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Hui-Ling Chen,1,2,* Yi-Bin Zeng,3,* Zheng-Yan Zhang,1,2,* Chao-Yue Kong,1,2 Shi-Long Zhang,1,2 Zhan-Ming Li,1,2 Jia-Ting Huang,1,2 Ya-Yun Xu,1,2 Yu-Qin Mao,1,2 Pei-Ran Cai,1,2 Bing Han,1,2 Wu-Qing Wang,3 Li-Shun Wang1,2 1Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of China; 2Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of China; 3Dermatological Department, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Shun Wang; Wu-Qing WangCenter for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of ChinaTel +86 21-64923400-6244Email lishunwang@fudan.edu.cn; wuqingw2006@sina.comBackground: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.Objective: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.Methods: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.Results: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.Conclusion: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.Keywords: gut microbiota, cutaneous microbiome, psoriasis, fecal microbiota transplantation, Lactobacillus reuteri, Th17

A new triterpenoid saponin ( 1 ), along with five known compounds ( 2-6 ), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro .

Precise positioning of the histone-H3 variant, CENP-A, ensures centromere stability and faithful chromosomal segregation. Mislocalization of CENP-A to extra-centromeric loci results in aneuploidy and compromised cell viability associated with formation of ectopic kinetochores. The mechanism that retargets mislocalized CENP-A back to the centromere is unclarified. We show here that the downregulation of the histone H3 lysine 36 (H3K36) methyltransferase Set2 can preserve centromere localization of a temperature-sensitive mutant cnp1-1 Schizosaccharomyces pombe CENP-A (SpCENP-A) protein and reverse aneuploidy by redirecting mislocalized SpCENP-A back to centromere from ribosomal DNA (rDNA) loci, which serves as a sink for the delocalized SpCENP-A. Downregulation of set2 augments Swc2 (SWR1 complex DNA-binding module) expression and releases histone chaperone Ccp1 from the centromeric reservoir. Swc2 and Ccp1 are directed to the rDNA locus to excavate the SpCENP-Acnp1-1, which is relocalized to the centromere in a manner dependent on canonical SpCENP-A loaders, including Mis16, Mis17 and Mis18, thereby conferring cell survival and safeguarding chromosome segregation fidelity. Chromosome missegregation is a severe genetic instability event that compromises cell viability. This mechanism thus promotes CENP-A presence at the centromere to maintain genomic stability., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Intestinal colonization with carbapenem-resistant Enterobacterales (CRE) has been shown as a significant risk factor for subsequent CRE infections, especially in intensive care units (ICUs). The aim of this study was to determine the prevalence of intestinal CRE colonization among ICU patients in a Chinese tertiary hospital. Fecal sample screenings for CRE were performed on ICU patients weekly. Antibiotic-susceptibility profile of CRE strains was determined using the Vitek-2 analysis system and broth microdilution method. The carbapenemases of all isolates were determined by phenotypes and genotypes. Clonal relatedness was analyzed by pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was used to identify the multilocus sequence type (ST), plasmid replicons, and insertion sequences (ISs) of isolates. The overall colonization rate of CRE was 40.4% (82/203). A total of 84 CRE strains were detected, mostly with Klebsiella pneumoniae (92.9%). Antibiotic susceptibility testing profile revealed that 84 CRE strains were resistant to most antibiotics except for tigecycline and colistin. The carbapenemase-encoding genes including bla KPC-2 , bla NDM-1 , and bla IMP-4 were detected, and bla KPC-2 was the predominant genotype (90.8%). A total of 9 STs were identified among 84 CRE strains, and ST11 was the most common type (83.3%). A variety of mobile genetic elements, including plasmids and ISs, were detected via online tool prediction. PFGE analysis of the 78 K. pneumoniae strains showed 8 different pulsotypes, and pulsotype A was highly prevalent. This study found that the prevalence of CRE colonization was alarmingly high in the ICU, and that effective infection control measures are urgently needed to prevent the dissemination of CRE.

Two new triterpenoid saponins ( 1 and 2 ), together with two known saponins ( 3 and 4 ) were isolated from Bupleurum marginatum Wall. ex DC. Their structures were elucidated by the comprehensive spectroscopic analysis. Compounds 1 and 2 represented the rare example of an oleanane-type triterpenoid with two sugar moieties at C-3 and C-28. The cytotoxic activity of four compounds was evaluated against normal heptocell BRL-3A in vitro .

Objective: Circular RNAs (circRNAs) participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases. This study aimed to investigate the role of circRNAs in neural tube defects (NTDs)., Method: We characterized circRNA-associated competitive endogenous RNA (ceRNA) networks in brain tissue of low folate -induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing. The expression levels of Circzfp644, miR-20-5p and Gas7 were detected by RT-PCR. Gas7 and Circzfp644 functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells (F9 cells), and luciferase gene reporter assay was assessed in the F9 cells. In addition, the expression levels of Circzfp644, miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues., Results: We detected 57 circRNA transcripts, 16 miRNAs, and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control (normal) tissues. Circzfp644 shared miRNA response elements with the growth arrest specific 7 ( Gas7 ) gene and competitively bound with miR-20-5p to increase the expression of Gas7 . Downregulation of Circzfp644 and Gas7 and upregulation of miR-20-5p were found in human NTD tissue., Conclusion: This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Poultry is one of the most commonly farmed species and the most widespread meat industries. However, numerous poultry flocks have been long threatened by pathogenic bacterial infections, especially antimicrobial resistant pathogens. Here the prevalence and the antimicrobial resistance (AMR) profiles of bacterial pathogens isolated from poultry in Jiangxi Province, China were investigated. From 2020 to 2022, 283 tissue and liquid samples were collected from clinically diseased poultry, including duck, chicken, and goose, with an overall positive isolation rate of 62.90%. Among all the 219 bacterial isolates, 29 strains were gram-positive and 190 strains were gram-negative. Major bacteria species involved were avian pathogenic Escherichia coli (APEC; 57.53%; 126/219), followed by Salmonella spp. (11.87%, 26/219), Pasteurella multocida (6.39%, 14/219), and Staphylococcus spp. (1.22%, 11/219). Antimicrobial susceptibility testing showed the APEC isolates displayed considerably higher levels of AMR than the Salmonella and P. multocida isolates. The APEC isolates showed high resistance rate to amoxicillin (89.68%), ampicillin (89.68%), and florfenicol (83.33%), followed by streptomycin (75.40%), cefradine (65.87%), and enrofloxacin (64.29%). Multidrug-resistant isolates were observed in APEC (99.21%), Salmonella spp. (96.16%), and P. multocida (85.71%), and nearly 3 quarters of the APEC strains were resistant to 7 or more categories of antimicrobial drugs. Moreover, bla NDM genes associated with carbapenemase resistance and mcr-1 associated with colisitin resistance were detected in the APEC isolates. Our findings could provide evidence-based guidance for veterinarians to prevent and control bacterial diseases, and be helpful for monitoring the emerging and development of AMR in poultry bacterial pathogens., (Copyright © 2023. Published by Elsevier Inc.)

5-Fluorouracil (5-FU) is a conventional chemotherapeutic drug widely used in clinics worldwide, but development of resistance that compromises responsiveness remains a major hurdle to its efficacy. The mechanism underlying 5-FU resistance is conventionally attributed to the disruption of nucleotide synthesis, even though research has implicated other pathways such as RNA processing and chromatin dysregulation. Aiming to clarify resistance mechanisms of 5-FU, we tested the response of a collection of fission yeast ( Schizosaccharomyces pombe ) null mutants, which confer multiple environmental factor responsiveness (MER). Our screen identified disruption of membrane transport, chromosome segregation and mitochondrial oxidative phosphorylation to increase cellular susceptibility towards 5-FU. Conversely, we revealed several null mutants of Ino80 complex factors exhibited resistance to 5-FU. Furthermore, attenuation of Ino80 function via deleting several subunit genes reversed loss of chromosome-segregation fidelity in 5-FU in the loss-of-function mutant of the Argonaute protein, which regulates RNA interference (RNAi)-dependent maintenance of pericentromeric heterochromatin. Our study thus uncovered a critical role played by chromatin remodeling Ino80 complex factors in 5-FU resistance, which may constitute a possible target to modulate in reversing 5-FU resistance., Competing Interests: The authors declare no conflict of interest.

Chemical constituents in soft coral Sarcophyton glaucum were separated and purified by various chromatographic methods. Based on the spectral data, physicochemical properties, and comparison with the data reported in the literature, nine cembranoids, including a new cembranoid named sefsarcophinolide(1) together with eight known cembranoids, namely(+)-isosarcophine(2), sarcomilitatin D(3), sarcophytonolide J(4),(1S,3E,7E,13S)-11,12-epoxycembra-3,7,15-triene-13-ol(5), sarcophytonin B(6),(-)-eunicenone(7), lobophytin B(8), and arbolide C(9), were identified. As revealed by biological activity experiment results, compounds 2-6 had weak acetylcholinesterase inhibitory activity, and compound 5 displayed weak cytotoxicity against K562 tumor cell line.

Objective: We performed this longitudinal 2-year follow-up study to determine the incidence and risk factors associated with MCI in middle-aged and older adults., Subjects and Methods: This community-based longitudinal study was conducted in adults aged ≥ 50 years with normal cognitive function in Shanghai community, China, over a period of two years. Information about the socio-demographic, behavioral, anthropometric, and biochemical parameters was obtained at the baseline and cognitive function was assessed at the end of the follow-up period using the Montreal cognitive assessment tool., Results: A total of 985 participants aged ≥ 50 years were included in the analysis. Incidence of MCI during the 2-year follow-up period among the study participants was 26.7% (95% CI: 24.0%-29.6%). Participants with lower level of education [primary - adjusted RR=2.79 (95% CI: 1.38-5.64 and secondary - adjusted RR=1.62 (95% CI: 1.17-2.24)], with history of cerebral infarction (adjusted RR=1.49; 95% CI: 1.05-2.12), history of cerebral hemorrhage (adjusted RR=3.20; 95% CI: 1.22-8.40) were found to have significantly higher risk of MCI. Regular tea consumption was associated with significantly reduced risk of MCI development (adjusted RR=0.69; 95% CI: 0.49-0.96)., Conclusions: Our study found that one in four participants developed MCI during the 2-year follow-up period. Lower educational level, history of cerebral infarction, cerebral hemorrhage and tea consumption were significant determinants of MCI incidence. The target groups identified in this study should be closely monitored with regular follow-up investigations for early diagnosis and appropriate management of the condition.

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe infections in humans and the swine industry. Acquisition and utilization of available carbon sources from challenging host environments is necessary for bacterial pathogens to ensure growth and proliferation. Glycogen is abundant in mammalian body and may support the growth of SS2 during infection in hosts. However, limited information is known about the mechanism between the glycogen utilization and host adaptation of SS2. Here, the pleiotropic effects of exogenous glycogen on SS2 were investigated through transcriptome sequencing. Analysis of transcriptome data showed that the main basic metabolic pathways, especially the core carbon metabolism pathways and virulence-associated factors, of SS2 responded actively to glycogen induction. Glycogen induction led to the perturbation of the glycolysis pathway and citrate cycle, but promoted the pentose phosphate pathway and carbohydrate transport systems. Extracellular glycogen utilization also promoted the mixed-acid fermentation in SS2 rather than homolactic fermentation. Subsequently, apuA , a gene encoding the unique bifunctional amylopullulanase for glycogen degradation, was deleted from the wild type and generated the mutant strain Δ apuA . The pathogenicity details of the wild type and Δ apuA cultured in glucose and glycogen were investigated and compared. Results revealed that the capsule synthesis or bacterial morphology were not affected by glycogen incubation or apuA deletion. However, extracellular glycogen utilization significantly enhanced the hemolytic activity, adhesion and invasion ability, and lethality of SS2. The deletion of apuA also impaired the pathogenicity of bacteria cultured in glucose, indicating that ApuA is indeed an important virulence factor. Our results revealed that exogenous glycogen utilization extensively influenced the expression profile of the S. suis genome. Based on the transcriptome response, exogenous glycogen utilization promoted the carbon adaption and pathogenicity of SS2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Tan, Zhang, Li, Ji, Fang, Wu, Rao, Zeng and Yang.)

Salt stress is one of the major abiotic factors limiting the productivity of bermudagrass ( Cynodon dactylon ). However, the role of hormonal reprogramming and crosstalk in regulating root growth and salt tolerance in bermudagrass was not reported. Here, we examined the physiological and hormonal responses of two contrasting bermudagrass genotypes; 'C43,' salt-tolerant 'C198' salt-sensitive. Under salt stress, 'C43' had better membrane stability and higher photosynthetic activity than the 'C198.' Salt stress promoted root growth and improved root/shoot ratio and root activity in 'C43,' but the root growth of 'C198' was inhibited by salt stress, leading to diminished root activity. The two bermudagrass genotypes also showed critical differences in hormonal responses, especially in the roots. The root contents of indole-3-acetic acid (IAA), cytokinin derivatives, such as trans- zeatin riboside ( t ZR) and dihydrozeatin riboside (DHZR) were increased in 'C43,' but decreased in 'C198' when exposed to salt stress. The root growth rate was positively correlated with the root IAA, tZR and DHZR, indicating their crucial role in root growth under salt stress. The expressions of TAA / YUCCA and CYP735A involved in IAA and tZR biosynthesis were induced by salt stress in 'C43,' but inhibited in 'C198,' leading to reduced hormone accumulations. Salt stress decreased the iP, tZ, and DHZ content in the roots of both genotypes, and no significant difference was observed between the two genotypes. Salt stress reduced the content of GA 3 in both genotypes by inhibiting GA20ox and GA2ox genes, which could be attributed to the reduced shoot growth in both genotypes. The increased ABA level by salt stress was significantly higher in 'C198' than 'C43.' Furthermore, there were positive and negative correlations between different hormones and root growth, suggesting that root growth could be regulated by complex hormonal reprogramming and crosstalk. This study provides a foundation for understanding the underlying mechanisms of hormonal-mediated root growth and salt tolerance in bermudagrass., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Wassie, Liu, Deng, Zeng, Xu and Hu.)

Although many studies have already described the physiological effects of bee products, such as honey, propolis, pollen, and royal jelly, on livestock farming, the health benefits of the honeycomb are still not fully understood. The problem of drug residues and bacterial resistance caused by the abuse of antibiotics is becoming increasingly serious. For this reason, a safe, green substitute has to be sought. We conducted a comparative study of honeycomb extract (HE) and an antibiotic on growth performance, carcass traits, immunity, antioxidant function and intestinal microorganisms of yellow bantam broilers. A total of four hundred eighty 21-day-old female yellow bantam broilers were randomly divided into 5 groups of 6 replicates of 16 birds each. The 5 groups were as follows, with birds receiving a basal diet supplemented with 150 ppm (mg/kg) of chlortetracycline (CTE), a basal diet without HE (control group), and a basal diet with 0.1%, 0.15%, or 0.2% HE for 60 days. The results showed that HE addition significantly increased average daily feed intake (ADFI), average daily gain (ADG), decrease feed gain ratio (F/G) from 21 to 80 and 51 to 80 days of age compared to the control group, with all 3 HE addition groups having statistically identical values to the antibiotic group. HE implementation dramatically increased spleen index, serum immunoglobulin A (IgA), immunoglobulin M (IgM,), glutathione peroxide (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and total cecum bacteria and Lactobacillus compared to the control group, numerically at the same level as, or even better than, the antibiotic group. HE and CTE both markly reduced serum malondialdehyde (MDA) concentration compared to the control group, with higher concentrations of HE reducing the effect more dramatically than antibiotics. Both HE and CTE significantly raised dressed yield compared to the control group. In summary, HE, as a potential antibiotic alternative, improved growth performance, carcass traits, immune function, serum antioxidant capacity and intestinal microorganisms in yellow bantam broilers. According to the cubic regression analyses, the recommended supplemental dose of HE was calculated to be 0.15 to 0.17% for female yellow bantam broilers between 21 and 80 d of age., (Copyright © 2022. Published by Elsevier Inc.)

Avian leukosis virus (ALV) induces multiple tumors in chicken and is still prevalent in a lot of local flocks in China. In this study, we analyzed the ALV infection status in an Anyi tile-like gray chicken flock by DF1-cells isolation, virus identification, and genome sequencing. Results showed a 29% (29/100) ALV positive rate in this flock. Homology analysis based on env genes illustrated that all these stains belong to subgroup J (92-100% identities) and can be further divided into 5 batches, suggesting a higher diversity of ALV-J within the same flock. The whole-genome analysis of representative stains from each batch confirmed the close relationship between these isolated strains with previously reported strains from different regions (Guangxi, Shandong, and Heilongjiang), revealing the enrichment of different strains in Anyi tile-like grey chickens. This study provides the epidemiological data of ALV-J in a special chicken flock and a reference for the further eradication of ALV in China., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

A new polychiral bisabolane sesquiterpene, bisabolanoic acid A ( 1 ), was isolated from the mangrove-derived fungus Colletotrichum sp. SCSIO KcB3-2. Its planar structure was identified on the basis of spectroscopic data analysis (HRESIMS, 1D, and 2D NMR), and the absolute configurations of three chiral carbons were determined by experimental and calculated electronic circular dichroism (ECD) and optical rotatory dispersion (ORD), together with Mo 2 (OAc) 4 -induced ECD methods. Bisabolanoic acid A ( 1 ) showed moderate inhibitory activity against acetylcholinesterase (AChE) with IC 50 value of 2.2 μM, and the in silico molecular docking was also performed.

Background: Oxidative stress may play an important role in the pathogenesis of schizophrenia (SCH), and there is considerable indirect evidence that hypoxia is closely related to SCH, but direct evidence of hypoxia in SCH has never been found. Methods: In this study, superoxide dismutase (SOD), venous blood gas, and Positive and Negative Syndrome Scale (PANSS) were examined in 40 SCH patients and compared with those of 40 healthy controls. The patients were treated with combination of atypical antipsychotics and Ditan Huayu Lishen decoction (a Chinese medicine decoction) and examined in the acute and stable period, respectively. Comparisons of indicators between two groups were performed using an independent-samples t -test, comparison of indicators between the acute and stable periods in the SCH group was performed using paired-samples t -test. Pearson correlation and multiple linear regression analyses were performed to investigate the relationships between the effect indicators. Results: Higher venous pH, PvO 2 , and fasting blood glucose levels and lower SOD, lactic acid, and PvCO 2 levels were found in SCH patients compared with the control group; SOD was negatively correlated with the general psychopathology subscale score (PANSS-G), and PvO 2 levels were closely related to venous pH in SCH and related to PvCO 2 in the control group. It was also found that SOD activity showed no significant difference in acute and stable period, whereas PvO 2 showed a downward trend, and venous pH was decreased significantly after treatment. Both the venous pH and PvO 2 were higher in patients with SCH than that in healthy controls. Conclusion: It suggests that histogenous hypoxia and acid retention exist in relation to SCH, and there is an improvement of acid retention and a downward trend in histogenous hypoxia after combination treatment. Venous pH, PvO 2 , and PvCO 2 are trait variables, but not state variables of SCH. The theory of histogenous hypoxia and acid retention can well explain the decrease in pH value and the increase in lactic acid in brain tissue of patients with SCH. Histogenous hypoxia and acid retention closely related to glucose metabolism. So they may play an important role in pathophysiology for SCH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Lu, Zhu, Zeng, Liu and Hu.)

Two new 2-(2-phenylethyl)chromone derivatives ( 1 - 2 ) were isolated from the ethyl acetate extract of artificial agarwood induced by holing method originating from Aquilaria sinensis (Lour.) Gilg, and they were isolated from this genus for the first time. The structures of these two new compounds were elucidated by extensive spectroscopic analyses, including UV, IR, one- and two-dimensional NMR and HRESIMS measurements. Bioassay tests of these two new compounds showed compounds 1 and 2 had weak inhibitory activity against acetylcholinesterase at a concentration of 50.0 μg/ml.

Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. Streptococcus suis , a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK ( m ultiple s ugar m etabolism protein K ), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in S. suis MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner in vitro Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ in vivo , and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall. IMPORTANCE Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen Streptococcus suis and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. In vitro protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment., (Copyright © 2021 Tan et al.)

Aims: This study aimed to investigate the antimicrobial resistance (AMR) profiles and genotypes of Streptococcus suis from Jiangxi Province, China., Methods and Results: A total of 314 nasal swab samples were collected from clinically healthy pigs, with a positive isolation rate of S. suis of 34·08%. Antimicrobial susceptibility testing showed that more than 80% of the isolates were susceptible to vancomycin, penicillin, minocycline and chloramphenicol. A high frequency of resistance to clindamycin, tetracycline, clarithromycin and erythromycin was observed. All of the isolates were resistant to three or more categories of antimicrobials. The erm(B) and tet(O) served as the most frequent genotypes that contributed to lincosamide, macrolide and tetracycline resistances. A part of macrolide-resistant genotypes could not exhibit specific phenotypes. Finally, integrative and conjugative elements (ICEs) were identified in 28·97% of the isolates., Conclusions: The multidrug resistance of S. suis has widely emerged in Jiangxi Province. The most prevalent resistance genes and genotypes were similar to those in other regions or countries. The presence of ICEs is increasing the risk of horizontal transfer of AMR genes., Significance and Impact of the Study: The findings could provide guidance for the rational use of antimicrobial drugs and be helpful for monitoring the AMR information of S. suis in China., (© 2020 The Society for Applied Microbiology.)

Recent studies have shown that chromium (Cr) could alleviate the negative effects of heat stress on livestock and poultry, but there is little information available to laying ducks. This study aimed to investigate the effects of dietary addition of chromium propionate on laying performance, egg quality, serum biochemical parameters and antioxidant status of laying ducks under hot (average 32 °C) and humid (average 75% relative humidity) summer conditions. A total of 900 66-week-old weight- and laying-matched Shanma laying ducks were randomly divided into five treatments, each with 6 replicates of 30 individually caged birds. The birds were fed either a basal diet or the basal diet supplemented with either 200, 400, 600, or 800 μg/kg Cr as chromium propionate. All laying ducks were given feed and water ad libitum for 5 weeks. The results showed that dietary supplementation with chromium propionate significantly increased the laying rate and yolk colour score (P < 0.05). Treatment with 400 μg/kg Cr as chromium propionate significantly decreased the feed/egg ratio by 5.4% (P < 0.05). Increased supplemental Cr from 0 to 800 μg/kg resulted in an increase in albumen height and the Haugh unit linearly (P < 0.05). Increased supplemental Cr decreased serum cortisol (P < 0.001, linear; P = 0.008, quadratic), heat shock protein-70 (P < 0.001, linear; P = 0.007, quadratic) and glucose (P = 0.007, linear), whereas it increased serum insulin (P = 0.011, Linear), total protein (P = 0.006, linear; P = 0.048, quadratic) and albumin (P = 0.035, linear; P = 0.088, quadratic). Dietary Cr levels increased the activities of superoxide dismutase and glutathione peroxidase, the total antioxidant capacity linearly and quadratically (P < 0.05). A linear and quadratic (P < 0.05) decrease of the malondialdehyde concentrations in response to dietary Cr level was observed. These results indicated that dietary supplementation of Cr as chromium propionate, particularly at 800 μg/kg could beneficially affect the laying rate, egg quality and antioxidant function, as well as modulate the blood biochemical parameters of laying ducks under heat stress conditions., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway, and its loss of function through polymorphisms is often associated with human conditions, including cancer, congenital heart disease, and Down syndrome. MTHFR is also required in the maintenance of heterochromatin, a crucial determinant of genomic stability and precise chromosomal segregation. Here, we characterize the function of a fission yeast gene met11 + , which encodes a protein that is highly homologous to the mammalian MTHFR. We show that, although met11 + is not essential for viability, its disruption increases chromosome missegregation and destabilizes constitutive heterochromatic regions at pericentromeric, sub-telomeric and ribosomal DNA (rDNA) loci. Transcriptional silencing at these sites were disrupted, which is accompanied by the reduction in enrichment of histone H3 lysine 9 dimethylation (H3K9me2) and binding of the heterochromatin protein 1 (HP1)-like Swi6. The met11 null mutant also dominantly disrupts meiotic fidelity, as displayed by reduced sporulation efficiency and defects in proper partitioning of the genetic material during meiosis. Interestingly, the faithful execution of these meiotic processes is synergistically ensured by cooperation among Met11, Rec8, a meiosis-specific cohesin protein, and the shugoshin protein Sgo1, which protects Rec8 from untimely cleavage. Overall, our results suggest a key role for Met11 in maintaining pericentromeric heterochromatin for precise genetic inheritance during mitosis and meiosis.

Centromere integrity underlies an essential framework for precise chromosome segregation and epigenetic inheritance. Although centromeric DNA sequences vary among different organisms, all eukaryotic centromeres comprise a centromere-specific histone H3 variant, centromeric protein A (CENP-A), on which other centromeric proteins assemble into the kinetochore complex. This complex connects chromosomes to mitotic spindle microtubules to ensure accurate partitioning of the genome into daughter cells. Overexpression of CENP-A is associated with many cancers and is correlated with its mistargeting, forming extra-centromeric kinetochore structures. The mislocalization of CENP-A can be counteracted by proteolysis. The amino ( N )-terminal domain (NTD) of CENP-A has been implicated in this regulation and shown to be dependent on the proline residues within this domain in Saccharomyces cerevisiae CENP-A, Cse4. We recently identified a proline-rich GRANT motif in the NTD of Schizosaccharomyces pombe CENP-A (SpCENP-A) that regulates the centromeric targeting of CENP-A via binding to the CENP-A chaperone Sim3. Here, we investigated whether the NTD is required to confer SpCENP-A turnover (i.e., counter stability) using various truncation mutants of SpCENP-A. We show that sequential truncation of the NTD did not improve the stability of the protein, indicating that the NTD of SpCENP-A does not drive turnover of the protein. Instead, we reproduced previous observations that heterochromatin integrity is important for SpCENP-A stability, and showed that this occurs in an NTD-independent manner. Cells bearing the null mutant of the histone H3 lysine 9 methyltransferase Clr4 ( Δclr4 ), which have compromised constitutive heterochromatin integrity, showed reductions in the proportion of SpCENP-A in the chromatin-containing insoluble fraction of the cell extract, suggesting that heterochromatin may promote SpCENP-A chromatin incorporation. Thus, a disruption in heterochromatin may result in the delocalization of SpCENP-A from chromatin, thus exposing it to protein turnover. Taken together, we show that the NTD is not required to confer SpCENP-A protein turnover.

It is critical to accurately identify patients with severe acute pancreatitis (SAP) in a timely manner. This study aimed to develop a new simplified AP scoring system based on data from Chinese population.We retrospectively analyzed a consecutive series of 585 patients diagnosed with SAP at the Changhai hospital between 2009 and 2017. The new Chinese simple scoring system (CSSS) was derived using logistic regression analysis and was validated in comparison to 4 existing systems using receiver operating characteristic curves.Six variables were selected for incorporation into CSSS, including serum creatinine, blood glucose, lactate dehydrogenase, heart rate, C-reactive protein, and extent of pancreatic necrosis. The new CSSS yields a maximum total score of 9 points. The cut-offs for predicting mortality and severity (discriminating moderately SAP from SAP) were set as 6 points and 4 points respectively. Compared with 4 existing scoring systems, the area under the receiver operating characteristic of CSSS for prediction of mortality was 0.838, similar to acute physiology and chronic health evaluation II (0.844) and higher than Ranson's score (0.702, P < .001), bedside index of severity in acute pancreatitis (0.615), and modified computed tomography severity index (MCTSI) (0.736). For predicting SAP severity, CSSS was the most accurate (0.834), followed by acute physiology and chronic health evaluation II (0.800), Ranson's score (0.702), MCTSI (0.660), and bedside index of severity in acute pancreatitis (0.570). Further, the accuracy of predicting pancreatic infection with CSSS was the highest (0.634), similar to that of MCTSI (0.641).A new prognostic scoring system for SAP was derived and validated in a Chinese sample. This scoring system is a simple and accurate method for prediction of mortality.

Objective: We conducted a randomized trial aiming at improving patients' informed consent for undergoing endoscopic retrograde cholangiopancreatography (ERCP) in clinical care by comparing the efficacy of an additional educational video to written informed consent with that of written informed consent alone., Methods: This was a single-center, randomized controlled trial. Consecutive patients undergoing ERCP were randomized to a video education or a control group. An educational video detailing ERCP procedure plus standard written informed consent was administered to the video education group, while the control group reviewed standard written informed consent only. The primary outcome was the patients' perception of the risk or possibility of ERCP complications. Their perception of the benefits of ERCP, alternative treatments and overall satisfaction with the process of informed consent were also compared., Results: In total 205 patients were included in the study (104 in the control group and 101 in the video education group). Patients' comprehension of ERCP-related complications in the video education group was significantly increased (P < 0.001), and these patients were more likely to correctly identify the incidence of such complications. Significantly more patients in the video education group were very satisfied with informed consent process (87.1% vs 76.0%, P = 0.040) and fewer patients needed additional explanations (31.7% vs 47.1%, P = 0.024)., Conclusions: A supplementary educational video could greatly improve patient's understanding of ERCP procedure, in particular, its potential risks and complications, as well as their overall satisfaction with the process of informed consent (ClinicalTrials.gov no. NCT02810379)., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the cost-benefit and cost-effectiveness of current strategy for preventing mother-to-child transmission (PMTCT) of hepatitis B virus. Methods: A decision tree model with the Markov process was developed and simulated over the lifetime of a birth cohort in Zhejiang Province in 2016. The current PMTCT strategy was compared with universal vaccination and non-vaccination. Costs were assessed from social perspective. Benefits were the savings from reduced costs associated with disease and effectiveness were measured by quality-adjusted of life-years (QALY) gained. The net present value (NPV), cost-benefit ratio (BCR) and incremental cost-effectiveness ratio (ICER) were calculated. Univariate and Probabilistic Sensitivity Analyses (PSA) were performed to assess parameter uncertainties. The parameters of costs and utilities value of hepatitis B-related disease came from the results of the field survey, which were obtained by face-to-face questionnaire survey combined with inpatient medical records, including eight county and municipal hospitals in Jinhua, Jiaxing and Taizhou. A total of 626 outpatients and 523 inpatient patients were investigated. The annual total costs of infection was calculated by combining the costs of outpatient and inpatient. Results: The PMTCT strategy showed a net-gain as 38 323.78 CNY per person, with BCR as 21.10, which was higher than 36 357.80 CNY per person and 13.58 respectively of universal vaccination. Compared with universal vaccination, the PMTCT strategy would save 2 787.07 CNY per additional QALY gained for every person, indicating that PMTCT would be cost-saving. The most important parameters that could affect BCR and ICER were the vaccine coverage rate and costs of hepatitis B related diseases respectively. The PSA showed the PMTCT strategy was preferable as it would gain more QALY and save costs. Conclusions: The PMTCT strategy appeared as highly cost-beneficial and highly cost-effective. High vaccination rate was a key factor of high economic value.

Salmonella is one of the most important foodborne pathogens associated with animal and human diseases. In this study, 672 samples of fresh meat (pork, 347; chicken, 196; and duck, 129) were collected from retail markets in different provinces of China from 2010 to 2014. We identified 10 different serotypes among 80 Salmonella isolates, whereas 12 isolates were nonmotile precluding conventional identification of complete serotype. Among these 92 isolates, Salmonella enterica serovar Derby ( n  = 21) was the most prevalent serotype, followed by Salmonella Enteritidis ( n  = 17), Salmonella Typhimurium ( n  = 15), Salmonella Indiana ( n  = 9), Salmonella Agona ( n  = 7), and Salmonella Assinie ( n  = 5). Antimicrobial resistance testing for 18 antimicrobial agents revealed that all 92 isolates were resistant to at least 1 antimicrobial agent, and 39 different resistance profiles were identified. The highest resistance was to trimethoprim-sulfamethoxazole ( n  = 87), followed by tetracycline ( n  = 51), carbenicillin ( n  = 38), amoxicillin/A.clav ( n  = 30), and piperacillin ( n  = 24). Our results demonstrated that meats presented a potential public health risk, thereby underlining the necessity for local regulatory enforcement agencies in China to monitor salmonellosis.

With the accelerating process of population aging in China, social pension system has been rapidly developed, but its service quality remains poor. How to provide quality and efficient elderly care services has become a major livelihood issue of general public. The existing evaluation standards for service quality in the elderly care institutions vary greatly in terms of literature review and practice, and they have only single perspective and lack systematic review. Based on the three-dimensional theory of "structure-process-result" quality evaluation, this paper systematically compares and evaluates the evaluation index system and evaluation management mechanism of service quality of pension institutions in typical countries and regions, and provides an evidence-based basis for establishing an evaluation management system, which is in line with China's national conditions and covers evaluation principles, subject and object, regulation, rewards and punishments, and classifications.

Objective: To investigate the frailty status and related determinants among the elderly in China. Methods: Frailty index (FI) was applied to evaluate the frailty status of the elderly. Data used in this study was from the China Health and Retirement Longitudinal Study (CHARLS) in 2011-2015. Binary logistic regression analysis was carried out to identify the determinants related to the status on frailty. Results: The prevalence rates of frailty in the elderly were 18.7 % , 20.6 % and 28.4 % in 2011, 2013 and 2015, respectively. Being female or elderly under advanced age, were both associated with the higher level of FI. Factors as hip fracture, falls, alcohol intake more than once a month, and less participation in social activities etc ., might serve as the risk factors for frailty. Conclusion: Chinese elderly showed relatively high prevalence on frailty and with annual increasing trend. The status of frailty was related to factors as adverse events and unhealthy lifestyles. Comprehensive intervention strategies should be adopted in early life of the elderly to delay the development process of frailty.

Polydopamine (PDA) can be formed by monomeric self-polymerization in water. This convenient behavior was exploited to prepare a molecularly imprinted polymer (MIP) layer on the surface of multi-walled carbon nanotubes (MWCNTs) with sunset yellow (SY) as a template molecule. The prepared nanocomposites were characterized, and their electrochemical behavior towards SY was investigated. Under the optimized conditions, a glassy carbon electrode modified with the imprinted nanocomposite showed a highly selective and ultrasensitive electrochemical response to SY compared with the performance of control electrodes and previously reported electrochemical sensors for SY. The improved behavior of the developed sensor can be attributed to its superficial highly matched imprinted cavities on the excellent electrocatalytic matrix of MWCNTs and the electronic barrier of the non-imprinted PDA to outside molecules. The fabricated sensor expressed a linear relationship to SY concentrations from 2.2nM to 4.64μM with a detection limit of 1.4nM (S/N = 3). The sensor also exhibited excellent selectivity for SY over its structural analogs, good stability, and adequate reproducibility. The prepared sensor was successfully used to detect SY in real spiked samples. This methodology has potential application value and may be readily adapted to design other PDA-based MIP sensors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC 50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 μg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg -1 ·d -1 , iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

Three new glycoalkaloids, N-formyl-asimilobine-2-O-β-D-glucoside (1), (-)-1-O-β-D-glucoside-8-oxotetrahydropalmatine (2), and 1-N-monomethylcarbamate-argentinine-3-O-β-D-glucoside (3) were isolated from tubers of Stephania succifera. The structures were established based on spectroscopic analysis, and the antimicrobial activities of the three glycoalkaloids are reported.

Objective: Diabetes affects the renal function at a certain stage. Oral medication glipizide plays a hypoglycemic effect mainly through releasing insulin, while more insulin is derived from islet β cells. It is still controversy whether antidiabetics. This study mainly intends to investigate the role of glipizide in inhibiting renal interstitial fibrosis., Materials and Methods: A total of 93 SD rats were purchased from Guangdong animal monitoring and established unilateral ureteral obstruction (UUO) model to simulate renal interstitial fibrosis. Forty rats in the experimental group received glipizide intraperitoneal injection for a week at 30 days after modeling, while another 40 rats in the control group received a normal saline injection. The last 10 rats were treated as blank group. Hematoxylin and eosin (HE) staining was applied to test renal interstitial fibrosis. Immunohistochemistry was used to detect fibronectin expression in glomerular and renal tubules. AKT signaling pathway related factors expression was measured by Western blot to determine AKT signal activation., Results: HE staining showed that the entire kidney cytoplasm red dye becomes shallow, renal medulla gradually disappears, renal tubular epithelial cells enlarge, vacuoles degeneration, renal tubule and collecting tube expansion, inflammatory cells infiltration after UUO modeling. Glipizide treatment decreased dilated renal tubule number, improved glomerulus integrity, and reduced inflammatory infiltration. Fibronectin level in the experimental group was significantly lower than that in control (p<0.05). Western blot revealed that p-AKT expression downregulated after glipizide treatment., Conclusions: Glipizide blocks renal interstitial fibrosis by inhibiting AKT signaling pathway.

Eleven new monoterpenoids including three 1-methyl cantharimide-type derivatives (1-3), five 1,2-dimethyl cantharimide-type derivatives (4, 5, 7-9), and three 1-hydroxymethyl-2-methyl cantharimide-type derivatives (10-12), together with seven known cantharimides (6, 13-18), were isolated from Mylabis phalerata Palla. The planar structures and absolute configurations of compounds 1-14 were fully elucidated on the basis of spectroscopic analysis, ECD spectra, single-crystal X-ray diffraction analysis, and chemical methods. Compounds 6, 15, 16, and 18 were found to be potent inhibitors of HBV virus, with IC50 values of 62, 42, 58, and 19 μM.

Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Many microRNAs (miRNAs), small non-coding RNAs, are involved in regulating cancer cell proliferation, metastasis, migration, invasion and apoptosis., Main Methods: We investigated the expression of miR-135a in HCC cell lines and clinical tissues. The effect of miR-135a on migration and invasion of HepG2 and MHCC-97L were examined using wound healing and Transwell assay. We determined the expression of miR-135a, forkhead box O1 (FOXO1), matrix metalloproteinase-2 (MMP-2) and Snail using real-time PCR and western blotting., Key Findings: We found miR-135a was upregulated in HCC cell lines and tissues. miR-135a overexpression promoted HCC cells migration and invasion, whereas miR-135a inhibition suppressed HCC cells migration and invasion. miR-135a overexpression could upregulate the expression of MMP2, Snail and the phosphorylation of AKT, but decreased FOXO3a phosporylation. Tumor suppressor FOXO1 was the direct target for miR-135a., Significance: Our results suggested that miR-135a might play an important role in promoting migration and invasion in HCC and presents a novel mechanism of miRNA-mediated direct suppression of FOXO1 in HCC cells.

One new monoterpenoid, nerol oxide-8-carboxylic acid (1), and one new flavonoid glycoside, claulansoside A (2), together with six known compounds, clausenamide (3), quercetin (4), isorhamnetin (5), dihydromyric (6), 2",3"-dihydroxyanisolactone (7) and (E,E)-8-(7-hydroxy-3,7-dimethylocta-2,5-dienyloxy)psoralen (8), have been isolated from the peels of Clausena lansium (Lour.) Skeels. Their structures were determined using a combination of 1D, and 2D NMR (HMQC, HMBC, COSY and NOESY) techniques, and HR-ESI-MS analyses. Compounds 1 and 7 exhibited antibacterial activity against Staphylococcus aureus with the diameter of inhibition zones of 11.5 mm and 14.2 mm. Compounds 3 and 6 showed α-glucosidase inhibitory activity in vitro.

New techniques are required for the rapid and sensitive detection of Escherichia coli O157:H7 (E. coli O157:H7), a pathogenic bacterium responsible for serious and sometimes life-threatening diseases in humans. In this study, we developed a highly sensitive and efficient biosensor for the quantitative detection of E. coli O157:H7 by integrating fluorescein-releasable biolabels with a magnetism-separable probe. Hollow silica nanospheres with a diameter of approximately 350 nm were synthesized, enriched with fluorescein, and surface-protected with macromolecule layers of poly (acrylic acid) and poly (dimethyldiallylammonium chloride). These fluorescein-enriched hollow silica nanospheres were characterized using scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. They were further functionalized as immune labels of E. coli O157:H7 for a sandwich-type immune reaction between this bacterium and magnetic nanoparticles (Fe3O4@SiO2). Next, the E. coli O157:H7 cells were captured, magnetically separated, and quantified based on the fluorescence intensity of the fluorescein released from the biolabels of the fluorescein-enriched hollow silica nanospheres. This analytic process can be completed within 75 min, and the biosensor showed a linear relationship ranging from 4 to 4.0 × 10(8)cfu/mL with a detection limit of 3 cfu/mL. These results show that the developed fluorescent sensor has excellent specificity, and good reproducibility and stability. This study used real spiked samples for detection, indicating that this technique has a wide range of potential applications and may be readily adapted for detecting other pathogens., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ten compounds were isolated from Mylabris phalerata by using preparative HPLC and column chromatography over MCI gel. On the basis of physical-chemical properties, NMR and MS data analysis, the compounds were identified as 5'-[(1 R,2 R,3 S,6R)-1-hydroxymethyl-2-methyl-3,6-epoxycyclohexane-1,2-dicarboximide]- ethyl-2'-methyl-2'-butenoate (1),cantharidin (2), cyclo-(L-Pro-L-Ala) (3), cyclo-(R-Pro-R-Leu) (4), cyclo-(S-Pro-R-Leu) (5), cyclo-(D-Pro-L-Tyr) (6), indole-3-aldehyde (7), 3-indoleacetic acid (8), valerolactam (9), and 4-hydroxyphthalid (10).Compound 1 was a new compound, and compounds 2-10 were obtained from this genus for the first time. Compounds 1-9 were subjected to cytotoxic activity on HCT-116, HepG2, BGC-823, NCI-H1650, A2780 cell lines, and only compound 2 showed inhibitory effect on all cancer cell lines., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

A new degraded sesquiterpene, tectoionol C (1), together with five known compounds wilsonol F (2), heterodendrin (3), epi-heterodendrin (4), 7-deoxogeayine (5), and 1H-indole-3-carboxylicacid, methyl ester (6), was isolated from the twigs of Trigonostemon lutescens. Their structures were determined by spectroscopic methods including 1D and 2D NMR techniques, as well as by comparison with published data.

Two new sesquiterpenoids, named 2α-hydroxyxylaranol B (1) and 4β-hydroxyxylaranol B (2), together with a known diterpenoid 3,4-seco-sonderianol (3) were isolated from the fermentation of endophytic fungus J3 of Ceriops tagal. Their structures were elucidated based on spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY and HMBC). All compounds were evaluated for their cytotoxic activities by MTT method, and compound 3 exhibited cytotoxic activities against K562, SGC-7901, and BEL-7402 cell lines.

A new eremophilane sesquiterpene, sporogen AO-2 (1), and a new beyerane diterpene, thecacorin C (2), together with two known compounds, longifoamide-B (3) and methylcholestane-3β,5α,6β-triol (4), were isolated from the stems of Manihot esculenta. The structures of the two new compounds were determined by spectroscopic techniques (UV, IR, MS, 1D, and 2D NMR). Antimicrobial assay showed that compound 3 possessed modest inhibitory effects on Saphylococcus aureus and methicillin-resistant S.aureus, diameters of inhibition zones of which were 7.5 and 8.0 mm, respectively. Compound 4 possessed modest inhibitory effect on S. aureus, the diameter of inhibition zone of which was 6.8 mm.

Objective: We aimed to identify the risk factors for predicting pancreatic infection in patients with severe acute pancreatitis (SAP)., Methods: In all, 163 patients with SAP were included and divided into two groups based on the presence or absence of pancreatic infection. Their demographic and clinical characteristics, laboratory examination results, complications and treatment modalities were collected from their medical records. Variables were initially screened by univariate analysis and those with statistical significance were then filtered by multivariate analysis to determine the independent risk factors for pancreatic infection in SAP., Results: Patients having SAP with pancreatic infection had a lower partial pressure of arterial carbon dioxide (PaCO2 ), peripheral white blood cell count and alkaline phosphatase levels, together with a higher computed tomography severity index (CTSI) than those without pancreatic infection, while their lactate dehydrogenase (LDH) levels and blood urea nitrogen were much higher. Pancreatic infection was also more common in patients receiving late fluid resuscitation than in those receiving early fluid resuscitation. Multivariate analyses revealed that increased LDH level, high CTSI, delayed fluid resuscitation and hypoxemia were independent risk factors for pancreatic infection in SAP. The sensitivity, specificity, positive and negative predictive values for a model combining the parameters in predicting pancreatic infection were 84%, 97%, 88% and 96%, respectively, with a cut-off value of 0.393, and the area under the receiver operating characteristic curve was 0.923., Conclusion: Increased LDH, high CTSI, delayed fluid resuscitation and hypoxemia are independent risk factors for predicting pancreatic infection in patients with SAP., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC., (© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of saponins with potent anti-tumor activity. In order to study the structure-activity relationship of GNTS, 24 oleanolic acid saponins with (1 --> 3)-linked, (1 --> 4)-linked, (1 --> 6)-linked N-acetylglucosamine oligosaccharide residues were synthesized in a combinatorial and concise method. The cytotoxicity of these compounds toward the leukemia cell line HL-60 and the colorectal cancer cell line HT-29 could not be improved. Half maximal inhibition below 10 μM was achieved in one single case. The study revealed that the activity decreased following the order of 3' > 4' > 6' glycosyl modifications. GNTS that incorporated (D/L)-xylose and L-arabinose at positions 3' and 4' were more potent than those bearing other sugars.

One new diterpenoid, 11alpha,12betaH-dolabella-4,8(17)-dien-3alpha,7beta,18-triol (1) and one new sesquilignan, 9-methoxy-7',8'-cis-7",8"-cis-buddlenol B (2), together with three known compounds, (+)-diasyringaresinol (3), N-methyl-5- hydroxy-delta3-pyrrolin-2-one (4) and marmin (5), have been isolated from Aglaia odorata var. microphyllina. Their structures were determined using 1D and 2D NMR spectroscopy. Compound 1 exhibited cytotoxic activity against the K562 cell line with an IC50 value of 12.5 microg/mL.

Agarwood is the fragrant resinous heartwood obtained from certain trees in the genus Aquilaria belonging to the family Thymelaeaceae. 2-(2-Phenylethyl)chromones and characteristic sesquiterpenes are the main classes of aromatic compounds isolated from agarwood. Although there are many sesquiterpenes, relatively few 2-(2-phenylethyl)chromones have been determined in agarwood by GC-MS. After analysis of the MS spectra of eighteen 2-(2-phenylethyl)chromone derivatives isolated from agarwood and identified by NMR spectroscopy, together with the reported MS data and characteristic of structures of 2-(2-phenylethyl)chromones, the MS characterization, fragmentation patterns and characteristic fragment peaks for the compounds were deduced and a table summarizing MS characterization of 2-(2-phenylethyl)chromones in agarwood is presented. All the 2-(2-phenylethyl)chromones previously reported in agarwood are substituted by methoxy or/and hydroxy groups, except for one compound. Due to the fact they all possess the same basic skeleton (molecular weight: 250) and similar substituent groups (methoxy or hydroxy groups), a formula (30m + 16n = MW - 250) is provided to calculate the number of methoxy (m) or hydroxy (n) groups according to molecular ion peak or molecular weight (MW). We deduced that the characteristic fragmentation behaviors of the 2-(2-phenylethyl)chromones are the cleavages of the CH₂-CH₂ bond between chromone moiety and phenyl moiety. Thus, characteristic fragment ions, such as m/z 91 [C₇H₇], 107 [C₇H₆+OH], 121 [C₇H₆+OCH₃], 137 [C₇H5+OH+OCH₃] are formed by different substituted benzyl moieties, while characteristic fragment ions such as m/z 160 [C₁₀H₈O₂], 176 [C₁₀H₇O₂+OH], 190 [C₁₀H₇O₂+OCH₃], 220 [C₁₀H₆O₂+OCH₃×2] are formed by different substituted chromone moieties. Furthermore, rules regarding to the relationship between the positions of hydroxy or methoxy groups and the relative abundances of benzyl and chromone fragment ions have been deduced. Elucidation of how the positions of hydroxy or methoxy groups affect the relative abundances of benzyl and chromone fragment peaks is also provided. Fifteen unidentified compounds of an artificial agarwood sample analyzed by GC-MS, were preliminary determined as 2-(2-phenylethyl)chromones by analysis of their MS characterization and by comparison of their MS spectra with those of 18 standard compounds or 2-(2-phenylethyl)chromones reported in literature according to the above-mentioned methods and rules. This report will be helpful for the analysis and structural elucidation of 2-(2-phenylethyl)chromones in agarwood by GC-MS, and provides fast and reliable characterization of the quality of agarwood.

Five new 2-(2-phenylethyl)chromone derivatives, qinanones A-E (1-5), together with eight known 2-(2-phenylethyl)chromone derivatives (6-13), were isolated from the Et2O extract of high-quality Chinese agarwood "Qi-Nan" originating from Aquilaria sinensis. The structures of the new 2-(2-phenylethyl)chromones were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. In the bioassay for acetylcholinesterase inhibitors, compounds 1-6, 10, and 12 exhibited weak inhibitory activities (inhibition percentage ranged from 10 % to 24 % at the concentration of 50 µg/mL). Compared with other agarwoods, "Qi-Nan" was different in containing 2-(2-phenylethyl)chromones with unsubstituted chromone rings., (Georg Thieme Verlag KG Stuttgart · New York.)

Six unprecedented bisindole alkaloids, trigolutesins A and B (1-2) with a unique polycyclic skeleton and trigolutes A-D (3-6) with another polycyclic skeleton, were isolated from the twigs of Trigonostemon lutescens. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction crystallography. Trigolutesin A (1) showed weak AChE inhibitory activity.

A white organic light-emitting device (WOLED) with a yellow phosphorescence material, bis[2-(4-tertbutylphenyl) benzothiazolato-N,C2 '] iridium (acetylacetonate) [(t-bt)2Ir(acac)], and two blue phosphorescence materials, iridium(Ill) bis (4', 6'-difluorophenylpyridinato) tetrakis(1-pyrazolyl) borate (FIr6) and bis[(4, 6-difluorophenyl)-pyridinato-N, C2 '] (picolinate) iridium (III) (FIrpic), were fabricated. Stable white emission was realized by using undoped ultrathin yellow emissive layer (EML), two doped blue EMLs together with the proper thickness of an interlayer confining the exciton. The WOLED performed pure white light emission with the Commissions Internationale de l'Eclairage (CIE) coordinates of (0.29+/-0.01, 0.34+/-0.01) from 6 to 14 V. Moreover, electroluminescence (EL) characteristics of the devices were also studied to verify the emissive mechanism from a phosphorescent system consisting of three iridium chelates. Also, the results showed that the triple-phosphor-element EMLs WOLED had lower efficiency roll-off owing to the stable recombination zone.