Application of Different Sampling Methods Combined with Metagenomic Next-Generation Sequencing to Detect Pathogens in Children with Severe Pneumonia on Mechanical Ventilation.

Objective: The aim of this study was to explore the value of applying different sampling methods combined with metagenomic next-generation sequencing (mNGS) to detect pathogens in children with severe pneumonia on mechanical ventilation. Methods: Forty children with severe pneumonia on mechanical ventilation were selected, and routine endotracheal suctioning and bronchoalveolar lavage fluid (BALF) sampling methods were performed. The diagnostic efficacy of different sampling methods combined with mNGS versus traditional etiological pathogen detection strategies was compared. Results: The positive rate of mNGS pathogen detection after routine endotracheal suctioning and BALF sampling was higher than that of traditional etiological detection strategies (P < 0.05). There was no significant difference in the positive rates of pathogen detection by routine endotracheal suctioning + mNGS and BALF + mNGS (P > 0.05). Conclusion: Compared with traditional etiological detection strategies, mNGS is more efficient for diagnosing pathogens. In clinical practice, an appropriate sampling method should be selected for mNGS-based detection according to the condition of the patient. These findings could be of great importance in the diagnosis and treatment of severe pneumonia.

Microbiota-induced lipid peroxidation impairs obeticholic acid-mediated antifibrotic effect towards nonalcoholic steatohepatitis in mice.

Obeticholic acid (OCA) has been examined to treat non-alcoholic steatohepatitis (NASH), but has unsatisfactory antifibrotic effect and deficient responsive rate in recent phase III clinical trial. Using a prolonged western diet-feeding murine NASH model, we show that OCA-shaped gut microbiota induces lipid peroxidation and impairs its anti-fibrotic effect. Mechanically, Bacteroides enriched by OCA deconjugates tauro-conjugated bile acids to generate excessive chenodeoxycholic acid (CDCA), resulting in liver ROS accumulation. We further elucidate that OCA reduces triglycerides containing polyunsaturated fatty acid (PUFA-TGs) levels, whereas elevates free PUFAs and phosphatidylethanolamines containing PUFA (PUFA-PEs), which are susceptible to be oxidized to lipid peroxides (notably arachidonic acid (ARA)-derived 12-HHTrE), inducing hepatocyte ferroptosis and activating hepatic stellate cells (HSCs). Inhibiting lipid peroxidation with pentoxifylline (PTX) rescues anti-fibrotic effect of OCA, suggesting combination of OCA and lipid peroxidation inhibitor could be a potential antifibrotic pharmacological approach in clinical NASH-fibrosis.

A tuff interlayer in deep potash-bearing salt rocks and its implication for potash mineralization in the Simao Basin, southwestern China.

The lithology and genesis of a dark grey clastic interlayer first encountered within the deepest potassium-rich salt body in the Simao Basin, southwestern China, were analysed. Analyses of the petrography, mineralogy, and element geochemistry of the layer revealed that (1) the layer contains quartz crystals with gulf corrosion edges and explosion cracks and angular volcanic ash-sized glasses; (2) the main mineral components of the crystal fragments are chlorite, illite, biotite, quartz, anhydrite, gypsum, magnesite, pyrite, molybdenite, clinopyroxene, and zircon; (3) the rare earth element patterns, Zr/TiO2 and Nb/Y diagrams as well as boron content all indicate a volcanic origin for the layer. Based on these observations, the layer is suggested to be an altered tuff associated with various volcanic fragments dominated by chlorite and formed after alteration of a parent tuff in an alkaline, salty, and low-temperature water body. Discovery of the layer indicates that the potash-bearing salt rocks could have taken in volcanic materials during these volcanic activities and provides the possibility of reliable zircon U‒Pb dating to determine the absolute age of the host rock, which is fundamental in studying the genetic mechanism of this deeply buried salt body.

Longitudinal 16S rRNA Sequencing Reveals Relationships among Alterations of Gut Microbiota and Nonalcoholic Fatty Liver Disease Progression in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and progressive disease spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), yet there is no effective treatment and efficient noninvasive diagnostic method for NASH. The present study investigated the longitudinal alternations of gut microbiota in the Western diet (WD) induced murine NAFLD model using 16S rRNA sequencing. Evident steatosis and inflammation were detected in the liver at the 8th and 12th week, while prompted hepatic oxidative injury and fibrosis were found at the 16th week. In this progressive process, impaired bile acid (BA) metabolism plays a vital part. Long-term WD intervention alters microbial richness and composition in the intestine, shaping characteristic microbial feature correspondence to each NAFLD stage. Descending abundances of Clostridia and Ruminococcaceae were found in NAFLD progression, while inflammation-related microbes [Eubacterium]_fissicatena_group, Romboutsia, and Erysipelatoclostridium were verified to identify borderline NASH at 8th and 12th week, and BA-associated taxa Dubosiella, Bosea, Helicobacter, and Alistipes were recognized as special symbols reflecting the state of oxidative damage and fibrosis in NASH at 16th week. Further, feces and colon abundances of Akkermansia were verified to be depleted in the process of borderline NASH progressed to NASH, and exhibited substantial correlations with NAFLD indexes ALT, AST, TC, and TBA. These characteristic taxa were effective to identify NAFLD and NASH, and microbiota-derived predictive models for NAFLD and NASH exhibited great potential (AUC 0.983 and 0.784). These findings demonstrate that a core set of gut microbiome especially BA-related taxa may be adopted as a noninvasive diagnostic tool for NAFLD and NASH. IMPORTANCE This study concentrates on longitudinal alternations of gut microbiota in NAFLD progression and discovers the interrelationships between them. These findings may uncover the role of gut microbiota in NAFLD progression and identify novel noninvasive diagnostic tools for NAFLD based on microbial biomarkers.

Genetic Model of Mud-Clast Conglomerates in Salt Rocks and Their Significance for Salt Mineralization in Mohei Area, Simao Basin, China: A Case Study of Well L-2.

The Simao Basin is one of the most important Mesozoic salt basins in China, and the salt rocks generally contain mud-clast conglomerates. The characteristics of mud-clast conglomerates can provide effective information indicating the evolution process of the salt deposits. A combined analysis of trace elements and clay minerals was performed to characterize the genetic model of mud-clast conglomerates in the salt rocks. The results show that the sedimentary materials are felsic rocks from the Upper Crust. Ternary plot diagrams show that the tectonic settings are between the continental margin and the continental island arc. The clay minerals in the samples mainly contain illite and illite-smectite mixed layers. A dry and hot climate prevailed during the deposition of the Mengyejing Formation, and the warm-humid climate that also occurred is interspersed in some periods. Evaporation makes the water bodies shallower, and the concentrated brine starts to precipitate salt under the arid and hot climate conditions. Redox proxies indicate that most of the samples were deposited in relatively oxic conditions. The Sr/Ba ratios (average of 0.5) and paleosalinity (average of ∼35‰) during the depositional period indicate an increase in terrigenous freshwater input and carry of clasts into the evaporation basin. Furthermore, the freshwater supply enhances the hydrodynamics; as a result, the detritus that deposited in the early stage is broken into mud-clast conglomerates and co-deposited with the salt rocks. The results provide a geochemical basis for further study of mud-clast conglomerates in the Simao Basin and supply recommendations for the origin of salt deposits in similar basins around the world.

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.

In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice.

Recently, probiotics have been widely used as an adjuvant therapy to cure, prevent, or improve certain diseases. However, no research has been carried out into the dose of probiotics, especially the maximum dose. Therefore, the effective and safe dosage of probiotics needs to be studied. Recently, L. Yang, X. Bian, W. Wu, L. Lv, et al. (Microb Biotechnol 13:1860-1876, 2020, https://doi.org/10.1111/1751-7915.13629) discovered that Lactobacillus salivarius Li01 had a protective effect on thioacetamide-induced acute liver injury and hyperammonemia, and a fixed concentration (3 × 109 CFU/mL) of L. salivarius Li01 was applied in their study. However, the most effective treatment concentration of L. salivarius Li01 remains unknown. Therefore, four concentration gradients of L. salivarius Li01 suspension were prepared for groups of mice to have different levels of bacterial colonization by gavage. Then, acute liver injury and hyperammonemia were induced via thioacetamide administration. By observation and detection, an inverted U-shaped protective effect from L. salivarius Li01 existed in thioacetamide-induced acute liver injury and hyperammonemia. Of note, significant deterioration was confirmed within the group that was orally administered with an excessive concentration of L. salivarius Li01 suspension, and this was attributed to endotoxemia that resulted from compromised immunity, a damaged intestinal barrier, and bacterial translocation. IMPORTANCE This research investigated the relationship between the concentration of Lactobacillus salivarius Li01 and its impact on mice that had a thioacetamide-induced acute liver injury and hyperammonemia. These findings could provide new insights into the effective, proper, and safe use of probiotics.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Multi-band terahertz superabsorbers based on perforated square-patch metamaterials.

This paper presents a multi-band terahertz superabsorber with a surface structure that consists of a square metallic patch with a very small rectangular hole whose area is only 3.94% of the square patch. The introduction of a rectangular hole in the square patch plays an important role in achieving multi-band absorption. Three resonant bands with very high absorption (>95%) were observed in the terahertz range. Different from the near-field distributions of the traditional square patch with no modification, the introduction of a rectangular hole in the square patch can break the near-field distributions of the traditional square patch with no modification or can rearrange them to form some new or extra resonance modes, thereby generating multi-band absorption. Considering the fact that the introduced rectangular hole plays the key role in the rearrangement of the near-field and the introduction of some new resonance modes, the parameter changes of the rectangular hole introduced in the square patch provide considerable freedom in controlling the number of absorption peaks, and the resonant bands can be tuned to quad- or dual-band absorption. The multi-band superabsorbers given here should have potential applications in numerous areas.

Design of a dual-band terahertz metamaterial absorber using two identical square patches for sensing application.

A dual-band terahertz metamaterial absorber composed of two identical square metallic patches and an insulating medium layer on top of a continuous metallic ground is demonstrated. Two resonance peaks (labeled A and B) with near 100% absorbance are obtained, of which peak A derived from the localized resonance of the two square patches has a line-width of 0.2571 THz and quality factor of 6.9156, while peak B which resulted from the hybrid coupling of the localized resonance of the two square patches and surface lattice resonance of the device has a very narrow line-width of 0.0083 THz and large quality factor of 296.2771. Narrow line-width and large quality factor have important prospects in sensing application. Based on this, the sensing performance of the device is explored; it is revealed that peak B exhibits highly sensitive sensing ability (including a sensing sensitivity of 1.9010 THz per RIU and figure of merit of 229.04) in terms of the surrounding index. In addition, the influence of structural parameters on the absorption performance is discussed to further verify the formation mechanism of these two absorption peaks.