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Ethnopharmacological Relevance: WenTongGanPi Decoction (WTGPD) is a representative medical practice of the Fuyang School of Traditional Chinese Medicine (TCM), which originated from the classical Lu's Guizhi method. WTGPD places emphasis on the balance and functionality of yang qi, and is effective in treating TCM symptoms related to liver qi stagnation and spleen yang deficiency. In TCM, diarrhea-predominant irritable bowel syndrome (IBS-D) is often diagnosed as liver depression and spleen deficiency, and the use of WTGPD has shown significant therapeutic effect. However, the underlying mechanism of WTGPD treating IBS-D remains unclear., Aim of the Study: To explore the effect and mechanism of WTGPD in the treatment of IBS-D., Materials and Methods: An IBS-D model with liver depression and spleen deficiency was constructed by chronic immobilization stress stimulation and sennae folium aqueous gavage. The impact of WTGPD on IBS-D rats was evaluated through measurements of body weight, fecal water content, and abdominal withdrawal reflex (AWR). Intestinal permeability was assessed using hematoxylin-eosin (HE), alcian blue-periodic acid schiff (AB-PAS), immunofluorescence (IF) staining, and quantitative real-time PCR (qRT-PCR). The components of WTGPD were analyzed using UPLC-Q-TOF-MS. The underlying mechanisms were investigated through network pharmacology, transcriptomics sequencing, western blot (WB), molecular docking, and 16S rRNA sequencing., Results: WTGPD treatment effectively alleviated diarrhea and abnormal pain in IBS-D rats (P < 0.05). It enhanced the intestinal barrier function by improving colonic structure and increasing the expression of tight junction proteins (P < 0.05). A total of 155 components were identified in WTGPD. Both network pharmacology and transcriptomics sequencing analysis highlighted MAPK as the key signaling pathway in WTGPD's anti-IBS-D effect. The WB results showed a significant decrease in p-p38, p-ERK and p-JNK expression after WTGPD treatment (P < 0.0001). Guanosine, adenosine and hesperetin in WTGPD may be involved in regulating the phosphorylation of p38, ERK and JNK. Additionally, WTGPD significantly enhanced microbial diversity and increased the production of colonic valeric acid in IBS-D rats (P < 0.01)., Conclusion: In conclusion, our findings suggest that WTGPD can effectively alleviate IBS-D and improve intestinal barrier likely via inhibiting MAPK signal pathway and improving micobial dysbiosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aeromonas salmonicida is an important pathogen that causes furunculosis in trout and salmon with high morbidity and mortality, resulting in significant economic losses in aquaculture. Overuse of antibiotics has led to the continuous emergence of drug-resistant strains. Hence, there is an urgent need to find an alternative environmentally friendly antimicrobial agent. In this study, we isolated a virulent phage of A. salmonicida , named ASG01, which belongs to the Myoviridae family and maintains lytic activity at a pH value range from 4 to 12 and in the temperature range from 30 °C to 60 °C. The whole genomic sequence of ASG01 showed 82% similarity to Aeromonas phage pAh6-C. The cell wall hydrolase (Cwh)-encoding gene from the genome of ASG01 was predicted and heterologously expressed. Notably, in the absence of additional phage genes, endogenous expression of Cwh could lyse E. coli cells and greatly inhibit the growth of tested fish pathogenic bacteria. The lytic activity of Cwh was eliminated when the predicted active site was mutated. These results indicate that Cwh of ASG01 possessed excellent lytic activity and a wide antibacterial spectrum, suggesting its potential as an effective enzybiotic.

Xenorhabdus, known for its symbiotic relationship with Entomopathogenic nematodes (EPNs), belongs to the Enterobacteriaceae family. This dual-host symbiotic nematode exhibits pathogenic traits, rendering it a promising biocontrol agent against insects. Our prior investigations revealed that Xenorhabdus stockiae HN&#95;xs01, isolated in our laboratory, demonstrates exceptional potential in halting bacterial growth and displaying anti-tumor activity. Subsequently, we separated and purified the supernatant of the HN&#95;xs01 strain and obtained a new compound with significant inhibitory activity on tumor cells, which we named XNAE. Through LC-MS analysis, the mass-to-nucleus ratio of XNAE was determined to be 254.24. Our findings indicated that XNAE exerts a time- and dose-dependent inhibition on B16 and HeLa cells. After 24 h, its IC 50 for B16 and HeLa cells was 30.178 µg/mL and 33.015 µg/mL, respectively. Electron microscopy revealed conspicuous damage to subcellular structures, notably mitochondria and the cytoskeleton, resulting in a notable reduction in cell numbers among treated tumor cells. Interestingly, while XNAE exerted a more pronounced inhibitory effect on B16 cells compared to HeLa cells, it showed no discernible impact on HUVEC cells. Treatment of B16 cells with XNAE induced early apoptosis and led to cell cycle arrest in the G2 phase, as evidenced by flow cytometry analysis. The impressive capability of X. stockiae HN&#95;xs01 in synthesizing bioactive secondary metabolites promises to significantly expand the reservoir of natural products. Further exploration to identify the bioactivity of these compounds holds the potential to shed light on their roles in bacteria-host interaction. Overall, these outcomes underscore the promising potential of XNAE as a bioactive compound for tumor treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Supramolecular radical chemistry is an emerging area bridging supramolecular chemistry and radical chemistry, and the integration of radicals into the supramolecular architecture offers a new dimension for tuning their structures and functions. Although various efforts have been devoted to the fabrication of supramolecular junctions, the charge transport characterization through the supramolecular radicals remained unexplored due to the challenges in creating supramolecular radicals at the single-molecule level. Here, we demonstrate the fabrication and charge transport investigation of a supramolecular radical junction using the electrochemical scanning tunneling microscope-based break junction (EC-STM-BJ) technique. We found that the conductance of a supramolecular radical junction was more than 1 order of magnitude higher than that of a supramolecular junction without a radical and even higher than that of a fully conjugated oligophenylenediamine molecule with a similar length. The combined experimental and theoretical investigations revealed that the radical increased the binding energy and decreased the energy gap in the supramolecular radical junction, which leads to the near-resonant transport through the supramolecular radical. Our work demonstrated that the supramolecular radical can provide not only strong binding but also efficient electrical coupling between building blocks, which provides new insights into supramolecular radical chemistry and new materials with supramolecular radicals.

Objective: The purpose of this study was to evaluate the clinical diagnostic value of metagenomic next-generation sequencing (mNGS) for tuberculosis (TB)., Methods: This retrospective study included 52 patients with suspected TB infection. mNGS, targeted PCR, acid-fast staining and, T-SPOT.TB assay were performed on the specimen. The positive rate of mNGS and traditional detection methods was statistically analyzed. Pathological tests were performed when necessary., Results: In total, 52 patients with suspected of TB in this study were included in the analysis, and 31 patients were finally diagnosed with TB. Among 52 patients, 14 (26.9%) cases were positive for acid-fast staining. The positive rate of T-SPOT.TB assay in 52 patients was 73.1% (38/52). Among 52 patients, 39 (75%) were detected positive for Mycobacterium tuberculosis ( M TB) by mNGS. Regarding the detection rate of MTB, mNGS were as high as 75% (39/52), whereas acid-resistant staining was only 26.9% (14/52), which showed a statistically significant difference (p<0.05). The positive rates of T-SPOT.TB assay and mNGS were not statistically significant (p>0.05). Of the 52 suspected TB patients, 24 had targeted PCR, of which 18 were PCR positive. In 24 patients, the positive rate of PCR was 75%, and the positive rate of mNGS was 100%, with statistical difference between them (p<0.05)., Conclusions: The detection rate of MTB by mNGS was higher than that by conventional acid-fast staining and PCR, but not statistically significant compared with T-SPOT.TB assay. As an adjunctive diagnostic technology, mNGS can be combined with traditional detection methods to play a guiding role in the diagnosis and treatment of TB., 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 © 2023 Liu, Wang, Li and Yu.)

Xenorhabdus can produce a large number of secondary metabolites with insecticidal, bacteriostatic, and antitumor activities. Efficient gene editing tools will undoubtedly facilitate the functional genomics research and bioprospecting in Xenorhabdus. In this study, BlastP analysis using the amino acid sequences of Redαβ or RecET recombinases as queries resulted in the identification of an operon (XBJ1&#95;operon 0213) containing RecET-like recombinases encoding genes from the genome of Xenorhabdus bovienii strain SS-2004. Three proteins encoded by this operon was indispensable for full activity of recombineering, namely XBJ1-1173 (RecE-like protein), XBJ1-1172 (RecT-like protein), and XBJ1-1171 (single-strand annealing protein). Using this newly developed recombineering system, a gene cluster responsible for biosynthesis of a novel secondary metabolite (Min16) was identified from X. stockiae HN&#95;xs01 strain. Min16 which exhibited antibacterial and cytotoxic activities was determined to be a cyclopeptide composed of Acyl-Phe-Thr-Phe-Pro-Pro-Leu-Val by using high-resolution mass spectrometry and nuclear magnetic resonance analysis, and was designated as changshamycin. This host-specific recombineering system was proven to be effective for gene editing in Xenorhabdus, allowing for efficient discovery of novel natural products with attractive bioactivities. KEY POINTS: • Screening and identification of efficient gene editing tools from Xenorhabdus • Optimization of the Xenorhabdus electroporation parameters • Discovery of a novel cyclopeptide compound with multiple biological activities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nocardia is an opportunistic pathogen that mainly involves immunosuppressed patients and causes a high mortality rate. As an emerging approach to detect infectious pathogens, metagenomic next-generation sequencing (mNGS) was reported in the detection of Nocardia . However, there is no evidence demonstrating the effect of mNGS on the prognosis of Nocardia infection. In this retrospective study, we included 18 nocardiosis patients. Nocardia species were detected by mNGS from their clinical samples. All the patients were diagnosed with nocardiosis by clinical experts through a comprehensive evaluation. Of these 18 patients, fever is the most frequent initial symptom. Compared to traditional culture methods, mNGS provides a faster turnaround time (TAT) and higher sensitivity. Pulmonary nocardiosis was the most common clinical presentation in the study. mNGS detected 13 types of Nocardia species, of which Nocardia abscessus and Nocardia cyriacigeorgica were the most common species. The study's most noteworthy discovery is that mNGS outperforms culture at detecting mixed infections (more than one pathogen detected in one clinical specimen, including bacteria, fungi, and excluding virus), and number of infectious species was an independent risk factor for nocardiosis patients' prognostics after adjusting age, ICU days, gender and underlying diseases (adjusted HR = 1.47, 95% CI: 1.09-1.98, p = 0.011). As a result, we believe that by detecting mixed infections (more than one pathogenic species), mNGS can provide a clinical risk warning for the prognosis of nocardiosis., 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 Jiao, Ma, Li, Wang, Liu, Guo and Lv.)

Objective: To analyze the clinical application and related influencing factors of metagenomic next-generation sequencing (mNGS) in patients with sepsis in intensive care unit (ICU)., Methods: The study included 124 patients with severe sepsis admitted to the ICU in the First Affiliated Hospital of Zhengzhou University from June 2020 to September 2021. Two experienced clinicians took blood mNGS and routine blood cultures of patients meeting the sepsis diagnostic criteria within 24 hours after sepsis was considered, and collection the general clinical data., Results: mNGS positive rate was higher than traditional blood culture (67.74% vs. 19.35%). APACHE II score [odds ratio ( OR )=1.096], immune-related diseases ( OR =6.544), and hypertension ( OR =2.819) were considered as positive independent factors for mNGS or culture-positive. The sequence number of microorganisms and pathogen detection (mNGS) type had no effect on prognosis. Age ( OR =1.016), female ( OR =5.963), myoglobin ( OR =1.005), and positive virus result ( OR =8.531) were independent risk factors of sepsis mortality. Adjusting antibiotics according to mNGS results, there was no statistical difference in the prognosis of patients with sepsis., Conclusion: mNGS has the advantages of rapid and high positive rate in the detection of pathogens in patients with severe sepsis. Patients with high APACHE II score, immune-related diseases, and hypertension are more likely to obtain positive mNGS results. The effect of adjusting antibiotics according to mNGS results on the prognosis of sepsis needs to be further evaluated., 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 Sun, Zhang, Yang, Yang, Wang, Li, Li and Sun.)

Though Saccharina japonica cultivation has been established for many decades in East Asian countries, the domestication process of sugar kelp (Saccharina latissima) in the Northeast United States is still at its infancy. In this study, by using data from our breeding experience, we will demonstrate how obstacles for accelerated genetic gain can be assessed using simulation approaches that inform resource allocation decisions. Thus far, we have used 140 wild sporophytes that were sampled in 2018 from the northern Gulf of Maine to southern New England. From these sporophytes, we sampled gametophytes and made and evaluated over 600 progeny sporophytes from crosses among the gametophytes in 2019 and 2020. The biphasic life cycle of kelp gives a great advantage in selective breeding as we can potentially select both on the sporophytes and gametophytes. However, several obstacles exist, such as the amount of time it takes to complete a breeding cycle, the number of gametophytes that can be maintained in the laboratory, and whether positive selection can be conducted on farm-tested sporophytes. Using the Gulf of Maine population characteristics for heritability and effective population size, we simulated a founder population of 1,000 individuals and evaluated the impact of overcoming these obstacles on rate of genetic gain. Our results showed that key factors to improve current genetic gain rely mainly on our ability to induce reproduction of the best farm-tested sporophytes, and to accelerate the clonal vegetative growth of released gametophytes so that enough gametophyte biomass is ready for making crosses by the next growing season. Overcoming these challenges could improve rates of genetic gain more than 2-fold. Future research should focus on conditions favorable for inducing spring reproduction, and on increasing the amount of gametophyte tissue available in time to make fall crosses in the same year., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Alcoholic liver damage has become a widespread health problem as alcohol consumption increases and is usually identified by elevated liver transaminase. We conducted this study to investigate the role of the gut microbiome in the individual susceptibility to alcoholic liver injury. We divided the participants into four groups based on alcohol consumption and liver transaminase elevation, which were drinking case group, drinking control group, non-drinking case group, and non-drinking control group. The drinking case group meant participants who were alcohol consumers with elevated liver transaminase. We found that alpha and beta diversities of the drinking case group differed from the other three groups. Species Faecalibacterium prausnitzii and Roseburia hominis were significantly in lower abundance in the drinking case group and were proved the protective effect against inflammatory liver damage in the former study. Ruminococcus gnavus exhibited the most positive association to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and contributed to liver inflammation., 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 Jiao, Yan, Shi, Liu, Li, Lv, Ding and Li.)

Saccharina latissima (sugar kelp) is one of the most widely cultivated brown marine macroalgae species in the North Atlantic and the eastern North Pacific Oceans. To meet the expanding demands of the sugar kelp mariculture industry, selecting and breeding sugar kelp that is best suited to offshore farm environments is becoming necessary. To that end, a multi-year, multi-institutional breeding program was established by the U.S. Department of Energy's (DOE) Advanced Research Projects Agency-Energy (ARPA-E) Macroalgae Research Inspiring Novel Energy Resources (MARINER) program. Hybrid sporophytes were generated using 203 unique gametophyte cultures derived from wild-collected Saccharina spp . for two seasons of farm trials (2019-2020 and 2020-2021). The wild sporophytes were collected from 10 different locations within the Gulf of Maine (USA) region, including both sugar kelp ( Saccharina latissima ) and the skinny kelp species ( Saccharina angustissima ). We harvested 232 common farm plots during these two seasons with available data. We found that farmed kelp plots with skinny kelp as parents had an average increased yield over the mean (wet weight 2.48 ± 0.90 kg m -1 and dry weight 0.32 ± 0.10 kg m -1 ) in both growing seasons. We also found that blade length positively correlated with biomass in skinny kelp x sugar kelp crosses or pure sugar kelp crosses. The skinny x sugar progenies had significantly longer and narrower blades than the pure sugar kelp progenies in both seasons. Overall, these findings suggest that sugar x skinny kelp crosses provide improved yield compared to pure sugar kelp crosses., Supplementary Information: The online version contains supplementary material available at 10.1007/s10811-022-02811-1., Competing Interests: Conflict of interest and consent for publicationAuthors declare no conflict of interest and provide consent for publication., (© The Author(s) 2022.)

Objectives: The health-related quality of life (HRQoL) and utilities of patients with chronic hepatitis B (CHB) virus infection, including compensated cirrhosis (CC), decompensated cirrhosis (DC) and different stages of hepatocellular carcinoma (HCC), have not been well described in China. This study aimed to evaluate HRQoL and utilities and provide parameters for the economic evaluation of CHB-related diseases., Methods: We conducted a multicentre cross-sectional and study to measure the HRQoL of patients with CHB, CC, DC and HCC using the Chinese short form (SF) 36 health survey V.2. The utilities were extracted based on the SF-six dimension scoring model. Multivariable regression analyses identified the effects on HRQoL., Results: A total of 1071 patients (639 with CHB, 125 with CC, 85 with DC and 222 with HCC) were invited to complete the questionnaire. Physical HRQoL was not impaired in the CHB stage, while mental HRQoL was significantly impaired. Physical composite summary scores have a more significant decrease than mental composite summary scores at the advanced stages (CC, DC and HCC). The utility scores of CHB only, CC, DC and HCC were 0.773, 0.750, 0.683 and 0.640, respectively. The utility scores in the early, middle and terminal stages of HCC were 0.656, 0.635 and 0.615, respectively., Conclusion: Slowing the progress of CHB-related diseases and providing psychological support early are the key points to improving the quality of life with the diseases. The utility values estimated in this study can provide a vital instrument for cost-effectiveness studies on CHB-related diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Key Message: The recessive Hessian fly resistance gene h4 and flanking SNP markers were located to a 642 kb region in chromosome 1A of the wheat cultivar 'Java.' Hessian fly (HF), Mayetiola destructor, is one of the most destructive insect pests in wheat worldwide. The wheat cultivar 'Java' was reported to carry a recessive gene (h4) for HF resistance; however, its chromosome location has not been determined. To map the HF resistance gene in Java, two populations of recombinant inbred lines (RILs) were developed from 'Bobwhite' × Java and 'Overley' × Java, respectively, and were phenotyped for responses to infestation of HF Great Plains biotype. Analysis of phenotypic data from the F 1 and the RIL populations confirmed that one recessive gene conditioned HF resistance in Java. Two linkage maps were constructed using single-nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). The h4 gene was mapped to the distal end of the short arm of chromosome 1A, which explained 60.4 to 70.5% of the phenotypic variation for HF resistance in the two populations. The GBS-SNPs in the h4 candidate interval were converted into Kompetitive Allele-Specific Polymerase Chain Reaction (KASP) markers to eliminate the missing data points in GBS-SNPs. Using the revised maps with KASP markers, h4 was further located to a 642 kb interval (6,635,984-7,277,935 bp). The two flanking KASP markers, KASP3299 and KASP1871, as well as four other closely linked KASP markers, may be useful for pyramiding h4 with other HF resistance genes in breeding.

In this contribution, the azo dye (E)-1-(4-((4-(phenylamino)phenyl)diazenyl) phenyl)ethanone (DPA) was combined with reduced graphene oxide (RGO) for the electrochemical modification of a pencil graphite electrode (RGO/DPA/PGE) surface. A series of electrochemical measurements were used for the characterization of the modified electrode surfaces. At the modified electrode, nicotine was irreversibly reduced. An obvious increase was observed in the reductive peak current of nicotine at the modified electrode, indicating the capability of the RGO/DPA composite to increase the electron transfer rate. The current was found proportional to the nicotine concentration in a range of 31 to 1900 μM, and the limit of detection (LOD) was calculated as 7.6 μM.

Polyphenols in whole grain wheat have potential health benefits, but little is known about the expression patterns of phenolic acid biosynthesis genes and the accumulation of phenolic acid compounds in different-colored wheat grains. We found that purple wheat varieties had the highest total phenolic content (TPC) and antioxidant activity. Among phenolic acid compounds, bound ferulic acid, vanillic, and caffeic acid levels were significantly higher in purple wheat than in white and red wheat, while total soluble phenolic acid, soluble ferulic acid, and vanillic acid levels were significantly higher in purple and red wheat than in white wheat. Ferulic acid and syringic acid levels peaked at 14 days after anthesis (DAA), whereas p-coumaric acid and caffeic acid levels peaked at 7 DAA, and vanillic acid levels gradually increased during grain filling and peaked near ripeness (35 DAA). Nine phenolic acid biosynthesis pathway genes (TaPAL1, TaPAL2, TaC3H1, TaC3H2, TaC4H, Ta4CL1, Ta4CL2, TaCOMT1, and TaCOMT2) exhibited three distinct expression patterns during grain filling, which may be related to the different phenolic acids levels. White wheat had higher phenolic acid contents and relatively high gene expression at the early stage, while purple wheat had the highest phenolic acid contents and gene expression levels at later stages. These results suggest that the expression of phenolic acid biosynthesis genes may be closely related to phenolic acids accumulation.

Background: Understanding the variance of antioxidant in wheat grain responses to irrigation and nitrogen (N) fertiliser management will improve the nutrient quality of wheat grain. Four N rates (0, 180, 240, and 300 kg ha(-1)) combined with irrigation times (I0, no irrigation; I1, jointing time irrigation; I2, jointing + flowering time irrigation), were used to determine the effect of N fertilisation and irrigation on total phenolic content (TPC), phenolic acid composition, and antioxidant activity (AOA) of wheat grain., Results: Irrigation, N fertilisation and their interactions had significant effect on TPC, total flavonoid content (TFC), AOA, p-coumaric acid (PCA), as well as vanillic acid (VA) and chlorogenic acid (CA). I1 N300 treatment had the highest TPC at Zhengzhou and Wenxian (1451.5 µg g(-1) and 1397.9 µg g(-1), respectively) location, while I1 N240 resulted in the highest TFC (0.75 mg g(-1)) and VA (19.77 µg g(-1)) at Wenxian. TPC, TFC, AOA, ferulic acid (FA), PCA and VA increased with N application rate (from 180 to 300 kg N ha(-1))., Conclusion: An appropriate irrigation and N management improved antioxidant content and AOA in wheat grain. Generally, I1 N240 and I1 N300 treatment resulted in the higher TPC, TFC, AOA, as well as phenolic acid, i.e. FA and VA., (© 2014 Society of Chemical Industry.)

Flavonoids are the low molecular weight polyphenolic secondary metabolic compounds, and have various functions in growth, development, reproduction, and stress defense. However, little is known about the roles of the key enzymes in the flavonoids biosynthesis pathway in response to drought stress in winter wheat. Here, we investigated the expression pattern of flavonoids biosynthesis genes and accumulation of flavonoids in wheat leaves under drought stress. Quantitative real-time PCR analysis showed that there were a rapid increase in expression levels of TaCHS, TaCHI, TaF3H, TaFNS, TaFLS, TaDFR, and TaANS under drought stress in two wheat cultivars Aikang 58 (AK) and Chinese Spring (CS). The cultivar CS exhibited higher genes expression levels of TaCHS, TaCHI, TaF3H, TaFLS, TaDFR, and TaANS, and the cultivar AK showed a higher expression level of TaFNS gene during drought treatment. The increase rates of genes expression were superior in AK compared to CS. Total phenolics content, total flavonoids content, anthocyanin content, and schaftoside content in wheat leaves were enhanced during drought treatment and cultivar CS had a relative higher accumulation. These results suggest that the flavonoids pathway genes expression and accumulation of flavonoids compounds may be closely related to drought tolerant in wheat. Further, flavonoids response mechanism may be different between wheat cultivars., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)