Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment.

BACKGROUND/AIMS: New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC. METHODS: Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA. RESULTS: Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09-28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis. CONCLUSION: ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.

Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses.

Background: The main objective was to evaluate the efficacy of intranasal photodynamic therapy (PDT) in SARS-CoV-2 mildly symptomatic carriers on decreasing the infectivity period. SARS-CoV-2-specific immune-stimulating effects and safety were also analysed. Methods: We performed a randomized, placebo-controlled, clinical trial in a tertiary hospital (NCT05184205). Patients with a positive SARS-CoV-2 PCR in the last 48 hours were recruited and aleatorily assigned to PDT or placebo. Patients with pneumonia were excluded. Participants and investigators were masked to group assignment. The primary outcome was the reduction in in vitro infectivity of nasopharyngeal samples at days 3 and 7. Additional outcomes included safety assessment and quantification of humoral and T-cell immune-responses. Findings: Patients were recruited between December 2021 and February 2022. Most were previously healthy adults vaccinated against COVID-19 and most carried Omicron variant. 38 patients were assigned to placebo and 37 to PDT. Intranasal PDT reduced infectivity at day 3 post-treatment when compared to placebo with a ß-coefficient of -812.2 (CI95%= -478660 - -1.3, p<0.05) infectivity arbitrary units. The probability of becoming PCR negative (ct>34) at day 7 was higher on the PDT-group, with an OR of 0.15 (CI95%=0.04-0.58). There was a decay in anti-Spike titre and specific SARS-CoV-2 T cell immunity in the placebo group 10 and 20 weeks after infection, but not in the PDT-group. No serious adverse events were reported. Interpretation: Intranasal-PDT is safe in pauci-symptomatic COVID-19 patients, it reduces SARS-CoV-2 infectivity and decelerates the decline SARS-CoV-2 specific immune-responses.

Dysbiosis and relapse-related microbiome in inflammatory bowel disease: A shotgun metagenomic approach.

Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), affect several million people worldwide. CD and UC are characterized by periods of clinical remission and relapse. Although IBD patients present chronic alterations of the gut microbiome, called dysbiosis, little attention has been devoted to the relapse-related microbiome. To address this gap, we generated shotgun metagenomic data from the stools of two European cohorts-134 Spanish (followed up for one year) and 49 Belgian (followed up for 6 months) subjects-to characterize the microbial taxonomic and metabolic profiles present. To assess the predictive value of microbiome data, we added the taxonomic profiles generated from a previous study of 130 Americans. Our results revealed that CD was more dysbiotic than UC compared to healthy controls (HC) and that strategies for energy extraction and propionate production were different in CD compared to UC and HC. Remarkably, CD and UC relapses were not associated with alpha- or beta-diversity, or with a dysbiotic score. However, CD relapse was linked to alterations at the species and metabolic pathway levels, including those involved in propionate production. The random forest method using taxonomic profiles allowed the prediction of CD vs. non-CD with an AUC = 0.938, UC vs. HC with an AUC = 0.646, and CD relapse vs. remission with an AUC = 0.769. Our study validates previous taxonomic findings, points to different relapse-related growth and defence mechanisms in CD compared to UC and HC and provides biomarkers to discriminate IBD subtypes and predict disease activity.

A Fermented Milk Product Containing B. lactis CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions.

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota.

Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?

Introduction: Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days. Methods: Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined. Results: Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this. Conclusion: This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.

Simulating the mechanisms of serrated flow in interstitial alloys with atomic resolution over diffusive timescales.

The Portevin-Le Chatelier (PLC) effect is a phenomenon by which plastic slip in metallic materials becomes unstable, resulting in jerky flow and the onset of inhomogeneous deformation. The PLC effect is thought to be fundamentally caused by the dynamic interplay between dislocations and solute atoms. However, this interplay is almost always inaccessible experimentally due to the extremely fine length and time scales over which it occurs. In this paper, simulations of jerky flow in W-O interstitial solid solutions reveal three dynamic regimes emerging from the simulated strain rate-temperature space: one resembling standard solid solution strengthening, another one mimicking solute cloud formation, and a third one where dislocation/solute coevolution leads to jerky flow as a precursor of dynamic strain aging. The simulations are carried out in a stochastic framework that naturally captures rare events in a rigorous manner, providing atomistic resolution over diffusive time scales using no adjustable parameters.

Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation.

BACKGROUND: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. METHODS: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. FINDINGS: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. INTERPRETATION: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. FUNDING: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).

A Fermented Milk Product with B. Lactis CNCM I-2494 and Lactic Acid Bacteria Improves Gastrointestinal Comfort in Response to a Challenge Diet Rich in Fermentable Residues in Healthy Subjects.

BACKGROUND: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets. METHODS: In an open design, a 3-day high-residue diet was administered to healthy subjects (n = 74 included, n = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. MAIN OUTCOMES: digestive sensations, number of daytime anal gas evacuations, and gas volume evacuated during 4 h after a probe meal. RESULTS: As compared to the habitual diet, the high-residue diet induced gas-related symptoms (flatulence score 4.9 vs. 1.2; p ≤ 0.0001), increased the daily number of anal gas evacuations (20.7 vs. 8.7; p < 0.0001), and impaired digestive well-being (1.0 vs. 3.4; p < 0.05). FMP consumption reduced flatulence sensation (by -1.7 [-1.9; -1.6]; p < 0.0001), reduced the number of daily evacuations (by -5.8 [-6.5; -5.1]; p < 0.0001), and improved digestive well-being (by +0.6 [+0.4; +0.7]; p < 0.05). FMP consumption did not affect the gas volume evacuated after a probe meal. CONCLUSION: In healthy subjects, consumption of a FMP containing B. lactis CNCM I-2494 and lactic acid bacteria improves the tolerance of a flatulogenic diet by subjective and objective criteria (sensations and number of anal gas evacuations, respectively).

A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis.

BACKGROUND: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised. METHODS: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting. FINDINGS: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features. INTERPRETATION: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.

Effect of a Multistrain Probiotic on Cognitive Function and Risk of Falls in Patients With Cirrhosis: A Randomized Trial.

Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < -4) and/or falls in the previous year were randomized to receive either a sachet of a high-concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid-binding protein 6 [FABP-6] and 2 [FABP-2] and zonulin and urinary claudin-3); bacterial translocation (lipopolysaccharide-binding protein [LBP]); and fecal microbiota. Thirty-six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES (P = 0.006), TUG time (P = 0.015) and gait speed (P = 0.02), and a trend toward a lower incidence of falls during follow-up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C-reactive protein (P = 0.01), tumor necrosis factor alpha (P = 0.01), FABP-6 (P = 0.009), and claudin-3 (P = 0.002), and an increase in poststimulation neutrophil oxidative burst (P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.

Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats.

Whether the interaction between the gut microbiota and the immune response influences the evolution of cirrhosis is poorly understood. We aimed to investigate modifications of the microbiome and the immune response during the progression of cirrhosis. Rats were treated with carbon tetrachloride (CCl4) to induce cirrhosis. We then assessed microbiome load and composition in stool, ileocecal contents (ICCs), mesenteric lymph nodes (MLNs), blood, and ascitic fluids (AFs) at 6, 8, and 10 weeks or ascites production and measured cytokine production in MLNs and blood. The microbiome of MLN, blood, and AF showed a distinct composition compared to that of stool and ICCs. Betaproteobacteria (Sutterella) were found associated with the appearance of a decompensated state of cirrhosis. Microbial load increased and showed a positive correlation with the relative abundance of pathobionts in the MLN of decompensated rats. Among several genera, Escherichia and "Candidatus Arthromitus" positively correlated with elevated levels of systemic proinflammatory cytokines. "Candidatus Arthromitus," a segmented filamentous bacteria, was detected in ICC, MLN, and AF samples, suggesting a possible translocation from the gut to the AF through the lymphatic system, whereas Escherichia was detected in ICC, MLN, AF, and blood, suggesting a possible translocation from the gut to the AF through the bloodstream. In the present study, we demonstrate that microbiome changes in distinct intestinal sites are associated with microbial shifts in the MLNs as well as an increase in cytokine production, providing further evidence of the role the gut-liver-immunity axis plays in the progression of cirrhosis. IMPORTANCE Cirrhosis severity in patients was previously shown to be associated with progressive changes in the fecal microbiome in a longitudinal setting. Recent evidence shows that bacterial translocation from the gut to the extraintestinal sites could play a major role in poor disease outcome and patient survival. However, the underlying mechanisms involving the microbiota in the disease progression are not well understood. Here, using an animal model of cirrhosis in a longitudinal and multibody sites setting, we showed the presence of a distinct composition of the microbiome in mesenteric lymph nodes, blood, and ascitic fluid compared to that in feces and ileocecal content, suggesting compartmentalization of the gut microbiome. We also demonstrate that microbiome changes in intestinal sites are associated with shifts in specific microbial groups in the mesenteric lymph nodes as well as an increase in systemic cytokine production, linking inflammation to decompensated cirrhosis in the gut-liver-immunity axis.

Micro-Raman Spectroscopy in Self-Catalyzed Indium Phosphide Nanostructures: Morphology and Substrate Effects.

We report the effect of morphology and substrate of self-catalyzed indium phosphide (InP) nanostructures on phonon vibration modes. Using liquid indium as a catalyst, we grew self-catalyzed InP nanocones and nanopillars on single crystal substrates of InP(111)B, Si(111), and Si(100) via metal-organic chemical vapor epitaxy. Due to crystal symmetry breaking in one-dimensional nanostructure, longitudinal-optical (LO) and transverse-optical (TO) phonon modes are clearly resolved with the strong anisotropic behavior. Broadening and downshift of LO phonon modes are found to be sensitive to the morphology (i.e., aspect ratio and surface-to-volume ratio) and crystal structure (i.e., Wurtzite and Zinc Blende) of the as-grown nanostructures. This work demonstrated that Raman spectroscopy provides statistical insights on the quality of as-grown nanostructures (i.e., growth orientation, crystal structures, and the presence of structural defects) without destroying samples.

Stretching Micro Metal Particles into Uniformly Dispersed and Sized Nanoparticles in Polymer.

There is a longstanding challenge to disperse metal nanoparticles uniformly in bulk polymers for widespread applications. Conventional scale-down techniques often are only able to shrink larger elements (such as microparticles and microfibers) into micro/nano-elements (i.e. nanoparticles and nanofibers) without much altering their relative spatial and size distributions. Here we show an unusual phenomenon that tin (Sn) microparticles with both poor size distribution and spatial dispersion were stretched into uniformly dispersed and sized Sn nanoparticles in polyethersulfone (PES) through a stack and draw technique in thermal drawing. It is believed that the capillary instability plays a crucial role during thermal drawing. This novel, inexpensive, and scalable method overcomes the longstanding challenge to produce bulk polymer-metal nanocomposites (PMNCs) with a uniform dispersion of metallic nano-elements.

A microbial signature for Crohn's disease.

OBJECTIVE: A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. DESIGN: We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. RESULTS: In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. CONCLUSIONS: Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.

MetaTrans: an open-source pipeline for metatranscriptomics.

To date, meta-omic approaches use high-throughput sequencing technologies, which produce a huge amount of data, thus challenging modern computers. Here we present MetaTrans, an efficient open-source pipeline to analyze the structure and functions of active microbial communities using the power of multi-threading computers. The pipeline is designed to perform two types of RNA-Seq analyses: taxonomic and gene expression. It performs quality-control assessment, rRNA removal, maps reads against functional databases and also handles differential gene expression analysis. Its efficacy was validated by analyzing data from synthetic mock communities, data from a previous study and data generated from twelve human fecal samples. Compared to an existing web application server, MetaTrans shows more efficiency in terms of runtime (around 2 hours per million of transcripts) and presents adapted tools to compare gene expression levels. It has been tested with a human gut microbiome database but also proposes an option to use a general database in order to analyze other ecosystems. For the installation and use of the pipeline, we provide a detailed guide at the following website (www.metatrans.org).

Self-Catalyzed Growth and Characterization of In(As)P Nanowires on InP(111)B Using Metal-Organic Chemical Vapor Deposition.

We report the growth of vertical <111>-oriented InAs x P1-x (0.11 ≤ x ≤ 0.27) nanowires via metal-organic chemical vapor deposition in the presence of indium droplets as catalysts on InP(111)B substrates at 375 °C. Trimethylindium, tertiarybutylphosphine, and tertiarybutylarsine are used as the precursors, corresponding to P/In and As/In molar ratios of 29 and 0.01, respectively. The as-grown nanowire growth morphologies, crystallinity, composition, and optical characteristics are determined using a combination of scanning and transmission electron microscopies, electron diffraction, and X-ray photoelectron, energy dispersive X-ray, and Raman spectroscopies. We find that the InAs x P1-x nanowires are tapered with narrow tops, wider bases, and In-rich In-As alloy tips, characteristic of vapor-liquid-solid process. The wires exhibit a mixture of zinc blende and wurtzite crystal structures and a high density of structural defects such as stacking faults and twins. Our results suggest that the incorporation of As into InP wires decreases with increasing substrate temperature. The Raman spectra obtained from the In(As)P nanowires reveal a red-shift and lower intensity of longitudinal optical mode relative to both InP nanowires and InP(111)B bulk, due to the incorporation of As into the InP matrix.

Alteration of the serum microbiome composition in cirrhotic patients with ascites.

The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.

Processing and properties of magnesium containing a dense uniform dispersion of nanoparticles.

Magnesium is a light metal, with a density two-thirds that of aluminium, is abundant on Earth and is biocompatible; it thus has the potential to improve energy efficiency and system performance in aerospace, automobile, defence, mobile electronics and biomedical applications. However, conventional synthesis and processing methods (alloying and thermomechanical processing) have reached certain limits in further improving the properties of magnesium and other metals. Ceramic particles have been introduced into metal matrices to improve the strength of the metals, but unfortunately, ceramic microparticles severely degrade the plasticity and machinability of metals, and nanoparticles, although they have the potential to improve strength while maintaining or even improving the plasticity of metals, are difficult to disperse uniformly in metal matrices. Here we show that a dense uniform dispersion of silicon carbide nanoparticles (14 per cent by volume) in magnesium can be achieved through a nanoparticle self-stabilization mechanism in molten metal. An enhancement of strength, stiffness, plasticity and high-temperature stability is simultaneously achieved, delivering a higher specific yield strength and higher specific modulus than almost all structural metals.

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

Paper-based chemiresistor for detection of ultralow concentrations of protein.

A new paper-based chemiresistor composed of a network of single-wall carbon nanotubes (SWCNTs) and anti-human immunoglobulin G (anti-HIgG) is reported herein. SWCNTs act as outstanding transducers because they provide high sensitivity in terms of resistance changes due to immunoreaction. As a result, the resistance-based biosensor reaches concentration detection as low as picomolar. The resulting paper-based biosensor is sensitive, selective and employs low-cost substrate and simple manufacturing stages. Since chemiresistors require low-power equipment and are able to detect low concentrations with inexpensive materials, the present approach may pave the way for the development of resistive biosensors at very low-cost with high performances.