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A 63-year-old female patient presented with "flashes of light in both eyes accompanied by decreased visual acuity for one year." Visual field examination revealed partial defects in the central 30° of the visual field in both eyes. Scanning laser ophthalmoscopy showed extensive atrophic lesions across the entire posterior pole of the retina in both eyes. Optical coherence tomography revealed atrophy and thinning of the retina in the macular regions, with significant atrophy of the photoreceptor inner segment and outer segment layer in the areas corresponding to the visual field defects. Fluorescein fundus angiography demonstrated thinning of the retinal arterioles. Early-phase imaging showed large window-like defects in the posterior retina with background fluorescence from choroidal macrovessels. In the late phase, patchy fluorescence staining with a circumferential hyperfluorescent area was observed. Pattern visual evoked potential and pattern electroretinography tests revealed a significant decrease in the P100 amplitude in both eyes. The patient was diagnosed with acute regional occult outer layer retinopathy in both eyes.

To study the effects of organic fertilizer combined with biochar on soil denitrification and denitrifying microbial community structure, this study took lemon orchard soil as the research object and adopted a pot experiment, setting up five fertilization treatments:no fertilization(CK), conventional fertilization(F), organic fertilizer(P), fertilizer+biochar(FP), and organic fertilizer+biochar(PP). The abundance and community structure of denitrifying microorganisms were studied using real-time quantitative PCR and T-RFLP. Redundancy analysis(RDA) was used to explore the environmental factors affecting the denitrifying microbial community structure, and PLS-PM analysis was used to explore the environmental factors affecting the denitrification potential of lemon orchard soil. The results showed as follows:① compared with that under the single fertilizer treatment(F), the organic fertilizer and biochar(P, FP, and PP) treatments significantly increased the denitrification potential of the soil, ranging from 147.8% to 1445.3%. The denitrification rate of soil treated with organic fertilizer combined with biochar was 23.8% lower than that treated with organic fertilizer alone. ② Compared with that in the CK treatment, fertilization treatment significantly increased the abundance of nirS and nirK denitrification microorganisms. Fertilizer treatments(F and FP) significantly reduced the abundance of nosZ denitrifying microorganisms. Biochar treatment significantly changed the diversity and uniformity of denitrifying microorganisms, but the specific law and mechanism quality remained unclear. ③ The results of RDA analysis showed that fertilization could affect the community structure of nirS , nirK , and nosZ denitrifying microorganisms by changing C/N, WC, NO 3 - -N, SOC, AK, and AP. ④ PLS-PM analysis showed that soil denitrification was positively correlated with pH and the abundance of nirK denitrification microorganisms, and NO 3 - -N indirectly affected soil denitrification by affecting the abundance of nirK denitrification microorganisms. In addition, the nirK microbial community was the dominant microbial community in soil denitrification in lemon orchards. In conclusion, organic fertilizer directly affected soil denitrification by regulating soil pH, whereas regulating NO 3 - -N content affected nirK denitrification microbial abundance, indirectly affecting soil denitrification. The application of organic fertilizer combined with biochar could slow down the improvement of soil denitrification caused by single application of organic fertilizer, which is more suitable for promotion in orchards in this region.

A total of 130 patients who underwent percutaneous testicular sperm aspiration from March 2021 to February 2023 were randomly divided into a Dezocine group and a control group. The Dezocine group received a muscle injection of 0.05mg/kg Dezocine 30 minutes before surgery, while the control group received a muscle injection of 0.01ml/kg normal saline. Both groups received 3ml of 2% lidocaine for spermatic cord block anesthesia. The anesthesia onset time, anesthesia duration, numeric rating scale (NRS) score, anesthesia satisfaction rate and incidence of adverse reactions were recorded and compared between the two groups. The statistical results showed that there were significant differences between the two groups in terms of anesthesia onset time, anesthesia duration, anesthesia satisfaction rate, non-steroidal anti-inflammatory drug (NSAID) use within 24 hours after surgery and NRS scores at 15 minutes, 1 hour and 2 hours after surgery. The incidence of adverse reactions in the Dezocine group was lower than that in the control group, but the difference was not statistically significant. The combination of Dezocine and lidocaine for spermatic cord block anesthesia during percutaneous testicular sperm aspiration is safe, effective and associated with fewer adverse reactions. It is suitable for clinical application and promotion in reproductive medicine outpatient surgery.

Background: The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs., Results: We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD ., Conclusions: As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The aim of this study was to examine the effects of different fertilization methods on the physicochemical properties and bacterial community structure of lemon rhizosphere/non-rhizosphere soil in order to provide theoretical basis for scientific and rational fertilization of orchards. A pot experiment was carried out, and six fertilization treatments were set up:control (CK), conventional fertilization (FM), organic fertilizer (P), fresh organic fertilizer (NP), 70% chemical fertilizer+30% organic fertilizer (70FP), and 50% chemical fertilizer+50% organic fertilizer (50FP). Chemical analysis, real-time fluorescence quantitative PCR, and terminal restriction fragment length polymorphism (T-RFLP) were used to study the effects of different fertilization treatments on the physicochemical properties of rhizosphere and non-rhizosphere soils, the abundance of the bacterial 16S rRNA gene, and bacterial community structure. Redundancy analysis (RDA) was used to explore the environmental factors affecting the bacterial community structure of lemon rhizosphere/non-rhizosphere soil. The results showed the following:① the pH and contents of organic matter, alkali-hydrolyzed nitrogen, available phosphorus, available potassium, and nitrate nitrogen in rhizosphere/non-rhizosphere soil were significantly increased by reducing the amount of chemical fertilizer and applying organic fertilizer (50FP and 70FP) ( P <0.05). Compared with conventional fertilization (FM) and single application of organic fertilizer (P and NP), the soil available P content, available K content, and nitrate nitrogen content increased by 24.76%-97.98%, 6.87%-45.11%, and 18.42%-55.82%, respectively. ② Fertilizer reduction combined with organic fertilizer significantly increased the abundance of soil bacteria and soil respiration intensity ( P <0.05), and the abundance of soil rhizosphere bacteria and soil respiration intensity under the 50FP treatment increased by 15.83%-232.98% and 8.0%-162.5% compared with that under conventional fertilization and organic fertilizer alone, respectively. The bacterial abundance of rhizosphere soil was positively correlated with the pH and contents of organic matter, total nitrogen, and total phosphorus. ③ The PCoA and RDA analysis results showed that the single organic fertilizer and organic fertilizer and chemical fertilizer de-weighting of rhizosphere bacterial community structure and not adding fertilizer had a bigger difference between processing, and the main environmental factors influencing the rhizosphere/non rhizosphere bacterial community structure were organic matter, total nitrogen, total phosphorus, total potassium, alkali solution nitrogen, nitrate nitrogen, and available potassium. Fertilizer reduction combined with organic fertilizer could significantly increase soil nutrient content, increase soil bacterial abundance, and change the bacterial community structure of rhizosphere soil, and the 50FP treatment yielded better results. Therefore, 50% Chemical fertilizer+50% organic fertilizer (50FP) was a better fertilization method to improve the physical and chemical properties of orchard soil, increase the abundance of soil bacteria, and improve the soil respiration intensity.

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P <0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal ( P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels ( F =2.474, P =0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P =0.182; anastrozole vs. exemestane, P =0.535; letrozole vs. exemestane, P =0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene ( P <0.01, P =0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Background: Inhaled corticosteroids (ICSs) have been used widely in the maintenance therapy of COPD. However, whether inhaled therapy containing ICSs can reduce the all-cause mortality risk and the possible benefited patient subgroups is unclear., Research Question: Does inhaled therapy containing ICSs reduce the all-cause mortality risk in patients with COPD compared with other inhaled therapies not containing ICSs?, Study Design and Methods: We searched PubMed, Cochrane Library, Embase, and ClinicalTrials.gov for relevant randomized clinical trials (RCTs). Pooled results were calculated using Peto ORs with corresponding 95% CIs., Results: Sixty RCTs enrolling 103,034 patients were analyzed. Inhaled therapy containing ICSs (Peto OR, 0.90; 95% CI, 0.84-0.97), especially triple therapy (Peto OR, 0.73; 95% CI, 0.59-0.91), was associated with a reduction in the all-cause mortality risk among patients with COPD when compared with inhaled therapy without ICSs. Subgroup analyses revealed that treatment duration of > 6 months (Peto OR, 0.90; 95% CI, 0.83-0.97), medium-dose ICSs (Peto OR, 0.71; 95% CI, 0.56-0.91), low-dose ICSs (Peto OR, 0.88; 95% CI, 0.79-0.97), and budesonide (Peto OR, 0.75; 95% CI, 0.59-0.94) were involved in this association. The predictors of this association included eosinophil counts of ≥ 200/μL or percentage of ≥ 2%, documented history of ≥ 2 moderate and severe exacerbations in the previous year, Global Initiative for Chronic Obstructive Lung Disease stages III or IV, age younger than 65 years, and BMI of ≥ 25 kg/m 2 , among which eosinophil counts of ≥ 200/μL (Peto OR, 0.58; 95% CI, 0.36-0.95) were the strongest predictor., Interpretation: Inhaled therapy containing ICSs, especially triple therapy, of longer than 6 months was associated with a reduction in the all-cause mortality risk in patients with COPD. The predictors of this association included medication factors and patient characteristics, among which eosinophil counts of ≥ 200/μL were the strongest predictor., Trial Registry: PROSPERO; No.: CRD42022304725; URL: https://www.crd.york.ac.uk/prospero/., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The beneficial metabolites of the microbiome could be used as a tool for screening drugs that have the potential for the therapy of various human diseases. Narrowing down the range of beneficial metabolite candidates in specific diseases was primarily a key step for further validation in model organisms. Herein, we proposed a reasonable hypothesis that the metabolites existing commonly in multiple beneficial (or negatively associated) bacteria might have a high probability of being effective drug candidates for specific diseases. According to this hypothesis, we screened metabolites associated with seven human diseases. For type I diabetes, 45 out of 88 screened metabolites had been reported as potential drugs in the literature. Meanwhile, 18 of these metabolites were specific to type I diabetes. Additionally, metabolite correlation could reflect disease relationships in some sense. Our results have demonstrated the potential of bioinformatics mining gut microbes' metabolites as drug candidates based on reported numerous microbe-disease associations and the Virtual Metabolic Human database. More subtle methods would be developed to ensure more accurate predictions., 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 Wang, Wen, Wang, Kuang, Dong, Deng and Guo.)

Triple-negative breast cancer (TNBC) is the most aggressive, high recurrence and metastatic breast cancer subtype. There are few safe and effective therapeutic drugs for treatment of TNBC. The marine natural product MHO7 has been determined to be a potential antitumor agent. However, its moderate activity and complex structure hampered its clinical application. In this study, a series of novel derivatives with modification on C24 of MHO7 were first synthesized. Some of the analogues were significantly more potent than MHO7 against all selected breast cancer cell lines. Among them, compound 4m had the best activity, and its IC 50 value against TNBC was up to 0.51 μM. A whole-genome transcriptomic analysis shown that the mechanism of compound 4m against TNBC cells was similar with that of parent compound MHO7. Subsequent cellular mechanism studies showed that compound 4m could induce apoptosis of MDA-MB-231 cells through mitochondria pathway and cause G1 phase arrest. Moreover, 4m could disrupt the expressions of MAPK/Akt pathway-associated proteins (p-p38 and p-Akt) and remarkably increase the ratio of Bax to Bcl-2 and activate cleaved caspase 3/9/PARP. Importantly, 4m could influence the expression of Smad 7, and p-Smad 3 to inhibit TNBC cells metastasis. Stability assays in rat plasma and liver microsomes indicated that 4m still have room for further optimization. And the results of the online molinspiration software predicted that 4m has desirable physicochemical properties but some properties still have violation from the Lipinski rule of five. Overall, the modification on C24 of MHO7 was a promising way for developing novel anti-TNBC agents with considerable potential for optimization., (Copyright © 2022. Published by Elsevier Masson SAS.)

Olives are a rich source of compounds with antioxidant and anti-inflammatory activities. This study was designed to investigate whether a standardized olive cake extract was able to alleviate oxidative stress, inflammation and intestinal villus damage in a model of lipopolysaccharide (LPS)-challenged piglets. Thirty weaned piglets (6.9 ± 0.9 kg) were assigned to five groups using a randomized complete block design. Piglets were fed a basal diet before intraperitoneal (i.p.) injection of physiological saline (C); fed a basal diet alone (CL) or fed a basal diet plus an olive cake extract (OL), antibiotics (AL), or olive cake extract plus antibiotics (OAL) before i.p. injection of LPS. The feeding period lasted for 2 weeks. Piglets were euthanized 4 h after the LPS injection. Systemic oxidative and inflammatory status and intestinal morphology were evaluated. LPS challenge significantly lowered the serum levels of GSH-Px, SOD and ALB and increased the serum concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose ( P < 0.05), as extracted from the comparison of piglets in the C and CL groups. Intestinal morphology was altered in the duodenum and ileum, displaying that the CL group had significantly lower villus height (VH), higher crypt depth (CD) and lower VH/CD compared with the control group ( P < 0.05). Moreover, feed supplementation was able to partially mitigate the negative effects of LPS challenge in all groups (OL, AL, and OAL), as evidenced by the significantly increased serum levels of GSH-Px, SOD, ALB and IL-10 and decreased concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose, compared with the CL group ( P < 0.05). Alterations in intestinal morphology were also prevented and the OL, AL, and OAL groups had significantly lower CD and higher VH/CD compared with the CL group ( P < 0.05), both in the ileum and duodenum. Furthermore, the positive effect in the relative abundance of intestinal Lactobacillus and Clostridium at the genus level was also observed for the OL group compared to the CL group. In summary, dietary supplementation with an olive cake extract stabilized the physiological condition of piglets subjected to an acute LPS challenge by reducing oxidative stress and the inflammatory status, improving intestinal morphology and increasing the abundance of beneficial intestinal bacteria. This trial was registered at Zhejiang University (http://www.lac.zju.edu.cn) as No. ZJU20170529.

Objectives: Purpose of the present study was to evaluate the effect of surface roughness on the time-dependent wear performance of lithium disilicate (LD) glass-ceramic., Methods: Friction pairs (pin and disk specimens) were prepared by IPS e.max® Press lithium disilicate glass-ceramic. The lateral faces of friction pairs (N = 12) were grinded with silicon carbide papers, and 6 friction pairs were polished with a 0.25 μm diamond suspension after grinding. The friction pairs were tested for wear performance using a pin-on-disk tribometer with 10 N for 1.02 × 10 6 wear cycles in artificial saliva. Wear analysis of the pin and disk was performed with a 3D profilometer. The microstructure and worn surface morphology were examined with scanning electron microscopy. One-way analysis of variance and Tukey's post-hoc pairwise comparison were used to analyze the wear data., Results: The two group LD friction pairs presented strong time-dependent wear performance. The polished group (GP) exhibited a high wear rate and extensive surface wear during 0-1 × 10 5 cycles (running-in wear stage). The wear rate, height loss and surface roughness were obviously lower than those of grinded group (GG) in running-in wear stage. However, these wear parameters were similar during the steady wear stage. The worn surface topographies of the pin and disk in GP were smoother at the same cycle before the GG entering the steady wear stage., Conclusion: Running-in, which means the initial stage of wear process, is a critical period to determine the final wear loss and surface degradation, when compare the wear behavior of lithium disilicate ceramic with different initial surface states. Ceramic layer with smooth contact area leads to low wear rate and short running-in wear stage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In order to explore biochar fertilizer addition, two types of industrial wastes (YM) and lees (JZ) and agricultural waste corn stover (JG) were used as the raw materials to make biochar, and the biochar was modified to make smoke-modified biochar (M-YM). The culture test method was used to study the law of ammonia volatilization and phosphorus fixation over a certain period of time with the different fertilizer ratios of the four biochars. We aimed to provide a scientific basis for the agricultural utilization of biochar. The results show that:① The cumulative volatilization and volatilization rate of ammonia of the four kinds of biochar with different fertilizer ratios were as follows:A1 > A2 > A3 (A1:2.25 g urea; A2:2.25g urea +2.25 g chlorination potassium; A3:2.25 g urea +2.25 g potassium dihydrogen phosphate). The addition of potassium chloride and potassium dihydrogen phosphate in urea reduced ammonia volatilization, and the cumulative ammonia volatilization and volatilization rate of different biochars under all chemical fertilizer ratios was JZ > M-YM > YM > JG; ② The amount of phosphorus by biochars fixation under the B1, B2, and B3 treatments (B1:0.4 g potassium dihydrogen phosphate; B2:0.4 g potassium dihydrogen phosphate +0.3 g urea; B3:0.4 g potassium dihydrogen phosphate +0.3 g potassium chloride) all increased and then decreased. Then, the fixation amount of phosphorus not significantly changed in period from 30th to 60th day. Among four biochar, the fixation rate of phosphorus was the highest under the B1 treatment.With the ratios of B1, B2, and B3 fertilizers, the order of the fixation rate of the four biochars to phosphorus was:M-YM > YM > JG > JZ. Therefore, in order to reduce the volatilization of ammonia in nitrogen fertilizers in agricultural fertilization, potassium chloride and potassium dihydrogen phosphate can be added to urea. At the same time, in the fixation of phosphorus, increasing the particle size of biochar may weaken the phosphorous fixation ability.

Chromanone is a privileged structure with a wide range of unique biological activities. A phosphine-promoted, three-component domino sequence of salicylaldehyde with but-3-yn-2-one was well designed for the construction of the chromanone skeleton under mild conditions. As a consequence, a series of novel chromanone analogues bearing an all-carbon quaternary center were facilely assembled from commercially available starting materials with moderate to good yields, which hold promising applications in pharmacological studies. Mechanistic experiments were conducted to confirm the proposed mechanism.

Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments. To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E 2 and leukotriene B4, in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4 + T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pomacea canaliculata , a freshwater snail from South America, has rapidly established natural populations from south to north subtropical region in China, since its original introductions in the 1980s. Low temperature in winter is a limiting factor in the geographic expansion and successfully establishment for apple snail populations. There have been some studies on population level of low temperature tolerance for P. canaliculata , yet little is quantified about its life-history traits in responses to cold temperatures. Whether these responses vary with the acclimation location is also unclear. We investigated the survivorship and longevity of P. canaliculata in responses to cold temperatures and examine whether these responses vary with the location and snail size. We hypothesized that survival of the snails depends on their shell height and the level of low temperature, and P. canaliculata population from the mid-subtropical zone may exhibit the highest viability over the cold thermal range.We sampled P. canaliculata populations from five latitude and longitude ranges of subtropical China: Guangzhou population in southernmost (SM-GZ), three populations of Yingtan (MR-YT), Ningbo (MR-NB), Ya'an (MR-YA) in midrange, and Huanggang population in northernmost (NM-HG) subtropical zone. For each P. canaliculata population, survival and longevity at six cold acclimation temperature levels (12, 9, 6, 3, 0, and -3°C) were quantified, and the effects of location and shell height were examined.The MR-YA population from mid-subtropical zone of China exhibited the highest survival rate and prolonged survival time regardless of the temperature acclimation treatments, whereas the SM-GZ population from southern subtropical was the most sensitive to cold temperatures, particular temperatures below 9°C. No individuals of the SM-GZ population could survive after stressed for 30 days (3°C), 5 days (0°C) and 2 days (-3°C), respectively. For each experimental P. canaliculata population held at 3, 0, and -3°C, individuals with intermediate shell height of 15.0-25.0 mm had significantly higher survivals.The results highlight a request of a more thorough investigation on acclimation responses in each of the life table demographic parameters for P. canaliculata , and pose the question of whether natural selection or some genetic changes may have facilitated adaptation in invasive locations., Competing Interests: The authors declare no conflicts of interests., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The aim of this study was to determine the effects of dietary inclusion of the combination of tributyrin with oregano or methyl salicylate as a substitute to antibiotics on gut health and microbiota of piglets. A total of 48 weaned crossbred piglets (Duroc × Large White × Landrace, 8.79 ± 0.97 kg, 21 ± 1 d) were randomly allocated to four experimental groups and fed for 4 weeks: the basal diet (Con); the control plus antibiotics (AB); the control plus oregano and tributyrin (OT); and the control plus methyl salicylate and tributyrin (MT). Although a numerical improvement on feed intake, weight gain and feed conversion ratio was observed in the OT and MT as well as the AB group, the difference was not significant ( p > 0.05). The OT and MT groups were larger in villus height in the duodenum compared to the Con ( p < 0.05), and were larger in relative abundance of Firmicutes / Bacaeroides in the intestine compared to Con and AB groups ( p < 0.01). The amount of major different metabolites was 6, 8 and 8 for the AB, OT and MT groups when compared to the Con, respectively. In conclusion, as a substitute for antibiotics the inclusion of the combination of tributyrin with either oregano or methyl salicylate to the diet of weaned piglets improved the intestinal morphological structure and altered intestinal microbiota and metabolites, which were beneficial to the animal health., Competing Interests: The authors declare no conflict of interest.

We herein report a phosphine-mediated domino process of MBH-type reaction/umpolung γ-addition through the rational integration of the privileged reactivities of alkynoate. Simply by manipulating the nucleophilic reagent, the developed protocol offers a facile, diversity-oriented construction of a wide range of three-substituted coumarins.

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

Objective: To evaluate Aptima HPV E6 and E7 mRNA assay (Aptima HPV) combined with Aptima HPV 16 and 18 or 45 (18/45) genotype assay (Aptima HPV-GT) as a means of cervical cancer opportunistic screening. Methods: From October 2016 to October 2017, a total of 23 258 women aged 25-65 years were enrolled in the physical examination center and gynecological clinic of Huzhou Maternity and Child Health Care Hospital. All the women had Aptima HPV tested, further Aptima HPV-GT testing for positive women and liquid-based thin layer cytology Thinprep cytologic test (TCT). Women with Aptima HPV (+) or ≥low-grade squamous intraepithelial lesion (LSIL) or obvious clinical symptoms (including vaginal bleeding after intercourse and watery, bloody vaginal discharge) were referred for colposcopy and further biopsy with or without endocervical curettage (ECC) if indicated. Expression of Aptima HPV, HPV 16 and HPV 18/45 with different cytological diagnostic groups and histological diagnosis groups were compared respectively. Sensitivity, specificity, positive predictive value and negative predictive value of Aptima HPV detection and TCT in identifying histological diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL(+)) were compared. Results: (1) The positive rates of Aptima HPV, HPV 16 and HPV 18/45 were 14.00% (3 257/23 258), 1.85% (430/23 258) and 0.86% (199/23 258) respectively.The positive rates of Aptima HPV, HPV 16 and HPV 18/45 increased with cytology grading in squamous epithelium [negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), LSIL, atypical squamous cell cannot exclude HSIL (ASC-H), HSIL and squamous cell carcinoma (SCC), all P =0.000)]. According to histology results, the positive rates of Aptima HPV, HPV 16 and HPV 18/45 increased with histology grading in squamous epithelium (normal cervical tissue, LSIL, HSIL and SCC, all P =0.000). The positive rate of Aptima HPV was significantly higher in HSIL(+) group than that in the LSIL or better (LSIL(-)) group [98.11% (311/317) vs 12.84% (2 946/22 941), P =0.000]. The positive rate of Aptima HPV-GT was significantly higher in HSIL(+) group than that in LSIL(-) group [58.36% (185/317) vs 1.91% (439/22 941), P =0.000]. (2) Compared with cytology, Aptima HPV resulted in significant higher sensitivity (98.11% vs 59.62%, P =0.000) and negative predictive value (99.97% vs 99.42%, P =0.000), significant lower specificity (87.16% vs 95.37%, P =0.000) and positive predictive value (9.55% vs 15.10%, P =0.000) when identified HSIL(+). Conclusions: Women with Aptima HPV positive, especially those with Aptima HPV-GT positive, are more likely to have histological diagnosis of HSIL(+). Aptima HPV combined with Aptima HPV-GT is feasible as a means of cervical cancer opportunistic screening in tertiary hospitals.

The high-resolution and accurate typing of human leukocyte antigen (HLA) is of great significance for the study of tissue matching in organ transplantation and the correlation between HLA and disease. In this study, the peripheral blood of 12 patients with primary hepatocellular carcinoma was used to compare the advantages and disadvantages of the next- and third-generation sequencing technology for high-resolution HLA typing. In addition, probe capture technology was used to capture the MHC region of YH and HeLa standard cell lines, and a primary hepatocellular carcinoma patient. The captured products were sequenced using PacBio platform to assess the potential of ultra-long reads sequencing technology for analysis of the entire MHC region. Our results showed that: (1) the next- and third-generation sequencing technology can both achieve 6-8 digit high resolution in HLA typing. However, the coverage of the third-generation is significantly better than the next-generation sequencing technology. (2) The ultra-long reads of the third generation sequencing can directly span the entire amplicon region, which has obvious advantages for haplotype phasing, with 92.79% of the HLA genes having accurate phasing results, which is much higher than the 75.65% from the next-generation data. (3) The long-reads from the third generating sequencing can not only be used to assemble the MHC region but also the ability to phase the entire MHC region of 3.6 Mb, thereby helping to clarify the localization information of the mutation sites, alleles and non-coding regions on each MHC haplotype, and providing a theoretical basis for the study of immune and other related diseases.

A one-pot squaramide-catalyzed enantioselective ring-reorganization domino sequence (Michael addition/intramolecular ring-opening/lactamization) of 3-hydroxyoxindole and methyleneindolinone, which can be readily derived from 3-oxindole, has been established in this work. As a result, novel polycyclic quinolinone-spirooxindoles bearing three contiguous chiral centers were efficiently and step-economically assembled under mild conditions in high yields (up to 97%) with excellent enantioselectivities (up to >99% ee) and moderate to good diastereoselectivities (up to >95:5 dr).

Objective: To investigate the feasibility of endoscopic surgery for treatment of rT1-rT2 recurrent nasopharyngeal carcinoma. Method: The clinical data and of 57 patients who had recurrence of the primary lesion after treatment of nasopharyngeal carcinoma from February 2011 to December 2015 were retrospectively analyzed. The patients were re-staged according to Union for International Cancer Control(UICC, 2010) staging system for nasopharyngeal carcinoma before surgery. Patients suitable for surgery underwent endoscopic surgery to remove nasopharyngeal lesions; those combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time; patients with positive surgical margins of pharyngeal lesions and cervical lymph node extramembranous filtration were treated with radiotherapy combined with chemotherapy; patients unsuitable for surgery were treated with radiotherapy combined with chemotherapy directly. All patients were followed up regularly to observe clinical efficacy and survival. Result: Fifty-seven patients were re-staged according to UICC(2010) staging system for nasopharyngeal carcinoma: 19 cases in stage Ⅰ,30 cases in stage Ⅱ, 6 cases in stage Ⅲ and 2 cases in stage Ⅳ,including 27 cases in stage rT1, 30 cases in stage rT2, and 43 cases in stage rN0,6 cases in stage rN1,6 cases in stage rN2,2 cases in stage rN3. Forty-four cases of primary lesions were sected for endoscopic surgery. Patients combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time, with 6 cases of positive surgical margins of pharyngeal lesions and 4 cases of cervical lymph node extramembranous infiltration, who were treated with radiotherapy combined with chemotherapy after surgery. Thirteen patients received radiotherapy combined with chemotherapy directly. At a median follow-up of 36 months, the 3-year overall survival rate of 57 patients was 61.4%. The 3-year overall survival rates of patients in stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 73.7%, 63.3%, 33.3%, 0.0% respectively. Kaplan-Meier survival curve analysis showed a significant difference in the overall survival rate of patients in different stages( P =0.002). The 3-year overall survival rates of rT1 and rT2 patients were 63.0%, 60.0% respectively, and KaplanMeier survival curve analysis showed no significant difference in the overall survival rate between rT1 and rT2 patients( P =0.707). The 3-year overall survival rates of patients in stages rN0, rN1, rN2, rN3 were 69.8%, 50.0%, 33.3%, 0.0% respectively, and Kaplan-Meier Survival curve analysis showed a significant difference in overall survival between patients in different rN stages( P =0.002). The 3-year overall survival rate was 68.2% in 44 surgical patients, and 38.5% in 13 non-surgical patients. Kaplan-Meier survival curve analysis showed significant difference in overall survival rate between surgical and non-surgical patients( P =0.014). Conclusion: Endoscopic surgery for recurrent nasopharyngeal carcinoma is a safe and effective treatment to improve survival., 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 Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

A new strategy for the synthesis of functionalized tetrahydrofuran derivatives was developed via a phosphine-catalysed [3 + 2] cyclization reaction of aromatic aldehydes with 4-phenylbut-3-yn-2-one. This is the first example of intermolecular cyclization of ynones with benzaldehydes, which essentially benefited from the intramolecular hydrogen bonding. This new protocol features a broad substrate scope, mild reaction conditions, operational simplicity and easy scale-up.

A palladium-catalyzed ring-opening oxo-formal [3 + 2]-cycloaddition reaction of novel donor-acceptor spirovinylcyclopropyl oxindole with 3-oxindole is described. The developed protocol provides facile access to oxo-bispirooxindole derivatives in good yields (up to 82% yield) with excellent diastereoselectivities (up to 20:1 dr).

An l-pyroglutamic acid-derived bifunctional organocatalyst was designed and applied in an organocatalytic asymmetric direct aldol reaction between isatins and cyclohexanone, in which an erosion of enantiomeric excess of aldol adduct was unexpectedly observed. Through closely monitoring the reaction and performing extensive control experiments, it was determined that the erosion of ee was attributed to a rare stereospecific retro-aldol process. Moreover, effective manipulation of the retro-aldol process by tuning the use of starting materials was ultimately accomplished, leading to evidently upgraded enantioselectivity and functional group tolerance. This study demonstrates the impact of the hidden reaction pathway on the enantioselectivity in asymmetric transformation.

Background: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients., Methods: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated., Results: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode., Conclusion: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

A 2 × 2 factorial arrangement (rearing room with or without pad-fan cooling × diet with or without 2.5 kg/t organic acid) was used to evaluate the effect of pad-fan cooling and dietary organic acid supplementation during perinatal period on reproductive performance and antioxidant status of sows in hot weather. This study was conducted in a subtropical city in Guangdong Province in South China between August and October, 2015. At day 85 of gestation, a total of 112 sows were randomly assigned to the four treatments with 28 sows per treatment, and maintained until day 21 of lactation, and the feeding trial lasted for 51 days. During the experimental period, room temperature and humidity were recorded hourly. The lactation feed intake of sows (P = 0.109) and stillbirths (P < 0.05) increased when the sows were reared in the room with the pad-fan cooling against the room without pad-fan cooling. The number of weak newborns per litter and the malondialdehyde content in days 14 and 21 milk decreased (P < 0.05), while the lactation feed intake of sows, weaned litter weights, and individual pig weights increased when the sows were fed the organic acid (P < 0.05). In conclusion, pad-fan cooling in rearing room improved the lactation feed intake of sows, and dietary organic acid supplementation improved reproductive performance and milk antioxidant status of sows. Pad-fan cooling is recommended in farrowing room, but not in gestating room.

The aim of this study was to elaborate the correlation between metastasis-associated protein (MTA) family and the occurrence, progression, prognosis and chemotherapy efficiency in nasopharyngeal carcinoma (NPC).The expression of MTA1, MTA2 and MTA3 protein were detected by immunohistochemistry in a tissue microarray (TMAs) which contains tissue samples of 152 NPC patients embedded by formalin-fixed paraffin. The MTA proteins were mainly expressed in the nuclei of NPC tissues and the correlations between MTAs expression and clinical parameters as well as prognosis of NPC patients showed ethnical differences according to statistically analysis. The results showed that in Han ethnic group, MTA1 expression was positively correlated with N staging, while the expression of MTA2 was negatively correlated with age, and the expression of MTA3 was positively correlated with gender. Patients with high MTA1 expression had poorprognosis. In Zhuang ethnic group, only MTA3 expression was positively correlated with age, recurrence and metastasis of NPC patients; neither MTA1 nor MTA2 expression had any correlation with clinical indexes. Patients with high MTA3 expression had unfavorable prognosis. In addition, our results showed that overall survival among Zhuang NPC patients with low expression of MTA2 increased significantly owing to "carboplatin + fluorouracil" chemotherapy. This therapeutic success, however, did not translate to longer overall survival among Han NPC patients. The biological function of MTA protein family in NPC patients was different among different ethnic groups. In conclusion, we demonstrated that MTAs had a certain tumor promoting function in patients with NPC, and the biological functions of MTAs might be ethnic differences, which suggesting MTAs to be important markers for guiding clinical treatment of NPC., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: To observe the clinical effect and safety of the Chinese patent medicine Ningmitai Capsules (NMT) in relieving lower urinary tract symptoms (LUTS) in the patient with benign prostatic hyperplasia (BPH)., Methods: We randomly assigned 40 BPH patients to an experimental and a control group of equal number to receive oral administration of NMT at 4 capsules tid and terazosin hydrochloride tablets at 2 mg qd, respectively, both for 14 days. At 7 and 14 days after medication, we recorded and compared the International Prostate Symptoms Score (IPSS), maximum urinary flow rate (Qmax), quality of life (QoL) scores, results of urinalysis and blood routine examination, and indexes of hepatic and renal function., Results: Both NMT and terazosin significantly improved the total IPSS score, the IPSS scores in the storage and voiding phases, increased Qmax and urine output, reduced post-void residual urine (PVR), and improved the QoL of the patients. The patients of the NMT group showed a better relief of incomplete bladder emptying, more improved QoL and fewer adverse reactions, while those treated with terazosin achieved a better attenuation of weak urine stream and PVR., Conclusions: NMT is safe and effective in relieving LUTS in BPH patients. Each of NMT and terazosin has its own advantages in attenuating urinary tract irritation and obstruction, but whether their combination may produce a better effect on LUTS and the specific mechanisms of NMT improving acute symptoms of BPH are yet to be further studied.

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ 2 = 4.403, p = 0.036; χ 2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

An intramolecular [3 + 2]-annulation of amide-linked donor-acceptor cyclopropane with in situ-generated imine is described. As a result, diverse hexahydropyrrolo[3,2-c]quinolinones, as the tricyclic core of martinellines, were efficiently assembled in good to excellent yield (up to 93%) with a good diastereomeric ratio (up to 98:2).

Highly diastereo- and enantioselective conjugate additions of azlactones to enolizable cyclic and linear enones were conducted by employing proline aryl sulfonamide as the organocatalyst in trifluorotoluene. The conjugate adducts bearing contiguous quaternary and tertiary stereocenters were obtained in moderate to good yields with excellent diastereoselectivities and moderate to good enantioselectivities. This developed protocol filled in the substrate gap for the organocatalytic conjugate addition of azlactone to enones.

A novel actinomycete strain 2803GPT1-18(T) was isolated from a composite mangrove soil sample collected from Beihai, Guangxi province, China. Phylogenetic analysis of the 16S rRNA gene sequence of strain 2803GPT1-18(T) indicated high similarity with 'Micromonospora harpali' NEAU-JC6(T) (99.2 %), Micromonospora haikouensis 232617(T) (99.1 %), Micromonospora wenchangensis 2602GPT1-05(T) (99.1 %), Micromonospora schwarzwaldensis HKI0641(T) (99.1 %). The gyrB gene sequence analysis also indicated that strain 2803GPT1-18(T) should be assigned to the genus Micromonospora but different from any established Micromonospora species. The strain harbored meso-DAP and glycine as major cell wall amino acids, MK-10(H6) (53.5 %), MK-9(H6) (25.1 %) and MK-9(H4) (13.4 %) as predominant menaquinones. The characteristic whole cell sugars are arabinose, xylose, glucose, galactose and mannose. The polar lipid profile comprises phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and unidentified polar lipids. The major cellular fatty acids present are iso-C16:0 (44.2 %) and iso-C15:0 (12.4 %). The DNA G+C content is 71.2 mol%. Furthermore, a combination of DNA-DNA relatedness and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from the closely related species. On the basis of these phenotypic and genotypic data, strain 2803GPT1-18(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora mangrovi sp. nov. is proposed. The type strain is 2803GPT1-18(T) (=CCTCC AA2012012(T) = DSM45761(T)).

The effects of technical cashew nut shell liquid (TCNSL) on the trans isomerization of edible oils during heating are investigated. Edible oils were subjected to thermal treatment at various heating times and temperatures. Our results show that the addition of TCNSL to edible oils at the appropriate concentration during heating suppresses trans fatty acid formation and induces formation of conjugated linoleic acid (CLA) isomers. A concentration of 0.2 % TCNSL demonstrates the best ability to inhibit formation of trans-oleic acid, trans-linoleic acid, and trans-linolenic acid isomers as well as increase the formation of 9 t,11 t-CLA and 10 t,12 t-CLA isomers. Our analysis indicates that the presence of 0.2 % TCNSL in corn oil does not significantly reduce the acid value, but may significantly lower the peroxide value. TCNSL is also observed to have better function compared to Vitamin E (VE) and tertiary butylhydroquinone (TBHQ), indicating that it may be considered an effective additive in edible oils.

Background: Hyperbaric oxygen (HBO) improves skin flap function and inhibits partial necrosis induced by ischemia-reperfusion (I/R) injury. Our study aimed to evaluate the mechanism underlying HBO regulation of the antiapoptosis factors associated with I/R injury of skin flaps., Methods: The rats were divided into sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was measured with laser Doppler flowmeters. Tissue morphology and apoptosis were subsequently assessed based on hematoxylin-eosinhe and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Protein expression of phosphorylated apoptosis signal-regulating kinase 1 (pASK-1), phosphorylated c-Jun N-terminal kinase (pJNK), B-cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) was examined by immunodetection, and Bcl-2 messenger RNA expression was detected by quantitative polymerase chain reaction. In addition, caspase-3 activity was also measured., Results: The result of microcirculation analysis showed that the survival and blood perfusion rates significantly increased in the skin flap after HBO exposure. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining revealed that cell apoptosis was significantly attenuated in the HBO group. Furthermore, HBO preconditioning increased the expression of Bcl-2 and inhibited pASK-1, pJNK, and Bax expression as determined by both immunohistochemistry and Western blot. Caspase-3 activity and the Bax/Bcl-2 ratio declined in the HBO group., Conclusions: HBO preconditioning effectively ameliorates I/R injury by regulating the apoptosis signal-regulating kinase 1 and/or c-Jun N-terminal kinase pathway and anti- and proapoptosis factors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The type II polyketide synthase (PKS) natural product enterocin (1) was isolated from a mangrove-derived novel species Streptomyces qinglanensis 172205 guided by genome sequence, and its putative biosynthetic gene cluster was revealed. Its natural analogues 5-deoxyenterocin (2) and wailupemycin A-C (3-5) were also identified by tandem mass spectrometry. By feeding experiments with aryl acids, strain 172205 was proved to incorporate partial exogenous starter units into enterocin- and wailupemycin-based analogues, thus being a new and suitable microorganism for engineering unnatural enc-derived polyketide metabolites. In addition, biological assays indicated that enterocin showed obvious inhibitory activity against β-amyloid protein (Aβ1-42) fibrillation and moderate cytotoxicity against HeLa and HepG2 for the first time.

Presented here is a draft genome sequence of Streptomyces sp. strain CT34, which produces a novel ribosomally synthesized and posttranslationally modified peptide (RiPP). Analysis of the deduced open reading frame set identified the putative RiPP biosynthesis gene cluster, as well as other secondary metabolite gene clusters., (Copyright © 2015 Zhai et al.)

Coupling titanium dioxide (TiO2) with other semiconductors is a popular method to extend the optical response range of TiO2 and improve its photon quantum efficiency, as coupled semiconductors can increase the separation rate of photoinduced charge carriers in photocatalysts. Differing from normal semiconductors, metallic oxides have no energy gap separating occupied and unoccupied levels, but they can excite electrons between bands to create a high carrier mobility to facilitate kinetic charge separation. Here, we propose the first metallic metal oxide-metal oxide (Ti5O9-TiO2) nanocomposite as a heterojunction for enhancing the visible-light photocatalytic activity of TiO2 nanoparticles and we demonstrate that this hybridized TiO2-Ti5O9 nanostructure possesses an excellent visible-light photocatalytic performance in the process of photodegrading dyes. The TiO2-Ti5O9 nanocomposites are synthesized in one step using laser ablation in liquid under ambient conditions. The as-synthesized nanocomposites show strong visible-light absorption in the range of 300-800 nm and high visible-light photocatalytic activity in the oxidation of rhodamine B. They also exhibit excellent cycling stability in the photodegrading process. A working mechanism for the metallic metal oxide-metal oxide nanocomposite in the visible-light photocatalytic process is proposed based on first-principle calculations of Ti5O9. This study suggests that metallic metal oxides can be regarded as partners for metal oxide photocatalysts in the construction of heterojunctions to improve photocatalytic activity.

Bacterial strain HV38(T) was isolated from mangrove soil, which was collected from Thailand. Chemotaxonomic and morphological characteristics were found to be typical of members of the genus Streptomyces. The strain was found to form a distinct phyletic line in the Streptomyces 16S rRNA gene tree and to be closely associated with the type strains of Streptomyces coeruleofuscus CGMCC 4.1667(T) (98.84 % sequence similarity), Streptomyces chromofuscus CGMCC 4.1451(T) (98.63 %) and Streptomyces albidoflavus CGMCC 4.1291(T) (98.56 %). The major menaquinones were identified as MK-9(H8) and MK-9(H10). Its major cellular fatty acids were found to be iso-C14:0, iso-C15:0, anteiso-C15:0, iso-C16:1ω8c, C16:0, anteiso-C16:1ω8c, iso-C16:0 and anteiso-C16:0. The DNA-DNA hybridization values between strain HV38(T) with S. coeruleofuscus CGMCC 4.1667(T), S. chromofuscus CGMCC 4.1451(T) and S. albidoflavus CGMCC 4.1291(T) were 32.7 ± 0.9, 21.8 ± 0.3 and 19.9 ± 0.9 %, respectively, which clearly supported the conclusion that they belong to separate genomic species. Cumulatively, the data indicated that strain HV38(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces ferrugineus sp. nov. is proposed. The type strain is HV38(T) (=CCTCC AA2014009(T )= DSM 42152(T)).

Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases.

Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.

In drug discovery, promiscuous targets, multifactorial diseases, and "dirty" drugs construct complex network relationships. Network pharmacology description and analysis not only give a systems-level understanding of drug action and disease complexity but can also help to improve the efficiency of target selection and drug design. Visual network pharmacology (VNP) is developed to visualize network pharmacology of targets, diseases, and drugs with a graph network by using disease, target or drug names, chemical structures, or protein sequence. To our knowledge, VNP is the first free interactive VNP server that should be very helpful for systems pharmacology research. VNP is freely available at http://cadd.whu.edu.cn/ditad/vnpsearch.

The purpose of this study was to investigate the effect of zircon-based tricolor pigments (praseodymium zircon yellow, ferrum zircon red, and vanadium zircon blue) on the color, thermal property, crystalline phase composition, microstructure, flexural strength, and translucency of a novel dental lithium disilicate glass-ceramic. The pigments were added to the glass frit, milled, pressed, and sintered. Ninety monochrome samples were prepared and the colors were analyzed. The effect of the pigments on thermal property, crystalline phase composition, and microstructure were determined by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM), respectively. Addition of the pigments resulted in the acquisition of subtractive primary colors as well as tooth-like colors, and did not demonstrate significant effects on the thermal property, crystalline phase composition, microstructure, and flexural strength of the experimental glass-ceramic. Although significant differences (p < 0.01) were observed between the translucencies of the uncolored and 1.0 wt % zircon-based pigment colored ceramics, the translucencies of the latter were sufficient to fabricate dental restorations. These results indicate that the zircon-based tricolor pigments can be used with dental lithium disilicate glass-ceramic to produce abundant and predictable tooth-like colors without significant adverse effects, if mixed in the right proportions., (Copyright © 2013 Wiley Periodicals, Inc.)

An actinomycete, strain 2602GPT1-05(T), was isolated from a composite mangrove soil sample collected from Wenchang, Hainan province, China. Strain 2602GPT1-05(T) showed closest 16S rRNA gene sequence similarity to Micromonospora haikouensis 232617(T) (99.05 %), and phylogenetically clustered with Micromonospora haikouensis 232617(T), Micromonospora matsumotoense IMSNU 22003(T) (98.7 %) and Micromonospora rifamycinica AM105(T) (98.6 %) based on the 16S rRNA and gyrB gene sequence phylogenetic analysis. The strain harboured meso-DAP and glycine as major cell-wall amino acids, and MK-10(H6) and MK-9(H6) as predominant menaquinones. The characteristic whole-cell sugars were xylose, arabinose, glucose and galactose. The polar lipid profile comprised phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol, phosphatidylglycerol, phosphatidylinositol mannosides, unknown phospholipid and an unknown phosphoglycolipid. The major cellular fatty acids were C18 : 1ω9c, iso-C15 : 0, 10-methyl C18 : 0 (tuberculostearic acid), C16 : 0, C18 : 0 and iso-C16 : 0. The DNA G+C content was 71.7 mol%. Furthermore, some physiological and biochemical properties and low DNA-DNA relatedness values enabled the strain to be differentiated from members of closely related species. On the basis of these phenotypic, genotypic and chemotaxonomic data, strain 2602GPT1-05(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora wenchangensis sp. nov. is proposed. The type strain is 2602GPT1-05(T) ( = CCTCC AA 2012002(T) = DSM 45709(T)).

Background: Excessive greater splanchnic nerve (GSN) activation contributes to the progression of gastric ischemia-reperfusion (GI-R) injury. This study was designed to investigate the protective mechanism of cerebellar fastigial nucleus (FN) stimulation against GI-R injury., Methods: The GI-R injury model was induced in rats by clamping the celiac artery for 30 min, and then reperfusion for 30 min, 1, 3, 6, or 24 h, respectively., Key Results: Microinjection of L-Glu (3, 6, 12 μg) into the FN dose-dependently attenuated GI-R injury and GSN activity. In addition, there was an enhancement of gastric mucosal blood flow in GI-R rats. Pretreatment with the glutamic acid decarboxylase antagonist into the FN, the GABAA receptor antagonist into the lateral hypothalamic area or lesion of superior cerebellar peduncle all reversed the protective effects of the FN stimulation. Furthermore, the FN stimulation reduced the TUNEL-positive gastric mucosal cell and Bax-positive gastric mucosal cell in GI-R rats., Conclusions & Inferences: These results indicate that the protective effects of the FN stimulation against GI-R injury may be mediated by attenuation of the excessive GSN activation, gastric mucosal cell apoptosis, and Bax expression in GI-R rats., (© 2012 Blackwell Publishing Ltd.)

The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.

Objective: Diabetes mellitus may impair bone healing after dental implant placement. The objective of this study was to evaluate the effects of the local delivery of basic fibroblast growth factor (bFGF) from poly(lactide-co-glycolide) (PLGA) microspheres on osseointegration around titanium implants in diabetic rats., Study Design: The bFGF-PLGA microspheres were prepared by the W/O/W double-emulsion solvent evaporation method. A total of 20 rats were used to create diabetic animal models by giving them a high-fat and high-sugar diet and a low-dose streptozotocin intraperitoneal injection. Titanium implants were planted into the tibias of the diabetic rats and into 10 normal rats. Microspheres were loaded on the surfaces of the implants in the bFGF intervention group before they were placed into the rats. After 4 or 8 weeks, the tibias containing the implants were removed and embedded with resin. Uncalcified tissue slices were prepared to compare osseointegration., Results: At 4 weeks, the bone-implant contact rate in the diabetic control group was less than that in the control group and the bFGF intervention group (P < .05). At 8 weeks, the results among the 3 groups were similar to those at 4 weeks., Conclusions: The local delivery of bFGF from PLGA microspheres into areas around titanium implants may improve osseointegration in diabetic rats., (Copyright © 2012 Elsevier Inc. All rights reserved.)