Homeostatic T helper 17 cell responses triggered by complex microbiota are maintained in ex vivo intestinal tissue slices.

Segmented filamentous bacteria (SFB) are members of the commensal intestinal microbiome. They are known to contribute to the postnatal maturation of the gut immune system, but also to augment inflammatory conditions in chronic diseases such as Crohn's disease. Living primary tissue slices are ultrathin multicellular sections of the intestine and provide a unique opportunity to analyze tissue-specific immune responses ex vivo. This study aimed to investigate whether supplementation of the gut flora with SFB promotes T helper 17 (Th17) cell responses in primary intestinal tissue slices ex vivo. Primary tissue slices were prepared from the small intestine of healthy Taconic mice with SFB-positive and SFB-negative microbiomes and stimulated with anti-CD3/CD28 or Concanavalin A. SFB-positive and -negative mice exhibited distinct microbiome compositions and Th17 cell frequencies in the intestine and complex microbiota including SFB induced up to 15-fold increase in Th17 cell-associated mediators, serum amyloid A (SAA), and immunoglobulin A (IgA) responses ex vivo. This phenotype could be transmitted by co-housing of mice. Our findings highlight that changes in the gut microbiome can be observed in primary intestinal tissue slices ex vivo. This makes the system very attractive for disease modeling and assessment of new therapies.

Development of brain-penetrable antibody radioligands for in vivo PET imaging of amyloid-ß and tau.

Introduction: Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aß) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood-brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aß aggregates via ex vivo imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled specifically engineered bispecific antibody probes for the selective detection of tau and Aß aggregates to evaluate their feasibility and specificity, particularly for in vivo PET imaging. Methods: We first created and evaluated (via both in vitro and ex vivo studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aß or tau or with their respective scFv. Using [18F]SFB as the prosthetic group, all four 18F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [18F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ~ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size exclusion gravity column. Results: Based on both in vitro and ex vivo evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [18F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [18F]SFB and bispecific antibodies showed a 65%-83% conversion efficiency with radiochemical purities of 95%-99% by radio-TLC. Conclusions: We successfully labeled four novel and specifically engineered bispecific antibodies with [18F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aß aggregates in the brain of transgenic AD mice via in vivo PET imaging.

Practice of sustainable fashion design considering customer emotions and personal tastes.

This study aimed to determine a sustainable design practice approach that can satisfy customer emotions and personal tastes, which designers need in the early stages of the SFD process, and improve environmental performance. The research was conducted through a case study and interviews. For case studies, the specific design methods of fashion brands, which have been ranked sustainable over the last 3 years in the world's top fashion magazines favored by the public, were researched. The results of the case studies were used to draw questions for the in-depth interviews. The results are as follows: first, the design approaches of SFBs were categorized into "eco-friendly materials," "functional durability design," "reuse and remanufacturing," "emotional durability design," and sustainable fashion technology. Each type's specific design approach methods were organized into a checklist for the practice of SFD and then reflected in the interview questions. From the results of the interviews, it was noted that the sustainable design approaches perceived by Korean designers were "eco-friendly materials," "reuse and remanufacturing," and "functional durability design." Moreover, it was mentioned that specific methods of emotional durability design and sustainable fashion technology need to be acquired. By applying the checklist to the interviewees, interview participants could conveniently and quickly recognize how to apply sustainable design through the inventory. This study is significant because it presents a checklist, an efficient tool for sustainable design approaches, and a sustainable design practice method that can satisfy customer emotions and personal tastes and improve environmental performance.

Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element.

T helper 17 (Th17) cells regulate mucosal barrier defenses but also promote multiple autoinflammatory diseases. Although many molecular determinants of Th17 cell differentiation have been elucidated, the transcriptional programs that sustain Th17 cells in vivo remain obscure. The transcription factor RORγt is critical for Th17 cell differentiation; however, it is not clear whether the closely related RORα, which is co-expressed in Th17 cells, has a distinct role. Here, we demonstrated that although dispensable for Th17 cell differentiation, RORα was necessary for optimal Th17 responses in peripheral tissues. The absence of RORα in T cells led to reductions in both RORγt expression and effector function among Th17 cells. Cooperative binding of RORα and RORγt to a previously unidentified Rorc cis-regulatory element was essential for Th17 lineage maintenance in vivo. These data point to a non-redundant role of RORα in Th17 lineage maintenance via reinforcement of the RORγt transcriptional program.

Comparative genome analysis of commensal segmented filamentous bacteria (SFB) from turkey and murine hosts reveals distinct metabolic features.

BACKGROUND: Segmented filamentous bacteria (SFB) are intestinal commensal microorganisms that have been demonstrated to induce the innate and adaptive immune responses in mouse and rat hosts. SFB are Gram-positive, spore-forming bacteria that fail to grow optimally under in vitro conditions due to unique metabolic requirements. Recently, SFB have been implicated in improved health and growth outcomes in commercial turkey flocks. To assess the nature and variations in SFB of turkeys and how they may differ from mammalian-associated SFB, the genome of turkey-associated SFB was compared with six representative genomes from murine hosts using an in silico approach. RESULTS: The SFB-turkey genome is 1.6 Mb with a G + C content of 26.14% and contains 1,604 coding sequences (CDS). Comparative genome analyses revealed that all the seven SFB strain possesses a common set of metabolic deficiencies and auxotrophies. Specifically, the inability of all the SFB strains to synthesize most of the amino acids, nucleotides and cofactors, emphasizing the importance of metabolite acquisition from the host intestinal environment. Among the seven SFB genomes, the SFB-turkey genome is the largest and contains the highest number of 1,604 predicted CDS. The SFB-turkey genome possesses cellular metabolism genes that are absent in the rodent SFB strains, including catabolic pathways for sucrose, stachyose, raffinose and other complex glycans. Other unique genes associated with SFB-turkey genome is loci for the biosynthesis of biotin, and degradation enzymes to recycle primary bile acids, both of which may play an important role to help turkey associated SFB survive and secure mutualism with its avian host. CONCLUSIONS: Comparative genomic analysis of seven SFB genomes revealed that each strain have a core set of metabolic capabilities and deficiencies that make these bacteria challenging to culture under ex vivo conditions. When compared to the murine-associated strains, turkey-associated SFB serves as a phylogenetic outgroup and a unique member among all the sequenced strains of SFB. This turkey-associated SFB strain is the first reported non-mammalian SFB genome, and highlights the impact of host specificity and the evolution of metabolic capabilities.

Control for chlorine resistant spore forming bacteria by the coupling of pre-oxidation and coagulation sedimentation, and UV-AOPs enhanced inactivation in drinking water treatment.

Spore forming bacteria (SFB) are strongly chlorine resistant. Their presence in drinking water may cause diseases and pose threat to public health. Three SFB strains, i.e. Bacillus alvei, Bacillus cereus, and Lysinibacillus fusiformis, were isolated and identified from the finished water of a drinking water treatment plant where bacteria colonies occasionally reached the limit value. Due to their chlorine resistance, a SFB control strategy coupling pre-oxidation, coagulation sedimentation, and UV-AOPs inactivation in water treatment process was studied in lab scale. Five minutes pre-oxidation treatment by applying Cl2 and ClO2 induced remarkable spore transformation. Longer pre-oxidation exposure time didn't have apparent improvement. Cl2 and ClO2 dosages of 0.9 mg/L and 0.5 mg/L were suggested, respectively. The formed spores can be efficiently removed by the following coagulation sedimentation treatment. At a suggested dosage combination of 20 mg/L PAC and 0.08 mg/L PAM, spore removal efficiency reached about 3.15-lg. Comparing to applying sole UV irradiation, enhanced UV inactivation by adding 0.1 mM H2O2, or Cl2, or peroxymonosulfate (PMS) substantially improved the inactivation of the most chlorine resistant SFB strain, Lysinibacillus fusiformis. UV-AOPs stably achieved 2-lg inactivation rate at UV dosage of 40 mJ/cm2. UV/H2O2, UV/Cl2 and UV/PMS inactivation kinetically enhanced 1.20 times, 1.36 times and 1.91 times over sole UV irradiation. Intracellular DNA and ATP leakages were detected, and remarkable damages of Lysinibacillus fusiformis cells' surface and ultrastructure were observed. These findings evidenced cell wall and cell membrane destructions, guaranteeing substantial SFB cells inactivation. This study was carried out based on three SFB strains isolated from a finished water, and common engineering practical operations. By providing engineeringly relevant references, the outcomes obtained would be helpful for dealing with SFB outbreak risk in drinking water treatment.

Characterization of Streptomyces nymphaeiformis sp. nov., and its taxonomic relatedness to other polyhydroxybutyrate-degrading streptomycetes.

A polyhydroxybutyrate (PHB)-degrading actinomycete, strain SFB5AT, was identified as a species of Streptomyces based on its membrane fatty acid profile and the presence of ll-diaminopimelic acid in the cell wall. It formed sporulating mycelia on most agar media, but flat or wrinkled, moist colonies on trypticase soy agar. Spores were smooth, cylindrical, and borne on long, straight to flexuous chains. It produced a light brown diffusible pigment, but not melanin. Comparison of genomic digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values indicated that strain SFB5AT was related to Streptomyces litmocidini JCM 4394T, Streptomyces vietnamensis GIMV4.0001T, Streptomyces nashvillensis JCM 4498T and Streptomyces tanashiensis JCM 4086T, plus 11 other species. However, the dDDH and ANI values were well below the species differentiation thresholds of <70 and <95 %, respectively; also, multilocus sequence analysis distances exceeded the species threshold of 0.007. Moreover, strain SFB5AT differed from the other species in pigmentation and its ability to catabolize arabinose. Strain SFB5AT and 11 of its 15 closest relatives degraded PHB and have genes for extracellular, short-chain-length denatured polyhydroxyalkanoate depolymerases. These enzymes from strain SFB5AT and its closest relatives had a type 1 catalytic domain structure, while those from other relatives had a type 2 structure, which differs from type one in the position of a consensus histidine in the active site. Thus, phenotypic and genotypic differences suggest that strain SFB5AT represents a new species of Streptomyces, for which we propose the name Streptomyces nymphaeiformis sp. nov. The type strain is SFB5AT (=NRRL B-65520T=DSM 112030T).

The transcatheter arterial chemoembolization combined with targeted nanoparticle delivering sorafenib system for the treatment of microvascular invasion of hepatocellular carcinoma.

to explore the value of transcatheter arterial chemoembolization (TACE) combined with targeted nanoparticle delivery system for sorafenib (SFB) to treat hepatocellular carcinoma (HCC) with microvascular invasion. 42 HCC patients with microvascular invasion after liver cancer surgery were selected from our hospital from December 2020 and February 2021. Patients were divided into experimental group and control group based on their willingness. Patients in experimental group (18 cases) were treated with combination therapy of TACE and Ab-SFB-NP system; while patients in control group (24 cases) took TACE and non-nano drug delivery system. There was no obvious difference in liver function and blood test results between two groups of patients before treatment and one month after treatment (P > 0.05). Three months after treatment, differences of alanine aminotransferase (ALT) were statistically significant (P < 0.05); while differences of other test results were not (P > 0.05). The disease control rate (DCR) of patients in experimental group was higher slightly (P > 0.05). The incidence of adverse reactions of patients in experimental group was lower than the control group and the differences were statistically significant (P < 0.05). After three months of TACE, the DCR in the experimental group was significantly higher compared to control group. The toxic reactions of taking SFB with Ab-SFB-NP nano-drug delivery system mainly included hand-foot syndrome, diarrhea, and bleeding, the toxic reactions were mainly at level 1 ~ 2. After symptomatic treatment, the toxicity was effectively controlled, so the security was high.

Depletion of Lipocalin 2 (LCN2) in Mice Leads to Dysbiosis and Persistent Colonization with Segmented Filamentous Bacteria.

Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity and metabolic syndrome by interfering with the composition of gut microbiota. Consequently, complete or hepatocyte-specific ablation of the Lcn2 gene is associated with higher susceptibility to bacterial infections. In the present study, we comparatively profiled microbiota in fecal samples of wild type and Lcn2 null mice and show, in contrast to previous reports, that the quantity of DNA in feces of Lcn2 null mice is significantly lower than that in wild type mice (p < 0.001). By using the hypervariable V4 region of the 16S rDNA gene and Next-Generation Sequencing methods, we found a statistically significant change in 16 taxonomic units in Lcn2-/- mice, including eight gender-specific deviations. In particular, members of Clostridium, Escherichia, Helicobacter, Lactococcus, Prevotellaceae_UCG-001 and Staphylococcus appeared to expand in the intestinal tract of knockout mice. Interestingly, the proportion of Escherichia (200-fold) and Staphylococcus (10-fold) as well as the abundance of intestinal bacteria encoding the LCN2-sensitive siderphore enterobactin (entA) was significantly increased in male Lcn2 null mice (743-fold, p < 0.001). This was accompanied by significant higher immune cell infiltration in the ileum as demonstrated by increased immunoreactivity against the pan-leukocyte protein CD45, the lymphocyte transcription factor MUM-1/IRF4, and the macrophage antigen CD68/Macrosialin. In addition, we found a higher expression of mucosal mast cell proteases indicating a higher number of those innate immune cells. Finally, the ileum of Lcn2 null mice displayed a high abundance of segmented filamentous bacteria, which are intimately associated with the mucosal cell layer, provoking epithelial antimicrobial responses and affecting T-helper cell polarization.

Heat Stress Alters the Intestinal Microbiota and Metabolomic Profiles in Mice.

BACKGROUND: Heat stress has negative effects on the intestinal health of humans and animals. However, the impact of heat stress on intestinal microbial and metabolic changes remains elusive. Here, we investigated the cecal microbial and metabolic profiles in mice in response to heat stress. METHODS: The mouse heat stress model was constructed by simulating a high-temperature environment. Twenty mice were randomly assigned to two groups, the control group (CON, 25°C) and the heat treatment group (HS, 40°C from 13:00 to 15:00 every day for 7 days). Serum and cecal contents were collected from the mice for serum biochemical analysis, 16S rRNA high-throughput sequencing, and non-targeted metabolomics. RESULTS: Both core body temperature and water intake were significantly increased in the HS group. Serum biochemical indicators were also affected, including significantly increased triglyceride and decreased low-density lipoprotein in the heat stress group. The composition and structure of intestinal microbiota were remarkably altered in the HS group. At the species level, the relative abundance of Candidatus Arthromitus sp. SFB-mouse-Japan and Lactobacillus murinus significantly reduced, while that of Lachnospiraceae bacterium 3-1 obviously increased after HS. Metabolomic analysis of the cecal contents clearly distinguished metabolite changes between the groups. The significantly different metabolites identified were mainly involved in the fatty acid synthesis, purine metabolism, fatty acid metabolism, cyanoamino acid metabolism, glyceride metabolism, and plasmalogen synthesis. CONCLUSION: In summary, high temperature disrupted the homeostatic balance of the intestinal microbiota in mice and also induced significant alterations in intestinal metabolites. This study provides a basis for treating intestinal disorders caused by elevated temperature in humans and animals and can further formulate nutritional countermeasures to reduce heat stress-induced damage.

Induction of IL-22-Producing CD4+ T Cells by Segmented Filamentous Bacteria Independent of Classical Th17 Cells.

The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.

Interactomes of SARS-CoV-2 and human coronaviruses reveal host factors potentially affecting pathogenesis.

Host-virus protein-protein interactions play key roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity-labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Further characterization of these interactions and comparison to other large-scale study of cellular responses to SARS-CoV-2 infection elucidated how distinct SARS-CoV-2 viral proteins participate in its life cycle. With these data mining, we discovered potential drug targets for the treatment of COVID-19. The interactomes of two key SARS-CoV-2-encoded viral proteins, NSP1 and N, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of SARS-CoV-2 provides valuable resources for the understanding and treating of this disease.

An Improved Synthesis of N-(4-[18F]Fluorobenzoyl)-Interleukin-2 for the Preclinical PET Imaging of Tumour-Infiltrating T-cells in CT26 and MC38 Colon Cancer Models.

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [18F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [18F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [18F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [18F]FB-IL-2. Significant improvements in the radiochemical manufacture of [18F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers.

Molecular and Evolutionary Characterization of Pollen S Determinant (SFB Alleles) in Four Diploid and Hexaploid Plum Species (Prunus spp.).

In more than 60 families of angiosperms, the self- and cross-fertilization is avoided through a complex widespread genetic system called self-incompatibility (SI). One of the major puzzling issues concerning the SI is the evolution of this system in species with complex polyploid genomes. Among plums, one of the first fruits species to attract human interest, polyploid species represent enormous genetic potential, which can be exploited in breeding programs. However, molecular studies in these species are very scarce due to the complexity of their genome. In order to study the SFB gene [the male component of gametophytic self-incompatibility system (GSI)] in plum species, 36 plum accessions belonging to diploid and hexaploid species were used. A total of 19 different alleles were identified; 1 of them was revealed after analyzing sequences. Peptide sequence analysis allowed identifying the five domains features of the SFB gene. Polymorphism analysis showed a subtle difference between domesticated and open pollinated Tunisian accessions and suggested a probable influence of the ploidy level. Divergence analysis between studied sequences showed that a new specificity may appear after 5.3% of divergence at synonymous sites between pairs of sequences in Prunus insititia, 6% in Prunus cerasifera, 8% and 9% in Prunus domestica and Prunus salicina respectively. Furthermore, sites under positive selection, the ones more likely to be responsible for specificity determination, were identified. A positive and significant Pearson correlation was found between the divergence between sequences, divergence time, fixed substitutions (MK test), and PSS number. These results supported the model assuming that functionally distinct proteins have arisen not as a result of chance fixation of neutral variants, but rather as a result of positive Darwinian selection. Further, the role that plays recombination can not be ruled out, since a rate of 0.08 recombination event per polymorphic sites was identified.

Oral Treatment With Ileal Spores Triggers Immunometabolic Shifts in Chicken Gut.

The animal gut is a major site affecting productivity via its role in mediating functions like food conversion and pathogen colonization. Live microorganisms like probiotics are widely used to improve poultry productivity. However, given that chicks receive their microbiota from the environment at-hatch, a bacterial treatment that can stimulate gut immune maturation in early life can benefit animal health. Thus, our lab has begun investigating alternative means to improve poultry health via single inoculation with microbial spores. In this study, we orally-inoculated day-old chicks with ileal scrapings (ISs) enriched for spores via chloroform treatment (SPORE) or non-treated (CON). At 3, 7, and 14 days post-inoculation (dpi), gut permeability was measured via FITC-dextran assay in serum. Additionally, small intestinal scrapings (SISs) were tested for in vitro Salmonella killing and total IgA. Lastly, distal ileum was either fixed or flash-frozen for microscopy or kinome peptide array, respectively. Using bacterial 16S rRNA gene sequencing, SPORE and CON inocula were highly-similar in bacterial composition. However, spores were detected in SPORE but not in CON inoculum. Segmented filamentous bacteria (SFB) filaments were observed in the distal ileum in SPORE birds as early as 3 dpi and all birds at 7 and 14 dpi. Additionally, SFB were detected via PCR in the ceca, colonizing all SPORE birds at 3 dpi. At 3 dpi, SPORE birds exhibited lower gut permeability vs. CON. In SPORE birds, SISs induced greater Salmonella growth in vitro at 3 dpi yet significantly-reduced Salmonella load at 7 and 14 dpi compared to CON in an IgA-independent manner. SPORE distal ileal tissue exhibited unique upregulation of several immunometabolic processes vs. CON birds, including innate (Toll-like receptor, JAK-STAT) and adaptive (T/B cell receptor, TH17 differentiation) immune pathways, PI3K/Akt signaling, mTOR signaling, and insulin-related pathways. Collectively, these data suggest oral inoculation with ileal spores generally-improved gut health. Importance: We report that ileal, spore-forming commensal microbes have potent effects on ileum immunometabolism. Additionally, we identify a functional ileal phenotype in spore-treated chickens, which matched several of the observed immunometabolic changes and was associated with SFB colonization in the ileum.

Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis.

Throughout a 24-h period, the small intestine (SI) is exposed to diurnally varying food- and microbiome-derived antigenic burdens but maintains a strict immune homeostasis, which when perturbed in genetically susceptible individuals, may lead to Crohn disease. Herein, we demonstrate that dietary content and rhythmicity regulate the diurnally shifting SI epithelial cell (SIEC) transcriptional landscape through modulation of the SI microbiome. We exemplify this concept with SIEC major histocompatibility complex (MHC) class II, which is diurnally modulated by distinct mucosal-adherent SI commensals, while supporting downstream diurnal activity of intra-epithelial IL-10+ lymphocytes regulating the SI barrier function. Disruption of this diurnally regulated diet-microbiome-MHC class II-IL-10-epithelial barrier axis by circadian clock disarrangement, alterations in feeding time or content, or epithelial-specific MHC class II depletion leads to an extensive microbial product influx, driving Crohn-like enteritis. Collectively, we highlight nutritional features that modulate SI microbiome, immunity, and barrier function and identify dietary, epithelial, and immune checkpoints along this axis to be potentially exploitable in future Crohn disease interventions.

2-D Joint Sparse Reconstruction and Micro-Motion Parameter Estimation for Ballistic Target Based on Compressive Sensing.

The sparse frequency band (SFB) signal presents a serious challenge to traditional wideband micro-motion curve extraction algorithms. This paper proposes a novel two-dimension (2-D) joint sparse reconstruction and micro-motion parameter estimation (2D-JSR-MPE) algorithm based on compressive sensing (CS) theory. In this technique, the 2D-JSR signal model and the micro-motion parameter dictionary are established based on the segmented SFB echo signal, in which the idea of piecewise effectively reduces the model complexity of ballistic target. With the accommodation of the CS theory, the 2D-JSR-MPE of the echo signal is transformed into solving a sparsity-driven optimization problem. Via an improved orthogonal matching pursuit (OMP) algorithm, the high-resolution range profiles (HRRP) can be reconstructed accurately, and the precise micro-motion curves can be simultaneously extracted on phase accuracy. The employment of 2-D joint processing can effectively avoid the interference of the sparse reconstruction error caused by cascaded operation in the subsequent micro-motion parameter estimation. The proposed algorithm benefits from the anti-jamming characteristic of the SFB signal and 2-D joint processing, thus remarkably enhancing its accuracy, robustness and practicality. Extensive experimental results are provided to verify the effectiveness and robustness of the proposed algorithm.

The dynamics of surface wave propagation based on the Benjamin Bona Mahony equation.

Modulation instability is one of the consequences of the water medium's inclination. It causes surface water waves to run into phenomena of splitting and merging in their propagation. An increase in wave amplitude follows this phenomenon, which can encourage the appearance of extreme waves. It is known that the Benjamin Bona Mahony (BBM) wave has modulation instability in its propagation, with the envelope evolving by the equation Nonlinear Schrodinger (NLS) equation dynamic. One of the NLS equation solution is known as Soliton on Finite Background (SFB). SFB is a continuation of the Benjamin-Feir nonlinear terms. Here, the probe of the BBM wave dynamics is conducted by transforming the complex amplitudes form of SFB variable into the polar form of displaced phase-amplitude. It was done to observe changes in the amplitude of the wave in a complex plane with phases that depend only on position. The description of the dynamics of the SFB can be illustrated through Argand diagrams. It was found that the modulation frequency affects the SFB phase: the smaller the modulation frequency, the higher the phase angle. Also, it is found that the phenomenon of SFB phase singularity occurs in extreme waves for certain frequency modulation intervals.

Enhancement of A Cationic Surfactant by Capping Nanoparticles: Synthesis, Characterization and Multiple Applications.

There is scarce information on cationic surfactants' biocidal and corrosion inhbibition effects on Slime-Forming Bacteria (SFB) isolated from oil field formation water. Therefore, this work focused on the the synthesis of a cationic surfactant (CS) to increase its features by capping different metal nanoparticles (zinc, ZnNPs-C-CS; manganese, MnNPs-C-CS and tin, SnNPs-C-CS) and used them as biocides and corrosion inhibitors. The cationic surfactant was synthesized and characterized by Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Afterwards, different nanoparticles were synthesized, characterized, and exploited to cap by the CS. The CS and the different nanoparticles capped by the CS were tested for their antimicrobial susceptibility against standard bacterial and yeast strains. The synthesized compounds were further evaluated as anti-biofilms agents against positively-developed bacterial biofilms. Moreover, the CS and the ZnNPs-C-CS, MnNPs-C-CS, and SnNPs-C-CS were assessed as potential biocides against SFB, particularly Pseudomonas sp. (isolated from contaminated formation water), and as corrosion inhibitors against cultivated salinity. The results revealed the great effect of the different CS-capped NPs as broad-spectrum antimicrobial and anti-biofilm agents at lower Minimum Inhibitory Concentrations (MICs), Minimum Bactericidal Concentrations (MBCs), Minimum Fungicidal Concentrations (MFCs) and Minimum Biofilm Inhibitory Concentrations (MBICs), and the activities were reported in order of SnNPs-C-CS > MnNPs-C-CS > ZnNPs-C-CS > CS. Furthermore, the ZnNPs-C-CS, MnNPs-C-CS, and SnNPs-C-CS demonstrated biocidal and corrosion inhibition effects against Pseudomonas sp. at a salinity of 3.5% NaCl, with metal corrosion inhibition efficiencies of 88.6, 94.0 and 96.9%, in comparison to a CS efficiency of 85.7%. In conclusion, the present work provides a newly synthesized cationic surfactant and has enhanced its antimicrobial and its metal corrosion inhibition effects by capping different nanoparticles, and it has been successfully applied against slime-forming bacteria at a salinity of 3.5% NaCl.

A new role for a COPII cargo adaptor in autophagy.

Endoplasmic reticulum (ER) homeostasis is maintained by the removal of misfolded ER proteins via different quality control pathways. Aggregation-prone proteins, including certain disease-linked proteins, are resistant to conventional ER degradation pathways and require other disposal mechanisms. Reticulophagy is a disposal pathway that uses resident autophagy receptors. How these receptors, which are dispersed throughout the ER network, target a specific ER domain for degradation is unknown. We recently showed in budding yeast, that ER stress upregulates the reticulophagy receptor, triggering its association with the COPII cargo adaptor complex, Sfb3/Lst1-Sec23 (SEC24C-SEC23 in mammals), to discrete sites on the ER. These domains are packaged into phagophores for degradation to prevent the accumulation of protein aggregates in the ER. This unconventional role for Sfb3/Lst1 is conserved in mammals and is independent of its role as a cargo adaptor on the secretory pathway. Our findings may have important therapeutic implications in protein-aggregation linked neurodegenerative disorders.