Correction and removal of expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Correction and removal of expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

Expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

Correction: Formal synthesis of cyclotheonellazole A.

Correction for 'Formal synthesis of cyclotheonellazole A' by Bohua Long et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00038a.

Formal synthesis of cyclotheonellazole A.

A convergent procedure for the formal synthesis of cyclotheonellazole A in high yields and excellent stereoselectivity has been developed. This synthesis features an efficient preparation of O-pivaloyl-protected α-hydroxy-ß-amino amides and a one-pot process to introduce the challenging thiazole moiety. The overall synthesis is very efficient and paves the way for the preparation of analogues for drug development.

A Retrospective, Nested Case-Control Study to Develop a Biomarker-Based Model for ARDS Diagnostics.

BACKGROUND: Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics. METHODS: There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes. RESULTS: C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered. CONCLUSIONS: A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.

Impact of posttranslational modifications in pancreatic carcinogenesis and treatments.

Pancreatic cancer (PC) is a highly aggressive cancer, with a 9% 5-year survival rate and a high risk of recurrence. In part, this is because PC is composed of heterogeneous subgroups with different biological and functional characteristics and personalized anticancer treatments are required. Posttranslational modifications (PTMs) play an important role in modifying protein functions/roles and are required for the maintenance of cell viability and biological processes; thus, their dysregulation can lead to disease. Different types of PTMs increase the functional diversity of the proteome, which subsequently influences most aspects of normal cell biology or pathogenesis. This review primarily focuses on ubiquitination, SUMOylation, and NEDDylation, as well as the current understanding of their roles and molecular mechanisms in pancreatic carcinogenesis. Additionally, we briefly summarize studies and clinical trials on PC treatments to advance our knowledge of drugs available to target the ubiquitination, SUMOylation, and NEDDylation PTM types. Further investigation of PTMs could be a critical field of study in relation to PC, as they have been implicated in the initiation and progression of many other types of cancer.

Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications.

Both hereditary and sporadic breast cancer are suggested to develop from a stem cell subcomponent retaining most key stem cell properties but with dysregulation of self-renewal pathways, which drives tumorigenic differentiation and cellular heterogeneity. Cancer stem cells (CSCs), characterized by their self-renewal and differentiation potential, have been reported to contribute to chemo-/radio-resistance and tumor initiation and to be the main reason for the failure of current therapies in breast cancer and other CSC-bearing cancers. Thus, CSC-targeted therapies, such as those inducing CSC apoptosis and differentiation, inhibiting CSC self-renewal and division, and targeting the CSC niche to combat CSC activity, are needed and may become an important component of multimodal treatment. To date, the understanding of breast cancer has been extended by advances in CSC biology, providing more accurate prognostic and predictive information upon diagnosis. Recent improvements have enhanced the prospect of targeting breast cancer stem cells (BCSCs), which has shown promise for increasing the breast cancer remission rate. However, targeted therapy for breast cancer remains challenging due to tumor heterogeneity. One major challenge is determining the CSC properties that can be exploited as therapeutic targets. Another challenge is identifying suitable BCSC biomarkers to assess the efficacy of novel BCSC-targeted therapies. This review focuses mainly on the characteristics of BCSCs and the roles of BCSCs in the formation, maintenance and recurrence of breast cancer; self-renewal signaling pathways in BCSCs; the BCSC microenvironment; potential therapeutic targets related to BCSCs; and current therapies and clinical trials targeting BCSCs.

Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

A concise and efficient procedure for the total synthesis of tubulysin U and N14-desacetoxytubulysin H has been developed with high stereoselectivity on a gram scale. This synthesis features an elegant cascade one-pot process to install the challenging thiazole moiety and the employment of stereoselective reductions and a series of high-yield mild reactions to ensure the requisite stereochemistry, reaction scale, and yield and to avoid the vexing epimerization occurring during peptide formation.

Chemical constituents from Lonicera japonica flower buds and their anti-hepatoma and anti-HBV activities.

Three new naturally occurring monoterpenoids, japopenoid A (1), japopenoid B (23) japopenoid C (24), and one new caffeoylquinic acid derivative (28), together with thirty-one known compounds (2-22, 25-27, 29-35), were isolated and identified from the flower buds of Lonicera japonica Thunb. Their structures were determined by extensive 1D and 2D NMR spectroscopic methods, high-resolution mass spectrometry, and the absolute configurations of 1, 23, 24 were determined by comparison of their electronic circular dichroism (ECD) spectrum with literature and theoretical calculation. Structurally, compound 1 is a monoterpenoid featured with an unusual tricyclic skeleton. All compounds (1-35) were evaluated for their cytotoxicities against human liver cancer cell lines (HepG 2 and SMMC-7721). Compound 12 exhibited the most potent activity with IC50 values of 26.54 ±â€¯1.95 and 8.72 ±â€¯1.57 µg/ml against HepG 2 and SMMC-7721, and the IC50 values of compound 13 were 26.54 ±â€¯1.95 and 12.35 ±â€¯1.43 µg/ml, respectively. Western blot results further proved that compound 13 induces hepatoma cell apoptosis via the intrinsic apoptosis pathway. In addition, most terpenoids showed inhibitory activity against HBsAg and HBeAg secretion, and HBV DNA replication. In particular, 25 µg/mlof compound 11 inhibits HBsAg and HBeAg secretion, and HBV DNA replication by 39.39 ±â€¯5.25, 15.64 ±â€¯1.25, and 16.13 ±â€¯4.10% compared to the control (p < 0.05). These results indicated that L. japonica flower buds could be served as functional food for anti-hepatoma and anti-HBV activities.

Deoxyshikonin isolated from Arnebia euchroma inhibits colorectal cancer by down-regulating the PI3K/Akt/mTOR pathway.

Context: Shikonins, a series of natural occurring naphthoquinones extracted from Arnebia euchroma (Royle) Jonst. (Boraginaceae), have antitumor activities and low toxicity. Objective: To illuminate potential activity and mechanism of shikonins against colorectal cancer (CRC). Materials and methods: Five shikonins were isolated from A. euchroma, and elucidated by extensive spectroscopic analysis. Anti-proliferative activities of shikonins (0-100 µg/mL) on human colorectal cells were evaluated by MTT and CCK-8 for 24 or 48 h. Cell apoptosis and cycle distribution were examined by FCM analysis. The expression of PI3K/Akt/mTOR pathway mRNAs and proteins was analysed by RT-PCR and Western blot, respectively. Cell viability, cell apoptosis, cell cycle and protein expression were measured, when co-treated with PI3K/Akt/mTOR pathway inhibitors. The in vivo activity of deoxyshikonin was evaluated using xenograft tumour model. Results: Deoxyshikonin and another four shikonins were isolated and identified. Deoxyshikonin exhibited anti-proliferative activity with IC50 of 10.97 µM against HT29 cells. Moreover, the percentage of early apoptotic cells and G0/G1 cells increased from 1 to 29% and 44 to 67% with 0-50 µg/mL deoxyshikonin, respectively. Deoxyshikonin also down-regulated the expression of PI3K, p-PI3K, Akt, p-Akt308 and mTOR proteins in HT29 and DLD-1 cells. Moreover, LY294002, NVP-BEZ235 and MK-2206 can make deoxyshikonin more cell proliferation inhibited, cell cycle arrested at G0/G1 and apoptosis promoted. In vivo study, the weight of tumour tissues at deoxyshikonin groups was significantly reduced compared with the control group, and PI3K, p-PI3K, Akt, p-Akt308 and mTOR expression was decreased. Discussion and conclusions: We can conclude that deoxyshikonin isolated from Arnebia euchroma inhibited CRC through the PI3K/Akt/mTOR pathway.

The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development.

DDX11 was recently identified as a cause of Warsaw breakage syndrome (WABS). However, the functional mechanism of DDX11 and the contribution of clinically described mutations to the pathogenesis of WABS are elusive. Here, we show that DDX11 is a novel nucleolar protein that preferentially binds to hypomethylated active ribosomal DNA (rDNA) gene loci, where it interacts with upstream binding factor (UBF) and the RNA polymerase I (Pol I). DDX11 knockdown changed the epigenetic state of rDNA loci from euchromatic structures to more heterochromatic structures, reduced the activity of UBF, decreased the recruitment of UBF and RPA194 (a subunit of Pol I) to rDNA promoter, suppressed rRNA transcription and thereby inhibited growth and proliferation of HeLa cells. Importantly, two indentified WABS-derived mutants, R263Q and K897del, and a Fe-S deletion construct demonstrated significantly reduced binding abilities to rDNA promoters and lowered DNA-dependent ATPase activities compared with wild-type DDX11. Knockdown of the zebrafish ortholog of human DDX11 by morpholinos resulted in growth retardation and vertebral and craniofacial malformations in zebrafish, concomitant with the changes in histone epigenetic modifications at rDNA loci, the reduction of Pol I recruitment to the rDNA promoter and a significant decrease in nascent pre-RNA levels. These growth disruptions in zebrafish in response to DDX11 reduction showed similarities to the clinically described developmental abnormalities found in WABS patients for the first time in any vertebrate. Thus, our results indicate that DDX11 functions as a positive regulator of rRNA transcription and provides a novel insight into the pathogenesis of WABS.

Therapeutic effects of Qian-Yu decoction and its three extracts on carrageenan-induced chronic prostatitis/chronic pelvic pain syndrome in rats.

BACKGROUND: Qian-Yu decoction (QYD) is a traditional Chinese medicinal recipe composed of Radix astragali (Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao, Fabaceae ), Herba epimedii (Epimedium brevicornum Maxim., Berberidaceae), Herba leonuri (Leonurus japonicus Houtt., Lamiaceae), Cortex phellodendri (Phellodendron chinense Schneid., Rutaceae) and Radix achyranthis bidentatae (Achyranthes bidentata Bl., Amaranthaceae). This study aimed to evaluate the therapeutic activity of QYD against carrageenan-induced chronic prostatic/chronic pelvic pain syndrome (CP/CPPS) in rats and further elucidate its effective components. METHODS: Three types of components, total polysaccharides, total flavonoids and total saponins were separately extracted from QYD. Carrageenan-induced CP/CPPS rats were intragastrically administered with lyophilized product of QYD, individual extracts and all the combined forms of extracts for three weeks. Prostatic index (PI) was determined and histopathological analysis was performed. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PEG2) in rat prostate tissues were measured using ELISA. The production of inducible nitric oxide synthase (iNOS) was evaluated by an enzymatic activity assay, and the release of nitric oxide (NO) was determined by a nitrate/nitrite assay. RESULTS: Treatment with QYD significantly ameliorated the histological changes of CP/CPPS rats and reduced the PI by 44.3%, with a marked downregulation of TNF-α (42.8% reduction), IL-1ß (45.3%), COX-2 (36.6%), PGE2 (44.2%), iNOS (54.1%) and NO (46.0%). Each of three extracts attenuated the symptom of CP/CPPS, but much more weakly than QYD. The combined administration of three extracts showed efficacy comparable to that of QYD while better than that of any combination of two extracts. A principal component analysis of the six inflammatory mediators as variables indicated that the effects of TS on CP/CPPS were rather different from those of TF and TP, which were similar. CONCLUSIONS: QYD can be beneficial in prevention and treatment of CP/CPPS. Polysaccharides, flavonoids and saponins, as the major effective components of QYD, exert a cooperative effect on CP/CPPS.

The fruits of wampee inhibit H2O2-induced apoptosis in PC12 cells via the NF-κB pathway and regulation of cellular redox status.

Wampee (Clausena lansium) fruits (CLS), whose pulp can be used to prepare fruit cups, desserts, jam, or jelly, can be eaten along with the peel. In this study, a PC12 cell model was built to observe the protective effect of CLS against H2O2-induced oxidative stress. We found that pretreatment with CLS increased cell viability and inhibited cytotoxicity, caspase-3 activity and DNA condensation. CLS also attenuated the increase in ROS production and MMP reduction. Moreover, we attempted to determine whether CLS suppressed the expression and phosphorylation of NF-κB. Western blot and immunostaining assay revealed that CLS inhibited H2O2-induced up-regulation of NF-κB p65 and pNF-κB p65. And CLS significantly suppressed the translocation of NF-κB p65 and pNF-κB p65 from cytoplasm to nuclear. Also, seven major compounds including a new flavanoid, luteolin-4'-O-ß-d-gluco-pyranoside (3) and six known compounds 1,2, 4-7 were isolated and identified from CLS. Their antioxidative and H2O2-induced PC12 cell apoptosis-reversing activity were determined. These findings suggest that CLS and its major constituents (flavanoids) may be potential antioxidant agents and should encourage further research into their use as a functional food for neurodegenerative diseases.

Serum apolipoprotein B to apolipoprotein A-I ratio predicts mortality in patients with heart failure.

AIMS: Apolipoproteins have been reported to be involved in many cardiovascular diseases. The aim of our study was to investigate the prognostic value of apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio (ApoB/ApoA-I) in patients with heart failure (HF). METHODS AND RESULTS: We randomly assigned 2400 HF patients into the training cohort (n = 1400) and the validation cohort (n = 1000). Using a receiver operating characteristic curve, we identified the optimal cut-off value of the ApoB/ApoA-I in the training cohort as 0.69, which was further validated in the validation cohort. A propensity score matching (PSM) analysis was conducted to eliminate the imbalance in the baseline characteristics of the high and low ApoB/ApoA-I group. A total of 2242 HF patients were generated in the PSM cohort. We also validated our results with an independent cohort (n = 838). Univariate and multivariate analyses were conducted to explore the independent prognostic value of ApoB/ApoA-I in the training cohort (n = 1400), the validation cohort (n = 1000), the PSM cohort (n = 2242), and the independent cohort (n = 838). Patients with high ApoB/ApoA-I ratio had significantly poorer prognosis compared with those with low ApoB/ApoA-I ratio in the training cohort, the validation cohort, the PSM cohort, and the independent cohort (P < 0.05). Multivariate analysis indicated that the ApoB/ApoA-I was an independent prognostic factor for HF in the training cohort [hazard ratio (HR) = 1.637, 95% confidence interval (CI) = 1.201-2.231, P = 0.002], the validation cohort (HR = 1.54, 95% CI = 1.051-2.257, P = 0.027), the PSM cohort (HR = 1.645, 95% CI = 1.273-2.125, P < 0.001), and the independent cohort (HR = 1.987, 95% CI = 1.251-3.155, P = 0.004). CONCLUSIONS: Serum ApoB/ApoA-I ratio is an independent predictor for the prognosis of HF patients.

Correction and Removal of Expression of Concern: Highly stereoselective gram scale synthesis of all the four diastereoisomers of Boc-protected 4-methylproline carboxylates.

[This corrects the article DOI: 10.1039/C9RA06827A.].

Classical famous prescription of Jichuan decoction improved loperamide-induced slow transit constipation in rats through the cAMP/PKA/AQPs signaling pathway and maintained inflammatory/intestinal flora homeostasis.

Introduction: Jichuan decoction (JCD) is a well-known traditional Chinese medicinal formula that moistens the intestines and is widely used for the treatment of constipation in China. However, its effects and mechanisms in alleviating slow transit constipation (STC) in vivo remain unclear. We attempted to demonstrate the effect of JCD, with and without essential oil (VO), on intestinal transit and its underlying molecular mechanisms in rats with loperamide-induced STC. Materials and methods: Water consumption, body weight, fecal water content, time to first melena excretion, and intestinal transit ratio of the animals were measured. 5-Hydroxytryptamine (5-HT), substance P (SP), vasoactive intestinal peptide (VIP), and interleukin-6 (IL-6) levels in the sera of rats were evaluated using ELISA. Hematoxylin and eosin and Periodic Acid-Schiff staining were used to determine intestinal tissue histology, while quantitative real-time PCR, western blotting, and immunohistochemical analysis were used to assess the relative expression levels of cAMP/PKA/AQPs pathway- and inflammation-related proteins. 16 S rDNA sequence analysis of rat feces was used to determine the diversity and abundance of the intestinal flora. Results: The JCD groups showed reduced time to first melena excretion and expression of VIP and IL-6. The JCD groups, specifically JCD + VO groups, showed increased fecal water content, intestinal transit rate, and SP expression. Further, these groups showed improved histological characteristics of the colon, with no significant change in the index of immune organs or morphological characteristics of other organs. In addition, a significant decrease in the activation of the cAMP/PKA/AQPs signaling pathway in the colon tissue was observed in these groups, specifically the JCD + VO groups. Moreover, treatment with JCD, with or without VO, downregulated the expression of inflammatory factors and enriched the diversity of intestinal flora as evidenced by polymorphism analysis and the contents of Bacteroides, Lactobacillus, and Erysipelas, with the JCD + VO groups showing better therapeutic outcomes. Conclusion: JCD improved loperamide-induced STC, and co-administration with VO exhibited better activity than sole JCD therapy. JCD may improve STC by inhibiting the cAMP/PKA/AQPs signaling pathway and maintaining inflammatory/intestinal flora homeostasis.

Tubuloside B, a major constituent of Cistanche deserticola, inhibits migration of hepatocellular carcinoma by inhibiting Hippo-YAP pathway.

BACKGROUND: Studies have shown that phenylethanoid glycosides (PhGs) have multiple pharmacological effects such as anti-inflammatory, hepatoprotective or neuroprotective functions, whereas their anti-tumor effects are rarely studied. Tubuloside B (Tub B) is a PhG isolated from Cistanche deserticola, a traditional Chinese medicine. To date, there is a lack of comprehensive research regarding the biological activity of Tub B. PURPOSE: The subject of the current study was to investigate the anti-hepatocellular carcinoma (HCC) cell activity and the underlying mechanism of Tub B. METHODS: We evaluated the in vitro anti-migratory effect of Tub B by scratch and transwell assays. RNA-seq was employed to identify the differential genes by Tub B. Besides, the functional mechanism of Tub B was investigated by distinct molecular biology techniques including immunofluorescent staining, quantitative PCR, as well as western blot analysis. Subsequently, we utilized Hep3B cells for in vivo metastasis assays through spleen injection and evaluated the anti-migratory effect of Tub B in hepatocellular carcinoma (HCC). RESULTS: Tub B exhibited in vitro and in vivo inhibition of HCC cell migration. Tub B decreased the expression of transcriptional target genes downstream of the Hippo pathway, including CTGF, CYR61, and N-cadherin as determined by RNA-seq. Furthermore, mechanistic studies confirmed that Tub B increased phosphorylation of YAP at S127, which contributes to YAP cytoplasmic localization. Additionally, overexpression of YAP abrogated Tub B-induced inhibition of HCC migration and the mRNA levels of CTGF, CYR61, and N-cadherin. CONCLUSIONS: Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.

Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis.

Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case-control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019-1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.

Robust positive association between serum urate and the risk of chronic obstructive pulmonary disease: hospital-based cohort and Mendelian randomisation study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and hyperuricaemia are both characterised by systemic inflammation. Preventing chronic diseases among the population with common metabolic abnormality is an effective strategy. However, the association of hyperuricaemia with the higher incidence and risk of COPD remains controversial. Therefore, replicated researches in populations with distinct characteristics or demographics are compellingly warranted. METHODS: This cohort study adopted a design of ambispective hospital-based cohort. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to minimise the effects of potential confounding factors. A Cox regression model and restricted cubic spline (RCS) model were applied further to assess the effect of serum urate on the risk of developing COPD. Finally, we conducted a two-sample Mendelian randomisation (MR) analysis to explore evidence of causal association. RESULTS: There is a higher incidence in the population with hyperuricaemia compared with the population with normal serum urate (22.29/1000 person-years vs 8.89/1000 person-years, p=0.009). This result is robust after performing PSM (p=0.013) and IPTW (p<0.001). The Cox model confirms that hyperuricaemia is associated with higher risk of developing COPD (adjusted HR=3.35 and 95% CI=1.61 to 6.96). Moreover, RCS shows that the risk of developing COPD rapidly increases with the concentration of serum urate when it is higher than the reference (420 µmol/L). Finally, in MR analysis, the inverse variance weighted method evidences that a significant causal effect of serum urate on COPD (OR=1.153, 95% CI=1.034 to 1.289) is likely to be true. The finding of MR is robust in the repeated analysis using different methods and sensitivity analysis. CONCLUSIONS: Our study provides convincing evidence suggesting a robust positive association between serum urate and the risk of developing COPD, and indicates that the population with hyperuricaemia is at high risk of COPD in the Chinese population who seek medical advice or treatment in the hospital.

Investigations on the antifungal effect of nerol against Aspergillus flavus causing food spoilage.

The antifungal efficacy of nerol (NEL) has been proved against Aspergillus flavus by using in vitro and in vivo tests. The mycelial growth of A. flavus was completely inhibited at concentrations of 0.8 µ L/mL and 0.1 µ L/mL NEL in the air at contact and vapor conditions, respectively. The NEL also had an evident inhibitory effect on spore germination in A. flavus along with NEL concentration as well as time-dependent kinetic inhibition. The NEL presented noticeable inhibition on dry mycelium weight and synthesis of aflatoxin B1 (AFB1) by A. flavus, totally restraining AFB1 production at 0.6 µ L/mL. In real food system, the efficacy of the NEL on resistance to decay development in cherry tomatoes was investigated in vivo by exposing inoculated and control fruit groups to NEL vapor at different concentration. NEL vapors at 0.1 µ L/mL air concentration significantly reduced artificially contaminated A. flavus and a broad spectrum of fungal microbiota. Results obtained from presented study showed that the NEL had a great antifungal activity and could be considered as a benefit and safe tool to control food spoilage.