the evaluation of hepatic function.

Composites of electrospun poly(ethylene oxide) (PEO) fibers and silver nanoparticles (Ag NPs) were used as a soft template for coating with TiO2 by atomic layer deposition (ALD). Whereas the as-deposited TiO2 layers on PEO fibers and Ag NPs were completely amorphous, the TiO2 layers were transformed into polycrystalline TiO2 nanotubes (NTs) with embedded Ag NPs after calcination. Their plasmonic effect can be controlled by varying the thickness of the dielectric Al2 O3 spacer between Ag NPs and dye molecules by means of the ALD process. Electronic and spectroscopic analyses demonstrated enhanced photocurrent generation and solar-cell performance due to the intense electromagnetic field of the dye resulting from the surface plasmon effect of the Ag NPs., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ethnopharmacological Relevance: Caesalpinia sappan L. is distributed in Southeast Asia and also used as herbal medicine for the treatment of various diseases such as burning sensations, leprosy, dysentery, osteoarthritis and rheumatoid arthritis (RA). The overproduction of IL-6 plays an important role in the prognosis of RA, but the active compounds from the extracts of Caesalpinia sappan L. suppressing IL-6 production remain unknown., Aims of the Study: Identifying the main active compounds of Caesalpinia sappan L. extracts inhibiting the IL-6 production in LPS-stimulated RAW 264.7 cells by partial least squares (PLS)., Materials and Methods: Sixty-four samples with different proportions of compounds were prepared from Caesalpinia sappan L. by supercritical CO2 fluid extraction (SCFE) and refluxing. Each of 64 samples was applied to RAW 264.7 cells with LPS to evaluate whether IL-6 production by LPS is affected by addition of each sample. The IL-6 production in medium was determined by ELISA and the inhibitory activity of each sample was analyzed. In addition, the fingerprints of these 64 samples were also established by ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS). We used the PLS, a simplified method, to evaluate the results from IL-6 production and fingerprints., Results: Each of 64 samples markedly suppressed LPS-induced IL-6 production in RAW cells. The fingerprints by UPLC-MS clearly revealed variations among 64 samples produced in different extract conditions. The PLS analysis with IL-6 production and fingerprints by UPLC-MS suggested that the peaks 71, 93, 150, 157, 168 have more influence on the inhibitory activity of Caesalpinia sappan L. extracts. The peaks 71, 93, 150 are likely representing sappanone A, protosappanin E and neoprotosappanin, respectively. The peaks 157 and 168 are still at large., Conclusion: This is the first report that sappanone A, protosappanin E, neoprotosappanin and two unidentified compounds can be considered as possible active compounds that might inhibit IL-6 production. Further studies are needed to confirm the effectiveness of these five compounds on IL-6 production and possible mechanism., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The impact of hepatic steatosis on outcome following hepatic ischemia-reperfusion injury (IRI) remains controversial with conflicting clinical results. A number of experimental studies have been published examining the relationship between hepatic steatosis and IRI. This systematic review evaluates these experimental studies., Methods: An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to identify studies that reported relevant outcomes in animal models of hepatic steatosis subjected to IRI., Results: A total of 1314 articles were identified, of which 33 met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration, and type of IRI and reporting of histological findings. Increased macrovesicular steatosis (>30%) was associated with increased histological damage, liver function derangement, and reduced survival. Increased duration of warm or cold ischemia had a negative impact on all outcomes measured. Microvesicular steatosis did not influence outcome., Conclusions: Findings from this systemic review support the hypothesis that livers with >30% macrovesicular steatosis are less tolerant of IRI. Clinically, it is likely that these findings are applicable to patients undergoing hepatic resection, but further studies are required to confirm these data.

We demonstrate that the use of poly(vinyl pyrrolidone) (PVP) and acetic acid during the synthesis of TiO(2) nanotubes may result in the synthesis of single-crystal-like anatase TiO(2) with a mainly exposed and chemically active (001) facet. An enhancement in the overall conversion efficiency of dye-sensitized solar cells was observed in a photoanode consisting of TiO(2) single-crystal-like anatase exposed (001) facets.

Objectives: The Allergic rhinitis and its impact on asthma (ARIA) guidelines were suggested for use to classify allergic rhinitis (AR). However, few studies have been performed in Asians. The objective of this study is to identify the clinical characteristics of AR in Korean patients according to the ARIA guidelines., Methods: For the study, 610 patients who had been diagnosed with allergic rhinitis at Seoul National University Bundang Hospital and 545 patients who had been diagnosed with allergic rhinitis at 3 local clinics were included. All the patients were categorized into 4 groups, such as the mild intermittent, mild persistent, moderate-severe intermittent and moderate-severe persistent groups. The patients were given a questionnaire on allergic rhinitis-related symptoms and they underwent blood tests, including the blood eosinophil count and the serum total IgE level., Results: The most prevalent type was the moderate-severe persistent group (34.7%), and the moderate-severe intermittent group (17.1%) was the rarest. There were significant differences among the 4 groups for olfaction (P<0.001), self-awareness of rhinitis (P=0.013), a previous history of AR (P<0.001), self-awareness of asthma (P=0.001) and allergic conjunctivitis (P<0.001). On the allergy laboratory tests, there was a significant difference between the groups for the eosinophi count (P=0.004). The number of blood eosinophil was more in the persistent groups than in the intermittent groups., Conclusion: According to the ARIA guidelines, the moderate-severe persistent group was the most prevalent for Korean patients. Blood eosinophilia and olfactory dysfunction were the most severe in the moderate-severe persistent group.

Although the LXXLL motif of nuclear receptor (NR) coactivators is essential for interaction with NRs, its role has not been assessed in unbiased animal models. The nuclear receptor coactivator 6 (NCoA6; also AIB3, PRIP, ASC-2, TRBP, RAP250, or NRC) is a coactivator containing an N-terminal LXXLL-1 (L1) and a C-terminal L2. L1 interacts with many NRs, while L2 interacts with the liver X receptor alpha (LXRalpha) and the estrogen receptor alpha (ERalpha). We generated mice in which L2 was mutated into AXXAL (L2m) to disrupt its interaction with LXRalpha and ERalpha. NCoA6(L2m/L2m) mice exhibited normal reproduction, mammary gland morphogenesis, and ERalpha target gene expression. In contrast, when treated with an LXRalpha agonist, lipogenesis and the LXRalpha target gene expression were significantly reduced in NCoA6(L2m/L2m) mice. The induction of Cyp7A1 expression by a high-cholesterol diet was impaired in NCoA6(L2m/L2m) mice, which reduced bile acid synthesis in the liver and excretion in the feces and resulted in cholesterol accumulation in the liver and blood. These results demonstrate that L2 plays a tissue- and NR-specific role: it is required for NCoA6 to mediate LXRalpha-regulated lipogenesis and cholesterol/bile acid homeostasis in the liver but not required for ERalpha function in the mammary gland.

BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.

Two new cytotoxic sterols, 24-methylcholesta-5,24(28)-diene-3beta, 15beta,19-triol (1) and 24-methylcholesta-5,24(28)-diene-3beta, 19-diol-7-one (2), as well as four cytotoxic sterols, 24-methylcholesta-5,24(28)-diene-3beta,19-diol (3), 24-methylcholesta-5,24(28)-diene-3beta,19-diol-7beta-mono aetate (4), 24-methylcholesta-5,24(28)-diene-3beta,7beta,19-triol (5), and 24-methylcholesta-24(28)-ene-3beta,5alpha,6beta,19-tet raol (6), have been isolated from the soft coral Nephthea erecta. The structures of compounds 1 and 2 were determined by spectral analysis.