Prebiotic effect of galacto-N-biose on the intestinal lactic acid bacteria as enhancer of acetate production and hypothetical colonization.

Galacto-N-biose (GNB) is an important core structure of glycan of mucin glycoproteins in the gastrointestinal (GI) mucosa. Because certain beneficial bacteria inhabiting the GI tract, such as bifidobacteria and lactic acid bacteria, harbor highly specialized GNB metabolic capabilities, GNB is considered a promising prebiotic for nourishing and manipulating beneficial bacteria in the GI tract. However, the precise interactions between GNB and beneficial bacteria and their accompanying health-promoting effects remain elusive. First, we evaluated the proliferative tendency of beneficial bacteria and their production of beneficial metabolites using gut bacterial strains. By comparing the use of GNB, glucose, and inulin as carbon sources, we found that GNB enhanced acetate production in Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus johnsonii. The ability of GNB to promote acetate production was also confirmed by RNA-seq analysis, which indicated the upregulation of gene clusters that catalyze the deacetylation of N-acetylgalactosamine-6P and biosynthesize acetyl-CoA from pyruvate, both of which result in acetate production. To explore the in vivo effect of GNB in promoting acetate production, antibiotic-treated BALB/cA mice were administered with GNB with L. rhamnosus, resulting in a fecal acetate content that was 2.7-fold higher than that in mice administered with only L. rhamnosus. Moreover, 2 days after the last administration, a 3.7-fold higher amount of L. rhamnosus was detected in feces administered with GNB with L. rhamnosus than in feces administered with only L. rhamnosus. These findings strongly suggest the prebiotic potential of GNB in enhancing L. rhamnosus colonization and converting L. rhamnosus into higher acetate producers in the GI tract. IMPORTANCE: Specific members of lactic acid bacteria, which are commonly used as probiotics, possess therapeutic properties that are vital for human health enhancement by producing immunomodulatory metabolites such as exopolysaccharides, short-chain fatty acids, and bacteriocins. The long residence time of probiotic lactic acid bacteria in the GI tract prolongs their beneficial health effects. Moreover, the colonization property is also desirable for the application of probiotics in mucosal vaccination to provoke a local immune response. In this study, we found that GNB could enhance the beneficial properties of intestinal lactic acid bacteria that inhabit the human GI tract, stimulating acetate production and promoting intestinal colonization. Our findings provide a rationale for the addition of GNB to lactic acid bacteria-based functional foods. This has also led to the development of therapeutics supported by more rational prebiotic and probiotic selection, leading to an improved healthy lifestyle for humans.

Mucin glycans and their degradation by gut microbiota.

The human intestinal tract is inhabited by a tremendous number of microorganisms, which are collectively termed "the gut microbiota". The intestinal epithelium is covered with a dense layer of mucus that prevents penetration of the gut microbiota into underlying tissues of the host. Recent studies have shown that the maturation and function of the mucus layer are strongly influenced by the gut microbiota, and alteration in the structure and function of the gut microbiota is implicated in several diseases. Because the intestinal mucus layer is at a crucial interface between microbes and their host, its breakdown leads to gut bacterial invasion that can eventually cause inflammation and infection. The mucus is composed of mucin, which is rich in glycans, and the various structures of the complex carbohydrates of mucins can select for distinct mucosa-associated bacteria that are able to bind mucin glycans, and sometimes degrade them as a nutrient source. Mucin glycans are diverse molecules, and thus mucin glycan degradation is a complex process that requires a broad range of glycan-degrading enzymes. Because of the increased recognition of the role of mucus-associated microbes in human health, how commensal bacteria degrade and use host mucin glycans has become of increased interest. This review provides an overview of the relationships between the mucin glycan of the host and gut commensal bacteria, with a focus on mucin degradation.

Psychosocial factors predicting symptoms of depression and anxiety in allogeneic hematopoietic stem cell transplant recipients in Japan.

OBJECTIVE: We explored whether a patient's psychosocial background before allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict the occurrence of psychiatric symptoms during treatment and after hospital discharge. METHOD: Logistic regression analysis was performed using INTERMED, a scale that comprehensively evaluates psychological factors such as psychiatric history, current mental status, and coping skills, and social factors such as social participation status, relationships with others, and living environment, which were used as independent variables. The Center for Epidemiologic Studies Depression Scale was used to measure depression, while the Profile of Mood States was used to measure anxiety and other symptoms. Both measures were used as dependent variables and were administered upon clean room admission, during clean room stay, at clean room discharge, and at 3, 6, and 12 months after hospital discharge. RESULTS: Participants included 70 patients (45 males and 25 females, mean age 53.3 ± 12.3 years). Thirty-eight patients participated in the program for the entire period, up to 12 months after hospital discharge. The total score on the Japanese version of the INTERMED and psychological factor scores assessed at baseline were significant predictors of depressed mood on discharge; however, there were no significant predictors of scores on the Profile of Mood States. CONCLUSIONS: A comprehensive pretransplant evaluation of psychosocial background can help predict the appearance of psychiatric symptoms after allo-HSCT. In patients who are expected to develop psychiatric symptoms after allo-HSCT, it is important to consider early intervention by a specialist and close monitoring by a medical team.

Role of Lipoteichoic Acid from the Genus Apilactobacillus in Inducing a Strong IgA Response.

Lactic acid bacterium-containing fermentates provide beneficial health effects by regulating the immune response. A naturally fermented vegetable beverage, a traditional Japanese food, reportedly provides health benefits; however, the beneficial function of its bacteria has not been clarified. Apilactobacillus kosoi is the predominant lactic acid bacterium in the beverage. Using murine Peyer's patch cells, we compared the immunoglobulin A (IgA)-inducing activity of A. kosoi 10HT to those of 29 other species of lactic acid bacteria and found that species belonging to the genus Apilactobacillus (A. kosoi 10HT, A. apinorum JCM30765T, and A. kunkeei JCM16173T) possessed significantly higher activity than the others. Thereafter, lipoteichoic acids (LTAs), important immunostimulatory molecules of Gram-positive bacteria, were purified from the three Apilactobacillus species, and their IgA-inducing activity was compared to those of LTAs from Lactiplantibacillus plantarum JCM1149T and a probiotic strain, Lacticaseibacillus rhamnosus GG. The results revealed that LTAs from Apilactobacillus species had significantly higher activity than others. We also compared the LTA structure of A. kosoi 10HT with that of L. plantarum JCM1149T and L. rhamnosus GG. Although d-alanine or both d-alanine and carbohydrate residues were substituents of free hydroxyl groups in the polyglycerol phosphate structure in LTAs from strains JCM1149T and GG, d-alanine residues were not found in LTA from strain 10HT by 1H nuclear magnetic resonance (NMR) analysis. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) analysis of the glycolipid structure of LTA revealed that LTA from strain 10HT contained dihexosyl glycerol, whereas trihexosyl glycerol was detected in LTAs from other strains. These structural differences may be related to differences in IgA-inducing activity. IMPORTANCE The components of lactic acid bacteria that exert immunostimulatory effects are of increasing interest for therapeutic and prophylactic options, such as alternatives to antibiotics, cognitive enhancements, and vaccine adjuvants. LTAs act as immunostimulatory molecules in the host innate immune system by interacting with pattern recognition receptors. However, as LTA structures differ among species, detailed knowledge of the structure-function relationship for immunostimulatory effects is required. Comparisons of the IgA-inducing activity of LTAs have demonstrated that LTAs from the genus Apilactobacillus possess distinctive activities to stimulate mucosal immunity. The first analysis of the LTA structure from the genus Apilactobacillus suggests that it differs from structures of LTAs of related species of lactic acid bacteria. This knowledge is expected to aid in the development of functional foods containing lactic acid bacteria and pharmaceutical applications of immunostimulatory molecules from lactic acid bacteria.

Ray-optics study of gentle non-conformal texture morphologies for perovskite/silicon tandems.

We investigate gentle front side textures for perovskite/silicon tandem solar cells. These textures enhance the absorption of sunlight, yet are sufficiently gentle to allow deposition of an efficient perovskite top cell. We present a tandem solar cell with such gentle texture, fabricated by Kaneka corporation, with an efficiency as high as 28.6%. We perform an extensive ray-optics study, exploring non-conformal textures at the front and rear side of the perovskite layer. Our results reveal that a gentle texture with steepness of only 23° can be more optically efficient than conventional textures with more than double that steepness. We also show that the observed anti-reflective effect of such gentle textures is not based a double bounce, but on light trapping by total internal reflection. As a result, the optical effects of the encapsulation layers play an important role, and have to be accounted for when evaluating the texture design for perovskite/silicon tandems.

Adverse effects of COVID-19 vaccines and measures to prevent them.

Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among the unvaccinated individuals. According to European Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible. The decrease in immunity can be caused by several factors such as N1-methylpseudouridine, the spike protein, lipid nanoparticles, antibody-dependent enhancement, and the original antigenic stimulus. These clinical alterations may explain the association reported between COVID-19 vaccination and shingles. As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination should be recorded in the medical record of patients. Several practical measures to prevent a decrease in immunity have been reported. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression. In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.

Chemical Synthesis and Evaluation of Exopolysaccharide Fragments Produced by Leuconostoc mesenteroides Strain NTM048.

Exopolysaccharides (EPSs) occur widely in natural products made by bacteria, fungi and algae. Some EPSs have intriguing biological properties such as anticancer and immunomodulatory activities. Our group has recently found that EPSs generated from Leuconostoc mesenteroides ssp. mesenteroides strain NTM048 (NTM048 EPS) enhanced a production of mucosal immunoglobulin A (IgA) of mouse. Herein, we described the synthesis and evaluation of the tetrasaccharide fragments of NTM048 EPS to obtain information about the molecular mechanism responsible for the IgA-inducing activity.

Lentilactobacillus kosonis sp. nov., isolated from kôso, a Japanese sugar-vegetable fermented beverage.

A novel lactic acid-producing, Gram-stain-positive, catalase-negative and rod-shaped strain, designated as strain C06_No.73T, was isolated from a traditional Japanese fermented beverage called kôso. According to the results of phylogenetic analysis based on 16S rRNA gene sequences, strain C06_No.73T belongs to the genus Lentilactobacillus. The closest type strain was Lentilactobacillus curieae CCTCC M 2011381T, with a sequence identity of 98.1 %. The identity values with other strains were all below 97 %. The isolate propagated under the conditions of 18-39 °C (optimum, 27 °C for 48 h incubation) and pH 4.0-7.0 (optimum, pH 6.5). The G+C content of its genomic DNA was determined to be 37.9 mol%. The main fatty acids were C16 : 0, C18 : 1 ω7c, C18 : 1 ω9c and C19 : 0 cyclopropane 11,12. The major polar lipid was identified as phosphatidylglycerol. No isoprenoid quinone was detected. The predominant cell-wall amino acids were lysine, alanine, glutamic acid and aspartic acid. Neither meso-diaminopimelic acid nor ornithine were detected. On the basis of this polyphasic taxonomic study, the isolate is concluded to represent a novel species, for which the name Lentilactobacillus kosonis sp. nov. is proposed. The type strain is C06_No.73T (=NBRC 111893T=BCRC 81282T).

Risk of heparinoid use in cosmetics and moisturizers in individuals vaccinated against severe acute respiratory syndrome coronavirus 2.

Recently, heparin-induced thrombocytopenia (HIT) after vaccination with the vaccines manufactured by AstraZeneca and Pfizer-BioNTech has been published in the New England Journal of Medicine. These reports state that heparin was not used around the vaccination period in all cases. HIT after vaccination is more common in women; thus, heparinoid use can be suspected to induce HIT.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

[Suspected Takotsubo Cardiomyopathy after Elective Mitral Valve Replacement:Report of a Case].

Reports of takotsubo cardiomyopathy following cardiac surgery are rare. We report a case of postoperative takotsubo cardiomyopathy after mitral valve replacement (MVR). The patient was a 70-yearold woman with mitral stenosis, regurgitation, and a medical history of long-standing persistent atrial fibrillation. Preoperative echocardiogram confirmed severe mitral regurgitation, severe mitral stenosis, severe tricuspid regurgitation, and slight left ventricular dysfunction. Coronary lesions were not observed on preoperative diagnostic coronary angiography. MVR with a bioprosthetic valve, tricuspid annuloplasty, and left atrial maze were performed. Electrocardiogram on postoperative day (POD) 1 revealed a deep negative T wave in V3-V6. Echocardiogram revealed "takotsubo-like" wall motion, and the ejection fraction( EF) was 19%. The EF improved on POD 7. After three months, the electrocardiogram findings and EF appeared normal. We suspected takotsubo cardiomyopathy although postoperative coronary angiography was not performed. Takotsubo cardiomyopathy should be considered as a possible complication of cardiac surgery, especially after MVR.

Administration of Enterococcus faecium HS-08 increases intestinal acetate and induces immunoglobulin A secretion in mice.

A probiotic is considered a live microbial feed supplement that has beneficial effects on the host. In this study, the probiotic property by which Enterococcus faecium HS-08 strengthens the immune system was investigated. Using a murine model, we evaluated the abilities of this strain to increase intestinal short-chain fatty acid contents and to induce the production of mucosal immunoglobulin A (IgA), which are crucial for mucosal immune systems. Various amounts (0%, 0.0038%, 0.038%, or 0.38%) of strain HS-08 cells were administered to BALB/cAJcl mice, which resulted in a dose-dependent increase of fecal IgA levels. A qRT-PCR analysis of Peyer's patch cells revealed that the gene expression of retinal-dehydrogenase, interleukin 6, B-cell-activating factor, and a proliferation-inducing ligand were increased, which leads to IgA secretion via a T-cell-independent mechanism. The administration of 0.038% and 0.38% of strain HS-08 cells also increased fecal acetate levels, which plays an important role for maintaining immune functions. This cecal floral analysis and the stability of strain HS-08 against gastrointestinal digestion suggest that this strain can inhabit the host intestine. In conclusion, the administration of E. faecium HS-08 increased intestinal acetate levels and enhanced IgA secretion, which may result in strengthening of the mucosal immune system.

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles.

Based on experimental concentration depth profiles of the antiinflammatory drug dexamethasone in human skin, we model the time-dependent drug penetration by the 1D general diffusion equation that accounts for spatial variations in the diffusivity and free energy. For this, we numerically invert the diffusion equation and thereby obtain the diffusivity and the free-energy profiles of the drug as a function of skin depth without further model assumptions. As the only input, drug concentration profiles derived from X-ray microscopy at three consecutive times are used. For dexamethasone, skin barrier function is shown to rely on the combination of a substantially reduced drug diffusivity in the stratum corneum (the outermost epidermal layer), dominant at short times, and a pronounced free-energy barrier at the transition from the epidermis to the dermis underneath, which determines the drug distribution in the long-time limit. Our modeling approach, which is generally applicable to all kinds of barriers and diffusors, allows us to disentangle diffusivity from free-energetic effects. Thereby we can predict short-time drug penetration, where experimental measurements are not feasible, as well as long-time permeation, where ex vivo samples deteriorate, and thus span the entire timescales of biological barrier functioning.

Modeling of Drug Diffusion Based on Concentration Profiles in Healthy and Damaged Human Skin.

Based on experimental drug concentration profiles in healthy as well as tape-stripped ex vivo human skin, we model the penetration of the antiinflammatory drug dexamethasone into the skin layers by the one-dimensional generalized diffusion equation. We estimate the position-dependent free-energy and diffusivity profiles by solving the conjugated minimization problem, in which the only inputs are concentration profiles of dexamethasone in skin at three consecutive penetration times. The resulting free-energy profiles for damaged and healthy skin show only minor differences. In contrast, the drug diffusivity in the first 10 µm of the upper skin layer of damaged skin is 200-fold increased compared to healthy skin, which reflects the corrupted barrier function of tape-stripped skin. For the case of healthy skin, we examine the robustness of our method by analyzing the behavior of the extracted skin parameters when the number of input and output parameters are reduced. We also discuss techniques for the regularization of our parameter extraction method.

Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration.

Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem-mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.

Investigation of the formation mechanism of proline-containing cyclic dipeptide from the linear peptide.

Cyclic dipeptides, 2,5-diketopiperazines (DKPs), are well-known bioactive and taste compounds in food. DKPs have also been reported in various foods and particularly, Pro-containing DKPs (cyclo(-X-Pro)) are more predominant in heated and fermented foods than other type of DKPs. However, the mechanism underlying the preferential formation of Pro-containing DKPs in food remains uncertain. Herein, we attempted to elucidate the effects of reaction conditions and the mechanism of DKPs formation. The reaction conditions (heating time, heating temperature, and pH) and amino acid sequence of the linear peptides were important for the DKPs formation from linear peptides. In addition, Pro-containing DKPs were significantly formed from linear peptides with the second amino acid from the N-terminus being Pro. Based on these results, the underlying mechanism of the enrichment of Pro-containing DKPs in foods was proposed.

Percutaneous Continuous Irrigation and Drainage for Infected Obturator Bypass Graft.

The treatment for obturator bypass graft infection has been rarely reported and is a surgical challenge because it is difficult to debride infected tissue around the graft located in the deep route and to ensure an alternative revascularization route in patients with a history of inguinal infection. Percutaneous continuous irrigation and drainage is an effective and less invasive definitive therapy for obturator bypass graft infection.

Homography based identification for automatic and robust calibration of projection integral imaging displays.

Recent advances in the creation of microlens arrays as holographic optical elements allow the creation of projector-based see-through light field displays suitable for augmented reality. These systems require an accurate calibration of the projector with relation to the microlens array, as any small misalignment causes the 3D reconstruction to fail. The methods reported so far require precise placement of the calibration camera w.r.t. the lens array screen, which affects the display configuration. We propose a calibration approach which is more robust, and which allows free camera placement. Hence, it does not limit the capabilities of the system. Both a homography-based technique and structured light play a central role in realizing such a method. The method was tested on a projection-based integral imaging display system consisting of a consumer-grade projector and a digitally designed holographic optical element based micromirror array screen. The calibration method compensates for the lens distortion, intrinsics, and positioning of the projector with relation to the screen. The method uses a single camera and does not require the use of obtrusive markers as reference. We give an in-depth explanation of the different steps of the algorithm, and verify the calibration using both a simulated and a real-world setup.

Specificity of Donor Structures for endo-ß-N-Acetylglucosaminidase-Catalyzed Transglycosylation Reactions.

To demonstrate the structural specificity of the glycosyl donor for the transglycosylation reaction by using endo-ß-N-acetylglucosaminidase from Mucor hiemalis (endo-M), a series of tetrasaccharide oxazoline derivatives was synthesized. These derivatives correspond to the core structure of an asparagine-linked glycoprotein glycan with a ß-mannose unit of a non-natural-type monosaccharide, including ß-glucose, ß-galactose, and ß-talose in place of the ß-mannose moiety. The transglycosylation activity of wildtype (WT) endo-M and two mutants, N175Q and N175A, was examined by using these tetrasaccharide donors with p-nitrophenyl N-acetylglucosaminide (GlcNAc-pNp). The essential configuration of the hydroxy group for the transglycosylation reaction was determined. On the basis of these results, the transglycosylation reaction was investigated by using chemically modified donors, and transglycosylated products were successfully obtained.

Digitally designed holographic optical element for light field displays.

Concave micro-mirror arrays fabricated as holographic optical elements are used in projector-based light field displays due to their see-through characteristics. The optical axes of each micro-mirror in the array are usually made parallel to each other, which simplifies the fabrication, integral image rendering, and calibration process. However, this demands that the beam from the projector be collimated and made parallel to the optical axis of each elemental micro-mirror. This requires additional collimation optics, which puts serious limitations on the size of the display. In this Letter, we propose a solution to the above issue by introducing a new method to fabricate holographic concave micro-mirror array sheets and explain how they work in detail. 3D light field reconstructions of the size 20 cm×10 cm and 6 cm in depth are achieved using a conventional projector without any collimation optics.